Research – Antley-Bixler Syndrome and Persistent Depressive Disorder

Brief

1. What is Antley-Bixler syndrome? Is it a degenerative disorder? Outline, treatment, management and prognosis.
2. The nature of Persistent Depressive Disorder, what are the causes, what are the treatments, and prognosis.

Date

October 01, 2020

Requester

S22(1)(A)(ii) (Assistant Director – TAB)

Researcher

S22(1)(A) (Tactical Research Advisor – TAB/AAT)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

• Summary: 2
• Antley-Bixler Syndrome: 2
  • What is Antley-Bixler syndrome?: 2
  • Treatment & Management: 4
• Persistent Depressive Disorder: 5
  • What is Persistent Depressive Disorder (PDD)?: 5
  • Causes: 5
  • Treatment & Management: 6
  • Prognosis: 6
• References: 7

Summary

Antley-Bixler Syndrome

• Antley-Bixler syndrome (ABS) is a rare genetic disorder that can cause structural changes of the skull, bones of the face and other skeletal abnormalities
• Prognosis varies depending on the pattern and severity of malformations
• No literature could be sourced which would indicate that the syndrome is a degenerative disorder
• Mortality has been reported to be as high as 80% within the neonatal period
• There are challenges to long-term treatment, where a staged surgical and multi-disciplinary approach is taken, and treatment is aimed at managing symptoms, which typically includes surgery.

Persistent Depressive Disorder

• Persistent Depressive Disorder is a less severe form of major depression
• Causes are not known but potential causes are biological differences, brain chemistry, inherited traits, and life events.
• The literature indicates best practice intervention as of medication and psychotherapy
• With treatment the prognosis is positive

Antley-Bixler Syndrome

What is Antley-Bixler syndrome?

Antley-Bixler syndrome (ABS) is a rare genetic disorder that can cause structural changes of the skull, bones of the face and other skeletal abnormalities. [1] Fewer than 50 cases have been described in the literature to date. [2] Mortality has been reported to be as high as 80% within the neonatal period, primarily due to airway compromise, and prognosis improves with increasing age.[3, 4]. Overall prognosis varies depending on the pattern and severity of malformations. [2] No literature could be sourced which would indicate that the syndrome is a degenerative disorder.

Research – Antley-Bixler Syndrome and Persistent Depressive Disorder Page | 2 Page 2 of 165

The syndrome is typically characterized by structural changes of the skull, bones of the face and other skeletal abnormalities.

In most affected infants, there is premature closure of the joints (sutures) between different portions of the skull (craniosynostosis). Additional craniofacial abnormalities may include a large, prominent forehead (frontal bossing), underdeveloped middle regions of the face (mid facial hypoplasia); a large nose with a low nasal bridge; protruding eyes (proptosis); and low-set, malformed (dysplastic) ears.

The syndrome is also characterized by other distinctive skeletal changes. These may include fusion of bones of the arms that are next to each other (adjacent), particularly the forearm bone on the thumb side of the arm (radius) and the long bone of the upper arm (radiohumeral synostosis). In addition, there can be permanent flexion or extension of certain joints in a fixed position (joint contractures), leading to limited movements of the fingers, wrists, ankles, knees, and/or hips. Affected individuals may also have unusually long, thin fingers and toes (camptodactyly), structural changes on the bottom of the feet (“rocker-bottom” feet); or bowing and/or fractures of the thigh bones.

Some individuals with the syndrome may have additional symptoms. These may include certain structural defects of the urinary and genital organs (urogenital defects), inability to produce cholesterol from steroids (impaired steroidogenesis), developmental delay, and intellectual disability.

Figure 1: Cranial - Clinical presentation at 14 years [5]

Research – Antley-Bixler Syndrome and Persistent Depressive Disorder Page | 3 Page 3 of 165

Treatment & Management

The literature sourced suggests that the complexity of malformations in patients require a multi-disciplinary approach to treatment [2, 7] which is usually tailored to each patient and to the severity of the anomaly and which typically includes surgery. [8]

Treatment strategies are symptomatic, focussing on the correction of the malformations present and depending on individual psychological problems. Complex impairment of the craniofacial growth pattern requires staged surgical correction because of functional and psychosocial problems, as in other craniofacial dysostosis syndromes. [2]

Solem et al [5] suggests that the unique clinical features of the syndrome present particular challenges to long-term treatment, where a staged surgical approach including fronto-orbital and midface advancements is required for intracranial pressure reduction, globe protection, airway patency, and malocclusion.

The table below [5] gives an example of long term staged surgical treatment of the syndrome of a patient from 5 months to 21 years of age.

The National Organisation for Rare Disorders [1] suggests that other therapies may aide in managing symptoms including occupational therapy and speech therapy. However no reference could be sourced in the literature where these interventions were being used apart from one case report where the patient developed hyper-nasal speech at five years and required speech therapy. [5]

Research – Antley-Bixler Syndrome and Persistent Depressive Disorder Page | 4 Page 4 of 165

Persistent Depressive Disorder

What is Persistent Depressive Disorder (PDD)?

Persistent depressive disorder (dysthymia) is a form of depression. It may be less severe than major depression, but as the name suggests, it lasts longer.

The symptoms of persistent depressive disorder are similar to those of major depression. In this disorder, the long duration is the key to the diagnosis, not the intensity of symptoms:

• Mood may be either low or irritable.
• Feeling less pleasure and a lack of energy.
• Feel relatively unmotivated and disengaged from life.
• Appetite and weight can increase or decrease.
• May sleep too much or have trouble sleeping.
• Indecisiveness, pessimism and poor self-image may also be present.

Symptoms can grow into a full-blown episode of major depression. People with PPD have a greater-than-average chance of developing major depression.

While major depression often occurs in episodes, PPD is defined as more constant, lasting for years. The disorder sometimes starts in childhood. As a result, a person with PPD tends to believe that depression is part of their character, and so self-defining that they may not even think to talk about this depression with doctors, family members or friends. [9]

Causes

Causes of PPD are not known, however the literature indicates the following potential causes [10]:

• Biological differences. People with persistent depressive disorder may have physical changes in their brains. The significance of these changes is still uncertain, but they may eventually help pinpoint causes.

Treatment & Management

The literature indicates the prevalent use of medication and psychotherapy in the treatment of PPD. [11]

A 2016 literature review aimed to provide an updated meta-analysis of the efficacy of pharmacotherapy in the acute phase, and of psychotherapy in its residual phase of treatment, in reducing the risk of relapse in major depressive disorder and to place these findings in the larger context of treatment selection. The review concluded that the sequential integration of cognitive-behavioural therapy and pharmacotherapy is a viable strategy for preventing relapse in major depressive disorder. The review suggests the sequential modality of integration of pharmacotherapy and psychotherapy appears to be a valuable therapeutic strategy for preventing relapse. [12]

PDD can be treated with various types of antidepressants, including [13]:

• selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and sertraline (Zoloft)

• tricyclic antidepressants (TCAs), such as amitriptyline (Elavil) and amoxapine (Asendin)

• serotonin and norepinephrine reuptake inhibitors (SNRIs), such as desvenlafaxine (Pristiq) and duloxetine (Cymbalta)

Prognosis

With treatment, the outlook for someone with this disorder is excellent. The duration and intensity of symptoms is often diminished significantly. Without treatment, the illness is more likely to persist, the person is likely to have a reduced quality of life and has an increased risk of developing major depression.

Even when treatment is successful, maintenance treatment often is required to prevent symptoms from returning. [9]

Research – Antley-Bixler Syndrome and Persistent Depressive Disorder Page | 6 Page 6 of 165

References

• National Organization for Rare Disorders. Rare Diseases Database: Antley-Bixler Syndrome. [Internet]. 2020 [cited 29 September 2020]. Available from: https://rarediseases.org/rare-diseases/antley-bixler-syndrome/
• Adolphs, N., Klein, M., Haberl, E., Graul-Neumann, L., Menneking, H. and Hoffmeister, B., 2011. Antley–Bixler-Syndrome – Staged management of craniofacial malformations from birth to adolescence – A case report. Journal of Cranio-Maxillofacial Surgery, 39 (7), pp.487-495.
• Hosalkar H, Shah H, Gujar P, et al. The Antley-Bixler syndrome: two new cases. J Postgrad Med 2001;47:252Y255
• Bradley J, Kawamoto H, Taub P, et al. Antley-Bixler syndrome: correction of facial deformities and long-term survival. Plast Reconstr Surg 2003;111:1454Y1460
• Solem, R., Martz, M., Weiss, E., Reese, P., Kawamoto, H. and Lee, J., 2017. Multidisciplinary Treatment of Antley-Bixler Syndrome. The Cleft Palate-Craniofacial Journal, 54 (1), pp.100-108.
• Fan L, Ren X, Song Y, Su C, Fu J, Gong C. Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: based on the first cohort of Chinese children. Orphanet Journal of Rare Diseases. 2019;14 (1).
• McGlaughlin, K., Witherow, H., Dunaway, D., David, D. and Anderson, P., 2010. Spectrum of Antley-Bixler Syndrome. Journal of Craniofacial Surgery, 21(5), pp.1560-1564.
• Ghazle, H. and Newcomb, P., 2014. Sonographic Diagnosis of Antley-Bixler PORD-Type Syndrome. Journal of Diagnostic Medical Sonography, 31 (2), pp.93-98.
• Persistent Depressive Disorder (Dysthymia) [Internet]. Harvard Health. 2020 [cited 30 September 2020]. Available from: https://www.health.harvard.edu/a_to_z/dysthymia-a-to-z
• Persistent depressive disorder (dysthymia), Symptoms and causes [Internet]. Mayo Clinic. 2020 [cited 30 September 2020]. Available from: https://www.mayoclinic.org/diseases-conditions/persistent-depressive-disorder/symptoms-causes/syc-20350929
• Ishizaki J, Mimura M. Dysthymia and Apathy: Diagnosis and Treatment. Depression Research and Treatment. 2011; 2011:1-7.
• Guidi J, Tomba E, Fava G. The Sequential Integration of Pharmacotherapy and Psychotherapy in the Treatment of Major Depressive Disorder: A Meta-Analysis of the Sequential Model and a Critical Review of the Literature. American Journal of Psychiatry. 2016;173(2):128-137.
• Dysthymia: Causes, Symptoms and Diagnosis [Internet]. Healthline. 2020 [cited 30 September 2020]. Available from: https://www.healthline.com/health/dysthymia#treatments

Research – Antley-Bixler Syndrome and Persistent Depressive Disorder Page | 7 Page 7 of 165

Research – Congestive Heart Failure Treatment Options

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

• Summary ………………………………………………………………………………………………………………………………. 2
• What is Congestive Heart Failure (CHF)? …………………………………………………………………………………… 2
  • Overview …………………………………………………………………………………………………………………………… 2
  • Types of CHF ……………………………………………………………………………………………………………………… 3
• Treatment & Management ……………………………………………………………………………………………………… 3
  • Overview …………………………………………………………………………………………………………………………… 3
  • CHF Stages & Treatment Outlook …………………………………………………………………………………………. 4
    • Specific Guidelines ……………………………………………………………………………………………………………… 5
      • Pharmacological Management …………………………………………………………………………………………. 6
      • Multidisciplinary Management …………………………………………………………………………………………. 7
      • Devices, Surgery and Other Management ………………………………………………………………………….. 7
• Rehabilitation Programs ……………………………………………………………………………………………………… 8 References ………………………………………………………………………………………………………………………….. 10

Summary

• Scientific research and open source literature on the subject is plentiful. The most substantial recent guideline resource in Australia, which offers strength of recommendation and quality of evidence is the “National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of heart failure”.

• There are two types of Congestive Heart Failure, left sided and right sided. It’s possible to have left-sided and right-sided Congestive Heart Failure at the same time.

• Congestive Heart Failure initially requires timely medical attention.

• Depending on the severity of the patient’s condition, a multidisciplinary management approach is taken with treatment which may include medications, heart failure programs and exercise training, devices implantation surgery, transplant surgery.

• Cardiac Rehabilitation Programs are available for health care professionals to refer their patients.

What is Congestive Heart Failure (CHF)?

Overview

Congestive Heart Failure (CHF) sometimes referred to as “heart failure” (HF) or “congestive cardiac failure” (CCF), is a condition in which the heart muscle is weakened and can’t pump as well as it usually does. The main pumping chambers of the heart (the ventricles) can change size and thickness, and either can’t contract (squeeze) or can’t relax (fill) as well as they should. This triggers fluid retention, particularly in the lungs, legs and abdomen.

The major causes of heart failure include coronary heart disease and heart attack, high blood pressure, damage to the heart muscle (cardiomyopathy), heart valve problems and abnormal heart rhythms. Of these, coronary heart disease and heart attack are the most common causes.

The major factors that contribute to coronary heart disease include:

• obesity
• unhealthy eating
• high blood pressure
• diabetes
• smoking
• high cholesterol
• excess alcohol intake
• reduced emotional and social wellbeing

Types of CHF

Left-sided CHF is the most common type of CHF. It occurs when your left ventricle doesn’t properly pump blood out to your body. As the condition progresses, fluid can build up in your lungs, which makes breathing difficult.

There are two kinds of left-sided heart failure:

1. Systolic heart failure occurs when the left ventricle fails to contract normally. This reduces the level of force available to push blood into circulation. Without this force, the heart can’t pump properly.

2. Diastolic failure, or diastolic dysfunction, happens when the muscle in the left ventricle becomes stiff. Because it can no longer relax, the heart can’t quite fill with blood between beats.

Right-sided CHF occurs when the right ventricle has difficulty pumping blood to your lungs. Blood backs up in your blood vessels, which causes fluid retention in your lower extremities, abdomen, and other vital organs.

It’s possible to have left-sided and right-sided CHF at the same time. Usually, the disease starts in the left side and then travels to the right when left untreated. [2]

Treatment & Management

Overview

Treatment for heart failure can include [1]:

• Pharmacological, such as
  • Diuretics – to remove excess fluid and improve symptoms of heart failure
  • Mineralcortiocoid receptor antagonists (MRAs) (as separate from loop diuretics which improve symptoms) – are also recommended and used in most patients with heart failure to reduce mortality and hospitalisation
  • ACE inhibitors – to open up blood vessels, reduce blood pressure and reduce sodium retention and water retention
  • Certain beta-blockers – to slow the heart rate and reduce its work
  • Aldosterone blockers – to reduce blood pressure and reduce the effects of damage to the heart muscle
  • ACE inhibitors, beta blockers and aldosterone blockers can increase survival and reduce the likelihood of hospitalisation.

• Addressing the underlying disorder – for example, treatment of high blood pressure
• Lifestyle changes – such as regular gentle physical activity, losing excess body fat, stopping smoking, adhering to healthy eating patterns with low salt, restricting alcohol and having adequate rest
• Insertion of implantable cardiac devices
• Surgery – to replace narrowed or leaking heart valves
• Coronary bypass surgery – in some cases
• Heart transplant – in extreme cases.

CHF Stages & Treatment Outlook

The table below shows the symptoms of CHF and a brief treatment outlook: [2]

Following clinical diagnosis, HF is generally categorised according to whether it is associated with a reduced left ventricular ejection fraction (LVEF) below 50% (heart failure with reduced ejection fraction [HFrEF]) or preserved LVEF of 50% or more (heart failure with preserved ejection fraction [HFpEF]). [3]

The image below shows the flow of treatment management of HFrEF [3]

Research – Congestive Heart Failure Treatment Options Page | 4

Page 11 of 165

Specific Guidelines

The summary of management of treatments below is sourced from the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of heart failure 2018. [3] [4] Each recommendation in the guidelines is presented with a Grading of Recommendations Assessment, Development and Evaluation (GRADE) strength of recommendation and quality of evidence.

Research – Congestive Heart Failure Treatment Options Page | 5 Page 12 of 165

Pharmacological Management

• An ACE inhibitor is recommended in all patients with HFrEF associated with an LVEF <40%, unless contraindicated or not tolerated, to decrease mortality and decrease hospitalisation. GRADE: Strong; Evidence: High.

• A b-blocker (specifically bisoprolol, carvedilol, controlled or extended release metoprolol or nebivolol) is recommended in all patients with HFrEF associated with an LVEF <40% unless contraindicated or not tolerated, and once stabilised with no or minimal clinical congestion on physical examination, to decrease mortality and decrease hospitalisation. GRADE: Strong; Evidence: High.

• A mineralocorticoid receptor antagonist (MRA) is recommended in all patients with HFrEF associated with an LVEF <40% unless contraindicated or not tolerated, to decrease mortality and decrease hospitalisation for HF. GRADE: Strong; Evidence: High.

• An angiotensin receptor blocker (ARB) is recommended in patients with HFrEF associated with an LVEF <40% if an ACE inhibitor is contraindicated or not tolerated, to decrease the combined endpoint of cardiovascular mortality and HF hospitalisation. GRADE: Strong; Evidence: Moderate.

• An angiotensin receptor neprilysin inhibitor (ARNI) is recommended as a replacement for an ACE inhibitor (with at least a 36-hour washout window) or an ARB in patients with HFrEF associated with an LVEF <40% despite receiving maximally tolerated or target doses of an ACE inhibitor (or ARB) and a b-blocker (unless contraindicated), with or without an MRA, to decrease mortality and decrease hospitalisation. GRADE: Strong; Evidence: High.

• Ivabradine should be considered in patients with HFrEF associated with an LVEF <35% and with a sinus rate >70 bpm, despite receiving maximally tolerated or target doses of an ACE inhibitor (or ARB) and a b-blocker (unless contraindicated), with or without an MRA, to decrease the combined endpoint of cardiovascular mortality and HF hospitalisation. GRADE: Strong; Evidence: High

• A diuretic should be considered in patients with HF and clinical symptoms, or signs of congestion, to improve symptoms and manage congestion. GRADE: Strong; Evidence: Very low.

• Unless a reversible cause has been corrected, neurohormonal antagonists (ACE inhibitors or ARBs or ARNIs, b-blockers and MRAs) should be continued at target doses in patients with HF associated with a recovered or restored ejection fraction, to decrease the risk of recurrence. GRADE: Strong; Evidence: Low.

Research – Congestive Heart Failure Treatment Options Page | 6 Page 13 of 165

Multidisciplinary Management

• Referral to a multidisciplinary HF disease management program is recommended in patients with HF associated with high risk features, to decrease mortality and rehospitalisation. GRADE: Strong; Evidence: High.

• In areas where access to a face-to-face multidisciplinary HF disease management program after discharge is limited, patients should be followed up with a multidisciplinary tele-monitoring or telephone support program. GRADE: Strong; Evidence: Moderate.

• Nurse-led medication titration is recommended in patients diagnosed with HFrEF who have not achieved maximum tolerated doses of ACE inhibitors, ARBs, ARNIs, b-blockers or MRAs, to decrease hospitalisation. GRADE: Strong; Evidence: High.

• Regular performance of up to moderate intensity (ie, breathe faster but hold conversation) continuous exercise is recommended in patients with stable chronic HF, particularly those with reduced LVEF, to improve physical functioning and quality of life and to decrease hospitalisation. GRADE: Strong; Evidence: High.

Devices, Surgery and Other Management

• Cardiac resynchronisation therapy (CRT) is recommended in patients with HFrEF associated with sinus rhythm, an LVEF <35% and a QRS duration >150 ms despite optimal medical therapy, to decrease mortality, decrease hospitalisation for HF, and improve symptoms. GRADE: Strong; Evidence: High.

• CRT should be considered in patients with HFrEF associated with sinus rhythm, an LVEF < 35% and a QRS duration of 130e149 ms despite optimal medical therapy, to decrease mortality, decrease hospitalisation for HF, and improve symptoms. GRADE: Strong; Evidence: Moderate.

• CRT should be considered in patients with HFrEF associated with an LVEF of <50% accompanied by high grade atrioventricular block requiring pacing, to decrease hospitalisation for HF. GRADE: Weak; Evidence: Moderate.

• CRT is contraindicated in patients with a QRS duration <130 ms, because of lack of efficacy and possible harm. GRADE: Strong Against; Evidence: Moderate.

• An implantable cardioverter defibrillator (ICD) should be considered as a primary prevention indication in patients with HFrEF associated with ischaemic heart disease and an LVEF <35%, to decrease mortality.

  GRADE: Strong; Evidence: Moderate.

• An ICD may be considered as a primary prevention indication in patients with HFrEF associated with dilated cardiomyopathy and an LVEF <35%, to decrease mortality.

  GRADE: Weak; Evidence: Low.

• Coronary artery bypass graft surgery should be considered in patients with HFrEF associated with ischaemic heart disease and an LVEF <35% if they have surgically correctable coronary artery disease, to improve symptoms (eg, relief of angina and HF symptoms) and decrease morbidity and long term mortality.

  GRADE: Strong; Evidence: Moderate.

• Surgical aortic valve replacement is recommended in patients with severe aortic stenosis or severe aortic regurgitation and HF in the absence of major comorbidities or frailty, to improve symptoms and decrease mortality.

  GRADE: Strong; Evidence: Low.

• Transcatheter aortic valve implantation should be considered in patients with severe aortic stenosis and HF at intermediate to high operative mortality risk, or considered inoperable for surgical aortic valve replacement, and who are deemed suitable for transcatheter aortic valve implantation following assessment by a heart team, to improve symptoms and decrease mortality.

  GRADE: Strong; Evidence: Moderate.

• Referral to a specialist centre for consideration of ventricular assist device implantation should be considered in patients with intractable, severe HF despite guideline-directed medical and pacemaker therapy, and who do not suffer from major comorbidities, to decrease mortality.

  GRADE: Strong; Evidence: Moderate.

• Referral for heart transplant assessment should be considered in patients with HF associated with intractable New York Heart Association class IIIeIV symptoms who have exhausted all alternative therapies and who do not have overt contraindications, to decrease mortality.

  GRADE: Strong; Evidence: Low.

Rehabilitation Programs

The Australian Heart Foundation recommends that all Australians who experience a heart event are referred to and attend a cardiac rehabilitation program. Cardiac rehabilitation supports long-term lifestyle changes. [5]

Cardiac Rehabilitation

Cardiac rehabilitation is a personalised support, exercise and education program led by healthcare professionals to manage cardiovascular risk factors and assist in a patient’s recovery after a heart event or diagnosis. [5]

Such programs are recognised as one of the most cost-effective interventions to improve patient outcomes and for the secondary prevention of heart attack in many cardiovascular diseases. [6]

At the start of a program, a comprehensive assessment of an individual’s medical, physical, mental and emotional health is conducted. This is followed by goal-setting with the patient based on their baseline function and what they value and what their motivators are.

Cardiac rehabilitation can be delivered in multiple settings (face to face, in hospital or community, online or over the phone).

Each session of the program includes:

• supervised and personalised physical activity session that is safely increased based on the patient’s function and goals
• delivery of education about key heart health topics to support patient knowledge, self-management and risk-factor modification (e.g. medicine safety, nutrition and return to work tips)
• the opportunity to ask questions and interact with others who are also participating in a cardiac rehabilitation program

After the program, an assessment is conducted to reviews the patient’s progress toward their agreed goals and health status. Information is shared with their healthcare team and plans are made to support ongoing secondary prevention. [5]

References

1. Better Health Channel. Congestive heart failure (CHF). Department of Health & Human Services, State Government of Victoria, Australia. (2020). [Date cited 30 September 2020]. Available from: https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/congestive-heart-failure-chf

2. Healthline. Congestive Heart Failure (CHF). 2020 [Date cited 02 October 2020]. Available from: https://www.healthline.com/health/congestive-heart-failure

3. Atherton, J., Sindone, A., De Pasquale, C., Driscoll, A., MacDonald, P., Hopper, I., Kistler, P., Briffa, T., Wong, J., Abhayaratna, W., Thomas, L., Audehm, R., Newton, P., OˈLoughlin, J., Connell, C. and Branagan, M., 2018. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of heart failure 2018: Guideline summary. Medical Journal of Australia, 209(8), pp.363-369.

4. Atherton J, Sindone A, De Pasquale C, Driscoll A, MacDonald P, Hopper I et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Guidelines for the Prevention, Detection, and Management of Heart Failure in Australia 2018. Heart, Lung and Circulation. 2018;27(10):1123-1208. https://www.heartlungcirc.org/action/showPdf?pii=S1443-9506%2818%2931777-3

5. National Heart Foundation of Australia. Cardiac rehabilitation information for health professionals. (2019) [Date cited 02 October 2020]. Available from: https://journals.sagepub.com/doi/full/10.1177/2047487320913379

6. Ambrosetti M, Abreu A, Corrà U, Davos C, Hansen D, Frederix I et al. Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. European Journal of Preventive Cardiology. 2020;:204748732091337.

Research – Congestive Heart Failure Treatment Options Page | 10 Page 17 of 165

Research – Arthrogryposis Multiplex Congenita

Does environmental temperature impact people diagnosed with Arthrogryposis Multiplex Congenita? • If so, to what extent? • If so, what are the recommended/evidence based management strategies to address impact from hot/cold temperature variations?

Has there been any research into treatment measures for adults diagnosed with this condition? What are the recommended evidence based treatment measures for adults diagnosed with this condition?

Date: November 12, 2020

Requester(s): S22(1)(A)(ii) - (Senior Technical Advisor – TAB)

Researcher: S22(1)(A)(ii) (Research Team Leader – TAB)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

What is Arthrogryposis Multiplex Congenita? ……………………………………………………………………………. 2 Does environmental temperature impact people diagnosed with Arthrogryposis Multiplex Congenita? ……………………………………………………………………………………………………………………………. 2 Evidence based treatment measures ……………………………………………………………………………………….. 3 References ……………………………………………………………………………………………………………………………. 4

Research – Arthrogryposis Multiplex Congenita Page | 1 Page 18 of 165

What is Arthrogryposis Multiplex Congenita?

Arthrogryposis Multiplex Congenita (AMC) refers to a syndrome, apparent at birth, characterised by fixed positions of multiple joints and an associated limitation of movement [1]. The term arthrogryposis is derived from the Greek and literally means ‘bent joint’. Arthrogryposis multiplex congenita is a syndrome, not a disease entity [1]. Overall, arthrogryposis multiplex congenita is not rare; the incidence is generally approximately 1 in 3000 live births [2].

1) Distal joints are more frequently and more severely affected than proximal joints. Most common manifestations are [1]:
    - Talipes equinovarus (clubfoot)
    - Flexion deformities of the wrist

2) Muscles are usually atrophic, thus giving a fusiform appearance to the joints [1].
    - Hypotonia and weakness of the preserved movement occur
    - Tendon reflexes are depressed and often absent
    - Elicitation of tendon reflexes is often hindered by the joint contractures.

At least half of patients with arthrogryposis multiplex congenita exhibit congenital anomalies of other organs, craniofacial structures, other parts of the musculoskeletal system, or the central nervous system [2-5].

Does environmental temperature impact people diagnosed with Arthrogryposis Multiplex Congenita?

Unable to locate any evidence to suggest that changes in environmental temperature have an impact on people diagnosed with AMC.

Looking from an Osteoarthritis (OA) perspective, results from previous research investigating the influence of various weather factors on pain exacerbation are conflicting.

- A 2 year cohort study showed that barometric pressure and relative humidity influenced OA symptoms (pain and disability) in people with hip OA, but the contribution of these weather variables to the severity of OA symptoms (such as pain score increase) was not clinically relevant [6].
- Changes in barometric pressure were found to be associated with pain severity in knee OA patients in the study by McAlindon, Formica [7]. This was explained by the equilibrium between intra-articular pressure and atmospheric pressure, which has a physical role in stabilizing the joint.
- The study by Timmermans, Schaap [8] did not replicate the findings that day-to-day change in weather conditions was associated with joint pain in people with OA across Europe.
- A study by Fu, Metcalf [9] did not find that weather factors influenced the risk of pain exacerbations in people with knee OA.

Research – Arthrogryposis Multiplex Congenita Page 19 of 165

Evidence based treatment measures

Treatment typically involves early (from birth) intensive and continuous rehabilitation including bracing, splinting, range of motion exercises, and surgeries, which may improve contractures, provide the potential for functional ambulation and promote daily activities [10].

There is little research or evidence on the treatments for adults with AMC. In the narrative review by Wagner, Cherry [11] the authors provide an overview of rehabilitation over the lifespan (see table below). The main recommendations for teenagers/adults include:

• Ongoing exercise as part of a healthy lifestyle will help maintain ROM and mobility skills
• Muscle stretching and strengthening
• Use of orthoses for walking varies from person to person depending on needs and preferences
• Maintaining a healthy weight

References

• Ghosh PS, Volpe JJ. Chapter 31 - Arthrogryposis Multiplex Congenita. In: Volpe JJ, Inder TE, Darras BT, de Vries LS, du Plessis AJ, Neil JJ, et al., editors. Volpe’s Neurology of the Newborn (Sixth Edition): Elsevier; 2018. p. 874-86.e4.
• Darras BT. Neuromuscular disorders of infancy, childhood, and adolescence : a clinician’s approach. Second edition. ed: London : Academic Press; 2015.
• Banker BQ. Arthrogryposis multiplex congenita: Spectrum of pathologic changes. Human Pathology. 1986;17(7):656-72.
• Beckerman RC, Buchino JJ. Arthrogryposis Multiplex Congenita as Part of an Inherited Symptom Complex: Two Case Reports and a Review of the Literature. Pediatrics. 1978;61(3):417.
• Hall JG. Genetic aspects of arthrogryposis. Clin Orthop Relat Res. 1985(194):44-53.
• Dorleijn DMJ, Luijsterburg PAJ, Burdorf A, Rozendaal RM, Verhaar JAN, Bos PK, et al. Associations between weather conditions and clinical symptoms in patients with hip osteoarthritis: A 2-year cohort study. PAIN® [Internet]. 2014; 2014/04/01/; 155(4):[808-13 pp.]. Available from: http://www.sciencedirect.com/science/article/pii/S0304395914000268.
• McAlindon T, Formica M, Schmid CH, Fletcher J. Changes in Barometric Pressure and Ambient Temperature Influence Osteoarthritis Pain. The American Journal of Medicine [Internet]. 2007; 2007/05/01/; 120(5):[429-34 pp.]. Available from: http://www.sciencedirect.com/science/article/pii/S0002934306010266.
• Timmermans EJ, Schaap LA, Herbolsheimer F, Dennison EM, Maggi S, Pedersen NL, et al. The Influence of Weather Conditions on Joint Pain in Older People with Osteoarthritis: Results from the European Project on OSteoArthritis. The Journal of Rheumatology [Internet]. 2015; 42(10):[1885-92 pp.]. Available from: https://www.jrheum.org/content/jrheum/42/10/1885.full.pdf.
• Fu K, Metcalf B, Bennell KL, Zhang Y, Deveza LA, Robbins SR, et al. Association of weather factors with the risk of pain exacerbations in people with hip osteoarthritis. Scandinavian Journal of Rheumatology. 2020:1-6.
• Gagnon M, Caporuscio K, Veilleux L-N, Hamdy R, Dahan-Oliel N. Muscle and joint function in children living with arthrogryposis multiplex congenita: A scoping review. American Journal of Medical Genetics Part C: Seminars in Medical Genetics [Internet]. 2019; 181(3):[410-26 pp.]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31726.
• Wagner LV, Cherry JS, Sawatzky BJ, Fąfara A, Elfassy C, Eriksson M, et al. Rehabilitation across the lifespan for individuals with arthrogryposis. American Journal of Medical Genetics Part C: Seminars in Medical Genetics [Internet]. 2019; 181(3):[385-92 pp.]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.c.31729.

Research – Treatment of Somatic Symptom Disorder

AAT Matter (Access)

Brief

Summary of best practice treatment interventions for Somatic symptom Disorder

Date

01/03/21

Requester(s)

S22(1)(A) (Director - TAB)

Researcher

S22(1)(A) (Tactical Research Advisor – TAB/AAT)

Cleared

S22(1)(A)(ii) (Research Team Leader - TAB)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

2 Summary ……………………………………………………………………………………………………………………….. 2

3 What is Somatic Symptom Disorder? ………………………………………………………………………………… 2

3.1 Overview ………………………………………………………………………………………………………………… 2

3.2 Diagnosis ………………………………………………………………………………………………………………… 3

3.3 Prognosis ………………………………………………………………………………………………………………… 3

4 Treatment ……………………………………………………………………………………………………………………… 3

4.1 Cognitive Behavioural Therapy ………………………………………………………………………………….. 4

4.2 Psychotherapy …………………………………………………………………………………………………………. 4

4.3 Mindfulness-based therapy ………………………………………………………………………………………. 5

4.4 Medication ……………………………………………………………………………………………………………… 5

4.5 Electroconvulsive Therapy ………………………………………………………………………………………… 6

5 References …………………………………………………………………………………………………………………….. 7

Summary

• Research suggests that a multidisciplinary approach is required for the treatment and management of somatic symptom disorder.

• Research indicates the prevalent use of psychotherapy, mindfulness-based therapy, cognitive behavioural therapy, and medication, as treatment strategies for somatic symptom disorder. Further investigation of academic research indicates the use of electroconvulsive therapy.

• Cognitive behavioural therapy and psychotherapy are the most widely used and effective treatment for somatic symptom disorder, and they appear to be the first line treatments

• Research suggests that mindfulness-based therapy has been used effectively to treat a variety of physical and psychological disorders, including depression, anxiety, and chronic pain.

• Electroconvulsive therapy has been suggested as an effective treatment for somatic symptom disorder, however, further large scale randomised controlled trials are still required.

• There is little evidence that medication interventions are effective for the treatment of somatic symptom disorder. Where medication is considered necessary for treatment, antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are the preferred first-line pharmacological treatment

What is Somatic Symptom Disorder?

Overview

Somatic symptom disorder is characterized by one or more somatic symptoms that are accompanied by excessive thoughts, feelings, and/or behaviours related to the symptoms [1, 2].

Symptoms of somatic symptom disorder can include [3] :

• Specific sensations, such as pain or shortness of breath, or more general symptoms, such as fatigue or weakness

• Unrelated to any medical cause that can be identified, or related to a medical condition such as cancer or heart disease, but more significant than what’s usually expected

• A single symptom, multiple symptoms or varying symptoms

Diagnosis

To fulfil the diagnostic criteria, the following must be present [4]:

• One or more somatic symptoms that are distressing and/or result in significant disruption in daily life.
• One or more excessive thoughts, feelings, and/or behaviours related to the following somatic symptoms or associated health concerns:
  • (i) disproportionate and persistent thoughts about the seriousness of one’s symptoms;
  • (ii) persistently high level of anxiety about health or symptoms; and
  • (iii) excessive time and energy devoted to these symptoms or health concern.
• Although any one symptom may not be continuously present, the state of being symptomatic is persistent and lasts more than 6 months.

The condition is considered to be [4]:

• Mild, when only one of the psychobehavioral symptoms is fulfilled
• Moderate, when two or more of these symptoms are fulfilled
• Severe, when two or more of the psychobehavioral symptoms are fulfilled, plus when there are multiple somatic complaints (or one very severe somatic symptom).

Prognosis

Medications may provide some relief. Psychotherapy tends to proceed slowly, because the person is likely to have been living with the disorder for many years before starting treatment. It is difficult to give up long-standing patterns of behaviour, but with persistence and support, progress is possible [5].

Treatment

Treatment of somatic symptom disorder is multifaceted and should be tailored to the needs of each patient, keeping aware of cultural factors that influence their physical symptoms. Establishing a strong relationship with a provider and legitimizing symptoms are important aspects of treatment. Treatment strategies include [1, 6, 7]:

• Medications (such as antidepressants to address any underlying anxiety or depression) [6]

Cognitive Behavioural Therapy

A recent 2018 systematic review and meta-analysis [11] sourced indicates CBT is effective for treatment of somatic symptom disorder. The study aimed to update and give an overview of the evidence from published literature that focused on the efficacy of CBT in the management of somatoform disorders and medically unexplained physical symptoms (MUPS).

A comprehensive literature search was carried out through an electronic search of various databases on randomized controlled trials (RCTs). Primary outcome was the severity of somatic symptoms. Secondary outcomes were also measured based on severity of anxiety symptoms, severity of depressive symptoms, social functioning, physical functioning, doctor visits and the compliance with CBT, as well as follow-up visits.

• The study concluded that CBT is effective for the treatment of somatoform disorders and MUPS by reducing physical symptoms, psychological distress and disability.

• The results based on this meta-analysis indicated that CBT was superior to the usual care or enhanced care or waiting list.

• CBT significantly reduced somatic symptoms, anxiety symptoms and depressive symptoms as well as improving physical functioning

• The efficacy of CBT on somatic symptoms, anxiety symptoms, and depressive symptoms were maintained from three months to one year of follow up.

• The efficacy of CBT on improving social functioning and reducing doctor visits were not significant. Possible reasons could be complex aetiology of disability, in addition to the fact that improvements in social functioning takes considerable time, given the chronic nature of this disorder.

• Overall, the clinical efficacy of CBT was relatively modest and was most noticeable in terms of somatic symptoms, anxiety symptoms and depressive symptoms.

Psychotherapy

Evidence supports that nearly one-fourth of the patients undergoing psychotherapy report improvement after a single session, and nearly half of the patients reported improvement by the end of the eight session [12, 13].

Research – Treatment of Somatic Symptom Disorder Page 4 of 8 Page 25 of 165

Research – Treatment of Somatic Symptom Disorder

Page 5 of 8

When to Stop Psychotherapy in Somatoform Disorder?

There is no general consensus on “when to stop psychotherapy in somatoform disorder?” Conventionally, patients require 10–20 sessions of therapy. However, some patients may need more. The therapy can be stopped, when [12]:

• There is a substantial improvement of the symptoms
• There is serious transference or counter-transference (may be shifted to another therapist)
• There is no improvement or little improvement despite therapy (with adequate adherence to therapy, and even after evaluating and addressing factors that might contribute to nonresponse)
• The patient is not willing to continue therapy (as it is a collaborative process)

Mindfulness-based Therapy

It is suggested that MBT has been used effectively to treat a variety of physical and psychological disorders, including depression, anxiety, and chronic pain. Recently, several lines of research have explored the potential for MBT in treating somatization disorders, including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome [14].

A 2013 systematic review and meta-analysis [14] was carried out where thirteen studies were identified as fulfilling the criteria of employing randomized controlled trials to determine the efficacy of any form of MBT in treating somatization disorders. A meta-analysis of the effects of mindfulness-based therapy on pain, symptom severity, quality of life, depression, and anxiety was performed to determine the potential of this form of treatment. While limited in power, the meta-analysis indicated a small to moderate positive effect of MBT (compared to wait-list or support group controls) in reducing pain associated with somatization disorders, and improving quality of life in patients with this disorder. The study suggests that MBT may be effective in treating at least some aspects of somatization disorders. However, further research is warranted.

Medication

There is little evidence that medication interventions are effective for the treatment of somatic symptom disorder. Where medication is considered necessary for treatment, antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are the preferred first-line pharmacological treatment [15].

In current practice many people are treated ‘off label’ with medications that are intended for the treatment of anxiety, depression, and other mental health problems. However, it is unclear why medications such as antidepressants help to reduce the severity of medically unexplained physical symptoms [16].

A 2014 review of evidence aimed to assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder,

— PAGE TEXT END –

Electroconvulsive Therapy

A 2015 retrospective study suggests that electroconvulsive therapy (ECT) could be included as part of the existing treatment for refractory somatic symptom disorder, particularly in refractory cases with comorbid mood disorders [17].

The study performed a retrospective chart review of all patients treated with an index course of ECT at the Neuropsychiatric Program at the University of British Columbia Hospital from 2000 to 2010. The primary outcomes consisted of changes in pseudoneurologic symptoms, pain symptoms, cardiopulmonary symptoms, and gastrointestinal symptoms. Complaints were examined pre- and post-ECT. Of the 28 include participants, 21 received right unilateral ECT, six bifrontal and one received bitemporal. Eleven of 14 participants reported improvement in pain symptoms; one participant reported improvement in cardiopulmonary symptoms; and one of two participants reported improvement in gastrointestinal symptoms.

The study concluded that:

• ECT should be used broadly for the treatment of SSD, and that the study adds further support to the existing literature on the effectiveness of ECT.
• Based on the cases presented, the majority of patients with chronic refractory SSD with comorbid MDD benefited from the ECT treatment.
• There was improvement in both somatic features and affective symptoms.

When drawing conclusions from the study, the authors suggested that:

• One should be mindful that this is a retrospective collection of case reports, with all the implied limitations
• It cannot be known if ECT would be beneficial for all disorders in the SSD DSM-5 classifications even though on the whole, the majority of patients appeared to have benefited from the treatment

A 2016 case report [8] describes ECT as being helpful in somatic symptoms and pain disorders dating back to 1968, when 66 inpatients with hypochondriasis were treated with ECT, with a reported

Research - Treatment of Somatic Symptom Disorder

improvement rate of 50% [8, 18]. Several case reports and studies supporting the use of ECT to treat SSD and related diagnoses have been published since [8].

• The literature reviewed suggests that ECT can be effective in treating patients with SSD and pain disorders

• Excellent response to ECT has been described in neuropathic pain conditions, such as burning mouth syndrome, brachial plexopathy and CRPS, as well as in treating unexplained gastrointestinal pain

• Unilateral and bilateral methods of ECT administration were described as being effective in the literature reviewed above; courses varied significantly in length

The author concluded that:

• Based on the preliminary evidence reviewed, ECT should be considered as a treatment option for patients with SSD, particularly in the presence of comorbid depression and suicidal ideation, and particularly if their somatic symptoms include pain

• Randomized controlled trials of ECT for SSD and pain disorders should be completed; ECT compared with sham ECT for these conditions without comorbid affective disorders would be particularly useful

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 2013 [Fifth Edition (DSM-5):[Available from: https://www.psychiatry.org/psychiatrists/practice/dsm.
2. UpToDate. Somatic symptom disorder: Epidemiology and clinical presentation 2021 [Available from: https://www.uptodate.com/contents/somatic-symptom-disorder-epidemiology-and-clinical- presentation?sectionName=CLINICAL%20PRESENTATION&topicRef=110022&anchor=H56442671&s ource=see_link#H56442671.
3. Mayo Clinic. Somatic symptom disorder 2021 [Available from: https://www.mayoclinic.org/diseases-conditions/somatic-symptom-disorder/symptoms-causes/syc-
5. P Henningsen. Management of somatic symptom disorder. Dialogues Clin Neurosci [Internet]. 2018; 20(1):[23-31 pp.].
6. Harvard Health Publishing (Harvard Medical School). Somatic Symptom Disorder 2021 [Available from: https://www.health.harvard.edu/a_to_z/somatic-symptom-disorder-a-to-z.
7. Psychology Today. Somatic Symptom Disorder 2021 [Available from: https://www.psychologytoday.com/au/conditions/somatic-symptom-disorder.
8. S Kurlansik and M Maffei. Somatic Symptom Disorder 2016 [49-54]. Available from: https://www.aafp.org/afp/2016/0101/p49.html?utm_cmpid=aafp&utm_campaign=afp&utm_div=p ub&utm_mission=pe&utm_prod=afpj&hootPostID=c749e985d60313439b31880256aea1c3.
9. Augsburger ABJ. Somatic symptom disorder treated with electroconvulsive therapy. Pain Management [Internet]. 2016; 7(3).

Research – Treatment of Somatic Symptom Disorder Page 7 of 8 Page 28 of 165

Research – Treatment of Somatic Symptom Disorder

• Borisovskaya A, Augsburger JA. Somatic symptom disorder treated with electroconvulsive therapy. Pain Manag [Internet]. 2017 May; 7(3):[167-70 pp.].
• Leong K, Tham J, Scamvougeras A, Vila-Rodriguez F. Electroconvulsive therapy treatment in patients with somatic symptom and related disorders. Neuropsychiatr Dis Treat [Internet]. 2015; 11:[2565-72 pp.].
• Neera J, Gill J, Teodorczuk A, Zhan-jiang L, Jing S. The efficacy of cognitive behavioural therapy in somatoform disorders and medically unexplained physical symptoms: A meta-analysis of randomized controlled trials. Journal of Affective Disorders [Internet]. 2019; 245:[98-112 pp.].
• Agarwal V, Nischal A, Praharaj SK, Menon V, Kar SK. Clinical Practice Guideline: Psychotherapies for Somatoform Disorders. Indian J Psychiatry [Internet]. 2020; 62(Suppl 2):[S263-S71 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/32055068 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001354/
• Kadera SW, Lambert MJ, Andrews AA. How much therapy is really enough?: A session-by-session analysis of the psychotherapy dose-effect relationship 1996 [132-51]. Available from: https://www-ncbi-nlm-nih-gov.ez.library.latrobe.edu.au/pmc/articles/PMC3330412/
• Lakhan SE, Schofield KL. Mindfulness-based therapies in the treatment of somatization disorders: a systematic review and meta-analysis. PLoS One [Internet]. 2013; 8(8):[e71834-e pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/23990997 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753315/
• Australian Government - Open Arms - Veterans & Families Counselling. Somatic symptoms 2019 [Available from: https://www.openarms.gov.au/health-professionals/assessment-and-treatment/somatic-symptoms.
• Kleinstäuber M, Witthöft M, Steffanowski A, van Marwijk H, Hiller W, Lambert MJ. Pharmacological interventions for somatoform disorders in adults. Cochrane Database of Systematic Reviews [Internet]. 2014; (11). Available from: https://doi.org//10.1002/14651858.CD010628.pub2
• KaWai L, Joseph CWT, Scamvougeras A, Vila-Rodriguez F. Electroconvulsive therapy treatment in patients with somatic symptom and related disorders. Neuropsychiatric Disease and Treatment [Internet]. 2015 2019-06-15; 11:[2565-72 pp.].
• Pilowsky I. The Response to Treatment in Hypochondriacal Disorders. Australian and New Zealand Journal of Psychiatry [Internet]. 1968 1968/01/01; 2(2):[88-94 pp.]. Available from: https://www.tandfonline.com/doi/abs/10.3109/00048676809159218

Page 29 of 165

Research – Correlation between Weight Loss and Pain

Brief

Studies/research which has measured the correlation between weight loss and pain relief. Morbid obesity and back pain in particular. Contraindications in bariatric surgery – in particular diabetes and asthma.

Date

22/07/21

Requester(s)

S22(1)(A)(ii) - Senior Technical Advisor (TAB/AAT) S22(1)(A)(ii) Irrelevant - Assistant Director (TAB/AAT)

Researcher

S22(1)(A)(ii) - Research Team Leader (TAB)

Cleared

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

The contents of this document are OFFICIAL

1 Contents

2 Summary ……………………………………………………………………………………………………………………….. 1 3 References …………………………………………………………………………………………………………………….. 8

Summary

• Obesity is related to low back pain with increased risk for spine degeneration due to mechanical and inflammatory factors.
• Weight loss surgery can reduce the severity and prevalence of low back pain symptoms, most notably in patients who begin at the morbidly obese level. However, non-surgical interventions that target weight loss have not shown as promising results.
• Exercise interventions for the treatment of low back pain may be effective from several aspects including muscle strengthening and reduction of other obesity-related diseases with minimal risk

OFFICIAL

Research – Correlation between Weight Loss and Pain Page 1 of 9 Page 30 of 165

Correlation between Weight Loss and Pain Reduction

Estimates of the prevalence of obesity among persons with low back pain (LBP) range from 49.4% to 68.1% in men and women, respectively [1]. The current consensus on treatment for subacute or chronic LBP involves some form of exercise [2-4] or physical activity, along with the use of medications, physical modalities, psychological/behavioural treatment, injections or surgery [5].

Patients with LBP who are overweight or obese are often recommended to undergo a weight-loss program with or without the exercise/activity program [5]. These patients want to know whether: 1) Their weight/size is contributing to their LBP. 2) A weight reduction program by itself will reduce or eliminate their LBP. 3) An exercise/physical activity treatment program for their LBP will be safe and have the same benefit as it would in a smaller/thinner person 4) Their size/obesity will limit the effect of the other forms of non-operative treatment for LBP such as medications, modalities, behavioural treatment or spinal injections. 5) They should ever consider surgical options for a disc herniation, degenerative lumbar stenosis or other degenerative problems.

The medical literature for weight reduction as a treatment for LBP has very good evidence that weight reduction is an effective measure following obesity surgery, but less evidence for nonsurgical programs.

A 2019 systematic review evaluated the role of bariatric surgery (BS) for lumbar spine symptoms in obese patients [6]. A total of 10 studies (n = 2526) were included, all of which were case-control studies or case series. All studies reported that BS had a positive impact in improving low back pain symptoms and decreasing disability in severely obese patients. Although these studies are lower on the level of evidence hierarchy, all studies showed significant improvements when comparing pre-surgical to post-surgical outcomes which gives weight to the outcome. The lack of longer term follow-up is of concern; prospective studies with longer follow-up are necessary to confirm conclusions.

The literature regarding successful reduction of LBP with non-operative treatment of obesity is less conclusive but shows some signs of success. Early studies demonstrated only possible beneficial effects of weight loss on LBP. However, these results must be interpreted with caution as they have a high risk of bias due to poor methodological design [7, 8].

A comprehensive review of physical and rehabilitation interventions (not weight loss specific) for LBP [9]. The majority of trials existed for exercise therapy, behavioural treatment, multidisciplinary treatment and back school, with very few good quality trials on other commonly used treatments

Contraindications of Bariatric Surgery

Various organisations have endorsed and recommended BS for [11, 12]:

• All individuals with type 2 diabetes and BMI ≥40 kg/m²
• Individuals with BMI 35–40 kg/m² with inadequate glycaemic control despite lifestyle and optimal medical therapy.

There are no absolute contraindications to BS. Most would be included in lists of contraindications of any elective surgical procedure. Patients deemed to have an excessive operative risk should not be offered surgery.

In the majority of cases, BS should not be performed on patients with [11-13]:

• Limited life expectancy.
  • Severe heart failure
  • Unstable coronary artery disease

Research - Correlation between Weight Loss and Pain

• End-stage lung disease
• Active cancer treatment
• Portal hypertension
• Patients who are pregnant or who expect to be pregnant should be deferred.
• Active drug or alcohol abuse.
• Impaired intellectual capacity, i.e. untreated severe psychiatric illness.

The Royal Australian College of General Practitioners (RACGP) recommends that certain obesity-related complications should be identified and optimised pre-operatively [12]. These key complications include.

| Table 1. Pre-operative optimisation of obesity related complications | | — | — | — | | Obesity-related complication | Pre-operative screening and optimisation | Improvement after weight loss post-surgery | | Type 2 Diabetes Mellitus | Glycated haemoglobin (HbA1c) and fasting glucose to screen for diabetes Aim for good glycaemic control (HbA1c <7%) prior to surgery | Better glycaemic control and a reduced medication burden Diabetes remission in some cases | | Cardiovascular disease | Electrocardiogram (ECG) and cardiac risk assessment Referral to cardiology if high cardiovascular risk, presence of cardiac symptoms or abnormal ECG | Reduction of cardiovascular morbidity of >50% (compared to body mass index [BMI] and age matched controls) | | Non-alcoholic fatty liver disease | Liver function tests Consider abdominal ultrasound scan if liver function test increased, specifically to detect fibrotic liver disease | Improved liver histological appearance Potential regression of established liver disease | | Obstructive sleep apnoea (OSA) and asthma | Screening questionnaire (eg STOP-BANG) to identify those at risk for OSA Refer to sleep specialist if STOP-BANG score ≥3 | Significant improvement in apnoea–hypopnoea index Remission of OSA in some cases |

OFFICIAL

Research – Correlation between Weight Loss and Pain Page 4 of 9 Page 33 of 165

OFFICIAL

Research – Correlation between Weight Loss and Pain

Page 5 of 9

Page 34 of 165

Table 2.

Table 2.

References

1. Heuch I, Hagen K, Heuch I, Nygaard Ø, Zwart J-A. The Impact of Body Mass Index on the Prevalence of Low Back Pain: The HUNT Study. Spine [Internet]. 2010; 35(7). Available from: https://journals.lww.com/spinejournal/Fulltext/2010/04010/The_Impact_of_Body_Mass_Index_on_the_Prevalence_of.9.aspx.

2. van Middelkoop M, Rubinstein SM, Verhagen AP, Ostelo RW, Koes BW, van Tulder MW. Exercise therapy for chronic nonspecific low-back pain. Best Practice & Research Clinical Rheumatology [Internet]. 2010; 24(2):[193-204 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S1521694210000033.

3. Hayden JA, van Tulder MW, Malmivaara AV, Koes BW. Meta-Analysis: Exercise Therapy for Nonspecific Low Back Pain. Annals of Internal Medicine [Internet]. 2005; 142(9):[765-75 pp.]. Available from: https://www.acpjournals.org/doi/abs/10.7326/0003-4819-142-9-200505030-00013.

4. Hayden J, van Tulder MW, Malmivaara A, Koes BW. Exercise therapy for treatment of non-specific low back pain. Cochrane Database of Systematic Reviews [Internet]. 2005; (3). Available from: https://doi.org//10.1002/14651858.CD000335.pub2.

5. Atchison JW, Vincent HK. Obesity and low back pain: relationships and treatment. Pain Management [Internet]. 2011; 2(1):[79-86 pp.]. Available from: https://doi.org/10.2217/pmt.11.64.

6. Joaquim AF, Helvie P, Patel AA. Bariatric Surgery and Low Back Pain: A Systematic Literature Review. Global Spine Journal [Internet]. 2019; 10(1):[102-10 pp.]. Available from: https://doi.org/10.1177/2192568219826935.

7. Kotowski SE, Davis KG. Influence of weight loss on musculoskeletal pain: Potential short-term relevance. Work [Internet]. 2010; 36:[295-304 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/20683164/.

8. Roffey DM, Ashdown LC, Dornan HD, Creech MJ, Dagenais S, Dent RM, et al. Pilot evaluation of a multidisciplinary, medically supervised, nonsurgical weight loss program on the severity of low back pain in obese adults. The Spine Journal [Internet]. 2011; 11(3):[197-204 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S1529943011000787.

9. van Middelkoop M, Rubinstein SM, Kuijpers T, Verhagen AP, Ostelo R, Koes BW, et al. A systematic review on the effectiveness of physical and rehabilitation interventions for chronic nonspecific low back pain. Eur Spine J [Internet]. 2011; 20(1):[19-39 pp.]. Available from: https://link.springer.com/article/10.1007/s00586-010-1518-3.

10. Robson EK, Hodder RK, Kamper SJ, O’Brien KM, Williams A, Lee H, et al. Effectiveness of Weight-Loss Interventions for Reducing Pain and Disability in People With Common Musculoskeletal Disorders: A Systematic Review With Meta-Analysis. Journal of Orthopaedic & Sports Physical Therapy [Internet]. 2020; 50(6):[319-33 pp.]. Available from: https://doi.org/10.2519/jospt.2020.9041.

11. National Institutes of Health. Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr [Internet]. 1992; 55(2 Suppl):[615s-9s pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/1733140/.

12. Ching Lee P, Dixon J. Bariatric–metabolic surgery: A guide for the primary care physician. Australian Family Physician [Internet]. 2017; 46:[465-71 pp.]. Available from: http://www.racgp.org.au/afp/2017/july/bariatric–metabolic-surgery-a-guide-for-the-primary-care-physician/.

OFFICIAL

13. Stahl JM, Malhotra S. Obesity Surgery Indications And Contraindications. 2021. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing

Copyright © 2021, StatPearls Publishing LLC. Available from: https://pubmed.ncbi.nlm.nih.gov/30020657/.

Research – Therapy Programs for Lupus

Treatment options available for any inpatient or outpatient therapy programs in Australia for Systemic Lupus Erythematosus or other arthritic conditions.

Brief

A potential participant seeking access. Uncertainty regarding permanency and the availability of evidence based treatments in Australia for Lupus (and other related arthritic conditions) and how these impact on permanency of the impairment.

Date

30/07/2021

Requester(s)

S22(1)(A) - Senior Technical Advisor (TAB/AAT)

Researcher

S22(1)(A)(ii) - Research Team Leader (TAB)

Cleared

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice.

The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

• Summary
• What is Lupus?
• Clinical Presentation
  • Skin
  • Musculoskeletal system
  • Pulmonary system
  • Cardiovascular
  • Gastrointestinal
  • Haematological
  • Central Nervous System
  • Renal

Summary

What is Lupus?

Clinical Presentation

• Skin
• Musculoskeletal system
• Pulmonary system
• Cardiovascular
• Gastrointestinal
• Haematological
• Central Nervous System
• Renal

Summary

Systemic lupus erythematosus is a chronic autoimmune disorder. Sufferers experience times of remission and flare ups of the disease.

The condition can affect many body systems including the skin, musculoskeletal, pulmonary system, cardiovascular, gastrointestinal, renal, and haematological and central nervous system.

First line treatment of the disease includes non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose steroids. General recommendations include avoiding triggers, sun protection, proper diet and nutrition, and smoking cessation.

Two non-medical treatments which have shown success in reducing pain, fatigue, depression, anxiety and improving quality of life for people with SLE are psychological and exercise interventions.

What is Lupus?

Lupus is a chronic disease that occurs due to abnormal immunological function. This leads to the body’s immune system attacking its own tissues and organs (autoimmune disease). Patients experience periodic flares of varying severity or instances in which no observable signs or symptoms are present. There are four main types of lupus:

• Neonatal
• Discoid
• Drug-induced
• Systemic lupus erythematosus (SLE)
  • SLE affects the majority of patients. It is differentiated from other types by its multi-organ system effects.
  • SLE is diagnosed in approximately 20 to 150 persons per 100,000 and is typically seen in females of child-bearing age; however, it may affect male or female patients at any age [1, 2].

References

[1] [2]

Clinical Presentation

The presentation of SLE can be complex, considering the number of organ systems that can be affected by the disease [4]. Patients experience flare-ups to varying degrees as well as periods of disease remission. Although certain signs and symptoms are common in SLE, every patient presents with a unique set of identifiers. General signs and symptoms observed in SLE include [2, 4]:

• Fever
• Fatigue
• Weight loss. The skin, musculoskeletal system, and pulmonary system are primarily affected [4]. Cardiovascular, gastrointestinal, renal, and haematological systems, as well as the central nervous system (CNS) are also affected, however, less commonly [4].

Skin

SLE patients who report symptoms involving the skin most commonly have a red rash on the nose and cheeks following exposure to the sun. This “butterfly” rash is identified in a significant number of SLE patients at some point during the disease course [4]. Patients experiencing photosensitivity reactions also report skin rashes on other areas of the body that were exposed to the sun. Other symptoms associated with skin manifestations include alopecia, Reynaud’s phenomenon, and sores in the mouth or nose [3].

Musculoskeletal system

Musculoskeletal involvement includes arthralgias, myalgia, and/or arthritis. Arthritis can affect any minor or major joints, commonly presenting as painful, stiff joints accompanied by either occasional or persistent inflammation [5]. Up to 95% of patients with SLE have intermittent arthritis [6].

Pulmonary system

Patients with pulmonary symptoms report painful breathing, coughing, and shortness of breath. Pleural effusion and pulmonary hypertension have also been reported [7].

Cardiovascular

Cardiovascular effects often include pericarditis, myocarditis, endocarditis, and coronary artery disease. It has been theorized that certain drugs used to treat SLE (e.g.,

Management

The approach to the treatment of signs and symptoms of lupus depends on the type and the severity of disease.

Pharmacological Treatment

The overall aim of pharmacotherapy is to control disease activity. Mild activity can be managed with non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose steroids, but more severe manifestations require prompt treatment with moderate-to-high doses of steroids to minimise organ damage [11]. Steroid-sparing immunosuppressive medications should be considered early to prevent steroid-related morbidities. Hydroxychloroquine is an effective treatment in SLE, especially for arthritis and rash [11]. Furthermore, it has a protective effect in reducing damage accrual in the long term, and confers a survival benefit in SLE patients. Hydroxychloroquine is well tolerated and, when dosed appropriately, ocular toxicity is very rare [12].

Non-pharmacological interventions

In addition to pharmacological interventions, the general recommendation for all patients include [4]:

• Sun protection
• Proper diet and nutrition
• Exercise
• Smoking cessation
• Appropriate immunizations
• Management of comorbid conditions.

The general signs and symptoms of SLE often lead to cognitive difficulties, depression and pain [14]. Although pharmacologic treatments have improved overall survival, SLE continues to have a profound impact on quality of life [15]. A study of health resource utilization cohort of 707 SLE patients showed that 50% used alternative therapies and at similar rates across Canada, the United States, and the United Kingdom [16]. Despite a high rate of integrative medical therapies used by SLE patients, the scientific study of various types of non-pharmacologic therapies in SLE is very limited.

Official

Research – Therapy Programs for Lupus Page 5 of 7

Page 43 of 165

Research - Therapy Programs for Lupus

A systematic review and meta-analysis by Zhang et al compared the effects of psychological interventions among SLE patients [17]. The authors identified 6 randomised controlled trials (RCTs) and found that psychological interventions significantly reduced anxiety, depression, stress and disease activity, compared to controls. No statistically significant differences were observed in mental health, fatigue and physical function.

In terms of exercise interventions, a systematic review with meta-analysis by O’Dwyer et al showed that exercise intervention improved cardiorespiratory capacity, reduced fatigue, and improved psychological functions, compared to controls [18]. Moreover, exercise interventions were safe, did not adversely affect disease activity and were well tolerated by a majority of SLE patients [18].

A more recent systematic review of RCTs investigating psychological, exercise and acupuncture interventions found promising results for the improvement of fatigue, depression, pain and quality of life for patients with SLE. Of note, no studies demonstrated an improvement in disease activity after 5–52 weeks of non-pharmacological therapies.

References

1. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis & Rheumatism [Internet]. 1998 1998/05/01; 41(5):[778-99 pp.]. Available from: https://doi.org/10.1002/1529-0131(199805)41:5<778::AID-ART4>3.0.CO;2-V.
2. Pons-Estel GJ, Alarcón GS, Scofield L, Reinlib L, Cooper GS. Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus. Seminars in Arthritis and Rheumatism [Internet]. 2010 2010/02/01/; 39(4):[257-68 pp.]. Available from: https://www.sciencedirect.com/science/article/pii/S0049017208001972.
3. D’Cruz DP. Systemic lupus erythematosus. Bmj [Internet]. 2006 Apr 15 PMC1440614]; 332(7546):[890-4 pp.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440614/.
4. Maidhof W, Hilas O. Lupus: an overview of the disease and management options. P T [Internet]. 2012; 37(4):[240-9 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/22593636.
5. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med [Internet]. 2008 Feb 28; 358(9):[929-39 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/18305268.
6. Mahmoud K, Zayat A, Vital EM. Musculoskeletal manifestations of systemic lupus erythmatosus. Current Opinion in Rheumatology [Internet]. 2017 //; 29(5):[486-92 pp.]. Available from: https://www.ingentaconnect.com/content/wk/bor/2017/00000029/00000005/art00010 https://doi.org/10.1097/BOR.0000000000000421.
7. Powers DB. Systemic lupus erythematosus and discoid lupus erythematosus. Oral Maxillofac Surg Clin North Am [Internet]. 2008 Nov; 20(4):[651-62 pp.]. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1042369908000757.
8. Sitia S, Atzeni F, Sarzi-Puttini P, Di Bello V, Tomasoni L, Delfino L, et al. Cardiovascular involvement in systemic autoimmune diseases. Autoimmun Rev [Internet]. 2009 Feb; 8(4):[281-6 pp.]. Available from: https://www.sciencedirect.com/science/article/abs/pii/S156899720800181X.
9. Quismorio JFP. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. Dubois’ lupus erythematosus [Internet]. 1997 1997:[802-5 pp.]. Available from: https://ci.nii.ac.jp/naid/10005224619/en/

OFFICIAL

Research – Therapy Programs for Lupus Page 6 of 7

Page 44 of 165

Research - Therapy Programs for Lupus

Nowling TK, Gilkeson GS. Mechanisms of tissue injury in lupus nephritis. Arthritis Res Ther [Internet]. 2011 PMC3334648]; 13(6):[250 p.]. Available from: https://arthritis-research.biomedcentral.com/articles/10.1186/ar3528. Apostolopoulos D, Hoi A. Systemic lupus erythmatosus When to consider and management options. Australian Family Physician [Internet]. 2013 10/01; 42:[696-700 pp.]. Available from: http://www.racgp.org.au/afp/2013/october/systemic-lupus-erythmatosus/. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology [Internet]. 2011 Feb; 118(2):[415-22 pp.]. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0161642010012091. Hahn BH. Belimumab for Systemic Lupus Erythematosus. New England Journal of Medicine [Internet]. 2013; 368(16):[1528-35 pp.]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMct1207259. Fangtham M, Kasturi S, Bannuru RR, Nash JL, Wang C. Non-pharmacologic therapies for systemic lupus erythematosus. Lupus [Internet]. 2019; 28(6):[703-12 pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/30961418. McElhone K, Abbott J, Teh LS. A review of health related quality of life in systemic lupus erythematosus. Lupus [Internet]. 2006; 15(10):[633-43 pp.]. Available from: https://journals.sagepub.com/doi/abs/10.1177/0961203306071710. Moore AD, Petri MA, Manzi S, Isenberg DA, Gordon C, Senécal JL, et al. The use of alternative medical therapies in patients with systemic lupus erythematosus. Trination Study Group. Arthritis Rheum [Internet]. 2000 Jun; 43(6):[1410-8 pp.]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/1529-0131(200006)43:6%3C1410::AID-ANR27%3E3.0.CO;2-U. Zhang J, Wei W, Wang CM. Effects of psychological interventions for patients with systemic lupus erythematosus: a systematic review and meta-analysis. Lupus [Internet]. 2012 Sep; 21(10):[1077-87 pp.]. Available from: https://journals.sagepub.com/doi/abs/10.1177/0961203312447667. O’Dwyer T, Durcan L, Wilson F. Exercise and physical activity in systemic lupus erythematosus: A systematic review with meta-analyses. Semin Arthritis Rheum [Internet]. 2017 Oct; 47(2):[204-15 pp.]. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0049017216303717.

OFFICIAL

Research – Therapy Programs for Lupus Page 7 of 7

                         Page 45 of 165

New daily persistent headache

The content of this document is OFFICIAL.

Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters, they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Research question: What is New daily persistent headache? How is it diagnosed? What are its causes, functional impacts, prevalence, treatment? Date: 23/06/2022 Requestor: S22(1)(A)(ii) - Irrelevant Endorsed by (EL1 or above): S22(1)(A)(ii) - Irrelevant Material Researcher: S22(1)(A)(ii) - Irrelevant Material Cleared by: S22(1)(A)(ii) - Irrelevant Material

Contents

New daily persistent headache …………………………………………………………………………………….. 1

• Contents ……………………………………………………………………………………………………….. 1
• Summary ………………………………………………………………………………………………………. 2
• Diagnosis ………………………………………………………………………………………………………. 2
• Symptoms and functional impact ………………………………………………………………………. 3
• Prevalence …………………………………………………………………………………………………….. 3
• Treatment ……………………………………………………………………………………………………… 4
• References ……………………………………………………………………………………………………. 4
• Version control ……………………………………………………………………………………………….. 5

Summary

New daily persistent headache (NDPH) is a kind of chronic daily headache that is characterised by sudden (rather than gradual) onset. While pain is a necessary feature of the condition, the type, location and severity of pain vary. Most people report experiencing moderate to severe pain with a type and location similar to migraine.

Little is known about prevalence, cause or effective treatments. Most cases of NDPH do not respond to existing treatments. Many cases last years or even decades, though more research is required around duration of the condition. As a treatment resistant chronic pain condition, it can have a disabling effect, interfering with the performance of everyday activities.

There is some disagreement in the research community regarding the diagnosis of NDPH. The condition is included in the International Classification of Headache Disorders 3rd Edition (ICHD-3) and some argue that its peculiar onset and resistance to treatment justifies a separate diagnostic entity. Others argue the diagnosis of NDPH is not distinct enough from chronic migraine or chronic tension-type headache to merit its own classification or that NDPH is an artefact of a psychiatric condition.

Diagnosis

According to the ICHD-3, NDPH is a primary headache disorder meeting the following criteria:

• A. Persistent headache
• B. Distinct and clearly remembered onset, with pain becoming continuous and unremitting within 24hrs
• C. Present for > 3 months
• D. Not better accounted for by another ICHD-3 diagnosis (Headache Classification Committee, 2018, p.55)

The type, severity and location of pain is not specified. Pain can be migraine-like or tension-type like. Criteria B is one of the distinct features of NDPH. People with NDPH can usually describe the day their headache started. ICHD-3 identifies two sub-types: a self-limiting subtype resolves spontaneously within a few months; and a refractory sub-type which is resistant to treatment and can last years or decades (Headache Classification Committee, 2018).

Criteria D requires particular attention. MRI and other neuroimaging methods will not reveal anything atypical but these methods are needed to exclude other potential diagnoses (Peng & Wang, 2022; Yamani & Olesen, 2019). If the symptoms of NDPH are observed with an underlying trigger, then the primary diagnosis should be the precipitating cause and a secondary diagnosis can be offered. For example, a common trigger for NDPH is infection and cases have been observed recently following COVID19 infection (Peng & Wang, 2022; Lobo et al, 2022; Uniyal et al, 2021; Yamani & Olesen, 2019). According to ICHD-3:

V1.0 23-06-2022 NDPH Page 2 of 5 OFFICIAL Page 47 of 165

Research paper

OFFICIAL For Internal Use Only

When a new headache occurs for the first time in close temporal relation to an infection, it is coded as a secondary headache attributed to that infection. This remains true when the new headache has the characteristics of any of the primary headache disorders classified in Part One of ICHD-3 (Headache Classification Committee, 2018, p.129).

Despite this, studies often identify triggers in people diagnosed with NDPH. Between 47-66% of instances of NDPH have some notable precipitating event with approximately 22% following infection (Papetti et al, 2021; Yamani & Olesen, 2019). Cases of NDPH following infection may not be classified as secondary headaches because pain continued for months after resolution of the infection (Papetti et al, 2021). In contrast, some argue that the distinction between primary and secondary headache is vague and arbitrary and that too little is known about the cause of NDPH to draw these distinctions reliably (Peng & Wang, 2022; Lobo et al, 2022).

There is further reason to be sceptical of NDPH’s existence as a separate condition. Lobo et al (2022) argue that there are no useful clinical differences between NDPH on the one hand, and chronic migraine or tension-type headache on the other. Uniyal et al (2021) suggest that characteristic features of NDPH, that is, the persistence and the vivid memory of onset, may be related to the presence of somatic symptom disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders 5th edition.

Prevalence

NDPH is rare and there are not many epidemiological studies. Prevalence predictions vary. NDPH is a kind of chronic daily headache and the prevalence of chronic daily headache is predicted to be around 4% in the general population (Peng & Wang, 2022). Uniyal et al (2021) put the proportion of people with chronic daily headache experiencing NDPH at 2.2-3.25%. This would mean the prevalence of NDPH is roughly 0.13% of the general population.

Two studies from Spain and Norway predicted 1 year prevalence at 0.03% and 0.1% respectively. However, both studies use older criteria which restrict NDPH to only tension-type headaches. Now, studies show that migraine-like headaches make up a higher proportion of NDPH. Hence, the prevalence of NDPH could be significantly higher than earlier studies predicted (Peng & Wang, 2022; Yamani & Olesen, 2019).

More children than adults experience NDPH (Peng & Wang, 2022; Lobo et al, 2022). More women than men experience NDPH (Yamani & Olesen, 2019; Evans & Turner, 2021).

Symptoms and functional impact

The main symptom of NDPH is head pain. However, the type, location and severity of pain is different among patients. In a study of 46 people, Papetti et al found 11 rated their pain as mild, 26 as moderate and 12 as severe (Papetti et al, 2021). In their larger study of 328 people, Evans and Turner found 28 rated their pain as mild, 190 as moderate and 102 as severe (Evans & Turner, 2021). In most cases NDPH is migraine-like (unilateral, pulsating,

V1.0 23-06-2022 NDPH Page 3 of 5 OFFICIAL Page 48 of 165

Research paper

OFFICIAL For Internal Use Only

moderate or severe pain) compared to tension-type-like (bi-lateral, pressing or tightening, mild or moderate pain), though both presentations are possible (Evans & Turner, 2021; Papetti et al, 2021; Headache classification committee, 2018). Other symptoms can include aversion to lights and sounds, vomiting, sleep disturbances, light-headedness, blurred vision, stiffness of the neck, numbness or tingling sensations, aura, vertigo and lethargy (Peng & Wang, 2022; Papetti et al, 2021; Evans & Turner, 2021).

Co-occurring mental health conditions are also common. Between 32.7% and 85.5% of NDPH patients also have a psychiatric condition (Peng & Wang, 2022). In Yamani and Olesen’s systematic review (2019), 65% of subjects had severe anxiety and 40% had severe depression. In Uniyal et al’s study (2021), just under 50% of people with NDPH met criteria for severe anxiety according to the Generalised Anxiety Disorder Assessment.

The disability impact of NDPH is high according to studies using the Migraine Disability Assessment Test, Headache Impact Test and Short Form 36 health Survey (Lobo et al, 2022; Peng & Wang, 2022).

Treatment

Most cases of NDPH are resistant to treatment. Some cases resolve themselves spontaneously within a few months (self-limiting sub-type), but these are the minority. In a study of 328 people, Evans and Turner note that 305 had the refractory sub-type and only 14 had the self-limiting sub-type. If NDPH does resolve itself, most cases resolve after 2 years and a lesser percentage resolve after 5 years (Evans & Turner, 2021). Some documented cases have lasted decades (Peng & Wang, 2022; Evans & Turner, 2021). With some variations in exact proportion, most studies agree that refractory-type NDPH is far more common (Lobo et al, 2022; Peng & Wang; Evans & Turner, 2021; Yamani & Olesen, 2019).

There is no specific treatment protocol for NDPH. Most treatments tend to follow the type of headache, that is, if a patient has migraine-like NDPH their physician is likely to prescribe treatments which are effective for migraine. There is some evidence that greater occipital nerve block, ketamine solution or OnabotulinumtoxinA therapy can reduce severity or frequency of headaches in a minority of cases (Peng & Wang, 2022; Lobo et al, 2022; Yemeni & Olesen, 2019).

References

Headache classification committee of the International Headache Society (IHS). (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia: An International Journal of Headache, 38(1), 1–211. https://doi.org/10.1177/0333102417738202 Lobo, R., Wang, M., Lobo, S., & Bahra, A. (2022). Time to retire “New daily persistent headache”: Mode of onset of chronic migraine and tension-type headache. Cephalalgia:

V1.0 23-06-2022 NDPH Page 4 of 5 OFFICIAL Page 49 of 165

Research paper

OFFICIAL For Internal Use Only

An International Journal of Headache, 42(4–5), 385–395.

https://doi.org/10.1177/03331024211044440

Papetti, L., Sforza, G., Tarantino, S., Moavero, R., Ruscitto, C., Ursitti, F., Ferilli, M. A. N., Vigevano, F., & Valeriani, M. (2021). Features and management of new daily persistent headache in developmental-age patients. Diagnostics (Basel, Switzerland, 11(3), 385).

https://doi.org/10.3390/diagnostics11030385

Peng, K.-P., & Wang, S.-J. (2022). Update of new daily persistent headache. Current Pain and Headache Reports, 26(1), 79–84.

https://doi.org/10.1007/s11916-022-01005-1

Uniyal, R., Chhirolya, R., Tripathi, A., Mishra, P., & Paliwal, V. K. (2022). Is new daily persistent headache a fallout of somatization? An observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(1), 541–547.

https://doi.org/10.1007/s10072-021-05236-9

Yamani, N., & Olesen, J. (2019). New daily persistent headache: a systematic review on an enigmatic disorder. The Journal of Headache and Pain, 20(1), 80.

https://doi.org/10.1186/s10194-019-1022-z

Version control

V1.0 23-06-2022 NDPH Page 5 of 5 OFFICIAL Page 50 of 165

Corticobasal syndrome

The content of this document is OFFICIAL.

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters, they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Research question:

What is Corticobasal syndrome? How is it diagnosed? What are effective treatments or management path?

Date: 6/7/22

Requestor: S22(1)(A)(ii) - Irrelevant Material

Endorsed by (EL1 or above): S22(1)(A)(ii) - Irrelevant

Researcher: S22(1)(A)(ii) - Irrelevant Material

Cleared by: S22(1)(A)(ii) - Irrelevant Material

Contents

• Corticobasal syndrome
  • Contents
  • Summary
  • Corticobasal syndrome
    • Background
    • Symptoms
    • Diagnosis
    • Imaging
    • Treatment
  • References/Bibliography
  • Version control

V1.0 06-07-2022 Corticobasal Syndrome Page 1 of 6 OFFICIAL Page 51 of 165

Research Paper

Official For Internal Use Only

Summary

Corticobasal syndrome (CBS) is a rare, slowly progressive, neurodegenerative disorder. Diagnosis of CBS is made by a neurologist based on clinical signs and symptoms. While pathological changes may be evident on MRI, the absence of changes does not exclude the disorder. Common manifestations of CBS are asymmetric progressive rigidity, apraxia, limb dystonia and frontal-cognitive deficits. CBS progresses to disability and loss of independence, with a poor long-term prognosis – average life expectancy post-diagnosis is 7 years. Death is typically related to complications of being bedridden such as pneumonia aspiration, pulmonary embolus and sepsis infection. There are no effective treatments to stop or slow progression of the disease. Clinical management is aimed at improving functional ability where possible and reducing the life-threatening risks from increasing immobility.

Corticobasal Syndrome

Background

Corticobasal syndrome is a rare, progressive neurodegenerative disorder (Mennella & Schub, 2018; Stasio et al, 2019). Prevalence of CBS is estimated to be 4.9-7.3:100,000 (Constantinides et al, 2019; Wilson et al, 2021), and average life expectancy after diagnosis is 7 years (Constantinides et al, 2019; Wilson et al, 2021). Death is typically from complications from being bedridden, such as aspiration pneumonia, pulmonary embolism, or sepsis infection (Mennella & Schub, 2018). Typical age of presentation for CBS is between 50-70 years old (Wilson et al, 2021). While some literature refers to CBS as corticobasal degeneration (CBD) or cortical basal ganglionic degeneration (Mennella & Schub, 2018), CBS requires a clinical diagnosis whereas CBD has pathological diagnostic criteria (Parmera et al, 2016; Wilson et al, 2021). Another difference is CBD diagnostic criteria has a particular age of onset and excludes anyone with a positive family history or known tau-protein mutation, which is not the case for CBS diagnosis (Constantinides et al, 2019). CBS is a disorder of movement, cognition and behaviour (Wilson et al, 2021). It has a gradual onset of neurologic symptoms in the absence of stroke or tumour, and progression of the disease is slow (Mennella & Schub, 2018; Wilson et al, 2021). Patients who experience a dramatic presentation or rapid degeneration should have other diagnoses considered, for example Creutzfeldt-Jacob disease or Hashimoto’s encephalitis (Wilson et al, 2021). Multiple pathologies may underlie CBS, such as CBD, Alzheimer’s disease, frontotemporal degeneration or progressive supranuclear palsy (Constantinides et al, 2021; Wilson et al, 2021). It is believed CBS results from abnormal levels of tau protein accumulating in certain brain cells leading to degeneration (Mennella & Schub, 2018).

V1.0 06-07-2022 Corticobasal Syndrome Page 2 of 6 OFFICIAL Page 52 of 165

[Research Paper]

Symptoms

Onset of CBS is gradual. Neurological degeneration manifests in motor, sensory, cognitive and behavioural signs and symptoms (Mannella & Schub, 2018). Presenting symptoms of CBS can vary between individuals as different parts of the brain may be affected (Monash Health, n.d.). Limb symptoms are typically asymmetrical early in the disease course, however eventually progress to the whole body (Mannella & Schub, 2018).

Most common symptoms reported in the literature include:

• Limb apraxia – disorder of skilled movement evident as an inability to execute purposeful movement (Mannella & Schub, 2018); occurs in approximately 70-80% of CBS cases, usually asymmetrical
• Alien-limb – loss of control over a limb such that it seems to have a mind of its own (Mannella & Schub, 2018); occurs in approximately 50% of cases of CBS (Constantinides et al, 2019; Wilson et al, 2021)
• Extrapyramidal dysfunction manifest as focal or asymmetric rigidity or focal or asymmetric limb dystonia early in the disease course (Mannella & Schub, 2018; Wilson et al, 2021); rigidity is evident in over 73% of cases (Wilson et al, 2021)
• Dystonia is present in 40% of cases, with 80% being upper limb; usually presents in first two years of disease course and related to myoclonus (Constantinides et al, 2019)
• Parkinsonism evident as slowed, awkward voluntary movements with additional involuntary movements, generally asymmetrical (Constantinides et al, 2019; Wilson et al, 2021)
• Tremors are typically not present, but if evident they are then usually a positional or action tremor; can be irregular with myoclonic quality (Constantinides et al, 2019)
• Postural instability
• Aphasia – typically non-fluent, slowed, effortful and/or groping apraxia of speech and grammatical errors, sometimes there will be difficulty with word retrieval and sentence repetition (Wilson et al, 2021)
• Cognitive deficits from frontal lobe executive dysfunction (Mannella & Schub, 2018)
• Persistent pain may be a common non-motor symptom (Mannella & Schub, 2018)

Diagnosis

Diagnosis of CBS is difficult due to overlapping features of other disorders, the lack of diagnostic tests and biological markers to confirm a CBS diagnosis, and the heterogenous presentation of the syndrome (Constantinides et al, 2021; Monash Health, n.d.; Parmera et al, 2016).

V1.0 06-07-2022 Corticobasal Syndrome Page 3 of 6

[Research Paper]

OFFICIAL For Internal Use Only

Table 1 shows Cambridge clinical criteria for CBS. For a positive diagnosis, patients must display all mandatory criteria, and two of both major and minor criteria (Wilson et al, 2021).

Table 1

Cambridge clinical criteria, modified Bak and Hodges, for CBS diagnosis (Wilson et al, 2021)

• Mandatory criteria

  • Insidious onset
  • No sustained response to levodopa treatment

• Major criteria

  • Akinetic rigid syndrome
  • Limb apraxia
  • Speech and language impairment

• Minor criteria

  • Focal or segmental myoclonus
  • Asymmetric dystonia
  • Alien limb syndrome
  • Cortical sensory loss or dyscalculia
  • Frontal executive dysfunction
  • Visuospatial defects

3.4 Imaging

It should be noted that CBS diagnosis can be supported, but not refuted, by features of imaging (Wilson et al, 2021). Although cortical and subcortical changes on MRI have been well described in the literature, it is unclear at what stage of the disease these findings have been identified.

Neural changes identified by imaging will depend on the underlying pathology responsible for the CBS (Constantinides et al, 2019). Most commonly, MRI will demonstrate asymmetric cortical changes such as grey matter atrophy or dysfunction evident as hypometabolism or hypoperfusion (Wilson et al, 2021). Changes particularly affect frontal-parietal regions encompassing the premotor, motor and sensory association cortices, and typically develop contralateral to the more affected side of the body (Wilson et al, 2021). Perirolandic patterns of change relate directly to the symptoms of CBS, and the finding of asymmetrical perirolandic atrophy or hypometabolism on imaging supports the clinical diagnosis of CBS (Wilson et al, 2021). (N.b. The perirolandic region of the brain is also known as the central lobe or paracentral area. It incorporates the primary motor cortex, primary somatosensory cortex (the main sensory receptive area) and paracentral lobule (motor and sensory region) (Zuo et al, 2020)).

V1.0 06-07-2022 Corticobasal Syndrome Page 4 of 6 OFFICIAL Page 54 of 165

Treatment

There are no effective treatments to stop or slow the progression of CBS (Mennella & Schub, 2018; Stasio et al, 2019; Wilson et al, 2021). The goal of treatment is to improve motor and cognitive-behavioural symptoms (Parmera et al, 2016) or reduce the risk of life-threatening complications such as falls, aspiration pneumonia, or sepsis (Mennella & Schub, 2018).

Management options/goals noted in the literature include (Constantinides et al, 2019; Mennella & Schub, 2018; Monash Health, n.d.):

• Botulinum toxin injections to temporarily improve the functionality of the affected limb and decrease pain and cramping or dystonic muscles
• Myoclonus may be helped by medications like clonazepam (tranquiliser)
• Physiotherapy/physical therapy – improve everyday functionality such as walking and balance problems, prevent contractures and improve rigidity, advise on assistive technology to support independence
• Occupational therapy – can advise on positional aides to support posture while eating, drinking, communication; provide home safety advice to minimise risk from falls; assess and advise on pressure relieving equipment such as specialised seating and mattresses
• Speech therapy – assess speech and language decline; swallowing difficulties are common, which can lead to loss of enjoyment of food, poor nutrition, or aspiration therefore support from a speech pathologist may be beneficial
• Dietician for management of nutrition if difficulties occur with swallowing or mood changes prevent the person from eating well
• Depression and anxiety – mood changes can be supported via prescribed medication or a social worker/psychologist
• There is little evidence of effective therapy to improve cognition or prevent cognitive decline

References/Bibliography

• Constantinides, V. C., Paraskevas, G. P., Paraskevas, P. G., Stefanis, L., & Kapaki, E. (2019). Corticobasal degeneration and corticobasal syndrome: A review. Clinical Parkinsonism & Related Disorders, 1, 66-71. https://doi.org/10.1016/j.prdoa.2019.08.005
• Di Stasio, F., Suppa, A., Marsili, L., Upadhyay, N., Asci, F., Bologna, M., Colosimo, C., Fabbrini, G., Pantano, P., & Berardelli, A. (2019). Corticobasal syndrome: neuroimaging and neurophysiological advances. European Journal of Neurology, 26, 701-710. http://doi:10.1111/ene.13928
• Mennella, H. D. A.-B., & Schub, T. B. (2018). Corticobasal syndrome. CINAHL Nursing Guide. Monash Health. (n.d.). Corticobasal degeneration [fact sheet]. Accessed from https://monashhealth.org/services/movement-disorders-program/understanding-movement-disorders/corticobasal-degeneration/
• Parmera, J. B., Rodriguez, R. D., Neto, A. S., Nitrini, R., & Dozzi Bruck, S. M. (2016). Corticobasal syndrome: A diagnostic conundrum. Dementia & Neuropsychologia, 10(4), 267-275. [http://doi: 10.1590/s1980-5764-2016dn1004003](http://doi: 10.1590/s1980-5764-2016dn1004003)
• Raypole, C., (2019). Understanding extrapyramidal symptoms and the medications that cause them. Healthline. Accessed from https://www.healthline.com/health/symptom/extrapyramidal-symptoms
• Wilson, D., Le Heron, C., & Anderson, T. (2021). Corticobasal syndrome: a practical guide. Practical Neurology, 21(4), 276-285. http://dx.doi.org/10.1136/practneurol-2020-002835
• Zuo, F., Hu, K., Kong, J., Zhang, Y., & Wan, J. (2020). Surgical management of brain metastases in the perirolandic region. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.572644

Version control

V1.0 06-07-2022 Corticobasal Syndrome Page 6 of 6 OFFICIAL Page 56 of 165

Dementia supports

The content of this document is OFFICIAL.

Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters, they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Research question: Are the recommendations in RES 203 regarding dementia therapy interventions still current? What are the common and uncommon presentations of dementia? What community and mainstream interventions are available to people diagnosed/living with dementia? Date: 01/09/2022 Requestor: S22(1)(A)(ii) - Irrelevant Endorsed by: n/a Researcher: S22(1)(A)(ii) - Irrelevant Material Cleared by: Review date:

Research paper

OFFICIAL For Internal Use Only

Contents

• Dementia supports: 1
  • Contents: 2
  • Summary: 2
  • Types and presentation of dementia: 2
    • Younger Onset Dementia: 4
  • Management and treatment: 4
    • Clinical guidelines: 4
    • Allied health therapies for management of symptoms: 5
  • Community and mainstream services: 6
    • Dementia Australia: 6
    • Dementia Support Australia: 7
    • Dementia Alliance International: 7
    • Dementia Carers Australia / Dementia Reframes: 7
• References: 7

Summary

Dementia can present differently in different people. There are multiple causes which are associated with different symptom presentations. Cognitive and behavioural / psychological symptoms are common. Some people may experience physical symptoms such as tremor or rigidity. Evidence-based supports exist including programs offered by physiotherapists, occupational therapists, psychologists and other allied health. Speech therapists are often consulted for advice on eating and drinking. There are a variety of publicly funded dementia-specific community services including services provided by Dementia Australia and Dementia Support Australia.

Types and presentation of dementia

Dementia presents differently in different people. The Diagnostic and Statistical Manual of Mental Disorders 5th edition uses the term Major Neurocognitive Disorder for dementia. The International Classification of Disease 11th edition retains the name dementia but classifies it as a type of Neurocognitive Disorder. Both classifications include the common subtypes of dementia associated with Alzheimer’s disease, frontotemporal lobe degeneration, Lewy body disease, Vascular disease, HIV, Huntington’s disease, Parkinson’s disease, substance use

01-09-2022 Therapy to manage dementia Page 2 of 9 OFFICIAL Page 58 of 165

Research paper

OFFICIAL For Internal Use Only

and multiple concurrent causes (American Psychiatric Association, 2013; World Health Organisation, 2019).

These sub-types share common features including cognitive and behavioural/psychological symptoms. Cognitive symptoms of dementia can include problems with:

• attention
• processing speed
• planning
• decision making
• memory
• language
• perceptual-motor abilities
• social cognition (American Psychiatric Association, 2013; World Health Organisation, 2019).

Behavioural and psychological symptoms include:

• psychosis
• aggression
• anxiety
• apathy
• agitation
• depression
• delusions
• disinhibition
• wandering
• hallucinations
• sleep disturbances (World Health Organisation, 2019; National Institute for Health and Care Excellence, 2018; Sansoni et al, 2016).

There is some variation among subtypes. People with Alzheimer’s disease generally present with initial memory problems and functional decline is gradual. In dementia caused by vascular disease, mood fluctuations may be more evident than memory loss in the initial stages. Personality and mood changes, disinhibition and language problems are common early symptoms of frontotemporal dementia. Dementia associated with Lewy body disease can present with visual hallucinations and physical symptoms such as tremor or rigidity (Guideline Adaptation Committee, 2016).

01-09-2022 Therapy to manage dementia Page 3 of 9 OFFICIAL Page 59 of 165

Research paper

OFFICIAL For Internal Use Only

3.1 Younger Onset Dementia

In the NDIA, we are more likely to encounter younger onset dementia (YOD) due to the age-requirements for access to the NDIS. YOD is diagnosed when symptoms occur before the age of 65 (Dementia Australia, n.d). Also, people are more likely to experience dementia when they have been diagnosed with other conditions for which they may gain access to NDIS, such as severe/profound intellectual disability, Down Syndrome, autism, Parkinson’s disease and Huntington’s disease, (Lauterescu et al, 2017; Vivanti et al, 2021; Wissing et al, 2022). About 75% of people with Down Syndrome show signs of dementia before the age of 60 (Lauterescu et al, 2017). YOD is much less common than later onset dementia. In 2021, estimates of all people experiencing dementia in Australia ranged from 386,200 to 472,000, while only about 23,308 people were living with YOD (Australian Institute of Health and Welfare, 2021). Dementia Australia estimates 28,800 people living with YOD in 2022 (Dementia Australia, 2022). YOD can be caused by any of the common diseases associated with later onset dementia and can present in similar ways (Dementia Australia, n.d; Sansoni et al, 2016). There is evidence of some difference in symptom presentation. For example, memory problems may be less common in the initial stages compared to later onset dementia (Koedam et al, 2010) and YOD may progress faster (Veira et al, 2013). Because symptoms occur before the age of 65, people with YOD may require different types of supports compared to people for whom symptoms present later in life. In 2021, AIHW estimates 64.7% of people with dementia were living in the community. This rises to 91% when only considering people with YOD. Younger people with dementia are more likely to be employed and still caring for children (Dementia Australia, n.d). This can change the dynamic of care, with caring responsibilities sometimes falling to younger children (Sansoni et al, 2016).

Management and treatment

Clinical guidelines

The Tactical Research Team’s 2021 research paper RES 203 Therapy Best Practice described best practice treatments for dementia based on the UK’s National Institute for Health and Care Excellence (NICE) 2018 clinical guidelines. The Guideline Adaptation Committee of Australia’s National Health and Medical Research Council (NHMRC) adapted the 2006 version of the NICE guideline for use in Australia. The Clinical Practice Guidelines and Principles of Care for People with Dementia was published in 2016 and approved by NHMRC for 5 years (Guideline Adaptation Committee, 2016). Approval is no longer valid. However, the document does not appear to have been either reviewed or rescinded. The following is a selection of recommendations relating to treatment and management. For more detail and additional recommendations refer to the NICE guideline Dementia:

— PAGE TEXT END –

Research paper

OFFICIAL For Internal Use Only

assessment, management and support for people living with dementia and their carers or the NHMRC’s Clinical Practice Guidelines and Principles of Care for People with Dementia.

• Overall health should be monitored and maintained, including:

  • adequate nutrition and hydration (NHMRC 64-65; NICE 104, 131)
  • exercise (NHMRC 68; NICE 104)
  • dental care (NHMRC 65).

• Offer a range of activities to promote wellbeing that are tailored to the person’s preferences (NHMRC 66; NICE 82).

• Offer group cognitive stimulation therapy to people living with mild to moderate dementia (NICE 83).

• Consider group reminiscence therapy for people living with mild to moderate dementia (NHMRC 84; NICE 84).

• Consider cognitive rehabilitation or occupational therapy to support functional ability in people living with mild to moderate dementia (NICE 85).

• Explore clinical or environmental causes for distress before starting treatment (NHMRC 77-78; NICE 91-92).

• Consider psychological treatments for people with mild to moderate dementia experiencing mild to moderate depression or anxiety (NHMRC 79; NICE 101).

• Consider sleep hygiene education, exposure to daylight, exercise and personalised activities as treatment for sleep problems (NICE 104).

Allied health therapies for management of symptoms

People with dementia may require referral to:

• Psychologist or behaviour support practitioner (NHMRC 82-84, 92; NICE 11, 101)
• Speech therapist (NHMRC 64; NICE 132)
• Dietician (NHMRC 64)
• Occupational therapist (NHMRC 67; NICE 85)
• Physiotherapist or exercise physiologist (NHMRC 68)

Other professionals may also be required including dentists, audiologists, orthoptists, podiatrists and social workers (Guideline Adaptation Committee, 2016). Woods et al found cognitive stimulation therapy could improve cognitive function in people with mild to moderate dementia. The support could be delivered by professionals (speech therapist, occupational therapist, nurse, support worker) or by family caregivers. Median session length

01-09-2022 Therapy to manage dementia Page 5 of 9 OFFICIAL Page 61 of 165

Research paper

OFFICIAL For Internal Use Only

across the studies reviewed was 45 minutes, and the median frequency was 3 times a week, ranging from 1 to 5 times a week. The total possible exposure to the intervention varied dramatically, from 10 to 12 hours to 375 hours in the two-year study. Across the 15 studies, the median exposure time was 30 hours (Woods et al, 2012).

A 2021 meta-analysis showed a multimodal occupational therapy program with a cognition- oriented approach can improve cognitive dysfunction and basic activities of daily living. The effect was achieved with 1 to 3 one-hour sessions per week for at least 16 weeks (Ham et al, 2021). Integrating activities which are tailored to the individual with dementia and activities which involve the carer are likely to reduce behavioural symptoms and improve quality of life for people with mild to moderate dementia (Tan et al, 2022; Mohler et al, 2020). The effect can be obtained with 2 – 8 sessions at 1 - 2 hours delivered face-to-face or over the phone (Mohler et al, 2020).

Cognitive training delivered by a neuropsychologist or both psychologist and occupational therapist together is shown to improve global cognition and verbal semantic fluency when delivered at least once per week. Effect sizes were larger if delivered more than 3 times per week (Bahar-Fuchs, 2019).

One 2022 systematic review found no evidence that exercise programs had a positive effect on cognition or improvement in activities of daily living. However, the authors note that there may be evidence to support the effect of aerobic activity on neuropsychiatric symptoms (Steichele et al, 2022). In contrast, another 2022 review found that when aerobic exercise is included in a multicomponent exercise program of low to moderate intensity, it may improve global cognition for people with dementia. The effect was obtained with 1 to 7 sessions per week of 30 to 90 minutes each session (Venegas-Sanabria et al, 2022).

Community and mainstream services

As well as MyAgedCare and Carer’s Gateway, people living with dementia may be able to access Medicare subsidised allied health services through their Chronic Disease Management plan. There are also several community services available for people living with dementia and their carers.

Dementia Australia

Dementia Australia provides information about dementia and living with dementia on their website as well as:

• in person and online library services
• support to access My Aged Care or NDIS
• counselling
• referrals to supports in the community

01-09-2022 Therapy to manage dementia Page 6 of 9 OFFICIAL Page 62 of 165

Research paper

OFFICIAL For Internal Use Only

• social support groups
• National Dementia Hotline

5.2 Dementia Support Australia

Dementia Support Australia offers: - educational resources to assist people living with dementia and their carers to understand and manage behaviour changes - 24-hour helpline - individual assessments and ongoing support - referral to medical and allied health services - Staying at Home program, which includes education and respite for carers and people living with dementia to encourage people to remain living in the community.

5.3 Dementia Alliance International

Dementia Alliance International facilitates online peer-to-peer support groups for people living with dementia.

5.4 Dementia Carers Australia / Dementia Reframes

Dementia Carers Australia / Dementia Reframed provides information resources as well as online workshops for people living with dementia and their carers.

References

• American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
• Australian Institute of Health and Welfare. (2021). Prevalence of Dementia in Australia.https://www.aihw.gov.au/reports/dementia/dementia-in-aus/contents/population-health-impacts-of-dementia/prevalence-of-dementia
• Bahar-Fuchs, A., Martyr, A., Goh, A. M. Y., Sabates, J., & Clare, L. (2020). Cognitive training for people with mild to moderate dementia: a Cochrane Review. BJPsych Advances, 26(2), 66–66.https://doi.org/10.1192/bja.2019.74
• Dementia Australia. (n.d.). About younger onset dementia. Younger Onset Dementia Hub.https://yod.dementia.org.au/about-younger-onset-dementia
• Dementia Australia. (2022). Dementia Statistics.https://www.dementia.org.au/statistics
• Guideline Adaptation Committee. (2016). Clinical Practice Guidelines and Principles of Care for People with Dementia. Sydney. National Health and Medical Research Council

Research paper

OFFICIAL For Internal Use Only Partnership Centre for Dealing with Cognitive and Related Functional Decline in Older People.

• Ham, M.-J., Kim, S., Jo, Y.-J., Park, C., Nam, Y., Yoo, D.-H., & Moon, M. (2021). The effect of a multimodal occupational therapy program with cognition-oriented approach on cognitive function and activities of daily living in patients with Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials. Biomedicines, 9(12), 1951. https://doi.org/10.3390/biomedicines9121951
• Koedam, E. L. G. E., Lauffer, V., van der Vlies, A. E., van der Flier, W. M., Scheltens, P., & Pijnenburg, Y. A. L. (2010). Early-versus late-onset Alzheimer’s disease: more than age alone. Journal of Alzheimer’s Disease: JAD, 19(4), 1401–1408. https://doi.org/10.3233/JAD-2010-1337
• Lautarescu, B. A., Holland, A. J., & Zaman, S. H. (2017). The early presentation of dementia in people with Down syndrome: A systematic review of longitudinal studies. Neuropsychology Review, 27(1), 31–45. https://doi.org/10.1007/s11065-017-9341-9
• Möhler, R., Renom, A., Renom, H., & Meyer, G. (2020). Personally tailored activities for improving psychosocial outcomes for people with dementia in community settings. Cochrane Database of Systematic Reviews, 8(8), CD010515. https://doi.org/10.1002/14651858.CD010515.pub2
• National Institute for Health and Care Excellence. (2018). Dementia: assessment, management and support for people living with dementia and their carers (NICE guideline NG97. https://www.nice.org.uk/guidance/ng97/evidence/full-guideline-pdf-4852695709
• Tan, D. G. H., Boo, B. M. B., Chong, C. S., Tan, M. M. L.-L., & Wong, B.-S. (2022). Effectiveness of home-based, non-exercise interventions for dementia: A systematic review. Frontiers in Aging Neuroscience, 14, 846271. https://doi.org/10.3389/fnagi.2022.846271
• Venegas-Sanabria, L. C., Cavero-Redondo, I., Martínez-Vizcaino, V., Cano-Gutierrez, C. A., & Álvarez-Bueno, C. (2022). Effect of multicomponent exercise in cognitive impairment: a systematic review and meta-analysis. BMC Geriatrics, 22(1), 617. https://doi.org/10.1186/s12877-022-03302-1
• Vieira, R. T., Caixeta, L., Machado, S., Silva, A. C., Nardi, A. E., Arias-Carrión, O., & Carta, M. G. (2013). Epidemiology of early-onset dementia: a review of the literature. Clinical Practice and Epidemiology in Mental Health: CP & EMH, 9(1), 88–95. https://doi.org/10.2174/1745017901309010088
• Vivanti, G., Tao, S., Lyall, K., Robins, D. L., & Shea, L. L. (2021). The prevalence and incidence of early-onset dementia among adults with autism spectrum disorder. Autism Research: Official Journal of the International Society for Autism Research, 14(10), 2189–2199. https://doi.org/10.1002/aur.2590

01-09-2022 Therapy to manage dementia Page 8 of 9 OFFICIAL Page 64 of 165

Research paper

OFFICIAL For Internal Use Only

Wissing, M. B. G., Ulgiati, A. M., Hobbelen, J. S. M., De Deyn, P. P., Waninge, A., & Dekker, A. D. (2022). The neglected puzzle of dementia in people with severe/profound intellectual disabilities: A systematic literature review of observable symptoms. Journal of Applied Research in Intellectual Disabilities: JARID, 35(1), 24–45. hhttps://doi.org/10.1111/jar.12920

Woods, B., Aguirre, E., Spector, A. E., & Orrell, M. (2012). Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database of Systematic Reviews, 2, CD005562. https://doi.org/10.1002/14651858.CD005562.pub2

World Health Organization. (2019). ICD-11: International classification of diseases (11th revision). https://icd.who.int/

01-09-2022 Therapy to manage dementia Page 9 of 9 OFFICIAL Page 65 of 165

Research Request – Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) & the Cunningham Panel Test

Diagnoses: ASD, OCD, ADHD and Pervasive Developmental Disorder Applicant believes he has been misdiagnosed and has Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and is requesting Agency to fund neurology appointments with intent of obtaining diagnostic test (Cunningham Panel Test). The following information is requested:

• The Cunningham Panel Test:
  • What it is?
  • Whether it is a valid diagnostic test?
  • Where/how someone can be tested?
  • What the test shows?
  • How this links to his current disabilities.
  • The link between neurology appointments and the Cunningham Test
  • Anything else that will be useful to know for the Tribunal.
• Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (‘PANDAS’
  • What it is?
  • The validity of this as a diagnosis?
  • How this condition is treated?
  • How are you diagnosed with the condition?
  • The link (if any) between PANDAS and the Applicant’s disabilities.
  • Anything else that will be useful to know for the Tribunal. What is the best practice for managing the Applicant’s current disabilities?

Date: 15/09/2020 Requester: S22(1)(A)(ii) (Senior Technical Advisor TAB/AAT) Researcher: S22(1)(A)(ii) (Research Team Leader)

Contents Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) ……………………………………………………………………………………………………………………………… 2 What it is? …………………………………………………………………………………………………………………………. 2 How are you diagnosed with the condition? ………………………………………………………………………….. 3 The validity of this as a diagnosis? ………………………………………………………………………………………… 4 How this condition is treated? ……………………………………………………………………………………………… 4

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)

What it is?

Paediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections (PANDAS) is a neurological and psychiatric condition in which symptoms are brought on or worsened by a Streptococcal (strep) infection. PANDAS is a subtype of obsessive-compulsive disorder (OCD) and/or tic disorders characterised by an abrupt, dramatic pattern of episodic or saw-tooth symptoms, with the initial episode occurring acutely or “overnight”. 1, 2 Over a period of 24 to 48 hours, parents of children with PANDAS report their child as experiencing OCD and/or tics, as well as cognitive decline and behavioural regression. A parent describing their child as “a changed child” is not uncommon The underlying cause of PANDAS is unclear, but studies suggest that a strep infection causes an abnormal immune response resulting in neuropsychiatric symptoms.

Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

The link (if any) between PANDAS and the Applicant’s disabilities. …………………………………………… 5 The Cunningham Panel Test ……………………………………………………………………………………………………. 5 What it is and what the test shows? ……………………………………………………………………………………… 5 Results …………………………………………………………………………………………………………………………… 5 Whether it is a valid diagnostic test? …………………………………………………………………………………….. 6 Where/how someone can be tested? …………………………………………………………………………………… 6 How this links to his current disabilities. ……………………………………………………………………………….. 7 The link between neurology appointments and the Cunningham Test ……………………………………… 7 What is the best practice for managing the Applicant’s current disabilities? …………………………………. 7 Pervasive Developmental Disorder/Autism ……………………………………………………………………………. 7 OCD ………………………………………………………………………………………………………………………………….. 7 ADHD ………………………………………………………………………………………………………………………………… 7

PANDAS

PANDAS was first defined by Susan Swedo and her colleagues in 1998. ¹ They described in detail 50 cases of this new clinical entity and established working criteria of PANDAS.

To meet the definition of PANDAS all 5 criteria must be met: ^1,2

* Presence of obsessive-compulsive disorder (OCD) or a tic disorder, particularly multiple, complex or unusual tics
* Pre-pubertal symptom onset
* Acute symptom onset and episodic (relapsing-remitting) course
* Temporal association between Group A streptococcal infection and symptom onset/exacerbations
* Associated with neurological abnormalities, (particularly motor hyperactivity and Choreiform (repetitive and rapid, jerky, involuntary movement that appears to be well-coordinated) movements).

In Swedo’s first study a total of 144 periods of symptom exacerbations with a known relationship with streptococcal infections were reported. ¹ The study also described some key clinical features of PANDAS that are not part of the diagnostic criteria, such as:

* Separation anxiety
* Deterioration in handwriting
* Choreiform movement (repetitive and rapid, jerky, involuntary movement that appears to be well-coordinated)

The first 50 patients also reported high rates of psychiatric comorbidity, including 66% reporting emotional lability and 54% reporting personality change. ¹ The clinical criteria for PANDAS proposed in 1998 are still the ones in clinical use today.

How are you diagnosed with the condition?

Diagnosis is based on clinical data (diagnostic criteria) rather than diagnostic biomarkers. At the present time the clinical features of the illness are the only means of determining whether or not a child might have PANDAS (5 diagnostic criteria are listed above in ‘what is it’ section). ^5,7

A streptococcus serology, (ASOT and anti DNAseB) or throat swab may help confirm a recent Group A beta-haemolytic streptococci (GABHS) infection. If positive, the tests help confirm the involvement of Streptococcus and aid in the diagnosis of PANDAS. ^5,7

An elevated anti-streptococcal titer (such as an ASOT or an AntiDNAse-B) means the child has had a strep infection sometime within the past few months, and his/her body created antibodies to fight the streptococcus bacteria. * This is a normal, healthy response and all healthy people create antibodies to fight infections * Antibodies stay in the body for some time after the infection is gone, but the amount of time that the antibodies persist varies greatly between different individuals. o Some children have

The validity of this as a diagnosis?

PANDAS is now broadly accepted, however, validity of the PANDAS diagnosis has previously been the subject of controversy in the medical community due to: 3-5

1. Theories regarding the pathogenesis of PANDAS are still in debate (microbes have been proposed to induce autoantibodies that bind to brain proteins and affect behaviour)
2. Difficulty in showing the association of a new Group A Streptococcus (GAS) infection with a sudden exacerbation of tics or OCD a. There are various studies which firmly deny the association between GAS and tics/OCD, however, there are considerably more that strongly support the association. 6
3. Diagnosis based on clinical data rather than diagnostic biomarkers

Arguments surrounding the validity may also arise from the rarity of the condition. The incidence and prevalence of PANDAS are not known, although it is rare. 7 In one prospective study, only 10 cases were identified among 30,000 throat cultures (1 in 3000) positive for group A streptococci (GAS). 7 Since then, the annual incidence has ranged between 0 per 10,000 cultures to 10 per 30,000 cultures, depending upon the strain of GAS and other factors. 7

How this condition is treated?

The literature on the treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking.

Cognitive behaviour therapy (CBT) including exposure and response prevention (ERP), and selective serotonin reuptake inhibitors (SSRIs) are the primary evidence-based therapies for OCD. 8 Approximately 50%–80% of patients with OCD respond to these treatments, 9 but a substantial proportion of patients subsequently experience lifelong treatment resistance. 9 Behavioural interventions, such as habit reversal training, and psychopharmacological treatment strategies are the recommended treatments for tic disorders. 10 In contrast to the recommended treatments, when an infectious or autoimmune aetiology is suspected, these treatments for OCD and tics may be insufficient.

A recent systematic review 11 has identified the following treatments for PANDAS:

• Antibiotics
• Intravenous immunoglobulin
• Therapeutic plasma exchange
• Tonsillectomy
• CBT
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids

The link (if any) between PANDAS and the Applicant’s disabilities.

• PANDAS is a sub-type of OCD
• Attention deficit hyperactivity disorder (ADHD) symptoms and psychosis have been found to be more common in youth with PANDAS OCD than in peers with non-PANDAS OCD. 12, 13

The Cunningham Panel Test

What it is and what the test shows?

The below is taken directly from the Moleculera Labs (Oklahoma City, OK, USA) website which owns the Cunningham Panel test. Results are conducted using a patient’s blood sample.

The purpose of the Cunningham Panel™ is to provide laboratory results that assist physicians in diagnosing infection-induced autoimmune neuropsychiatric disorders (predominantly Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) or PANDAS). The panel measures the level of circulating antibodies directed against antigens concentrated in the brain, and measures the ability of these and other autoantibodies to increase the activity of an enzyme (CaMKII) that upregulates neurotransmitters in the brain.

The panel consists of five tests. Four of these tests provide results that are expressed as a titer, or final dilution, at which an endpoint reaction was observed on an Enzyme-Linked Immunosorbent Assay (ELISA) format. These tests measure circulating levels of autoantibodies directed against specific neuronal antigens, including: Dopamine D1 receptor (DRD1), Dopamine D2L receptor (DRD2L), Lysoganglioside GM1, and Tubulin. Autoimmune antibodies that bind to these targets may interfere or potentially lead to a blocking or stimulation of the function of these antigen. This, in turn, may trigger movement and neuropsychiatric disorders, along with OCD and abnormal neurologic behaviour

The 5th test, CaM Kinase II (CaMKII, Calcium-dependent Calmodulin Protein Kinase II) activation, produces a laboratory value (expressed as a numeric score) that reflects the percent above or below baseline CaMKII activity in a human neuronal cell line. CaMKII is a key enzyme that is involved in the upregulation of many neurotransmitters such as dopamine. CaMKII is also understood to increase the “plasticity” or sensitivity and responsiveness of neurologic receptors to neurotransmitters.

Results

The collective results of the panel of five tests provide a current assessment as to the autoimmune and anti-neuronal status of the patient at the time of the blood draw. Because it is a metabolic test, the laboratory values may vary over time, with treatment, and in conjunction with the presence and absence of symptoms. At present, the Cunningham Panel does not include testing for infectious agents such as streptococcus or measure anti-streptococcal antibody titers. The goal is to assist physicians by determining if there are elevated anti-neuronal antibodies and neuronal cell activating antibodies circulating in the patient’s blood, rather than attempting to identify the infection associated with the autoimmune condition. In short, it cannot be used to diagnose PANDAS.

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) & the Cunningham Panel Test Page 70 of 165

Whether it is a valid diagnostic test?

Of concern is the fact that Moleculera Labs, (who markets and performs this test) is owned/co-founded by the person who developed the Cunningham Panel, Dr Madeline Cunningham. The website lists various peer reviewed publications which they state confirms the validity and reliability of the test, however, there are several issues with this:

1. Creator of the test is an author on almost all publications a. Few independent assessments of the test and only positive results listed b. Some of the publications listed on the website don’t even use the Cunningham Panel test in their experiments
2. Primary aim of studies isn’t to test the validity and reliability of the Cunningham Panel test. Most studies are showing an association between high test results and a particular neuropsychiatric condition
3. Most studies are investigating the Cunningham Panel in the diagnosis of Sydenham Chorea rather than PANDAS a. Sydenham Chorea (SC) is a neurological disorder of childhood resulting from infection via Group A beta-haemolytic streptococcus (GABHS), the bacterium that causes rheumatic fever. SC is characterized by rapid, irregular, and aimless involuntary movements of the arms and legs, trunk, and facial muscles)
4. No large scale, high quality randomised controlled trials

In a 2017 study, ¹⁴ researchers evaluated the diagnostic accuracy of the 5 biomarkers used in the Cunningham Panel in 53 Swedish patients with PANS or PANDAS. Their results showed that the sensitivities of individual biomarkers in the Cunningham Panel ranged from 15 to 60 %, and specificities from 28 to 92 %. Positive predictive values ranged from 17 to 40 %, with negative predictive values from 44 to 74 %. A majority of the healthy controls (18/21) had pathological Cunningham Panel results, and test-retest reliability proved insufficient.

Note: As a rule, the sensitivity and specificity of a screening test should be above 80%. External authors have critically analysed publications by the creator of the Cunningham Panel test and have concluded that “it is still unclear whether these biomarkers are sensitive and specific blood tests for PANS or PANDAS.” ¹⁵ Furthermore, no association has been shown between biomarker levels and symptom exacerbations in previous studies. ^16-18

Where/how someone can be tested?

Patients can get a Cunningham Panel test through NutriPATH. This is an ‘Integrative Pathology Service’ that is privately owned and specialises in the area of functional health and wellbeing pathology testing. Patients are required to order a NutriPATH blood collection kit which they then take to a blood collection centre (e.g. Melbourne Pathology).

Website: http://nutripath.com.au/product/the-cunningham-profile-pandas-pans-test-code-3432/ Email: info@nutripath.com.au Phone: 1300 688 522 (within Australia) +61 3 9880 2900 (international) The types of Healthcare practitioners listed on the NutriPATH website include:

• Osteopath
• Naturopath
• Nutritionist

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) & the Cunningham Panel Test

How this links to his current disabilities.

The Cunningham Panel test is specifically designed to assist with the diagnosis of infection-induced autoimmune neuropsychiatric disorders. The participant has a diagnosis of OCD which PANDAS is associated with. Given there is insufficient evidence to show that the Cunningham Panel test is clinically useful or accurate it is not recommended.

The link between neurology appointments and the Cunningham Test

Unable to find any information which links neurology appointments to the Cunningham Panel test. The provider of the test in Australia doesn’t list neurologists as a healthcare provider that utilises their services. Given that the condition is neuropsychiatric there would need to be input from a psychologist and/or psychiatrist, neurologist, neuropsychologist or general practitioner. Many of the treatments for the condition require medically prescribed medication.

What is the best practice for managing the Applicant’s current disabilities?

Pervasive Developmental Disorder/Autism

This is an extremely complex disorder with many evidence based treatment modalities. Treatments include a range of behavioural, psychosocial, educational, medical, and complementary approaches. The options vary by age and developmental status. 19 Chronic management is often required to maximize functional independence and quality of life by minimizing core deficits in social skills and communication, facilitating development and learning, promoting socialization, reducing maladaptive behaviours, and educating and supporting families. 19

OCD

As mentioned above, Cognitive behaviour therapy (CBT) including exposure and response prevention (ERP), and selective serotonin reuptake inhibitors (SSRIs) are the primary evidence-based therapies for OCD.

ADHD

Multimodal approach is recommended for treatment of ADHD. This may include medication, psychosocial management strategies and, where appropriate, educational interventions. 20 The National Institute for Health Care Excellence guideline recommends drug treatment as the first-line treatment for adults with ADHD with either moderate or severe levels of impairment. Methylphenidate is the first-line drug. 21

References

• Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Dow S, Zamkoff J, Dubbert BK, Lougee L. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. American Journal of Psychiatry. 1998 Feb 1;155(2):264-71.
• Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Therapeut. 2012;2(2):113.
• Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004 Apr 1;113(4):883-6.
• Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004 Apr 1;113(4):907-11.
• Murphy TK, Gerardi DM, Parker-Athill EC. The PANDAS Controversy: why (and how) is it still unsettled?. Current Developmental Disorders Reports. 2014 Dec 1;1(4):236-44.
• Orefici G, Cardona F, Cox CJ, Cunningham MW. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). In Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet] 2016 Feb 10. University of Oklahoma Health Sciences Center.
• Genetic and Rare Diseases Information Center (GARD). Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus infections. [Internet]. 2020 [cited 14 September 2020]. Available from: https://rarediseases.info.nih.gov/diseases/7312/pediatric-autoimmune-neuropsychiatric-disorders-associated-with-streptococcus-infections#ref_11819.
• Pediatric OCD Treatment Study (POTS) Team. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. Jama. 2004 Oct 27;292(16):1969.
• Grant JE. Obsessive–compulsive disorder. New England Journal of Medicine. 2014 Aug 14;371(7):646-53.
• Hollis C, Pennant M, Cuenca J, Glazebrook C, Kendall T, Whittington C, Stockton S, Larsson L, Bunton P, Dobson S, Groom M. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis.
• Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neuroscience & Biobehavioral Reviews. 2018 Mar 1;86:51-65.
• Bernstein GA, Victor AM, Pipal AJ, Williams KA. Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and childhood obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2010;20:333–40.
• Murphy TK, Storch EA, Lewin AB, Edge PJ, Goodman WK. Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. J Pediatr. 2012;160:314–9. This publication adds to the literature by describing characteristics of youth with PANDAS OCD compared to non-PANDAS OCD.
• Hesselmark E, Bejerot S. Biomarkers for diagnosis of pediatric acute neuropsychiatric syndrome (PANS)–Sensitivity and specificity of the Cunningham Panel. Journal of neuroimmunology. 2017 Nov 15;312:31-7.

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) & the Cunningham Panel Test Page | 8 Page 73 of 165

Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) & the Cunningham Panel Test

15. Vojdani A, Turnpaugh CC. Antibodies against Group A Streptococcus, dopamine receptors, and ganglioside GM1 cross-react with a variety of food antigens, potentially interfering with biomarkers for PANS and PANDAS. Biomarkers in Neuropsychiatry. 2020 Dec 1;3:100023.
16. Morris-Berry CM, Pollard M, Gao S, Thompson C, Singer HS, Tourette Syndrome Study Group. Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with PANDAS and Tourette syndrome: single-point and longitudinal assessments. Journal of Neuroimmunology. 2013 Nov 15;264(1-2):106-13.
17. Singer HS, Mascaro-Blanco A, Alvarez K, Morris-Berry C, Kawikova I, Ben-Pazi H, Thompson CB, Ali SF, Kaplan EL, Cunningham MW. Neuronal antibody biomarkers for Sydenham’s chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection. PloS one. 2015 Mar 20;10(3):e0120499.
18. Singer HS, Gause C, Morris C, Lopez P. Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Pediatrics. 2008 Jun 1;121(6):1198-205.
19. Subramanyam AA, Mukherjee A, Dave M, Chavda K. Clinical practice guidelines for autism spectrum disorders. Indian journal of psychiatry. 2019 Jan;61(Suppl 2):254.
20. Royal Australian and New Zealand College of Psychiatrists. Adult ADHD - practice guidelines. [Internet]. 2020 [cited 15 September 2020]. Available from: https://www.ranzcp.org/practice-education/guidelines-and-resources-for-practice/adult- adhd-practice-guidelines
21. National Institute for Clinical Excellence. Attention Deficit Hyperactivity Disorder: Diagnosis and Management of ADHD in Children, Young People and Adults. NICE Clinical Guidelines, No. 72. National Collaborating Centre for Mental Health (UK). British Psychological Society (UK), Leicester (UK). 2009.

Research Request – Russell Silver Syndrome

Is there evidence of Russell Silver Syndrome causing issues with dental formation? If so, what are the issues and evidence based interventions recommended? Brief Is there evidence of Russell Silver Syndrome causing issues with muscle tone, core strength and gross motor skills? If so, what are the issues and evidence based interventions recommended?

Date: 07/09/2020

Requester: S22(1)(A)(ii) - (Senior Technical Advisor TAB/AAT)

Researcher: S22(1)(A)(ii) (Research Team Leader)

Contents

• What is Russell-Silver Syndrome? …………………………………………………………………………………………….. 2
• Evidence of issues relating to dental formation …………………………………………………………………………. 2
• Evidence of issues relating to muscle tone, core strength and gross motor skills ………………………………….. 4
  • Treatment Recommendations ……………………………………………………………………………………………… 5
• References ……………………………………………………………………………………………………………………………. 7

Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Russell Silver Syndrome Page 75 of 165

What is Russell-Silver Syndrome?

Russell-Silver Syndrome (RSS) is a rare condition associated with poor growth both before and after birth. ¹ Signs and symptoms vary significantly between individuals and may include:

• Low birth weight
• Short stature
• Characteristic facial features
• Large head in relation to body size
• Body asymmetry
• Feeding difficulties Other features may include poor appetite, clinodactyly (curved finger), digestive system abnormalities, delayed development, and/or learning disabilities. ^1,2

The genetic causes of RSS are complex and relate to certain genes that control growth. Sometimes, the genetic cause cannot be identified. Most cases are not inherited from a parent and occur sporadically. In rare cases, RSS may be inherited in an autosomal dominant or autosomal recessive manner. ² Because RSS can lead to a wide variety of physical abnormalities and health problems, treatment ideally should be managed by a team of specialists with knowledge of RSS. Early intervention is recommended to help children with RSS reach their full potential.¹

Evidence of issues relating to dental formation

Various dental manifestations ^3-8 have been reported in the literature including:

• Crowding of the teeth, especially in the mandible
  • Orthodontics Australia recommends the below treatments
    • Traditional metal or clear braces
    • Lingual braces
    • Clear aligner (Invisalign, Clear Correct or Spark Aligners)
    • Veneers or crowns
• Microdontia (one or more teeth appear smaller than normal)
  • Treatment is primarily for aesthetic reasons. Occasionally, the patient may present with functional difficulties such as food trapping.⁹
    • Veneers
    • Crowns
    • Composite bonding
• Prenatal and permanent enamel defects

Clinical problems include compromised aesthetics, tooth sensitivity and increased risk for caries and tooth wear. ¹⁰Treatment depends on the severity of the problem. Goals of treatment are to:

• Prevent tooth decay
• Maintain a good bite
• Preserve tooth structure
• Keep teeth looking their best

Some of the smaller defects that aren’t causing decay or sensitivity may not need treatment right away. In the case of sensitivity, cavities, or tooth structure showing wear, treatment options include ¹⁰:

• Application of topical fluoride
• Resin-bonded sealant. This can improve tooth sensitivity.
• Resin-based composite fillings. These can be made to closely match tooth colour, which makes them ideal for use on front or back teeth. They’re also quite durable.
• Dental amalgam fillings. These are made from a combination of durable metals. Due to the silver colour, you may not want them on your front teeth.
• Gold fillings. Like dental amalgam fillings, gold fillings are durable but lack a natural look. They also tend to be the most expensive.
• Crowns. These completely cover the tooth.
• Enamel micro abrasion. This is a minimally invasive procedure to improve appearance of the teeth.
• Professional dental whitening.

• Congenital absence of lateral incisors and second premolars

  • Treatment options for missing lateral incisors include ¹¹:
    • orthodontic space closure
    • Resin-bonded bridgework
    • Single-tooth implants
    • Auto-transplantation of developing premolars

  Treatment options for missing second premolars include ¹²: * Single-tooth implants * maintain the primary tooth until the patient is old enough to place the implant * Reducing the size of the primary molar * Push first pre molar into second pre molar position

Evidence of issues relating to muscle tone, core strength and gross motor skills

The Human Phenotype Ontology website collects information on symptoms of rare diseases (including RSS) that have been described in medical resources.

Issues relating to muscle tone, core strength and gross motor skills identified include:

Treatment Recommendations

Patients with RSS should receive multidisciplinary care in a centre of expertise in SRS in coordination with their local centre. The multidisciplinary team should be composed of paediatric subspecialists such as an endocrinologist (coordinator), gastroenterologist, dietician, clinical geneticist, craniofacial team, orthopaedic surgeon, neurologist, speech and language therapist and psychologist. The below management recommendations have been taken from the recently published consensus guidelines for RSS.

1. Early feeding and nutritional support

• The main therapeutic goals for the first 2 years of life in patients with SRS are nutritional support, prevention of hypoglycaemia and recovery of any calorie-related length or height deficit, which should be addressed before initiation of GH therapy.
• Children with RSS have an abnormal body composition with low muscle mass, and are typically light for their length or height. The target for healthy nutritional status is narrow, and is dependent on individual innate muscle mass and even slight over nourishment.

2. Growth hormone

• Apart from increases in height potential benefits of GH treatment are increases in appetite, lean body mass and muscle power, which can result in improved mobility

3. Neurocognitive problems

• Motor development skills may be delayed due to low muscle tone (hypotonia) and relatively large head size, especially in infancy and toddlerhood. Delay in speech development is also common, particularly in those patients with maternal uniparental disomy of chromosome 7. Early intervention (physical, occupational and/or speech therapy) is important and parents should ask their paediatrician for more information.

4. Orthopaedic problems

• Limb or body asymmetry, scoliosis, hip dysplasia and hand and/or foot anomalies are seen in RSS.
• Limb lengthening surgery performed to equalize limb lengths in patients with SRS has shown positive results.
• Shoe lifts

• Physical therapy
• Where necessary, refer to a paediatric orthopaedic surgeon for collaborative management of body asymmetry, limb length discrepancy and scoliosis.

References

• Wakeling EL, Brioude F, Lokulo-Sodipe O, O’Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B. Diagnosis and management of Silver–Russell syndrome: first international consensus statement. Nature Reviews Endocrinology. 2017 Feb;13(2):105.
• Genetics Home Reference. Russell-Silver syndrome [Internet]. Genetics Home Reference. 2020 [cited 7 September 2020]. Available from: https://ghr.nlm.nih.gov/condition/russell-silver-syndrome
• Kotilainen J, Hölttä P, Mikkonen T, Arte S, Sipilä I, Pirinen S. Craniofacial and dental characteristics of Silver-Russell syndrome. American journal of medical genetics. 1995 Mar 27;56(2):229-36.
• Cullen CL, Wesley RK. Russell-Silver syndrome: microdontia and other pertinent oral findings. ASDC Journal of Dentistry for Children. 1987 May 1;54(3):201-4.
• Bergman A, Kjellberg H, Dahlgren J. Craniofacial morphology and dental age in children with Silver–Russell syndrome. Orthodontics & Craniofacial Research. 2003 Feb;6(1):54-62.
• Bedi R, Moody GH. A primary double molar tooth in a child with Russell-Silver syndrome. British dental journal. 1991 Nov;171(9):284-6.
• Rubenstein LK. Dental management of patients with Russell-Silver syndrome. J Pedod. 1988;12:215-9.
• Subklew D, Höck S. Tooth and jaw development in the Silver-Russel syndrome. Fortschritte der Kieferorthopadie. 1990 Dec;51(6):378-83.
• Laverty DP, Thomas MB. The restorative management of microdontia. British dental journal. 2016 Aug;221(4):160-6.
• Seow WK. Developmental defects of enamel and dentine: challenges for basic science research and clinical management. Australian Dental Journal. 2014 Jun;59:143-54.
• Turpin DL. Treatment of missing lateral incisors. American Journal of Orthodontics and Dentofacial Orthopedics. 2004 Feb 1;125(2):129.
• Kokich VG, Kokich VO. Congenitally missing mandibular second premolars: clinical options. American Journal of Orthodontics and Dentofacial Orthopedics. 2006 Oct 1;130(4):437-44.
• Kulkarni VK, Ragavendra TR, Deshmukh J, Vanka A, Duddu MK, Patil AK. Endodontic treatment and esthetic management of a primary double tooth with direct composite using silicone buildup guide. Contemporary Clinical Dentistry. 2012 Apr;3(Suppl1):S92.
• Wakeling EL, Brioude F, Lokulo-Sodipe O, O’Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B. Diagnosis and management of Silver–Russell syndrome: first international consensus statement. Nature Reviews Endocrinology. 2017 Feb;13(2):105.

Research Request – Persistent Postural Perception Dizziness (PPPD)

Advice request for AAT Access Matter

Information about the nature of Persistent Postural Perception Disorder (PPPD):

• Treatment options (best practice) and
• Possible implications on disability.

Is there any correlations with PPPD and the following conditions?

• Borderline Personality Disorder
• Peripheral Perception disorder
• Chronic Vertigo (has been re-diagnosed as PPPD)
• Diabetes Type 2
• Morbid Obesity
• Osteoarthritis
• Sleep Apnoea
• Asthma

Date: September 07, 2020

Requester: S22(1)(A)(ii) - Irrelevant (Assistant Director – TAB)

Researcher: S22(1)(A) (Tactical Research Advisor – TAB/AAT)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

• Summary ………………………………………………………………………………………………………………………………. 2
• What is Persistent Postural Perception Dizziness (PPPD)? …………………………………………………………… 2
• Treatment …………………………………………………………………………………………………………………………….. 3
  • Education ………………………………………………………………………………………………………………………….. 3
  • Vestibular Rehabilitation Therapy (VRT) ………………………………………………………………………………… 4
  • Cognitive Behavioural Therapy (CBT) ……………………………………………………………………………………. 4
  • Medication ………………………………………………………………………………………………………………………… 5

Summary

• As PPPD is a newly defined diagnostic syndrome, research is limited, however there are several recent medium quality research papers available.

• It appears that best practice treatment intervention is multidisciplinary, focusing on education, Vestibular Rehabilitation Therapy, Cognitive Behavioural Therapy, and medication.

• With regard to implications on disability, it appears that the presence of long duration symptoms does not preclude a good outcome with treatment. Studies of phobic postural vertigo and chronic subjective dizziness suggest that long-term benefit probably depends on starting treatment early.

• With the exception of diabetes no correlation to PPPD could be found with those suggested in the research brief.

What is Persistent Postural Perception Dizziness (PPPD)?

Persistent postural-perceptual dizziness (PPPD) is a chronic functional disorder of the nervous system, characterised by

• Non-spinning vertigo
• Perceived unsteadiness.

The symptoms are exacerbated when patients

• Assume upright postures and
• Are in situations with complex or moving visual stimuli.

The most common provocations are benign circumstances such as standing, walking, looking at traffic or sitting in a busy restaurant, which may be perceived as noxious or threatening.

Symptoms of PPPD may be alleviated transiently in moments of distraction and may flare fleetingly without apparent provocation. PPPD is precipitated by episodes of vertigo or unsteadiness of vestibular, neurological or psychiatric origin. These triggers appear to induce involuntary utilisation of high demand postural control strategies and an over-reliance on visual stimuli for spatial orientation.

Research Request – Persistent Postural Perception Dizziness Page 2 Page 83 of 165

Treatment

PPPD management is steadily advancing, and treating clinicians are now able to access internationally sanctioned diagnostic criteria, World Health Organization International Classification of Diseases, 11th Revision (WHO, 2018) classification, and advancing treatment protocols.

Treatment protocols integrate:

• Medications
• Cognitive Behavioural Therapy (CBT)
• Vestibular Rehabilitation Therapy (VRT)
• Education
• Visual/Optokinetic Motion Desensitization (Often integrated with VRT)
• Graded habitation (Often integrated with VRT)
• Balance retraining (Often integrated with VRT)
• Relaxation/mindfulness. (Often integrated with VRT) [2]

These interventions are mostly based on studies looking into the benefit of treatments with respect to its precursors. It is estimated that approximately 78% of patients with chronic dizziness in general will improve with such a neurotological and psychotherapeutic regime after an average of 32 months. This is likely to hold true for PPPD as well. [3]

Education

The Trinidade & Goebel study suggests that patient education is key in first laying the foundations for further interventions to be introduced, and before further appointments are arranged with the physical therapist for VRT and the psychologist for CBT where appropriate. Healthy lifestyle habits such as a good sleep hygiene, physical exercise, and a balanced diet, may also help to relieve anxiety and improve general mental health, which may in turn help to shift patients out of the maladaptation cycle of PPPD, and are to be encouraged.

Research Request – Persistent Postural Perception Dizziness Page 3 | Page 84 of 165

Vestibular Rehabilitation Therapy (VRT)

Vestibular rehabilitation is an umbrella term for a range of physical treatments that aim to compensate or retune impaired balance control in various vestibular and neurological disorders. In PPPD and related disorders, the guiding principle is to desensitize a balance control system that is stuck on “high alert” by use of habituation exercises and relaxation techniques. Although vestibular rehabilitation was initially developed as a purely physical therapy, it has evolved to incorporate various cognitive-behavioural principles such as graded exposure and cognitive reframing, and often CBT and vestibular exercises are combined into one hybrid therapy. A wide range of exercises can be used in vestibular rehabilitation: from more general and natural exercises, such as walking programs (gradual build-up of brisk walk of up to 30 min), to more specific dizziness-provoking head movements, which should be performed relatively slowly. Patients should be encouraged to become aware of any dizziness, but at the same time remain calm about it and persist with the exercises. To further promote the desensitization of the dizziness-alert-anxiety response, relaxation exercises such as diaphragmatic breathing or autogenic training can be used. To help with the desensitization of visual vertigo or motion sensitivity, simulator-based exercises using head-mounted displays or wall projections can be used. [4]

A recent 2019 study set out to test the effect of VRT on patients with PPPD. Participants were diagnosed as having PPPD by the exclusion of organic vestibular lesions. The study involved 2 groups with PPPD. Group I was treated with the VRT, and Group II was treated with the VRT plus placebo. The Dizziness Handicap Inventory (DHI), a self-assessment scale, was used to evaluate the VRT outcomes.

The study found that here was a significant decrease in functional, physical, and total scores on the DHI in both groups after VRT. Adding the placebo did not have supplementary outcomes. The patients who did not benefit from the VRT had a significantly longer duration of PPPD, more complex aggravating factors, more composite VRT exercises, and a higher DHI score than the patients who benefited from VRT.

The study concluded that VRT adequately reduced symptoms and improved quality of life in subjects with PPPD. [5]

Cognitive Behavioural Therapy (CBT)

In their systematic review, Trinidade and Goebel, suggested that much of the work done on the role of CBT in PPPD is based on work done on its precursors. One example is a case series by Holmberg et al. that examined the effectiveness of CBT in 39 patients with PPV. CBT was shown to have an additional positive effect when used as part of a multidisciplinary approach that included medication and physical therapy, but the effect was found to be transient one year later. As well, Schmid et al. found in their study of 32 patients that CBT, when combined with vestibular rehabilitation and psychoeducation was more significantly effective in patients experiencing dizziness independent of a balance deficit when compared with those who were found to have a quantifiable balance deficit, despite balance control in the latter improving to near normal in the latter group. In both groups, phobic anxiety scores were seen to reduce the most. It is likely that more focus was placed on phobic anxiety in the dizzy-only group as no quantifiable (and thus treatable) balance disorder could be found, and may have relevance in PPPD.

Research Request – Persistent Postural Perception Dizziness Page | 4 Page 85 of 165

The Trinidad and Goebel review highlights that more recently, specific research has supported CBT’s role in PPPD.

Medication

Serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) remain the recommended medications in the treatment of PPPD, but there is currently little published on their role specifically for it (Trinidade and Goebel).

With regard to medication the Popkirov et al. study suggests that the evidence level of the commonly cited studies reviewed is low, and that existing studies are all open-label non-randomized studies, which is problematic for two reasons. First, in functional disorders, symptom expectations are highly relevant and significant placebo responses are to be expected. Second, only subjective investigator-rated and/or patient self-report outcome measures were used as study endpoints, potentially introducing various biases. Different agents have been studied, with two studies evaluating more than one SSRI.

The study further suggests that from an intention-to-treat perspective, about half to two-thirds of patients can be expected to respond well to treatment with SSRI. Taken together, these studies suggest that SSRI (or SNRI) can be a useful treatment option in patients with PPPD. Randomized controlled and blinded trials are needed, however, to provide more robust evidence for this common and potentially useful clinical practice. Since rehabilitation from PPPD relies on “re-adaptation” of vestibular and balance control systems, vestibular suppressant drugs such as antihistamines and benzodiazepines can be expected to delay rather than help rehabilitation, and should be avoided if possible.

Implications on Disability

Undiagnosed or untreated patients can suffer for many years on end, which is why neurologists need to be familiar with functional dizziness and PPPD, must not shy away from a firm diagnosis and be aware of the treatment options. The presence of long duration symptoms does not preclude a good outcome with treatment. Studies of phobic postural vertigo and chronic subjective dizziness suggest that long-term benefit probably depends on starting treatment early. Years of chronification usually imply a higher degree of maladaptation, more severe disability and more engrained illness.

(Popkirov S, Staab J, Stone J, [1])

Correlation with other conditions

With the exception of diabetes no correlation could be found in the research on the following conditions:

• Borderline Personality Disorder
• Peripheral Perception disorder
• Chronic Vertigo (has been re-diagnosed as PPPD)
• Diabetes Type 2
• Morbid Obesity
• Osteoarthritis
• Sleep Apnoea
• Asthma

A study [6] which set out to evaluate the clinical characteristics of patients with PPPD, analysed 81 patients through questionnaire to identify the predisposition to PPPD. The study found the following comorbidities associated with PPPD including diabetes:

• Werehypercholesterolemia (31%)
• Migraine (26%)
• Carbohydratemetabolic disorder (22%)
• Cervical syndrome (21%)
• Benignparoxysmal positional vertigo (15%)
• Dysautonomia (7%)
• Dis-orders of the middle ear (7%)
• Hypertension (5%)
• Cardiacarrhythmia (5%)
• Diabetes (5%)
• Hypothyroidism (5%)
• Menière’s syndrome (5%)

In addition to the described comorbidities, the following were found, accounting for less than 2% of prevalence:

• Elderly unbalance syndrome,
• Peripheral facial palsy,
• Vestibular neuritis
• Epilepsy
• Sudden deafness
• Hepatitis C

Literature Review

References

• Popkirov S, Staab J, Stone J. Persistent postural-perceptual dizziness (PPPD): a common, characteristic and treatable cause of chronic dizziness. Practical Neurology. 2017;18(1):5-13.

• Holmberg J. Pathophysiology, Differential Diagnosis, and Management of Persistent Postural-Perceptual Dizziness: A Review. Perspectives of the ASHA Special Interest Groups. 2020;5(1):181-191.

• Trinidade A, Goebel J. Persistent Postural-Perceptual Dizziness—A Systematic Review of the Literature for the Balance Specialist. Otology & Neurotology. 2018;39(10):1291-1303.

• Popkirov S, Stone J, Holle-Lee D. Treatment of Persistent Postural-Perceptual Dizziness (PPPD) and Related Disorders. Current Treatment Options in Neurology. 2018;20(12).

• Nada E, Ibraheem O, Hassaan M. Vestibular Rehabilitation Therapy Outcomes in Patients With Persistent Postural-Perceptual Dizziness. Annals of Otology, Rhinology & Laryngology. 2019;128(4):323-329.

• Bittar, R. and von Söhsten Lins, E., 2015. Clinical characteristics of patients with persistent postural-perceptual dizziness. Brazilian Journal of Otorhinolaryngology, 81(3), pp.276-282.

Research Request – Persistent Postural Perception Dizziness Page | 10 Page 91 of 165

Research Request – Lyme disease

Brief

1. What is the evidence base for Lyme disease (US acquired), the typical / atypical symptoms or presentation, standard treatment options and potential changes in functional performances over time – long term?
2. Is there evidence of adverse side effects such as myoclonic jerks (in the form of screeching vocally and ‘lunging forward’ when walking) and fatigue, as a result of usual antibiotic treatments for Lyme disease?

Date 24/06/2020

Requester S22(1)(A)(ii) - Irrelevant (TAB Director)

Researcher S22(1)(A)(ii) (Research Team Leader) Irrelevant

Cleared by S22(1)(A)(ii) - Irrelevant (Research Team Leader)

Table of Contents

• What is Lyme disease? … 2
• Signs and symptoms … 2
  • Early (3 to 30 days after tick bite) untreated Lyme disease [2] … 2
  • Later (days to months after tick bite) untreated Lyme disease [2] … 2
  • Post-treatment Lyme disease syndrome … 2
• Why is Lyme disease so controversial? … 4
  • Diagnostic testing … 5
• Treatment … 5
• Potential changes in functional performances over time … 6
• Evidence of myoclonus and/or fatigue following antibiotic treatment for Lyme disease … 7
• Reference List … 8

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

What is Lyme disease?

Lyme disease is an infectious illness caused by the bacterium known as Borrelia, which creates a condition more correctly known as Borreliosis or Lyme Borreliosis [1]. The bacteria is transmitted when an individual is bitten by a vector usually a tick. Lyme disease can impact many bodily systems and organs and can, in some cases, mimic other illnesses i.e. lupus. People with Lyme disease are frequently diagnosed with other co-infections caused by vector-borne bacteria and parasites such as Babesia, Bartonella, Rickettsia, Mycoplasma and Ehrlichia [1].

Signs and symptoms

3.1 Early (3 to 30 days after tick bite) untreated Lyme disease [2]

Fever, chills, headache, fatigue, muscle and joint aches, and swollen lymph nodes may occur in the absence of rash Erythema migrans rash:

• Occurs in approximately 70-80% of infected persons
• Begins at the site of a tick bite after a delay of 3 to 30 days (average is about 7 days)
• Expands gradually over several days reaching up to 12 inches or more (30 cm) across
• May feel warm to the touch but is rarely itchy or painful
• Sometimes clears as it enlarges, resulting in a target or “bull’s-eye” appearance
• May appear on any area of the body
• Does not always appear as a “classic” erythema migrans rash

3.2 Later (days to months after tick bite) untreated Lyme disease [2]

• Severe headaches and neck stiffness
• Additional Erythema migrans rashes on other areas of the body
• Facial palsy (loss of muscle tone or droop on one or both sides of the face)
• Arthritis with severe joint pain and swelling, particularly the knees and other large joints.
• Intermittent pain in tendons, muscles, joints, and bones
• Heart palpitations or an irregular heart beat
• Episodes of dizziness or shortness of breath
• Inflammation of the brain and spinal cord
• Nerve pain
• Shooting pains, numbness, or tingling in the hands or feet

3.3 Post-treatment Lyme disease syndrome

Although most cases of Lyme disease can be cured within 2- to 4-weeks, patients can sometimes have symptoms of pain, fatigue, or difficulty thinking that lasts for more than 6 months after they finish treatment [2]. This condition is called Post-Treatment Lyme Disease

Table 1: Reported symptoms associated with Post-treatment Lyme disease syndrome

| Head, face and neck | • Unexplained hair loss • Headache, mild or severe, Seizures • Pressure in head, white matter lesions in brain (MRI) • Facial paralysis (Bell’s Palsy, Homer’s syndrome) • Tingling of nose, (tip of) tongue, cheek or facial flushing • Stiff or painful neck • Twitching of facial or other muscles • Jaw pain or stiffness • Dental problems (unexplained) • Sore throat, clearing throat a lot, phlegm ( flem ), hoarseness, runny nose | | Eyes and vision | • Double or blurry vision • Increased floating spots • Pain in eyes, or swelling around eyes • Oversensitivity to light • Flashing lights/peripheral waves/phantom images in corner of eyes | | Ears and hearing | • Decreased hearing in one or both ears, plugged ears • Buzzing in ears • Pain in ears, oversensitivity to sounds • Ringing in one or both ears | | Digestive and excretory systems | • Diarrhea • Constipation • Irritable bladder (trouble starting, stopping) or interstitial cystitis • Upset stomach (nausea or pain) or GERD (gastroesophageal reflux disease) | | Musculoskeletal system | • Bone pain, joint pain or swelling, carpal tunnel syndrome • Stiffness of joints, back, neck, tennis elbow • Muscle pain or cramps (fibromyalgia) | | Respiratory and circulatory systems | • Shortness of breath, can’t get full/satisfying breath, cough • Chest pain or rib soreness • Night sweats or unexplained chills • Heart palpitations or extra beats • Endocarditis, heart blockage | | Neurological system | • Tremors or unexplained shaking • Burning or stabbing sensations in the body • Fatigue, chronic fatigue syndrome, weakness, peripheral neuropathy or partial paralysis • Pressure in the head • Numbness in body, tingling, pinpricks • Poor balance, dizziness, difficulty walking • Increased motion sickness • Light-headedness, wooziness • Seizures – often ‘atypical’ | | Psychological wellbeing | • Mood swings, irritability, bi-polar disorder • Unusual depression • Disorientation (getting or feeling lost) • Feeling as if you are losing your mind |

Why is Lyme disease so controversial?

The controversy surrounding the disease arises over treatment of people who don’t respond to short courses of antibiotics [3]. Up to one in six patients with erythema migrans continue to experience fatigue, myalgia, or arthralgia a year after the rash has gone. About one in ten still has non-specific symptoms five years after their original treatment [4].

Lobby groups: Believe long term symptoms are caused by persisting infection with live organisms [3].

Mainstream medicine: Believe ongoing symptoms are caused by permanent tissue damage from the initial infection, persistent inflammation not driven by live infection, some kind of autoimmune process, or a second illness triggered by Lyme disease such as anxiety, depression, fibromyalgia, or chronic fatigue syndrome [5]. None of these conditions would respond to further antibiotics [3].

Both sides present opposing literature on the issue, however, mainstream opinion takes a harder line when it comes to what information it deems acceptable. For instance, mainstream medicine cites two randomised controlled trials which reported that long term antibiotic treatment doesn’t work [6], whereas Lyme disease lobby groups rely on case studies and anecdotal evidence [3].

Lyme Disease

Disagreement also stems from the diagnosis of Lyme disease which is often subjective. Physical signs are often absent or variable in appearance, and blood tests for antibodies can be unreliable, especially in the long term [3].

Diagnostic testing

The Centre for Disease Control and Prevention recommends the following multi-step approach to diagnostic testing for Lyme disease [2].

• No tests recommended for patients with a typical pattern of symptoms that includes erythema migrans.
• Atypical patients should have a blood sample tested by enzyme linked immunosorbent assay (ELISA).
• If the first ELISA result is negative, no further tests are done. The patient is seronegative.
• If the ELISA result is positive or equivocal, the same sample is retested using Western immunoblot analysis. A patient is seropositive if both tests are positive All tests should be carried out by a qualified laboratory. Patients in the early stages of Lyme disease may still be seronegative and should be retested during the convalescent phase.

Treatment

Antibiotics are the only proven treatment for Lyme disease [2]. People treated with appropriate antibiotics in the early stages of Lyme disease usually recover rapidly and completely [2]. Antibiotics commonly used for oral treatment include doxycycline, amoxicillin, or cefuroxime axetil. People with certain neurological or cardiac forms of illness may require intravenous treatment with antibiotics such as ceftriaxone or penicillin [2]. Treatments listed in Table 2 below are for localised (early) Lyme disease. These regimens are guidelines only and may need to be adjusted depending on a person’s age, medical history, underlying health conditions, pregnancy status, or allergies [2]. Treatment recommendations for PTLDS are fiercely debated. Studies funded by the National Institutes of Health (NIH) have found that long-term outcomes are no better for patients who received additional prolonged antibiotic treatment than for patients who received placebo [2]. Long-term antibiotic treatment for Lyme disease has been associated with serious complications including bacterial infection, drug induced Lupus, anaemia and death [6, 7].

Additional treatment modalities have been propagated; most of them with no or little scientific evidence – and no proven effect [8]. Neither hyperbaric oxygen, immuno-modulators or psychotropic medication have been shown to be beneficial, although medication for reducing pain or coexistent mood disorders may be tried [8].

Lyme Disease Page 96 of 165

Table 2: Recommended antibiotic treatments and regimes for Lyme disease

Potential changes in functional performances over time

Literature describing the symptoms and impact on functioning is difficult to interpret due to a lack of standardised measures used and inconsistent methodology. Many studies do not objectively measure functional performance because functional status is not included in the definition of PTLDS. This is because many sufferers do not meet the criteria for functional impairment [9].

Many studies use self-reported questionnaires to determine function which are insufficiently valid. For example, mean quality of life (physical and mental) scores have been reported to be lower than the United States national average [10]. However, this same study also found that long-term symptoms were more likely to be caused by other comorbidities unrelated to Lyme disease [10]. Alarmingly, two studies have documented that many patients referred to Lyme disease clinics had psychiatric diagnoses and/or maladaptive psychological traits, such as catastrophization and negative affect [11, 12].

A study which used both objective and subjective measures of function found that physical exam and clinical laboratory tests showed few objective abnormalities between those with PTLDS and healthy controls [13]. However, subjective questionnaires founds that PTLDS patients exhibited clinically significantly higher levels of fatigue, musculoskeletal pain, sleep disturbance, and depression [13].

A prospective cohort study of children with a previous diagnosis of Lyme disease compared to controls has shown that residual facial palsy can be more frequent, whereas headache and fatigue are not [14]. Similarly, it has been reported that fatigue and fibromyalgia among

Evidence of myoclonus and/or fatigue following antibiotic treatment for Lyme disease

There is no peer reviewed evidence which shows that antibiotics used to treat Lyme disease causes myoclonic jerks or fatigue. Fatigue is consistently reported as a symptom of Lyme disease and is most often present before any treatment is administered. A literature search identified two reported cases of myoclonus in patients diagnosed with Lyme disease. Both patients presented to hospital with myoclonus and symptoms resolved after the delivery of antibiotics [17, 18].

Anti-biotic induced myoclonus is very rare and has been reported in several case studies after the use of high dose antibiotics in those with renal disease [19 20]. Drugs that have been reported most frequently as a cause of myoclonus are levodopa, cyclic antidepressants, serotonin reuptake inhibitors, bismuth salts and anti-epileptic drugs. In most cases, withdrawal of the offending drug leads to the resolution of myoclonus [21].

Reference List

• Lyme disease Association of Australia. About Lyme disease. 2020. Accessed June 24, 2020. Available from https://www.lymedisease.org.au/about-lyme-disease-2/
• Wormser GP. Early Lyme disease. New England Journal of Medicine. 2006 Jun 29;354(26):2794-801.
• Tonks A. Lyme wars. Bmj. 2007 Nov 1;335(7626):910-2.
• Feder Jr HM, Johnson BJ, O’Connell S, Shapiro ED, Steere AC, Wormser GP, Ad Hoc International Lyme Disease Group. A critical appraisal of “chronic Lyme disease”. New England Journal of Medicine. 2007 Oct 4;357(14):1422-30.
• Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Norton D, Levy L, Wall D, McCall J, Kosinski M. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New England Journal of Medicine. 2001 Jul 12;345(2):85-92.
• Centre for Disease Control and Prevention. Lyme Disease. April 13, 2020. Accessed June 24, 2020. Available from https://www.cdc.gov/lyme/index.html
• Strizova Z, Patek O, Vitova L, Horackova M, Bartunkova J. Internet-based self-diagnosis of Lyme disease caused death in a young woman with systemic lupus erythematosus. Joint, bone, spine: revue du rhumatisme. 2019 Oct;86(5):650.
• Nemeth J, Bernasconi E, Heininger U, Abbas M, Nadal D, Strahm C, Erb S, Zimmerli S, Furrer H, Delaloye J, Kuntzer T. Update of the Swiss guidelines on post-treatment Lyme disease syndrome. Swiss medical weekly. 2016;146.
• Shor S, Green C, Szantyr B, Phillips S, Liegner K, Burrascano Jr J, Bransfield R, Maloney EL. Chronic Lyme disease: An evidence-based definition by the ILADS Working Group. Antibiotics. 2019 Dec;8(4):269.
• Wills AB, Spaulding AB, Adjemian J, Prevots DR, Turk SP, Williams C, Marques A. Long-term follow-up of patients with Lyme disease: longitudinal analysis of clinical and quality-of-life measures. Clinical Infectious Diseases. 2016 Jun 15;62(12):1546-51.
• Sigal LH. Summary of the first 100 patients seen at a Lyme disease referral center. The American journal of medicine. 1990 Jun 1;88(6):577-81.
• Hassett AL, Radvanski DC, Buyske S, Savage SV, Sigal LH. Psychiatric comorbidity and other psychological factors in patients with “chronic Lyme disease”. The American journal of medicine. 2009 Sep 1;122(9):843-50.
• Rebman AW, Bechtold KT, Yang T, Mihm EA, Soloski MJ, Novak CB, Aucott JN. The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with posttreatment Lyme disease syndrome. Frontiers in medicine. 2017 Dec 14;4:224.
• Pachner AR, Steiner I. Lyme neuroborreliosis: infection, immunity, and inflammation. The Lancet Neurology. 2007 Jun 1;6(6):544-52.
• Lantos, Paul M. “Chronic Lyme disease.” Infectious disease clinics of North America vol. 29,2 (2015): 325-40. doi:10.1016/j.idc.2015.02.006
• Weitzner E, McKenna D, Nowakowski J, Scavarda C, Dornbush R, Bittker S, Cooper D, Nadelman RB, Visintainer P, Schwartz I, Wormser GP. Long-term assessment of post-treatment symptoms in patients with culture-confirmed early Lyme disease. Clinical Infectious Diseases. 2015 Dec 15;61(12):1800-6.

Lyme Disease

• Peter L, Jung J, Tilikete C, Ryvlin P, Mauguiere F. Opsoclonus–myoclonus as a manifestation of Lyme disease. Journal of Neurology, Neurosurgery & Psychiatry. 2006 Sep 1;77(9):1090-1.
• De la Sayette V, Schaeffer S, Queruel C, Bertran F, Defer G, Hazera P, Gallet E. Lyme neuroborreliosis presenting with propriospinal myoclonus. Journal of neurology, neurosurgery, and psychiatry. 1996 Oct;61(4):420.
• Ong CY, Qin Y. Myoclonus from Antibiotic Therapy (Ceftazidime-induced Neurotoxicity): A Case Report and Review. Cureus. 2018;10(3):e2250. Published 2018 Mar 1. doi:10.7759/cureus.2250
• Sarva H, Panichpisal K. Gentamicin-induced myoclonus: a case report and literature review of antibiotics-induced myoclonus. The neurologist. 2012 Nov 1;18(6):385-8.
• Jimenez-Jimenez FJ, Puertas I, de Toledo-Heras M. Drug-Induced Myoclonus. CNS drugs. 2004 Feb 1;18(2):93-104.

L y m e D i s e a s e P a g e | 9 Page 100 of 165

Research Request – Down Syndrome and Sleep Apnoea

Brief

Research supporting the link between down syndrome and sleep apnoea caused by anatomical reasons. The use of CPAP machines or any alternate treatment for sleep apnoea.

Date

11 October 2019

Requester

S22(1)(A)

Researcher

S22(1)

Summary of TAPS interaction (de-identified)

TAPS Interaction Advice:

TAPS QUERY: Team leader called TAPS to request advice regarding request for a CPAP machine to manage severe obstructive sleep apnoea for a 35 years old participant with Down syndrome (de-identified name Emily).

• Emily undertook a sleep study at the Sydney Hospital in May 2019 with the polysomnography results confirming that she has severe obstructive sleep apnoea (report by Doctor provided - 8/5/19).
• The report outlines Emily’s height is 142cm and weight is 60kg. Using these figures to calculate BMI indicates that Emily is overweight¹.

TAPS Advice Provided:

In principle a CPAP machine could be considered reasonable and necessary for the NDIS to fund for a person with Down syndrome as there is enough information to consider that obstructive sleep apnoea is related to the diagnosis of Down syndrome. However, all requests for funding by the NDIS must be considered against the criteria in Section 34.1 of the NDIS Act (2013). In this instance, consideration should be given to whether there are other appropriate treatment options including weight loss/management and/or use of a mouthguard.

Types of sleep apnoea

There are two types of sleep apnea:

• Obstructive sleep apnea (OSA): The more common of the two forms of apnea, it is caused by a blockage of the airway, usually when the soft tissue in the back of the throat collapses during sleep.
• Central sleep apnea: Unlike OSA, the airway is not blocked, but the brain fails to signal the muscles to breathe, due to instability in the respiratory control centre.

Link between Down syndrome and Obstructive Sleep Apnoea

Anatomy

The US National Down Syndrome Society (NDSS) reports that:

• “There is a 50-100% incidence of obstructive sleep apnoea in individuals with Down Syndrome” and that “anatomy accounts for many of the reasons why there is a higher incidence of obstructive sleep apnoea in individuals with Down syndrome. Some of those factors include: central apnoea, low muscle tone in the mouth and upper airway, poor condition of airway movements, narrowed air passages in the midface and throat, a relatively large tongue, and hypertrophy (enlargement) of adenoid and tonsillar tissues. Increased upper airway infections and nasal secretions and a higher incidence of obesity further contribute to collapse and obstruction of both the oropharynx and the hypopharynx when the individual is sleeping”².

1 National Heart Foundation of Australia, BMI Calculator, 2019, https://www.heartfoundation.org.au/your-heart/know-your-risks/healthy-weight/bmi-calculator, accessed 10 October 2019. 2 National Down Syndrome Society, Obstructive Sleep Apnea & Down Syndrome, 2019, https://www.ndss.org/resources/obstructive-sleep-apnea-syndrome/, accessed 14 October 2019.

Page 102 of 165

As part of a 2009 cohort study, a literature review was conducted to assess the anatomical reasons for why people with Down syndrome have a predisposition to having OSA.

The study found that:

• “Patients with DS have many predisposing factors for OSAS, including midfacial hypoplasia and mandibular hypoplasia, glossoptosis, an abnormally small upper airway with superficially positioned tonsils and relative tonsillar and adenoidal encroachment, increased secretions, an increased incidence of lower respiratory tract anomalies, and a reduced tracheal diameter. In addition, in DS there is generalized hypotonia. As children with DS grow up, they maintain their anatomic abnormalities and generalized hypotonia. In addition, they have an increased risk of developing hypothyroidism and obesity, which are also risk factors for OSAS. Despite this high preponderance of risk factors for OSAS, there are few studies evaluating OSAS in adults with Down syndrome”3.

Mayo Clinic lists the causes/risk factors of obstructive sleep apnoea4. The main anatomical cause is the relaxing of muscles in the back of the throat causing the airway to narrow.

The risk factors are:

• Excess weight
  • Most but not all people with obstructive sleep apnea are overweight. Fat deposits around the upper airway may obstruct breathing. Medical conditions that are associated with obesity, such as hypothyroidism and polycystic ovary syndrome, also can cause obstructive sleep apnea. However, not everyone with obstructive sleep apnea is overweight and vice versa. Thin people can develop the disorder, too.
• Narrowed airway
  • You may inherit naturally narrow airways. Or your tonsils or adenoids may become enlarged, which can block your airway.
• High blood pressure (hypertension)
  • Obstructive sleep apnea is relatively common in people with hypertension.
• Chronic nasal congestion
  • Obstructive sleep apnea occurs twice as often in those who have consistent nasal congestion at night, regardless of the cause. This may be due to narrowed airways.
• Smoking
  • People who smoke are more likely to have obstructive sleep apnea.
• Diabetes
  • Obstructive sleep apnea may be more common in people with diabetes.
• Sex
  • In general, men are twice as likely as premenopausal women to have obstructive sleep apnea. The frequency of obstructive sleep apnea increases in women after menopause.
• A family history of sleep apnea

3 Trois MS, et al, ‘Obstructive Sleep Apnea in Adults with Down Syndrome’, Journal Clinical Sleep Med, 2009, vol. 5 no. 4, pp.317-323, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725249/, accessed 14 October 2019.

4 Mayo Clinic, Obstructive Sleep Apnea, 2019, https://www.mayoclinic.org/diseases-conditions/obstructive-sleep-apnea/symptoms-causes/syc-20352090, accessed 10 October 2019.

• If you have family members with obstructive sleep apnea, you may be at increased risk.

• Research has found an association between asthma and the risk of obstructive sleep apnea.

The National Association for Childhood Development (US based) states that OSA is common in children with Down syndrome due to several anatomical factors: the flattened midface, narrowed nasopharyngeal area, low tone of the muscles of the upper airway, larger than usual soft palates and enlarged adenoids and/or tonsils⁵.

Figure 1: Obstructive Sleep Apnoea – Melbourne Dental Sleep Clinic⁶

Children with Down syndrome

A high proportion of children with Down syndrome (DS) have the obstructive sleep apnea syndrome (OSAS)⁷. The Royal Children’s Hospital Melbourne outlines a screening schedule for children with Down syndrome, acknowledging that children with Down syndrome may have a number of associated medical problems. This includes screening for sleep disorders including obstructive sleep apnoea⁸.

⁵The National Association for Childhood Development, Sleep Apnea, 2019, http://downsyndrome.nacd.org/sleep_apnea.php, accessed 10 October 2019. ⁶Melbourne Dental Sleep Clinic, Obstructive Sleep Apnoea, 2019, https://sleepclinicmelbourne.com.au/sleep-apnoea-melbourne/ ⁷Trois, loc. cit. ⁸The Royal Children’s Hospital Melbourne, Screening for children with Down syndrome, 2019, https://www.rch.org.au/genmed/clinical_resources/Screening_for_children_with_Down_Syndrome/

A study from 1991 examined obstructive sleep apnoea in children with Down syndrome which concluded that children with DS frequently have obstructive sleep apnoea syndrome, with OSA, hypoxemia and hypoventilation.

Of the 53 study subjects studied “Nap polysomnograms 9sleep studies) were abnormal in 77% of children; 45% had obstructive sleep apnea (OSA), 4% had central apnea, and 6% had mixed apneas; 66% had hypoventilation (end-tidal PCO2 greater than 45 mm Hg) and 32% desaturation (arterial oxygen saturation less than 90%)”

Another study from 2003 assessed the prevalence of sleep-disordered breathing in a nonselected group of children with Down syndrome and to determine significant predisposing factors for this condition. This study concluded that:

• “The prevalence of sleep-disordered breathing in children with Down syndrome is very high, particularly in boys. Tonsillar hyperplasia may play a role in the pathophysiology of sleep-disordered breathing in these patients. Adenoid hyperplasia, obesity, and congenital heart disease were not important risk factors for sleep-disordered breathing”.

• From the 108 children with Down syndrome that were part of the study “The prevalence of sleep-disordered breathing was 54.6%, with a significantly higher prevalence in boys (64.7%) than in girls (38.5%)”

This 2:1 male/female sex ratio for children with Down syndrome and OSA is in line with the information provided by the Mayo Clinic website.

A study from 2016, conducted through the Cincinnati Children’s Hospital Medical Center, examined the high prevalence of comorbidity between obesity and sleep apnoea for children with Down syndrome. The study evaluated 303 children, 47.3% of whom were obese, compared to the general paediatric population which had a 12.1% obesity rate. The majority of children with Down syndrome also had OSAS.

Adults with Down syndrome

A cohort study from 2009 examined obstructive sleep apnoea in 16 adults with Down syndrome through evaluating for sleep disordered breathing. The study was conducted because despite the high preponderance of risk factors for OSA for people with Down syndrome and established high prevalence of OSA in children, there were few studies evaluating OSA in adults. The study “hypothesized that OSAS was common in adults with DS [and] also hypothesized that the severity of OSAS would be worse in those adults with DS who were most obese”. The study concluded that:

• “That adults with Down syndrome frequently have OSAS, with obstructive apnea, hypoxemia, hypoventilation, and sleep fragmentation. This could put them at risk for cardiovascular and neurologic complications . . . More and more studies are showing the consequences of untreated OSAS. Therefore, diagnosing and treating a common disorder such as OSAS prior to the development of serious complications is both reasonable and

Treatment Options for Sleep Apnoea

Research indicates that there is a general medical consensus for what the most common and effective treatments and interventions are for sleep apnoea.

Better Health Channel (Victorian Government) outlines some of the causes and treatments for sleep apnoea. This website suggests four treatment options:

1. Lifestyle changes including weight management are identified as the ‘first line of treatment for sleep apnoea’.
2. In addition to lifestyle changes, the most effective treatment available is a mask worn at night that prevents the throat from collapsing by transmitting increased air pressure to the collapsible segment of the throat. This is called ‘nasal continuous positive airway pressure’ (CPAP). The key to this treatment is finding a mask and machine that match your needs
3. Other treatment options may include the use of a specially made mouthguard or oral appliance or mandibular advancement splint15. Mouthguards work by holding your jaw forward during sleep.

13 Marcus, loc. cit. 14 Trois, loc. cit. 15 Victorian Government, Better Health Channel, ‘Sleep Apnoea’, https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/sleep-apnoea, accessed 14 October 2019.

As a last resort surgery to the palate and base of tongue is sometimes considered as an option.

The National Down Syndrome Society provides the following information about treatments for sleep apnoea for people with Down syndrome, which is consistent with those listed in the Better Health Channel (surgery, weight loss, BPAP and dental appliances”):

• If the primary care physician identifies any airway disturbances during sleep, a referral to an otolaryngologist should be done to determine if a sleep study and/or surgical intervention is needed. Non-invasive treatment options include a continuous positive airway pressure (CPAP) machine and weight loss.
• Removal of enlarged tonsils and adenoids is the first line surgical treatment. In individuals with Down syndrome, because of their midface hypoplasia and contracted nasopharynx, even mildly enlarged tonsil and adenoids may have a greater than expected effect in regards to airway obstruction. If the tonsils and adenoids do not appear enlarged, it has been suggested that a sleep study should be done to confirm that the individual does not have sleep apnea.
• Although tonsillectomy and adenoidectomy (T&A) is the most common initial surgical intervention, studies have shown that persistent obstructive sleep apnea after T&A is possible and more common in individuals with Down syndrome. Further interventions may be needed, both surgical and medical. All of these studies illustrate the need for post-operative evaluation of patients with Down syndrome for residual sleep apnea after T&A surgery with a post-operative sleep study or polysomnogram. Because of the higher rate of respiratory complications after removal of the tonsils and adenoids in individuals with Down syndrome, overnight observation in the hospital after this surgery is also recommended.
• If residual obstruction is present despite T&A surgery, medical treatments such as continuous positive pressure ventilation (CPAP/BiPAP) and oxygen use during sleep are still an option. Weight loss can also help to alleviate symptoms. Evaluations to determine the site or sites of residual airway obstruction include flexible nasopharyngoscopy and laryngoscopy examination in the office to rule out enlarged lingual tonsils, residual or regrowth of adenoid tissue, and possible glossoptosis. Radiographic studies using cine MRI studies have shown that the base of tongue obstruction from a combination of relative macroglossia and glossoptosis, enlarged lingual tonsils and also adenoid regrowth are some of the most common sites of residual obstruction in individuals with Down syndrome despite previous T&A.
• Surgical options for persistent obstructive sleep apnea in children with Down syndrome need to be tailored to each child’s individual pattern of obstruction. Surgical approaches currently being used include lingual tonsillectomy, uvulopalatopharyngoplasty, midline posterior glossectomy, genioglossus advancement, hyoid advancement and craniofacial surgery, including mandibular and midface advancements. Dental appliances to promote mandibular stabilization have also been shown to be helpful in cases of mild residual sleep apnea. However, in cases of severe sleep apnea with associated pulmonary hypertension, severe hypoxemia and/or cardiac complications, tracheostomy may also need to be considered”16.

The Healthline website (US based health and wellness information website – comparable to WebMD) also writes that the best methods to ensure airflow is not obstructed during sleep are weight loss, nasal decongestants, CPAP, BPAP, surgery and positional therapy17.

Notes:

• The reference number 16 at the bottom of the page appears to be a citation for

Healthline discusses the link between CPAP, BPAP and positional therapy:

• Continuous Positive Airway Pressure (CPAP): Continuous positive airway pressure (CPAP) therapy is the first line of treatment for obstructive sleep apnea. CPAP is administered through a facemask that’s worn at night. The facemask gently delivers positive airflow to keep the airways open at night. The positive airflow props the airways open. CPAP is a highly effective treatment for sleep apnea. A dental device may also be necessary to keep the lower jaw positioned forward.

• Bilevel Positive Airway Pressure (BiPAP or BPAP): Bilevel positive airway pressure machines are sometimes used for the treatment of OSA if CPAP therapy is not effective. BiPAP machines have settings, high and low, that respond to your breathing. This means the pressure changes during inhaling versus exhaling.

• Positional Therapy: Since sleeping on the back (supine position) can make sleep apnea worse for some people, positional therapy is used to help those with sleep apnea learn to sleep in other positions. Positional therapy and the use of CPAP can be discussed with a professional at a sleep center.

According to this information a person with Down syndrome may require the use of a CPAP, positioning therapy and a dental device concurrently.

Sleep Disorder Centres – available treatments

Sleep centres are specialist medical centres that offer treatments for a range of sleep disorders, including Sleep Apnoea. These specialist medical centres offer information on the most common and innovative treatments for sleep apnoea. Most sleep disorder clinics list CPAP as the first and most effective treatment option. For example, the Geelong Sleep Disorder Centre states that “the treatments that are used for sleep apnoea include:

General measures

- Reduce weight
- Reduce overall cardiovascular risk: As sleep apnoea increases the risk of cardiovascular disease, patients with sleep apnoea should actively reduce their overall cardiovascular risk with smoking cessation, blood pressure treatment, reducing cholesterol, improved physical fitness and weight reduction
- Reduce alcohol: sleep apnoea is worsened by muscular relaxation that occurs during sleep and is worsened by the muscular relaxing effects of alcohol.

CPAP therapy

- Continuous positive airway pressure (CPAP) is the most effective treatment for obstructive sleep apnoea. When pressure settings are adequate, and there is little air leak, CPAP completely controls sleep apnoea. However, whilst CPAP is a very effective treatment, it can be difficult to get used to, so it is important to work closely with your treating team to get the best results when using CPAP.

Dental appliances

• Oral appliances, called mandibular advancement splints are useful in treating OSA, and although not on average as effective as CPAP, are usually well tolerated. The best candidates for an oral appliance are those who are not obese and have mild or moderate sleep apnoea.

Provent

• Provent is a novel treatment for snoring and sleep apnoea that involves the application of self-adhesive valves over each nostril prior to bed. These one-way valves make it relatively easy to breathe in but hard to breathe out, creating a back-pressure in the throat, known as EPAP. On average in clinical trials, these have shown similar effectiveness to oral appliances (that is, best for mild-to-moderate sleep apnoea) but are a reasonable treatment option to consider at all severities of OSA, particularly where other treatments have been poorly tolerated.

Surgery

• Surgery for sleep apnoea is generally not an effective long-term treatment unless there are specific upper airway abnormalities such as markedly enlarged tonsils or nasal obstruction. If surgery is being considered, knowing the severity of sleep apnoea and health effects of sleep apnoea is important prior to surgery. This information is used to provide a safe anaesthetic as well as plan the most effective surgical treatment possible.

The Future

• Experimental treatments currently include medications to treat sleep apnoea and electronic pacemakers to strengthen muscle tone in the throat dilator muscles at night. For the time being, these treatment are only typically used as part of clinical trials”.19

The Melbourne Dental Sleep Clinic also recommends CPAP as an effective treatment, but recognises that CPAP is not appropriate for everyone. The clinic specialises in dental splints and states that:

• “Here at our dental sleep apnea clinic in Melbourne, we can offer patients an alternative to CPAP (continuous positive airway pressure). With CPAP therapy, a breathing mask is worn over your face at night which blows pressurised air into the airway to prevent it from closing. Some patients find this therapy uncomfortable and inconvenient. The machine is also very noisy. As an alternative, we provide state-of-the-art customised oral appliances known as Mandibular Advancement Splints or MAS for short”.

• These specialised dental appliances are made from the latest 3D printed nylon using CAD/CAM technology. Customised to each individual for a perfect fit, they are less bulky and much stronger than other dental splints made from acrylic. They are worn at night just like a mouthguard and work by holding the bottom jaw and the tongue forward. This opens the airway and prevents the soft tissues at the back of the throat from vibrating – which is heard as a snore. Dental splints are extremely easy to use and because of their compact size, they are also handy devices to have with you when travelling”20.

19 Geelong Sleep Disorders Centre, ‘Snoring Sleep Apnoea’, 2019, http://geelongsleep.com.au/snoring-sleep- apnoea, accessed 14 October 2019.

20 Melbourne Dental Sleep Clinic,’ Obstructive Sleep Apnea’, 2019, https://sleepclinicmelbourne.com.au/sleep- apnoea-melbourne/, accessed 14 October 2019.

P a g e | 9

Types of CPAP machines and masks.

CPAP Australia provide a comprehensive list of machines, accessories, sleep sets and masks. Information can be found here: https://www.cpapaustralia.com.au/

ResSleep is an Australian sleep technology provider for the treatment of snoring and sleep apnoea. They provided a comprehensive list of products. Note: this company may have a financial interest in advocating for specific brands.

Information can be found here: https://www.ressleep.com.au/our-products/

Is a referral / prescription from a sleep clinical required?

Yes. The CPAP Australia website states that “Patients require a prescription from a sleep specialist or GP before starting on CPAP treatment”21.

The ResSleep website does require a referral form to be filled out by the patients GP and then a follow up appointment with an independent sleep physician is required to prescribe the correct equipment.

One sleep clinic in Sydney’s discusses the prescribing of sleep assistive technology and highlights potential risks.

• “Our approach is to advise patients on the most appropriate masks and machines but we do not sell equipment. Our doctors support professional guidelines that describe substantial ethical issues when doctors directly sell equipment or encourage only one form of treatment only to patients.

• Other treatments we may use include mandibular (dental) advancement splints, upper airway surgery (nose and/or throat), body position devices during sleep and weight loss. Our interdisciplinary clinics can provide all these treatments using a range of expert specialists many of who are at the forefront of research in sleep disorders. Our research also is investigating a range of new treatments including low flow oxygen during sleep and medications in carefully selected patients. In 2015, we expect to introduce special new dental devices and even upper airway “pacemakers” as alternative treatments for sleep apnea”22.

Medicare Australia

In Australia there are some Medicare rebate sleep studies.

In general, to be eligible for the subsidised sleep study

• “GPs will need to administer screening questionnaires before directly ordering a Medicare rebatable sleep study.

• Only if these screening questionnaires are positive, can GPs refer directly for a Medicare rebatable sleep study test.

21 CPAP Australia, 2019, https://www.cpapaustralia.com.au/cpap-general-faqs/

22 Professor. Grunstein, R, ‘Obstructive Sleep Apnoea Treatments’, 2019, https://sleepclinicsydney.com.au/clinic/obstructive-sleep-apnoea/, accessed 14 October 2019.

P a g e | 10

• The screening questionnaires restrict testing to patients with a “high probability for symptomatic, moderate to severe obstructive sleep apnoea”.

• Following sleep study testing, “the results and treatment options following any diagnostic sleep study should be discussed during a professional attendance with a medical practitioner before the initiation of any therapy”23.

Information about the MBS sleep studies can be found here:

http://www.mbsonline.gov.au/internet/mbsonline/publishing.nsf/Content/2A5587834B9229ADCA2 5831A000B5FDA/$File/Sleep%20Disorders%204%20Feb%202019.pdf

http://www.mbsonline.gov.au/internet/mbsonline/publishing.nsf/Content/2A5587834B9229ADCA2 5831A000B5FDA/$File/FAQ%20-%20Thoracic%20Medicine.pdf

Weight Management for people with Down syndrome

A literature review from 2018 examined 45 original research articles to identify the common determinants causing obesity and overweightness in children with Down syndrome. The outcomes of this literature review concluded that:

• “Youth with DS had higher rates of overweight and obesity than youths without DS. Likely determinants of obesity included increased leptin, decreased resting energy expenditure, comorbidities, unfavorable diet, and low physical activity levels. Obesity was positively associated with obstructive sleep apnea, dyslipidemia, hyperinsulinemia, and gait disorder. Interventions for obesity prevention and control were primarily based on exercise-based programs, and were insufficient to achieve weight or fat loss”24.

Another literature review publication (Polish) from 2015 examining Down syndrome and the genetic and nutritional aspects of accompanying disorders found that:

(acknowledging issues with contemporary language)

• “Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases…Symptoms include intellectual disability . . ., early onset of Alzheimer’s disease and the appearance of various phenotypic features such as narrow slanted eyes, flat nose and short stature. There are other health problems throughout the body, consisting in part of cardiac defects and thyroid function abnormalities along with nutritional disorders (ie. overweight, obesity, hypercholesterolemia and deficiencies of vitamins and minerals)”. . . Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (eg. celiac disease) or malabsorption. DS persons with overweight or obesity are linked with a slow metabolic rate, abnormal blood leptin concentrations and exhibit low levels of physical activity. Vitamin B group deficiencies and abnormal blood homocysteine levels decrease the rate of intellectual development in DS cases. Zinc deficiencies result in short stature, thyroid function disorders and an increased appetite caused by excessive

23 Healthed, Changes to Medicare for Home Sleep Study Testing, 2019, https://www.healthed.com.au/clinical- articles/in-depth-articles/changes-to-medicare-for-home-sleep-study-testing/, accessed 14 October 2019.

24 Bertapelli, F, ‘Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: A literature review’, Research in Developmental Disabilities, 2016, vol. 57, pp. 181-92, https://www.ncbi.nlm.nih.gov/pubmed/27448331, accessed 14 October 2019.

P a g e | 11

supplementation. Scientific advances in the research and diagnosis of DS, as well as prevention of any associated conditions, have significantly increased life expectancies of those with this genetic disorder. Early dietary interventions by parents or guardians of DS children afford an opportunity for decreasing the risk or delaying some of the DS associated conditions from appearing, thus beneficially impacting on their quality of life”25.

Conclusion

• There is a significant amount of high quality peer reviewed research, including cohort studies and expert medical opinion that substantiates the link between Down syndrome and Obstructive Sleep Apnoea (OSA) / Obstructive Sleep Apnoea Syndrome (OSAS) and other sleep disorders in general. • Evidence also indicates that overweightness/obesity plays an important role in the pathophysiology of OSA in this population, acting as an exacerbating factor. • Treatment information indicates that CPAP is considered the first line / most effective treatment option of sleep apnoea, but due to noise and the mask it may not be the most appropriate for everyone. • A CPAP machine needs to be prescribed by a sleep specialist or GP.

Recommendation

• Before approving the funding of a CPAP machine or any other AT for sleep related disorders, a participant should provide information to show that: o they have been to a sleep specialist at a clinic or centre; o that a CPAP machine is going to be effective and beneficial to them; and o that an alternative treatment approach is not more appropriate e.g. positional therapy, weight management, mouthguard, provent or surgery.

25 Mazurek, D & Wyka, J, ‘Down syndrome–genetic and nutritional aspects of accompanying disorders’, Roczniki Panstwowego Zakladu Higieny, 2015, vol. 66, pp.189-94, https://www.ncbi.nlm.nih.gov/pubmed/26400113, accessed 14 October 2019.

P a g e | 12

Reference List

Basil, JS, ‘Retrospective Study of Obesity in Children with Down Syndrome’, Journal Paediatrics, June 2016, vol.173, pp.143-8, https://www.ncbi.nlm.nih.gov/pubmed/26987801, accessed 14 October 2019.

Bertapelli, F, ‘Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: A literature review’, Research in Developmental Disabilities, 2016, vol. 57, pp. 181-92, https://www.ncbi.nlm.nih.gov/pubmed/27448331, accessed 14 October 2019.

De Miguel-Diez, J, Villa-Anseni, JR & Alvarex-Sala, JL, Prevalence of sleep-disordered breathing in children with Down syndrome: polygraphic findings in 108 children’, Sleep, 2003, vol.26 no.8, pp.1006-9, https://www.ncbi.nlm.nih.gov/pubmed/14746382, accessed 14 October 2019.

Geelong Sleep Disorders Centre, ‘Snoring Sleep Apnoea’, 2019, http://geelongsleep.com.au/snoring-sleep- apnoea, accessed 14 October 2019.

Healthed, Changes to Medicare for Home Sleep Study Testing, 2019, https://www.healthed.com.au/clinical- articles/in-depth-articles/changes-to-medicare-for-home-sleep-study-testing/, accessed 14 October 2019.

Healthline, Obstructive Sleep Apnea, 2019, https://www.healthline.com/health/sleep/obstructive-sleep- apnea#treatment, accessed 14 October 2019.

Marcus CL, et al., ‘Obstructive sleep apnea in children with Down syndrome’, Paediatrics, 1991, vo.88 no.1, pp. 132-, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725249/#B6, accessed 14 October.

Mayo Clinic, Obstructive Sleep Apnea, 2019, https://www.mayoclinic.org/diseases-conditions/obstructive- sleep-apnea/symptoms-causes/syc-20352090, accessed 10 October 2019.

Mazurek, D & Wyka, J, ‘Down syndrome–genetic and nutritional aspects of accompanying disorders’, Roczniki Panstwowego Zakladu Higieny, 2015, vol. 66, pp.189-94, https://www.ncbi.nlm.nih.gov/pubmed/26400113, accessed 14 October 2019.

Melbourne Dental Sleep Clinic, Obstructive Sleep Apnoea, 2019, https://sleepclinicmelbourne.com.au/sleep- apnoea-melbourne/

Melbourne Dental Sleep Clinic,’ Obstructive Sleep Apnea’, 2019, https://sleepclinicmelbourne.com.au/sleep- apnoea-melbourne/, accessed 14 October 2019.

National Down Syndrome Society, Obstructive Sleep Apnea & Down Syndrome, 2019, https://www.ndss.org/resources/obstructive-sleep-apnea-syndrome/, accessed 14 October 2019.

National Heart Foundation of Australia, BMI Calculator, 2019, https://www.heartfoundation.org.au/your- heart/know-your-risks/healthy-weight/bmi-calculator, accessed 10 October 2019.

Professor. Grunstein, R, ‘Obstructive Sleep Apnoea Treatments’, 2019, https://sleepclinicsydney.com.au/clinic/obstructive-sleep-apnoea/, accessed 14 October 2019.

The National Association for Childhood Development, Sleep Apnea, 2019, http://downsyndrome.nacd.org/sleep_apnea.php, accessed 10 October 2019.

The Royal Children’s Hospital Melbourne, Screening for children with Down syndrome, 2019, https://www.rch.org.au/genmed/clinical_resources/Screening_for_children_with_Down_Syndrome/

P a g e | 13

Trois MS, et al, ‘Obstructive Sleep Apnea in Adults with Down Syndrome’, Journal Clinical Sleep Med, 2009, vol. 5 no. 4, pp.317-323, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725249/, accessed 14 October 2019.

Victorian Government, Better Health Channel, ‘Sleep Apnoea’, https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/sleep-apnoea, accessed 14 October 2019.

P a g e | 14

DOCUMENT 15

Research Request – Efficacy of an Eating Disorder Exercise Program Development by an Exercise Physiologist

Contents

Summary ………………………………………………………………………………………………………………………………. 1 Exercise as an Intervention for Eating Disorders (ED) …………………………………………………………………. 2 Scope of Practice of Exercise Physiologists ………………………………………………………………………………… 4 Scope of Practice of other Exercise Professionals ………………………………………………………………………. 5 Reference List ………………………………………………………………………………………………………………………… 6

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making.

Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice.

The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Summary

• The extent of research regarding the use of exercise as an intervention in eating disorders treatment is plentiful, and there have been recent themes in the research surrounding it’s efficacy as an adjunct to standard eating disorder treatments.

• Research indicates that the most suitable use of exercise as an intervention in eating disorder treatment is within a program developed by a multidisciplinary team of experts.

• It appears that the scope of practice of an Exercise Physiologist in Australia does not encompass the development and supervision of an exercise program as an intervention for the treatment of eating disorders, as a sole program for such treatment. It does however appear to encompass the scope of an Exercise Physiology to design, implement and evaluate exercise interventions based on referral information, presenting pathologies and co- morbidities, clinical reasoning, pre-intervention assessments and the analysis, interpretation

Research Request – Efficacy of an Eating Disorder Exercise Program Development by an Exercise Physiologist Page 1 of 7

and application of scientific evidence.

• It would appear that the an Exercise Physiologist has the scope of practice to develop and supervise an exercise program for a client with bulimia and anorexia nervosa disorders, as part of a multidisciplinary team approach to treatment.

• Research and evolving trends in recent research suggests that the multidisciplinary team approach to treatment is best practice.

• It appears that the scope of practice of other exercise professionals such as Personal Trainers, Gym Instructors, Group Exercise Instructors and Group Exercise Leaders, does not give them the scope to develop exercise programs or offer nutritional advice, to clients with eating disorders.

Exercise as an Intervention for Eating Disorders (ED)

Although asserting that person-centred, stepped care is the most effective way to treat someone with an eating disorder, the Australian based Butterfly Foundation for Eating Disorders, outlines the following evidence-based treatments which have been found to be effective in the treatment of eating disorders1:

• Psychotherapy • Nutritional management • Medication • Family Approaches • Self Help Approaches

However, there is a rapidly growing body of evidence suggesting that exercise may be manageable in some, but not all, people with an eating disorder.

In a 2016 systematic review and proposal for guidelines2, Brian Cook PhD, a prolific researcher and sought after expert in the field of eating disorders and associated psychiatric illnesses, found that:

• Several recent narrative and meta-analytic reviews have concluded that when nutritional needs are satisfied, exercise appears to be a safe option in ED treatment.

• These preliminary results are encouraging and suggest that under close supervision and in the absence of medical or nutritional contraindications, exercise may be an efficacious adjunct to standard ED treatments.

• These reviews suggest that one key to reversing exercise from being a compensatory behaviour to that of a healthy behaviour may be to change a person’s pathological attitudes

1 Butterfly Foundation for Eating Disorders, “How are Eating Disorders Treated?”, [website], 2020. https://thebutterflyfoundation.org.au/understand-eating-disorders/how-are-eating-disorders- treated, (accessed 21 January 2020)

2 B. Cook et at., “Exercise in eating disorders treatment: Systematic review and proposal of guidelines”, Medicine & Science in Sport & Exercise, Vol 48, No 7, pp.1408-1414, 2016, https://cfe.keltyeatingdisorders.ca/sites/default/files/resource/Cook%20et%20al%202016%20MSSE. pdf

Research Request – Efficacy of an Eating Disorder Exercise Program Development by an Exercise Physiologist Page 2 of 7

and thoughts about exercise itself.

• Exercise may then be introduced at low intensity and small amounts to support physiological and psychological healing and recovery

In the research review and proposal, the author consolidated various techniques and considerations that influence how exercise has been successfully used as part of ED treatment programs, including that “a multidisciplinary team of experts in exercise, nutrition, mental health, physical therapy, and medicine should work collaboratively to develop individually tailored exercise programs with participation contingent upon adherence to ED therapy and should closely monitor ED patients to ensure safety”

Aligning with other research sourced on the subject of exercise as a treatment for ED, the author suggests that it “is also important to note that there will be times when exercise needs to be prevented or seriously modified, given a patient’s clinical status. Therapeutic exercise programs are ideally conducted with ED patients under close monitoring and supervision by a multidisciplinary treatment team”. 3

A 2018 research study taking place within a centre for eating disorders in Norway, set out to examine 15 years of clinical experience with exercise approaches as an integrated part our inpatients treatment multidisciplinary program, in a bid to form clinical program guidelines. The author’s recommendations support their earlier proposals for treatment approaches to exercise and exercise- related issues as a beneficial supplement to the treatment of ED inpatients. They did not experience any adverse influences on patients’ recovery processes, such as their rate of weight gain. 4

With a focus on anorexia and bulimia nervosa, a 2013 systematic review summarised the evidence from randomised controlled trials, examining the effectiveness of physical therapy compared with care as usual or a wait-list condition on eating pathology and on physiological and psychological parameters in patients.

The results of the study demonstrated that aerobic and resistance training result in significantly increased muscle strength, body mass index and body fat percentage in anorexia patients. In addition, aerobic exercise, yoga, massage and basic body awareness therapy significantly lowered scores of eating pathology and depressive symptoms in both anorexia and bulimia nervosa patients. No adverse effects were reported. 5

A more recent 2018 cohort study with a focus on long standing Anorexia Nervosa (AN), and with the awareness that compulsive exercise is a common symptom, looked at the effectiveness of maximal strength training (MST), acknowledging that such training has not been prescribed to those with AN due to uncertainty of tolerance. The study tested muscle strength, bone mineral density, AN psychopathology, and compulsive exercise at baseline, posttest, and 6-month follow-up. Attendance

3 Butterfly Foundation for Eating Disorders, “How are Eating Disorders Treated?”, [website], 2020. https://thebutterflyfoundation.org.au/understand-eating-disorders/how-are-eating-disorders-treated, (accessed 21 January 2020)

4 M. Danielsen et al.,

rate was 100%. The subject improved muscle strength by 20% to 40%. BMD in lumbar spine improved by 4% to posttest, and by 8% from baseline to 6-month follow-up. No changes in AN psychopathology or levels of compulsive exercise were detected. Perceived psychological benefits including new bodily experiences were self-reported by the subject, emphasizing the importance of close follow-up by competent instructors. 6

Scope of Practice of Exercise Physiologists

Exercise & Sports Science Australia (ESSA), is a professional organisation which is committed to establishing, promoting and defending the career paths of tertiary trained exercise and sports science practitioners.

In looking at the scope of an Exercise Physiologist in developing and supervising an exercise program for a client with Bulimia and Anorexia Nervosa, the following ESSA documents are pertinent:

• ESSA: Accredited Exercise Physiologist Scope and Practice 2018 • ESSA: Accredited Exercise Physiologist Professional Standards 2015

Accredited Exercise Physiologists (AEP) specialise in clinical exercise interventions for a broad range of pathological populations. These persons may be at risk of developing, or have existing, medical conditions and injuries. The aims of AEP interventions are to prevent or manage acute, sub-acute or chronic disease or injury, and assist in restoring one’s optimal physical function, health or wellness. 7

Graduate Attributes of an AEP

It is expected that a graduate will include the following attributes aligned to the five generic Professional Standards of the AEP (Professional Standards, Attributes 6-9, page 5) 8:

• Broad and coherent knowledge and understanding of the pathophysiological bases of AEP target conditions, and the associated medical, surgical and other allied health treatment modalities and interventions for these conditions.

• Broad and coherent knowledge and understanding of interactions between AEP target conditions, their treatments and the effects of exercise interventions in managing chronic and complex clinical presentations.

6 S. Solfrid-Sandra et al.,

• Well-developed cognitive and technical skills to design, implement and evaluate safe and effective exercise interventions, based on referral information, presenting pathologies and co-morbidities, clinical reasoning, pre-intervention assessments and the analysis, interpretation and application of scientific evidence.

• Well-developed cognitive and technical skills to select, design or modify and then analyse, interpret and apply assessment protocols and methodologies appropriate to the client and situation for acute, sub-acute and chronic disease and injury management, workplace health and rehabilitation and other clinical exercise services.

Design of Exercise Interventions

Standard 4 of the Professional Standards indicates:

• Graduates of an accredited course in clinical exercise physiology can design safe and effective exercise interventions, and health and wellness interventions to effect behaviour change and increase exercise and functional capacity across diverse contexts and settings.

• Graduates of an accredited course in clinical exercise physiology can design safe and effective exercise plans that consider available scientific evidence, client treatment goals, medical history, clinical status, screening and assessments information and other influencing factors.

• Graduates of an accredited course in clinical exercise physiology can design and revise functional capacity assessments and interventions that consider the clients’ needs, capabilities, duties and/or workplace setting/requirements. 9

Scope of Practice of other Exercise Professionals

Fitness Australia is a not-for-profit industry association, which exists to professionalise the fitness industry through engaging in partnerships, advocacy, delivering education, quality and accreditation.

Exercise professionals registered with Fitness Australia provide a variety of exercise services for a range of clientele across many varied settings. Competency to practice is represented through the registration category held and associated continuing education completed.

A Registered Exercise Professional undertakes one or more of the following roles:

• Personal Trainer • Gym Instructor • Group Exercise Instructor • Group Exercise Leader

9 Exercise and Sports Science Australia, “

Fitness Australia has a position statement which addresses the scope of practice of the above roles. The position statements suggests that “Registered Exercise Professionals are qualified to plan and deliver exercise for low and moderate risk clientele based on the guidelines defined in the Adult Pre- exercise Screening System (APSS) document.” 10

It would appear that in the case of a potential client with Bulimia and Anorexia Nervosa, the exercise professional registered with Fitness Australia would be required to “seek guidance from an appropriate allied health professional or medical practitioner prior to undertaking exercise”.

As well, Fitness Australia has a position statement addressing the scope of practice of their registered exercise professionals and nutrition advice to clients. The scope of practice indicates that a registered professional would not have a capacity to give nutritional advice to client’s with an eating disorder. 11

Fitness Australia also has guidelines which were developed with the Centre for Eating & Dieting Disorders, which assists registered professionals in identifying and managing clients with eating disorders and/or problems with excessive exercise. 12

Reference List

B. Cook et at.,

Exercise and Sports Science Australia, “

DOCUMENT 16

Research Request – Cystic Fibrosis in Children

Contents

Cystic Fibrosis – “Chest PT” and Disability related Health Supports for children …………………………….. 2 For children with Cystic Fibrosis, what is the best practice for Airway clearance techniques and what are the AT considerations? ………………………………………………………………………………………….. 2 What NDIS supports should be provided to Children with Cystic Fibrosis? ………………………………… 2 Notes ………………………………………………………………………………………………………………………………… 3 Reference List ………………………………………………………………………………………………………………………… 4

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making.

Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice.

The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Research Request – Cystic Fibrosis in Children Page 1 of 5

Cystic Fibrosis – “Chest PT” and Disability related Health Supports

for children

For children with Cystic Fibrosis, what is the best practice for Airway clearance techniques

and what are the AT considerations?

Airway clearance techniques (ACT) are a cornerstone of CF care and should be performed across the lifespan [1] of the participant. ACT’s such as postural drainage, percussion and vibration are referred to in many of the documents reviewed as “Chest PT” or “Chest Physiotherapy”. These treatments are often administered by non-clinical supports (family/informal supports, support workers or therapy assistants) who have received training from the physiotherapist, in accordance to the therapist’s instructions [2][4]. Lived experience statements published by CF groups suggest benefits to this therapy being performed by a family member [2].

“I firmly believe that I am better off for focusing on chest PT done manually by my dad … It was a more personal connection. I wasn’t sitting alone for an hour a day with a vest on. I know it’s time consuming, but I think there’s a value to it.” – Chris Kvam, adult with CF [2]

Therapeutic techniques to achieve airway clearance are advocated in UK and US guidelines. In most circumstances, there is little evidence to support the use of one technique over another. Individually tailored schedules and application of airway clearance technique are recommended [3]. Practitioner Flexibility and appreciation of patient preference are essential when prescribing a suitable airway clearance technique are also strongly indicated [3].

What NDIS supports should be provided to Children with Cystic Fibrosis?

Evidence is not concisely available in this regard. Following an extensive literature review, all available clinical guidelines indicate that supports are determined on a case-by-case basis[10]. In light of current agency practices, it would appear appropriate that participants with Cystic Fibrosis should be assessed by a physiotherapist and funded for supports based on the recommendations of that assessment. Indicatively, the Standards of Care and Good Clinical Practice for the Physiotherapy Management of Cystic Fibrosis (Second edition, June 2011) recommend that a physiotherapy annual review should be carried out by a Specialist CF Physiotherapist. The recommend that a second yearly visit should be the minimum, with additional visits as indicated from the annual review [10].

For newly diagnosed participants, frequency of input from the physiotherapist should be tailored to the individual but frequent assessment and advice will be likely required in the months following diagnosis [10], and consideration will likely be required for this circumstance in planning. Access to a specialist dietician may in some cases be relevant [3] and regular exercise throughout the life of the participant is recommended [5][6] which may conceivably warrant access to an exercise physiologist when supported by evidence of the assessing physiotherapist.

Of note, chest physiotherapy or chest PT is widely discussed in relation to Airway Clearance Techniques (ACTs) such as postural drainage, percussion and vibration. It is suggested that an emphasis be placed on distinguishing these techniques from Physiotherapy when selecting

terminology. While these techniques should be directed by a physiotherapist, there is no requirement for a physiotherapist to perform them in general circumstances [2][4]. Informal supports and/or support workers/therapy assistants should perform the majority of implementation of the physiotherapist’s recommendations, with monitoring and adjustments to schedule, and/or AT assessments performed by a Physiotherapist.

Notes

The sources below appear to be consistent with all available literature. No contradictory or challenging positions were identified during this research.

Reference List

[1] Physiotherapy for Cystic Fibrosis in Australia: A Consensus Statement.

https://www.thoracic.org.au/journal- publishing/command/download_file/id/19/filename/Physiotherapy_for_Cystic_Fibrosis_in_Australia _A_Consensus_Statement.pdf

[2] Cystic Fibrosis Foundation - Chest Physical Therapy. Date of Access 31/01/2019.

https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Airway-Clearance/Chest-Physical- Therapy/

[3] European Cystic Fibrosis Society (ECFS) Best Practice Guide 2018.

https://www.ncbi.nlm.nih.gov/pubmed/29506920

[4] Royal Children’s Hospital Melbourne - Clinical Guidelines: Nurses role in advanced secretion clearance. Date of Access 31/01/2019.

https://www.rch.org.au/rchcpg/hospital_clinical_guideline_index/Nurses_role_in_advanced_secreti on_clearance/

[5] Thoracic Society of Australia and New Zealand Physiotherapy for Cystic Fibrosis in Australia and New Zealand - Clinical Practice Guideline April 2016

http://onlinelibrary.wiley.com/doi/10.1111/resp.12764/full

https://www.thoracic.org.au/journal-publishing/command/download_file/id/32/filename/TSANZ- Physio-Guidelines-2016-web.pdf

[6] Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline. Button Et Al 2016

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840479/

https://onlinelibrary.wiley.com/doi/full/10.1111/resp.12764

[7] Association of Chartered Physiotherapists in Cystic Fibrosis statement on the VEST. Date of Access 31/01/2019.

https://www.cysticfibrosis.org.uk/what-is-cystic-fibrosis/cystic-fibrosis- care/physiotherapy/physiotherapy-faqs/vest-statement

[8] Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline. Button Et Al 2016

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840479/

https://onlinelibrary.wiley.com/doi/full/10.1111/resp.12764

[9] Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis

Cochrane Systematic Review, November 2019.

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003147.pub5/full

[10] Standards of Care and Good Clinical Practice for the Physiotherapy Management of Cystic Fibrosis. Second edition. June 2011.

https://www.cysticfibrosis.org.uk/~/media/documents/the-work-we-do/care/consensus-docs-with- new-address/physio-management-of-cf.ashx?la=en

FOI 24/25-0413 DOCUMENT 17

Research Request – Syndromic obesity & causative link to disability

Contents

Issue: DRHS for NDIS participants with obesity ………………………………………………………………………….. 3 Gap in current guidance and legislation re: obesity ………………………………………………………………… 3 Syndromic obesity - overview ………………………………………………………………………………………………….. 4 Syndromic Forms of Human Obesity …………………………………………………………………………………….. 5 Obesity in Australia ………………………………………………………………………………………………………………… 6 Cost to Public Health System ……………………………………………………………………………………………….. 7 National Healthcare Agreement (2018) …………………………………………………………………………………. 7

1. Prader-Willi Syndrome (PWS) …………………………………………………………………………………………… 9 Causes of obesity in PWS ………………………………………………………………………………………………….. 9 Early Intervention …………………………………………………………………………………………………………….. 10 Further research in PWS ………………………………………………………………………………………………….. 11
2. Bardet-Biedl syndrome (BBS) ………………………………………………………………………………………….. 11 Causes of obesity in Bardet-Biedl syndrome ……………………………………………………………………… 12 Early intervention……………………………………………………………………………………………………………… 13
3. Alstrom syndrome …………………………………………………………………………………………………………. 13 Causes of obesity in Alstrom syndrome ……………………………………………………………………………….. 14 Early intervention……………………………………………………………………………………………………………… 14
4. WAGR syndrome ………………………………………………………………………………………………….. 15 Causes of obesity in WAGRO syndrome ………………………………………………………………………………. 15 Early intervention……………………………………………………………………………………………………………… 16
5. Albright’s Hereditary Osteodystrophy ……………………………………………………………………… 16 Causes of obesity in Albright’s Hereditary Osteodystrophy ……………………………………………………. 17 Early intervention……………………………………………………………………………………………………………… 17

Research Request – Obesity and direct link to disability | Page 1 of 37

Further research ………………………………………………………………………………………………………………. 18 6) Down syndrome ……………………………………………………………………………………………………………. 18 Causes of Obesity in Down syndrome ……………………………………………………………………… 18 Open source information …………………………………………………………………………………………………… 19 Academic Research sources ……………………………………………………………………………………. 19 Early Intervention ………………………………………………………………………………………………….. 21 Further Research Needed for Obesity and DS ……………………………………………………….. 22 7) Autism Spectrum Disorder (ASD) ……………………………………………………………………… 22 Causes of obesity in ASD ………………………………………………………………………………………………….. 22 Open Source Information ………………………………………………………………………………………………….. 23 Academic Research Sources ……………………………………………………………………………………. 23 16p11.2 deletion in ASD…………………………………………………………………………………………………. 24 Further Research Needed for Obesity and ASD ……………………………………………………….. 26 8) Intellectual Disability (in general) ……………………………………………………………………… 26 Causes of obesity in Intellectual Disability ……………………………………………………………………… 27 Academic Research Resources ……………………………………………………………………………………. 27 Early Intervention ………………………………………………………………………………………………….. 28 Further Research Needed for Intellectual Disability ……………………………………………………….. 28 9) Psychosocial disability (medication side effects) ……………………………………………………….. 29 Weight loss interventions for psychosocial disability ……………………………………………………….. 31 Conclusion ………………………………………………………………………………………………………………… 32 Reference List ………………………………………………………………………………………………………………… 33

Please note: • The research and literature reviews collated by our TAT Research Team are not to be shared external to the Branch. These are for internal TAT use only and are intended to assist our advisors with their reasonable and necessary decision making. • Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. • The Research Team are unable to ensure that the information listed below provides a holistic and contemporary snapshot of the aetiology of obesity in these disability groups.

Research Request – Obesity and direct link to disability | Page 2 of 37

Scope of this document

This document examines the most common genetic disorders of obesity or syndromic forms of obesity for which the genetic basis of obesity has been partially or completely elucidated. These disorders include:

• Prada-Willi Syndrome, Bardet-Biedl syndrome, Alstrom syndrome, WAGR syndrome and other conditions with genetic deletions, particularly 16p11.2 deletions (commonly found in people with Autism Spectrum Disorder).

The document also examines:

• Down syndrome, Intellectual Disabilities (in general) and the impact that psychiatric medications have on weight gain / obesity have also been considered.

Issue: DRHS for NDIS participants with obesity

Gap in current guidance and legislation re: obesity

In the context of the NDIS and the funding of Disability Related Health Supports (DRHS), disabilities and chronic health conditions that may lead to obesity (directly and indirectly) require further consideration. This is because of:

• the stated ‘whole of person’ approach that must be taken during NDIS planning; and • the associated functional impairment(s) that obesity commonly cause.

As outlined in the current guidance, the NDIS will fund a DRHS when it:

• directly relates to a person’s ongoing functional impairment, and • is a regular part of daily life, and • is most appropriately funded or provided by the NDIS, and • is evidenced meaning supporting information can generally be obtained.

A DRHS support must still meet the NDIA’s legislative framework. As outlined in the DRHS PG:

• The NDIA takes a whole of person approach when funding supports in a participant’s NDIS plan. This means that funding for supports is based on the reasonable and necessary criteria in section 34 of NDIS Act and Rules and is not limited to the impairments which satisfy the criteria for accessing the NDIS.

• Specifically, in accordance with section 34(1)(f) of the NDIS Act, the NDIA needs to determine whether a disability-related health support for a participant is most appropriately funded or provided by the NDIS.

• The NDIS Supports for Participants Rules 2013, provide that the NDIS is responsible for supports related to a person’s ongoing functional impairment and that enable the person to undertake activities of daily living, including maintenance supports delivered or supervised by clinically trained or qualified health practitioners, where these are directly related to a functional impairment and integrally linked to the care and support a person requires to live in the community and participate in education and employment.

This legislation and guidance does not effectively consider how functional impairments associated with obesity factors into reasonable and necessary considerations.

Research Request – Obesity and direct link to disability | Page 3 of 37

Syndromic obesity - overview

While overweight and obesity is most commonly due to excess caloric intake, it is well established that genetic mutations or chromosomal abnormalities can cause excess weight gain. The term ‘syndromic obesity’ is used to describe obese children and adults with cognitive delay, dysmorphic features, organ-specific abnormalities, hyperphagia [abnormally increased appetite for consumption of food], and/or other signs of hypothalamic dysfunction”

The Royal Australian College of General practitioners (RACGP) published a review in 2017 examining recent genetic discoveries about the basis of human obesity and familial or syndromic obesity. The review found that obesity is sometimes part of a rare but recognised syndrome². The RACGP review lists the following syndromes:

• “Prader–Willi syndrome, an imprinting disorder, is the most common, occurring at a rate of one in 15,000. Babies with this syndrome are born ‘floppy’, have weak muscles and up-slanted eyes, and feed poorly. Over the first two years, the infant slowly develops a ravenous appetite, and has cognitive delay and behavioural issues. It is an imprinting defect, in the region of chromosome 15q11–13.

• A variant of the Fragile X syndrome has also been described that has features of Prader–Willi syndrome, with severe obesity developing early.

• Bardet−Biedel syndrome is an autosomal recessive disorder of ciliary function characterised by obesity, cognitive delay, polydactyly and retinitis pigmentosa, renal dysfunction and hypogonadism, sometimes resulting in diabetes. It has so far been mapped to 19 different genes.

• Albright’s hereditary osteodystrophy (pseudohypoparathyroidism) is associated with hyperphagia, obesity, short stature, round face, skeletal anomalies and cognitive delay. The GNAS gene mutation results in resistance to hormones such as parathormone, thyroid hormone and gonadotrophins.

• WAGR syndrome (11p14 deletions leading to brain-derived neurotrophic factor haploinsufficiency) is characterised by aniridia, obesity, growth retardation, cognitive delay and genitourinary deformities.

• Copy-number variations (CNVs) in the genome have also been described in association with obesity. CNVs are segments of the genome that differ in the number of diploid copies carried by healthy individuals. About 5% of healthy people have common varieties of CNV, and 1% have rare varieties. Common CNVs include chromosome 10q11.22, a region associated with the pancreatic polypeptide receptor, where low CNV was recently reported to be associated with high BMI, and also on chromosome 11q11 around the olfactory receptor genes with early onset extreme obesity”.

Similarly, a publication from 2011 by W. Chung examining ‘Mongenic and Syndromic Obesities in Humans’ considers the above conditions, but also lists Alstom syndrome and conditions with 16p11.2 deletions as syndromic obesity conditions.

¹ Irizarry, KA & Haqq, AM, ‘Syndromic Obesity’, Pediatric Obesity, Contemporary Endocrinology, 12 October 2017, pp. 153-182, https://link.springer.com/chapter/10.1007/978-3-319-68192-4_9, accessed 18 November 2019. ² Campbell, LV, ‘Genetics of obesity’, Australian Family Physician, Royal Australian College of General Practitioners, vol. 46, No. 7, 2017, pp-456-459, https://www.racgp.org.au/afp/2017/july/genetics-of-obesity/, accessed 18 November 2019. ³ Ibid.

Syndromic Forms of Human Obesity

According to Chung, these are the genetic causes and common phenotypes for the disorders that were considered.

4 Chung, WK. ‘An Overview of Mongenic and Syndromic Obesities in Human’. Paediatric Blood and Cancer. vol. 58, no. 1, 12 October 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215910/. accessed 12 November 2019.

5 Bell AJ, Bhate MS. Prevalence of overweight and obesity in Down’s syndrome and other mentally handicapped adults living in the community. J Intellect Disabil Res. 1992;36 ( Pt 4):359–364. https://www.ncbi.nlm.nih.gov/pubmed/1388077. accessed 29 November 2019.

Research Request – Obesity and direct link to disability | Page 5 of 37 Page 131 of 165

Obesity in Australia

In 2017-18, the Australian Bureau of Statistics’ National Health Survey showed that two thirds (67.0%) of Australian adults were overweight or obese (12.5 million people), an increase from 63.4% in 2014-15. Slightly more than a third (35.6%) were overweight and slightly less than a third were obese (31.3%). Just under one third (31.7%) were within the healthy weight range and one percent (1.3%) were underweight⁷. The National Health Survey also indicated that almost one quarter (24.9%) of children aged 5-17 years were overweight or obese in 2017-18 (17% overweight and 8.1% obese)⁸.

According to the Australian Government Department of Health:

Body mass index (BMI) is an index of weight-for-height that is commonly used to classify underweight, overweight and obesity in adults. It is calculated by dividing weight by the square of height: weight (kg)/height (m)⁹².

• Source: (WHO 2000).

The Australian Institute of Health and Welfare (AIHW) published a snapshot from 2014-2015 of prevalence of chronic health conditions in adults by weight status. It found that approximately 24%

Cost to Public Health System

The AIHW found that:

• “The estimated cost of obesity on the Australian economy in 2011–12 was $8.6 billion, which included $3.8 billion in direct costs and $4.8 billion in indirect costs—including absences from work, forgone tax and government subsidies. It has been estimated that, if no preventative action is taken to slow the growth of obesity, up to $87.7 billion in additional direct and indirect costs due to obesity may be incurred by 2025”12. Given that 2/3 adults and 1/4 children are overweight or obese (3/7 Australians), this poses a significant risk to Scheme sustainability if NDIS were to absorb the costs associated with obesity.

National Healthcare Agreement (2018)

The current National Healthcare Agreement (2018) firmly places obesity in the mainstream health care space:

• The National Healthcare Agreement affirms the agreement of all governments that Australia’s health system should:
  • be shaped around the health needs of individual patients, their families and communities;
  • focus on the prevention of disease and injury and the maintenance of health, not simply the treatment of illness;

10 Australian Institute of Health and Welfare, ‘A picture of overweight and obesity’, 2017, p.28, h<https://www.aihw.gov.au/getmedia/45f6ecc6-0caf-4af4-9ffc-a44c885b33d2/aihw-phe- 216.pdf.aspx?inline=true>, accessed 11 The Centers for Disease Control and Prevention, Disability and Obesity, 16 September 2019, hhttps://www.cdc.gov/ncbddd/disabilityandhealth/obesity.html, accessed 8 November 2019. 12 Ibid, p. 3.

Research Request – Obesity and direct link to disability

Page 134 of 165

• support an integrated approach to the promotion of healthy lifestyles, prevention of illness and injury, and diagnosis and treatment of illness across the continuum of care; and
• provide all Australians with timely access to quality health services based on their needs, not ability to pay, regardless of where they live in the country.

Specific genetic disorders and syndromes

The remainder of this paper provides a literature review on the common disorders and syndromes linked to obesity. These include:

1. Prada-Willi syndrome
2. Bardet-Biedl syndrome
3. Alstrom syndrome
4. WAGR syndrome
5. Albright’s Hereditary Osteodystrophy
6. Down syndrome
7. Autism Spectrum Disorder (16p11.2 deletion)
8. Intellectual disability (in general)
9. Psychosocial disability (medication side effects) This list of conditions is not exhaustive. These are the most common disorders/syndromes that research identifies. If there is information supporting early intervention or if there is an identified requirement for further research to be completed to substantiate the link to obesity this will be listed.

1) Prader-Willi Syndrome (PWS)

• Prader-Willi is the most common obesity syndrome.
• Prader-Willi Syndrome Australia describe PWS as “a rare and very complex, non-inherited genetic disorder. Several genes on chromosome 15 are deleted or unexpressed. The commonly observed characteristics include small hands and feet, abnormal growth and body composition (small stature, very low lean body mass and early onset childhood obesity), weak muscles, insatiable hunger, extreme obesity, intellectual disability and anxiety-driven behavioural outbursts. There is an underlying hormone deficiency”13.
• There is significant research on PWS indicating a causative genetic link to obesity.
• Most of the research suggests that obesity usually arises in later childhood, and that early intervention actions can assist in the management of obesity.

Causes of obesity in PWS

The research sourced suggests the following as the causes of obesity in PWS:

• Genetic disorder
• Insatiable appetite
• Imbalance between energy intake and expenditure due to hyperphagia
• Decreased physical activity

13 Prader-Willi Syndrome Australia, ‘About Prader-Willi Syndrome’, 2016, http://www.pws.org.au/prader-willi-syndrome/, accessed 12 November 2019.

Research Request – Obesity and direct link to disability | Page 9 of 37 Page 135 of 165

• Metabolic disorders (low metabolism)
• Inability to vomit Prader-Willi syndrome is a rare genetic disorder that causes a range of physical, intellectual and behavioural issues. Although it has no cure, treatment, especially if received early on, can help with symptoms. As adolescents and adults, people with PWS tend to have breathing and sleeping issues, as well as a general lack of energy. Combined with an insatiable appetite, this can lead to life-threatening obesity14. A substantial academic article by Professor Merlin G. Butler, MD, PhD of the Kansas University Medical Center, suggests that PWS often leads to childhood obesity [and that]:

“Obesity is a significant health problem, if uncontrolled. PWS is considered the most common known genetic cause of morbid obesity in children . . . that can be life-threatening . . . The clinical course of PWS has historically been divided into two distinct clinical stages (early failure-to-thrive and later childhood obesity). . . The obesity associated with PWS results from a chronic imbalance between energy intake and expenditure due to hyperphagia, decreased physical activity, reduced metabolic rate and an inability to vomit”15. A systematic review of PWS and chromosomal abnormalities from 2014 reports that: “PWS is characterized by hypotonia during the neonatal stage and in childhood, accompanied by a delay in neuropsychomotor development. Overeating, obesity, and mental deficiency arise later on . . . It is worth mentioning that an early and precise diagnosis of PWS is essential for avoiding obesity and related co-morbidities. It also allows for the provision of adequate genetic counseling for the patients and their families. . . The onset of the second phase is marked by obesity, which usually occurs as a consequence of hyperphagia around 2 years of age”16. Furthering the evidence of obesity arising later on in childhood, a cohort study of forty patients and literature review, supported that: “The typical features [of PWS] begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later”17.

Early Intervention

Research indicates that early intervention actions are the most effective way to assist with the issue of obesity for people with PWS.

14 Health Direct, “Prader-Willi syndrome”, [website], 2019, https://www.healthdirect.gov.au/prader-willi-syndrome, (accessed 14 September 2019) 15 M. Butler, “Prader-Willi Syndrome: Obesity due to Genomic Imprinting”, Curr Genomics, vol. 12, no. 3, pp 204-215, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137005 16 C. Rocha and C. Paiva, “Prader-Willi-like phenotypes: a systematic review of their chromosomal abnormalities”, Genet. Mol. Res. vol. 13, no. 1, pp. 2290-2298, 2014. http://www.funpecrp.com.br/gmr/year2014/vol13-1/pdf/gmr4395.pdf 17 G. Bray et al., “The Prader-Willi syndrome: a study of 40 patients and a review of the literature”, Medicine, vol. 62, no. 2, pp. 59-80, 1983. https://europepmc.org/abstract/med/6338343

Research Request – Obesity and direct link to disability | Page 10 of 37 Page 136 of 165

Further research in PWS

There is significant research into PWS indicating a causative genetic link to obesity. It is likely that the available PWS genetic research will be used to inform obesity research into other genetic conditions. In 2014 an international conference on hyperphagia was held at the Pennington Biomedical Research Center, Baton Rouge, Louisiana with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates. This conference had a particular focus on PWS and highlighted that given the obesity epidemic “the interest in the study of PWS and other rare or uncommon single gene causes of obesity has the potential to gain specific knowledge to address obesity in the general population. . . The research community also believes that PWS presents a ‘Window of Opportunity’ to study appetite control in the extreme situation of PWS and uncover new science with application to the general population”22.

Bardet-Biedl syndrome (BBS)

The National Organization of Rare Disorders (NORD) defines Bardet-Biedl syndrome (BBS) as • “A genetic condition that impacts multiple body systems. It is classically defined by six features. Patients with BBS can experience problems with obesity, specifically with fat deposition along the abdomen. They often also suffer from intellectual impairments.”

Causes of obesity in Bardet-Biedl syndrome

The research sourced suggests the following as the causes of obesity in BBS:

• Ciliopathy
• Inherited genetic disorder leading to truncal obesity / severe early-onset obesity
• Insatiable hunger
• Defective leptin hormone receptor signalling

According to NORD:

“The cardinal features of BBS are truncal obesity, intellectual impairment, renal anomalies, polydactyly, retinal degeneration and hypogenitalism… The term ‘truncal obesity’ refers to a condition where fat is disproportionately distributed onto the abdomen and chest rather than the arms and legs. Individuals can be described as having an apple-shape body type. Weight is usually normal at birth but weight gain is quickly evident through the first year of life in as many as 90% of people with BBS. Diabetes mellitus (specifically, type II diabetes, non-insulin dependent) has been estimated to affect up to 45% of patients with BBS. Weight management problems may further complicate problems with the heart and blood vessels seen in patients with BBS… BBS can be caused by changes (mutations) in more than 20 different genes. It is usually inherited as an autosomal recessive condition. Patients with mutations in the BBS10 gene generally have significantly increased tendency to obesity and insulin resistance”25.

Obesity is one of the more common symptoms of the syndrome. A publication by DF Guo & K Rahmouni from 2011 found that dysfunction in leptin hormone receptor signalling is a contributing factor to obesity in people with BSS. This article states that:

“Obesity is highly prevalent in BBS individuals and present in almost all patients carrying homozygous mutations. Of note, relative to non-BBS subjects with comparable body mass index (BMI), BBS subjects tend to have higher adiposity. Additionally, patients with BBS were found to have significantly more abdominal visceral fat compared to BMI-matched control subjects. Conversely, lean mass tends to be lower in BBS patients relative to non-BBS subjects. Predominance of morbid obesity (BMI over 40 kg/m²) is also elevated in BBS patients”26.

23 The National Organization of Rare Disorders, ‘Bardet Biedl Syndrome’, 2017, https://rarediseases.org/rare-diseases/bardet-biedl-syndrome/, accessed 12 November 2019. 24 U.S. National Library of Medicine, ‘Bardet-Biedl syndrome’, 29 October 2019, https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome#statistics, accessed 12 November 2019. 25 Ibid. 26 Guo, DF & Rahmouni, K, ‘Molecular basis of the obesity associated with Bardet-Biedl syndrome’, Trends in Endocrinology & Metabolism, vol.22, no., pp268-293, 21 April 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130119/, accessed 12 November 2019.

Research Request – Obesity and direct link to disability | Page 12 of 37 Page 138 of 165

Early intervention

As obesity is a common component of BSS, NORD acknowledges that it is

“a particularly important factor to address. This feature manifests typically by an age of two-three years. An active lifestyle incorporating athletic hobbies can make a significant impact. Both diet and exercise programs are also highly recommended. Good diet management can prevent the weight-related problems that manifest in later life. Consulting with a primary care physician and a dietician can help in planning for adequate nutrition and prevention of excess weight gain”28.

A publication from 2016 states that “Clinical management of BBS is largely limited to a symptomatic treatment”, that is managing the common features of the condition29.

Guo & Rahmouni conclude in their 2011 publication that “The progress in defining the biological basis for energy imbalance and obesity in BBS may help the patients with this disorder to dispel any perception of obesity as a lack of discipline and personal behavioral failure. Such progress will also be helpful for clinical management of BBS patients and for rationale mechanism-based therapies”30.

The Bardet Biedl Syndrome Foundation acknowledges that while there is currently no cure for BBS, this does not mean that there is nothing that can be done to help people with BBS. “Children with BBS benefit greatly from therapies like physical therapy, occupational therapy, speech therapy and vision services. Everyone with BBS benefits from exercise and careful attention to diet to limit weight gain”31. The BBS Foundation also notes that Obesity is primary characteristic and is typically apparent by age one.

Alstrom syndrome

The U.S. National Library of Medicine describes Alstrom Syndrome as follows:

• “Alström syndrome is a rare condition that affects many body systems. Many of the signs and symptoms of this condition begin in infancy or early childhood, although some appear later in life.”
• “Alström syndrome is characterized by a progressive loss of vision and hearing, a form of heart disease that enlarges and weakens the heart muscle (dilated cardiomyopathy), obesity, type 2 diabetes (the most common form of diabetes), and short stature. This disorder can also cause serious or life-threatening medical problems involving the liver, kidneys, bladder, and lungs. Some individuals with Alström syndrome have a skin condition called acanthosis nigricans, which causes the skin in body folds and creases to become thick,”

27 Heymsfield et al. loc cit. 28 The National Organization of Rare Disorders, loc cit. 29 Suspitsin EN & Imyanitov EN, ‘Bardet-Biedl Syndrome’, Molecular Syndromology, vol. 7 no. 2 May 2016, hhttps://www.ncbi.nlm.nih.gov/pubmed/27385962, accessed 22 November 2019. 30 Guo & Rahmouni, loc cit. 31 Bardet Biedl Syndrome Foundation, ‘What is BBS’, 2019, hhttps://www.bardetbiedl.org/what-is-bbs/#ten, accessed 22 November 2019.

Research Request – Obesity and direct link to disability | Page 13 of 37 Page 139 of 165

Causes of obesity in Alstrom syndrome

The research sourced suggests the following as the causes of obesity in Alstrom syndrome:

• Mutations in the ALMS1 gene cause Alström syndrome
• Ciliopathy
• Genetic disorder resulting in disruption to neural pathways that regulate hunger
• Higher level of blood lipids

The National Organization for Rare Disorders explains that obesity is a common symptom of Alstrom syndrome:

“Birth weight is normal in infants with Alström syndrome, but excessive eating beyond the normal need to satisfy hunger (hyperphagia) and rapid weight gain may occur during the first year of life. Some affected children develop childhood truncal obesity, a condition in which fat is disproportionately distributed on the abdomen and chest rather than the arms and legs. As affected individuals age, some may see their body weight fall, often regaining normal or slightly above-average weight for their size”33.

The U.S. National Library of Medicine explains the impact that the mutation in the ALMS1 gene has on people with Alstrom syndrome:

“More than 80 mutations in the ALMS1 gene have been identified in people with Alström syndrome. Most of these mutations lead to the production of an abnormally small version of the ALMS1 protein that does not function properly. Researchers propose that a lack of normally functioning ALMS1 protein in the brain could lead to overeating. A loss of this protein in the pancreas may cause insulin resistance, a condition in which the body cannot use insulin properly. The combined effects of overeating and insulin resistance impair the body’s ability to handle excess sugar, leading to diabetes and obesity (two common features of Alström syndrome). It is unclear how ALMS1 mutations cause the other signs and symptoms of Alström syndrome. Researchers suspect that this condition is associated with malfunctioning cilia in many of the body’s tissues and organs”34.

Early intervention

Strict dietary measures and exercise programs may help to control obesity, as well as aid in the management of diabetes mellitus and/or glucose intolerance associated with Alström syndrome. In most of the diagnosed patients of Alström syndrome, diabetes is controlled by diet and exercise alone35. While the early onset obesity is common in Alstrom syndrome the permanency of obesity is not established. One UK based study from 2006 found that in AS cases, “severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases”36.

32 U.S. National Library of Medicine, ‘Alstrom syndrome’, 12 November 2019, hhttps://ghr.nlm.nih.gov/condition/alstrom-syndrome, accessed 22 November 2019. 33 National Organization for Rare Disorders, ‘Alstrom Syndrome’, 2016, https://rarediseases.org/rare-diseases/alstrom-syndrome, accessed 22 November 2019. 34 U.S. National Library of Medicine, ‘ALMS1 gene’, 12 November 2019, hhttps://ghr.nlm.nih.gov/gene/ALMS1#conditions, accessed 22 November 2019. 35 Ibid. 36 Minton, JA et al., ‘Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome’, The Journal of Clinical

WAGR syndrome

• WAGR syndrome is a chromosomal disorder caused by chromosome 11 deletion.
• WAGR syndrome affects many body systems and is named for its main features: Wilms tumor, anirida, genitourinary anomalies, and intellectual disability… When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome37.
• Synonyms for WAGR syndrome include: WAGR Complex, WAGRO syndrome, Chromosome 11p deletion syndrome, 11p deletion syndrome, Aniridia-Wilms Tumor Association/ATWA, Aniridia-Ambiguous Genitalia-Mental Retardation, AGR Triad38

Causes of obesity in WAGRO syndrome

The U.S. National Library of Medicine states that the cause of WAGR Syndrome is the deletion of genetic material on the short (p) arm of chromosome 11.

“In people with WAGRO syndrome, the chromosome 11 deletion includes an additional gene, BDNF [brain derived neurotrophic factor]. This gene is active (expressed) in the brain and plays a role in the survival of nerve cells (neurons). The protein produced from the BDNF gene is thought to be involved in the management of eating, drinking, and body weight. Loss of the BDNF gene is likely responsible for childhood-onset obesity in people with WAGRO syndrome. People with WAGRO syndrome may be at greater risk of neurological problems such as intellectual disability and autism than those with WAGR syndrome. It is unclear whether this increased risk is due to the loss of the BDNF gene or other nearby genes”39. A case study from 2019 examined the symptoms of WAGR Syndrome displayed in an eight year old boy. : The presence of obesity (

Early intervention

In 2007 the International WAGR Syndrome Association published a ‘Guide for Physicians’. The booklet was designed to assist both primary and specialty care physicians caring for individuals with WAGR syndrome. Information about diagnosis, associated conditions, treatment, and follow-up care throughout life are given, along with resources for additional information and assistance’. One of the primary treatment considerations was for a dietary consultation. The booklet states that:

Some individuals with WAGR syndrome may have a genetic predisposition to Early Onset Overweight and/or obesity. Consultation with a dietician and assistance with appropriate levels of physical activity may be necessary [and to] Encourage family to establish optimal dietary and physical exercise patterns to help prevent/manage obesity”42.

5) Albright’s Hereditary Osteodystrophy

The US Genetic and Rare Disease Information Center (GARD) describes Albright’s hereditary osetodystrophy as:

• A rare disorder with a wide range of signs and symptoms, including short stature, obesity, round face, subcutaneous ossifications (formation of bone under the skin), and short fingers and toes (brachydactyly). When the disorder is inherited from the mother, the features of AHO can be associated with resistance to certain hormones, in particular the parathyroid hormone (PTH). This is called pseudohypoparathyroidism type 1a (PHP1a). When inherited from the father, an individual will have AHO without any hormone issues, which is called pseudopseudohypoparathyroidism (PPHP). This condition is inherited in an autosomal dominant manner due to a mutation in the GNAS gene”43.
• The condition is sometimes just referred to as Pseudohypothyroidism.
• The obesity generally occurs very early (within the first year) and tends to be severe in early childhood44.

41 Han, JC et al., ‘Brain-Derived Neurotrophic Factor and Obesity in the WAGR Syndrome’, The New England Journal of Medicine, vol. 359, pp. 918-927, 2008, https://www.nejm.org/doi/full/10.1056/NEJMoa0801119, accessed 25 November 2019. 42 International WAGR Syndrome Association, loc cit. 43 Genetic and Rare Disease Information Center, ‘Albright’s hereditary osetodystrophy’, March 2018, https://rarediseases.info.nih.gov/diseases/5770/albrights-hereditary-osteodystrophy, accessed 25 November 2018. 44 Weinstein, LS et al., ‘The Role of GNAS and Other Imprinted Genes in the Development of Obesity’, International Journal of Obesity, vol.34, no.1 pp.6-17, 2010, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931809, accessed 25 November 2019.

Research Request – Obesity and direct link to disability | Page 16 of 37 Page 142 of 165

Causes of obesity in Albright’s Hereditary Osteodystrophy

The causes of obesity in Albright’s are complex. Put simply, the mutation in the GNAS gene disrupts gene expression and function causing irregular energy regulation. There have been several studies, regarding the role of GNAS in weight regulation in humans, however a literature review from 2010 highlights that while the link between Albright’s and obesity is acknowledged, the genetic causation is not fully understood45. This literature review lists some on the conclusions that research has found to date:

“Few studies have been performed in humans examining the underlying mechanism for the obesity in PHPIA. Although one study showed evidence that adipocytes from PHP1A patients have reduced lipolytic responsiveness to epinephrine due to reduced levels of Gsα/cAMP signaling, the adipose tissue is unlikely to be involved in this parent-of-origin effect on energy balance as studies have shown no evidence for Gsα imprinting in adipose tissue. This same study did show PHP1A patients to have extremely low circulating norepinephrines, even when compared to similarly obese children without PHP1A, suggesting that the defect may lie in central nervous system (CNS) regulation leading to low sympathetic nervous system activity and metabolic rates.

Although food intake has not been systematically examined in these patients, one recent case was reported in which severe obesity developed in the first year of life in the absence of hyperphagia, suggesting that low energy expenditure rates may be the major contributor to obesity in this disorder.

There is some evidence that growth hormone deficiency due to growth hormone releasing hormone resistance in the pituitary may contribute to obesity in some cases. Although the incidence of comorbid metabolic abnormalities such as insulin resistance and diabetes in PHP1A has not been systematically examined, recently a case of severe insulin resistance in a young PHP1A patient has been reported.

In addition to the monogenic obesity resulting from clear loss-of-function mutations, two single nucleotide polymorphisms have been identified within the GNAS locus that have been associated with altered body weight or response to weight loss regimens”46.

Early intervention

Ain 2018 an expert consensus statement on the ‘Diagnosis and management of pseudohypoparathyroidism and related disorders’ was published. The expert consensus provides 67 diagnostic and management recommendations. The expert consensus states that:

“To date, no prospective clinical trials have been conducted in patients with PHP and related disorders that focus on the management and outcomes of treatment in these disorders. Large cohorts of molecularly diagnosed patients are needed for recruitment into clinical studies, which should also include long-term follow-up. As a result of the rarity of the disease, cohorts and research forces are scattered; there is a need to coordinate and implement multicentre international clinical trials. A multidisciplinary follow-up and early,

45 Ibid. 46 Ibid.

Further research

The expert consensus concludes that:

Given the lack of strong evidence-based data, particularly for management of these patients, international collaboration and long-term clinical trials looking at the natural history, the diseases’ classification and the outcome of treatments are urgently needed50.

Down syndrome

Down syndrome is a common genetic disorder caused by an extra chromosome 21. People with DS will have:

• some characteristic physical features
• some health and development challenges
• some level of intellectual disability51. There is significant research on DS indicating a link to obesity. Whilst there is research indicating such, the open source type information provided by advocacy group or public health websites does not bring this issue to prominence. This lack of published discourse may indicate a general desire from advocates not to create a common stigma around Down syndrome (DS) and overweight/obesity.

Causes of Obesity in Down syndrome

The research sourced suggests the following as the causes of obesity in DS:

• Metabolic disorders (low metabolism)
• Prevalence of dyslipidaemia (abnormal amounts of lipids in the blood)
• Pre-diabetes

Open source information

Open source information websites were researched including Australian associations and support groups, and no reference to obesity as a direct feature of Down syndrome could be found. Sites sourced were: Down Syndrome Australia, Down Syndrome Western Australia, Down Syndrome Victoria, Better Health Channel (Victoria), Down Syndrome NSW, WebMD, Healthline, National Down Syndrome Society.

Neither the Raising Children website, nor the HealthDirect website suggest that obesity is a feature of DS. Health Direct suggests the risk of those with DS being overweight, whilst Raising Children has no mention of the weight factor.

Down Syndrome Australia, a peak body providing a voice for people living with DS, asserts only that “there can be a tendency for both children and adults with Down syndrome to become overweight. An active lifestyle with plenty of physical activity helps to counterbalance this tendency and encourages general health and fitness”52.

Similarly, the UK’s Down Syndrome Association suggests that

Setting out to assess whether children with DS in the US are at an increased risk for obesity, the evaluation of 303 individuals in a 2015 cohort study, found that children with DS are at a substantial risk for obesity

The issue of low metabolism as having an effect on obesity in Down syndrome is commonly featured in the research sourced.

A journal publication from 2015 highlights the common link to secondary health and developmental challenges that people with DS commonly experience, noting that:

“Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases… Symptoms include intellectual disability/mental retardation, early onset of Alzheimer’s disease and the appearance of various phenotypic features… In addition, there are other health problems throughout the body, consisting in part of cardiac defects and thyroid function abnormalities along with nutritional disorders (i.e. overweight, obesity, hypercholesterolemia and deficiencies of vitamins and minerals)… Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (e.g. celiac disease) or malabsorption. DS persons with overweight or obesity are linked with a slow metabolic rate, abnormal blood leptin concentrations and exhibit low levels of physical activity. Vitamin B group deficiencies and abnormal blood homocysteine levels decrease the rate of intellectual development in DS cases. Zinc deficiencies result in short stature, thyroid function disorders and an increased appetite caused by excessive supplementation”56.

While this article focusses on lifestyle factors including excessive food intake and lack of exercise, there is an acknowledgement that people with DS typically have a slower metabolic rate and high lipid levels.

Several other studies have considered this metabolic connection to obesity:

• A control study from 1994 investigated the relationship between energy expenditure and obesity in DS children, using 10 control subjects matched for age, weight, and percentage of fat, using indirect calorimetry and the doubly labelled water method. The results of the study indicated that prepubescent children with DS have decreased resting metabolic rate compared with control children57.
• Another observational, cross-sectional study from 1995 set out to compare the resting metabolic rates (RMRs) of adults with and without DS while controlling for potential confounds. The study demonstrated that persons with DS have lower RMRs than do persons without DS58.

https://search.proquest.com/openview/17e743f38ff81c67a9d3f8ecf85aaaf3/1?pq-origsite=gscholar&cbl=47659, accessed 7 November 2019 [secondary referenced research in quote could not be accessed].

55 J. Basil et al.,

Early Intervention

There is a theme in the research of early intervention having a positive effect on obesity and weight issues within those with DS. The majority of studies sourced recommend early interventions during childhood to assist with the issue.

A significant cohort study of children with DS suggested “that children with Down syndrome are at a substantial risk for obesity and OSAS (obstructive sleep apnoea syndrome). These findings support the need for more aggressive weight management in early childhood and throughout the lifespan”63.

A comprehensive article from Paediatric Nursing asserts that children with Down syndrome

“Have a higher risk for developing obesity. The primary care provider can assist the family in preventing or managing obesity by recognizing the physiological and behavioural factors that place children and adolescents with Down syndrome at increased risk to become obese, and establishing a screening and management plan early to prevent or treat excess weight gain. By using adapted strategies, the negative physiological and psychological outcomes associated with obesity may be lessened or avoided in this specific population”64.

59 D. de Asua et al.,

Further Research Needed for Obesity and DS

While the academic research verifies that there is a link between DS and obesity due to both physiological and behavioural factors, there is a theme in much of the literature calling for further research to understand and substantiate the link.

A 2016 literature review on the subject concluded that “population-based research is needed to identify risk factors and support multi-factorial strategies for reducing overweight and obesity in children and adolescents with DS”66. The review found that the “combined prevalence of overweight and obesity varied between studies from 23% to 70%. Youth with DS had higher rates of overweight and obesity than youths without DS. Likely determinants of obesity included increased leptin, decreased resting energy expenditure, comorbidities, unfavourable diet, and low physical activity levels. Obesity was positively associated with obstructive sleep apnea, dyslipidemia, hyperinsulinemia, and gait disorder. Interventions for obesity prevention and control were primarily based on exercise-based programs, and were insufficient to achieve weight or fat loss”67.

An earlier case control study suggested that “the impact on the health of people with Down syndrome of being overweight or obese is uncertain, this is an area that requires further study”68.

While people with Down syndrome may experience metabolic disorders making weight gain more likely, it appears from the research that this risk can easily be mitigated/effectively managed through early dietary intervention and encouraging a healthy active lifestyle choices. That is, just because someone has Down syndrome does not mean they will inevitably become overweight.

7) Autism Spectrum Disorder (ASD)

• There is significant research on ASD indicating a link to obesity.
• The prevalence of overweight and obesity in people with ASD is high and is attributed to a variety of factors: common comorbidities, medication side effects, social/environmental factors.

Causes of obesity in ASD

The research sourced suggests the following as the causes of obesity in ASD:

• Psychopharmacological effects
• Genetic Basis
• Gastrointestinal disorders

• Sensory processing disorders
• Physical activity and sedentary behaviours
• Sleep disorders
• Food as reward for learning and behaviour management

Open Source Information

The popular Australian websites HealthDirect and Raising Children, although providing comprehensive information and referral on ASD, make no reference to obesity or weight control being common issues. The following popular sites were also researched and provided no reference to obesity or weight issues: Amaze, Australian Institute of Health and Welfare, Autism SA, Brain Foundation, Australian Autism Alliance, Autism CRC, Australian Medical Association, Scope, Autism Western Australia. Autism Spectrum Australia does make reference to diet, nutrition and obesity stating that: “When comparing autistic teens with their typically-developing peers, perhaps the most obvious difference when it comes to eating is the high prevalence of restricted diets in those on the spectrum, due to their inherent sensory defensiveness and/or rigidity [which can] lead to nutritional deficiencies”69. Another common concern for adolescents with ASD is not participating in team sports. Autism Spectrum Australia state that “The obvious corollary from lack of exercise is becoming overweight [and that] A recent American study found that nearly half of young autistic people aged 10 to 17 were overweight or obese, compared with less than one-third of their typically developing peers“70. However this indicates that the cause of weight concerns for people with ASD stem from sensory or behavioural issues.

Academic Research Sources

There is a significant amount of academic research examining the link between ASD and obesity. In 2017 a comprehensive literature review or ‘meta-analysis’ of epidemiological studies examined the association among obesity, overweight and ASD. The research included 15 studies published on databases such as PubMed, Embase, and Cochrane Library. The 15 studies collectively included a total of 49,937,078 participants and 1,045,538 individuals with ASD. The results showed that obesity was clearly associated with ASD. However, no significant association were identified between overweight and ASD71. Citing other studies, the meta-analysis identified four major causes of obesity in ASD patients:

“First, individuals with ASD often have eating problems, such as food selectivity and specialized dietary habits, which make healthy dietary interventions less effective. Second, individuals with ASD spend less time on physical activities and more time on sedentary activities. They also have difficulty in participating in standard obesity prevention initiatives due to behavioral problems. Third, individuals with ASD have more chances to be treated with various antipsychotic medications, which are known to be associated with weight gain. Fourth, individuals with ASD also have comorbidities associated with obesity, such as sleep problems, gastrointestinal disorders, ADHD. Finally, some individuals with ASD have been

69 Autism Awareness Australia, “Let’s talk about HEEADSSS”, [website], 2019, https://www.autismawareness.com.au/news-events/aupdate/lets-talk-about-heeadsss, (accessed 15 September 2019) 70 Ibid. 71 Z. Zheng et al., “Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis”, Scientific Reports, Vol 7, No. 1, 2017. https://www.nature.com/articles/s41598-017- 12003-4

Research Request – Obesity and direct link to disability | Page 23 of 37 Page 149 of 165

16p11.2 deletion in ASD

Noting the above mentioned link between ASD and genetic microdeletions, 16p11.2 ‘deletion syndrome’ is listed on the U.S. National Library of Medicine website and acknowledges that “People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities”74. It cannot be concluded that all people with ASD have this predisposition.

A recent literature review from 2014 published in the Harvard Review of Psychiatry by Carol Curtin et al. examined Obesity in Children with Autism Spectrum Disorder75. This article examined prevalence of obesity in people with ASD when linked with: genetics, psychopharmacological effects (antipsychotics, mood stabilizers, and antidepressants), sleep problems, food selectivity, delayed/impaired motor development, family functioning and other factors. The ‘other factors’ considered is the use of applied behavioural analysis treatment as a cause because food is often used as a primary reinforcer and this may impact of ongoing food intake. The altered social dimensions of eating and drinking that people with ASD experience also need to be researched further.

Regarding genetic causes of obesity in people with ASD, the Curtin et al publication also noted the 16p11.2 genomic deletion, however “given the significant gene variability and penetrance emerging in both animal and human models of ASD, more work is needed to draw definitive genetic associations between ASD and obesity”76. A more recent publication from 2019 has found that approximately 15% of people with ASD have the duplication or deletion of genome 16p11.277.

This Curtin et al publication concluded that:

“The prevalence of obesity is at least as high, if not higher, in children with ASD compared to other children. Research has documented that atypical antipsychotic medication is a clear risk for weight gain in this clinical population. Studies on diet, physical activity, and sleep in typically developing children have shown positive associations with obesity, but this work remains to be done in children with ASD, as do other investigations on the implications of gastrointestinal disorders and using food as a reward for learning and behaviour management. Obesity and its associated sequelae represent significant threats to

Research Request – Obesity and direct link to disability

independent living, self-care, quality of life, and long-term health outcomes for individuals with ASD78.

In 2019, Sylwia Trambacz-Oleszak from the Adam Mickiewicz University, Poland, conducted a comprehensive literature search and review of the PubMed database for papers published between January 2000 and June 2019. The intention of the review was to summarize the current state of knowledge on the genetic basis of obesity in ASD and answer the question ‘Why are individuals with autism spectrum disorder at risk group for unhealthy weight?’79

Trambacz-Oleszak states that several studies have indicated that the prevalence of overweight and obesity is high in autistic children and adolescents. There are significantly higher odds of being overweight or obese for children and adolescents with ASD, in comparison to typically developing children and youths. Both, overweight and obesity are risk factors for the incidence of multiple comorbidities, such as type 2 diabetes, cardiovascular diseases, sleep apnoea, cancers, psychological and social disorders80.

Some of the outcomes of the review are as follows:

• Genetic basis of ASD: It is currently well-known that autism has a genetic basis and the mapping of key genomes is becoming more understood. “Genomic imbalances and high rates of recurrent CNVs (misplaced or duplicated segments of chromosomes) are also emerging as risk factors for obesity. The genetic basis of different types of obesity, including monogenic and polygenic obesity, pleiotropic syndromes and chromosomal rearrangement are also well-documented now”81.
• Gastrointestinal disorders: Gastrointestinal disorders [vomiting, diarrhoea, constipation, abdominal pain, bloating, gaseousness, belching and reflux] are often observed among individuals with ASD and can affect up to 54% of patients. The review found that “On one hand, gastrointestinal problems may cause body mass loss. On the other hand, epidemiologic data indicated that obesity is associated with chronic gastrointestinal disorders. Therefore, gastrointestinal problems can contribute to an unhealthy body weight, either underweight or overweight, and obesity in children and adolescents with ASD”82.
• Sensory processing disorders: “Children with ASD very often suffer from sensory processing disorders, including irregularities in the reception and processing of sensory stimuli . . . Sensory processing disorders may be one of the causes of food selectivity and affect body weight”83.
• Depression: “A growing body of research has demonstrated the increased prevalence of comorbid depression among individuals with ASD . . . The association between depression and obesity is ambiguous. Although some studies have indicated a certain relation between obesity and depression, other studies have not confirmed it . . . However, psychological disorders comorbid with ASD, including depression and anxiety, are possible risk factors associated with unhealthy weight in this group”84.

78 Curtin, loc cit. 79 Trambacz-Oleszak, p.313. 80 Trambacz-Oleszak, p. 314. 81 Op cit, p.316. 82 Op cit, p.317. 83 Ibid. 84 Op cit, p.318.

Research Request – Obesity and direct link to disability | Page 25 of 37 Page 151 of 165

Further Research Needed for Obesity and ASD

There is a clearly rising trend in the academic research examining the link between obesity and ASD, particularly in examining genetic anomalies. The majority of the academic resources discussed above advocate for further research to be conducted to draw definitive genetic association between ASD and obesity.

For example, a 2017 critical review that investigated potential contributing factors to the aetiology [cause; origin] and maintenance of obesity within the ASD child population concluded that “Research should continue to investigate excess weight gain in this population in order to adapt weight loss interventions for children with ASD”88.

In conclusion, the majority of research examines the secondary impact of symptoms/behaviours associated with the disability: e.g. issues with sensory processing, gastrointestinal disorders, sleeping disorders, medication, and physical issues resulting from lack of exercise.

While research demonstrates that the prevalence of obesity in people with ASD is high, there is not a definitive understanding of the genetic causative factors. Also, the available information highlights that the symptoms and experiences of people with ASD are unique and that this genetic predisposition to weight gain would not be experienced by all people with ASD. There is also no evidence to suggest that this genetic predisposition could not be effectively managed/controlled by mainstream capacity building behavioural therapy and health education.

8) Intellectual Disability (in general)

• There is significant research on Intellectual Disabilities in general indicating an increased risk of obesity for this cohort.

Causes of obesity in Intellectual Disability

The research sourced suggests the following as the common causes of obesity in people with Intellectual Disability:

• Behavioural, environmental and biological factors
• Independent living without supervision
• Lack of exercise
• The disability hindering the persons understanding of managing nutrition and exercise.

Academic Research Resources

The majority of studies sourced identified lack of exercise and food choices in those with intellectual disability as the key contributing factors to obesity. In 2016, an Australian cross-sectional survey looked at the prevalence and associated characteristics of obesity in adolescents with ID. The study examined obesity in a community sample of adolescents with ID attending special education facilities in South-East Queensland across a four-year period. Information on age, gender, weight, height, syndrome-specific diagnoses, problematic behaviours, mobility, taking psychotropic or epileptic medication, and perceived household financial difficulties was collected. The study concluded that the prevalence of obesity and overweight were increased compared to general Australian adolescents. The study also found that adolescents with Down syndrome were more likely to be obese than other participants with ID89. Another Australian cohort study from 2015 set out to describe the nutrition, food choice, physical activity, and weight status in a group of adults with intellectual disability in Victoria. 51 disability workers and 68 adults with ID participated in the research. Disability workers provided information about the nutrition, food choice, and physical activity levels of adults with ID through a questionnaire administered by a general practitioner or research nurse. The questionnaire also included the Australian Nutrition Screening Initiative checklist. The study found that “people with ID are at risk of developing diseases associated with obesity, inactivity, and poor nutrition [and that] Strategies to encourage people with ID to engage in physical activity and healthy eating are, therefore, a matter of priority and should involve their disability workers”90. A 2016 literature review published by The University of Hertfordshire (UK) found that “The higher prevalence of obesity in people with intellectual disabilities is due to a complex mix of behavioural,

89 S. Krause et al.,

Early Intervention

Research suggests that people with ID may benefit greatly from early interventions targeted at preventing and managing obesity. In fact, a great deal of the studies cited were initiated in order to identify early intervention efficacy. Much of the literature suggests physical exercise and nutrition choices as the key early interventions.

Further Research Needed for Intellectual Disability

Much of the research sourced calls for further studies regarding early intervention and other obesity management interventions. For example, the literature review published by The University of Hertfordshire concluded that “there is a need for methodologically robust studies to investigate further, both the aetiology and management of obesity in this population for prevention and early intervention”92.

A recent 2018 UK systematic review by A.J. Doherty et al. encapsulates this point clearly: “Responding to obesity and obesity-related health risks in individuals with intellectual disabilities should be seen as an important health inequality issue by healthcare policymakers, service commissioners, providers and practitioners. . . There is also an identified lack of evidence-based research in this field”93.

In the conclusion of this Doherty et al. study, the authors listed considerations for future research in the field. There suggestions are as follows:

• Information on the theoretical underpinning for weight management interventions should be included in future published studies.
• Published studies to provide more detail regarding the actual components of the weight management interventions under investigation.
• Further studies should explore the organisational culture and resources that enable staff to implement interventions over time.
• Justification for sample sizes needs to be included in future studies, and the sampling and settings used in studies should reflect that people with intellectual disabilities are not a homogeneous group.
• Further controlled studies of multi-component weight management interventions including cluster-randomised designs—based on MRC guidelines for complex interventions and CONSORT guidance for trials.
• Systematic reviews of multi-component weight management interventions for all adults who are obese (including adults from different population groups).

91 A. Biswas et al.,

• Qualitative studies seeking out the views and experiences of participants, their carers (and or support workers) and service providers to improve our understanding of the barriers and facilitators to weight management.
• Research to explore the longer-term effectiveness of multi-component weight management interventions for different population groups.
• A range of outcome measures (e.g. body mass index, waist circumference, dietary quality, physical activity levels, and satisfaction with life) may be needed in future intervention studies.
• Any unintended consequences of an intervention should be reported in future studies.
• An intervention may need to be adapted during implementation to suit local settings and a description of any such adaptation should be described in the study’s findings94.

9) Psychosocial disability (medication side effects)

The link between psychosocial disability and obesity is complex and one condition often exacerbates the symptoms of the other. People who use psychotropic medications [any medication capable of affecting the mind, emotions, and behaviour] often gain significant weight or experience difficulty with weight loss. This is particularly so for antipsychotics and some classes of antidepressants. People with obesity often experience secondary psychological burden related to mood, self-esteem, quality of life and body image95. Conversely, weight loss is typically associated with improvements in psychosocial status and functioning. The Australian Department of Health website states that:

Some people taking certain medications find they put on weight very easily. This is most likely to happen within the first six months of starting a medication. Medications that may increase your risk of gaining weight include:

• medications for mental illness, including:

  • atypical antipsychotics, such as clozapine and olanzapine
  • lithium
  • tricyclic antidepressants, such as amitriptyline

• medications for diabetes, such as insulin, chlorpropamide, glibenclamide, glimepiride, glipizide and pioglitazone

• sodium valproate (for epilepsy and other conditions)

• beta blockers, such as propranolol and atenolol (for high blood pressure and other conditions)96.

94 Doherty, loc cit. 95 Darwer, DB & Polonsky, HM, ‘The Psychosocial Burden of Obesity’, Endocrinology and Metabolism Clinics of North America, vol. 45 no. 3, 2018, pp.677-688, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052856/ accessed 25 November 2019. 96 Australian Government, Department of Health ‘ Medications and weight’, 2019, https://www.health.gov.au/

Research Request – Obesity and direct link to disability | Page 29 of 37 Page 155 of 165

FOI 24/25-0413

The website Psychiatry Advisor - which offers comprehensive up-to-date psychiatry-based clinical and drug information – acknowledges this clear link between obesity and mental illness, stating that97:

“Medication is one factor that explains why mentally ill patients are at higher risk of obesity. A 2007 study published in the American Journal of Managed Care found an increased incidence of weight gain and glucose regulation problems in people taking antipsychotic medication.98 Metabolic syndrome, which arises from insulin resistance due to increased abdominal fat levels, is especially prevalent in patients with schizophrenia. The link between psychiatric medication and obesity may be due to the fact that psychotropic drugs not only contribute to weight gain but also create changes in the sensitivity of the body to insulin. Shrivastava and Johnston observed this phenomenon and noted that weight gain caused by psychiatric medications further exacerbated the psychological problems experienced by patients. It would be easy to assume that the choice of medication is responsible for this, but almost all psychiatric medications cause weight gain, according to a meta-analysis by Bak and colleagues99.

According to Taylor and colleagues, linking all cases of obesity caused by mental illness to medication is too simplistic a view.12 Psychiatric disorders such as depression, attention deficit disorder, and posttraumatic stress disorder can lead to weight gain owing to “comfort eating,” a lack of interest in preparing healthy meals, and impulsive eating habits. The effect caused by the stress hormone, cortisol, emitted during times of distress also plays a role in weight gain“100.

In their 2010 review examining weight-gain in psychiatric treatment, Shrivastava and Johnston found that:

• “Clinical studies indicate that a high prevalence of metabolic syndrome exists in individuals afflicted with serious mental illnesses, particularly those with schizophrenia. In addition, psychotropic agents, including antipsychotic medications and antidepressants, have been found to be associated with substantial weight-gain”

• “Research examining the differential effects of various antipsychotic medications has shown that both the frequency as well as the amount of weight-gained is high in patients treated with olanzapine (average gain of 2.3 kg/month), clozapine (1.7 kg/month), quetiapine (1.8 kg/month), and zotepine (2.3 kg/month), (Wetterling, 2001). Additionally, they also report that some changes in weight have also been observed in treatment with risperidone (average gain of 1.0 kg/month), and ziprasidone seems to induce only small changes in weight (0.8 kg/month). Overall, the largest body of research exists to support an association between weight-gain and treatment with olazapine and clozapine (Gebhardt et al. 2009; Haddad, 2005).”

• “Weight-gain is not restricted to individuals treated with antipsychotics; antidepressants and lithium have also been shown to lead to unwanted weight-gain Studies have found that antidepressants lead to an increase of weight in anywhere between 24–100% of patients,

97 Davies, N, ‘mental Illness and Obesity, February 2016, Psychiatry Today,’ https://www.psychiatryadvisor.com/home/conference-highlights/aaic-2015-coverage/mental-illness-and-obesity/ accessed 25 November 2019.

98 Newcomer J, Metabolic syndrome and mental illness. American Journal Managed Care. 2007;13(7 Suppl):S170–177.

99 Shrivastava A, Johnston ME, Weight-gain in psychiatric treatment: risks, implications, and strategies for prevention and management. Mens Sana Monographs. 2010;8(1):53–68,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031940/ accessed 25 November 2019.

100 Taylor VH, McIntyre RS, Gary Remington MD, Levitan RD, Sharma AM, Beyond pharmacotherapy: understanding the links between obesity and chronic mental illness. Canada Journal Psychiatry. 2012;57(1):5.

Research Request – Obesity and direct link to disability | Page 30 of 37 Page 156 of 165

Weight loss interventions for psychosocial disability

A significant area of focus of Shrivastava and Johnston was to provide options for prevention and management of weight gain in this cohort based on the scientific findings. They found that there are various effective pharmacological (e.g., switching medications), nonpharmacological (e.g., diet and exercise) and cognitive/behavioural interventions for patients who have gained weight as a result of psychiatric treatment¹⁰³. They also note that in extreme cases bariatric surgery remains an option.

This review is comprehensive and provides information about specific psychiatric conditions, medications and weight management options. In general they list the best prevention and management measures for weight gain in this cohort as follows

• Thorough baseline assessment of family history, risk factors, health psychology, life style and dietary habits.
• Monitor weight and metabolic parameters closely throughout the course of treatment.
• Work with a meaningful multidisciplinary team to target all vulnerable areas.
• Incorporate behavioral intervention programs.
• Involve dieticians to monitor nutritional requirement.
• Avoid polypharmacy as much as possible.
• Attempt to treat weight-gain with behavioral and pharmacological measures.
• Treat metabolic conditions, like hyperlipidemia and diabetes.
• Obtain good control over hypertension.
• Obtain adequate remission of depressive and negative symptoms.
• Implement motivational therapy when required.

¹⁰¹ Shrivastava & Johnston, loc it. ¹⁰² Lambert, T, ‘Managing the metabolic adverse effects of antipsychotic drugs in patients with psychosis’, NPS Medicinewise, August 2011, https://www.nps.org.au/australian-prescriber/articles/managing-the-metabolic-adverse-effects-of-antipsychotic-drugs-in-patients-with-psychosis, accessed 26 November 2019. ¹⁰³ Shrivastava & Johnston, loc it.

Conclusion

There are several conditions that fall under the syndromic obesity umbrella where there is a proven genetic cause of obesity.

• Prader Willi syndrome
• Bardet-Biedl syndrome
• Alstrom syndrome
• WAGR syndrome
• 16p11.2 deletion
• Albright’s hereditary osteodystrophy Note: There are other very rare genetic conditions that are also considered syndromic obesity, but have not been included due to them being so uncommon.

ASD and Down syndrome

Autism Spectrum Disorder and Down syndrome are not classified under the syndromic obesity umbrella, however a small percentage of people with ASD may have 16p11.2 or 11p14.1 genetic microdeletions, which encompass genes related to obesity susceptibility. Similarly, people with Down syndrome are proven to have lower metabolic rates than others, but early intervention to manage behavioural and lifestyle choices leading to weight gain is generally effective.

Psychiatric medications:

While there is evidence to suggest that certain psychiatric medications cause increased weight gain, linking all medications to obesity is too simplistic. There are a complex combination of factors that may result in weight gain for this cohort, such as lifestyle choices, lack of motivation/self-esteem etc. There are also a variety of supports available to prevent or manage weight gain in this cohort and many of the sequelae conditions that follow the primary psychosocial condition (e.g., diabetes, dyslipidemia, and hypertension) require multidisciplinary health treatment. The permanency of obesity and associated functional impairments would be difficult to establish when the cause is medication.

104 Ibid. 105 Lambert, loc cit.

Reference List

Allison, D, “Decreased resting metabolic rate among persons with Down Syndrome”, International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity, vol. 19, no. 12, pp. 858-861, 1995. https://europepmc.org/abstract/med/8963352

Australian Bureau of Statistics, National Health Survey: First Results, 2017-18, Overweight and Obesity, 4364.0.55.001, https://www.abs.gov.au/ausstats/abs@.nsf/Lookup/by%20Subject/4364.0.55.001~2017-18~Main%20Features~Overweight%20and%20obesity~90, accessed 29 November 2019.

Australian Government, Department of Health ‘Medications and weight’, 2019, https://www.health.gov.au/

Australian Government, Department of Health, ‘Weight and body mass index’, 2019, https://www.health.gov.au/resources/pregnancy-care-guidelines/part-d-clinical-assessments/weight-and-body-mass-index, accessed 29 November 2019.

Australian Institute of Health and Welfare, ‘A picture of overweight and obesity’, 2017, p.28, https://www.aihw.gov.au/getmedia/45f6ecc6-0caf-4af4-9ffc-a44c885b33d2/aihw-phe-216.pdf.aspx?inline=true, accessed

Autism Awareness Australia,

Research Request – Obesity and direct link to disability

Page 160 of 165

Butler, M, “Prader-Willi Syndrome: Obesity due to Genomic Imprinting”, Curr Genomics, vol. 12, no. 3, pp 204-215, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137005 Campbell, LV, ‘Genetics of obesity’, Australian Family Physician, Royal Australian College of General Practitioners, vol. 46, No. 7, 2017, pp-456-459, https://www.racgp.org.au/afp/2017/july/genetics-of-obesity/ accessed 18 November 2019. Chung, WK, ‘An Overview of Mongenic and Syndromic Obesities in Human’, Paediatric Blood and Cancer, vol. 58, no. 1, 12 October 2011, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215910/ accessed 12 November 2019. Crino, A,

Research Request – Obesity and direct link to disability

Page 161 of 165

FOI 24/25-0413

Health Direct, “Prader-Willi syndrome”, [website], 2019, https://www.healthdirect.gov.au/prader-willi-syndrome, (accessed 14 September 2019) Heymsfield, SB et al., ‘Hyperphagia: Current Concepts and Future Directions Proceedings of the 2nd International Conference on Hyperphagia’, Obesity (Silver Spring), vol. 22, no.1, February 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159941, accessed 17 November 2019. International WAGR Syndrome Association, ‘WAGR Syndrome: A guide for Physicians’, 2007, https://wagr.org/wp-content/uploads/2017/11/IWSA-Physicians-Guide-pdf-Nov-2017.pdf, accessed 25 November 2019. Irizarry, KA & Haqq, AM, ‘Syndromic Obesity’, Pediatric Obesity, Contemporary Endocrinology, 12 October 2017, pp. 153-182, https://link.springer.com/chapter/10.1007/978-3-319-68192-4_9, accessed 18 November 2019. Koritsas, S, and Iacono, T,

Research Request – Obesity and direct link to disability

Page 162 of 165

FOI 24/25-0413

Murray, J, and Ryan-Krause, P, “Obesity in Children with Down Syndrome: Background and Recommendations for Management”, Pediatric Nursing, Vol. 36, No. 6, pp. 314-9, 2010. https://search.proquest.com/openview/17e743f38ff81c67a9d3f8ecf85aaaf3/1?pq-origsite=gscholar&cbl=47659, accessed 7 November 2019 [secondary referenced research in quote could not be accessed].

National Organization for Rare Disorders, ‘Alstrom Syndrome’, 2016, https://rarediseases.org/rare-diseases/alstrom-syndrome/, accessed 22 November 2019.

Newcomer J, Metabolic syndrome and mental illness. American Journal Managed Care. 2007;13 (7 Suppl):S170-177.

Pierce, M, et al.,

FOI 24/25-0413

• U.S. National Library of Medicine, ‘ALMS1 gene’, 12 November 2019, https://ghr.nlm.nih.gov/gene/ALMS1#conditions, accessed 22 November 2019.
• U.S. National Library of Medicine, ‘Alstrom syndrome’, 12 November 2019, https://ghr.nlm.nih.gov/condition/alstrom-syndrome, accessed 22 November 2019.
• U.S. National Library of Medicine, ‘Bardet-Biedl syndrome’, 29 October 2019, https://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome#statistics, accessed 12 November

• U.S. National Library of Medicine, WAGR Syndrome, 2019, https://ghr.nlm.nih.gov/condition/wagr- syndrome, accessed 25 November 2019.
• Weinstein, LS et al., ‘The Role of GNAS and Other Imprinted Genes in the Development of Obesity’, International Journal of Obesity, vol.34, no.1 pp.6-17, 2010, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931809/, accessed 25 November 2019.
• Zheng, Z et al.,

Research Request – Duchenne Muscular Dystrophy

| Brief | Duchenne Muscular Dystrophy. Thermoregulation and the condition. |—| | Date | 31/10/19 | Requester | S22(1)(A)(ii) - Irrelevant | Researcher | S22(1)(A) (Tactical Research Advisor – TAT/AAT)

Reference List

• H. Kelfer et al., “Malignant Hyperthermia in a Child with Duchenne Muscular Dystrophy”, Pediatrics, vol 71, no 1, pp. 118-119, 1983, https://pediatrics.aappublications.org/content/71/1/118

• J. Wang and T. Stanley, “Duchenne muscular dystrophy and malignant hyperthermia -two case reports”, Canadian Anaesthetists’ Society Journal, vol 33, no 4, pp 492–497, 1986, https://link.springer.com/article/10.1007/BF03010977

• H. Gurnaney et al., “Malignant Hyperthermia and Muscular Dystrophies”, Anesthesia & Analgesia, Vol 109, No 4, pp. 1043-1048, 2009, https://journals.lww.com/anesthesia-analgesia/Fulltext/2009/10000/Malignant_Hyperthermia_and_Muscular_Dystrophies.10.aspx

2 J. Wang and T. Stanley, “Duchenne muscular dystrophy and malignant hyperthermia -two case reports”, Canadian Anaesthetists’ Society Journal, vol 33, no 4, pp 492–497, 1986, https://link.springer.com/article/10.1007/BF03010977

3 H. Gurnaney et al., “Malignant Hyperthermia and Muscular Dystrophies”, Anesthesia & Analgesia, Vol 109, No 4, pp. 1043-1048, 2009, https://journals.lww.com/anesthesia-analgesia/Fulltext/2009/10000/Malignant_Hyperthermia_and_Muscular_Dystrophies.10.aspx

Research Request – Duchenne Muscular Dystrophy Page 2 of 2 Page 165 of 165