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XXXXXXXX HOSPITAL

Research Protocol Version 1, XXXXXXX date

AUSTRALIAN SCLERODERMA SCREENING PROGRAM (ASSP)

1.0 SCLERODERMA GENERAL OVERVIEW.................................................................2

2.0 AUSTRALIAN SCLERODERMA INTEREST GROUP...............................................3

3.0 THE AUSTRALIAN SCLERODERMA SCREENING PROGRAM (ASSP) AND RESEARCH PROJECT..............................................................................................43.1 ASSP primary aims:............................................................................................53.2 ASSP secondary aims:.......................................................................................5

4.0 ASSP RESEARCH COMPONENT.............................................................................54.1 Two part research component............................................................................5

Part One: use of de-identified data.....................................................................5Part Two: blood sample for Pro-NT BNP, other novel markers and DNA..........6

4.2 Elements of the screening program....................................................................8History and clinical examination.........................................................................8Investigations......................................................................................................9

4.3 Criteria for participation in research component.................................................9Inclusion Criteria.................................................................................................9Exclusion Criteria..............................................................................................10

4.4 Recruitment to the research.............................................................................104.5 Ethics approval.................................................................................................114.6 Governance and staffing...................................................................................114.7 Statistical Analyses...........................................................................................124.8 Funding.............................................................................................................124.9 Publication of results.........................................................................................12

REFERENCES.....................................................................................................................13

APPENDIX ONE: ASSP DATASETAPPENDIX TWO: FLOW CHART FOR USE OF GENETIC MATERIALAPPENDIX THREE: INCLUSION CRITERIAAPPENDIX FOUR: PARTICIPANT INFORMATION AND CONSENT FORMAPPENDIX FIVE: CORRESPONDENCE WITH REFERRING PHYSICIANSAPPENDIX SIX: LETTER CONFIRMING APPOINTMENT TIMEAPPENDIX SEVEN: BROCHURE ON SCREENING PROGRAMAPPENDIX EIGHT: ROUTINE SCREENING FORMS

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1.0 SCLERODERMA GENERAL OVERVIEWScleroderma is a rare, chronic disease characterized by excessive deposits of

collagen. Collagen is the main protein of connective tissue in animals. It has great

tensile strength, and is the main component of cartilage, ligaments, tendons, bone

and teeth. Collagen is responsible for skin strength and elasticity, it strengthens

blood vessels and plays a role in tissue development. Systemic sclerosis (SSc) is

generalised disease of excess collagen deposition which can affect various parts of

the body. SSc is often linked with mixed connective tissue disease (MCTD) which

is a human autoimmune disease in which the immune system attacks the body.

SSc can also affect connective tissue in the pulmonary arteries, the blood vessels

that carry blood away from the heart and to the lungs, severely restricting the flow

of blood from the heart to the lungs, and increasing the pressure in the pulmonary

arteries resulting in Pulmonary Arterial Hypertension (PAH). The heart must

pump against this increased pressure to maintain blood flow to the lungs and then

to the rest of the body. The heart adapts to this increased pressure by gradually

becoming larger, particularly on its right side. However, this is only a short term

solution and the heart eventually fails to pump efficiently. As a result, the body does

not receive sufficient oxygen supply from the blood to fulfil all its needs and the

patient may experience shortness of breath, dizziness, fainting, and other

symptoms, all of which are exacerbated by exertion. This complication is

particularly common in the limited form of SSc which is a more slowly progressive

form with less extensive involvement. Nonetheless, it may also occur in patients

with the more rapidly progressive, diffuse form.

The disease process in the pulmonary arteries which leads to PAH can sometimes

occur over several years. The signs and symptoms of this disease are often hard to

distinguish from other diseases or conditions, particularly in the early stages. This

frequently delays the formal diagnosis of PAH. During this time, symptoms such as

unexplained tiredness and breathlessness are experienced. These symptoms are

generally first only noticed during physical activity, but as the disease progresses

they are present all the time, even when resting. Understandably this impacts

greatly on daily life, limiting daily activities. More importantly the disease can lead

to right-sided heart failure.

Scleroderma and connective tissue disease can also contribute to a disease of the

lung tissue called Interstitial Lung Disease (ILD). In ILD, the walls of the air sacs in

the lung and the lung tissue become inflamed. If this inflammation continues then


scarring, otherwise know as fibrosis, occurs and the lung becomes stiff. Symptoms

of ILD are similar to the breathlessness of PAH; however there may also be a

cough that can become quite distressing for patients.

PAH and ILD are recognised as the number one cause of death in patients with

scleroderma [1]. Reports of the prevalence of SSc and of PAH associated with SSc

vary. It has been estimated that in Australia, the point prevalence of SSc is

approximately 2300 patients [2] and that SSc PAH in Australia could be expected

to affect approximately 600 patients [3], confirmed by a study that found the

prevalence of PAH within the SSc or MCTD population to be 26% [4]. However

there is evidence that PAH is under-diagnosed, with recent studies suggesting

more than 13% of patients followed up in a community rheumatology setting had

undiagnosed PAH prior to formal assessment [4].

As well as the condition often being silent until late in the disease, it may not be

detected in investigations such as the echocardiogram (ECHO), if there is no minor

leakiness of the tricuspid valve on the right side of the heart (approximately 25% of

people) or if the technicians performing the investigations do not have the specific

skills required for detecting PAH.

There is now effective treatment available [5-8] which will reduce the severity of the

complications of this disease if provided early in the illness, so timely and ongoing

screening for SSc patients is currently recommended by the British Thoracic

Society [9] and the Royal Free Hospital Connective Tissue Disease Clinic. A

screening trial for patients with SSc has been underway in Perth, Western Australia

since April 2005 and had screened over 100 patients in the first 12 months. Twenty

six (22%) of 119 patients were thought likely to have PAH based on ECHO

findings, of these 21 (81%) had the limited form of SSc. Of the 26 patients, 13

(11%) had PAH confirmed on Right Heart Catheter, with PAH defined as mean

pulmonary artery pressure >25 mmHg. There are currently several international

groups who have established databases and registries such as PHAROS

(Pulmonary Hypertension Registry of Scleroderma), the EUSTAR data base, SSc

QuERI (Toronto) and the Scleroderma Clinical Trials Consortium.

2.0 AUSTRALIAN SCLERODERMA INTEREST GROUPThe Australian Scleroderma Interest Group (ASIG) was formed in November 2005

to bring together physicians interested in improving the care of patients with

Systemic Sclerosis (SSc) by better management of its complications, especially

pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). Given the


evidence of the benefits of screening and the current lack of facilities to provide this

service, the group determined that it would establish designated screening centres

around Australia so that all patients in Australia with a diagnosis of SSc or Mixed

Connective Tissue Disease (MCTD) could have access to high quality annual

screening for the presence of disease-related cardio-respiratory complications,

regardless of whether respiratory symptoms were present.

3.0 THE AUSTRALIAN SCLERODERMA SCREENING PROGRAM (ASSP) AND RESEARCH PROJECT

The ASSP is the result of a collaboration between members of ASIG from across

Australia and currently comprises the following physicians:

Dr Wendy Stevens, St Vincent’s Health, Victoria

Dr Joanne Sahhar, Monash Medical Centre, Victoria

Assoc Prof Susanna Proudman, Royal Adelaide Hospital, South Australia

Dr Janet Roddy, Royal Perth Hospital, Western Australia

Assoc Prof Peter Youssef, Royal Prince Alfred, New South Wales

Assoc Prof Peter Nash, Sunshine Coast Rheumatology, Queensland

Assoc Prof Kathleen Tymms, Canberra Rheumatology ACT

Dr Jane Zochling, Menzies Institute, Tasmania

Assoc Prof Les Schrieber, Royal North Shore Hospital, New South Wales

Assoc Prof Allan Sturgess, St George Hospital, New South Wales

Assoc Prof Gabor Major and Assoc Prof Glenn Reeves, John Hunter Hospital,

New South Wales

Assoc Prof Catherine Hill, Queen Elizabeth Hospital, South Australia

Dr Vivek Thakkar, Liverpool Hospital, New South Wales

Dr Gemma Strickland, St Vincent’s Health, Victoria

With assistance from:

Prof David Celermajer (cardiologist), Royal Prince Alfred, New South Wales

Dr Mandy Nikpour (rheumatologist and epidemiologist), St Vincent’s Health,

Victoria


3.1 ASSP primary aims: To increase the rate of screening for cardiopulmonary complications in SSc

and MCTD, by establishing screening centres around Australia staffed by

clinicians with expertise in the disease.

To ensure screened patients receive appropriate and timely treatment

according to evidenced based practice.

3.2 ASSP secondary aims: To promote the adoption of best practice guidelines for the assessment of

PAH and ILD associated with SSc or MCTD into routine clinical practice.

To create a system to link data collected from the screening centres in de-

identified form to be used for investigating whether there are predisposing

factors associated with the progression of SSc.

To achieve the secondary aims a research component of the program is

proposed.

4.0 ASSP RESEARCH COMPONENT

4.1 Two part research component

Part One: use of de-identified dataAs a part of standard care, each screening centre will collect routine clinical data

according to a defined dataset (see Appendix 1) as well as a history from the

referring physician. Patients will be asked to consent to the use of this data in de-

identified form.

For patients who have not consented to the research component of the project, the

dataset will be on a form that will be located on the local hospital server so that it

can be completed and printed off for inclusion in the patient record.

The dataset will also be located within a custom made application on a secure

server within a public hospital setting. Negotiations are currently underway for this

to be based at St Vincent’s Health, Victoria. Clinicians from around Australia will be

able to access the form via a secure log-in to enter data while seeing consented

patients, as well as edit data later on as test results become available. Clinicians

will only have access to their own patient data and they will also be able to print off

a copy of the form to store in paper format in the patient’s hospital file.

The full or aggregated database will only be able to be accessed by the ASIG

Project Officer, ASIG Data Manager and the IT Manager. Each patient will be


assigned a unique code when entered into the database, so that when the data is

aggregated there will not be any identifying information visible. The link between

the unique code and patient identification will be kept in a secure location by the

lead researcher at each site. The aggregated database with de-identified data will

be in a format that can be exported to a statistical software package to enable

statistical analysis.

The security for the server will be the same as that for all files stored electronically

within St Vincent’s Health with data backed up daily.

Part Two: blood sample for Pro-NT BNP, other novel markers and DNATo assist in assessing predisposing factors, patients will be asked to consent to

extra blood which will usually be taken at the same time as routine tests. The two

extra samples of 10ml each will be examined to explore links to the progression of

SSc, specifically:

The whole blood in one tube will be spun to collect the serum. ‘Markers’ in

blood serum sometimes indicate that disease is present or help predict how

severe the disease will be in the future. Researchers often make new

discoveries about the body and new or ‘novel markers’ become recognised.

Pro-NT BNP is a novel marker that is associated with heart disease

including PAH, that is rapidly becoming part of standard care; however as it

is not routine at all hospitals yet the sample may need to be transported to

another hospital for analysis. It is planned to have this test performed once

funding for the kits becomes available.

The researchers would like to store the remainder of this blood serum

sample for up to ten years to explore links with other known novel markers

in the future. This blood sample will be collected at each screening visit.

The whole blood in the second tube will be spun down to collect the buffy

coat from which DNA is extracted. Similarly, researchers often make new

discoveries about the genes associated with disease, so the second sample

will also be stored for up to ten years to serve as a DNA bank for analyses

by the current research team of potentially relevant genes related to SSc as

they emerge in the future. This sample will only be collected once.

The use of a portion of the patient’s blood for extraction and storage of

DNA:


DNA will be stored and serve as a DNA bank for studies of potentially

relevant genes as they emerge by members of the ASIG project. Any

studies would require the permission of the Custodian of the DNA bank and

database, Dr XXXXX, and approval from the ASIG Blood Research

Committee as well as Institutional Ethics Committee. The use of database

material will be controlled according to a flow chart (see Appendix 2) that

has been devised according to current NHMRC guidelines. The key

attributes of this scheme are: 1) the identification code is kept separate from

the material; 2) there is a designated custodian and 3) there is a committee

to determine usage of the material. Nevertheless, the ‘right to know’ of

patients that the DNA could be used in future studies is addressed in the

patient information sheet. The samples will be de-identified and at no time

will patients be contacted based on the results of their genetic analysis.

Patients will also be asked if they wish to be contacted if clinically relevant

genetic information is uncovered.

Patients will be asked to consent to Part 2 of the research separately from Part 1

(the use of routine clinical data) and will have the option to consent to have their

data being included but not to have the extra blood samples taken and stored.

Blood samples collected by centres associated with the Australian Scleroderma

Interest Group (ASIG) are frozen and sent to the Arthritis Research Laboratory

(ARL) located at The Queen Elizabeth Hospital, Woodville South, SA for storage.

Proposed studies using the DNA sample:

1. A comprehensive analysis of the immunogenetics of scleroderma.

To undertake this genetic study the DNA samples will be sent to Prof Matt Brown's

laboratory in the Diamantina Institute for Cancer, Immunology and Metabolic

Medicine in Queensland for analysis. All samples will remain de-identified, labelled

only with the ASIG unique ID number.

ASIG will be genotyping common variants (single nucleotide polymorphisms

(SNPs)) in genes previously associated with immunological diseases.

Individually these genes have little predictive value for disease, and the utility

of the genetic findings in clinical diagnosis is currently uncertain; however by

analysing the samples of a large group of patients for whom extensive data

is available in the ASIG database it is hoped to explore links between genes

and disease onset and progression.


ASIG will not be testing rare variants known to have strong disease

associations in humans as the SNPs selected were chosen to identify lower

penetrance moderate and common variants, rather than as a screen for

monogenic diseases.

2. Genetics of Scleroderma

As with the immunogenetics study, the de-identified DNA samples with only ASIG

IDs as labels will be sent to Professor Matt Brown’s laboratory.

The study has two parts. First is to identify genetic factors involved in scleroderma

by sequencing a nucleotide (exon 37) of the fibrillin gene in a large case collection.

The study will compare mutations associated in scleroderma patients against that

of healthy controls who have already been sequenced by Professor Brown’s group,

and healthy controls of white European descent for whom exome sequence data is

already publicly available.

Second, a genome-wide association study (GWAS) and meta-analysis of available

GWAS data will be undertaken. Case data from the ASIG cohort will be compared

with common control data publicly available, including from Australian cohorts such

as the Older Age Twin Study, which have been genotyped using the same chips.

The GWAS data will be analysed as per a typical GWAS on its own, then meta-

analysed with the available GWAS data from European and North American

Cohorts in order to increase the power of the study. This dataset will represent the

largest available scleroderma GWAS, and is very likely to identify further genetic

factors involved in the disease.

4.2 Elements of the screening programThere are three parts to the screening – history, clinical examination and

investigations – and the process for this will be the same regardless of whether

patients choose to participate in the research. As stated above, routine clinical data

defined in the dataset will be recorded in patients’ files as per standard practice;

however for those who have consented to the research an online version will also

be created for entry into the aggregated database.


Baseline data will be collected at the first appointment and the patient will be

contacted for review every 12 months; however not all investigations will be

repeated annually.

History and clinical examinationA clinician with a special interest in the management of SSc and/or PAH who will

be a member of the research team will take a history and then complete a clinical

examination. The clinician may be assisted by a registrar and/or research nurse.

The patient will have received an information pack (includes symptom

questionnaire, past medical history questionnaire and Quality of life Questionnaires

including HAQ, SF-36, sHAQ, PROMIS-29, FACIT-fatigue and dyspnoea, UCLA

SCTC GIT) that they are encouraged to complete and bring to the first appointment

for discussion with the clinician. This assessment will usually take place in the

public hospital outpatient setting, with the exception of private patients already

being seen by a research clinician who can undertake this assessment in the

private rooms during the course of routine care. After the assessment, the clinician

will refer patients for investigations.

The history will include:

demographics and social data

current health

past disease – diagnosis, organ involvement, treatment

The clinical examination will include:

Current symptoms

Body mass index, blood pressure

Skin Score

Examination of the cardiorespiratory system

InvestigationsThe investigations will be conducted within the public hospital according to

standard care with recommendations for the timing of repeat tests determined after

assessment of the results. A standard set of screening investigations would

include:

Lung function tests (spirometry and diffusing capacity)

Electrocardiograph (ECG)


Echocardiogram (Echo)

Chest Xray

Six minute walk test

Blood test for full blood count, renal and liver function, muscle enzymes and

autoantibody screen

Urine test

High-resolution computed tomography (HRCT) may be performed if

abnormalities are detected on lung function testing

The screening centre will be staffed by highly skilled technicians who have the

training and expertise to detect PAH and ILD.

The patient will not incur any costs if they choose to participate in the research, and

they will have no out of pocket expenses from the screening program.

4.3 Criteria for participation in research component

Inclusion Criteria Patients eligible for and participating in the screening program (aged

greater than 18 years with a clinical diagnosis of SSc or MCTD according

to either the American College of Rheumatology criteria or the LeRoy

criteria for limited or diffuse scleroderma – see Appendix 3)

Screening program patients who are willing to participate and have signed

the consent form – see Appendix 4.

Exclusion Criteria Patients unable to be screened due to

- Difficulty accessing a screening centre because of geographic

isolation or poor mobility.

- Factors likely to limit compliance with screening requirements.

- Factors likely to render screening investigations unsafe (modified

protocol may be permitted).

Patients do not wish to participate in research component

4.4 Recruitment to the researchAll doctors in Australia caring for patients with SSc and MCTD will be invited to

refer their patients to the most convenient screening centres using a preformatted

referral form – see Appendix 5, Parts a and b. Referrals may come from


rheumatologists, cardiologists, respiratory physicians, immunologists or general

practitioners. In the invitation, the physician will be informed of the benefits of the

screening program and what the program involves, be requested to supply relevant

patient history from the file, and asked to consider the agreement for ongoing

management. Physicians will also be told of the research component to the

screening program and that participation in this is optional for the patient. Referring

doctors will receive the results of the screening on a standard from – see Appendix

5 Part c.

Information on the screening program and research component will also be

disseminated to patients through support groups such as Scleroderma Australia

and the Arthritis society so that patients can approach their physician to discuss the

benefits of participation if they are interested.

Once a referral to the screening program is made the patient will be asked to ring

the screening centre to make an appointment. The patient will receive a letter

confirming the appointment time and informing them of the optional research

component – see Appendix 6. The letter will be accompanied by an information

pack which will include:

A brochure describing PAH and the investigations that are routinely

conducted as part of the screening program – Appendix 7

A symptom questionnaire based on the Vital Activities and Lifestyle Index

that patients are encouraged to complete before attending the first

appointment, that are all part of routine care – Appendix 8.

The Plain Language Statement and Consent Form for the research

component of the program. This will ensure that patients have time to

consider whether they have any queries about the research before

deciding whether they wish to participate - Appendix 4.

Cardio-respiratory complications can occur at any stage in the disease. PAH often

occurs after 10 years of disease duration. We are therefore keen to recruit both

recently diagnosed scleroderma patients and those with more long standing

disease into this project therefore the baseline appointment will review the patient

history and for research participants, the past information on the progress of the

disease will also be entered on the web based database. This process will ensure

that investigations are not repeated before there is a clinical need to do so, and

that all investigations are performed according to the standard now accepted as

best practice.


4.5 Ethics approval

Researchers attached to each of the screening centres will be responsible for

obtaining ethics approval from their local Human Research Ethics Committee for

the research component of the screening program. Each centre will use the same

research protocol with the only variations being information that is site specific –

names and contact details of researchers. All sites have obtained approval for the

project as at 2009.

4.6 Governance and staffingThe Australian Scleroderma Interest Group (ASIG) is a committee formed under

the auspice of the Australian Rheumatology Association (ARA). All researchers on

the project are members of the committee and of the ARA, with the exception of the

cardiologist and respiratory physicians who are co-opted members. The committee

meets regularly by teleconference or face to face and meetings are co-ordinated by

the Chair. One staff member, employed as a Project Officer, reports to the

committee and manages the implementation of the research protocol with the

assistance of the committee members who all donate their time to the project

voluntarily.

4.7 Statistical AnalysesThe data will be analysed to produce descriptive statistics. Tests for

correlations between clinical and genetic findings will be determined by the

type and distribution of the data. Power calculation: not applicable.

4.8 FundingFunding for the screening program and research component has been provided by

Actelion Australia as an unrestricted educational grant. The funding covered the

cost of the project for the initial three years (2007-2009) and this has been

extended on a yearly basis since 2012. Further funding will be sought to extend the

program.

4.9 Publication of resultsFindings of the research will be published in de-identified form in medical journals

and a summary will be available for participants through patient support groups

such as Scleroderma Australia.


REFERENCES

1. Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, Black CM, Coghlan JG. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 2003;62(11):1088-93.

2. Englert H, Small-McMahon J, Davis K, O'Connor H, Chambers P, Brooks P. Systemic sclerosis prevalence and mortality in Sydney 1974-88. Aust N Z J Med 1999;29(1):42-50.

3. Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, Rich S, Barst RJ, Barrett PS, Kral KM, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 2000;132(6):425-34.

4. Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C. The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study). Arthritis Rheum 2005;52(7):2125-32.

5. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347(5):322-9.

6. Williams MH, Das C, Handler CE, Akram MR, Davar J, Denton CP, Smith CJ, Black CM, Coghlan JG. Systemic sclerosis associated pulmonary hypertension: improved survival in the current era. Heart 2006;92(7):926-32.

7. Joglekar A, Tsai FS, McCloskey DA, Wilson JE, Seibold JR, Riley DJ. Bosentan in pulmonary arterial hypertension secondary to scleroderma. J Rheumatol 2006;33(1):61-8.

8. Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346(12):896-903.

9. British Cardiac Society Guidelines and Medical Practice Committee. Recommendations on the management of pulmonary hypertension in clinical practice. Heart 2001;86:i1-i13.


Appendix One

APPENDIX ONE: ASSP DATASET

SYSTEMIC SCLEROSIS DATA ENTRY SHEETS

First visit – PART I & Part II Annual review – PART II only but confirm ‘patient data’.Where there are options please circle appropriate response or use drop down box if entered electronically.

Appendix One

Appendix Two

APPENDIX TWO: FLOW CHART FOR THE USE OF GENETIC MATERIAL

Custodian of database: Dr Wendy StevensCommittee to consider projects that use database material: Drs S Proudman, Dr W Stevens,

Dr J. Sahhar, Dr J. Roddy, A/Prof P. Nash, A/Prof P Youssef.

Coded

Blood

Storage of Code(Dr XXXX)

Storage of Blood/DNA with coded identifier

Committee determines access.If for research purposes, specific projects must be approved by the Research Ethics Committee

Appendix Three

APPENDIX THREE: INCLUSION CRITERIA (a) American College of Rheumatology (ACR) criteria for systemic sclerosis

Clinical Features - Classification Related

Major criterion:Proximal scleroderma: symmetric thickening, tightening, and induration of the skin proximal to the metacarpophalangeal or metatarsophalangeal joints

Minor criteria:1. Sclerodactyly: above skin changes, limited to the fingers.

2. Digital pitting scars or loss of substance from the finger pad: Depressed areas at tips of fingers or loss of digital pad tissue as a result of ischemia

Investigations - Classification Related

3. Bibasilar pulmonary fibrosis: Bilateral reticular pattern of linear or lineonodular densities most pronounced in basilar portions of the lungs on standard chest radiograph; may assume appearance of diffuse mottling or “honeycomb lung”. These changes should not be attributable to primary lung disease.

Presence of the major criterion or 2 of the 3 minor criteria indicates systemic sclerosis.(Adapted from the Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary Criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23:581-90, 1980).

(b) Systemic Scleroderma subsets according to LeRoy et al.

[20<http://dermatology.cdlib.org/DOJvol8num1/reviews/scleroderma/haustein.html#20> ]

Limited Cutaneous SSc

Raynaud's phenomenon for years at presentation Skin sclerosis limited to hands, feet, face, and forearms, or absent Significant late incidence of pulmonary hypertension, trigeminal neuralgia,

calcinosis, and telangiectasia Dilated nailfold capillary loops, usually without capillary dropouts

Diffuse cutaneous SSc

Onset of Raynaud's phenomenon within 1 year of onset of skin changes Truncal and acral skin involvement Presence of tendon friction rubs Early and significant incidence of interstitial lung disease, oliguric renal failure,

diffuse gastrointestinal disease, and myocardial involvement Presence of anti-DNA topoisomerase I (anti-Scl-70) antibodies Absence of anticentromere antibodies

http://dermatology.cdlib.org/DOJvol8num1/reviews/scleroderma/haustein.html#20

Appendix Three

Nailfold capillary dilatation and destruction (detected by widefield nailfold capillaroscopy)

Appendix Four

HOSPITAL XXXX

PARTICIPANT INFORMATION AND CONSENT FORM

Protocol No. XXXX

Version XXXX, Dated XXXXSite: XXXX

Full Project Title: Australian Scleroderma Screening ProgramResearchers at St Vincent’s Health: XXXX

Associate Researcher in the national collaboration: XXXX

This Participant Information and Consent Form is 7 pages long. Please make sure you have all the pages.

1. Your ConsentYou are invited to take part in this research project because you have either Scleroderma (SSc) or Mixed Connective Tissue Disease (MCTD). The Participant Information section contains detailed information about the research project. Its purpose is to explain to you as openly and clearly as possible all the procedures involved in this project before you decide whether or not to take part in it.

Please read this Participant Information carefully. Feel free to ask questions about any information in the document. You may also wish to discuss the project with a relative or friend or your local health worker. Feel free to do this.

Once you understand what the project is about and if you agree to take part in it, you will be asked to sign the Consent Form. By signing the Consent Form, you indicate that you understand the information and that you give your consent to participate in the research project.

You will be given a copy of the Participant Information and Consent Form to keep as a record.

2. Purpose and BackgroundScleroderma (Systemic Sclerosis) is a rare, chronic disease characterized by excessive deposits of collagen in the connective tissue which can affect various parts of the body. SSc can also affect connective tissue in the pulmonary arteries, the blood vessels that carry blood away from the heart and to the lungs, restricting the flow of blood from the heart to the lungs, and increasing the pressure in the pulmonary arteries resulting in Pulmonary Arterial Hypertension (PAH).

Previous research has suggested that some patients with Scleroderma or Mixed Connective Tissue Disease may develop these complications which can impact on their heart and lungs and long term health. In the early stages the complications are difficult to detect however there is now effective treatment available which will reduce the severity of the symptoms if provided early in the illness. Therefore screening centres are being established around Australia and all patients confirmed to have either Scleroderma or Mixed Connective Tissue Disorder will be encouraged to use the service.

Those patients who do attend for annual screening at one of the Australian Scleroderma Screening Centres will be invited to participate in a research project. The physicians who

Participant Information and Consent Form Version XXXXX Page 1 of 7

Appendix Four

are setting up the centres would like to use the health information that is collected during routine care at the centre, so that the information can be examined to better understand why some people develop the serious complications.

Patients will also be asked if they are willing to provide two extra blood samples that are NOT part of routine care, but will also be used to understand why some people develop the serious complications. One sample will be spun in a lab to collect the sera and it will be used to test for markers in the blood that sometimes indicate that disease is present or help to predict how severe the disease will be in the future. BNP is a marker that can sometimes indicate that the heart is under some strain. It is thought that BNP may be raised in patients with scleroderma or mixed connective tissue disease who have pulmonary hypertension. With ongoing medical research new markers may be recognised so the researchers would like to store the remainder of this sample for future testing.The other sample will be used to explore links between your genes and how your illness progresses. Genes that are found in the blood are different for each person and they provide instructions for processes in the body. To perform this test, genetic material (DNA) is extracted from the blood cells. We are asking your permission to store some of the excess DNA for future studies of genes which future research suggests are related in some way to arthritis. The study does not involve storage of any living cells. Any future studies which did occur with the stored DNA would require the permission of the Custodian of the DNA bank of blood collected from St Vincent’s Hospital patients (Dr W Stevens) and be reported to the Research Ethics Committee before they could proceed.

The blood samples will be labelled only with your unique study code. The sera sample will be stored in 3 smaller tubes. One of the sera tubes will be stored at XXXXX Hospital to be used for blood marker studies involving only the scleroderma patients who attend XXXXX. The other sera sample and the genetic sample will both be transported to the Arthritis Research Laboratory in Adelaide for storage and future analysis with blood from other sites participating in the national study. The blood samples will be compared with samples from other people to help researchers understand why some people with SSc develop serious complications.

As you have made an appointment at the XXXXX screening centre, you have received this invitation. If you choose not to participate in the research your attendance at the screening centre will not be affected, and the ongoing management of your illness will proceed as per standard care.

3. ProceduresParticipation in this project will involve:

The use of your de-identified health information (information about you that does not include your name, address, date of birth or anything that would allow someone to know who you are) that will be collected as a part of routine care at the screening centre located at St Vincent’s Health. If you consent to this, there will be no change in the way your screening is conducted or the ongoing management of your illness. This de-identified data may be entered into international databases for studies of long term outcomes of patients with scleroderma. You will also be asked to complete a symptoms and quality of life questionnaires. These will allow your doctor to assess your health history, current health and general wellbeing. The questionnaires may take from 15 to 20 minutes to fill during the first visit and about 10 minutes for subsequent annual visits.

Two extra blood samples taken at the time of the routine screening procedure. You will be asked to consent to this procedure separately and have the option of with-holding consent to the extra blood samples but still including your information in the research.


Appendix Four

The consent includes taking two samples, one of 10 ml (approximately 2 teaspoons full) and one of 16ml (approximately 3 teaspoons) at the same time as the routine test for the screening program which is 20 ml. This means one procedure will be performed and from this collection three separate samples will be taken totalling 46 ml. The BNP test will be performed when the next batch is processed; however the researchers would like to store the other sera samples for testing in the future. Researchers often make new discoveries about genes, so they would like to keep the sample rather than asking you to repeat it again at a later date and this means it may be stored for several years. The research on your blood will only be related to finding out more information about Scleroderma.

4. Possible BenefitsPossible benefit from the research part of the program is knowing that you are contributing to a project that may be able to predict the characteristics of people who are likely to go on to develop the serious complications. Depending on the stage of your illness this may not provide a direct benefit to you; however it may benefit others diagnosed with your illness in the future.

5. Possible RisksAs the procedures to be performed are all part of routine care there are no additional risks or side effects, other than that experienced during the taking of the routine blood test. This would be possible discomfort and pain, minor bruising, and swelling at the site of the needle prick.

Your health information will be stored securely with access limited to research staff and in a format that would make identification of you extremely unlikely. All reports on the findings of the research will be on information that is grouped together so that it will be impossible to identify individuals.

6. Alternatives to ParticipationIf you choose not to participate you can still participate in the screening program.

7. Privacy, Confidentiality and Disclosure of InformationYour health information that will be used in the research will not include anything that easily identifies you; however your information will be linked to a unique code. There are two reasons why this is done. Firstly it means that we can link your information from each annual visit to compare how your health is over time and the progression of any symptoms that may develop. The second reason is that at some point in the future if during our research we become aware of any clinical concerns regarding your health we would be able to let your treating doctor know of these concerns so that he or she can advise you on the best treatment options. Your health information will be stored electronically with information collected from other screening centres around Australia. It will be stored on a secure computer associated St Vincent’s Health.

The link between your unique code and your identifying information will be kept in a separate place from the health information. Access to the health information will be limited to those directly involved in the research. Your data will be kept confidential in accordance with the standards followed by medical researchers in compliance will all applicable privacy laws.

This project started in 2007 and has funding committed until 2014. The researchers continue to seek funding grants and if ongoing funding is made available the project will continue as long as the information collected is relevant for researching this illness.


Appendix Four

Research like this is called a longitudinal study, which means that the information may be able to provide valuable findings that will help patient care for many years.

We would like to keep your unused stored blood samples for up to ten years so they can be used in scleroderma research. One sera sample will be stored at St Vincent’s Hospital and Dr Stevens will seek approval from the HREC before using it in any scleroderma research projects. The other serum and genetic blood samples will be stored at the Arthritis Research Laboratory, Adelaide. The National research collaboration has approval to use the sera for any scleroderma research projects conducted by the researchers in the collaboration, however approval from the HREC will be sought for all genetic studies. All samples will be labelled only with your unique code.

Any information obtained in connection with this project and that can identify you will remain confidential. It will only be disclosed with your permission, except as required by law.

The researchers plan to publish the results of this research for scientific purposes but your identity will not be given.

8. Results of ProjectThe researchers intend to publish the results of this study in scientific journals. Participants will be able to request that they receive copies of these publications. A summary of the findings will also be provided to Scleroderma Australia, the national support group for distribution to any interested participants or patients.

9. Further Information or Any ProblemsThis research is a collaboration set up by a group of doctors from around Australia. If you require further information or if you have any problems concerning this project, you can contact the principal researcher located at St Vincent’s Hospital, Dr Wendy Stevens, on Ph: 9288 2211. For your information the other doctors involved in this project are:

Dr Joanne Sahhar, Monash Medical Centre, VIC

A Prof Susanna Proudman, Royal Adelaide Hospital, SA

Dr Janet Roddy, Royal Perth Hospital, WA

Assoc Prof Peter Youssef, Royal Prince Alfred, NSW

A Prof Peter Nash, Sunshine Rheumatology, QLD

A Prof Allan Sturgess, St George Hospital, NSW

A Prof Kathleen Tymms, Canberra Rheumatology, ACT

A Prof Catherine Hill, Queen Elizabeth Hospital, SA

A Prof Jane Zochling, Menzies Institute, TAS

Dr Gabor Major and A Prof Glenn Reeves, John Hunter Hospital, NSW

Dr Vivek Thakkar, Liverpool Hospital, NSW

A Prof Les Schrieber, Royal North Shore Hospital, NSW

10. ComplaintsIf you have any complaints about any aspect of the study or the way in which it is being conducted you may contact the Patient Representative at XXXXX on Telephone XXXXX.


Appendix Four

You will need to tell the Patient Representative the name of the person who is noted above as principal investigator.

11. Participation is VoluntaryParticipation in any research project is voluntary. If you do not wish to take part you are not obliged to. If you do consent to any aspect of this research you can change your mind later. This means that you can ask that your health information that has not been processed be removed from the research, or that your stored blood sample be destroyed. You can also provide consent to the blood test at some time in the future if you decide that you would like to do this later. Any changes to your consent to the research will not in any way change your involvement in the screening program, the ongoing management of your illness or your relationship with XXXXX.

Before you make your decision whether to participate, a member of the research team will be available to answer any questions you have about the research project. You can ask for any information you want. Sign the Consent Form only after you have had a chance to ask your questions and have received satisfactory answers.

If you decide to withdraw from this project, please notify a member of the research team before you withdraw. This notice will allow that person or the research supervisor to inform you if there are any health risks or special requirements linked to withdrawing.

12. Research Participant Rights

If you have any questions about your rights as a research participant, then you may contact the Executive Officer Research at XXXXXon Telephone: XXXXX.

12. Ethical GuidelinesThis project will be carried out according to the National Statement on Ethical Conduct in Research Involving Humans (June 1999) produced by the National Health and Medical Research Council of Australia. This statement has been developed to protect the interests of people who agree to participate in human research studies.

The ethical aspects of this research project have been approved by the Human Research Ethics Committee of XXXXX.

13. Reimbursement for your costsYou will not be paid for your participation in this project.


Appendix Four

XXXX HOSPITAL

CONSENT FORM Protocol NO. XXXXX

Version XXXXX, Dated XXXXX

Site: XXXXX

Full Project Title: Australian Scleroderma Screening Program

I have read, or have had read to me, and I understand the Participant Information Version XXXXX.

I freely agree to participate in the following parts of the project according to the conditions in the Participant Information (place a cross in the box for items for which you are willing to consent):

Use of de-identified health information yes

A blood sample to be stored at XXXXXuntil it is used in blood marker studies specifically related to understanding the disease of scleroderma

yes no

A blood sample to be tested for blood markers including BNP protein level with the remainder to be stored for several years for testing for other new blood markers, specifically related to understanding the disease of scleroderma and conducted by members of the ASIG research team yes no

A blood sample to be stored for several years and used for genetic research specifically related to understanding the disease of scleroderma and conducted by members of the ASIG research team yes no

I wish to be contacted in the future if genetic information is uncovered which may be important for my future health. yes no

I will be given a copy of the Participant Information and Consent Form to keep

The researcher has agreed not to reveal my identity and personal details if information about this project is published or presented in any public form.

Participant’s Name (printed) ……………………………………………………

Signature Date

Name of Witness to Participant’s Signature (printed) ……………………………………………

Signature Date

Declaration by researcher*: I have given a verbal explanation of the research project, its procedures and risks and I believe that the participant has understood that explanation.

Researcher’s Name (printed) ……………………………………………………

Signature Date* A senior member of the research team must provide the explanation and provision of information concerning the research project.


Appendix Four

Note: All parties signing the Consent Form must date their own signature.


Appendix Four

XXXX HOSPITAL

REVOCATION OF CONSENT FORM

(To be used for participants who wish to withdraw from the project.)

Protocol NO. XXXXVersion XXXX, Dated XXXX

Site: XXXX

Full Project Title: Australian Scleroderma Screening Program

I hereby wish to WITHDRAW my consent to participate in the research proposal described above and understand that such withdrawal WILL NOT jeopardise any treatment or my relationship with XXXX.

Participant’s Name (printed) …………………………………………………….

Signature Date


Appendix 5 - Version 1, Dated 23rd February 2007

APPENDIX FIVE: CORRESPONDENCE WITH REFERRING PHYSICIANS

APPENDIX 5a: Letter inviting physicians to refer to screening centre

AUSTRALIAN SCLERODERMA INTEREST GROUPRESEARCH PROJECT

XXXXX HOSPITALDear Colleague,

The Australian Scleroderma Interest Group (ASIG) was formed in November 2005 to bring together physicians interested in research and management of patients with Systemic Sclerosis (SSc) with a focus on pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). ASIG is in the process of establishing designated screening centres around Australia so that all patients in Australia with a diagnosis of SSc or Mixed Connective Tissue Disease (MCTD) can have access to high quality annual screening for the presence of disease-related cardio-respiratory complications, regardless of whether respiratory symptoms are present. This practice is currently recommended by the British Thoracic Society [9] and the Royal Free Hospital Connective Tissue Disease Clinic. There are three components to the screening which are all part of routine care - an interview to take a history, a clinical examination and investigations based on the protocol developed by The Australian Scleroderma Interest Group. It is important to standardise these procedures eg. ECHO to maximise diagnostic accuracy.

The benefit to the patient includes echocardigraphy and pulmonary function testing as indicated yearly with no out of pocket expense, with all patients being returned to the care of their referring Rheumatologist with a results report.

All patients undergoing screening will be invited to participate in a research component of the project that has two parts and will be under ARA governance. The first is consent to the collection of their de-identified data that will be aggregated with data from other centres around Australia. This will enable powerful statistical analyses to explore predisposing factors linked to the progression of the disease. The second part is consent to two extra blood samples that are not part of routine care (for DNA analysis and serum for novel markers), that will be used to examine potential links between these markers and disease outcomes. Involvement in the research is optional and patients may consent to the use of their data but not the extra blood test. Patients will be informed of the research component when their screening appointment is confirmed. The research protocol has received ethics approval from XXXX Health Human Research Ethics Committee.

We would like to continue to follow these patients on an annual basis to look at predictors for development of cardiorespiratory disease. However we do not intend to take over their day to day management and copies of all tests will be sent to you and you would be consulted if any significant abnormalities were detected that may require further investigation or management prior to this being instituted.

We would like to encourage you to discuss the benefits of this screening program with your existing and recently diagnosed SSc patients. If you wish to proceed with a referral, please complete the attached sheets, including a signed treatment agreement.


If you have any queries we would be delighted to discuss this program further. You can contact Dr XXXX on XXXX.

Yours sincerely,

Dr XXXXConsultant Rheumatologist

References

Gibbs JSR. Recommendations on the manangement of pulmonary hypertension in clinical practice. Heart 2001;86 (Suppl 1): I1-I13.

Mukerjee D et al. Prevalence and outcome in systemic sclerosis assocaited pulmonary arterial hypertension: application of a registry approach. Ann Rhuem Dis 2003;62: 1088-1093.


APPENDIX 5b: Form for referral to screening centre

REFERRAL TO AUSTRALIAN SCLERODERMA SCREENING PROGRAMXXXX HOSPITAL

To: Dr XXXXConsultant Rheumatologist

Patient details:Name:

Address:

Telephone:

Date of Birth:

Referring Doctor:Name:

Address:

Telephone:

Provider Number:

Disease subset:Diffuse SSc Limited SSc MCTD

ANA titre: _________ ANA pattern: _______

Scl70: _________

Other antibodies: _________

Treatment agreement: Could you please tell us how you would like the ongoing management of your patient to be arranged by ticking the appropriate boxes below.

Basic screening (clinical assessment, pulmonary function tests, ECG echocardiogram, chest xray, bloods, urinalysis, 6MWT)

Yes

Further assessment if indicated (eg right heart catheter, high resolution CT scan chest)

Yes No Consult me before proceeding

Management of pulmonary hypertension, if identified

Yes No Consult me to discuss treatment

Management of interstitial lung disease, if identified


Yes No Consult me to discuss treatment

Would you like to be notified when we contact your patient for their annual screen? Please note that frequency of investigations will vary according to risk as determined by results screening.

Yes No

Signed Treatment Agreement:

I would like my patient to be enrolled in the Australian Scleroderma Screening Program with future management of my patient to occur according to the above options that I have selected. I am aware that my patient will be asked whether they wish to participate in the research component of the project, but if they do not wish to participate in the research, the screening will proceed as per standard clinical care.

Signature: Date:

* Could you please attach copies of PFT, ECHO, Xray, HRCT scan of chest performed in the last two years, if available?

Your patient will be notified by mail of appointment times and sent more information about the programme

Office use: Screening number assigned:Dates of PFT: Echo: 6MWT: clinic review:


APPENDIX 5c: SUMMARY OF RESULTS LETTER TO BE SENT TO REFERRING PHYSICIAN

AUSTRALIAN SCLERODERMA INTEREST GROUPSCREENING PROGRAM BASED AT

XXXX HOSPITALSummary of results

Date:Visit number:Referring doctor’s name and address:Patient’s name address and date of birth:

Procedures performed: Results:Symptom questionnaire

Physical examination

Pulmonary function tests

Echocardiogram

ECG

Chest Xray

Six minute walk test

Implication of resultsFollowing these assessments, we believe that your patient:

Interstitial Lung Disease Mild

Moderate

Severe

Pulmonary hypertension Low risk

Moderate risk

High risk - requires further confirmation with RHC

Has…..

Recommendation:Should have repeat testing in __ Months with PFT

Echo

Further assessment with......................

Treatment for should be considered..................


Please note, if the above indicates further assessment or treatment is required you will be contacted by Dr XXXX before this proceeds according to the treatment agreement, however you can contact Dr XXXX at any time if you wish to discuss the progress of your patient.

Signature: __________________Dr XXXXConsultant Rheumatologist

Appendix Six

APPENDIX SIX: LETTER CONFIRMING APPOINTMENT TIME

XXXX Hospital Letterhead

Dear ____,

We have received a request for you to attend the Scleroderma screening clinic based at XXXX Hospital Melbourne. This letter is to confirm your appointment at the Clinic Your appointment is for:

Day,and DateLocationDoctor

Enclosed with this letter you will find:

A brochure that provides information about Scleroderma, the complications that patients sometimes experience and the importance of screening for these complications. The tests that will be conducted are also explained.

A symptom questionnaire that we would ask you to read and fill out as much as possible before your appointment. However if you find any of it difficult to complete do not be concerned you can be assisted at your appointment.

Information on a research project that the group of doctors who have set up the screening centres around Australia are also involved in. This project hopes to learn more about the disease of Scleroderma and how the doctors can provide better care for their patients. Patients who consent to involvement in the research will receive exactly the same care as those who choose not to participate. We would ask that you read the Patient Information and Consent form for the research project so that you can consider whether you would like to participate in the project. If you would like to participate you will be asked to sign the form during your visit; however there will be a chance to ask any questions you may have before you make a decision.

Please bring to your appointment any previous Xrays you have of your chest or lungs.

If you have any queries about your appointment please contact the Scleroderma Nurse – XXXX on XXXX.

Yours sincerely,

Scleroderma NurseXXXX HOSPITAL

Appendix Seven

APPENDIX SEVEN: BROCHURE ON SCREENING PROGRAM

Appendix Seven

Appendix Eight – ASSP Patient Questionnaire 1st Appointment - Version 1 dated 1st May 2014

Australian Scleroderma Screening Program4.10 PATIENT QUESTIONNAIRE FOR THE FIRST APPOINTMENT

Thank you for completing this form before your appointment. We ask that you read carefully the instructions and fill in all of the sections below. Your Doctor will discuss the answers with you, so if you are unsure do not worry – just skip that question and move onto the next.

4.11 1. YOUR PERSONAL INFORMATION Date: … / … / …

Surname: First name:Date of birth: Gender:

Male FemaleAddress:

Phone (H):Phone (W):Phone (M):Email address:

Medicare number:

Name of your Rheumatologist:

Referring doctor/physician involved in care:Name:Address:

Phone:

GP if not referring doctor:Name:Address:

Phone:Have you received information about the option to participate in the research? Yes No

(Please note, you will have a chance to discuss this with the doctor before you make a decision)Can you give us the name, address and phone number of a person not living with you who we can contact if you move from your current address?

4.12

ASSP First visit : Patient Questionnaire - Version 1 dated 1st May 2014 Page 18 of 65


4.13 2. YOUR BACKGROUND INFORMATION

Your country of birth: Your mother’s country of birth:

Your father’s country of birth:Are you confident reading English? Yes No

What is your cultural/ethnic background?

Aboriginal or Torres Strait Islander Asian Caucasian Hispanic Black African-American Other If other, please specify:

Has any first degree relative (parent, sibling) had:

Heart Disease? Yes No Stroke? Yes No Diabetes? Yes No

Do you know if anyone else in your family has/had Scleroderma? Yes No

If yes, tick for each relative:

Relative

Gender From which side?

Relationship with you

1 Male Female

Father Mother

Parent Grandparent

Sibling Aunt/Uncle

Cousin2 Male

Female Father Mother

Parent Grandparent

Sibling Aunt/Uncle

Cousin3 Male


Parent Grandparent

Sibling Aunt/Uncle

Cousin4 Male


Parent Grandparent

Sibling Aunt/Uncle

CousinWhat is your current marital status?

single married or defacto separated divorced widowed

At this time, are you working? part time full time student

unemployed home-duties (full time)

disability preventing work retired

If working, what is your current occupation?

What was your occupation when you were first diagnosed with Scleroderma?

Please tick up to 3 of the main industries you worked in prior to your diagnosis:



Petrochemical Automotive Electrical Textile Beauty Cleaning

Agriculture Manufacturing Computing/electronic Driving Nursing Teaching/education

Mining Plumbing Construction Laboratory Health care Retail

Other (specify):

What is your highest level of education?

Primary school Secondary school Trade qualification Diploma Degree

Other, please specify:

Have you ever been pregnant (if female)? Yes No

If yes, HOW MANY TIMES have you been pregnant? Please tick your response for each pregnancy:Pregnancy 1 Live birth

If live birth, what is the sex of baby? Male Female Which year?

Stillborn

Miscarriage If miscarriage, when is the trimester of loss? 1 2 3 Which year?

Pregnancy 2 Live birth If live birth, what is the sex of baby? Male Female Which year?

Stillborn

Miscarriage If miscarriage, when is the trimester of loss? 1 2 3 Which year?

Pregnancy 3 Live birth If live birth, what is the sex of baby? Male Female Which year?

Stillborn

Miscarriage If miscarriage, when is the trimester of loss? 1 2 3Which year?

Use back of paper for further pregnancy information…



Have you had any exposure to any of the following BEFORE scleroderma was diagnosed?

Vinyl chloride Appetite suppressant Organic solvents

Epoxy resin L-tryptophan Silica dust

None of these

Other please specify:

3. THE HISTORY OF YOUR SCLERODERMA Please answer as much of this as you are able to.

Have you been told you have:

Diffuse scleroderma Limited scleroderma Mixed connective tissue diseaseHave you ever had Raynaud’s phenomena (fingers changing to white/blue in the cold)? Yes No

If yes, when did you first start to get Raynaud’s phenomena (month/year):

Have you noticed thickening of your skin? Yes No

If yes, when did this start (month/year):

When was the first time (month/year) your fingers became swollen and never returned to normal?Other than Raynaud’s phenomena, what was the first symptom of scleroderma (please tick one):

swollen fingers pleuropericarditis Sjogrens (dry mouth and eyes) telangiectasia if other, please specify:

joint/tendon involvement gastrointestinal problems pulmonary arterial

hypertension calcinosis

muscle disease vascular/digital ulcers scleroderma renal crisis severe reflux

When did you first had the above change/s (month/year)?

When was your scleroderma first diagnosed (month/year)?

Who first diagnosed the scleroderma?

PRIOR TO THIS VISIT

Have you ever had a gastroscopy (camera to look in your stomach)? Yes No

If yes, when was this done (month/year)? Have you had lung function tests? Yes No

If yes, when was this done (month/year)?

Where was the test done?



Have you had an echocardiogram? Yes No

If yes, when was this done (month/year)?

Where was the test done?



4. YOUR SCLERODERMA PAST HISTORYPlease tell us if you have ever had any of the following. If you answer “Yes”, please write AGE or YEAR

when it began below:

GAVE (Gastric antral vascular ectasia , also called watermelon stomach)

Yes No If yes, Age or Year:

Reflux Oesophagitis Yes No If yes, Age or Year:

Oesophageal Stricture Yes No If yes, Age or Year: Oesophageal Dysmotility Yes No If yes, Age or Year: Small bowel involvement by scleroderma Yes No If yes, Age or Year: Episode of Bowel Pseudo-obstruction Yes No If yes, Age or Year:

Pulmonary Arterial Hypertension (PAH) Yes No If yes, Age or Year: Pulmonary Fibrosis or Interstitial Lung Disease (ILD)

Yes No If yes, Age or Year:

Heart Problems related your scleroderma: Yes No If yes, Age or Year: Please specify type of heart problem:

Renal Crisis due to scleroderma Yes No If yes, Age or Year: Primary Biliary Cirrhosis Yes No If yes, Age or Year: Muscle involvement by scleroderma Yes No If yes, Age or Year: Inflammatory arthritis Yes No If yes, Age or Year: Digital Ulcers Yes No If yes, Age or Year: Digital Gangrene/Amputation Yes No If yes, Age or Year: Cancer Yes No If yes , please answer below:

Site of cancer 1: Type of cancer 1: Age or Year: Site of cancer 2: Type of cancer 2: Age or Year: Site of cancer 3: Type of cancer 3: Age or Year:



5. TREATMENTPlease write below all the drugs or medicines you have taken over the last week for any condition. Include

all drugs, pills, medicines bought with or without prescription, including birth control pills, hormone replacement, arthritis tablets, aspirin, natural therapies and any others.

Name of medicine How much is the

dose?How many per day?

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

Have you ever had any of the following (please tick as many as you can)?

Prednisolone Antibiotics to control my

diarrhoea Methotrexate Mycophenolate

Azathioprine Feeding through my veins Iloprost infusions

Cyclophosphamide Home oxygen Penicillamine

Are there any other drugs or therapies you can remember having for your scleroderma (please list below):



Have you ever had any of the following (please tick and write year)?

SympathectomyAge or Year:

Coronary artery bypassAge or Year:

Right heart cathetherAge or Year:

Heart valve surgeryAge or Year:

Coronary artery stentAge or Year:

Operation for peripheral vascular disease

Stent Age or Year:

Angioplasty Age or Year:

Bypass Age or Year:

Have been admitted to the hospital in the last 12 months? Yes No

If yes, please list details of your admission:

Admission # Reason for admission Date Number of days in hospital

1

2

3

4

5

6

7

Please use the back of this sheet if you need more space



6. YOUR CURRENT SYMPTOMSCan you please indicate with a tick if you have experienced any of the following over the last year?

Raynaud’s (fingers changing to white/blue in the cold) Yes No

Ulcers on the fingers Yes No If yes, how many ulcers? Ulcers elsewhere on the hands Yes No If yes, how many ulcers?

Episodes of heart burn/acid reflux Yes NoIf yes, how often?

Occasional Regular

Difficulty swallowing Yes No

If yes, is it due to any of the following?

just dry foods all solids both liquids and solid

Bloating after meals Yes No

Do you have episodes of vomiting? Yes No

If yes, how often? Once per day Once per week Once per month

Number of bowel actions per day

Please tick the number of times per day:

0-1 4-10 1-3 >10

Constipation Yes NoDiarrhoea Yes No

Anal incontinence Yes NoHigh blood pressure Yes NoAngina Yes No If yes, what month and year? Heart attack Yes No If yes, what month and year? High cholesterol Yes No If yes, what month and year? Stroke/TIA Yes No If yes, what month and year? Diabetes Yes No If yes, what month and year? Palpitations (heart pounding) Yes No If yes, what month and year? Asthma/Wheezing Yes No If yes, what month and year? Peripheral vascular disease Yes No If yes, what month and year? DVT/Clot in leg Yes No If yes, what month and year? Pulmonary embolus (blood clot in lung) Yes No If yes, what month and year? Emphysema Yes No If yes, what month and year? Impotence Yes No

Dry eyes Yes No

Dry mouth Yes No

Have you ever smoked? Yes No If yes, year first started:



Are you a current smoker? Yes No

If yes, average smoked per day now: If no, proceed to the next question.

If you have stopped smoking, average per day while a smoker: And if you have stopped smoking, year stopped: Do you currently drink alcohol? Yes NoIf yes, how many standard drinks do you have per week now? If not sure, list type of alcohol and number of glasses/bottles below

Do you use drugs not sold in stores? Yes No

When you get up in the morning do you feel stiff? Yes No

If yes, how long is it until you are as limber as you will be for that day? Please write:Number of minutes: ORNumber of hours: Which of the following best describes you TODAY? Please tick only one.

I can do everything I want to do I can do most of the things I want to do, but have some limitations I can do some, but not all, of the things I want to do and I have many limitations

How do you feel TODAY compared to ONE MONTH AGO? Please tick only one.

Much better today than one month ago Better today than one month ago The same today as one month ago Worse today than one month ago Much worse today than one month

How SATISFIED are you with your ability to do your usual activities? Please tick only one.

Very satisfied Somewhat satisfied Somewhat dissatisfied Very dissatisfied

4.14



7. YOUR CURRENT BREATHING Can you please indicate the response that applies to you in the last month?

After climbing JUST one flight of stairs would you describe your breathing as:

0 no breathlessness0.5 very, very slight (just noticeable)1 very slight2 slight3 moderate4 somewhat severe5 severe67 very severe89 very, very severe (almost maximal)10 most severe breathlessness

Are you breathless when you do any of the following?

1. Walking on flat All the time Most of the time Sometimes Never2. Walking up incline All the time Most of the time Sometimes Never3. Showering All the time Most of the time Sometimes Never4. Dressing All the time Most of the time Sometimes Never6. Housework All the time Most of the time Sometimes Never

Has your Raynaud’s phenomena been worse in the last month? Yes NoHow many times do you experience Raynaud’s per week: Have you been more breathless in the last month? Yes NoHas your skin thickening been worse in the last month? Yes No

Has your skin been itchy in the last month?0 no itch1 very slight itch2 slight3 moderate4 somewhat severe5 severe67 very severe89 very, very severe (almost maximal)10 maximal itch



8. YOUR PAST HEALTH HISTORY Please list below all operations you have ever had. Please write N/A on the following box if there is none.

Operation Year Surgeon Hospital, City State1.

2.

3.

4.

5.

Please use the back of this sheet if you need more space

Please list below all major illnesses or admissions to a hospital (other than for operations). Please write N/A on the following box if there is none.

Illness or reason for hospitalisation Year Hospital, City State1.

2.

3.

4.

5.

Please list any major medical problems you have had other than scleroderma. Please write N/A on the following box if there is none.

Medical problems Year1.

2.

3.

4.


Appendix Eight –UCLA SCTC GIT 2.0

4.15 9. THE LEVEL THAT YOUR ILLNESS AFFECTS YOUR LIFE Please cross out the numbered box below each item to indicate the level it applies to you.

a. We are interested in learning whether or not you are affected by pain because of your illness.How much pain have you had because of your illness IN THE PAST WEEK?

NO PAINVERY SEVERE

PAIN

b. IN THE PAST WEEK how much have your intestinal problems affected your daily activities?

INTESTINAL PROBLEMSDO NOT LIMIT ACTIVITIES

VERY SEVERELIMITATION

c. IN THE PAST WEEK how much has your breathing problems interfered with you daily activities?

BREATHING PROBLEMSDO NOT LIMIT ACTIVITIES


d. IN THE PAST WEEK how much has your Raynaud’s interfered with your daily activities?

RAYNAUD’S DOESNOT LIMIT ACTIVITIES


e. IN THE PAST WEEK how much have your finger ulcers interfered with your daily activities?

FINGER ULCERSDO NOT LIMIT


f. Overall, considering how much pain, discomfort, limitations in your daily life and other changes in your body and life, how severe would you rate your disease today?

NODISEASE



0 1 2 3 4 5 6 7 8 109

0 1 2 3 4 5 6 7 8 109

0 1 2 3 4 5 6 7 8 109

0 1 2 3 4 5 6 7 8 109

0 1 2 3 4 5 6 7 8 109

0 1 2 3 4 5 6 7 8 109

Appendix Eight –UCLA SCTC GIT 2.0 Please complete the extra sheets for HAQ (health assessment questionnaire) and SF-36 Health Survey which are

standard questionnaires that we would like to use so that we can compare the impact of this illness with people who have other health issues.


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