CHS – Bayer – ADVANCE Canada Research Program

/CHS – Bayer – ADVANCE Canada Research Program
CHS – Bayer – ADVANCE Canada Research Program2018-12-06T16:22:52+00:00

                  

The Canadian Hemophilia Society – Bayer ADVANCE Canada Research Program was created to engage Canadian hemophilia treaters in activities to identify and research key issues in the ageing hemophilia population.

This program is offered in partnership with ADVANCE Canada (ADVANCE: age-related developments and co-morbidities in hemophilia) who’s Mission is as follows:

To improve the health and Quality of Life (QoL) of older Canadians living with hemophilia by underpinning our actions and recommendations in the rigour of science conducted with and for older Canadians living with hemophilia.

In order to optimize management of age-related co-morbidities in the adult hemophilia population, ADVANCE Canada will foster patient-centred research, and disseminate scientific information to assist Canadian hemophilia-treating physicians.

Life expectancy for people with hemophilia has improved and is now approaching that of the general population. The growing population of older people with hemophilia will therefore increasingly face age-related morbidities such as cardiovascular diseases, malignancies, liver disease, and bone and joint related disease, as well as the lifestyle and psychosocial factors that accompany and predispose to many of these conditions. Little is known about how to manage cardiovascular disease, cancer, dementia, and other age-related diseases in the older hemophilia population. Recognizing the importance of how age-related diseases might affect people with hemophilia, this research program’s goal is to support research that will help inform how management and treatment should best be adapted for people ageing with hemophilia.

The research program will support studies that aim to:

  • Identify and provide insight into key issues associated with the ageing hemophilia population
  • Identify how management of age-related co-morbidities should be adapted to those with hemophilia
  • Create and deliver evidence-based information to health care practitioners (HCPs), the public and policy makers that will lead to improved care and QoL for older Canadians living with hemophilia

The Research Grants are made possible thanks to generous financial support from Bayer Canada. Bayer creates innovative products, breakthrough treatments and healthier alternatives to improve quality of life for Canadians through products that fight disease, protect crops and animals, and provide high-performance materials for numerous daily life uses. The CHS is proud to be in a partnership with Bayer Canada in order to offer this important Research Program.

The primary intent of this program is to offer one or two $30,000 research grants, to a maximum of $60,000 for one year.

Depending upon the number and quality of applications, funding for different amounts is possible, as is the offering of more than one research grant, within however, the allotted total budget stated above.
 

Eligibility
To be eligible the applicant must be a physician or Ph.D. with professional experience in a hemophilia treatment centre (HTC) or other comparable settings in which care has been provided to people with hemophilia and other inherited bleeding disorders. Professionals who have appointments in universities and who can dedicate time to research are encouraged to apply. Applicants must be Canadian citizens or permanent residents and affiliated with a Canadian university or not-for-profit health-related organization.

The proposed research must have relevance to current practice in bleeding disorders care and may incorporate a broad spectrum of quantitative and qualitative research methods addressing professional practice with individuals, families, groups and communities, organizational issues, public health, and education.

The research studies should aim to provide better data and tools to help the treaters assist patients in successful ageing.

Interest areas and methodologies might include but are not limited to:

  • musculoskeletal problems – loss of joint and muscle function and chronic pain that can impair daily activities and worsen quality of life.
  • cardiovascular disease – risk factors most frequently seen in hemophilia patients include hypertension, or high blood pressure, and being overweight.
  • viral infections such as HIV and hepatitis – these conditions imply treatment with antiviral drugs, which may affect patients’ kidneys and liver.
  • chronic kidney disease – this condition causes hypertension. Because of hemophilia patients’ deficient blood clotting ability, it could increase their risk of a brain hemorrhage.
  • chronic pain – this condition also implies treatments that could adversely affect hemophilia patients.
  • cancer – chemotherapy can cause loss of white blood cells, which could worsen hemophilia patients’ tendency to bleed.


Multidisciplinary Collaboration
Collaboration with multidisciplinary care providers and/or between two or more hemophilia centres is accepted and encouraged. Collaboration efforts are welcome as co-applicants and may include, for example, nursing, social work, physical therapy and genetics. It thus may be possible for a hemophilia centre team to jointly submit a cooperative research project. Additionally, inter-regional applications will be considered.

Applications and Deadline: February 8, 2019.
All completed application forms and support documents must arrive at the National Office of the Canadian Hemophilia Society on or before February 8, 2019. If the CHS receives the application after the deadline date but it is postmarked on or before the deadline date, then it is considered to have been submitted on time. The names of the successful applicants will be announced by March, 2019.

Multidisciplinary and multi-centre applications are welcomed.  Please note that if a multidisciplinary or multi-centre project is sought, you are encouraged to indicate in the application how the project would proceed if a grant was to be awarded to only one portion of the proposed project.

Grants will be offered for a one-year period to begin in April 2019.

The Canadian Hemophilia Society – Bayer ADVANCE Canada Research Program was created to engage Canadian hemophilia treaters in activities to identify and research key issues in the ageing hemophilia population.

This program is offered in partnership with ADVANCE Canada (ADVANCE: age-related developments and co-morbidities in hemophilia) who’s Mission is as follows:

To improve the health and Quality of Life (QoL) of older Canadians living with hemophilia by underpinning our actions and recommendations in the rigour of science conducted with and for older Canadians living with hemophilia.

In order to optimize management of age-related co-morbidities in the adult hemophilia population, ADVANCE Canada will foster patient-centred research, and disseminate scientific information to assist Canadian hemophilia-treating physicians.

Life expectancy for people with hemophilia has improved and is now approaching that of the general population. The growing population of older people with hemophilia will therefore increasingly face age-related morbidities such as cardiovascular diseases, malignancies, liver disease, and bone and joint related disease, as well as the lifestyle and psychosocial factors that accompany and predispose to many of these conditions. Little is known about how to manage cardiovascular disease, cancer, dementia, and other age-related diseases in the older hemophilia population. Recognizing the importance of how age-related diseases might affect people with hemophilia, this research program’s goal is to support research that will help inform how management and treatment should best be adapted for people ageing with hemophilia.

The research program will support studies that aim to:

  • Identify and provide insight into key issues associated with the ageing hemophilia population
  • Identify how management of age-related co-morbidities should be adapted to those with hemophilia
  • Create and deliver evidence-based information to health care practitioners (HCPs), the public and policy makers that will lead to improved care and QoL for older Canadians living with hemophilia


Eligibility
To be eligible the applicant must be a physician or Ph.D. with professional experience in a hemophilia treatment centre (HTC) or other comparable settings in which care has been provided to people with hemophilia and other inherited bleeding disorders. Professionals who have appointments in universities and who can dedicate time to research are encouraged to apply. Applicants must be Canadian citizens or permanent residents and affiliated with a Canadian university or not-for-profit health-related organization.

The proposed research must have relevance to current practice in bleeding disorders care and may incorporate a broad spectrum of quantitative and qualitative research methods addressing professional practice with individuals, families, groups and communities, organizational issues, public health, and education.

The research studies should aim to provide better data and tools to help the treaters assist patients in successful ageing.

Interest areas and methodologies might include but are not limited to:

  • musculoskeletal problems – loss of joint and muscle function and chronic pain that can impair daily activities and worsen quality of life.
  • cardiovascular disease – risk factors most frequently seen in hemophilia patients include hypertension, or high blood pressure, and being overweight.
  • viral infections such as HIV and hepatitis – these conditions imply treatment with antiviral drugs, which may affect patients’ kidneys and liver.
  • chronic kidney disease – this condition causes hypertension. Because of hemophilia patients’ deficient blood clotting ability, it could increase their risk of a brain hemorrhage.
  • chronic pain – this condition also implies treatments that could adversely affect hemophilia patients.
  • cancer – chemotherapy can cause loss of white blood cells, which could worsen hemophilia patients’ tendency to bleed.


Multidisciplinary Collaboration
Collaboration with multidisciplinary care providers and/or between two or more hemophilia centres is accepted and encouraged. Collaboration efforts are welcome as co-applicants and may include, for example, nursing, social work, physical therapy and genetics. It thus may be possible for a hemophilia centre team to jointly submit a cooperative research project. Additionally, inter-regional applications will be considered.

Stipend/Duration of Support
The primary intent of this program is to offer one or two $30,000 research grants, to a maximum of $60,000 for one year.

Depending upon the number and quality of applications, funding for different amounts is possible, as is the offering of more than one research grant, within however, the allotted total budget stated above.

The Research Grant will normally begin on April 1, 2019. Research projects must be initiated by December 31 of the year awarded.

Grantees must devote full or part time to the research program during the tenure of the Grant as per their proposal, which the CHS will have accepted.


General Conditions, Application Form and Deadlines
All completed application forms and support documents must arrive at the National Office of the Canadian Hemophilia Society on or before February 8, 2019. If the CHS receives the application after the deadline date but it is postmarked on or before the deadline date, then it is considered to have been submitted on time. The names of the successful applicants will be announced by March, 2019.

Multidisciplinary and multi-centre applications are welcomed.  Please note that if a multidisciplinary or multi-centre project is sought, you are encouraged to indicate in the application how the project would proceed if a grant was to be awarded to only one portion of the proposed project.

Applications must be completed and submitted electronically to the Canadian Hemophilia Society and one (1) original paper copy, including signatures, must be sent to the National Office of the Canadian Hemophilia Society:

301-666 Sherbrooke Street West, Montreal, QC  H3A 1E7

Please click below for the General Conditions and the Application Form.

Evaluation
All applications are subjected to a rigorous peer review process and will be reviewed by an independent peer review committee composed of Canadian medical and healthcare professionals and a patient representative. Applications are critiqued on scientific merit and relevance to CHS research priorities and scored in terms of significance, approach, innovation, investigator, and environment/support. The committee will rank the applications and will make recommendations to the CHS Board of Directors on funding of the proposals. The final decisions regarding awards will be made by the CHS Board of Directors. No appeals will be considered.

A review, prior to submission, by the ADVANCE Canada Steering Committee may provide potential candidates research with guidance and assistance. This is not mandatory to the submission or acceptance of the project by the CHS.

Should a candidate wish to have the ADVANCE Canada Steering Committee review the application prior to submitting it to the CHS, please provide by e-mail a copy of the application to Robert Martone of Glia Scientific Communication at rmartone@gliasc.com. He will act as your liaison with the Steering Committee.

  1. GENERAL CONDITIONS

1.1 Application Forms
Application form must be completed and submitted electronically to the Canadian Hemophilia Society  and one (1) original paper copy, including signatures, must be sent to the National Office of the Canadian Hemophilia Society:

301-666 Sherbrooke Street West
Montreal, QC H3A 1E7

1.2 Application Deadline
Completed application forms and supporting documents must arrive at the National Office of the Canadian Hemophilia Society by February 8, 2019. If the CHS receives the application after the deadline date but it is postmarked on or before the deadline date, then it is considered to have been submitted on time. The names of the successful applicants will be announced by March, 2019.

First time applicants are encouraged to seek advice from experienced investigators in the preparation of their applications. A review, prior to submission, by the ADVANCE Canada Steering Committee may provide potential candidates research with guidance and assistance. This is not mandatory to the submission or acceptance of the project by the CHS.

Should a candidate wish to have the ADVANCE Canada Steering Committee review the application prior to submitting it to the CHS, please provide by email a copy of the application to Robert Martone of Glia Scientific Communication at rmartone@gliasc.com. He will act as your liaison with the Steering Committee.

Please note that the Research Proposal (Item 13 of the application) must not exceed 2,500 words or 5 pages, excluding figures and references.

Supporting materials should include only previously published articles or materials accepted for publication.

1.3 Grant Year and Amount
Support for the Grant in the maximum amount of $60,000 is normally made for a one-year period starting on April 1, 2019. Awards must be initiated by December 31 of the year awarded. The primary intent of this program is to offer one or two $30,000 research grants, to a maximum of $60,000 for one year.

Depending upon the number and quality of applications, funding for different amounts is possible, as is the offering of more than one grant, within however, the allotted total budget stated above.

1.4 Payments
Yearly grants will normally be disbursed in two payments in each year and sent to the financial officer of the host institution.

1.5 Research Summaries
The Canadian Hemophilia Society (CHS) requires, within the application form, a 200-word typewritten lay description of the research to be undertaken (in non-scientific, Grade 12 readability) for inclusion in the Society’s publications should the proposal be accepted.

1.6 Notification of Grants
Following funding decisions, successful applicants will be sent official notification informing them of the type, duration and amount of their grant. A copy of the notification is sent to the accountant at the institution concerned. The award must be acknowledged by returning an acceptance note within 15 days of the CHS notification otherwise the award will be withdrawn. Unsuccessful applicants are also advised at the conclusion of the project application review process.

1.7 Appeals
The Research Peer Review Committee of the Canadian Hemophilia Society will make recommendations on the awarding of the grants and the final decision will be made by the CHS Board of Directors. No appeals will be considered.

2.  ADDITIONAL GRANT CONDITIONS AND GRANTEE OBLIGATIONS

2.1 Statement of Expenditures
A statement of all expenditures for the grant, signed by the candidate and the financial officer of each institution, must be received at the CHS’s offices within 2 months of the end date of the grant term. An institution finance/expenditure report is acceptable to avoid duplication of effort by the researcher. Failure to fulfill this requirement may lead to exclusion from future research grant competitions. If delay is anticipated, the CHS must be informed.

2.2 Use of the Grants
The Grant is to be used mainly to support the salary of the grantee, research assistant and project expenses.
Grantees must devote full time or part time to the research during the tenure of the Grant as per their proposal which has been accepted by the CHS.
Please note that awardees must notify the Canadian Hemophilia Society immediately if there is any change to the research or its term.
The use of funds for purposes other than stated in the application must be approved in advance by the CHS.

2.3 Unexpended Balances
The Canadian Hemophilia Society does not permit carrying forward into the next grant year an unexpected balance in excess of $5,000. Prior written request to the CHS is required to carry forward a balance that exceeds $5,000.

2.4 Termination of the Grant

Upon termination of the Grant, any unexpended balance of funds must be returned to the CHS.

2.5 Travel Expenses
A grantee may use $1,500 annually from the award for the purpose of travel in connection with the grant and, if needed, an additional amount representing one percent (1%) of the annual value of the award.

2.6 Title to Equipment
Title to any equipment obtained with the Canadian Hemophilia Society’s funds shall be held by the host institution on the condition that for a 12 month period following termination of grant, the CHS may transfer title to another institution. Prior written authorization for the transfer of funds or equipment by a grantee to another institution must be obtained from the CHS.

2.7 Interim, Final Report & Abstract Requirements
Research grant recipients are required to provide a project progress report; this report summarizing the progress to date will serve as the basis for project continuance and will also provide supporting rationale, if required, for approval of project modifications, and/or extension requests.

Within 2 months of the end of the funding period, the Canadian Hemophilia Society requires a final report on activities undertaken during the tenure of the Grant and on the results of the project. The CHS also requires that the researcher provide an approximately 250-word lay abstract (Grade 12 readability) describing his or her activities and the results of the project for inclusion in the Society’s publications and for presentation at the CHS medical and scientific symposia.

Failure to fulfill these requirements can lead to exclusion from future fellowship/research grant competitions. If delay is anticipated, the CHS must be informed.

2.8 Acknowledgement of Support
The Canadian Hemophilia Society MUST be informed of any publications that are based on research funded by the Canadian Hemophilia Society and all such publications, scientific communications and media releases related to the award MUST acknowledge the support of the Canadian Hemophilia Society and Bayer Canada. Researchers are encouraged to present study results, when possible, even if preliminary, at hemophilia conferences (e.g., World Federation of Hemophilia Congress, Rendez-Vous, etc.).

2.9 Proprietary Rights
The CHS must be informed of any commercial exploitation arising from the CHS-supported activity. However, the CHS does not claim proprietary rights to inventions resulting from research supported by its funds. The onus is on the grantee to seek patent protection in collaboration with the university or institute for inventions or developments arising from the CHS-supported research.

2.10 Indirect / Overhead Costs
Grant funds must contribute towards the direct costs of the research program or project for which the funds were awarded. The Institution provides for indirect or overhead costs, such as the costs associated with facilities and basic utilities, the purchase and repair of office equipment, administration fees, insurance for equipment and research vehicles, and basic communication devices such as telephones and fax machines. The funds must be used effectively and economically, and the expenses must be essential for the research supported by the grant.


Health Charities Coalition of Canada Position Statement on Indirect Costs of Research (May 14, 2007):

It is the policy of the Health Charities Coalition of Canada (HCCC) that health charities should not fund the indirect costs associated with the research they fund. All HCCC members have agreed not to fund indirect costs. While the HCCC recognizes that these may indeed be legitimate expenditures, we believe the funding of such costs is the responsibility of governments and not donors.

While the CHS is not a member of HCCC, it nonetheless supports the position that indirect costs associated with research it funds and fellows it supports are the responsibility of governments and/or research institutions and not its donors.

3. Ethical Considerations

3.1 Adherence to Research Guidelines
An application to the Canadian Hemophilia Society for research support constitutes a pledge on the part of the applicants and their research institutions to respect all the guidelines of the Canadian Hemophilia Society, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010 (TCPS2), the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada and the Canadian Council on Animal Care. In the event that these guidelines are not adhered to, the CHS will withhold funding.

Completed forms required for research involving human subjects, gene therapy in humans, animals and biohazards must be received by the CHS as soon as possible; funding of successful applications for research will be withheld by the CHS until full Research Ethics Board approval is provided in writing to the CHS. CHS review of the applications, by its Peer Review Committee, can proceed prior to Research Ethics Board (REB) approval.

3.2 Research Involving Human Subjects
Each project in a research proposal involving human subjects and gene therapy in humans must submit the complete designated form, authorized by the local institutional Research Ethics Board in accordance with the TCPS2 document of the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada,and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010. The Tri-Council Policy Statement is available from the following website: www.pre.ethics.gc.ca/pdf/eng/tcps2/TCPS_2_FINAL_Web.pdf

The responsibility for filing a Clinical Trial Application ( CTA) with Health Canada for a human drug clinical trial rests with the Principal Investigator. Guidance on whether a CTA is required is found at:

www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta-eng.php See: Overview of the Clinical Trial Application Process and Institution/Investigator Initiated Clinical Trials

In addition, all continuing grantees involved in human subjects must submit the complete designated form on an annual basis. Receipt of this form is required for continuation of payment by the CHS of any funds committed for the following year.

3.3 Research on Somatic Cell Gene Therapy in Humans
The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010 must be adhered to. Any research related to this area must be reviewed by the local institutional Research Ethics Board.

3.4 Care and Use of Experimental Animals

The CHS requires that all experiments involving animals be conducted in an ethical way. The facilities for, and the care and use of animals, in any investigation the CHS supports must be in strict accordance with the guidelines set out by the Canadian Council on Animal Care (CCAC) in its publication, Guide to the Care and Use of Experimental Animals (Vol. 1, 1980 and revised in 1993; Vol. 2, 1984), available from:

The Canadian Council on Animal Care
1000 – 151 Slater St.
Ottawa, Ontario Canada K1P 5H3

Each proposal involving animals must have one copy of the designated form, completed and authorized by a local institutional Animal Care Committee, confirming its ethical acceptability (the composition of the committee is set forth in the CCAC Guide). In addition, all continuing grantees involved in research using animals must submit one complete form on an annual basis. Receipt of this form is required for continuation of payment by the CHS of any funds committed for the following year.

3.5 Research Involving Biohazards

Investigators proposing to engage in research involving animal and human pathogens and animal cells are required to comply with the Canadian Institutes of Health Research and Health and Welfare Canada Biosafety Laboratory Guidelines, 3rd Edition – 2004. These guidelines were jointly prepared with the Office of Biosafety of the Laboratory Centre for Disease Control of Health Canada and are available from:

Office of Biosafety
Laboratory Centre for Disease Control
Health Protection Branch
Health Canada
Ottawa, Ontario Canada K1A 0L2
Tel: 613-957-1779

or at www.phac-aspc.gc.ca/publicat/lbg-ldmbl-04/index-eng.php

These Guidelines cover the following types of research:

a) research involving animal and human pathogens;
b) research involving animal cells in culture;
c) research involving recombinant DNA molecules which might be harmful to humans, animals or the environment.

Each proposal involving research proposals covering the areas noted above must have one completed form, authorized by a local institutional committee, confirming that the level of containment implemented by the investigator meets the Canadian Institutes of Health Research’s requirements.

In addition, all continuing grantees participating in research involving biohazards must submit a completed form on an annual basis. Receipt of this form is required for continuation of payment by CHS of any funds committed for the following year.

Disposal of Hazardous and Radio Active Materials

3.6 Research Involving Hazardous Compounds
Researchers are responsible for ensuring that their research conforms with the provincial statutes regarding disposal of chemical wastes. Researchers are also responsible for ensuring that research assistants and laboratory personnel are aware of any hazards posed by materials required for the research, that these personnel are adequately trained in handling and containment of such compounds, and that protective procedures are enforced, in compliance with the Occupational Health and Safety regulations of the province in which work is carried out.

3.7 Research Involving Radioactive Materials
Applicants who will be carrying out research using radioactive materials must be aware of, and comply with, all Atomic Energy Control Board regulations, recommended procedures, and safety precautions governing the use of such materials in Canada. Further information may be obtained from:

Office of Public Information
Atomic Energy Control Board
P.O. Box 1046, Station ‘B’
270 Albert Street
Ottawa, Ontario Canada K1P 5S9
Tel:  613-995-5894 Fax: 613-995-5086

Application form

or contact:
Canadian Hemophilia Society
chs@hemophilia.ca
1-800-668-2686

Incidence and burden of bone fracture in patients with hemophilia

Dr. Adrienne Lee
University of Calgary – Calgary, AB
One year funding
Co-Investigators:
Dr. Linda Sun, University of Alberta – Edmonton, AB
Dr. Chatree Chai-Adisaksopha, McMaster University – Hamilton, ON
Dr. Man-Chiu Poon, University of Calgary – Calgary, AB

Hemophilia patients suffer from recurrent joint and muscle bleeding. This causes damage to the tissues and results in pain, arthritis, and disability. To prevent this, hemophilia patients receive regular clotting factor replacement which has allowed them to live longer and suffer less joint damage. In addition to joint damage, hemophilia patients have bones which are less dense than non-hemophilia individuals of similar age and sex. It is well known that low bone density can lead to weaker bones that are at risk of fracture. This process of bone density loss worsens with age. Currently, the majority of the hemophilia patients in Canada are still quite young with an average age of about 40. As these patients age, we expect the low bone density to worsen, putting them at higher risk of fracture. However, whether hemophilia patients suffer from more fractures that the normal population is not known. The goal of this study is to compare the fracture rate in hemophilia patients living in Alberta compared to the non-hemophilia population by extracting clinical data from a provincial database. A better understanding of the rates of fracture in hemophilia patients will help us to develop plans to best identify those at risk and how we might prevent progression of bone density loss and fracture.

______________________________________________________________________________________________________________

The risk of arterial disease in patients with hemophilia and von Willebrand Disease: A retrospective, cohort study using administration data in Ontario

Dr. Michelle Sholzberg
St. Michael’s Hospital – Toronto, ON
One year funding
Co-Investigators:
Dr. Jerome Teitel, St. Michael’s Hospital – Toronto,ON
Dr. Shannon Jackson, University of British Columbia – Vancouver, BC
Dr. Leonard Minuk, Cancer Care Manitoba/University of Manitoba – Winnipeg, MB
Dr. Tara Gomez, Institute for Clinical Evaluative Sciences (ICES) – Toronto, ON

We propose a study of arterial disease risk in patients with inherited hemophilia and VWD in Ontario using population-based data from large, linked administrative databases housed by the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. ICES holds Ontario-based health services administrative data, which includes physician billings, prescription drug claims for those ≥ 65 years, inpatient hospital discharges, emergency and ambulatory care visits, home care claims, and long-term care visits. ICES research is widely used by governments, hospitals and practitioners to make decisions about care delivery and to help inform policy. For the first time, we plan on using these datasets to systematically evaluate the risk of arterial disease (peripheral, cardiac and cerebral) in PWH and PWVWD compared to age and gender matched controls. This will address an important knowledge gap, as we will have the opportunity to adjust for important covariates and analyze data over the last three decades in Ontario using sound epidemiological methods.

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