Scholar – Page 21 – Health Research BC

The dynamic interplay between women’s stress and reproductive axes across reproductive transitions: post-partum amenorrhea, the resumption of ovarian cyclicity and early pregnancy

Stress is often cited as having negative effects on women’s health. Most research, however, does not adequately account for the changes in stress physiology women experience as they transition between key reproductive phases (post-partum amenorrhea, resumption of ovarian cyclicity, and pregnancy). Reproductive function is modulated by the HPG (hypothalamic-pituitary-gonadal) axis, while stress response is controlled by the HPA (hypothalamic-pituitary-adrenal) axis. These two axes overlap and interact in manner a that affects both reproductive function and stress.

Dr. Pablo Nepomnaschy’s research focuses on investigating the relationship over time between the HPA and HPG axes. Understanding this relationship is paramount to all research focused on how stress affects women’s health and reproduction and their children’s development. The aims of this research are to: 1) produce the first longitudinal description of stress and reproductive hormones for healthy women as they transition across reproductive phases; 2) study the dynamic interactions between the HPA and HPG axes across those phases; 3) evaluate the role of psychosocial, energetic, and health stressors as modulators of reproductive transitions and the effect these transitions have on the physiologic responses to those stressors; 4) conduct an exploratory pilot study of the effects that peri-conceptional stress has on the development of the HPA axis in children.

Nepomnaschy will use data and bio-specimens from British Columbian and Guatemalan women and children. The socio-economic and ethnic homogeneity of the Guatemalan population provides a unique opportunity for the development of a basic model of the longitudinal relationship between the HPA and HPG axes. Those results will be used to develop studies to investigate stress-related health outcomes for women and children in BC, particularly among disenfranchised groups facing higher risk of stress exposure, such as BC’s Aboriginal population, new immigrants, and the homeless.

HIV risk environments among illicit drug users: A longitudinal ethno-spatial approach

Dr. Will Small’s research program will examine the influence of social, structural and physical environments upon illicit drug users’ HIV risk behaviour and HIV treatment-related outcomes. The study is nested within a larger program that includes three epidemiological cohort studies of adult drug users and street-involved youth. This approach integrates ethnographic observational fieldwork, in-depth interviews, and geo-spatial mapping techniques with quantitative laboratory and survey data to identify how the social, structural and physical features of drug-use scenes impact HIV outcomes.

Informed by ecological perspectives on health, and the HIV risk environment framework, this study will develop and pilot a novel ethno-spatial approach to identify the complex pathways and dynamics between contextual factors shaping the risk environments of drug use and HIV prevention and treatment for drug users. Building on 10 years of experience studying illicit drug use and HIV/AIDS in the local context, this program of ethno-spatial epidemiology seeks to address the following specific aims:

Examine the influence of evolving social and physical features of “drug scenes” on HIV risk behaviours and HIV incidence among drug users.
Assess the influence of evolving structural and physical factors on critical initiation and transitional events (e.g. initiation into drug use or sex work; transitions in drug use patterns) among drug users and inform epidemiological models of HIV risk.
Examine the impact of evolving structural and physical factors on initiation and adherence to antiretroviral therapy and suppression of HIV-1 RNA among HIV-positive drug users.
Create a platform for the ongoing ethno-spatial evaluation of future public health and public policy interventions targeting drug users.

Linking socioeconomic status to environmental pollution exposures over the life course: population-based research using biomarkers to investigate the effects of exposure on small for gestational age …

Dr. Scott Venners is studying the impact of exposures to environmental pollutants and their links to health inequalities between richer and poorer people, specifically small size at birth and diabetes in adulthood. As in many Canadian cities, babies born to mothers in socially and materially poorer parts of Vancouver are more likely to be born under-sized than those born in other parts of the city, and higher levels of second-hand smoke exposure may be a factor.

Venners will test exposure to second-hand smoke by measuring cotinine (a byproduct of nicotine) in serum (blood) samples from non-smoking pregnant women. He will then investigate whether non-smoking women with higher levels of serum cotinine (and thus with higher second-hand smoke exposures) are more likely to have a baby that is too small. The project will also test whether some babies are genetically more susceptible to adverse effects of second-hand smoke during pregnancy. Finally, Venners will test whether non-smoking pregnant women who live in poorer areas of Vancouver have higher levels of serum cotinine compared to others, which would suggest that they were exposed to more second-hand smoke. This evidence will provide a better understanding of whether reducing exposures to second-hand smoke will reduce disparities between poorer and richer areas in the likelihood a baby will be born too small.

In addition to passive smoking, the project will study other important classes of pollutants that may be linked to small size at birth. The project will also study the links between socioeconomic status, exposure to mixtures of persistent organic pollutants in adulthood, and inequalities in diabetes risk between richer and poorer Canadians.

Responding to the health crisis among street-involved youth in Vancouver: Evidence to inform interventions and policy responses

Street-involved youth are extremely vulnerable to health-related harms resulting from high rates of illegal drug use and sexually-risky behaviour, poverty, and neglect, as well as precarious living conditions, either on the street or in risky relationships. There is an estimated 150,000 street youth in Canada, with approximately 40 percent reporting injection drug use. This puts street youth at a very high risk for sexually transmitted infections (STI) and hepatitis C (HCV) infection.

Dr. DeBeck’s research seeks to address gaps that exist in our understanding of how street youth are initiated in illegal drug use and the dynamic of how STI and HCV are transmitted.

Her work will examine individual (e.g. stimulant use), social (e.g. childhood trauma), structural (e.g. access and coverage of addiction treatment), and environmental (e.g. homelessness) factors and how they intersect to promote a “risk environment” that elevates sexual risk and drug-related harms.

The outcome of her analysis will be a body of evidence that can support the development and evaluation of behavioural and structural interventions to prevent sexual and drug-related harms among street-involved youth. Her work will also support clinical trials to address critical issues in the diagnosis and treatment of hepatitis C among street-involved youth.

Ultimately, the results of her work will help prevent high-risk drug use, infectious diseases and other health harms among street-involved youth. It will also provide critical guidance for the effective management and treatment of infectious diseases among street involved youth.

End of Award Update – April 2024

Results

Having dedicated research time through a Michael Smith/Providence Health Care Research Institute-St. Paul’s Hospital Scholar Award allowed Dr. DeBeck to build research networks and engage in inclusive collaborations through the At-Risk Youth Study (ARYS) cohort platform. As a Michael Smith Scholar she published more than 160 peer reviewed publications, 55 of which research trainees were the first author and she was the senior author. Dr. DeBeck has also been able to publish with nine different co-authors with lived or living experiences of substance use, the majority of whom identify as Indigenous. Her Scholar Award gave her time to network and collaborate with organizations like the Western Aboriginal Harm Reduction Society, the First Nations Health Authority, Vancouver Coastal Health and the BC Ministry of Mental Health and Addictions. She was also able to facilitate the creation of a program of ARYS Peer Research Associates (PRA) and more recently an Indigenous Peer Collaborators Circle to lead research involving Indigenous people who use drugs.

Impact

Collectively, Dr. DeBeck’s activities as a Michael Smith Scholar have contributed to a scientific evidence-based model that demonstrates that prevailing models of drug law enforcement are ineffective and carry serious unintended harms for structurally marginalized populations. Her work has documented that the criminalization of drug use hinders HIV prevention; incarceration is linked to a decreased likelihood of quitting drug injection and an increased likelihood of relapse into substance use; and incarceration has been discriminatory, disproportionately affecting young Indigenous people in Vancouver. Cumulatively, this body of work provides evidence that despite continuing to receive significant government funding, drug law enforcement has not been demonstrated to be effective and has serious unintended negative harms. This paves the way for evidence-based policy reforms that are not punitive in nature.

Other research contributions include characterizing the early stages of problematic substance use which underscores the role of social determinants of health (e.g., adverse childhood events, child welfare exposure, and intergenerational trauma) as drivers of substance. Documenting the role of social determinants of substance use draws attention to the necessity of policy reforms that attend to social and structural drivers of risk and counters popular narratives of individual moral failings and individual responsibility for substance use.

Contributions during her Scholar Award also include work on addiction treatment engagement that inform responses to the drug toxicity poisoning crisis. The policy implications of this body of work are that addiction treatment, despite demonstrated clinical effectiveness for some people who use drugs, has limited overall reach and impact. Based on these studies, expansion of addiction treatment cannot be expected to adequately respond to the toxic drug crisis. Additional interventions that span prevention and harm reduction, including addressing the toxic drug supply, are needed. Monitoring and evaluating innovative models that make regulated drugs or “safer supply” available is a critical next step for drug policy development and one that the ARYS cohort is ideally positioned to contribute to.

Another impact of Dr. DeBeck’s Scholar Award was the opportunity to leverage drug consumption data from the ARYS cohort and be part of the working group that drafted the City of Vancouver’s 2021 application to Health Canada for the decriminalization of drug possession. The introduction of drug decriminalizing has been symbolically monumental as it reflects the growing understanding that drug criminalization has been ineffective and harmful and different approaches to substance use are needed.

Potential Influence

Holding a Scholar Award allowed the ARYS cohort research platform to thrive under the leadership of Dr. DeBeck. It also gave her the opportunity to build critical research networks and collaborations that positioned her to transition to a CIHR Applied Public Health Chair and Dorothy Killam Fellowship in 2024. With this foundation in place, she is well positioned to continue to generate responsive, high-quality data to inform substance use interventions and drug policy. Current priorities are to engage in community-based collaboration with people who use drugs and government partners, to evaluate interventions and inform policy responses to prevent toxic drug poisonings, increase service engagement, and promote health and wellness among street-involved young people who use drugs in Vancouver and beyond.

Next Steps

With a CIHR APHC and Dorothy Killam Fellowship Dr. DeBeck can continue a research-intensive trajectory. Collaboration with ARYS PRAs and a newly formed Indigenous Peer Collaborator Circle are ongoing. Data sharing with government and community partners is also continuing with multiple research products under development.

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Health, Creative Arts, and Northern Communities

With the highest rates of premature mortality at 3.71/1,000 people, the Northern Health Authority has the lowest health status in BC. Dr. Sarah de Leeuw’s research seeks to address this issue by examining how creative arts and the humanities can help resolve health inequities experienced by Indigenous and non-Indigenous people in northern BC.

To do this, she will draw on her previous research as well as growing global evidence that shows how medical humanities and health-based creative arts can enhance well-being. She will also look at how social determinants of health frameworks can explain health disparities.

She will lead a team of northern BC community advisors, health researchers, and medical/health science students. The team will develop and deploy multi-disciplinary creative methods and methodologies to harness, document, translate, and disseminate existing northern strengths – especially First Nations’ – as a population health and wellness initiative.

Her research will:

Advance new methods, approaches, and models – anchored in creative arts and social determinants of health frameworks – that produce and translate innovative ways of addressing health inequities.
Promote rural, northern and First Nations communities through the creative arts as places where health service providers want to live and work.
Use creative arts to increase interest by locals – particularly First Nations – to pursue health and medical education and training within the region and to then stay in the region.
Encourage multi-disciplinary cross-community collaborations.
Augment northern health education curricula (nursing, social work, medicine, community health) with accessible, targeted, and affecting knowledge.
Circulate strengths-based evidence about populations in the Northern Health Authority – especially First Nations – beyond the borders of the health authority with the intent of encouraging southern, urban, and non-Indigenous British Columbians to feel vested in the wellness of BC’s northern populations.

Translation of next-generation sequencing to HIV treatment and prevention in British Columbia

Next-generation sequencing (NGS) is the automation of high-throughput DNA sequencing on a massive scale that is rapidly transforming biology and medicine. It can enable laboratories to detect small, but clinically significant, numbers of drug-resistant viruses in blood samples from infected individuals.

The lack of computational tools to process and interpret NGS data collected from rapidly-evolving populations such as HIV remains a major obstacle in the application of NGS to HIV treatment and prevention. Dr. Poon’s research will bridge this divide by developing computational methods for NGS analysis designed to address key issues in HIV prevention and treatment. He will share his software as a free resource to the basic and clinical research communities.

He will take advantage of resources available to him through the BC Centre for Excellence in HIV/AIDS (BC-CfE): an extensive archive of HIV plasma specimens; one of the world’s few NGS cores dedicated to HIV research; and his own expertise in molecular evolution and bioinformatic sequence analysis.

As part of his research, he is developing and validating a new method to reconstruct the time of HIV infection from NGS data. Using specimens from the BC-CfE, he will estimate times of HIV infection and reconstruct the historical trend of HIV incidence (the rate of new HIV infections) in BC. This will help assess the long-term impact of expanding access to HIV therapy in BC and identify other correlates of HIV incidence.

He will also use “phylogenetic” methods, which can infer the ancestral tree that relates observed genetic sequences, to reconstruct the history of HIV transmissions in BC. This will allow him to evaluate the impact of expanding access to HIV therapy in BC on the rate of transmitting drug-resistant HIV, and to characterize the variation in rates of HIV transmission over the course of the epidemic.

Finally, he will develop a new class of methods for analyzing NGS data to characterize the adaptation of HIV to the host-specific immune response, and to reconstruct the genetic sequence of the transmitted HIV strain. The results from these methods can provide key information for the development of HIV vaccine candidates – a core aim of HIV prevention research.

Biomechanically-informed non-invasive treatment for knee osteoarthritis

Osteoarthritis is one of the leading causes of physical disability in adults worldwide and is associated with a significant personal and economic burden. It is estimated that one in eight Canadian adults currently have osteoarthritis, which results in $10.2 billion in annual health-care costs and an additional $17.3 billion in economic impact due to loss of employment productivity and other indirect health-care costs. Most commonly affecting the knee, osteoarthritis is characterized by the breakdown of articular cartilage, a smooth lining at the ends of bones that allows ease of movement and shock absorption. It is believed that high magnitude and poorly distributed loads that pass through the knee joint play a strong role in the development and progression of knee osteoarthritis. Improvements in pain, physical function, and quality of life can be achieved by developing treatments that effectively reduce and more evenly distribute these loads.

Dr. Michael Hunt’s research will focus on the use of sophisticated motion analysis equipment and techniques as a way to measure the loads experienced by the knee joint during walking. A better understanding of the factors that influence the magnitude and distribution of knee joint load will inform the development of treatment methods that effectively target these factors. He will focus on methods to optimize the load-reducing capacity and methods of clinical delivery of three treatments: lower limb exercises, gait modification, and shoe insoles. These treatments are designed to be non-invasive (non-surgical and non-pharmacological) in order to improve patient safety while minimizing health-care costs.

This research will be the only program in BC (and one of only a few in Canada) using analysis of motion and knee joint loading to inform clinical treatment for knee osteoarthritis. The focus on non-invasive treatments is in stark contrast to the majority of current osteoarthritis research, which is in the areas of surgery or drugs. Hunt’s research will provide effective treatment alternatives that have lower costs of delivery, fewer side-effects, and wider availability to patients. In addition, new treatment strategies that minimize joint loads have great potential in slowing the rate of disease progression, thereby reducing economic costs in the long-term and significantly improving the quality of life of those affected.

Improving the integration of informal caregiving in long-term residential care

Informal caregiving is defined as care provided by family and friends to a relative or friend residing in a long-term residential care (LTRC) situation. The role of informal caregivers is significant. Informal caregivers contribute more than 44 million hours of care work in LTRC facilities each year; a number that will more than double to 107 million hours in 2038 (source: Canadian Alzheimer Society). These contributions are essential given the current pressures on LTRC, which include an increasingly acute and medically/socially complex resident population and staffing levels that are typically below industry standards. Dr. Jennifer Baumbusch is conducting a series of studies focused on understanding how informal caregivers currently participate in LTRC. Dr. Baumbusch is asking the following research questions in order to better understand the role of informal caregiving and to develop and refine policies and practices to improve the integration of informal caregiving in LTRC. In what ways do informal caregivers contribute to the care of their relative? In what ways do informal caregivers contribute to the care of other residents? How do the informal caregivers’ contributions affect the everyday facility routines, such as recreational activities and meal times? Research will take place on regular units and on Special Care Units for residents with Alzheimer disease and related dementias and will recognize the unique needs of this specialized population. This program will incorporate ethnographic approaches and will be guided by input from community stakeholders. Research findings will be consolidated with existing literature to provide the basis for knowledge translation activities which will include policy forums that foster a national dialogue about caregiving in LTRC, collaborative knowledge translation research, and arts-based knowledge translation approaches. The aim of this program is to improve the integration and recognize the unique contributions of both informal caregivers and formal caregivers (staff) to care provision. Generating new policy directions will contribute to more effective healthcare services within LTRC and will ultimately improve the health of aging Canadians living in LTRC.

Promotion of metastasis by hypoxic tumour cells

Nine out of ten Canadians who are killed by cancer die because their tumour has metastasized, or spread, to other parts of their body. Metastasis occurs when tumour cells escape from the original, or primary, tumour and then grow into life-threatening metastatic tumours in other organs. Despite the fact that thousands of tumour cells can escape from a primary tumour every day, most cells do not live long enough to grow into metastatic tumours. As well, metastatic tumour cells can only grow in specific organs. Most primary tumours contain cells at lower oxygen levels than normal tissues, and these low-oxygen tumour cells make tumours more aggressive and metastatic.

Based on these facts, Dr. Bennewith's team is developing new approaches to help identify tumours that contain low-oxygen tumour cells in patients. In addition, Dr. Bennewith and his colleagues have recently discovered that proteins made by low-oxygen tumour cells cause the body's normal bone marrow cells to enter the bloodstream and build up in specific organs. These cells create an environment where metastasizing tumour cells can survive and grow into metastatic tumours. Dr. Bennewith’s team intends to identify the specific proteins that control bone marrow cell behavior in order to develop targeted therapies that will prevent the build-up of bone marrow cells in organs and thus inhibit metastatic tumour growth. Metastatic tumours are very difficult to treat, but by studying how tumour cells spread and grow into tumour metastases, more effective cancer treatments can be designed. Dr. Bennewith's expertise in metastasis research combined with his unique research program will improve our understanding of how low-oxygen tumour cells promote metastasis. Importantly, his work will help to create more effective methods to both detect and to treat metastatic cancer in the clinic.

A program of research to optimize public health immunization programs

Vaccines and immunization programs are the best way to prevent infectious diseases, improve child health, and save lives. According to the Public Health Agency of Canada, vaccines have saved the lives of more babies and children than any other medical intervention in the past 50 years. Through immunization, we have eliminated smallpox and have nearly eliminated eight other deadly diseases of childhood, including chickenpox and some kinds of pneumonia and meningitis. We need to continue to immunize all children so that we maintain high levels of protection throughout communities, which will prevent these diseases from re-emerging. Despite having province-wide immunization programs in place, not everyone gets vaccinated, as shown by several disease outbreaks in the past few years.

Dr. Julie Bettinger is working to address key questions about vaccines and immunization programs to ensure optimal disease protection in the population. Her research assesses the effectiveness of existing vaccination programs, evaluates the effectiveness of new vaccines, and also studies the best way to deliver them to children, adults and communities. Her approach uses quantitative and qualitative methods and includes collecting and analyzing surveillance data on select vaccine-preventable diseases and vaccine-adverse events from the Canadian Immunization Monitoring Program Active, an active surveillance network in 12 pediatric centers across Canada.

Dr. Bettinger’s research also focuses on evaluating the safety and effectiveness of vaccines through grant-funded clinical trials and observational studies and promoting improved immunization uptake through qualitative studies that assess the factors affecting vaccine use. Her work is used by local, provincial, and national public health decision makers, other research scientists, health care providers, and the public. This work, which is conducted at the Vaccine Evaluation Center at the Child and Family Research Institute and BC Children's Hospital, will create a centre for applied, population-based immunization research unique to BC and Canada.