R&D during public health emergencies: the value(s) of trust, governance and collaboration.

In January 2021, Dr Tedros Adhanom Ghebreyesus, director-general of the WHO, warned that the world was 'on the brink of a catastrophic moral failure [that] will be paid with lives and livelihoods in the world's poorest countries'. We are now past the brink. Many high-income countries have vaccinated their populations (which, in some cases, includes third and even fourth doses) and are loosening public health and social measures, while low-income and middle-income countries are struggling to secure enough supply of vaccines to administer first doses. While injustices abound in the deployment and allocation of COVID-19 vaccines, therapies and diagnostics, an area that has hitherto received inadequate ethical scrutiny concerns the upstream structures and mechanisms that govern and facilitate the research and development (R&D) associated with these novel therapies, vaccines and diagnostics. Much can be learnt by looking to past experiences with the rapid deployment of R&D in the context of public health emergencies. Yet, much of the 'learning' from past epidemics and outbreaks has largely focused on technical or technological innovations and overlooked the essential role of important normative developments; namely, the importance of fostering multiple levels of trust, strong and fair governance, and broad research collaborations. In this paper, we argue that normative lessons pertaining to the conduct of R&D during the 2014-2016 Ebola epidemic in West Africa provide important insights for how R&D ought to proceed to combat the current COVID-19 pandemic and future infectious disease threats.

Primary Care Severe Asthma Registry and Education Project (PCSAR-EDU): Phase 1 - an e-Delphi for registry definitions and indices of clinician behaviour.

INTRODUCTION: Although most asthma is mild to moderate, severe asthma accounts for disproportionate personal and societal costs. Poor co-ordination of care between primary care and specialist settings is recognised as a barrier to achieving optimal outcomes. The Primary Care Severe Asthma Registry and Education (PCSAR-EDU) project aims to address these gaps through the interdisciplinary development and evaluation of both a 'real-world' severe asthma registry and an educational programme for primary care providers. This manuscript describes phase 1 of PCSAR-EDU which involves establishing interdisciplinary consensus on criteria for the: (1) definition of severe asthma; (2) generation of a severe asthma registry and (3) definition of an electronic-medical record data-based Clinician Behaviour Index (CBI). METHODS AND ANALYSIS: In phase 1, a modified e-Delphi activity will be conducted. Delphi panellists (n≥13) will be invited to complete a 30 min online survey on three separate occasions (i.e., three separate e-Delphi 'rounds') over a 3-month period. Expert opinion will be collected via an open-ended survey ('Open' round 1) and 5-point Likert scale and ranking surveys ('Closed' round 2 and 3). A fourth and final Delphi round will occur via synchronous meeting, whereby panellists approve a finalised ideal 'core criteria list', CBI and corresponding item weighting. ETHICS AND DISSEMINATION: Ethical approval has been obtained for the activities involved in phase 1 from the University of Toronto's Human Research Ethics Programme (approval number 39695). Future ethics approvals will depend on information gathered in the proceeding phase; thus, ethical approval for phase 2 and 3 of this study will be sought sequentially. Findings will be disseminated through conference presentations, peer-reviewed publications and knowledge translation tools.

Guidelines should not recommend the type of decision-making for the medical encounter.

Clinical practice guidelines (CPGs) often include a recommendation regarding how to approach a clinical encounter and which decision-making model should be used. The GRADE framework, a popular method for developing CPGs, suggests a paternalistic model when recommendations are "strong" and shared decision making (SDM) when recommendations are "weak". Tying the model of decision making and patient participation to the strength of a recommendation is not justified theoretically and/or empirically in the GRADE literature. Thus, why a CPG should offer any advice on which model to use in the clinical encounter is not clear. We argue that including such instruction is not justified and potentially violates the bioethical norms of autonomy and respect for individual choice and may even violate the clinician's legal obligation. Rather, the model to be used is better determined by the participants in the individual encounter during the encounter and not the panel developing the CPG.

"On the Margins and Not the Mainstream:" Case Selection for the Implementation of Community Based Primary Health Care in Canada and New Zealand.

Healthcare system reforms are pushing beyond primary care to more holistic, integrated models of community based primary health care (CBPHC) to better meet the needs of aging populations and their carers. Across the world CBPHC is at varying stages of evolution and no standard model exists. In order to scale up and spread successful models of care it is important to study what works well and why to support broader efforts to implement, scale-up and spread promising innovations. The first step in this endevour is to select appropriate cases to study. In this paper we share our adaptation of case study methodology to iteratively select models of CBPHC in three jurisdictions: Ontario, Quebec (Canada) and New Zealand. A combination of literataure searches (of empirical and gray sources) and stakeholder engagement enabled the selection of cases to study, with the latter providing the most fruitful method. We conclude that it is possible to use personal networks and experts exclusively. It is not clear how much value formal searching adds over and above expert advice. However in a situation where there is no existing definitive list of potential cases, and no acknowledged "gold standard" way to create such a list, it seems appropriate to gather cases using multiple methods and to document those methods systematically.

Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust

Material en inglés, Access and use of human tissues from the developing world: ethical challenges and a way forward using a tissue trust, que analiza los diferentes desafíos éticos que supone el acceso a tejidos humanos para investigación en un contexto en el que no han estado ausentes la explotación y abuso de ciertas prácticas.

From pharmaco-therapy to pharmaco-prevention: trends in prescribing to older adults in Ontario, Canada, 1997-2006.

BACKGROUND: The developed world is undergoing a demographic transition with greater numbers of older adults and higher rates of chronic disease. Most elder care is now provided by primary care physicians, who prescribe the majority of medications taken by these patients. Despite these significant trends, little is known about population-level prescribing patterns to primary care patients aged 65+. METHODS: We conducted a population-based retrospective cohort study to examine 10-year prescribing trends among family physicians providing care to patients aged 65+ in Ontario, Canada. RESULTS: Both crude number of prescription claims and prescription rates (i.e., claims per person) increased dramatically over the 10-year study period. The greatest change was in prescribing patterns for females aged 85+. Dramatic increases were observed in the prescribing of preventive medications, such as those to prevent osteoporosis (+2,347%) and lipid-lowering agents (+697%). And lastly, the number of unique classes of medications prescribed to older persons has increased, with the proportion of older patients prescribed more than 10 classes of medications almost tripling during the study period. CONCLUSIONS: Prescribing to older adults by family physicians increased substantially during the study period. This raises important concerns regarding quality of care, patient safety, and cost sustainability. It is evident that further research is urgently needed on the health outcomes (both beneficial and harmful) associated with these dramatic increases in prescribing rates.

Health care service utilization among the elderly: findings from the Study to Understand the Chronic Condition Experience of the Elderly and the Disabled (SUCCEED project).

RATIONALE AND OBJECTIVES: Age-related effects on health service utilization are not well understood. Most previous studies have examined only a single specific health care service or disease condition or have focused exclusively on economic variables. We aim to measure age-related change in health care utilization among the elderly. METHODS: A population-based retrospective cohort study was conducted using linked data from four administrative databases (OHIP, ODB, CIHI and RPDB). All Ontario residents over the age of 65 years and eligible for public health coverage were included in the analysis (approximately 1.6 million residents). Main outcome measures include utilization indicators for family physician visits, specialist physician visits, Emergency Department visits, drugs, lab claims, X-rays, inpatient admissions, CT scans and MRI scans. RESULTS: The mean number of utilization events for Ontarians aged 65+ years for the 1-year study period was 70 events (women = 76, men = 63). The overall absolute difference between the 65-69 age group and the 85+ age group was 155% (women = 162%, men = 130%), or 76 more events per person in the older group (women = 82, men = 61). Women averaged more events per person than men, as well as greater percentage differences by age. Drugs and diagnostics account for the majority of events. Only MRI and specialist visits were not higher among the older age groups. CONCLUSIONS: At the population level, overall health care utilization would appear to increase significantly with age. It is unclear whether increasing health care utilization prevents morbidity, decreases mortality, or improves quality of life.

On pandemics and the duty to care: whose duty? who cares?

BACKGROUND: As a number of commentators have noted, SARS exposed the vulnerabilities of our health care systems and governance structures. Health care professionals (HCPs) and hospital systems that bore the brunt of the SARS outbreak continue to struggle with the aftermath of the crisis. Indeed, HCPs - both in clinical care and in public health - were severely tested by SARS. Unprecedented demands were placed on their skills and expertise, and their personal commitment to their profession was severely tried. Many were exposed to serious risk of morbidity and mortality, as evidenced by the World Health Organization figures showing that approximately 30% of reported cases were among HCPs, some of whom died from the infection. Despite this challenge, professional codes of ethics are silent on the issue of duty to care during communicable disease outbreaks, thus providing no guidance on what is expected of HCPs or how they ought to approach their duty to care in the face of risk. DISCUSSION: In the aftermath of SARS and with the spectre of a pandemic avian influenza, it is imperative that we (re)consider the obligations of HCPs for patients with severe infectious diseases, particularly diseases that pose risks to those providing care. It is of pressing importance that organizations representing HCPs give clear indication of what standard of care is expected of their members in the event of a pandemic. In this paper, we address the issue of special obligations of HCPs during an infectious disease outbreak. We argue that there is a pressing need to clarify the rights and responsibilities of HCPs in the current context of pandemic flu preparedness, and that these rights and responsibilities ought to be codified in professional codes of ethics. Finally, we present a brief historical accounting of the treatment of the duty to care in professional health care codes of ethics. SUMMARY: An honest and critical examination of the role of HCPs during communicable disease outbreaks is needed in order to provide guidelines regarding professional rights and responsibilities, as well as ethical duties and obligations. With this paper, we hope to open the social dialogue and advance the public debate on this increasingly urgent issue.

Traumatic deep vein thrombosis in a soccer player: A case study.

A 42 year-old male former semi-professional soccer player sustained a right lower extremity popliteal contusion during a soccer game. He was clinically diagnosed with a possible traumatic deep vein thrombosis (DVT), and sent for confirmatory tests. A duplex doppler ultrasound was positive for DVT, and the patient was admitted to hospital for anticoagulation (unfractionated heparin, warfarin). Upon discharge from hospital the patient continued oral warfarin anticoagulation (six months), and the use of compression stockings (nine months). He followed up with his family doctor at regular intervals for serial coagulation measurements, and ultrasound examinations. The patient's only identified major thrombotic risk factor was the traumatic injury. One year after the initial deep vein thrombosis (DVT) the patient returned to contact sport, however he continued to have intermittent symptoms of right lower leg pain and right knee effusion.Athletes can develop vascular injuries in a variety of contact and non-contact sports. Trauma is one of the most common causes of lower extremity deep vein thrombosis (DVT), however athletic injuries involving lower extremity traumatic DVT are seldom reported. This diagnosis and the associated risk factors must be considered during the initial physical examination. The primary method of radiological diagnosis of lower extremity DVT is a complete bilateral duplex sonography, which can be augmented by other methods such as evidence-based risk factor analysis. Antithrombotic medication is the current standard of treatment for DVT. Acute thrombolytic treatment has demonstrated an improved therapeutic efficacy, and a decrease in post-DVT symptoms.There is a lack of scientific literature concerning the return to sport protocol following a DVT event. Athletic individuals who desire to return to sport after a DVT need to be fully informed about their treatment and risk of reoccurrence, so that appropriate decisions can be made.

Autoregression as a means of assessing the strength of seasonality in a time series.

BACKGROUND: The study of the seasonal variation of disease is receiving increasing attention from health researchers. Available statistical tests for seasonality typically indicate the presence or absence of statistically significant seasonality but do not provide a meaningful measure of its strength. METHODS: We propose the coefficient of determination of the autoregressive regression model fitted to the data () as a measure for quantifying the strength of the seasonality. The performance of the proposed statistic is assessed through a simulation study and using two data sets known to demonstrate statistically significant seasonality: atrial fibrillation and asthma hospitalizations in Ontario, Canada. RESULTS: The simulation results showed the power of the in adequately quantifying the strength of the seasonality of the simulated observations for all models. In the atrial fibrillation and asthma datasets, while the statistical tests such as Bartlett's Kolmogorov-Smirnov (BKS) and Fisher's Kappa support statistical evidence of seasonality for both, the quantifies the strength of that seasonality. Corroborating the visual evidence that asthma is more conspicuously seasonal than atrial fibrillation, the calculated for atrial fibrillation indicates a weak to moderate seasonality ( = 0.44, 0.28 and 0.45 for both genders, males and females respectively), whereas for asthma, it indicates a strong seasonality ( = 0.82, 0.78 and 0.82 for both genders, male and female respectively). CONCLUSIONS: For the purposes of health services research, evidence of the statistical presence of seasonality is insufficient to determine the etiologic, clinical and policy relevance of findings. Measurement of the strength of the seasonal effect, as can be determined using the technique, is also important in order to provide a robust sense of seasonality.

Global plagues and the Global Fund: Challenges in the fight against HIV, TB and malaria.

BACKGROUND: Although a grossly disproportionate burden of disease from HIV/AIDS, TB and malaria remains in the Global South, these infectious diseases have finally risen to the top of the international agenda in recent years. Ideal strategies for combating these diseases must balance the advantages and disadvantages of 'vertical' disease control programs and 'horizontal' capacity-building approaches. DISCUSSION: The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) represents an important step forward in the struggle against these pathogens. While its goals are laudable, significant barriers persist. Most significant is the pitiful lack of funds committed by world governments, particularly those of the very G8 countries whose discussions gave rise to the Fund. A drastic scaling up of resources is the first clear requirement for the GFATM to live up to the international community's lofty intentions. A directly related issue is that of maintaining a strong commitment to the treatment of the three diseases along with traditional prevention approaches, with the ensuing debates over providing affordable access to medications in the face of the pharmaceutical industry's vigorous protection of patent rights. SUMMARY: At this early point in the Fund's history, it remains to be seen how these issues will be resolved at the programming level. Nevertheless, it is clear that significant structural changes are required in such domains as global spending priorities, debt relief, trade policy, and corporate responsibility. HIV/AIDS, tuberculosis and malaria are global problems borne of gross socioeconomic inequality, and their solutions require correspondingly geopolitical solutions.