Clinical and serological predictors of post COVID-19 condition-findings from a Canadian prospective cohort study.

Introduction: More than 3 years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates. Methods: We compared clinical and serological predictors among COVID-19 survivors with (n = 102 cases) and without (n = 122 controls) persistent symptoms ≥12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori. Results: Similar proportions of PCC-cases (66.7%, n = 68) and infected-controls (71.3%, n = 87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n = 96) and anti-RBD (95.1%, n = 97) IgG, as compared with controls (anti-Spike: 89.3%, n = 109; anti-RBD: 84.4%, n = 103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11-4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64-7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p = 0.02), number of months post COVID-19 (OR 1.1, p < 0.01), allergies (OR 1.8, p = 0.04), and need for medical support (OR 4.1, p < 0.01). Conclusion: Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings.

Results of the Stop the Spread Ottawa (SSO) cohort study: a Canadian urban-based prospective evaluation of antibody responses and neutralisation efficiency to SARS-CoV-2 infection and vaccination.

BACKGROUND: Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation. METHODS: Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine. RESULTS: Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22-56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses. CONCLUSION: The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.

A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial.

BACKGROUND: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients. OBJECTIVE: The FLUID trial is a pragmatic, multicenter, 2×2 cluster crossover comparative effectiveness randomized trial that aims to evaluate the effectiveness of a hospital-wide policy that stocks either NS or RL as the main crystalloid fluid in 16 hospitals across Ontario, Canada. METHODS: All hospitalized adult and pediatric patients (anticipated sample size 144,000 patients) with an incident admission to the hospital over the course of each study period will be included. Either NS or RL will be preferentially stocked throughout the hospital for 12 weeks before crossing to the alternate fluid for the subsequent 12 weeks. The primary outcome is a composite of death and hospital readmission within 90 days of hospitalization. Secondary outcomes include death, hospital readmission, dialysis, reoperation, postoperative reintubation, length of hospital stay, emergency department visits, and discharge to a facility other than home. All outcomes will be obtained from health administrative data, eliminating the need for individual case reports. The primary analysis will use cluster-level summaries to estimate cluster-average treatment effects. RESULTS: The statistical analysis plan has been prepared "a priori" in advance of receipt of the trial data set from ICES and any analyses. CONCLUSIONS: We describe the protocol and statistical analysis plan for the evaluation of primary and secondary outcomes for the FLUID trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04512950; https://classic.clinicaltrials.gov/ct2/show/NCT04512950. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51783.

No time for complacency: The CoVaRR-Net Biobank is an essential element of laboratory preparedness for infectious disease outbreaks.

The SARS-CoV-2 pandemic highlighted the need for rapid, collaborative, and population-centric research to define health impact, develop health care policies and establish reliable diagnostic and surveillance tests. Critical for these objectives were in-depth clinical data collected in standardized fashion and large numbers of various types of human samples prior and post-viral encounter. As the pandemic evolved with the emergence of new variants of concern (VOCs), access to samples and data from infected and vaccinated individuals were needed to monitor immune durability, the possibility of increased transmissibility and virulence, and vaccine protection against new and emerging VOCs. Therefore, essential to the pandemic response is a strong laboratory and data research component, supported by effective biobanking and data sharing. Critically important to the speed of the research response is the rapid access to biobanked samples. To address critical challenges brought to light by the pandemic, the Coronavirus Variants Rapid Response Network (CoVaRR-Net), funded by the Canadian Institutes of Health Research, was established to coordinate research efforts to provide rapid evidence-based responses to emerging VOCs. The purpose of this paper is to introduce the CoVaRR-Net Biobank and define its contribution to pandemic preparedness.

La pandémie de SRAS-CoV-2 a fait ressortir la nécessité de réaliser des recherches rapides, coopératives et populationnelles pour en définir les effets sur la santé, promulguer des politiques sanitaires et établir des tests diagnostiques et des tests de surveillance fiables. Pour réaliser ces objectifs, il était essentiel de colliger des données cliniques approfondies d'une manière standardisée et d'amasser un grand nombre de divers types d'échantillons humains avant et après le contact viral. Lorsque la pandémie a évolué par l'émergence de nouveaux variants préoccupants (VOC), il est devenu nécessaire d'accéder à des échantillons et à des données de personnes infectées et vaccinées pour surveiller la durabilité de l'immunité, la possibilité d'une transmissibilité et d'une virulence accrues et la protection conférée par les vaccins contre les VOC nouveaux et émergents. Ainsi, il est essentiel de disposer d'un vigoureux volet de recherches de laboratoire et de recherches à partir de données pour répondre à la pandémie, soutenu par une mise en biobanque et un partage des données efficaces. Pour assurer une réponse rapide par la recherche, il est tout aussi important d'accéder rapidement aux échantillons mis en biobanque. Afin de relever les défis cruciaux soulevés par la pandémie, le Coronavirus Variants Rapid Response Network (réseau de réponse rapide aux variants du coronavirus; CoVaRR-Net), financé par les Instituts de recherche en santé du Canada, a été créé pour coordonner les efforts de recherche afin de fournir des réponses rapides fondées sur des données probantes aux VOC en émergence. Le présent article vise à présenter la Biobanque CoVaRR-Net et à en définir la contribution à la préparation aux pandémies.

What do we talk about when we talk about "equipoise"? Stakeholder interviews assessing the use of equipoise in clinical research ethics.

INTRODUCTION: Equipoise, generally defined as uncertainty about the relative effects of the treatments being compared in a trial, is frequently referenced as an ethical standard for the conduct of randomized clinical trials. However, it seems to be defined in several different ways and may be used differently by different individuals. We explored how clinical researchers, chairs of research ethics boards, and philosophers of science define and reason with this term. METHODS: We completed semi-structured interviews about clinical trial ethics with 15 clinical researchers, 15 research ethics board chairs, and 15 philosophers of science/bioethicists. Each participant was asked a standardized set of 10 questions, 4 of which were specifically about equipoise. All interviews were conducted telephonically and transcribed. Responses were grouped and analysed via a modified grounded theory method. RESULTS: Forty-three respondents defined equipoise in 7 logically distinct ways, and 2 respondents could not explicitly define it. The most common definition, offered by 14 respondents (31%), defined "equipoise" as a disagreement at the level of a community of physicians. There was significant variability in definitions offered between and within groups. When asked how they would "operationalize" equipoise - i.e. check or test for its presence - respondents provided 7 alternatives, the most common being in relation to a literature review (15/45, 33%). The vast majority of respondents (35/45, 78%) felt the concept was helpful, though many acknowledged that the lack of a clear definition or operationalization was problematic. CONCLUSION: There is significant variation in definitions of equipoise offered by respondents, suggesting that parties within groups and between groups may be referring to different concepts when they reference "equipoise". This non-uniformity may impact fairness and transparency and opens the door to potential ethical problems in the evaluation of clinical trials - for instance, a patient may understand equipoise very differently than the researchers enrolling her in a trial, which could cause her agreement to participate to be based upon false premises.

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate.

OBJECTIVES: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes. DESIGN: FLUID was a pragmatic pilot cluster randomised cross-over trial. SETTING: Four hospitals in the province of Ontario, Canada PARTICIPANTS: All hospitalised adult and paediatric patients with an incident admission to the hospital over the course of each study period. INTERVENTIONS: A hospital wide policy/strategy which stocked either NS or RL throughout the hospital for 12 weeks before crossing over to the alternate fluid for the subsequent 12 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary feasibility outcome was study fluid protocol adherence. Secondary feasibility outcomes included time to Research Ethics Board (REB) approval and trial initiation. Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes were analysed descriptively. RESULTS: Among 24 905 included patients, mean age 59.1 (SD 20.5); 13 977 (56.1%) were female and 21 150 (85.0%) had medical or surgical admitting diagnoses. Overall, 96 821 L were administered in the NS arm, and 78 348 L in the RL arm. Study fluid adherence to NS and RL was 93.7% (site range: 91.6%-98.0%) and 79.8% (site range: 72.5%-83.9%), respectively. Time to REB approval ranged from 2 to 48 days and readiness for trial initiation from 51 to 331 days. 5544 (22.3%) patients died or required hospital re-admission in the first 90 days. CONCLUSIONS: The future large trial is feasible. Anticipating and addressing logistical challenges during the planning stages will be imperative. TRIAL REGISTRATION NUMBER: NCT02721485.

How are randomized clinical trials ethically justified? A systematic scoping review and thematic analysis of reasons that ethically justify randomized clinical trials.

OBJECTIVES: We set out to identify and count the types of reasons that are used in contemporary scholarship about the ethical permissibility of randomized trials, with the goal of developing a finer grained taxonomy of reasons than what is currently used by most participants in this literature. Because of its central role in justifying normative conclusions about randomized clinical trials (RCTs), we paid particular attention to both uses of the keyword "equipoise" and to the different concepts associated with it. METHODS: We conducted a scoping review to identify articles that included arguments that were likely to express reasons justifying RCTs. Text excerpts that expressed reasoning about the ethical permissibility of RCTs were extracted from relevant papers, and our data were generated by coding these excerpts using a mixed-methods protocol that fused elements of a grounded analysis and thematic coding. In our study, each theme corresponded to a specific type of reason that was contentful and stable when applied to our corpus of text extracts. RESULTS: Our search, screening, and text extraction process yielded 1,335 unique text excerpts, which then formed the basis of our coding. Although we found that 16 themes were sufficient to saturate this corpus, slightly less than 100% of our excerpts were covered by just 10 themes. We also tracked uses of 16 keywords in the text excerpts to explore whether there was any relationship between the keywords and our themes and found that keywords frequently did not cooccur with the presence of our themes. CONCLUSIONS: Our data and analysis support the conclusion that there is significant diversity in the types of reasons offered to justify RCTs; 10 themes effectively captured all the text excerpts we analyzed, and these themes cannot be reduced to the occurrence of relevant keywords. This result highlights how individuals and organizations may use different reasons to consider randomized trials to be justified and even when they use similar language the concepts they are referencing may not be consistent.

Cohort profile: Stop the Spread Ottawa (SSO)-a community-based prospective cohort study on antibody responses, antibody neutralisation efficiency and cellular immunity to SARS-CoV-2 infection and vaccination.

PURPOSE: To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa-SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants. PARTICIPANTS: Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months). FINDINGS TO DATE: The median age of the baseline sample was 44 (IQR 23, range: 18-79) and just over two-thirds (n=688; 67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants). FUTURE PLANS: SSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.

Rheumatic heart disease in Indigenous young peoples.

Indigenous children and young peoples live with an inequitable burden of acute rheumatic fever and rheumatic heart disease. In this Review, we focus on the epidemiological burden and lived experience of these conditions for Indigenous young peoples in Australia, New Zealand, and Canada. We outline the direct and indirect drivers of rheumatic heart disease risk and their mitigation. Specifically, we identify the opportunities and limitations of predominantly biomedical approaches to the primary, secondary, and tertiary prevention of disease among Indigenous peoples. We explain why these biomedical approaches must be coupled with decolonising approaches to address the underlying cause of disease. Initiatives underway to reduce acute rheumatic fever and rheumatic heart disease in Australia, New Zealand, and Canada are reviewed to identify how an Indigenous rights-based approach could contribute to elimination of rheumatic heart disease and global disease control goals.

Protocol for a systematic scoping review of reasons given to justify the performance of randomised controlled trials.

INTRODUCTION: Randomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials. METHODS AND ANALYSIS: We will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials. ETHICS AND DISSEMINATION: No research ethics board approval is necessary because we are not examining patient-level data. This protocol complies with the reported guidance for conducting systematic scoping reviews. The findings of this paper will be disseminated via presentations and academic publication. In a subsequent phase of this research, we hope to engage with stakeholders and translate any recommendations derived from our findings into operational guidelines.

FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial.

INTRODUCTION: 0.9% saline and Ringer's lactate are the two most common resuscitation crystalloid fluids. 0.9% saline may lead to hyperchloraemic metabolic acidosis and may be associated with impaired kidney function and death. Few large multicentre randomised trials have been conducted to evaluate the effect of these two fluids on clinically important outcomes. METHODS: FLUID is a pragmatic pilot cluster randomised crossover trial in which four hospitals will be randomised to normal saline or Ringer's lactate for 14 weeks, then crossover to the alternative fluid for the subsequent 14 weeks after 1 to 3 week transition. With waiver of informed consent, all adult and paediatric patients admitted to participating sites will be included in the FLUID trial except for neonates. Primary feasibility outcome is study fluid protocol adherence (target:≥80%). Secondary feasibility outcomes include time to research ethics board (REB) approval and readiness to trial initiation (≤3 months from REB submission and approval). Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes for the future large FLUID trial will be described. Protocol adherence will be collected by site at specified time points. All clinical data will be obtained at patient level through provincial health administrative data held at the Institute for Clinical Evaluative Sciences (ICES). Event rates for the primary and secondary outcomes will be described using frequencies and proportions with 95% CIs. Intracluster and interperiod correlation coefficients will be calculated from population-level data available at ICES. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ottawa Health Science Research Ethics Board. The FLUID pilot will determine feasibility, and ICES data across all potential sites in Ontario will allow calculation of sample size parameter estimates to inform the design and implementation of the large trial. TRIAL REGISTRATION NUMBER: NCT02721485; Pre-results.

Management of infectious diseases in remote northwestern Ontario with telemedicine videoconference consultations.

Northwestern Ontario in Canada provides a unique clinical challenge for providing optimal medical care. It is a large geographic area (385,000 km2) and is home to 32 remote First Nations communities, most without road access. These communities suffer a heavy burden of infectious disease and specialist consultations are difficult to obtain. The Division of Infectious Diseases at the Ottawa Hospital and the Sioux Lookout Meno Ya Win Health Centre established a telemedicine-based infectious disease consultation service in July 2014. We describe the implementation of this service, types of cases seen and patient satisfaction, as well as some of the challenges encountered. Information on visits was prospectively collected through an administrative database, and patient satisfaction surveys were administered after each initial consultation. During our first year of operation, 191 teleconsultations occurred: 76 initial consultations, 82 follow-up appointments and 33 case conferences. The scope of cases has been broad, mostly involving musculoskeletal infections (26%), followed by skin and soft tissue infections (23%). HCV, acute rheumatic fever, and respiratory infections (including pulmonary tuberculosis) were other diagnoses. Patient satisfaction has been very high and 28 telemedicine patient visits have occurred in their remote home communities, minimizing travel. The infectious disease consulting service and local clinicians have succeeded in addressing needs for care in infectious diseases in northwestern Ontario, where important gaps in service to First Nations' communities continue to exist. Regular scheduled available access to an infectious disease specialist is a well-received advancement of care in this remote region of Canada.

A Scoping Review of Empirical Research Relating to Quality and Effectiveness of Research Ethics Review.

BACKGROUND: To date there is no established consensus of assessment criteria for evaluating research ethics review. METHODS: We conducted a scoping review of empirical research assessing ethics review processes in order to identify common elements assessed, research foci, and research gaps to aid in the development of assessment criteria. Electronic searches of Ovid Medline, PsychInfo, and the Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED, were conducted. After de-duplication, 4234 titles and abstracts were reviewed. Altogether 4036 articles were excluded following screening of titles, abstracts and full text. A total of 198 articles included for final data extraction. RESULTS: Few studies originated from outside North America and Europe. No study reported using an underlying theory or framework of quality/effectiveness to guide study design or analyses. We did not identify any studies that had involved a controlled trial--randomised or otherwise--of ethics review procedures or processes. Studies varied substantially with respect to outcomes assessed, although tended to focus on structure and timeliness of ethics review. DISCUSSION: Our findings indicate a lack of consensus on appropriate assessment criteria, exemplified by the varied study outcomes identified, but also a fragmented body of research. To date research has been largely quantitative, with little attention given to stakeholder experiences, and is largely cross sectional. A lack of longitudinal research to date precludes analyses of change or assessment of quality improvement in ethics review.

Elements of informed consent and decision quality were poorly correlated in informed consent documents.

OBJECTIVES: Although informed consent (IC) documents must contain specific elements, inclusion of these elements may be insufficient to encourage high-quality decision making. We assessed the extent to which documents conform to IC standards and how well conformity to decision quality (DQ) standards can be predicted by IC standards, IC document characteristics, and study characteristics. STUDY DESIGN AND SETTING: We obtained 139 IC documents for trials registered with ClinicalTrials.gov from study investigators. Using a four-point scale, two raters independently assessed each IC document on 36 IC standard items and 9 DQ items. RESULTS: Overall agreement between raters across all 45 items was 93%. Across the 36 IC standards items, conformity was generally quite high but variable, with 20 items showing conformity of 80% or more and seven items showing conformity of 50% or lower. IC standards concordance, overall length of the IC document, and country of study were all significant predictors of DQ standards but together accounted for less than 20% of the variance in DQ standards. CONCLUSION: Conformity to recommendations for improving IC documents was relatively high but variable. The extent to which an IC document conformed to these recommendations was only moderately related to whether it conformed to recommendations for improving DQ. Existing IC regulations may not describe the optimal approach to helping people make good study participation decisions.

Vancomycin use in a rural hospital: a 3-year retrospective study.

INTRODUCTION: Urban centres often perform audits of vancomycin use as they face outbreaks of resistant organisms. We undertook this study to understand the indications and duration of intravenous vancomycin in a rural setting. METHODS: We conducted a retrospective chart audit for all patients who received intravenous vancomycin over a 3-year period at a rural hospital in northwestern Ontario. RESULTS: Vancomycin was used intravenously in 180 patients during the study period. It was used for short courses (median 3 d), and serum levels were below target 72% of the time. CONCLUSION: High rates of invasive methicillin-resistant Staphylococcus aureus bacteremia and limited antibiotic choices in the field likely contributed to short courses of this antibiotic. Further study on clinical severity and antibiotic choice is needed. Additionally, weight-based dosing may result in target serum levels being achieved more frequently.

INTRODUCTION: Les centres urbains effectuent souvent des vérifications de l'utilisation de la vancomycine en raison du risque d'éclosions d'infections causées par des agents pathogènes résistants. Nous avons entrepris cette étude pour comprendre les indications et la durée de l'antibiothérapie par vancomycine intraveineuse en région rurale. MÉTHODES: Nous avons procédé à une analyse rétrospective des dossiers de tous les patients qui ont reçu de la vancomycine intraveineuse sur une période de 3 ans dans un hôpital rural du Nord-Ouest de l'Ontario. RÉSULTATS: La vancomycine a été administrée par voie intraveineuse chez 180 patients durant la période de l'étude. Elle a été utilisée pendant de courtes périodes (durée médiane 3 jours) et les taux sériques étaient inférieurs aux taux ciblés 72 % du temps. CONCLUSION: Les taux élevés de bactériémie invasive à Staphylococcus aureus méthicillinorésistant et le choix limité d'antibiotiques sur le terrain ont probablement contribué à la brièveté des antibiothérapies avec cet agent. Des études plus approfondies sur la gravité des cas cliniques et le choix des antibiotiques s'imposent. De plus, l'établissement de la dose en fonction du poids corporel pourrait favoriser l'atteinte plus fréquente des taux sériques cibles.

Epidemiology and outcomes of bloodstream infections in patients discharged from the emergency department.

OBJECTIVE: To determine the outcomes of patients discharged from the emergency department (ED) with a bloodstream infection (BSI) and how these outcomes are influenced by antibiotic treatment. METHOD: We identified every BSI in adult patients discharged from our ED to the community between July 1, 2002, and March 31, 2011. The medical records of all cases were reviewed to determine antibiotic treatment in the ED and at discharge. Microorganism sensitivities were used to determine whether antibiotics were appropriate. These data were linked to population-based administrative data to determine specific patient outcomes within the subsequent 2-week period: death, urgent hospitalization, or an unplanned return to the ED. RESULTS: A total of 480 adults with BSI were identified (1.49 cases per 1,000 adults discharged from the department). Compared to controls (321,048 patients), BSI patients had a significantly higher risk of urgent hospitalization (adjusted OR 2.1 [95% CI 1.6-2.8]) and unplanned return to the ED (adjusted OR 4.1 [95% CI 3.3-4.9]). Outcome risk was significantly lowered in BSI patients who received appropriate antibiotics in the ED and at discharge. In elderly patients, the risk of urgent hospitalization increased significantly as the time to appropriate antibiotics was delayed. CONCLUSIONS: BSI patients discharged from the ED have a significantly increased risk of urgent hospitalization and unplanned return to the ED in the subsequent 2 weeks. These risks decrease significantly with the timely provision of appropriate antibiotics. Our results support the aggressive use of measures ensuring that such patients receive appropriate antibiotics as soon as possible.

Acute rheumatic fever in First Nations communities in northwestern Ontario: Social determinants of health "bite the heart".

OBJECTIVE: To document a case series of 8 young First Nations patients diagnosed with acute rheumatic fever (ARF), a preventable disease that resulted in the death of 2 patients, in northwestern Ontario in the context of late diagnosis, overcrowded housing, and inadequate public health response. DESIGN: Retrospective case series over an 18-month period. SETTING: Remote First Nations communities in northwestern Ontario. PARTICIPANTS: Eight patients with ARF. MAIN OUTCOME MEASURES: Incidence, mortality, residual rheumatic heart disease, time to diagnosis, barriers to diagnosis and treatment, housing situation of patients, patient demographic characteristics (age, sex), and investigation results. RESULTS: The incidence of ARF in this population was 21.3 per 100,000, which is 75 times greater than the overall Canadian estimated incidence. The average patient age was 9.4 years. Most cases developed joint findings, and 5 of the surviving patients had rheumatic heart disease when they received echocardiography. The average time to diagnosis was 88 days. Two 4-year-old children died from ARF. Most patients lived in inadequate and crowded housing. CONCLUSION: This rare disease still exists in remote First Nations communities. These communities demonstrate an incidence equal to that in aboriginal communities in Australia and New Zealand, which have among the highest international incidence of ARF. Primordial prevention, including improved on-reserve housing, is urgently needed. Case detection and ongoing surveillance for primary and secondary prophylaxis requires a well resourced regional strategy.

What makes public health studies ethical? Dissolving the boundary between research and practice.

BACKGROUND: The generation of evidence is integral to the work of public health and health service providers. Traditionally, ethics has been addressed differently in research projects, compared with other forms of evidence generation, such as quality improvement, program evaluation, and surveillance, with review of non-research activities falling outside the purview of the research ethics board. However, the boundaries between research and these other evaluative activities are not distinct. Efforts to delineate a boundary - whether on grounds of primary purpose, temporality, underlying legal authority, departure from usual practice, or direct benefits to participants - have been unsatisfactory.Public Health Ontario has eschewed this distinction between research and other evaluative activities, choosing to adopt a common framework and process to guide ethical reflection on all public health evaluative projects throughout their lifecycle - from initial planning through to knowledge exchange. DISCUSSION: The Public Health Ontario framework was developed by a working group of public health and ethics professionals and scholars, in consultation with individuals representing a wide range of public health roles. The first part of the framework interprets the existing Canadian research ethics policy statement (commonly known as the TCPS 2) through a public health lens. The second part consists of ten questions that guide the investigator in the application of the core ethical principles to public health initiatives.The framework is intended for use by those designing and executing public health evaluations, as well as those charged with ethics review of projects. The goal is to move toward a culture of ethical integrity among investigators, reviewers and decision-makers, rather than mere compliance with rules. The framework is consonant with the perspective of the learning organization and is generalizable to other public health organizations, to health services organizations, and beyond. SUMMARY: Public Health Ontario has developed an ethics framework that is applicable to any evidence-generating activity, regardless of whether it is labelled research. While developed in a public health context, it is readily adaptable to other health services organizations and beyond.