Inequities in organ and tissue donation and transplantation for sexual orientation and gender identity diverse people: A scoping review.

Sexual orientation and gender identity (SOGI)-diverse populations experience discrimination in organ and tissue donation and transplantation (OTDT) systems globally. We assembled a multidisciplinary group of clinical experts as well as SOGI-diverse patient and public partners and conducted a scoping review including citations on the experiences of SOGI-diverse persons in OTDT systems globally to identify and explore the inequities that exist with regards to living and deceased OTDT. Using scoping review methods, we conducted a systematic literature search of relevant electronic databases from 1970 to 2021 including a grey literature search. We identified and screened 2402 references and included 87 unique publications. Two researchers independently coded data in included publications in duplicate. We conducted a best-fit framework synthesis paired with an inductive thematic analysis to identify synthesized benefits, harms, inequities, justification of inequities, recommendations to mitigate inequities, laws and regulations, as well as knowledge and implementation gaps regarding SOGI-diverse identities in OTDT systems. We identified numerous harms and inequities for SOGI-diverse populations in OTDT systems. There were no published benefits of SOGI-diverse identities in OTDT systems. We summarized recommendations for the promotion of equity for SOGI-diverse populations and identified gaps that can serve as targets for action moving forward.

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.

BACKGROUND: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. RESULTS: We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. CONCLUSIONS: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.).

Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19-compatible illness. We measured hydroxychloroquine whole-blood concentrations. RESULTS: We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44-1.16; P = .18) and for twice-weekly was .74 (95% CI, .46-1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19-compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08). CONCLUSIONS: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness among healthcare workers. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT04328467.

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

BACKGROUND: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). OBJECTIVE: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668). SETTING: Internet-based trial across the United States and Canada (40 states and 3 provinces). PARTICIPANTS: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. INTERVENTION: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. MEASUREMENTS: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. RESULTS: Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29). LIMITATION: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. CONCLUSION: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19. PRIMARY FUNDING SOURCE: Private donors.

Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. METHODS: We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. DISCUSSION: These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. TRIALS REGISTRATION: clinicaltrials.gov (NCT04308668); registered 16 March, 2020.

RéSUMé: CONTEXTE: Le syndrome respiratoire aigu sévère du coronavirus 2 (SARS-CoV-2) est apparu en décembre 2019, provoquant la pandémie de la COVID-19. À l'heure actuelle, il n'existe aucun traitement fondé sur des données probantes permettant de prévenir la COVID-19 suite à une exposition au virus ou de prévenir l'aggravation des symptômes suite à une infection confirmée. Nous décrivons la conception d'une étude clinique examinant l'utilisation d'hydroxychloroquine en tant que prophylaxie post-exposition (PPE) et de traitement préventif (TP) pour la COVID-19. MéTHODE: Nous réaliserons deux études cliniques imbriquées contrôlées par placebo, randomisées, à double insu, internationales et multicentriques examinant l'utilisation d'hydroxychloroquine pour : 1) la prophylaxie post-exposition des contacts asymptomatiques dans un même foyer ou les travailleurs de la santé exposés à la COVID-19 au cours des quatre derniers jours, et 2) le traitement préventif des patients symptomatiques en ambulatoire atteints de COVID-19 et présentant des symptômes pour une durée totale de moins de quatre jours. Nous recruterons 1500 patients pour chaque bras de l'étude (PPE et TP). Les participants seront randomisés à un ratio de 1 : 1 pour recevoir cinq jours d'hydroxychloroquine ou de placebo. Le critère d'évaluation principal de l'étude PPE sera l'incidence de COVID-19 symptomatique. Le critère d'évaluation principal de l'étude TP consistera en une échelle ordinale de la gravité de la maladie (pas d'hospitalisation, hospitalisation sans soins intensifs, hospitalisation avec soins intensifs, ou décès). La sélection des participants, le consentement éclairé et le suivi se feront exclusivement en ligne après avoir obtenu les consentements réglementaires et des comités d'éthique de la recherche appropriés au Canada et aux États-Unis. DISCUSSION: Ces études randomisées contrôlées complémentaires sont conçues de façon innovatrice et disposent de la puissance nécessaire pour répondre rapidement aux questions urgentes quant à l'efficacité de l'hydroxychloroquine pour réduire la transmission et la gravité de la maladie de la COVID-19 pendant une pandémie. Le suivi des participants ne sera pas réalisé en personne afin de faciliter les stratégies de distanciation sociale et de réduire le risque d'exposition du personnel de l'étude. Des approches innovatrices d'études sont nécessaires afin d'évaluer rapidement les options thérapeutiques pour mitiger l'impact global de cette pandémie. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04308668); enregistrées le 16 mars 2020.

Is there a rural/urban gap in the quality of HIV care for treatment-naïve HIV-positive individuals initiating antiretroviral therapy in British Columbia?

Rurally located people living with HIV (PLWH) face unique challenges associated with remoteness that may negatively affect their HIV care outcomes. The Programmatic Compliance Score (PCS) has been used previously as a quality of care metric, and is predictive of mortality for treatment-naïve individuals initiating combination antiretroviral therapy (cART). This study looked at whether the rurality of PLWH impacted their PCS. PCS was calculated for PLWH (≥19 years old) initiating cART in British Columbia between 2000 and 2013. Rurality was determined at the time of cART initiation using two methodologies: (1) a categorical postal code method; and (2) the General Practice Rurality Index (GPRI), a score representing an individual's degree of rurality. Ordinal logistic regression modeling was used to assess the relationship between rurality and PCS. Among 4616 PLWH with an evaluable PCS, 176 were classified as rural and 3512 as urban (928 had an unknown postal code). After adjusting for age, sex, hepatitis C status, Indigenous ancestry, and year of cART initiation, categorical rurality was not associated with a worse PCS (adjusted odds ratio (AOR) 1.04; 95% CI: 0.77-1.39). However, an increasing degree of rurality was associated with a worse PCS (AOR (per 10 increase in GPRI) 1.13; 95% CI: 1.06-1.20). Given that a poor PCS has been shown to be predictive of all-cause mortality for individuals initiating cART, strategies to improve access to HIV care for rural individuals should be evaluated.

Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS CoV-2 in healthcare workers at high-risk of exposure. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with Covid-19, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations. RESULTS: We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18) and for twice weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19 (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08). CONCLUSIONS: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.

Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19.

INTRODUCTION: Use of hydroxychloroquine in hospitalized patients with COVID-19, especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from three outpatient randomized clinical trials. METHODS: We conducted three randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, post-exposure prophylaxis and early treatment for COVID-19. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. RESULTS: We enrolled 2,795 participants. The median age of research participants was 40 (IQR 34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2,324 (84%) participants reported side effect data, and 638 (27%) reported at least one medication side effect. Side effects were reported in 29% with daily, 36% with twice weekly, 31% with once weekly hydroxychloroquine compared to 19% with placebo. The most common side effects were upset stomach or nausea (25% with daily, 18% with twice weekly, 16% with weekly, vs. 10% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for daily, 16% twice weekly, 12% weekly, vs. 6% for placebo). Two individuals were hospitalized for atrial arrhythmias, one on placebo and one on twice weekly hydroxychloroquine. No sudden deaths occurred. CONCLUSION: Data from three outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.

Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.

BACKGROUND: Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials. METHODS: We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. RESULTS: We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred. CONCLUSIONS: Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19. CLINICALTRIALSGOV IDENTIFIER: NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.

Anaplasmosis: An emerging tick-borne disease of importance in Canada.

Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Anaplasma phagocytophilum. As a tick-borne disease, the public health impact of HGA continues to increase with range expansion of the disease vector. The clinical presentation of HGA is often a non-specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an appropriate diagnosis. Herein we present three cases of HGA, highlighting the spectrum of disease by which HGA can manifest. Although each case has their unique features, we outline important shared clinical elements to facilitate an empiric diagnosis while definitive laboratory investigations are pending. Our case series further serves to highlight the critical importance of prompt antimicrobial treatment to reduce morbidity and potential mortality.

The Continuum of HIV Care in Rural Communities in the United States and Canada: What Is Known and Future Research Directions.

The nature of the HIV epidemic in the United States and Canada has changed with a shift toward rural areas. Socioeconomic factors, geography, cultural context, and evolving epidemics of injection drug use are coalescing to move the epidemic into locations where populations are dispersed and health care resources are limited. Rural-urban differences along the care continuum demonstrate the implications of this sociogeographic shift. Greater attention is needed to build a more comprehensive understanding of the rural HIV epidemic in the United States and Canada, including research efforts, innovative approaches to care delivery, and greater community engagement in prevention and care.