Enhanced Recovery After Surgery Cardiac Society turnkey order set for surgical-site infection prevention: Proceedings from the American Association for Thoracic Surgery ERAS Conclave 2023.

OBJECTIVES: Surgical-site infections (SSIs) after cardiac surgery increase morbidity and mortality, consume health care resources, impair recovery, and diminish patients' quality of life. Numerous guidelines and expert consensus documents have been published to address the prevention and management of SSIs. Our objective is to integrate these documents into an order set that will facilitate the adoption and implementation of evidence-based best practices for preventing and managing SSIs after cardiac surgery. METHODS: Subject matter experts were consulted to translate existing guidelines and literature into a sample turnkey order set for SSI reduction. Orders derived from consistent class I, IIA, or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the turnkey order set in bold type. Selected orders that were inconsistent class I or IIA, class IIB or otherwise supported by published evidence, were also included in italicized type. RESULTS: Preventative care begins with the preoperative identification of both modifiable and nonmodifiable SSI risks by health care providers. Assessment tools can be used to assist in identifying patients at a high risk of SSI. Preoperative recommendations include screening for and treating Staphylococcus aureus nasal carriage. Intraoperatively, tailored prophylactic intravenous antibiotics and maintaining blood glucose levels below 180 mg/dL are essential elements. Postoperative care includes maintaining normothermia, glucose control and patient engagement. CONCLUSIONS: Despite the well-documented advantages of a multidisciplinary care pathway for SSI in cardiac surgery, there are inconsistencies in its adoption and implementation. This article provides an order set that incorporates recommendations from existing guidelines to prevent SSI in the cardiac surgical population.

Disparities in access to and timing of interventional therapies for pulmonary embolism across the United States.

BACKGROUND: Interventional therapies (ITs) are an emerging treatment modality for pulmonary embolism (PE); however, the degree of racial, sex-based, and sociodemographic disparities in access and timing is unknown. OBJECTIVES: To investigate barriers to access and timing of ITs for PE across the United States. METHODS: A retrospective cohort study utilizing the Nationwide Inpatient Sample from 2016-2020 included adult patients with PE. The use of ITs (mechanical thrombectomy and catheter-directed thrombolysis) was identified via International Classification of Diseases 10th revision codes. Early IT was defined as procedure performed within the first 2 days after admission. RESULTS: A total of 27 805 273 records from the 2016-2020 Nationwide Inpatient Sample database were examined. There were 387 514 (1.4%) patients with PE, with 14 249 (3.6%) of them having undergone IT procedures (11 115 catheter-directed thrombolysis, 2314 thrombectomy, and 780 both procedures). After multivariate adjustment, factors associated with less use of IT included Black race (odds ratio [OR], 0.90; 95% CI, 0.86-0.94; P < .01), Hispanic race (OR, 0.73; 95% CI, 0.68-0.79; P < .01), female sex (OR, 0.88; 95% CI, 0.85-0.91; P < .01), treatment in a rural hospital (OR, 0.49; 95% CI, 0.44-0.54; P < .01), and lack of private insurance (Medicare OR, 0.77; 95% CI, 0.73-0.80; P < .01; Medicaid OR, 0.65; 95% CI, 0.61-0.69; P < .01; no coverage OR, 0.87; 95% CI, 0.82-0.93; P < .01). Among the patients who received IT, 11 315 (79%) procedures were conducted within 2 days of admission and 2934 (21%) were delayed. Factors associated with delayed procedures included Black race (OR, 1.12; 95% CI, 1.01-1.26; P = .04), Hispanic race (OR, 1.52; 95% CI, 1.28-1.80; P < .01), weekend admission (OR, 1.37; 95% CI, 1.25-1.51; P < .01), Medicare coverage (OR, 1.24; 95% CI, 1.10-1.40; P < .01), and Medicaid coverage (OR, 1.29; 95% CI, 1.12-1.49; P < .01). CONCLUSION: Significant racial, sex-based, and geographic barriers exist in overall access to IT for PE in the United States.

Outcomes with severe pulmonary coccidioidomycosis and respiratory failure in the United States.

Background: Coccidioidomycosis is a fungal infection with presentations ranging from asymptomatic illness to severe pneumonia and respiratory failure. The outcomes of patients with severe pulmonary coccidioidomycosis requiring mechanical ventilation (MV) are not well understood. Methods: We performed a retrospective cohort analysis utilizing the Nationwide Inpatient Sample (NIS) from 2006 to 2017. Patients >18 years of age with a diagnosis of pulmonary coccidioidomycosis were included in the cohort. Results: A total of 11,045 patients were hospitalized with a diagnosis of pulmonary coccidioidomycosis during the study period. Of these, 826 (7.5%) patients required MV during their hospitalization with a mortality rate of 33.5% compared to 1.3% (p < 0.01) for patients not requiring MV. Results of the multivariable logistic regression model show that risk factors for MV included the history of neurological disorders and paralysis (OR 3.38[95% CI 2.70 to 4.20] p < 0.01; OR 3.13[95% CI 1.91 to 5.15] p < 0.01, respectively) and HIV (OR 1.63[95% 1.10 to 2.43] p < 0.01). Risk factors for mortality among patients requiring MV included older age (OR 1.24 per 10-year increase[95% CI 1.08 to 1.42] p < 0.01), coagulopathy (OR 1.61[95% CI 1.09 to 2.38] p = 0.01) and HIV (OR 2.83 [95% CI 1.32 to 6.10] p < 0.01). Conclusions: Approximately 7.5% of patients admitted with coccidioidomycosis in the United States require MV, and MV is associated with high mortality (33.5%).

Historique: La coccidioïdomycose est une infection fongique dont les manifestations vont d'une affection asymptomatique à une pneumonie grave et à une insuffisance respiratoire. Les résultats cliniques des patients atteints d'une coccidioïdomycose pulmonaire grave qui ont besoin d'une ventilation mécanique (VM) sont mal compris. Méthodologie: Les chercheurs ont procédé à une analyse de cohorte rétrospective au moyen d'un échantillon national de patients hospitalisés (NIS) entre 2006 et 2017. Les patients de plus de 18 ans ayant un diagnostic de coccidioïdomycose pulmonaire ont été inclus dans la cohorte. Résultats: Au total, 11 045 patients ont été hospitalisés à cause d'un diagnostic de coccidioïdomycose pulmonaire pendant la période de l'étude. De ce nombre, 826 (7,5 %) ont eu besoin d'une VM pendant leur hospitalisation, dont 33,5 % sont décédés par rapport à 1,3 % (p < 0,01) de ceux qui n'ont pas eu besoin de VM. Les résultats du modèle de régression logistique multivariable révèlent que les facteurs de risque de VM incluaient des antécédents de troubles neurologiques et de paralysie (rapport de cotes [RC] 3,38, IC à 95 % 2,70 à 4,20, p < 0,01; RC 3,13, IC à 95 % 1,91 à 5,15, p < 0,01, respectivement) et de virus de l'immunodéficience humaine (RC 1,63, IC à 95 % 1,10 à 2,43, p < 0,01). Les facteurs de risque de mortalité chez les patients qui avaient besoin de VM incluaient un âge plus avancé (RC 1,24 par tranche de dix ans, IC à 95 % 1,08 à 1,42, p < 0,01), une coagulopathie (RC 1,61, IC à 95 % 1,09 à 2,38, p = 0,01) et le virus de l'immunodéficience humaine (RC 2,83; IC à 95 % 1,32 à 6,10; p < 0,01). Conclusions: Environ 7,5 % des patients hospitalisés à cause d'une coccidioïdomycose aux États-Unis ont eu besoin d'une VM, laquelle est associée à un taux de mortalité élevé (33,5 %).

Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality. METHODS AND ANALYSIS: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI. ETHICS AND DISSEMINATION: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04851015.

Surgical Triage and Timing for Patients With Coronavirus Disease: A Guidance Statement from The Society of Thoracic Surgeons.

The coronavirus disease 2019 (COVID-19) pandemic continues to disrupt the provision of cardiac procedural services due to overwhelming interval surges in COVID-19 cases and the associated crisis of cardiac intervention deferment. Despite the availability of widespread testing, highly efficacious vaccines, and intensive public health efforts, the pandemic is entering its third year, where new severe acute respiratory syndrome-coronavirus-2 variants have increased the likelihood that patients scheduled for a cardiac intervention will contract COVID-19 in the perioperative period. The Society of Thoracic Surgeons (STS) Workforce on Critical Care, the STS Workforce on Adult Cardiac and Vascular Surgery, and the Canadian Society of Cardiac Surgeons have developed this document, endorsed by the STS and affirmed by the Society of Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology, to provide guidance for cardiac procedure deferment and intervention timing for preoperative patients diagnosed with COVID-19. This document is intended for the perioperative cardiac surgical team and outlines the present state of the pandemic, the impact of COVID-19 on intervention outcome, and offers a recommended algorithm for individualized cardiac procedure triage and timing.

Perioperative Coronavirus Vaccination-Timing and Implications: A Guidance Document.

EXECUTIVE SUMMARY: Cardiothoracic surgical patients are at risk of increased coronavirus disease severity. Several important factors influence the administration of the coronavirus disease vaccine in the perioperative period. This guidance statement outlines current information regarding vaccine types, summarizes recommendations regarding appropriate timing of administration, and provides information regarding side effects in the perioperative period for cardiac and thoracic surgical patients.

Inguinal Ulceroglandular Tularemia Caused by Francisella tularensis Subspecies holarctica, Canada.

Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis, a Biosafety Level 3 pathogen and potential agent of bioterrorism. We describe 2 cases of perigenital ulcer disease caused by Francisella tularensis subspecies holarctica in Manitoba, Canada. These cases caused inadvertent exposure among laboratory personnel.

Outcomes With Severe Blastomycosis and Respiratory Failure in the United States.

BACKGROUND: Outcomes of patients with severe pulmonary blastomycosis requiring mechanical ventilation (MV) are not well understood in the modern era. Limited historical case series reported 50-90% mortality in patients with acute respiratory distress syndrome caused by blastomycosis. The objective of this large retrospective cohort study was to describe the risk factors and outcomes of patients with severe pulmonary blastomycosis. METHODS: We performed a retrospective cohort analysis utilizing the Nationwide Inpatient Sample from 2006-2014. Patients aged >18 years with a diagnosis of blastomycosis who received MV were included. RESULTS: There were 1848 patients with a diagnosis of blastomycosis included in the study. Of these, 219 (11.9%) underwent MV with a mortality rate of 39.7% compared with 2.5% in patients not requiring ventilatory support (P < .01). The median (IQR) time to death for patients requiring MV was 12 (8-16) days. The median length of hospital stay for survivors of MV was 22 (14-37) days. The rate of MV was higher for patients treated in teaching hospitals (63.4% vs 57.2%, P = .05) and lower for those receiving care at a rural hospital (12.3% vs 17.2%, P = .04). In a multivariate model, female gender was associated with increased risk of mortality (OR, 1.84; 95% CI, 1.06-3.20; P = .03) as was increasing patient age (10-year age increase OR, 1.64; 95% CI, 1.33-2.02; P < .01). CONCLUSIONS: In the largest published cohort of patients with blastomycosis, mortality for patients on MV is high at ~40%, 16-fold higher than those without MV.

Location of residence and mortality for patients diagnosed with Fournier's gangrene.

INTRODUCTION: Fournier's gangrene (FG) is a necrotizing infection of the genitalia. Time from to surgical intervention is a critical determinant of prognosis. We sought to investigate whether patients from rural locations have worse clinical outcomes given distance from a tertiary center. METHODS: The Manitoba Intensive Care Unit (ICU) registry includes patients who have been admitted into ICUs across Manitoba. We identified patients admitted with FG from February 1999 to October 2019. Age, gender, Charlson comorbidity index (CCI), presence of colostomy and scrotal debridement, length of stay (LOS), and mortality outcomes were obtained. Patients were categorized as being rural or urban. RESULTS: From 1999-2019, a total of 79 patients were admitted with FG. The median age was 60 years [interquartile range [IQR] 48-67). The mortality rate during hospitalization was 16.5%. There was no statistically significant difference in the number of deaths for patients from urban vs. rural dwellings (9/47 [19.1%] vs. 4/32 [12.5%], p=0.434]. A comparison of the 66 (83.5%) patients that survived and the 13 (16.5%) that died during ICU hospitalization demonstrated no difference in age, gender, CCI, presence of colostomy, and rates of scrotal re-debridement (p>0.05). Multivariable analysis demonstrated that living in a rural area was not associated with increased mortality (odds ratio 0.64, 95% confidence interval 00.16-2.57, p=0.527). CONCLUSIONS: Location of residence was not predictive of death from FG. In addition, baseline characteristics such as age, gender, CCI, surgical interventions, or LOS were not found to be associated with mortality.

Decontamination of N95 masks for re-use employing 7 widely available sterilization methods.

The response to the COVID-19 epidemic is generating severe shortages of personal protective equipment around the world. In particular, the supply of N95 respirator masks has become severely depleted, with supplies having to be rationed and health care workers having to use masks for prolonged periods in many countries. We sought to test the ability of 7 different decontamination methods: autoclave treatment, ethylene oxide gassing (ETO), low temperature hydrogen peroxide gas plasma (LT-HPGP) treatment, vaporous hydrogen peroxide (VHP) exposure, peracetic acid dry fogging (PAF), ultraviolet C irradiation (UVCI) and moist heat (MH) treatment to decontaminate a variety of different N95 masks following experimental contamination with SARS-CoV-2 or vesicular stomatitis virus as a surrogate. In addition, we sought to determine whether masks would tolerate repeated cycles of decontamination while maintaining structural and functional integrity. All methods except for UVCI were effective in total elimination of viable virus from treated masks. We found that all respirator masks tolerated at least one cycle of all treatment modalities without structural or functional deterioration as assessed by fit testing; filtration efficiency testing results were mostly similar except that a single cycle of LT-HPGP was associated with failures in 3 of 6 masks assessed. VHP, PAF, UVCI, and MH were associated with preserved mask integrity to a minimum of 10 cycles by both fit and filtration testing. A similar result was shown with ethylene oxide gassing to the maximum 3 cycles tested. Pleated, layered non-woven fabric N95 masks retained integrity in fit testing for at least 10 cycles of autoclaving but the molded N95 masks failed after 1 cycle; filtration testing however was intact to 5 cycles for all masks. The successful application of autoclaving for layered, pleated masks may be of particular use to institutions globally due to the virtually universal accessibility of autoclaves in health care settings. Given the ability to modify widely available heating cabinets on hospital wards in well-resourced settings, the application of moist heat may allow local processing of N95 masks.

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.

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.

Adult cardiac surgery and the COVID-19 pandemic: Aggressive infection mitigation strategies are necessary in the operating room and surgical recovery.

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.

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.).

Adult Cardiac Surgery and the COVID-19 Pandemic: Aggressive Infection Mitigation Strategies Are Necessary in the Operating Room and Surgical Recovery.

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.

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.

Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons.

The coronavirus disease 2019 (COVID-19) has had a profound global effect. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, most Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This "flattening of the curve" has inevitably prompted discussions around reopening of the economy, relaxing some public health restrictions, and resuming nonurgent health care delivery. This document provides a template for cardiac surgical programs to begin to ramp-up the delivery of cardiac surgery in a deliberate and graded fashion as the COVID-19 pandemic burden begins to ease that is guided by 3 principles. First, all recommendations from public health authorities regarding COVID-19 containment must continue to be followed to minimize disease spread, ensure patient safety, and protect health care personnel. Second, patients awaiting elective cardiac surgery need to be proactively managed, reprioritizing those with high-risk anatomy or whose clinical status is deteriorating. Finally, case volumes should be steadily increased in a mutually agreed upon fashion and must balance the clinical needs of patients awaiting surgery against the overall requirements of the health care system.