Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19.

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

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.

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.

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.

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.).

Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.

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.

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.

Emerging group C and group G streptococcal endocarditis: A Canadian perspective.

OBJECTIVES: The aim of this study was to determine the incidence of infective endocarditis (IE) in patients with bacteremia caused by group C and group G streptococci (GCGS) and to characterize the burden of disease, clinical characteristics, and outcomes through a case series of patients with GCGS IE. METHODS: Individuals with blood cultures growing GCGS in Manitoba, Canada, between January 2012 and December 2015 were included. Clinical and echocardiographic parameters were collected retrospectively. IE was suspected or confirmed according to the modified Duke criteria. RESULTS: Two hundred and nine bacteremic events occurred in 198 patients. Transthoracic echocardiography (TTE) was performed in 33%. Suspected or confirmed IE occurred in 6% of all patients and in 18% of those with TTE. Native valve infection was more common than prosthetic valve and device-related infections (75%, 17%, and 8%, respectively). Metastatic infection was observed in 64%, primarily to the lungs (57%), skin (43%), osteoarticular system (29%), and central nervous system (29%). Sepsis occurred in 58% and streptococcal toxic shock syndrome in 50% of those with IE, with overall mortality of 17%. CONCLUSIONS: IE from GCGS bacteremia is common and is frequently associated with severe disease, embolic events, and mortality. In the appropriate clinical context, GCGS bacteremic events should prompt investigation for IE.

Once-Daily Treatments for Methicillin-Susceptible Staphylococcus aureus Bacteremia: Are They Good Enough?

PURPOSE OF THE REVIEW: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a common cause of morbidity and mortality. First-line treatment requires frequent daily doses of an anti-staphylococcal beta-lactam. However, some physicians prescribe simpler once-daily regimens to improve compliance and improve healthcare utilization. We reviewed the literature regarding advantages, pitfalls, and efficacy of once-daily treatment options for MSSA bacteremia. RECENT FINDINGS: Several once-daily antibiotics are effective in vitro against MSSA (ceftriaxone, daptomycin, telavancin, dalbavancin, oritavancin, tedizolid, ertapenem, fluoroquinolones, and others), but there is insufficient evidence to support these agents for MSSA bacteremia. Ceftriaxone may be considered for therapy completion with MSSA bacteremia from osteomyelitis, and daptomycin may be considered in patients who cannot tolerate first-line therapy. However, they have not been compared to traditional second-line agents, and their role remains uncertain. Current evidence does not support the use of once-daily treatment options for MSSA bacteremia.

Clonal Clusters and Virulence Factors of Group C and G Streptococcus Causing Severe Infections, Manitoba, Canada, 2012-2014.

The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012-2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.