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2.
Br J Hosp Med (Lond) ; 82(3): 1-6, 2021 Mar 02.
Article in English | MEDLINE | ID: covidwho-1168179

ABSTRACT

Antibiotics are one of the most widely used classes of drugs within hospitals in the UK. They have a wide range of uses within all surgical specialties, both as preoperative prophylaxis and for treatment of acute surgical conditions. Antimicrobial resistance has increasingly been seen as a major issue, as the production of new antibiotics has decreased and overall use worldwide has increased. With the COVID-19 pandemic increasing concerns about antimicrobial resistance, there is an ever-increasing need for action. This article examines the particular challenges of antibiotic stewardship in surgical departments within the UK, and outlines possible solutions for improving adherence and reducing the risk of antimicrobial resistance in the future.


Subject(s)
Antibiotic Prophylaxis/methods , Antimicrobial Stewardship/methods , Surgery Department, Hospital , Surgical Wound Infection/prevention & control , Appendicitis/therapy , Cholecystitis/therapy , Diverticulitis/therapy , Humans , Preoperative Care , Surgical Wound Infection/drug therapy , United Kingdom
3.
PLoS One ; 16(1): e0244778, 2021.
Article in English | MEDLINE | ID: covidwho-1013217

ABSTRACT

BACKGROUND: Populations such as healthcare workers (HCW) that are unable to practice physical distancing are at high risk of acquiring Coronavirus disease-2019 (COVID-19). In these cases pharmacological prophylaxis would be a solution to reduce severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) transmission. Hydroxychloroquine has in vitro antiviral properties against SARS CoV-2. We therefore sought to determine the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19. METHODS AND FINDINGS: We electronically searched EMBASE, MEDLINE, the Cochrane COVID-19 Register of Controlled Trials, Epistemonikos COVID-19, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to September 28th, 2020 for randomized controlled trials (RCTs). We calculated pooled relative risks (RRs) for dichotomous outcomes with the corresponding 95% confidence intervals (CIs) using a random-effect model. We identified four RCTs (n = 4921) that met our eligibility criteria. The use of hydroxychloroquine, compared to placebo, did not reduce the risks of developing COVID-19 (RR 0.82, 95% CI 0.65 to 1.04, moderate certainty), hospitalization (RR 0.72, 95% CI 0.34 to 1.50, moderate certainty), or mortality (RR 3.26, 95% CI 0.13 to 79.74, low certainty), however, hydroxychloroquine use increased the risk of adverse events (RR 2.76, 95% CI 1.38 to 5.55, moderate certainty). CONCLUSION: Although pharmacologic prophylaxis is an attractive preventive strategy against COVID-19, the current body of evidence failed to show clinical benefit for prophylactic hydroxychloroquine and showed a higher risk of adverse events when compared to placebo or no prophylaxis.


Subject(s)
COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Antibiotic Prophylaxis/methods , Antiviral Agents/therapeutic use , COVID-19/metabolism , Humans , Hydroxychloroquine/metabolism , Pre-Exposure Prophylaxis/methods , Randomized Controlled Trials as Topic , SARS-CoV-2/pathogenicity
4.
Trials ; 21(1): 867, 2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-883594

ABSTRACT

BACKGROUND: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. METHODS: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. DISCUSSION: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. TRIAL REGISTRATION: ClinicalTrials.gov NCT04322396 . Registered on 26 March 2020.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/prevention & control , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Aged , Anti-Bacterial Agents/adverse effects , Antibiotic Prophylaxis/methods , Antimalarials/adverse effects , Azithromycin/adverse effects , Betacoronavirus/genetics , COVID-19 , Case-Control Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Denmark/epidemiology , Double-Blind Method , Drug Therapy, Combination , Female , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/adverse effects , Intensive Care Units/statistics & numerical data , Intention to Treat Analysis/methods , Male , Noninvasive Ventilation/adverse effects , Placebos/administration & dosage , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Risk Reduction Behavior , SARS-CoV-2
5.
Cell ; 181(4): 865-876.e12, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-684968

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , CRISPR-Cas Systems , Influenza A Virus, H1N1 Subtype/drug effects , RNA, Viral/antagonists & inhibitors , A549 Cells , Antibiotic Prophylaxis/methods , Base Sequence , Betacoronavirus/genetics , Betacoronavirus/growth & development , COVID-19 , Clustered Regularly Interspaced Short Palindromic Repeats , Computer Simulation , Conserved Sequence , Coronavirus/drug effects , Coronavirus/genetics , Coronavirus/growth & development , Coronavirus Infections/drug therapy , Coronavirus Nucleocapsid Proteins , Coronavirus RNA-Dependent RNA Polymerase , Epithelial Cells/virology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/growth & development , Lung/pathology , Lung/virology , Nucleocapsid Proteins/genetics , Pandemics , Phosphoproteins , Phylogeny , Pneumonia, Viral/drug therapy , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2 , Viral Nonstructural Proteins/genetics
6.
Am J Perinatol ; 37(8): 866-868, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-116830

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) infection occurring during pregnancy is associated with an increased risk of preterm delivery. This case report describes successful treatment of preterm labor during acute COVID-19 infection. Standard treatment for preterm labor may allow patients with acute COVID-19 infection to recover without the need for preterm delivery. KEY POINTS: · Acute COVID-19 infection is associated with a high rate of preterm delivery.. · Standard treatment for preterm labor such as intravenous magnesium sulfate, antepartum steroid therapy and antibiotic prophylaxis for group B streptococcus infection were effective in this patient.. · In the absence of maternal or fetal compromise, acute COVID-19 infection is not an indication for early elective delivery..


Subject(s)
Coronavirus Infections , Glucocorticoids/administration & dosage , Magnesium Sulfate/administration & dosage , Pandemics , Pneumonia, Viral , Pregnancy Complications, Infectious , Premature Birth , Antibiotic Prophylaxis/methods , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Humans , Infant, Newborn , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Premature Birth/etiology , Premature Birth/prevention & control , SARS-CoV-2 , Streptococcal Infections/prevention & control , Tocolytic Agents/administration & dosage
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