IMPORTANCE: Nasopharyngeal swab nucleic acid amplification testing (NAAT) is the noninvasive criterion standard for diagnosis of coronavirus disease 2019 (COVID-19). However, it requires trained ...personnel, limiting its availability. Saliva NAAT represents an attractive alternative, but its diagnostic performance is unclear. OBJECTIVE: To assess the diagnostic accuracy of saliva NAAT for COVID-19. DATA SOURCES: In this systematic review, a search of the MEDLINE and medRxiv databases was conducted on August 29, 2020, to find studies of diagnostic test accuracy. The final meta-analysis was performed on November 17, 2020. STUDY SELECTION: Studies needed to provide enough data to measure salivary NAAT sensitivity and specificity compared with imperfect nasopharyngeal swab NAAT as a reference test. An imperfect reference test does not perfectly reflect the truth (ie, it can give false results). Studies were excluded if the sample contained fewer than 20 participants or was neither random nor consecutive. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the risk of bias. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed for the systematic review, with multiple authors involved at each stage of the review. To account for the imperfect reference test sensitivity, we used a bayesian latent class bivariate model for the meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was pooled sensitivity and specificity. Two secondary analyses were performed: one restricted to peer-reviewed studies, and a post hoc analysis limited to ambulatory settings. RESULTS: The search strategy yielded 385 references, and 16 unique studies were identified for quantitative synthesis. Eight peer-reviewed studies and 8 preprints were included in the meta-analyses (5922 unique patients). There was significant variability in patient selection, study design, and stage of illness at which patients were enrolled. Fifteen studies included ambulatory patients, and 9 exclusively enrolled from an outpatient population with mild or no symptoms. In the primary analysis, the saliva NAAT pooled sensitivity was 83.2% (95% credible interval CrI, 74.7%-91.4%) and the pooled specificity was 99.2% (95% CrI, 98.2%-99.8%). The nasopharyngeal swab NAAT had a sensitivity of 84.8% (95% CrI, 76.8%-92.4%) and a specificity of 98.9% (95% CrI, 97.4%-99.8%). Results were similar in secondary analyses. CONCLUSIONS AND RELEVANCE: These results suggest that saliva NAAT diagnostic accuracy is similar to that of nasopharyngeal swab NAAT, especially in the ambulatory setting. These findings support larger-scale research on the use of saliva NAAT as an alternative to nasopharyngeal swabs.
IMPORTANCE: Clostridium difficile infection (CDI) is associated with significant morbidity, mortality, and a high risk of recurrence. Proton pump inhibitor (PPI) use is associated with an initial ...episode of CDI, and PPIs are frequently overprescribed. For many, the use of PPIs could likely be discontinued before CDI recurrence. OBJECTIVES: To determine whether PPI use was associated with a risk of initial CDI recurrence, to assess what proportion of patients who developed CDI were taking a PPI for a non–evidence-based indication, and to evaluate whether physicians discontinued unnecessary PPIs in the context of CDI. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of incident health care–associated CDI cases to determine the association between continuous PPI use and CDI recurrence within 90 days. The setting was 2 university-affiliated hospitals, the 417-bed Montreal General Hospital (Montreal, Quebec, Canada) and the 517-bed Royal Victoria Hospital (Montreal, Quebec, Canada). The cohort consisted of 754 patients who developed health care–associated CDI between January 1, 2010, and January 30, 2013, and who survived for a minimum of 15 days after their initial episode of nosocomial CDI. EXPOSURE: Continuous PPI use. MAIN OUTCOMES AND MEASURES: Recurrence of CDI within 15 to 90 days of the initial episode. RESULTS: Using a multivariable Cox proportional hazards model, the cause-specific hazard ratios for recurrence were 1.5 (95% CI, 1.1-2.0) for age older than 75 years, 1.5 (95% CI, 1.1-2.0) for continuous PPI use, 1.003 (95% CI, 1.002-1.004) per day for length of stay, and 1.3 (95% CI, 0.9-1.7) for antibiotic reexposure. The use of PPIs was common (60.7%), with only 47.1% of patients having an evidence-based indication. Proton pump inhibitors were discontinued in only 3 patients with CDI. CONCLUSIONS AND RELEVANCE: After adjustment for other independent predictors of recurrence, patients with continuous PPI use remained at elevated risk of CDI recurrence. We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.
IMPORTANCE: Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to ...outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed. OBJECTIVE: To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients. DATA SOURCES: PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022. STUDY SELECTION: Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection. DATA EXTRACTION AND SYNTHESIS: In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. MAIN OUTCOMES AND MEASURES: Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs. RESULTS: Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, −0.17%; 95% CI, −0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.
Nirmatrelvir-ritonavir for COVID-19 McDonald, Emily G; Lee, Todd C
CMAJ. Canadian Medical Association journal,
02/2022, Volume:
194, Issue:
6
Journal Article
Peer reviewed
Open access
McDonald and Lee present several facts about nirmatrelvir-ritonavir. Ritonavir-boosted nirmatrelvir is a Health Canada-approved oral antiviral medication with activity against SARS-CoV-2 Treatment is ...indicated for adult (≥ 18 yr) outpatients with nonhypoxic COVID-19 who are at high risk of severe disease progression.
IMPORTANCE: Health care–associated infections are often caused by multidrug-resistant organisms and substantially factor into hospital costs and avoidable iatrogenic harm. Although it is recommended ...that new facilities be built with single-room, low-acuity beds, this process is costly and evidence of reductions in health care–associated infections is weak. OBJECTIVE: To examine whether single-patient rooms are associated with decreased rates of common multidrug-resistant organism transmissions and health care–associated infections. DESIGN, SETTING, AND PARTICIPANTS: A time-series analysis comparing institution-level rates of new multidrug-resistant organism colonization and health care–associated infections before (January 1, 2013-March 31, 2015) and after (April 1, 2015-March 31, 2018) the move to the hospital with 100% single-patient rooms. In the largest hospital move in Canadian history, inpatients in an older, tertiary care, 417-bed hospital in Montréal, Canada, that consisted of mainly mixed 3- and 4-person ward-type rooms were moved to a new 350-bed facility with all private rooms. EXPOSURES: A synchronized move of all patients on April 26, 2015, to a new hospital with 100% single-patient rooms equipped with individual toilets and showers and easy access to sinks for hand washing. MAIN OUTCOMES AND MEASURES: Rates of nosocomial vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) colonization, VRE and MRSA infection, and Clostridioides difficile (formerly known as Clostridium difficile) infection (CDI) per 10 000 patient-days. RESULTS: Compared with the 27 months before, during the 36 months after the hospital move, an immediate and sustained reduction in nosocomial VRE colonization (from 766 to 209 colonizations; incidence rate ratio IRR, 0.25; 95% CI, 0.19-0.34) and MRSA colonization (from 129 to 112 colonizations; IRR, 0.57; 95% CI, 0.33-0.96) was noted, as well as VRE infection (from 55 to 14 infections; IRR, 0.30, 95% CI, 0.12-0.75). Rates of CDI (from 236 to 223 infections; IRR, 0.95; 95% CI, 0.51-1.76) and MRSA infection (from 27 to 37 infections; IRR, 0.89, 95% CI, 0.34-2.29) did not decrease. CONCLUSION AND RELEVANCE: The move to a new hospital with exclusively single-patient rooms appeared to be associated with a sustained decrease in the rates of new MRSA and VRE colonization and VRE infection; however, the move was not associated with a reduction in CDI or MRSA infection. These findings may have important implications for the role of hospital construction in facilitating infection control.
In this double-blind, randomized trial, 821 asymptomatic persons with a high-risk or moderate-risk exposure to SARS-CoV-2 were assigned to receive hydroxychloroquine or placebo within 4 days after ...the exposure. No benefit in preventing illness compatible with Covid-19 was found.
No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).
To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.
Randomized, ...double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).
Internet-based trial across the United States and Canada (40 states and 3 provinces).
Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.
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.
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.
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;
= 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (
= 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (
< 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 (
= 0.29).
Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.
Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.
Private donors.
The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory ...recommendations for and against use.
To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements.
Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022.
Randomised controlled trials; all languages.
All hospitalized adults with COVID-19.
Remdesivir, in comparison to either placebo, or standard of care.
We used the ROB-2 criteria.
The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important.
We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5–1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79–0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88–1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen.
Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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