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BACKGROUND The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear. METHODS We systematically identified randomized controlled trials (RCTs) and realworld studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the [I.sup.2] statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/study quality and conducted trial sequential analysis of the evidence from RCTs. RESULTS We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged [greater than or equal to] 18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID- 19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; [I.sup.2] = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; [I.sup.2] = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; [I.sup.2] = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; [I.sup.2] = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; [I.sup.2] = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; [I.sup.2] = 49.9%; 3 RCTs, 3,806 persons), although trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; [I.sup.2] = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; [I.sup.2] = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment. CONCLUSIONS Nirmatrelvir/ritonavir appears to be promising for preventing hospitalization and potentially decreasing all-cause mortality for persons with mild/moderately severe COVID-19, but the evidence is weak. More studies are needed. Key words: nirmatrelvir/ritonavir; Paxlovid; laboratory-confirmed COVID-19; systematic review; quantitative methods: meta-analysis; trial sequential analysis; efficacy/effectiveness; safety https://doi.org/10.1370/afm.3120, INTRODUCTION The virus responsible for the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains in circulation. It mutates and keeps infecting large proportions of populations, with attributable substantial [...]

Background: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. Methods: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials (Ovid) and ClinicalTrials.gov. Results: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, [I.sup.2] = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, [I.sup.2] = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, [I.sup.2] = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, [I.sup.2] = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, [I.sup.2] = 0%). No antibiotic-related adverse events were reported. Conclusion: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens. Contexte : Un traitement préopératoire par néomycine orale associée à de l'érythromycine ou du métronidazole est recommandé pour réduire le risque d'infection du site opératoire (ISO) lors de la chirurgie colorectale non urgente. Or, la néomycine orale n'est pas disponible sur le marché au Canada et par conséquent, n'est pas utilisée. Les fluoroquinolones sont facilement accessibles et exercent une excellente activité contre les bactéries aérobies à Gram négatif. Le but de cette revue systématique était d'identifier, d'évaluer de façon critique et de résumer les données probantes sur l'efficacité et l'innocuité de l'administration préopératoire de fluoroquinolones orales pour la prévention des ISO chez des adultes soumis à une résection colorectale élective. Méthodes : Conformément aux lignes directrices Cochrane, nous avons inclus les essais randomisés et contrôlés (ERC) de langue anglaise ayant comparé des fluoroquinolones orales en association avec les antibiotiques intraveineux préopératoires habituels et aux antibiotiques intraveineux seuls, recensés dans les bases de données MEDLINE (Ovid), Embase (Ovid), le Registre central Cochrane des essais contrôlés (Ovid) et ClinicalTrials.gov. Résultats : Nous avons inclus 3 ERC (1136 patients). Le risque de biais était incertain pour 2 essais et élevé pour 1 essai. Les fluoroquinolones orales préopératoires ont donné lieu à une diminution significative du nombre total d'ISO (risque relatif [RR] 0,43, intervalle de confiance [IC] de 95 % 0,32-0,7, [I.sup.2] = 0 %), superficielles (RR 0,38, IC de 95 % 0,22-0,68, [I.sup.2] =32 %), profondes (RR 0,19, IC de 95 % 0,06-0,65, [I.sup.2] = 0 %) et des cavités/organes (RR 0,34, IC de 95 % 0,12-0,90, [I.sup.2] = 33 %). On a aussi noté une réduction significative des fuites anastomotiques (RR 0,22, IC de 95 % 0,06-0,87, [I.sup.2] = 0 %). Aucun effet indésirable lié à l'antibiothérapie n'a été signalé. Conclusion : Selon cette revue, les fluoroquinolones orales préopératoires avec antibiothérapie intraveineuse sont supérieures aux antibiotiques intraveineux seuls pour la prévention des ISO après la chirurgie colorectale. En l'absence de néomycine, les fluoroquinolones orales représentent une solution de rechange acceptable. Il faudra procéder à d'autres essais pour mieux comparer l'efficacité relative des différents schémas d'antibiothérapie orale., Colorectal surgical procedures are associated with some of the highest rates of surgical site infections (SSIs) of any intra-abdominal procedures, which are frequently caused by anaerobic bacterial flora and Gram-negative [...]

Background: The literature on fatigue in children and adolescents undergoing cancer treatment is highly variable, creating uncertainties about its prevalence and identifying those at higher risk. Objectives: The primary purpose was to describe the prevalence of fatigue among patients (< 21 years) undergoing cancer treatment across cancer types. Secondary outcomes included the prevalence of severe fatigue and factors associated with fatigue. Methods: Systematic searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO were conducted from inception to May 22, 2023. Two reviewers independently identified relevant citations and extracted data. Pooled prevalence estimates were derived using an inverse variance, random‐effects model. We used Joanna Briggs's critical appraisal checklist to assess study quality. (PROSPERO: CRD42020179307). Results: We included 47 studies: 26 for prevalence and 29 for factors associated with fatigue. The pooled prevalence of fatigue was 73% (95% [Confidence Interval, CI: 66%–79%; I2 96%; 26 studies; 2699 patients], and severe fatigue was 30% [95% CI 14%–46%, I2 98%; 8 studies; 1027 patients]). Subgroup analyses based on cancer type, study design, fatigue scale, fatigue reporting personnel, sample frame, and response rate did not reveal significant differences in fatigue prevalence. Fatigue prevalence significantly differed by treatment setting (inpatient [83%] vs. outpatient [55%] vs. inpatient and outpatient [69%]; p: 0.02). Due to considerable heterogeneity among studies, data on fatigue‐associated factors are presented descriptively. Conclusions: The prevalence of fatigue among children and adolescents undergoing cancer treatment is variable but notably high. Systematic evaluation of factors associated with fatigue is essential to understanding which children are at high risk of developing fatigue. Trial Registration: PROSPERO: CRD42020179307 [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the 95% confidence interval (CI) cutoff for sonographic renal artery stenosis (RAS) parameters. A secondary objective was to determine the diagnostic accuracy parameters of peak systolic velocity (PSV), renal aortic ratio (RAR), acceleration index (AI), and acceleration time (AT) for diagnosing RAS. Materials and Methods: Diagnostic test accuracy (DTA) parameters and 95% CIs were evaluated for the sonographic cutoff values. A total of 31 articles were extracted and subjected to statistical analysis. Results: The mean 95% CI cutoff for PSV, RAR, AI, and AT were 192.50 (175.16, 209.84), 3.10 (2.83, 3.38), 3.39 (2.51, 4.27), and 80.78 (68.56, 93.01), respectively. The pooled mean 95% CI sensitivity of PSV, RAR, AI, and AT were 85.90% (79.84, 91.97), 82.34% (77.58, 87.11), 74.92% (64.53, 85.33), and 73.57% (63.01, 84.13), respectively, whereas the pooled mean specificity of the same parameters was 82.52% (75.78, 89.25), 86.97% (83.12, 90.82), 78.93% (66.34, 91.52), and 82.57% (70.70, 94.44), respectively. Conclusion: The pooled mean 95% CI for sensitivity and specificity of the sonographic parameters was concordant with the literature. Based on this higher level of evidence, except RAR, the mean 95% CI cutoff for PSV, AI, and AT were consistent with the cutoff values encountered in the published literature. [ABSTRACT FROM AUTHOR]

Efficacy of remdesivir for COVID-19 remains unclear. We updated our published systematic review to better inform on the use of remdesivir for COVID-19. We searched for randomized controlled trials (RCTs) among hospitalized COVID-19 patients. Meta-analysis was conducted using an inverse variance, random-effects model, presenting relative risk (RR) or mean difference (MD) and their associated 95% confidence intervals (CIs). Statistical heterogeneity was calculated using the I2 statistic. In addition, we conducted trial sequential analysis (TSA). Outcomes with additional data were clinical progression, hospitalization days, and all-cause mortality. We included nine RCTs (12,876 individuals). Three trials each were of a low, unclear, and a high risk of bias. Compared with no treatment/placebo, remdesivir (100 mg daily, over 10 days) significantly improved clinical progression (RR 1.06, CI 1.02–1.11), but did not significantly reduce hospitalization days (MD −0.48, CI −2.18–1.21) and all-cause mortality (RR 0.92, CI 0.84–1.01). TSA suggested that further information is not required to conclude on the efficacy of remdesivir in improving clinical progression, and that, while more information is required for hospitalization days and all-cause mortality, further RCTs to prove fewer hospitalization days may be futile, as efficacy of remdesivir for this outcome is unlikely. Remdesivir appeared promising for COVID-19, but there is insufficient evidence of its efficacy. High quality RCTs are needed for a stronger evidence base. [ABSTRACT FROM AUTHOR]

Considering the alterations in gait patterns and increase in metabolic demands during walking on an inclined surface, inclined treadmill training (ITT) may be an alternative treatment to non-inclined treadmill training (NITT) for improving gait and balance among people with chronic stroke. We searched eight electronic databases (August 2021), assessed risk of bias (Cochrane RoB 2.0 tool), and meta-analysed data (RevMan 3.5). Results were reported according to the PRISMA guidelines. Outcomes were gait parameters such as walking speed and balance-related outcome measures such as Berg Balance Scale scores. Risk of bias assessment was performed according to Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Of the screened citations, four met our inclusion criteria. Quantitative analysis showed ITT was significant in improving walking speed, stride length, paretic step length, Berg Balance Scale scores and Overall Stability Index (p < 0.05) but not in cadence, non-paretic step length, stance time on the non-paretic and paretic leg (p > 0.05). Only one study was rated low risk of bias. There was limited evidence for the superiority of ITT over NITT, in adjunct to other conventional intervention, for improving gait and balance among chronic stroke patients. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to conduct a systematic review and qualitative evidence synthesis (QES) to identify best practices, benefits, harms, facilitators, and barriers to the routine collection of sociodemographic variables in emergency departments (EDs). Methods: This work is a systematic review and QES. We conducted a comprehensive search of Medline (Ovid), CINAHL (Ebsco), Cochrane Central (OVID), EMBASE (Ovid), and the multidisciplinary Web of Science Core database using peer‐reviewed search strategies, complemented by a gray literature search. We included citations containing perspectives on routine sociodemographic variable collection in EDs and recommendations on definitions or processes of collection or benefits, harms, facilitators, or barriers related to the routine collection of sociodemographic variables in EDs. We conducted this systematic review and QES adhering to the Joanna Briggs Institute guidelines. Two reviewers independently selected included studies and extracted data. We conducted a best‐fit framework synthesis and paired inductive thematic analysis of the included studies. We generated recommendations based on the QES. Results: We included 21 unique reports that enrolled 10,454 patients or respondents in our systematic review and QES. Publication dates of included studies ranged from 2011 to 2021. Included citations were published in Australia, Canada, and the United States. We synthesized 11 benefits, 14 potential harms, 15 barriers, and 19 facilitators and identified 14 best practice recommendations from included citations. Conclusions: Health systems should routinely collect sociodemographic variables in EDs guided by recommendations that minimize harms and maximize benefits and consider relevant barriers and facilitators. Our recommendations can serve as a guide for the equity‐focused reformation of emergency medicine health information systems. [ABSTRACT FROM AUTHOR]