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Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children: A Systematic Review and Network Meta-analysis
IMPORTANCE Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection children younger than 5 years; effective prevention strategies are urgently needed. OBJECTIVE To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children. DATA SOURCES In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022. STUDY SELECTION Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebowere included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched. DATA EXTRACTION AND SYNTHESIS The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework. MAIN OUTCOMES AND MEASURES The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use. RESULTS Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37%[IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, - 58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest. CONCLUSIONS AND RELEVANCE In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.
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Molnupiravir for the treatment of non-severe COVID-19: a systematic review and meta-analysis of 14 randomized trials with 34 570 patients
Background Molnupiravir has been considered a promising candidate for COVID-19. Its efficacy and safety in non-severe COVID-19 patients and the differences between patients with different risk factors need further evaluation. Methods We conducted a systematic review and meta-analysis of randomized controlled trials that allocated adult patients with non-severe COVID-19 to molnupiravir or a control. We used random-effects models, and conducted subgroup analyses and meta-regression for COVID-19 patients with high-risk factors. The GRADE approach was used to rate the certainty of evidence. Results Fourteen trials with 34 570 patients were included. Moderate- to low-certainty evidence showed that molnupiravir was associated with a reduction in the risk of hospitalization (relative risk [RR] = 0.63, 95% CI: 0.47-0.85), risk of mechanical ventilation (RR = 0.37, 95% CI: 0.19-0.72) and time to symptom resolution (mean differences [MD] = -2.91 days, 95% CI: -3.66 to -2.16). However, no significant differences were found in adverse events, all-cause mortality, rate of and time to viral clearance, or duration of hospitalization. For the rate of viral clearance, subgroup effects were found between trials with low and high risk of bias (P = 0.001) and between trials with male or female majority (P < 0.001). For admission to hospital, subgroup effects were also found between trials with & GE;50% and <50% of the participants being female (P = 0.04). Meta-regression showed a significant association between higher trial mean age and elevated risk of hospitalization (P = 0.011), and female majority and elevated risk of hospitalization (P = 0.011). Conclusions Molnupiravir was found to be effective in non-severe COVID-19, but the efficacy varied with age and sex.
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Efficacy and safety of unrestricted visiting policy for critically ill patients: a meta-analysis
Aim To compare the safety and effects of unrestricted visiting policies (UVPs) and restricted visiting policies (RVPs) in intensive care units (ICUs) with respect to outcomes related to delirium, infection, and mortality. Methods MEDLINE, Cochrane Library, Embase, Web of Science, CINAHL, CBMdisc, CNKI, Wanfang, and VIP database records generated from their inception to 22 January 2022 were searched. Randomized controlled trials and quasi-experimental studies were included. The main outcomes investigated were delirium, ICU-acquired infection, ICU mortality, and length of ICU stay. Two reviewers independently screened studies, extracted data, and assessed risks of bias. Random-effects and fixed-effects meta-analyses were conducted to obtain pooled estimates, due to heterogeneity. Meta-analyses were performed using RevMan 5.3 software. The results were analyzed using odds ratios (ORs), 95% confidence intervals (CIs), and standardized mean differences (SMDs). Results Eleven studies including a total of 3741 patients that compared UVPs and RVPs in ICUs were included in the analyses. Random effects modeling indicated that UVPs were associated with a reduced incidence of delirium (OR = 0.4, 95% CI 0.25-0.63, I-2 = 71%, p = 0.0005). Fixed-effects modeling indicated that UVPs did not increase the incidences of ICU-acquired infections, including ventilator-associated pneumonia (OR = 0.96, 95% CI 0.71-1.30, I-2 = 0%, p = 0.49), catheter-associated urinary tract infection (OR 0.97, 95% CI 0.52-1.80, I-2 = 0%, p = 0.55), and catheter-related blood stream infection (OR = 1.15, 95% CI 0.72-1.84, I-2 = 0%, p = 0.66), or ICU mortality (OR = 1.03, 95% CI 0.83-1.28, I-2 = 49%, p = 0.12). Forest plotting indicated that UVPs could reduce the lengths of ICU stays (SMD = - 0.97, 95% CI - 1.61 to 0.32, p = 0.003). Conclusion The current meta-analysis indicates that adopting a UVP may significantly reduce the incidence of delirium in ICU patients, without increasing the risks of ICU-acquired infection or mortality. Further large-scale, multicenter studies are needed to confirm these indications.
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Quality Assessment of Cancer Pain Clinical Practice Guidelines
Introduction: Several clinical practice guidelines (CPGs) for cancer pain have been published; however, the quality of these guidelines has not been evaluated so far. The purpose of this study was to evaluate the quality of CPGs for cancer pain and identify gaps limiting knowledge. Methods: We systematically searched seven databases and 12 websites from their inception to July 20, 2021, to include CPGs related to cancer pain. We used the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist to assess the methodology and reporting quality of eligible CPGs. The overall agreement among reviewers with the intraclass correlation coefficient (ICC) was calculated. The development methods of CPGs, strength of recommendations, and levels of evidence were determined. Results: Eighteen CPGs published from 1996 to 2021 were included. The overall consistency of the reviewers in each domain was acceptable (ICC from 0.76 to 0.95). According to the AGREE II assessment, only four CPGs were determined to be recommended without modifications. For reporting quality, the average reporting rates for all seven domains of CPGs was 57.46%, with the highest domain in domain 3 (evidence, 68.89%) and the lowest domain in domain 5 (review and quality assurance, 33.3%). Conclusion: The methodological quality of cancer pain CPGs fluctuated widely, and the complete reporting rate in some areas is very low. Researchers need to make greater efforts to provide high-quality guidelines in this field to clinical decision-making.
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