Effectiveness and Safety of Measures to Prevent Infections and Other Complications Associated With Peripheral Intravenous Catheters: A Systematic Review and Meta-analysis.

BACKGROUND: Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL, and reference lists for controlled studies from 1 January 1980-16 March 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with 3 or more trials, we conducted Bayesian random-effects meta-analyses. RESULTS: 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for 8 research questions. Based on findings of low to high COE, wearing gloves reduced the risk of overall adverse events related to insertion compared with no gloves (1 non-randomized controlled trial [non-RCT]; adjusted risk ratio [RR], .52; 95% CI, .33-.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR, 0.74, 95% credible interval, .49-1.01) compared with clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared with non-chlorhexidine-containing disinfection (1 RCT; 0.14 vs 0.68; P = .003). No statistically significant differences were found for other measures. CONCLUSIONS: Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications. CLINICAL TRIALS REGISTRATION: The protocol was registered in the Open Science Framework (https://osf.io/exdb4).

Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Evidence Review for the American College of Physicians (Version 2).

BACKGROUND: Clinicians and patients want to know the benefits and harms of outpatient treatment options for the Omicron variant of SARS-CoV-2. PURPOSE: To assess the benefits and harms of 22 different COVID-19 treatments. DATA SOURCES: The Epistemonikos COVID-19 L·OVE platform, the iSearch COVID-19 portfolio, and the World Health Organization (WHO) COVID-19 Research Database from 26 November 2021 to 2 March 2023. STUDY SELECTION: Two reviewers independently screened abstracts and full texts against a priori-defined criteria. DATA EXTRACTION: One reviewer extracted the data and assessed the risk of bias and certainty of evidence (COE). A second reviewer verified the data abstraction and assessments. DATA SYNTHESIS: Two randomized controlled trials and 6 retrospective cohort studies were included. Nirmatrelvir-ritonavir was associated with a reduction in hospitalization due to COVID-19 (for example, 0.7% vs. 1.2%; moderate COE) and all-cause mortality (for example, <0.1% vs. 0.2%; moderate COE). Molnupiravir led to a higher recovery rate (31.8% vs. 22.6%; moderate COE) and reduced time to recovery (9 vs. 15 median days; moderate COE) but had no effect on all-cause mortality (0.02% vs. 0.04%; moderate COE) and the incidence of serious adverse events (0.4% vs. 0.3%; moderate COE). Ivermectin had no effect on time to recovery (moderate COE) and resulted in no difference in adverse events compared with placebo (low COE). Sotrovimab resulted in no difference in all-cause mortality compared with no treatment (low COE). No eligible studies for all other treatments of interest were identified. LIMITATION: Evidence for nirmatrelvir-ritonavir and sotrovimab is based on nonrandomized studies only. CONCLUSION: Nirmatrelvir-ritonavir and molnupiravir probably improve outcomes for outpatients with mild to moderate COVID-19. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42023406456).

The importance of additional intracranial injuries in epidural hematomas: detailed clinical analysis, long-term outcome, and literature review in surgically managed epidural hematomas.

Objective: Epidural hematomas (EDH) occur in up to 8.2% of all traumatic brain injury patients, with more than half needing surgical treatment. In most patients suffering from this perilous disease, good recovery with an excellent clinical course is possible. However, the clinical course is mainly dependent on the presence of additional intracerebral injuries. Few studies comparing isolated and combined EDH in detail exist. Methods: We performed a retrospective single-center study from April 2002 to December 2014. The mean follow-up time was more than 6 years. In addition to analyzing diverse clinicoradiological data, we performed a systematic literature review dealing with a detailed comparison of patients with (combined) and without (isolated) additional intracerebral injuries. Results: We included 72 patients in the study. With increasing age, combined EDH had a higher incidence than isolated EDH. The mortality rate of the patients in the cohort was 10%, of which 0% had isolated EDH and 10% had combined EDH. Good recovery was achieved in 69% of patients, of which 91% had isolated EDH and 50% had combined EDH. A subgroup analysis of the different additional intracerebral injuries in combined EDH demonstrated no significant difference in outcome. A systematic literature review only identified six studies. Patients with isolated EDH had a statistically significantly lower mortality risk [relative risk (RR): 0.22; 95% CI: 0.12-0.39] and a statistically significantly lower risk of unfavorable Glasgow outcome scale score (RR: 0.21; 95% CI: 0.14-0.31) than patients with combined EDH. Conclusions: An excellent outcome in patients with surgically treated isolated EDH is possible. Furthermore, patients with combined EDH or isolated EDH with a low Glasgow coma scale (GCS) score may have favorable outcomes in 50% of the cases. Therefore, every possible effort for treatment should be made for this potentially lethal injury.

Evaluation of the interim Cochrane rapid review methods guidance-A mixed-methods study on the understanding of and adherence to the guidance.

The Cochrane Rapid Review Methods Group (RRMG) first released interim guidance in March 2020 to support authors in conducting rapid reviews (RRs). The objective of this mixed-methods study was to assess the adherence and investigate authors' understanding of the RRMG guidance. We identified all documents citing the Interim Cochrane RRMG guidance up to February 17, 2022 and performed an exploratory adherence analysis. We interviewed 20 RR authors to assess the recommendations' comprehensibility and reasons for any deviations. Further, we surveyed nine authors of COVID-19-related Cochrane reviews for their reasons for not conducting a RR. We analyzed 128 RRs (111 non-Cochrane, 17 Cochrane) that cited the RRMG guidance. Several recommendations were not followed by a large proportion of RR authors such as stepwise approach to study design inclusion or peer review of search strategies, whereas others were exceeded, for example, dual independent screening of abstracts/full texts. The most reported reasons for deviating from the guidance were time constraints, unclarities in the recommended approach, or inapplicability to the specific RR. Overall, the guidance was viewed as user-friendly; however, without pre-existing knowledge of systematic review (SR) conduct, the application was perceived as difficult. The main reasons for conducting a full SR over a RR were late availability of the guidance, preset mandate to conduct a SR, uncertainty regarding methodological distinctions between SR and RR, and inapplicability to the evidence base. Clarifications are warranted throughout the Interim Cochrane RRMG guidance to ensure that users with various experience levels can understand and apply its recommendations accordingly.

Rapid reviews methods series: Guidance on literature search.

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RR) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. In this paper, we address considerations for RR searches. We cover the main areas relevant to the search process: preparation and planning, information sources and search methods, search strategy development, quality assurance, reporting, and record management. Two options exist for abbreviating the search process: (1) reducing time spent on conducting searches and (2) reducing the size of the search result. Because screening search results is usually more resource-intensive than conducting the search, we suggest investing time upfront in planning and optimising the search to save time by reducing the literature screening workload. To achieve this goal, RR teams should work with an information specialist. They should select a small number of relevant information sources (eg, databases) and use search methods that are highly likely to identify relevant literature for their topic. Database search strategies should aim to optimise both precision and sensitivity, and quality assurance measures (peer review and validation of search strategies) should be applied to minimise errors.

Mammography in combination with breast ultrasonography versus mammography for breast cancer screening in women at average risk.

BACKGROUND: Screening mammography can detect breast cancer at an early stage. Supporters of adding ultrasonography to the screening regimen consider it a safe and inexpensive approach to reduce false-negative rates during screening. However, those opposed to it argue that performing supplemental ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments. OBJECTIVES: To assess the comparative effectiveness and safety of mammography in combination with breast ultrasonography versus mammography alone for breast cancer screening for women at average risk of breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov up until 3 May 2021. SELECTION CRITERIA: For efficacy and harms, we considered randomised controlled trials (RCTs) and controlled non-randomised studies enrolling at least 500 women at average risk for breast cancer between the ages of 40 and 75. We also included studies where 80% of the population met our age and breast cancer risk inclusion criteria. DATA COLLECTION AND ANALYSIS: Two review authors screened abstracts and full texts, assessed risk of bias, and applied the GRADE approach. We calculated the risk ratio (RR) with 95% confidence intervals (CI) based on available event rates. We conducted a random-effects meta-analysis. MAIN RESULTS: We included eight studies: one RCT, two prospective cohort studies, and five retrospective cohort studies, enrolling 209,207 women with a follow-up duration from one to three years. The proportion of women with dense breasts ranged from 48% to 100%. Five studies used digital mammography; one study used breast tomosynthesis; and two studies used automated breast ultrasonography (ABUS) in addition to mammography screening. One study used digital mammography alone or in combination with breast tomosynthesis and ABUS or handheld ultrasonography. Six of the eight studies evaluated the rate of cancer cases detected after one screening round, whilst two studies screened women once, twice, or more. None of the studies assessed whether mammography screening in combination with ultrasonography led to lower mortality from breast cancer or all-cause mortality. High certainty evidence from one trial showed that screening with a combination of mammography and ultrasonography detects more breast cancer than mammography alone. The J-START (Japan Strategic Anti-cancer Randomised Trial), enrolling 72,717 asymptomatic women, had a low risk of bias and found that two additional breast cancers per 1000 women were detected over two years with one additional ultrasonography than with mammography alone (5 versus 3 per 1000; RR 1.54, 95% CI 1.22 to 1.94). Low certainty evidence showed that the percentage of invasive tumours was similar, with no statistically significant difference between the two groups (69.6% (128 of 184) versus 73.5% (86 of 117); RR 0.95, 95% CI 0.82 to 1.09). However, positive lymph node status was detected less frequently in women with invasive cancer who underwent mammography screening in combination with ultrasonography than in women who underwent mammography alone (18% (23 of 128) versus 34% (29 of 86); RR 0.53, 95% CI 0.33 to 0.86; moderate certainty evidence). Further, interval carcinomas occurred less frequently in the group screened by mammography and ultrasonography compared with mammography alone (5 versus 10 in 10,000 women; RR 0.50, 95% CI 0.29 to 0.89; 72,717 participants; high certainty evidence). False-negative results were less common when ultrasonography was used in addition to mammography than with mammography alone: 9% (18 of 202) versus 23% (35 of 152; RR 0.39, 95% CI 0.23 to 0.66; moderate certainty evidence). However, the number of false-positive results and necessary biopsies were higher in the group with additional ultrasonography screening. Amongst 1000 women who do not have cancer, 37 more received a false-positive result when they participated in screening with a combination of mammography and ultrasonography than with mammography alone (RR 1.43, 95% CI 1.37 to 1.50; high certainty evidence). Compared to mammography alone, for every 1000 women participating in screening with a combination of mammography and ultrasonography, 27 more women will have a biopsy (RR 2.49, 95% CI 2.28 to 2.72; high certainty evidence). Results from cohort studies with methodological limitations confirmed these findings. A secondary analysis of the J-START provided results from 19,213 women with dense and non-dense breasts. In women with dense breasts, the combination of mammography and ultrasonography detected three more cancer cases (0 fewer to 7 more) per 1000 women screened than mammography alone (RR 1.65, 95% CI 1.0 to 2.72; 11,390 participants; high certainty evidence). A meta-analysis of three cohort studies with data from 50,327 women with dense breasts supported this finding, showing that mammography and ultrasonography combined led to statistically significantly more diagnosed cancer cases compared to mammography alone (RR 1.78, 95% CI 1.23 to 2.56; 50,327 participants; moderate certainty evidence). For women with non-dense breasts, the secondary analysis of the J-START study demonstrated that more cancer cases were detected when adding ultrasound to mammography screening compared to mammography alone (RR 1.93, 95% CI 1.01 to 3.68; 7823 participants; moderate certainty evidence), whilst two cohort studies with data from 40,636 women found no statistically significant difference between the two screening methods (RR 1.13, 95% CI 0.85 to 1.49; low certainty evidence). AUTHORS' CONCLUSIONS: Based on one study in women at average risk of breast cancer, ultrasonography in addition to mammography leads to more screening-detected breast cancer cases. For women with dense breasts, cohort studies more in line with real-life clinical practice confirmed this finding, whilst cohort studies for women with non-dense breasts showed no statistically significant difference between the two screening interventions. However, the number of false-positive results and biopsy rates were higher in women receiving additional ultrasonography for breast cancer screening. None of the included studies analysed whether the higher number of screen-detected cancers in the intervention group resulted in a lower mortality rate compared to mammography alone. Randomised controlled trials or prospective cohort studies with a longer observation period are needed to assess the effects of the two screening interventions on morbidity and mortality.

The effectiveness of interventions to prevent loneliness and social isolation in the community-dwelling and old population: an overview of systematic reviews and meta-analysis.

BACKGROUND: Loneliness and social isolation have comparable health effects to widely acknowledged and established risk factors. Although old people are particularly affected, the effectiveness of interventions to prevent and/or mitigate social isolation and loneliness in the community-dwelling older adults is unclear. The aim of this review of reviews was to pool the findings of systematic reviews (SRs) addressing the question of effectiveness. METHODS: Ovid MEDLINE®, Health Evidence, Epistemonikos and Global Health (EBSCO) were searched from January 2017 to November 2021. Two reviewers independently assessed each SR in two consecutive steps based on previously defined eligibility criteria and appraised the methodological quality using a measurement tool to assess SRs 2, AMSTAR 2. One author extracted data from both SRs and eligible studies; another checked this. We conducted meta-analyses to pool the study results. We report the results of the random-effects and common-effect models. RESULTS: We identified five SRs containing a total of 30 eligible studies, 16 with a low or moderate risk of bias. Our random-effects meta-analysis indicates an overall SMD effect of 0.63 [95% confidence interval (CI): -0.10 to 1.36] for loneliness and was unable to detect an overall effect of the interventions on social support [SMD: 0.00; 95% CI: -0.11 to 0.12]. DISCUSSION: The results show interventions can potentially reduce loneliness in the non-institutionalized, community-dwelling and older population living at home. As confidence in the evidence is low, rigorous evaluation is recommended. REGISTRATION: International Prospective Register of SRs (PROSPERO): Registration number: CRD42021255625.

A Systematic Review and Meta-Analysis on the Efficacy of Locally Delivered Adjunctive Curcumin (Curcuma longa L.) in the Treatment of Periodontitis.

This meta-analysis intended to assess evidence on the efficacy of locally delivered curcumin/turmeric as an adjunctive to scaling and root planing (SRP), on clinical attachment level (CAL) and probing pocket depth (PPD), compared to SRP alone or in combination with chlorhexidine (CHX). RCTs were identified from PubMed, Cochrane Library, BASE, LIVIVO, Dentistry Oral Sciences Source, MEDLINE Complete, Scopus, ClinicalTrials.gov, and eLibrary, until August 2022. The risk of bias (RoB) was assessed with the Cochrane Risk of Bias tool 2.0. A random-effects meta-analysis was performed by pooling mean differences with 95% confidence intervals. Out of 827 references yielded by the search, 23 trials meeting the eligibility criteria were included. The meta-analysis revealed that SRP and curcumin/turmeric application were statistically significantly different compared to SRP alone for CAL (-0.33 mm; p = 0.03; 95% CI -0.54 to -0.11; I2 = 62.3%), and for PPD (-0.47 mm; p = 0.024; 95% CI -0.88 to -0.06; I2 = 95.5%); however, this difference was considered clinically meaningless. No significant differences were obtained between patients treated with SRP and CHX, compared to SRP and curcumin/turmeric. The RoB assessment revealed numerous inaccuracies, thus raising concerns about previous overestimates of potential treatment effects.

Cost-Effectiveness of First- and Second-Step Treatment Strategies for Major Depressive Disorder : A Rapid Review.

BACKGROUND: Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect. PURPOSE: To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD. DATA SOURCES: Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022). STUDY SELECTION: Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria. DATA EXTRACTION: Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility. DATA SYNTHESIS: Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions. LIMITATIONS: Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available. CONCLUSION: Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions. PRIMARY FUNDING SOURCE: American College of Physicians.

Values and Preferences of Patients With Depressive Disorders Regarding Pharmacologic and Nonpharmacologic Treatments : A Rapid Review.

BACKGROUND: Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorder. PURPOSE: To assess patient values and preferences regarding pharmacologic and nonpharmacologic treatments of depressive disorder. DATA SOURCES: MEDLINE (Ovid) and PsycINFO (EBSCO) were searched for eligible studies published from 1 January 2014 to 30 November 2022. STUDY SELECTION: Pairs of reviewers independently screened 30% of search results. The remaining 70% of the abstracts were screened by single reviewers; excluded abstracts were checked by a second reviewer. Pairs of reviewers independently screened full texts. DATA EXTRACTION: One reviewer extracted data and assessed the certainty of evidence, and a second reviewer checked for completeness and accuracy. Two reviewers independently assessed risk of bias. DATA SYNTHESIS: The review included 11 studies: 4 randomized controlled trials, 5 cross-sectional studies, and 2 qualitative studies. In 1 randomized controlled trial, participants reported at the start of therapy that they expected supportive-expressive psychotherapy and antidepressants to yield similar improvements. A cross-sectional study reported that non-Hispanic White participants and men generally preferred antidepressants over talk therapy, whereas Hispanic and non-Hispanic Black participants and women generally did not have a preference. Another cross-sectional study reported that the most important nonserious adverse events for patients treated with antidepressants were insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction. For other comparisons and outcomes, no conclusions could be drawn because of the insufficient certainty of evidence. LIMITATIONS: The main limitation of this review is the low or insufficient certainty of evidence for most outcomes. No evidence was available on second-step depression treatment or differences in values and preferences based on gender, race/ethnicity, age, and depression severity. CONCLUSION: Low-certainty evidence suggests that there may be some differences in preferences for talk therapy or pharmacologic treatment of depressive disorders based on gender or race/ethnicity. In addition, low-certainty evidence suggests that insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction may be the most important nonserious adverse events for patients treated with antidepressants. Evidence is lacking or insufficient to draw any further conclusions about patients' weighing or valuation of the benefits and harms of depression treatments. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42020212442).

Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). PURPOSE: To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. DATA SOURCES: English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. STUDY SELECTION: 2 investigators independently selected randomized trials of at least 6 weeks' duration. DATA EXTRACTION: Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. DATA SYNTHESIS: 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. LIMITATIONS: Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. CONCLUSION: Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42020204703).

Update alert: nonpharmacologic and pharmacologic treatments of adult patients with major depressive disorder: a systematic review and network meta-analysis for a clinical guideline by the American College of Physicians

This first update alert reports the surveillance results of the living systematic review on "Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians" (1), which informed the American College of Physicians living clinical guideline (2).

Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians.

BACKGROUND: Clinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection. PURPOSE: To assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting. DATA SOURCES: Epistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022. STUDY SELECTION: Two reviewers independently screened abstracts and full texts against a priori-defined criteria. Randomized controlled trials (RCTs) that compared COVID-19 treatments in adult outpatients with confirmed SARS-CoV-2 infection were included. DATA EXTRACTION: One reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments. DATA SYNTHESIS: The 26 included studies collected data before the emergence of the Omicron variant. Nirmatrelvir-ritonavir and casirivimab-imdevimab probably reduced hospitalizations (1% vs. 6% [1 RCT] and 1% vs. 4% [1 RCT], respectively; moderate COE). Nirmatrelvir-ritonavir probably reduced all-cause mortality (0% vs. 1% [1 RCT]; moderate COE), and regdanvimab probably improved recovery (87% vs. 72% [1 RCT]; moderate COE). Casirivimab-imdevimab reduced time to recovery by a median difference of 4 days (10 vs. 14 median days [1 RCT]; high COE). Molnupiravir may reduce all-cause mortality, sotrovimab may reduce hospitalization, and remdesivir may improve recovery (low COE). Lopinavir-ritonavir and azithromycin may have increased harms, and hydroxychloroquine may result in lower recovery rates (low COE). Other treatments had insufficient evidence or no statistical difference in efficacy and safety versus placebo. LIMITATION: Many outcomes had few events and small samples. CONCLUSION: Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42022323440).

Risk of Contrast-Associated Acute Kidney Injury in Patients Undergoing Peripheral Angiography with Carbon Dioxide Compared to Iodine-Containing Contrast Agents: A Systematic Review and Meta-Analysis.

The aim of this systematic review was to summarise the comparative evidence on the risk of contrast-associated acute kidney injury (CA-AKI) with CO2 or iodinated contrast medium (ICM) for peripheral vascular interventions. We searched Ovid MEDLINE, Cochrane Library, Embase, Epistemonikos, PubMed-similar-articles, clinical trial registries, journal websites, and reference lists up to February 2022. We included studies comparing the risk of CA-AKI in patients who received CO2 or ICM for peripheral angiography with or without endovascular intervention. Two reviewers screened the references and assessed the risk of bias of the included studies. We extracted data on study population, interventions and outcomes. For the risk of CA-AKI as our primary outcome of interest, we calculated risk ratios (RRs) with a 95% confidence interval (CI) and performed random-effects meta-analyses. We identified three RCTs and five cohort studies that fully met our eligibility criteria. Based on a random-effects meta-analysis, the risk of CA-AKI was lower with CO2 compared to ICM (8.6% vs. 15.2%; RR, 0.59; 95% CI 0.33-1.04). Only limited results from a few studies were available on procedure and fluoroscopy time, radiation dose and CO2-related adverse events. The evidence suggests that the use of CO2 for peripheral vascular interventions reduces the risk of CA-AKI compared to ICM. However, due to the relevant residual risk of CA-AKI with the use of CO2, other AKI risk factors must be considered in patients undergoing peripheral vascular interventions.

Characteristics and recovery methods of studies falsely excluded during literature screening-a systematic review.

BACKGROUND: Due to the growing need to provide evidence syntheses under time constraints, researchers have begun focusing on the exploration of rapid review methods, which often employ single-reviewer literature screening. However, single-reviewer screening misses, on average, 13% of relevant studies, compared to 3% with dual-reviewer screening. Little guidance exists regarding methods to recover studies falsely excluded during literature screening. Likewise, it is unclear whether specific study characteristics can predict an increased risk of false exclusion. This systematic review aimed to identify supplementary search methods that can be used to recover studies falsely excluded during literature screening. Moreover, it strove to identify study-level predictors that indicate an elevated risk of false exclusions of studies during literature screening. METHODS: We performed literature searches for eligible studies in MEDLINE, Science Citation Index Expanded, Social Sciences Citation Index, Current Contents Connect, Embase, Epistemonikos.org, and Information Science & Technology Abstracts from 1999 to June 23, 2020. We searched for gray literature, checked reference lists, and conducted hand searches in two relevant journals and similar article searches current to January 28, 2021. Two investigators independently screened the literature; one investigator performed the data extraction, and a second investigator checked for correctness and completeness. Two reviewers assessed the risk of bias of eligible studies. We synthesized the results narratively. RESULTS: Three method studies, two with a case-study design and one with a case-series design, met the inclusion criteria. One study reported that all falsely excluded publications (8%) could be recovered through reference list checking compared to other supplementary search methods. No included methods study analyzed the impact of recovered studies on conclusions or meta-analyses. Two studies reported that up to 8% of studies were falsely excluded due to uninformative titles and abstracts, and one study showed that 11% of non-English studies were falsely excluded. CONCLUSIONS: Due to the limited evidence based on two case studies and one case series, we can draw no firm conclusion about the most reliable and most valid method to recover studies falsely excluded during literature screening or about the characteristics that might predict a higher risk of false exclusion. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/v2pjr/.

Searching two or more databases decreased the risk of missing relevant studies: a metaresearch study.

BACKGROUND AND OBJECTIVES: Assessing changes in coverage, recall, review, conclusions and references not found when searching fewer databases. METHODS: In randomly selected 60 Cochrane reviews, we checked included study publications' coverage (indexation) and recall (findability) using different search approaches with MEDLINE, Embase, and CENTRAL and related them to authors' conclusions and certainty. We assessed characteristics of unfound references. RESULTS: Overall 1989/2080 included references, were indexed in ≥1 database (coverage = 96%). In reviews where using one of our search approaches would not change conclusions and certainty (n = 44-54), median coverage and recall were highest (range 87.9%-100.0% and 78.2%-93.3%, respectively). Here, searching ≥2 databases reached >95% coverage and ≥87.9% recall. In reviews with unchanged conclusions but less certainty (n = 2-8): 63.3%-79.3% coverage and 45.0%-75.0% recall. In reviews with opposite conclusions (n = 1-3): 63.3%-96.6% and 52.1%-78.7%. In reviews where a conclusion was no longer possible (n = 3-7): 60.6%-86.0% and 20.0%-53.8%. The 265 references that were indexed but unfound were more often abstractless (30% vs. 11%) and older (28% vs. 17% published before 1991) than found references. CONCLUSION: Searching ≥2 databases improves coverage and recall and decreases the risk of missing eligible studies. If researchers suspect that relevant articles are difficult to find, supplementary search methods should be used.

Assessing the magnitude of reporting bias in trials of homeopathy: a cross-sectional study and meta-analysis.

OBJECTIVES: To assess the magnitude of reporting bias in trials assessing homeopathic treatments and its impact on evidence syntheses. DESIGN: A cross-sectional study and meta-analysis. Two persons independently searched Clinicaltrials.gov, the EU Clinical Trials Register and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials. To determine whether registered trials were published and to detect published but unregistered trials, two persons independently searched PubMed, Allied and Complementary Medicine Database, Embase and Google Scholar up to April 2021. For meta-analyses, we used random effects models to determine the impact of unregistered studies on meta-analytic results. MAIN OUTCOMES AND MEASURES: We report the proportion of registered but unpublished trials and the proportion of published but unregistered trials. We also assessed whether primary outcomes were consistent between registration and publication. For meta-analyses, we used standardised mean differences (SMDs). RESULTS: Since 2002, almost 38% of registered homeopathy trials have remained unpublished, and 50% of published randomised controlled trials (RCTs) have not been registered. Retrospective registration was more common than prospective registration. Furthermore, 25% of primary outcomes were altered or changed compared with the registry. Although we could detect a statistically significant trend toward an increase of registrations of homeopathy trials (p=0.001), almost 30% of RCTs published during the past 5 years had not been registered.A meta-analysis stratified by registration status of RCTs revealed substantially larger treatment effects of unregistered RCTs (SMD: -0.53, 95% CI -0.87 to -0.20) than registered RCTs (SMD: -0.14, 95% CI -0.35 to 0.07). CONCLUSIONS: Registration of published trials was infrequent, many registered trials were not published and primary outcomes were often altered or changed. This likely affects the validity of the body of evidence of homeopathic literature and may overestimate the true treatment effect of homeopathic remedies.