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).

Full publication of preprint articles in prevention research: an analysis of publication proportions and results consistency.

There is concern that preprint articles will lead to an increase in the amount of scientifically invalid work available. The objectives of this study were to determine the proportion of prevention preprints published within 12 months, the consistency of the effect estimates and conclusions between preprint and published articles, and the reasons for the nonpublication of preprints. Of the 329 prevention preprints that met our eligibility criteria, almost half (48.9%) were published in a peer-reviewed journal within 12 months of being posted. While 16.8% published preprints showed some change in the magnitude of the primary outcome effect estimate, 4.4% were classified as having a major change. The style or wording of the conclusion changed in 42.2%, the content in 3.1%. Preprints on chemoprevention, with a cross-sectional design, and with public and noncommercial funding had the highest probabilities of publication. The main reasons for the nonpublication of preprints were journal rejection or lack of time. The reliability of preprint articles for evidence-based decision-making is questionable. Less than half of the preprint articles on prevention research are published in a peer-reviewed journal within 12 months, and significant changes in effect sizes and/or conclusions are still possible during the peer-review process.

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).

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.

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).

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).

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/.

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.

Effectiveness of interventions for the remediation of lead-contaminated soil to prevent or reduce lead exposure - A systematic review.

OBJECTIVE: To summarize the evidence on the effectiveness of soil remediation to prevent or reduce lead exposure. METHODS: We systematically searched MEDLINE, the Agricultural & Environmental Science Database, Web of Science, and Scopus from 1980 to February 15, 2021. We also performed reference list checking, hand-searched websites, and contacted experts. Eligible studies evaluated the effect of soil remediation to prevent or reduce lead exposure in humans of any age. We screened all records dually; one investigator performed the data extraction; a second checked for completeness and accuracy. Two investigators independently rated the risk of bias of included studies and graded the certainty of evidence. We synthesized findings narratively. RESULTS: We identified 6614 potentially relevant publications, all focused on children, of which five studies (six records) fulfilled our prespecified inclusion criteria. The number of evaluated participants ranged from 31 to 1425, with follow-up periods of 11 months to one year. The primary soil remediation method was the replacement of the upper layer with clean soil. Outcomes were limited to blood lead levels (BLL), dust lead levels, and soil lead levels. The largest study, a controlled before- after study (n = 1425) reported favorable effects of soil remediation compared to no intervention. This finding was consistent with results from two cross-sectional studies and one uncontrolled before-after study. One year post-remediation, the mean reduction in BLL was 2.1 µg/dL (p < 0.0001) greater in the intervention group than in the control group. Two randomized controlled trials with a total of 511 participants showed no statistically significant incremental effect of soil remediation when combined with paint and/or dust abatement. The certainty of evidence for all outcomes was low. CONCLUSION: Soil remediation appears to reduce BLL in children when used as a single intervention. The incremental benefit of soil remediation when part of other interventions is limited.

Point-of-Care Ultrasonography in Patients With Acute Dyspnea: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Dyspnea is a common and often debilitating symptom with a complex diagnostic work-up. PURPOSE: To evaluate the benefits, harms, and diagnostic test accuracy of point-of-care ultrasonography (POCUS) in patients with acute dyspnea. (PROSPERO: CRD42019126419). DATA SOURCES: Searches of multiple electronic databases without language limitations (January 2004 to August 2020) and reference lists of pertinent articles and reviews. STUDY SELECTION: Five randomized controlled trials (RCTs) and 44 prospective cohort-type studies in patients with acute dyspnea evaluated POCUS as a diagnostic tool to determine the underlying cause of dyspnea. Two investigators independently screened the literature for inclusion. DATA EXTRACTION: Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias and determined certainty of evidence. DATA SYNTHESIS: Point-of-care ultrasonography, when added to a standard diagnostic pathway, led to statistically significantly more correct diagnoses in patients with dyspnea than the standard diagnostic pathway alone. In-hospital mortality and length of hospital stay did not differ significantly between patients who did or did not receive POCUS in addition to standard diagnostic tests. Finally, POCUS consistently improved the sensitivities of standard diagnostic pathways to detect congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax; specificities increased in most but not all studies. LIMITATIONS: Most studies assessed diagnostic test accuracy, which has limited utility for clinical decision making. Studies rarely reported on the proportion of indeterminate sonography results, and no evidence is available on adverse health outcomes of false-positive or false-negative POCUS results. CONCLUSION: Point-of-care ultrasonography can improve the correctness of diagnosis in patients with acute dyspnea. PRIMARY FUNDING SOURCE: American College of Physicians.

Household interventions for secondary prevention of domestic lead exposure in children.

BACKGROUND: Lead exposure is a serious health hazard, especially for children. It is associated with physical, cognitive and neurobehavioural impairment in children. There are many potential sources of lead in the environment, therefore trials have tested many household interventions to prevent or reduce lead exposure. This is an update of a previously published review. OBJECTIVES: To assess the effects of household interventions intended to prevent or reduce further lead exposure in children on improvements in cognitive and neurobehavioural development, reductions in blood lead levels and reductions in household dust lead levels. SEARCH METHODS: In March 2020, we updated our searches of CENTRAL, MEDLINE, Embase, 10 other databases and ClinicalTrials.gov. We also searched Google Scholar, checked the reference lists of relevant studies and contacted experts to identify unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of household educational or environmental interventions, or combinations of interventions to prevent lead exposure in children (from birth to 18 years of age), where investigators reported at least one standardised outcome measure. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all eligible studies for inclusion, assessed risk of bias and extracted data. We contacted trialists to obtain missing information. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 17 studies (three new to this update), involving 3282 children: 16 RCTs (involving 3204 children) and one quasi-RCT (involving 78 children). Children in all studies were under six years of age. Fifteen studies took place in urban areas of North America, one in Australia and one in China. Most studies were in areas with low socioeconomic status. Girls and boys were equally represented in those studies reporting this information. The duration of the intervention ranged from three months to 24 months in 15 studies, while two studies performed interventions on a single occasion. Follow-up periods ranged from three months to eight years. Three RCTs were at low risk of bias in all assessed domains. The other 14 studies were at unclear or high risk of bias; for example, we considered two RCTs and one quasi-RCT at high risk of selection bias and six RCTs at high risk of attrition bias. National or international research grants or governments funded 15 studies, while the other two did not report their funding sources. Education interventions versus no intervention None of the included studies in this comparison assessed effects on cognitive or neurobehavioural outcomes, or adverse events. All studies reported data on blood lead level outcomes. Educational interventions showed there was probably no evidence of a difference in reducing blood lead levels (continuous: mean difference (MD) -0.03, 95% confidence interval (CI) -0.13 to 0.07; I² = 0%; 5 studies, 815 participants; moderate-certainty evidence; log-transformed data), or in reducing floor dust levels (MD -0.07, 95% CI -0.37 to 0.24; I² = 0%; 2 studies, 318 participants; moderate-certainty evidence). Environmental interventions versus no intervention Dust control: one study in this comparison reported data on cognitive and neurobehavioural outcomes, and on adverse events in children. The study showed numerically there may be better neurobehavioural outcomes in children of the intervention group. However, differences were small and the CI included both a beneficial and non-beneficial effect of the environmental intervention (e.g. mental development (Bayley Scales of Infant Development-II): MD 0.1, 95% CI -2.1 to 2.4; 1 study, 302 participants; low-certainty evidence). The same study did not observe any adverse events related to the intervention during the eight-year follow-up, but observed two children with adverse events in the control group (1 study, 355 participants; very low-certainty evidence). Meta-analysis also found no evidence of effectiveness on blood lead levels (continuous: MD -0.02, 95% CI -0.09 to 0.06; I² = 0%; 4 studies, 565 participants; moderate-certainty evidence; log-transformed data). We could not pool the data regarding floor dust levels, but studies reported that there may be no evidence of a difference between the groups (very low-certainty evidence). Soil abatement: the two studies assessing this environmental intervention only reported on the outcome of 'blood lead level'. One study showed a small effect on blood lead level reduction, while the other study showed no effect. Therefore, we deem the current evidence insufficient to draw conclusions about the effectiveness of soil abatement (very low-certainty evidence). Combination of educational and environmental interventions versus standard education Studies in this comparison only reported on blood lead levels and dust lead levels. We could not pool the studies in a meta-analysis due to substantial differences between the studies. Since the studies reported inconsistent results, the evidence is currently insufficient to clarify whether a combination of interventions reduces blood lead levels and floor dust levels (very low-certainty evidence). AUTHORS' CONCLUSIONS: Based on available evidence, household educational interventions and environmental interventions (namely dust control measures) show no evidence of a difference in reducing blood lead levels in children as a population health measure. The evidence of the effects of environmental interventions on cognitive and neurobehavioural outcomes and adverse events is uncertain too. Further trials are required to establish the most effective intervention for reducing or even preventing further lead exposure. Key elements of these trials should include strategies to reduce multiple sources of lead exposure simultaneously using empirical dust clearance levels. It is also necessary for trials to be carried out in low- and middle-income countries and in differing socioeconomic groups in high-income countries.

Abbreviated and comprehensive literature searches led to identical or very similar effect estimates: a meta-epidemiological study.

OBJECTIVES: The objective of this study was to assess the agreement of treatment effect estimates from meta-analyses based on abbreviated or comprehensive literature searches. STUDY DESIGN AND SETTING: This was a meta-epidemiological study. We abbreviated 47 comprehensive Cochrane review searches and searched MEDLINE/Embase/CENTRAL alone, in combination, with/without checking references (658 new searches). We compared one meta-analysis from each review with recalculated ones based on abbreviated searches. RESULTS: The 47 original meta-analyses included 444 trials (median 6 per review [interquartile range (IQR) 3-11]) with 360045 participants (median 1,371 per review [IQR 685-8,041]). Depending on the search approach, abbreviated searches led to identical effect estimates in 34-79% of meta-analyses, to different effect estimates with the same direction and level of statistical significance in 15-51%, and to opposite effects (or effects could not be estimated anymore) in 6-13%. The deviation of effect sizes was zero in 50% of the meta-analyses and in 75% not larger than 1.07-fold. Effect estimates of abbreviated searches were not consistently smaller or larger (median ratio of odds ratio 1 [IQR 1-1.01]) but more imprecise (1.02-1.06-fold larger standard errors). CONCLUSION: Abbreviated literature searches often led to identical or very similar effect estimates as comprehensive searches with slightly increased confidence intervals. Relevant deviations may occur.

Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease that has been classified a pandemic by the World Health Organization (WHO). To support WHO with their recommendations on quarantine, we conducted a rapid review on the effectiveness of quarantine during severe coronavirus outbreaks. OBJECTIVES: We conducted a rapid review to assess the effects of quarantine (alone or in combination with other measures) of individuals who had contact with confirmed cases of COVID-19, who travelled from countries with a declared outbreak, or who live in regions with high transmission of the disease. SEARCH METHODS: An information specialist searched PubMed, Ovid MEDLINE, WHO Global Index Medicus, Embase, and CINAHL on 12 February 2020 and updated the search on 12 March 2020. WHO provided records from daily searches in Chinese databases up to 16 March 2020. SELECTION CRITERIA: Cohort studies, case-control-studies, case series, time series, interrupted time series, and mathematical modelling studies that assessed the effect of any type of quarantine to control COVID-19. We also included studies on SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) as indirect evidence for the current coronavirus outbreak. DATA COLLECTION AND ANALYSIS: Two review authors independently screened 30% of records; a single review author screened the remaining 70%. Two review authors screened all potentially relevant full-text publications independently. One review author extracted data and assessed evidence quality with GRADE and a second review author checked the assessment. We rated the certainty of evidence for the four primary outcomes: incidence, onward transmission, mortality, and resource use. MAIN RESULTS: We included 29 studies; 10 modelling studies on COVID-19, four observational studies and 15 modelling studies on SARS and MERS. Because of the diverse methods of measurement and analysis across the outcomes of interest, we could not conduct a meta-analysis and conducted a narrative synthesis. Due to the type of evidence found for this review, GRADE rates the certainty of the evidence as low to very low. Modeling studies consistently reported a benefit of the simulated quarantine measures, for example, quarantine of people exposed to confirmed or suspected cases averted 44% to 81% incident cases and 31% to 63% of deaths compared to no measures based on different scenarios (incident cases: 4 modelling studies on COVID-19, SARS; mortality: 2 modelling studies on COVID-19, SARS, low-certainty evidence). Very low-certainty evidence suggests that the earlier quarantine measures are implemented, the greater the cost savings (2 modelling studies on SARS). Very low-certainty evidence indicated that the effect of quarantine of travellers from a country with a declared outbreak on reducing incidence and deaths was small (2 modelling studies on SARS). When the models combined quarantine with other prevention and control measures, including school closures, travel restrictions and social distancing, the models demonstrated a larger effect on the reduction of new cases, transmissions and deaths than individual measures alone (incident cases: 4 modelling studies on COVID-19; onward transmission: 2 modelling studies on COVID-19; mortality: 2 modelling studies on COVID-19; low-certainty evidence). Studies on SARS and MERS were consistent with findings from the studies on COVID-19. AUTHORS' CONCLUSIONS: Current evidence for COVID-19 is limited to modelling studies that make parameter assumptions based on the current, fragmented knowledge. Findings consistently indicate that quarantine is important in reducing incidence and mortality during the COVID-19 pandemic. Early implementation of quarantine and combining quarantine with other public health measures is important to ensure effectiveness. In order to maintain the best possible balance of measures, decision makers must constantly monitor the outbreak situation and the impact of the measures implemented. Testing in representative samples in different settings could help assess the true prevalence of infection, and would reduce uncertainty of modelling assumptions. This review was commissioned by WHO and supported by Danube-University-Krems.

Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease classified as a pandemic by the World Health Organization (WHO). To support the WHO with their recommendations on quarantine, we conducted a rapid review on the effectiveness of quarantine during severe coronavirus outbreaks. OBJECTIVES: To assess the effects of quarantine (alone or in combination with other measures) of individuals who had contact with confirmed or suspected cases of COVID-19, who travelled from countries with a declared outbreak, or who live in regions with high disease transmission. SEARCH METHODS: An information specialist searched the Cochrane COVID-19 Study Register, and updated the search in PubMed, Ovid MEDLINE, WHO Global Index Medicus, Embase, and CINAHL on 23 June 2020. SELECTION CRITERIA: Cohort studies, case-control studies, time series, interrupted time series, case series, and mathematical modelling studies that assessed the effect of any type of quarantine to control COVID-19. We also included studies on SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) as indirect evidence for the current coronavirus outbreak. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and titles in duplicate. Two review authors then independently screened all potentially relevant full-text publications. One review author extracted data, assessed the risk of bias and assessed the certainty of evidence with GRADE and a second review author checked the assessment. We used three different tools to assess risk of bias, depending on the study design: ROBINS-I for non-randomised studies of interventions, a tool provided by Cochrane Childhood Cancer for non-randomised, non-controlled studies, and recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) for modelling studies. We rated the certainty of evidence for the four primary outcomes: incidence, onward transmission, mortality, and costs. MAIN RESULTS: We included 51 studies; 4 observational studies and 28 modelling studies on COVID-19, one observational and one modelling study on MERS, three observational and 11 modelling studies on SARS, and three modelling studies on SARS and other infectious diseases. Because of the diverse methods of measurement and analysis across the outcomes of interest, we could not conduct a meta-analysis and undertook a narrative synthesis. We judged risk of bias to be moderate for 2/3 non-randomized studies of interventions (NRSIs) and serious for 1/3 NRSI. We rated risk of bias moderate for 4/5 non-controlled cohort studies, and serious for 1/5. We rated modelling studies as having no concerns for 13 studies, moderate concerns for 17 studies and major concerns for 13 studies. Quarantine for individuals who were in contact with a confirmed/suspected COVID-19 case in comparison to no quarantine Modelling studies consistently reported a benefit of the simulated quarantine measures, for example, quarantine of people exposed to confirmed or suspected cases may have averted 44% to 96% of incident cases and 31% to 76% of deaths compared to no measures based on different scenarios (incident cases: 6 modelling studies on COVID-19, 1 on SARS; mortality: 2 modelling studies on COVID-19, 1 on SARS, low-certainty evidence). Studies also indicated that there may be a reduction in the basic reproduction number ranging from 37% to 88% due to the implementation of quarantine (5 modelling studies on COVID-19, low-certainty evidence). Very low-certainty evidence suggests that the earlier quarantine measures are implemented, the greater the cost savings may be (2 modelling studies on SARS). Quarantine in combination with other measures to contain COVID-19 in comparison to other measures without quarantine or no measures When the models combined quarantine with other prevention and control measures, such as school closures, travel restrictions and social distancing, the models demonstrated that there may be a larger effect on the reduction of new cases, transmissions and deaths than measures without quarantine or no interventions (incident cases: 9 modelling studies on COVID-19; onward transmission: 5 modelling studies on COVID-19; mortality: 5 modelling studies on COVID-19, low-certainty evidence). Studies on SARS and MERS were consistent with findings from the studies on COVID-19. Quarantine for individuals travelling from a country with a declared COVID-19 outbreak compared to no quarantine Very low-certainty evidence indicated that the effect of quarantine of travellers from a country with a declared outbreak on reducing incidence and deaths may be small for SARS, but might be larger for COVID-19 (2 observational studies on COVID-19 and 2 observational studies on SARS). AUTHORS' CONCLUSIONS: The current evidence is limited because most studies on COVID-19 are mathematical modelling studies that make different assumptions on important model parameters. Findings consistently indicate that quarantine is important in reducing incidence and mortality during the COVID-19 pandemic, although there is uncertainty over the magnitude of the effect. Early implementation of quarantine and combining quarantine with other public health measures is important to ensure effectiveness. In order to maintain the best possible balance of measures, decision makers must constantly monitor the outbreak and the impact of the measures implemented. This review was originally commissioned by the WHO and supported by Danube-University-Krems. The update was self-initiated by the review authors.

Universal screening for SARS-CoV-2 infection: a rapid review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the novel betacoronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with unspecific symptoms, but about 5% become critically ill with respiratory failure, septic shock and multiple organ failure. An unknown proportion of infected individuals never experience COVID-19 symptoms although they are infectious, that is, they remain asymptomatic. Those who develop the disease, go through a presymptomatic period during which they are infectious. Universal screening for SARS-CoV-2 infections to detect individuals who are infected before they present clinically, could therefore be an important measure to contain the spread of the disease. OBJECTIVES: We conducted a rapid review to assess (1) the effectiveness of universal screening for SARS-CoV-2 infection compared with no screening and (2) the accuracy of universal screening in people who have not presented to clinical care for symptoms of COVID-19. SEARCH METHODS: An information specialist searched Ovid MEDLINE and the Centers for Disease Control (CDC) COVID-19 Research Articles Downloadable Database up to 26 May 2020. We searched Embase.com, the CENTRAL, and the Cochrane Covid-19 Study Register on 14 April 2020. We searched LitCovid to 4 April 2020. The World Health Organization (WHO) provided records from daily searches in Chinese databases and in PubMed up to 15 April 2020. We also searched three model repositories (Covid-Analytics, Models of Infectious Disease Agent Study [MIDAS], and Society for Medical Decision Making) on 8 April 2020. SELECTION CRITERIA: Trials, observational studies, or mathematical modelling studies assessing screening effectiveness or screening accuracy among general populations in which the prevalence of SARS-CoV2 is unknown. DATA COLLECTION AND ANALYSIS: After pilot testing review forms, one review author screened titles and abstracts. Two review authors independently screened the full text of studies and resolved any disagreements by discussion with a third review author. Abstracts excluded by a first review author were dually reviewed by a second review author prior to exclusion. One review author independently extracted data, which was checked by a second review author for completeness and accuracy. Two review authors independently rated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for diagnostic accuracy studies and a modified form designed originally for economic evaluations for modelling studies. We resolved differences by consensus. We synthesized the evidence in narrative and tabular formats. We rated the certainty of evidence for days to outbreak, transmission, cases missed and detected, diagnostic accuracy (i.e. true positives, false positives, true negatives, false negatives) using the GRADE approach. MAIN RESULTS: We included 22 publications. Two modelling studies reported on effectiveness of universal screening. Twenty studies (17 cohort studies and 3 modelling studies) reported on screening test accuracy. Effectiveness of screening We included two modelling studies. One study suggests that symptom screening at travel hubs, such as airports, may slightly slow but not stop the importation of infected cases (assuming 10 or 100 infected travellers per week reduced the delay in a local outbreak to 8 days or 1 day, respectively). We assessed risk of bias as minor or no concerns, and certainty of evidence was low, downgraded for very serious indirectness. The second modelling study provides very low-certainty evidence that screening of healthcare workers in emergency departments using laboratory tests may reduce transmission to patients and other healthcare workers (assuming a transmission constant of 1.2 new infections per 10,000 people, weekly screening reduced infections by 5.1% within 30 days). The certainty of evidence was very low, downgraded for high risk of bias (major concerns) and indirectness. No modelling studies reported on harms of screening. Screening test accuracy All 17 cohort studies compared an index screening strategy to a reference reverse transcriptase polymerase chain reaction (RT-PCR) test. All but one study reported on the accuracy of single point-in-time screening and varied widely in prevalence of SARS-CoV-2, settings, and methods of measurement. We assessed the overall risk of bias as unclear in 16 out of 17 studies, mainly due to limited information on the index test and reference standard. We rated one study as being at high risk of bias due to the inclusion of two separate populations with likely different prevalences. For several screening strategies, the estimates of sensitivity came from small samples. For single point-in-time strategies, for symptom assessment, the sensitivity from 12 cohorts (524 people) ranged from 0.00 to 0.60 (very low-certainty evidence) and the specificity from 12 cohorts (16,165 people) ranged from 0.66 to 1.00 (low-certainty evidence). For screening using direct temperature measurement (3 cohorts, 822 people), international travel history (2 cohorts, 13,080 people), or exposure to known infected people (3 cohorts, 13,205 people) or suspected infected people (2 cohorts, 954 people), sensitivity ranged from 0.00 to 0.23 (very low- to low-certainty evidence) and specificity ranged from 0.90 to 1.00 (low- to moderate-certainty evidence). For symptom assessment plus direct temperature measurement (2 cohorts, 779 people), sensitivity ranged from 0.12 to 0.69 (very low-certainty evidence) and specificity from 0.90 to 1.00 (low-certainty evidence). For rapid PCR test (1 cohort, 21 people), sensitivity was 0.80 (95% confidence interval (CI) 0.44 to 0.96; very low-certainty evidence) and specificity was 0.73 (95% CI 0.39 to 0.94; very low-certainty evidence). One cohort (76 people) reported on repeated screening with symptom assessment and demonstrates a sensitivity of 0.44 (95% CI 0.29 to 0.59; very low-certainty evidence) and specificity of 0.62 (95% CI 0.42 to 0.79; low-certainty evidence). Three modelling studies evaluated the accuracy of screening at airports. The main outcomes measured were cases missed or detected by entry or exit screening, or both, at airports. One study suggests very low sensitivity at 0.30 (95% CI 0.1 to 0.53), missing 70% of infected travellers. Another study described an unrealistic scenario to achieve a 90% detection rate, requiring 0% asymptomatic infections. The final study provides very uncertain evidence due to low methodological quality. AUTHORS' CONCLUSIONS: The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR. Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.

Assessing the accuracy of machine-assisted abstract screening with DistillerAI: a user study.

BACKGROUND: Web applications that employ natural language processing technologies to support systematic reviewers during abstract screening have become more common. The goal of our project was to conduct a case study to explore a screening approach that temporarily replaces a human screener with a semi-automated screening tool. METHODS: We evaluated the accuracy of the approach using DistillerAI as a semi-automated screening tool. A published comparative effectiveness review served as the reference standard. Five teams of professional systematic reviewers screened the same 2472 abstracts in parallel. Each team trained DistillerAI with 300 randomly selected abstracts that the team screened dually. For all remaining abstracts, DistillerAI replaced one human screener and provided predictions about the relevance of records. A single reviewer also screened all remaining abstracts. A second human screener resolved conflicts between the single reviewer and DistillerAI. We compared the decisions of the machine-assisted approach, single-reviewer screening, and screening with DistillerAI alone against the reference standard. RESULTS: The combined sensitivity of the machine-assisted screening approach across the five screening teams was 78% (95% confidence interval [CI], 66 to 90%), and the combined specificity was 95% (95% CI, 92 to 97%). By comparison, the sensitivity of single-reviewer screening was similar (78%; 95% CI, 66 to 89%); however, the sensitivity of DistillerAI alone was substantially worse (14%; 95% CI, 0 to 31%) than that of the machine-assisted screening approach. Specificities for single-reviewer screening and DistillerAI were 94% (95% CI, 91 to 97%) and 98% (95% CI, 97 to 100%), respectively. Machine-assisted screening and single-reviewer screening had similar areas under the curve (0.87 and 0.86, respectively); by contrast, the area under the curve for DistillerAI alone was just slightly better than chance (0.56). The interrater agreement between human screeners and DistillerAI with a prevalence-adjusted kappa was 0.85 (95% CI, 0.84 to 0.86%). CONCLUSIONS: The accuracy of DistillerAI is not yet adequate to replace a human screener temporarily during abstract screening for systematic reviews. Rapid reviews, which do not require detecting the totality of the relevant evidence, may find semi-automation tools to have greater utility than traditional systematic reviews.

A Novel 3q29 Deletion in Association With Developmental Delay and Heart Malformation-Case Report With Literature Review.

3q29 deletion syndrome is a rare disorder, causing a complex phenotype. Clinical features are variable and relatively non-specific. Our report aims to present an atypical, de novo deletion in chromosome band 3q29 in a preschool boy, first child of healthy non-consanguineous parents, presenting a particular phenotype (microcephaly, "full moon" face, flattened facial profile, large ears, auricular polyp, and dental dystrophies), motor and cognitive delay, characteristics of autism spectrum disorder and aggressive behavior. He also presented intrauterine growth restriction (birth weight 2,400 g) and a ventricular septal defect. SNP Array revealed a 962 kb copy number loss, on the chromosome 3q29 band (195519857-196482211), consistent with 3q29 microdeletion syndrome. FISH analysis using a RP11-252K11 probe confirmed the deletion in the proband, which was not present in the parents. Although the patient's deletion is relatively small, it partly overlaps the canonical 3q29 deletion (defined between TFRC and DLG1 gene) and extends upstream, associating a different facial phenotype compared to the classic 3q29 deletion, nonetheless showing a similar psychiatric disorder. This deletion is different from the canonical region, as it does not include the PAK2 and DLG1 genes, considered as candidates for causing intellectual disability. Thus, narrowing the genotype-phenotype correlation for the 3q29 band, FBX045 is suggested as a candidate gene for the neuropsychiatric phenotype.