Search

We developed guidance to inform decisions regarding the inclusion of nonrandomized studies of interventions (NRSIs) in systematic reviews (SRs) of the effects of interventions.The guidance workgroup comprised SR experts and used an informal consensus generation method.Instead of recommending NRSI inclusion only if randomized controlled trials (RCTs) are insufficient to address the SR key question, different topics may require different decisions regarding NRSI inclusion. We identified important considerations to inform such decisions from topic refinement through protocol development. During topic scoping and refinement, considerations were related to the clinical decisional dilemma, adequacy of RCTs to address the key questions, risk of bias in NRSIs, and the extent to which NRSIs are likely to complement RCTs. When NRSIs are included, during SR team formation, familiarity with topic-specific data sources and advanced analytic methods for NRSIs should be considered. During protocol development, the decision regarding NRSI inclusion or exclusion should be justified, and potential implications explained. When NRSIs are included, the protocol should describe the processes for synthesizing evidence from RCTs and NRSIs and determining the overall strength of evidence.We identified specific considerations for decisions regarding NRSI inclusion in SRs and highlight the importance of flexibility and transparency.

We compared the effectiveness of audio care to usual care for managing mental health and substance use disorders.

Background Borderline personality disorder (BPD) is a debilitating psychiatric disorder that affects 0.4–3.9% of the population in Western countries. Currently, no medications have been approved by regulatory agencies for the treatment of BPD. Nevertheless, up to 96% of patients with BPD receive at least one psychotropic medication. Objectives The objective of this systematic review was to assess the general efficacy and the comparative effectiveness of different pharmacological treatments for BPD patients. Methods We conducted systematic literature searches limited to English language in MEDLINE, EMBASE, the Cochrane Library, and PsycINFO up to April 6, 2021, and searched reference lists of pertinent articles and reviews. Inclusion criteria were (i) patients 13 years or older with a diagnosis of BPD, (ii) treatment with anticonvulsive medications, antidepressants, antipsychotic medications, benzodiazepines, melatonin, opioid agonists or antagonists, or sedative or hypnotic medications for at least 8 weeks, (iii) comparison with placebo or an eligible medication, (iv) assessment of health-relevant outcomes, (v) randomized or non-randomized trials or controlled observational studies. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. For meta-analyses, we used restricted maximum likelihood random effects models to estimate pooled effects. Results Of 12,062 unique records, we included 21 randomized controlled trials (RCTs) with data on 1768 participants. Nineteen RCTs compared pharmacotherapies with placebo; two RCTs assessed active treatments head-to-head. Out of 87 medications in use in clinical practice, we found studies on just nine. Overall, the evidence indicates that the efficacy of pharmacotherapies for the treatment of BPD is limited. Second-generation antipsychotics, anticonvulsants, and antidepressants were not able to consistently reduce the severity of BPD. Low-certainty evidence indicates that anticonvulsants can improve specific symptoms associated with BPD such as anger, aggression, and affective lability but the evidence is mostly limited to single studies. Second-generation antipsychotics had little effect on the severity of specific BPD symptoms, but they improved general psychiatric symptoms in patients with BPD. Conclusions Despite the common use of pharmacotherapies for patients with BPD, the available evidence does not support the efficacy of pharmacotherapies alone to reduce the severity of BPD. Registration PROSPERO registration number, CRD42020194098. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00855-4.

ImportanceAnxiety in children and adolescents is associated with impaired functioning, educational underachievement, and future mental health conditions.ObjectiveTo review the evidence on screening for anxiety in children and adolescents to inform the US Preventive Services Task Force.Data SourcesPubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022.Study SelectionEnglish-language, randomized clinical trials (RCTs) of screening; diagnostic test accuracy studies; RCTs of cognitive behavioral therapy (CBT) or US Food and Drug Administration–approved pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms.Data Extraction and SynthesisTwo reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.Main Outcomes and MeasuresTest accuracy, symptoms, response, remission, loss of diagnosis, all-cause mortality, functioning, suicide-related symptoms or events, adverse events.ResultsThirty-nine studies (N = 6065) were included. No study reported on the direct benefits or harms of screening on health outcomes. Ten studies (n = 3260) reported the sensitivity of screening instruments, ranging from 0.34 to 1.00, with specificity ranging from 0.47 to 0.99. Twenty-nine RCTs (n = 2805) reported on treatment: 22 on CBT, 6 on pharmacotherapy, and 1 on CBT, sertraline, and CBT plus sertraline. CBT was associated with gains on several pooled measures of symptom improvement (magnitude of change varied by outcome measure), response (pooled relative risk [RR], 1.89 [95% CI, 1.17 to 3.05]; n = 606; 6 studies), remission (RR, 2.68 [95% CI, 1.48 to 4.88]; n = 321; 4 studies), and loss of diagnosis (RR range, 3.02-3.09) when compared with usual care or wait-list controls. The evidence on functioning for CBT was mixed. Pharmacotherapy, when compared with placebo, was associated with gains on 2 pooled measures of symptom improvement—mean difference (Pediatric Anxiety Rating Scale mean difference, −4.0 [95% CI, −5.5 to −2.5]; n = 726; 5 studies; and Clinical Global Impression–Severity scale mean difference, −0.84 [95% CI, −1.13 to −0.55]; n = 550; 4 studies) and response (RR, 2.11 [95% CI, 1.58 to 2.98]; n = 370; 5 studies)—but was mixed on measures of functioning. Eleven RCTs (n = 1293) reported harms of anxiety treatments. Suicide-related harms were rare, and the differences were not statistically significantly different.Conclusions and RelevanceIndirect evidence suggested that some screening instruments were reasonably accurate. CBT and pharmacotherapy were associated with benefits; no statistically significant association with harms was reported.

Introduction: Nonrandomized studies of interventions (NRSIs) are observational or experimental studies of the effectiveness and/or harms of interventions, in which participants are not randomized to intervention groups. There is increasingly widespread recognition that advancements in the design and analysis of NRSIs allow NRSI evidence to have a much more prominent role in decision making, and not just as ancillary evidence to randomized controlled trials (RCTs). Objective: To guide decisions about inclusion of NRSIs for addressing the effects of interventions in systematic reviews (SRs), this chapter updates the 2010 guidance on inclusion of NRSIs in Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) SRs. The chapter focuses on considerations for decisions to include or exclude NRSIs in SRs. Methods: In November 2020, AHRQ convened a 20-member workgroup that comprised 13 members representing 8 of 9 AHRQ-appointed EPCs, 3 AHRQ representatives, 1 independent consultant with expertise in SRs, and 3 representatives of the AHRQ-appointed Scientific Resource Center. The workgroup received input from the full EPC Program regarding the process and specific issues through discussions at a virtual meeting and two online surveys regarding challenges with NRSI inclusion in SRs. One survey focused on current practices by EPCs regarding NRSI inclusion in ongoing and recently completed SRs. The other survey focused on the appropriateness, completeness, and usefulness of existing EPC Program methods guidance. The workgroup considered the virtual meeting and survey input when identifying aspects of the guidance that needed updating. The workgroup used an informal method for generating consensus about guidance. Disagreements were resolved through discussion. Results: We outline considerations for the inclusion of NRSIs in SRs of intervention effectiveness. We describe the strengths and limitations of RCTs, study design features and types of NRSIs, and key considerations for making decisions about inclusion of NRSIs (during the stages of topic scoping and refinement, SR team formation, protocol development, SR conduct, and SR reporting). We discuss how NRSIs may be applicable for the decisional dilemma being addressed in the SR, threats to the internal validity of NRSIs, as well as various data sources and advanced analytic methods that may be used in NRSIs. Finally, we outline an approach to incorporating NRSIs within an SR and key considerations for reporting. Conclusion: The main change from the previous guidance is the overall approach to decisions about inclusion of NRSIs in EPC SRs. Instead of recommending NRSI inclusion only if RCTs are insufficient to address the Key Question, this updated guidance handles NRSI evidence as a valuable source of information and lays out important considerations for decisions about the inclusion of NRSIs in SRs of intervention effectiveness. Different topics may require different decisions regarding NRSI inclusion. This guidance is intended to improve the utility of the final product to end-users. Inclusion of NRSIs will increase the scope, time, and resources needed to complete SRs, and NRSIs pose potential threats to validity, such as selection bias, confounding, and misclassification of interventions. Careful consideration must be given to both concerns.

Objective : To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable. Study Design and Setting : A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. Results : We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient: 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decisionmakers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers. Conclusion : Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users.

This paper summarizes the published Cochrane Review, “Buprenorphine for Managing Opioid Withdrawal,” by L. Gowing, R. Ali, J. M. White, & D. Mbewe (https://doi.org/10.1002/14651858.CD002025.pub5), and discusses it through a treatment policy and practice lens.

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RRs) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. This paper addresses considerations for rating the certainty of evidence (COE) in RRs. We recommend the full implementation of GRADE (Grading of Recommendations, Assessment, Development and Evaluation) for Cochrane RRs if time and resources allow.If time or other resources do not permit the full implementation of GRADE, the following recommendations can be considered: (1) limit rating COE to the main intervention and comparator and limit the number of outcomes to critical benefits and harms; (2) if a literature review or a Delphi approach to rate the importance of outcomes is not feasible, rely on informal judgements of knowledge users, topic experts or team members; (3) replace independent rating of the COE by two reviewers with single-reviewer rating and verification by a second reviewer and (4) if effect estimates of a well-conducted systematic review are incorporated into an RR, use existing COE grades from such a review. We advise against changing the definition of COE or the domains considered part of the GRADE approach for RRs.

Background The exponential growth of the biomedical literature necessitates investigating strategies to reduce systematic reviewer burden while maintaining the high standards of systematic review validity and comprehensiveness. Methods We compared the traditional systematic review screening process with (1) a review-of-reviews (ROR) screening approach and (2) a semi-automation screening approach using two publicly available tools (RobotAnalyst and AbstrackR) and different types of training sets (randomly selected citations subjected to dual-review at the title-abstract stage, highly curated citations dually reviewed at the full-text stage, and a combination of the two). We evaluated performance measures of sensitivity, specificity, missed citations, and workload burden Results The ROR approach for treatments of early-stage prostate cancer had a poor sensitivity (0.54) and studies missed by the ROR approach tended to be of head-to-head comparisons of active treatments, observational studies, and outcomes of physical harms and quality of life. Title and abstract screening incorporating semi-automation only resulted in a sensitivity of 100% at high levels of reviewer burden (review of 99% of citations). A highly curated, smaller-sized, training set (n = 125) performed similarly to a larger training set of random citations (n = 938). Conclusion Two approaches to rapidly update SRs—review-of-reviews and semi-automation—failed to demonstrate reduced workload burden while maintaining an acceptable level of sensitivity. We suggest careful evaluation of the ROR approach through comparison of inclusion criteria and targeted searches to fill evidence gaps as well as further research of semi-automation use, including more study of highly curated training sets.

ImportanceSocial needs interventions aim to improve health outcomes and mitigate inequities by addressing health-related social needs, such as lack of transportation or food insecurity. However, it is not clear whether these studies are reducing racial or ethnic inequities.ObjectiveTo understand how studies of interventions addressing social needs among multiracial or multiethnic populations conceptualize and analyze differential intervention outcomes by race or ethnicity.Evidence ReviewSources included a scoping review of systematic searches of PubMed and the Cochrane Library from January 1, 1995, through November 29, 2021, expert suggestions, and hand searches of key citations. Eligible studies evaluated interventions addressing social needs; reported behavioral, health, or utilization outcomes or harms; and were conducted in multiracial or multiethnic populations. Two reviewers independently assessed titles, abstracts, and full text for inclusion. The team developed a framework to assess whether the study was “conceptually thoughtful” for understanding root causes of racial health inequities (ie, noted that race or ethnicity are markers of exposure to racism) and whether analyses were “analytically informative” for advancing racial health equity research (ie, examined differential intervention impacts by race or ethnicity).FindingsOf 152 studies conducted in multiracial or multiethnic populations, 44 studies included race or ethnicity in their analyses; of these, only 4 (9%) were conceptually thoughtful. Twenty-one studies (14%) were analytically informative. Seven of 21 analytically informative studies reported differences in outcomes by race or ethnicity, whereas 14 found no differences. Among the 7 that found differential outcomes, 4 found the interventions were associated with improved outcomes for minoritized racial or ethnic populations or reduced inequities between minoritized and White populations. No studies were powered to detect differences.Conclusions and RelevanceIn this review of a scoping review, studies of social needs interventions in multiracial or multiethnic populations were rarely conceptually thoughtful for understanding root causes of racial health inequities and infrequently conducted informative analyses on intervention effectiveness by race or ethnicity. Future work should use a theoretically sound conceptualization of how race (as a proxy for racism) affects social drivers of health and use this understanding to ensure social needs interventions benefit minoritized racial and ethnic groups facing social and structural barriers to health.

ObjectivesEpilepsy treatment decision making is complex and understanding what informs caregiver decision making about treatment for childhood epilepsy is crucial to better support caregivers and their children. We synthesised evidence on caregivers’ perspectives and experiences of treatments for childhood epilepsy.DesignSystematic review of qualitative studies using a best-fit framework and Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual) approach.Data sourcesSearched Embase, PubMed, CINAHL, PsycINFO, SocINDEX and Web of Science from 1 January 1999 to 19 August 2021.Eligibility criteriaWe included qualitative studies examining caregiver’s perspectives on antiseizure medication, diet or surgical treatments for childhood epilepsy. We excluded studies not reported in English.Data extraction and synthesisWe extracted qualitative evidence into 1 of 14 domains defined by the Theoretical Domains Framework (TDF). One reviewer extracted study data and methodological characteristics, and two reviewers extracted qualitative findings. The team verified all extractions. We identified themes within TDF domains and synthesised summary statements of these themes. We assessed our confidence in our summary statements using GRADE-CERQual.ResultsWe identified five studies (in six reports) of good methodological quality focused on parent perceptions of neurosurgery; we found limited indirect evidence on parents’ perceptions of medications or diet. We identified themes within 6 of the 14 TDF domains relevant to treatment decisions: knowledge, emotion; social/professional role and identity; social influence; beliefs about consequences; and environmental context and resources.ConclusionsParents of children with epilepsy navigate a complex process to decide whether to have their child undergo surgery. Educational resources, peer support and patient navigators may help support parents through this process. More qualitative studies are needed on non-surgical treatments for epilepsy and among caregivers from different cultural and socioeconomic backgrounds to fully understand the diversity of perspectives that informs treatment decision making.

Background. In the United States, patients referred to as high-need, high-cost (HNHC) constitute a very small percentage of the patient population but account for a disproportionally high level of healthcare use and cost. Payers, health systems, and providers would like to improve the quality of care and health outcomes for HNHC patients and reduce their costly use of potentially preventable or modifiable healthcare services, including emergency department (ED) and hospital visits. Methods. We assessed evidence of criteria that identify HNHC patients (best fit framework synthesis); developed program theories on the relationship among contexts, mechanisms, and outcomes of interventions intended to change HNHC patient behaviors (realist review); and assessed the effectiveness of interventions (systematic review). We searched databases, gray literature, and other sources for evidence available from January 1, 2000, to March 4, 2021. We included quantitative and qualitative studies of HNHC patients (high healthcare use or cost) age 18 and over who received intervention services in a variety of settings. Results. We included 110 studies (117 articles). Consistent with our best fit framework, characteristics associated with HNHC include patient chronic clinical conditions, behavioral health factors including depression and substance use disorder, and social risk factors including homelessness and poverty. We also identified prior healthcare use and race as important predictors. We found limited evidence of approaches for distinguishing potentially preventable or modifiable high use from all high use. To understand how and why interventions work, we developed three program theories in our realist review that explain (1) targeting HNHC patients, (2) engaging HNHC patients, and (3) engaging care providers in these interventions. Theories identify the need for individualizing and tailoring services for HNHC patients and the importance of building trusting relationships. For our systematic review, we categorized evidence based on primary setting. We found that ED-, primary care–, and home-based care models result in reduced use of healthcare services (moderate to low strength of evidence [SOE]); ED, ambulatory intensive caring unit, and primary care-based models result in reduced costs (low SOE); and system-level transformation and telephonic/mail models do not result in changes in use or costs (low SOE). Conclusions. Patient characteristics can be used to identify patients who are potentially HNHC. Evidence focusing specifically on potentially preventable or modifiable high use was limited. Based on our program theories, we conclude that individualized and tailored patient engagement and resources to support care providers are critical to the success of interventions. Although we found evidence of intervention effectiveness in relation to cost and use, the studies identified in this review reported little information for determining why individual programs work, for whom, and when.

PROSPERO, CRD42019124057.

Background Multiple national organizations recommend screening and counseling adults for unhealthy alcohol use. Methods An evidence-based approach to screening and counseling using Epic electronic health record (EHR) tools was implemented in a general medicine clinic. A dissemination package with actionable steps for clinics and systems wishing to implement similar processes was then produced. To evaluate the initial implementation and quality improvement project, run charts were created to track patients screened, patients counseled, and fidelity to protocols, and members of the original project team were interviewed to assess facilitators and barriers. The draft dissemination package was revised after feedback from health system representatives (key informants). Results More than 9,000 patients (73.9% of those eligible) were screened in 20 months. Sixty-four percent of patients with positive initial screens had documented screening-related assessment; 39.7% (141/355) were offered counseling when indicated. Initial project team members identified EHR tools, clinic leadership, quality improvement culture, a multidisciplinary team, and training for providers and nurses as facilitators; and competing demands, patient population size, and nursing staff/resident turnover as barriers. Six key informants evaluated the dissemination package. Most rated 10 of the 12 sections as very useful; all rated components specific to implementing alcohol screening and counseling as very useful. Ratings for general guidance on implementing evidence-based services in primary care were more mixed. Conclusion Evidence-based screening and counseling for unhealthy alcohol use can be implemented with EHR tools. A dissemination guide was viewed favorably by key informants and can serve as a guide for other clinics and systems.

Introduction: Intracerebral hemorrhage remains one of the leading causes of death and disability worldwide with few established interventions that improve neurologic outcome. Research dedicated to better understanding and treating hemorrhagic strokes has multiplied in the past decade. Areas Covered: This review aims to discuss the current landscape of management of intracerebral hemorrhage in a critical care setting and provide updates regarding developments in therapeutic interventions and targets. PubMed was utilized to review recent literature, with a focus on large trials and meta-analyses, which have shaped current practice. Published committee guidelines were also included. A focus was placed on research published after 2015 in an effort to supplement previous reviews included in this publication. Expert Opinion: Literature pertaining to ICH management has allowed for a greater understanding of ineffective strategies as opposed to those of benefit. Despite this, mortality has improved worldwide, which may be the result of growing research efforts. Areas of future research that will impact mortality and improve neurologic outcomes include prevention of hematoma expansion, optimization of blood pressure targets, effective coagulopathy reversal, and minimally invasive surgical techniques to reduce hematoma burden.

Background: Healthcare decision makers strive to operate on the best available evidence. The Agency for Healthcare Research and Quality Evidence-based Practice Center (EPC) Program aims to support healthcare decision makers by producing evidence reviews that rate the strength of evidence. However, the evidence base is often sparse or heterogeneous, or otherwise results in a high degree of uncertainty and insufficient evidence ratings. Objective: To identify and suggest strategies to make insufficient ratings in systematic reviews more actionable. Methods: A workgroup comprising EPC Program members convened throughout 2020. We conducted interative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. Results: Several themes emerged across the literature review, review of systematic reviews, and review of technical brief methods. In the purposive sample of 43 systematic reviews, the use of the term “insufficient” covered both instances of no evidence and instances of evidence being present but insufficient to estimate an effect. The results of the literature review and review of the EPC Program systematic reviews illustrated the importance of clearly stating the reasons for insufficient evidence. Results of both the literature review and review of systematic reviews highlighted the factors decision makers consider when making decisions when evidence of benefits or harms is insufficient, such as costs, values, preferences, and equity. We identified five strategies for supplementing systematic review findings when evidence on benefit or harms is expected to be or found to be insufficient, including: reconsidering eligible study designs, summarizing indirect evidence, summarizing contextual and implementation evidence, modelling, and incorporating unpublished health system data. Conclusion: Throughout early scoping, protocol development, review conduct, and review presentation, authors should consider five possible strategies to supplement potential insufficient findings of benefit or harms. When there is no evidence available for a specific outcome, reviewers should use a statement such as “no studies” instead of “insufficient.” The main reasons for insufficient evidence rating should be explicitly described.

Background. Untreated maternal mental health disorders can have devastating sequelae for the mother and child. For women who are currently or planning to become pregnant or are breastfeeding, a critical question is whether the benefits of treating psychiatric illness with pharmacologic interventions outweigh the harms for mother and child. Methods. We conducted a systematic review to assess the benefits and harms of pharmacologic interventions compared with placebo, no treatment, or other pharmacologic interventions for pregnant and postpartum women with mental health disorders. We searched four databases and other sources for evidence available from inception through June 5, 2020 and surveilled the literature through March 2, 2021; dually screened the results; and analyzed eligible studies. We included studies of pregnant, postpartum, or reproductive-age women with a new or preexisting diagnosis of a mental health disorder treated with pharmacotherapy; we excluded psychotherapy. Eligible comparators included women with the disorder but no pharmacotherapy or women who discontinued the pharmacotherapy before pregnancy. Results. A total of 164 studies (168 articles) met eligibility criteria. Brexanolone for depression onset in the third trimester or in the postpartum period probably improves depressive symptoms at 30 days (least square mean difference in the Hamilton Rating Scale for Depression, -2.6; p=0.02; N=209) when compared with placebo. Sertraline for postpartum depression may improve response (calculated relative risk [RR], 2.24; 95% confidence interval [CI], 0.95 to 5.24; N=36), remission (calculated RR, 2.51; 95% CI, 0.94 to 6.70; N=36), and depressive symptoms (p-values ranging from 0.01 to 0.05) when compared with placebo. Discontinuing use of mood stabilizers during pregnancy may increase recurrence (adjusted hazard ratio [AHR], 2.2; 95% CI, 1.2 to 4.2; N=89) and reduce time to recurrence of mood disorders (2 vs. 28 weeks, AHR, 12.1; 95% CI, 1.6 to 91; N=26) for bipolar disorder when compared with continued use. Brexanolone for depression onset in the third trimester or in the postpartum period may increase the risk of sedation or somnolence, leading to dose interruption or reduction when compared with placebo (5% vs. 0%). More than 95 percent of studies reporting on harms were observational in design and unable to fully account for confounding. These studies suggested some associations between benzodiazepine exposure before conception and ectopic pregnancy; between specific antidepressants during pregnancy and adverse maternal outcomes such as postpartum hemorrhage, preeclampsia, and spontaneous abortion, and child outcomes such as respiratory issues, low Apgar scores, persistent pulmonary hypertension of the newborn, depression in children, and autism spectrum disorder; between quetiapine or olanzapine and gestational diabetes; and between benzodiazepine and neonatal intensive care admissions. Causality cannot be inferred from these studies. We found insufficient evidence on benefits and harms from comparative effectiveness studies, with one exception: one study suggested a higher risk of overall congenital anomalies (adjusted RR [ARR], 1.85; 95% CI, 1.23 to 2.78; N=2,608) and cardiac anomalies (ARR, 2.25; 95% CI, 1.17 to 4.34; N=2,608) for lithium compared with lamotrigine during first- trimester exposure. Conclusions. Few studies have been conducted in pregnant and postpartum women on the benefits of pharmacotherapy; many studies report on harms but are of low quality. The limited evidence available is consistent with some benefit, and some studies suggested increased adverse events. However, because these studies could not rule out underlying disease severity as the cause of the association, the causal link between the exposure and adverse events is unclear. Patients and clinicians need to make an informed, collaborative decision on treatment choices.

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.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.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.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.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.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.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.배경: 코로나 바이러스 질병 2019 (COVID‐19)는 새로운 베타 코로나 바이러스, 중증 급성 호흡기 증후군 코로나 바이러스 ‐2 (SARS‐CoV‐2)에 의해 발생합니다. SARS‐CoV‐2에 감염된 대부분의 사람들은 특이한 증상이없는 경증의 질병을 가지고 있지만 약 5 %는 호흡 부전, 패 혈성 쇼크 및 다발성 장기 부전으로 중병에 걸립니다. 감염된 개인의 알려지지 않은 비율은 감염성이 있지만 증상이없는 상태로 남아 있지만 COVID‐19 증상을 경험하지 않습니다. 질병에 걸린 사람들은 감염되기 전 증상이있는 기간을 거치게됩니다. SARS‐CoV‐2 감염에 대한 보편적 인 스크리닝은 임상 적으로 존재하기 전에 감염된 개인을 탐지하므로 질병의 확산을 억제하는 중요한 수단이 될 수 있습니다. 목적: 우리는 (1) SARS‐CoV‐2 감염에 대한 보편적 검사의 효과와 (2) COVID‐19 증상에 대한 임상 치료를받지 않은 사람들의 보편적 검사의 정확성을 평가하기 위해 신속한 검토를 수행했습니다. . 검색 전략: 정보 전문가가 2020 년 5 월 26 일까지 Ovid MEDLINE과 질병 통제 센터 (CDC) COVID‐19 연구 기사 다운로드 가능한 데이터베이스를 검색했습니다. 2020 년 4 월 14 일에 Embase.com, CENTRAL 및 Cochrane Covid‐19 연구 등록부를 검색했습니다. LitCovid를 2020 년 4 월 4 일까지 검색했습니다. 세계 보건기구 (WHO)는 2020 년 4 월 15 일까지 중국 데이터베이스와 PubMed의 일일 검색 기록을 제공했습니다. 또한 2020 년 4 월 8 일에 3 개의 모델 저장소 (Covid‐Analytics, MIDAS (Infectious Disease Agent Study) 모델, 의료 의사 결정 협회)를 검색했습니다. 선정 기준: SARS‐CoV2의 유병률이 알려지지 않은 일반 인구의 선별 효과 또는 선별 정확도를 평가하는 시험, 관찰 연구 또는 수학적 모델링 연구. 자료 수집 및 분석: 파일럿 테스트 검토 양식 후 한 검토 작성자가 제목과 초록을 선별했습니다. 두 명의 리뷰 저자가 독립적으로 연구의 전체 텍스트를 선별하고 세 번째 리뷰 저자와의 토론을 통해 의견 불일치를 해결했습니다. 첫 번째 리뷰 작성자가 제외시킨 초록은 제외 전에 두 번째 리뷰 작성자가 이중 검토했습니다. 한 리뷰 작성자가 독립적으로 데이터를 추출하여 두 번째 리뷰 작성자가 완전성과 정확성을 확인했습니다. 두 명의 검토 저자가 진단 정확도 연구를위한 진단 정확도 연구의 품질 평가 (QUADAS‐2) 도구와 모델링 연구를위한 경제적 평가를 위해 원래 설계된 수정 된 양식을 사용하여 포함 된 연구의 품질을 독립적으로 평가했습니다. 우리는 합의를 통해 차이를 해결했습니다. 우리는 내러티브 및 표 형식으로 증거를 종합했습니다. 우리는 GRADE 접근법을 사용하여 발병, 전염, 누락 및 감지 된 사례, 진단 정확도 (예: 참 양성, 거짓 양성, 참 음성, 거짓 음성)에 대한 증거의 확실성을 평가했습니다. 주요 결과: 22 개의 출판물을 포함했습니다. 보편적 스크리닝의 효과에 대한 두 가지 모델링 연구가보고되었습니다. 스크리닝 테스트 정확도에 대한 20 건의 연구 (코호트 연구 17 건 및 모델링 연구 3 건)가보고되었습니다. 스크리닝의 효과 두 가지 모델링 연구를 포함했습니다. 한 연구에 따르면 공항과 같은 여행 허브에서 증상 선별 검사가 약간 느려질 수 있지만 감염 사례의 유입을 막지는 못할 수 있습니다 (주당 10 명 또는 100 명의 감염된 여행자가 현지 발병 지연을 각각 8 일 또는 1 일로 줄 였다고 가정). . 우리는 편견의 위험을 사소하거나 전혀 우려하지 않는 것으로 평가했으며 증거의 확실성이 낮았으며 매우 심각한 간접적 인 것으로 인해 하향 조정되었습니다. 두 번째 모델링 연구는 실험실 테스트를 사용하여 응급실의 의료 종사자를 선별하면 환자와 다른 의료 종사자에게 전염이 감소 할 수 있다는 매우 낮은 불확실성 증거를 제공합니다 (1 만 명당 1.2 개의 새로운 감염의 전파 상수를 가정하고 매주 선별을 통해 감염을 5.1 % 감소 시킨다고 가정). 30 일 이내). 근거의 확실성은 매우 낮았으며, 편견 (주요 우려) 및 간접 성 위험이 높기 때문에 하향 조정되었습니다. 스크리닝의 위해에 대해보고 된 모델링 연구는 없습니다. 스크리닝 테스트 정확도 17 개 코호트 연구 모두 인덱스 스크리닝 전략을 참조 역전사 효소 중합 효소 연쇄 반응 (RT‐PCR) 테스트와 비교했습니다. 한 연구를 제외한 모든 연구는 단일 시점 선별 검사의 정확성에 대해보고했으며 SARS‐CoV‐2의 유병률, 설정 및 측정 방법이 매우 다양했습니다. 17 개 연구 중 16 개 연구에서 전반적인 비뚤림 위험을 명확하지 않은 것으로 평가했습니다. 주로 지수 테스트 및 참조 표준에 대한 정보가 제한되어 있기 때문입니다. 우리는 한 연구를 유병률이 다른 두 개의 개별 모집단을 포함하여 비뚤림 위험이 높은 것으로 평가했습니다. 여러 선별 전략에서 민감도 추정치는 작은 샘플에서 나왔습니다. 단일 시점 전략의 경우 증상 평가를 위해 12 개 코호트 (524 명)의 민감도 범위는 0.00 ~ 0.60 (매우 낮은 불확실성 증거)이고 12 개 코호트 (16,165 명)의 특이도 범위는 0.66 ~ 1.00입니다 ( 낮은 불확실성 증거). 직접 체온 측정 (3 개 코호트, 822 명), 해외 여행 이력 (2 개 코호트, 13,080 명) 또는 알려진 감염자 (3 개 코호트, 13,205 명) 또는 의심되는 감염자 (2 개 코호트, 954 명)에 대한 노출을 사용한 스크리닝의 경우, 민감도 범위는 0.00 ~ 0.23 (매우 낮음에서 낮음 증거)이고 특이도 범위는 0.90 ~ 1.00 (낮음에서 중간 정도의 증거)입니다. 증상 평가와 직접 체온 측정 (2 개 코호트, 779 명)의 경우 민감도 범위는 0.12 ~ 0.69 (매우 낮은 확실성 증거), 특이도는 0.90 ~ 1.00 (낮은 확실성 증거)이었습니다. 신속한 PCR 검사 (1 코호트, 21 명)의 경우 민감도는 0.80 (95 % 신뢰 구간 (CI) 0.44 ~ 0.96, 매우 낮은 불확실성 증거)이었고 특이도는 0.73 (95 % CI 0.39 ~ 0.94, 매우 낮은 불확실성 증거)이었습니다. ). 한 코호트 (76 명)는 증상 평가와 함께 반복 스크리닝에 대해보고했으며 민감도는 0.44 (95 % CI 0.29 ~ 0.59, 매우 낮은 확실성 증거) 및 특이도 0.62 (95 % CI 0.42 ~ 0.79, 낮은 확실성 증거)를 보여줍니다. . 세 가지 모델링 연구는 공항에서 스크리닝의 정확성을 평가했습니다. 측정 된 주요 결과는 공항에서 출입국 심사 또는 둘 다에서 누락되거나 감지 된 사례였습니다. 한 연구에 따르면 0.30 (95 % CI 0.1 ~ 0.53)에서 민감도가 매우 낮아 감염된 여행자의 70 %가 누락되었습니다. 또 다른 연구에서는 90 %의 탐지율을 달성하기위한 비현실적인 시나리오에 대해 설명했으며 0 %의 무증상 감염이 필요했습니다. 최종 연구는 낮은 방법 론적 질로 인해 매우 불확실한 증거를 제공합니다. 연구진 결론: 스크리닝의 효과에 대한 근거 기반은 두 가지 수학적 모델링 연구에서 비롯되며 그 가정에 의해 제한됩니다. 낮은 불확실성 증거는 여행 허브에서 선별 검사가 감염된 사례의 수입을 약간 늦출 수 있음을 시사합니다. 이 검토는 스크리닝 전략의 정확성의 불확실성과 변동을 강조합니다. 감염된 개인의 높은 비율은 놓치고 다른 사람을 감염시킬 수 있으며, 일부 건강한 개인은 양성으로 잘못 식별되어 확인 검사가 필요하며 잠재적으로 이러한 개인을 불필요하게 격리시킬 수 있습니다. 추가 연구는 신속한 실험실 테스트, 조합 스크리닝 및 반복 스크리닝의 유용성을 평가해야합니다. RT‐PCR보다 더 정확한 기준 표준에 대한 더 많은 연구가 필요합니다. 기존 접근 방식의 민감도가 낮다는 점을 감안할 때, 우리의 연구 결과는 얼굴 가리개, 물리적 거리 유지, 격리 및 일선 작업자를위한 적절한 개인 보호 장비와 같은 전파를 방지 할 수있는 다른 방법에 더 많은 강조가 필요함을 지적합니다.บทนำ: โรคโคโรนาไวรัส 2019 (COVID‐19) เกิดจากเชื้อเบตาโคโรนาไวรัสสายพันธุ์ใหม่ กลุ่มอาการทางเดินหายใจเฉียบพลันรุนแรง coronavirus‐2 (SARS‐CoV‐2) คนส่วนใหญ่ที่ติดเชื้อ SARS‐CoV‐2 มีอาการไม่รุนแรงโดยมีอาการไม่เฉพาะเจาะจง แต่ประมาณ 5% ป่วยหนักด้วยระบบหายใจล้มเหลว ภาวะช็อกจากติดเชื้อ และอวัยวะล้มเหลว ผู้ติดเชื้อที่ไม่ทราบสัดส่วนไม่เคยพบอาการ COVID‐19 แม้ว่าจะมีการติดเชื้อ กล่าวคือยังคงไม่มีอาการ ผู้ที่เป็นโรค จะต้องผ่านช่วงเวลาที่ไม่มีอาการซึ่งเป็นช่วงที่มีการแพร่เชื้อ การตรวจคัดกรองทั่วไปสำหรับการติดเชื้อ SARS‐CoV‐2 เพื่อตรวจหาบุคคลที่ติดเชื้อก่อนที่จะมีอาการทางคลินิก จึงอาจเป็นมาตรการสำคัญในการควบคุมการแพร่กระจายของโรค วัตถุประสงค์: เราได้ทำการทบทวนวรรณกรรมอย่างรวดเร็วเพื่อประเมิน (1) ประสิทธิผลของการตรวจคัดกรองแบบครอบคลุมสำหรับการติดเชื้อซาร์ส ‐ โควี ‐2 เปรียบเทียบกับการไม่ตรวจคัดกรองและ (2) ความแม่นยำของการตรวจคัดกรองแบบครอบคลุมในผู้ที่ไม่ได้รับการดูแลทางคลินิกสำหรับอาการของ COVID‐19 วิธีการสืบค้น: ผู้เชี่ยวชาญด้านข้อมูลค้นหา Ovid MEDLINE และศูนย์ควบคุมโรค (CDC) COVID‐19 Research Articles Downloadable Database ถึง 26 พฤษภาคม 2020 เราสืบค้น Embase.com, CENTRAL และ Cochrane Covid‐19 Study Register ในวันที่ 14 เมษายน 2020 เราค้นหา LitCovid ถึง 4 เมษายน 2020 องค์การอนามัยโลก (WHO) จัดทำบันทึกจากการค้นหารายวันในฐานข้อมูลภาษาจีนและใน PubMed ถึง 15 เมษายน 2020 นอกจากนี้เรายังสืบค้นที่เก็บโมเดล 3 แห่ง (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS] และ Society for Medical Decision Making) ในวันที่ 8 เมษายน 2020 เกณฑ์การคัดเลือก: การทดลอง การศึกษาเชิงสังเกต หรือการศึกษาแบบจำลองทางคณิตศาสตร์เพื่อประเมินประสิทธิผลการคัดกรองหรือความแม่นยำในการคัดกรอง ในกลุ่มประชากรทั่วไปที่ไม่ทราบความชุกของโรค SARS‐CoV2 การรวบรวมและวิเคราะห์ข้อมูล: หลังจากการทดสอบนำร่องแบบฟอร์มการทบทวนวรรณกรรม ผู้เขียนการทบทวนวรรณกรรมคนหนึ่งได้คัดกรองชื่อเรื่องและบทคัดย่อ ผู้ประพันธ์ 2 คนคัดกรองการศึกษาฉบับเต็ม และแก้ไขความเห็นที่ไม่ตรงกันโดยการปรึกษากับผู้ประพันธ์คนที่สาม บทคัดย่อที่ถูกคัดออกโดยผู้เขียนการทบทวนวรรณกรรมคนแรกได้รับการตรวจสอบโดยผู้เขียนคนที่สองก่อนที่จะคัดออก ผู้ประพันธ์การทบทวนวรรณกรรม 1 คน คัดลอกข้อมูลการศึกษาโดยอิสระ ซึ่งตรวจสอบโดยผู้ประพันธ์การทบทวนวรรณกรรมคนที่สอง ผู้เขียนการทบทวนวรรณกรรม 2 คนประเมินคุณภาพของการศึกษาที่รวมไว้อย่างอิสระ โดยใช้เครื่องมือการประเมินคุณภาพของการศึกษาความแม่นยำในการวินิจฉัย (QUADAS‐2) สำหรับการศึกษาความแม่นยำในการวินิจฉัย และรูปแบบที่แก้ไขซึ่งออกแบบมาสำหรับการประเมินทางเศรษฐศาสตร์สำหรับการศึกษาแบบจำลอง เราแก้ไขความแตกต่างโดยฉันทามติ เราสังเคราะห์หลักฐานในรูปแบบบรรยายและตาราง เราประเมินความเชื่อมั่นของหลักฐานสำหรับ จำนวนวันถึงการแพร่ระบาด การแพร่เชื้อ ผู้ป่วยที่วินิจฉัยไม่ได้และได้ ความแม่นยำในการวินิจฉัย (เช่นผลบวกจริง ผลบวกลวง ผลลบจริง ผลลบลวง) โดยใช้วิธี GRADE ผลการวิจัย: เรารวมสิ่งตีพิมพ์ 22 รายการ การศึกษาแบบจำลอง 2 รายการรายงานประสิทธิผลของการคัดกรองแบบครอบคลุม การศึกษา 20 รายการ (17 cohort studies และการศึกษาแบบจำลอง 3 รายการ) รายงานเกี่ยวกับความแม่นยำในการทดสอบการคัดกรอง ประสิทธิผลของการคัดกรอง เราได้รวมการศึกษาการสร้างแบบจำลอง 2 รายการ การศึกษา 1 รายการชี้ให้เห็นว่าการตรวจคัดกรองอาการที่ศูนย์กลางการเดินทาง เช่นสนามบิน อาจทำให้การนำเข้าผู้ติดเชื้อช้าลงเล็กน้อย แต่ไม่ได้หยุด (สมมติว่ามีผู้ติดเชื้อ 10 หรือ 100 คนต่อสัปดาห์จะลดความช้าในการระบาดในพื้นที่เหลือ 8 วันหรือ 1 วันตามลำดับ) เราประเมินความเสี่ยงของการมีอคติว่าเป็นเรื่องเล็กน้อยหรือไม่มีเลย และความเชื่อมั่นของหลักฐานอยู่ในระดับต่ำโดยลดระดับลงสำหรับ very serious indirectness การศึกษาแบบจำลองรายการที่ 2 ให้หลักฐานที่มีความเชื่อมั่นต่ำมากว่า การตรวจคัดกรองบุคลากรสุขภาพในแผนกฉุกเฉินโดยใช้การตรวจทางห้องปฏิบัติการ อาจลดการแพร่เชื้อไปยังผู้ป่วยและบุคลากรสุขภาพอื่น ๆ (สมมติว่ามีการแพร่เชื้อคงที่ 1.2 การติดเชื้อใหม่ต่อ 10,000 คน การตรวจคัดกรองรายสัปดาห์ลดการติดเชื้อลง 5.1% ภายใน 30 วัน) ความเชื่อมั่นของหลักฐานอยู่ในระดับต่ำมาก โดยลดระดับลงเนื่องจากมีความเสี่ยงสูงต่อการเกิดอคติ (ข้อกังวลหลัก) และ indirectness ไม่มีการศึกษาแบบจำลองที่รายงานเกี่ยวกับอันตรายของการตรวจคัดกรอง ความแม่นยำในการทดสอบการคัดกรอง การศึกษาแบบ cohort 17 รายการเปรียบเทียบกลยุทธ์การคัดกรองกับการทดสอบมาตรฐาน ปฏิกิริยาลูกโซ่โพลีเมอเรสแบบย้อนกลับ transcriptase (RT‐PCR) การศึกษาทั้งหมดยกเว้น 1 รายการรายงานเกี่ยวกับความแม่นยำของการตรวจคัดกรองแบบจุดเดียวในเวลาเดียว และมีความแตกต่างกันอย่างมากในความชุกของ SARS‐CoV‐2 บริบทและวิธีการตรวจ เราประเมินความเสี่ยงโดยรวมของอคติว่าไม่มีความชัดเจนในการศึกษา 16 จาก 17 การศึกษาสาเหตุหลักมาจากข้อมูลที่จำกัดของการทดสอบที่ทำและมาตรฐานอ้างอิง เราประเมินการศึกษา 1 รายการว่ามีความเสี่ยงสูงที่จะเกิดอคติเนื่องจากการรวมประชากรสองกลุ่มที่แยกจากกัน ซึ่งมีแนวโน้มที่จะมีความชุกต่างกัน สำหรับกลยุทธ์การคัดกรองหลาย ๆ แบบ การประมาณความไวมาจากกลุ่มตัวอย่างขนาดเล็ก สำหรับกลยุทธ์จุดเดียวในเวลาสำหรับการประเมินอาการความไวจาก 12 cohorts (524 คน) อยู่ระหว่าง 0.00 ถึง 0.60 (หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะจาก 12 cohorts (16,165 คน) อยู่ในช่วง 0.66 ถึง 1.00 ( หลักฐานที่มีความเชื่อมั่นต่ำ) สำหรับการตรวจคัดกรองโดยใช้การวัดอุณหภูมิโดยตรง (3 cohorts, 822 คน) ประวัติการเดินทางระหว่างประเทศ (2 cohorts, 13,080 คน) หรือการสัมผัสผู้ติดเชื้อที่รู้จัก (3 cohorts, 13,205 คน) หรือผู้ที่สงสัยว่าติดเชื้อ (2 cohorts, 954 คน) ความไวอยู่ในช่วง 0.00 ถึง 0.23 (หลักฐานที่มีความเชื่อมั่นต่ำถึงต่ำมาก) และความจำเพาะอยู่ระหว่าง 0.90 ถึง 1.00 (หลักฐานที่มีความเชื่อมั่นต่ำถึงปานกลาง) สำหรับการประเมินอาการร่วมกับการวัดอุณหภูมิโดยตรง (2 cohorts, 779 คน) ความไวอยู่ระหว่าง 0.12 ถึง 0.69 (หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะตั้งแต่ 0.90 ถึง 1.00 (หลักฐานที่มีความเชื่อมั่นต่ำ) สำหรับการทดสอบ PCR อย่างรวดเร็ว (1 cohort, 21 คน) ความไวเท่ากับ 0.80 (ช่วงความเชื่อมั่น 95% (CI) 0.44 ถึง 0.96 หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะเท่ากับ 0.73 (95% CI 0.39 ถึง 0.94 หลักฐานที่มีความเชื่อมั่นต่ำมาก ) การศึกษา 1 cohort (76 คน) รายงานเกี่ยวกับการตรวจคัดกรองซ้ำด้วยการประเมินอาการ แสดงให้เห็นถึงความไว 0.44 (95% CI 0.29 ถึง 0.59 หลักฐานที่มีความเชื่อมั่นต่ำมาก) และความจำเพาะ 0.62 (95% CI 0.42 ถึง 0.79; หลักฐานที่มีความเชื่อมั่นต่ำ) การศึกษาแบบจำลอง 3 รายการประเมินความถูกต้องของการคัดกรองที่สนามบิน ผลลัพธ์หลักที่วัดได้คือกรณีที่พลาดหรือตรวจพบโดยการคัดกรองการเข้าหรือออกหรือทั้งสองอย่างที่สนามบิน การศึกษาชิ้นหนึ่งชี้ให้เห็นความไวต่ำมากที่ 0.30 (95% CI 0.1 ถึง 0.53) ซึ่งพลาด 70% ของผู้เดินทางที่ติดเชื้อ การศึกษาอีก 1 รายการอธิบายถึงสถานการณ์ที่ไม่เป็นจริงเพื่อให้ได้อัตราการตรวจพบ 90% โดยต้องมีการติดเชื้อที่ไม่มีอาการ 0% การศึกษาสุดท้ายให้หลักฐานที่ไม่แน่นอนเนื่องจากคุณภาพของวิธีการต่ำ ข้อสรุปของผู้วิจัย: หลักฐานสำหรับประสิทธิผลของการคัดกรองมาจากการศึกษาแบบจำลองทางคณิตศาสตร์ 2 รายการ และถูกจำกัดโดยสมมติฐาน หลักฐานที่มีความเชื่อมั่นต่ำ ชี้ให้เห็นว่าการตรวจคัดกรองที่ศูนย์กลางการเดินทางอาจทำให้การนำเข้าผู้ติดเชื้อช้าลงเล็กน้อย การทบทวนวรรณกรรมนี้เน้นให้เห็นถึงความไม่แน่นอนและความแตกต่างในความแม่นยำของกลยุทธ์การคัดกรอง ผู้ติดเชื้อในสัดส่วนที่สูงอาจพลาดไปและแพร่เชื้อไปสู่ผู้อื่น และบุคคลที่มีสุขภาพดีบางคนอาจถูกระบุว่าเป็นผลบวกโดยต้องได้รับการทดสอบยืนยันและอาจนำไปสู่การแยกบุคคลเหล่านี้โดยไม่จำเป็น การศึกษาเพิ่มเติมจำเป็นต้องประเมินประโยชน์ของการทดสอบในห้องปฏิบัติการอย่างรวดเร็ว การตรวจคัดกรองแบบรวม และการตรวจคัดกรองซ้ำ จำเป็นต้องมีการวิจัยเพิ่มเติมเกี่ยวกับมาตรฐานอ้างอิงที่มีความแม่นยำมากกว่า RT‐PCR ด้วยความไวที่ไม่ดีของแนวทางที่มีอยู่ การค้นพบของเราชี้ให้เห็นถึงความจำเป็นในการให้ความสำคัญกับวิธีการอื่น ๆ ที่อาจป้องกันการแพร่เชื้อ เช่นการปกปิดใบหน้า ระยะห่างทางกายภาพการกักกัน และอุปกรณ์ป้องกันส่วนบุคคลที่เพียงพอสำหรับพนักงานส่วนหน้า.پیشینه: بیماری کروناویروس 2019 (COVID‐19) توسط بتاکوروناویروس جدید، سندرم حاد تنفسی شدید کروناویروس ‐2 (SARS‐CoV‐2) ایجاد می‌شود. بیشتر افراد آلوده به SARS‐CoV‐2 مبتلا به بیماری خفیف با نشانه‌های غیراختصاصی هستند، اما حدود 5% از آنها به دلیل نارسایی تنفسی، شوک سپتیک و نارسایی چند عضو به شدت بیمار می‌شوند. نسبت نامشخصی از افراد آلوده هرگز دچار نشانه‌های COVID‐19 نمی‌شوند، اگرچه آلوده هستند، یعنی بدون نشانه باقی می‌مانند. افرادی که به این بیماری مبتلا می‌شوند، از یک دوره پیش‌علامت عبور می‌کنند که در طول آن عفونی هستند. غربالگری جهانی برای عفونت‌های SARS‐CoV‐2 به منظور تشخیص افراد آلوده پیش از آنکه از نظر بالینی تظاهر پیدا کنند، می‌تواند اقدامی مهم برای مهار گسترش بیماری باشد. اهداف: ما یک مرور سریع را انجام دادیم تا (1) اثربخشی غربالگری جهانی را برای عفونت SARS‐CoV‐2 در مقایسه با عدم انجام غربالگری و (2) دقت غربالگری جهانی را در افرادی که برای نشانه‌های COVID‐19 تحت مراقبت‌های بالینی قرار نگرفته‌اند، ارزیابی کنیم. روش‌های جست‌وجو: یک متخصص اطلاعات، Ovid MEDLINE و بانک اطلاعاتی مقالات پژوهشی قابل دانلود COVID‐19 را در سایت مراکز کنترل بیماری (CDC) تا 26 می 2020 جست‌وجو کرد. ما Embase.com؛ CENTRAL، و Cochrane Covid‐19 Register Study Register را در تاریخ 14 اپریل 2020 جست‌وجو کردیم. LitCovid تا 4 اپریل 2020 بررسی شد. سازمان بهداشت جهانی (WHO) رکوردها را از جست‌وجوهای روزانه در بانک‌های اطلاعاتی چینی و در PubMed تا 15 اپریل 2020 فراهم کرد. ما همچنین در 8 اپریل 2020، سه مخزن مدل‌سازی (Covid‐Analytics؛ Models of Infectious Disease Agent Study [MIDAS]، و Society for Medical Decision Making) را جست‌وجو کردیم. معیارهای انتخاب: کارآزمایی‌ها، مطالعات مشاهده‌ای، یا مطالعات ریاضی مدل‌سازی که به ارزیابی اثربخشی غربالگری یا دقت غربالگری میان جمعیت‌های عمومی پرداختند که در آنها شیوع SARS‐CoV2 ناشناخته است. گردآوری و تجزیه‌وتحلیل داده‌ها: پس از پایلوت فرم‌های مرور تست، یکی از نویسندگان مطالعه عناوین و خلاصه مقالات را بررسی کرد. دو نویسنده مرور به‌طور مستقل از هم متن کامل مطالعات را غربالگری کرده و هر گونه اختلاف‌نظری، با بحث با نویسنده سوم مرور برطرف شد. خلاصه مقالاتی که توسط نویسنده اول مرور رد شدند، پیش از حذف کامل، توسط نویسنده دوم مجددا بررسی شدند. یکی از نویسندگان مرور مستقلا داده‌ها را استخراج کرد، که توسط نویسنده دوم مرور از نظر کامل بودن و دقت بررسی شدند. دو نویسنده مرور به‌طور مستقل از هم کیفیت مطالعات وارد شده را با استفاده از ابزار ارزیابی کیفیت مطالعات دقت تشخیصی (QUADAS‐2) برای مطالعات دقت تشخیصی و فرم اصلاح شده‌ای از آن که در ابتدا برای ارزیابی‌های اقتصادی برای مطالعات مدل‌سازی طراحی شده بود، رتبه‌بندی کردند. ما تفاوت‌ها را با همفکری و اجماع‌نظر حل کردیم. شواهد را در قالب‌های روایت‌گونه (narrative) و جدولی (tabular) سنتز کردیم. با استفاده از رویکرد GRADE، قطعیت شواهد را برای روزهای شیوع و طغیان، انتقال، موارد از دست رفته و تشخیص داده شده، دقت تشخیصی (یعنی مثبت واقعی، مثبت کاذب، منفی واقعی، منفی کاذب) ارزیابی کردیم. نتایج اصلی: 22 مقاله وارد شدند. دو مطالعه مدل‌سازی، در مورد اثربخشی غربالگری جهانی گزارش دادند. بیست مطالعه (17 مطالعه کوهورت و 3 مطالعه مدل‌سازی) در مورد دقت آزمون غربالگری به ارائه گزارش پرداختند. اثربخشی غربالگری ما دو مطالعه مدل‌سازی را وارد کردیم. یک مطالعه نشان می‌دهد که غربالگری نشانه بیماری در مراکز مسافرتی، مانند فرودگاه‌ها، ممکن است ورود موارد عفونی را اندکی کاهش دهد اما آن را متوقف نمی‌کند (با فرض 10 یا 100 مسافر آلوده در هر هفته، تاخیر را در شیوع محلی به ترتیب، به 8 روز یا 1 روز کاهش داد) . ما خطر سوگیری (bias) را در سطح پائین یا بدون نگرانی ارزیابی کردیم، و قطعیت شواهد پائین بود، که به دلیل غیرمستقیم بودن بسیار جدی، تنزل رتبه پیدا کرد. مطالعه مدل‌سازی دوم شواهدی را با قطعیت بسیار پائین نشان می‌دهد که غربالگری کارکنان بخش مراقبت‌‌های سلامت در بخش‌های اورژانس با استفاده از تست‌های آزمایشگاهی ممکن است انتقال ویروس را به بیماران و دیگر کارکنان بخش مراقبت‌‌های سلامت کاهش دهد (با فرض انتقال ثابت 1.2 مورد عفونت جدید در هر 10,000 نفر، غربالگری هفتگی باعث کاهش عفونت تا 5.1% طی 30 روز شد). قطعیت شواهد بسیار پائین بود، که دلیل کاهش سطح کیفیت آن، خطر بالای سوگیری (نگرانی‌های اساسی) و غیرمستقیم بودن آنها گزارش شد. هیچ یک از مطالعات مدل‌سازی در مورد مضرات غربالگری گزارشی ارائه ندادند. دقت تست غربالگری همه 17 مطالعه کوهورت یک استراتژی غربالگری شاخص را با واکنش زنجیره‌ای پلیمراز ترانس‌کریپتاز معکوس (RT‐PCR) مرجع مقایسه کردند. همه مطالعات به جز یک مورد در مورد دقت انجام یک بار غربالگری گزارش داده و در شیوع SARS‐CoV‐2، شرایط، و روش‌های اندازه‌گیری تفاوت بسیاری داشتند. ما خطر کلی سوگیری را در 16 مطالعه از 17 مورد در سطح نامشخص ارزیابی کردیم، که دلیل اصلی آن، به اطلاعات محدود در مورد تست شاخص و استاندارد مرجع باز می‌گشت. یک مطالعه را به دلیل وارد کردن دو جمعیت جداگانه با احتمال شیوع متفاوت بیماری، در معرض خطر بالایی از سوگیری قرار دادیم. برای چندین استراتژی غربالگری، برآوردها از حساسیت آنها، از نمونه‌های کوچکی به دست آمدند. برای استراتژی‌های تکی که یک بار انجام شدند، به منظور ارزیابی نشانه‌ها، محدوده حساسیت از 12 مطالعه کوهورت (524 نفر) از 0.00 تا 0.60 (شواهد با قطعیت بسیار پائین) و محدوده ویژگی از 12 مطالعه کوهورت (16,165 نفر) از 0.66 تا 1.00 (شواهد با قطعیت پائین) متغیر بودند. برای غربالگری با استفاده از اندازه‌گیری مستقیم دمای بدن (3 مطالعه کوهورت، 822 نفر)، سابقه مسافرت بین‌المللی (2 مطالعه کوهورت، 13,080 نفر)، یا تماس با افراد آلوده شناخته شده (3 مطالعه کوهورت، 13,205 نفر) یا مواجهه با افراد آلوده مشکوک (2 مطالعه کوهورت، 954 نفر)، محدوده حساسیت از 0.00 تا 0.23 (شواهد با قطعیت بسیار پائین تا پائین) و محدوده ویژگی از 0.90 تا 1.00 (شواهد با قطعیت پائین تا متوسط) بود. برای ارزیابی نشانه‌ها به‌علاوه اندازه‌گیری مستقیم درجه حرارت بدن (2 مطالعه کوهورت، 779 نفر)، محدوده حساسیت از 0.12 تا 0.69 (شواهد با قطعیت بسیار پائین) و محدوده ویژگی از 0.90 تا 1.00 (شواهد با قطعیت پائین) قرار داشت. برای تست PCR سریع (1 مطالعه کوهورت، 21 نفر)، حساسیت معادل 0.80 (95% فاصله اطمینان (CI): 0.44 تا 0.96؛ شواهد با قطعیت بسیار پائین) و ویژگی معادل 0.73 (95% CI؛ 0.39 تا 0.94؛ شواهد با قطعیت بسیار پائین) گزارش شد. یک مطالعه کوهورت (76 نفر) در مورد غربالگری مکرر با ارزیابی نشانه‌ها گزارش دادند و حساسیتی را معادل 0.44 (95% CI؛ 0.29 تا 0.59؛ شواهد با قطعیت بسیار پائین) و ویژگی را معادل 0.62 (95% CI؛ 0.42 تا 0.79؛ شواهد با قطعیت پائین) اعلام کردند. سه مطالعه مدل‌سازی دقت غربالگری را در فرودگاه‌ها ارزیابی کردند. پیامدهای اصلی اندازه‌گیری شده عبارت بودند از مواردی که با غربالگری ورود یا خروج، یا هر دو، در فرودگاه‌ها از دست رفتند یا شناسایی شدند. یک مطالعه حساسیت بسیار کمی را معادل 0.30 (95% CI؛ 0.1 تا 0.53) نشان داد، بدان معنی که 70% مسافران آلوده را از دست داد. مطالعه دیگر یک سناریوی غیر‐واقعی را برای دستیابی به نرخ تشخیص معادل 90% توصیف کرد، که نیاز به 0% عفونت بدون علامت دارد. مطالعه نهایی به دلیل کیفیت پائین روش‌شناسی، شواهد بسیار نامطمئنی را ارائه می‌دهد. نتیجه‌گیری‌های نویسندگان: پایه شواهد برای اثربخشی غربالگری از دو مطالعه مدل‌سازی ریاضی به دست آمده و با فرضیات آنها محدود می‌شود. شواهدی با قطعیت پائین نشان می‌دهد که غربالگری در مراکز مسافرتی ممکن است ورود موارد آلوده را اندکی آهسته کند. این مرور عدم قطعیت و تغییر در دقت استراتژی‌های غربالگری را برجسته می‌کند. ممکن است نسبت بالایی از افراد آلوده تشخیص داده نشوند و دیگران را آلوده کنند، و برخی از افراد سالم نیز به اشتباه مثبت شناخته شوند، این امر به آزمایشات تأ‌ییدی نیاز دارد و به‌طور بالقوه منجر به ایزوله کردن غیرضروری این دسته از افراد می‌شود. مطالعات بیشتر نیاز به ارزیابی سودمندی آزمایشات سریع آزمایشگاهی، غربالگری ترکیبی، و غربالگری مکرر دارند. همچنین انجام تحقیقات بیشتری در مورد استانداردهای مرجع، با دقت بیشتری از RT‐PCR لازم است. با توجه به حساسیت ضعیف رویکردهای موجود، یافته‌های ما به لزوم تأکید بیشتر بر راه‌های دیگری که ممکن است از انتقال پیشگیری کنند، از جمله پوشش صورت، فاصله‌گذاری فیزیکی، قرنطینه، و تجهیزات محافظتی شخصی مناسب برای کارکنان خط مقدم، اشاره دارد.La maladie à coronavirus 2019 (COVID‐19) est causée par le nouveau bêtacoronavirus, le coronavirus 2 du syndrome respiratoire aigu sévère (SARS‐CoV‐2). La plupart des personnes infectées par le SARS‐CoV‐2 ont une maladie bénigne avec des symptômes non spécifiques, mais environ 5 % d'entre elles deviennent gravement malades avec une insuffisance respiratoire, un choc septique et une défaillance de plusieurs organes. Une proportion inconnue de personnes infectées ne présentent jamais de symptômes de la COVID‐19 bien qu'elles soient infectieuses, c'est‐à‐dire qu'elles restent asymptomatiques. Celles qui développent la maladie passent par une période présymptomatique pendant laquelle elles sont infectieuses. Le dépistage universel des infections par le SARS‐CoV‐2 pour détecter les personnes infectées avant qu'elles ne se présentent cliniquement, pourrait donc être une mesure importante pour contenir la propagation de la maladie.Nous avons procédé à une revue rapide pour évaluer (1) l'efficacité du dépistage universel de l'infection par le SARS‐CoV‐2 par rapport à l'absence de dépistage et (2) la précision du dépistage universel chez les personnes ne s’étant pas présentées en soins cliniques pour des symptômes de la COVID‐19. STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Un spécialiste de l'information a effectué des recherches sur Ovid MEDLINE et dans la base de données téléchargeable des articles de recherche sur la COVID‐19 des Centres pour le contrôle et la prévention des maladies (Centers for Disease Control (CDC) COVID‐19 Research Articles Downloadable Database) jusqu'au 26 mai 2020. Nous avons effectué des recherches sur Embase.com, CENTRAL et le registre des études sur la Covid‐19 de Cochrane le 14 avril 2020. Nous avons recherché LitCovid jusqu'au 4 avril 2020. L'Organisation mondiale de la santé (OMS) a fourni des enregistrements issus de recherches quotidiennes dans les bases de données chinoises et dans PubMed jusqu'au 15 avril 2020. Nous avons également effectué des recherches dans trois répertoires de modèles (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS], et la Société pour la prise de décision médicale) le 8 avril 2020. CRITÈRES DE SÉLECTION: Essais, études observationnelles ou études de modélisation mathématique évaluant l'efficacité ou la précision du dépistage parmi la population générale où la prévalence du SARS‐CoV‐2 est inconnue. RECUEIL ET ANALYSE DES DONNÉES: Après avoir réalisé un test pilote des formulaires d'évaluation, un auteur a passé en revue les titres et les résumés. Deux auteurs ont examiné de manière indépendante le texte intégral des études et ont résolu les éventuels désaccords par une discussion avec un troisième auteur. Les résumés exclus par un premier auteur ont été doublement examinés par un deuxième auteur avant d'être exclus. Un des auteurs de la revue a extrait de manière indépendante les données, dont l'exhaustivité et l'exactitude ont été vérifiées par un deuxième auteur. Deux auteurs de la revue ont évalué de manière indépendante la qualité des études incluses en utilisant l'outil QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies) pour les études de précision diagnostique et un formulaire modifié conçu à l'origine pour les évaluations économiques, pour les études de modélisation. Nous avons résolu les divergences par consensus. Nous avons synthétisé les données probantes sous forme narrative et de tableaux. Nous avons évalué le niveau de confiance dans les données probantes pour les jours précédant l'épidémie, la transmission, les cas manqués et détectés, la précision diagnostique (c'est‐à‐dire les vrais positifs, les faux positifs, les vrais négatifs, les faux négatifs) en utilisant l'approche GRADE. RÉSULTATS PRINCIPAUX: Nous avons inclus 22 publications. Deux études de modélisation ont porté sur l'efficacité du dépistage universel. Vingt études (17 études de cohorte et 3 études de modélisation) ont porté sur la précision des tests de dépistage. Efficacité du dépistage Nous avons inclus deux études de modélisation. Une étude suggère que le dépistage des symptômes dans les terminaux de voyage, tels que les aéroports, pourrait légèrement ralentir mais pas arrêter l'importation de cas infectés (en supposant que 10 ou 100 voyageurs infectés par semaine réduisent le délai d'une épidémie locale à 8 jours ou 1 jour, respectivement). Nous avons évalué le risque de biais comme étant mineur ou ne suscitant pas de préoccupations, et le niveau de confiance dans les données probantes était faible, rétrogradé pour très sérieuses préoccupations quant à leur caractère indirecte. La deuxième étude de modélisation fournit des données probantes d’un niveau de confiance très faible indiquant que le dépistage du personnel de santé travaillant dans les services d'urgence au moyen de tests de laboratoire pourrait réduire la transmission aux patients et aux autres personnels de santé (en supposant une constante de transmission de 1,2 nouvelle infection pour 10 000 personnes, le dépistage hebdomadaire a réduit les infections de 5,1 % dans les 30 jours). Le niveau de confiance dans les données probantes était très faible, rétrogradé en raison du risque élevé de biais (préoccupations majeures) et de leur caractère indirect. Aucune étude de modélisation n'a rapporté les effets néfastes du dépistage. Précision des tests de dépistage Les 17 études de cohorte ont comparé une stratégie de dépistage index à un test de référence de réaction de polymérisation en chaîne par transcription inverse (RT‐PCR). Toutes les études, sauf une, ont fait état de la précision du dépistage à un moment précis et variaient largement en ce qui concerne la prévalence du SARS‐CoV‐2, les milieux de vie et les méthodes de mesure. Nous avons estimé que le risque global de biais n'était pas clair dans 16 études sur 17, principalement en raison du peu d'informations sur le test index et le standard de référence. Nous avons estimé qu'une étude présentait un risque élevé de biais en raison de l'inclusion de deux populations distinctes ayant probablement des prévalences différentes. Pour plusieurs stratégies de dépistage, les estimations de la sensibilité sont issues de petits échantillons. Pour les stratégies à moment précis, pour l'évaluation des symptômes, la sensibilité de 12 cohortes (524 personnes) variait de 0,00 à 0,60 (données probantes d’un niveau de confiance très faible) et la spécificité de 12 cohortes (16 165 personnes) variait de 0,66 à 1,00 (données probantes d’un niveau de confiance faible). Pour le dépistage par mesure directe de la température (3 cohortes, 822 personnes), les antécédents de voyages internationaux (2 cohortes, 13 080 personnes), ou l'exposition à des cas connus de COVID‐19 (3 cohortes, 13 205 personnes) ou des cas suspects (2 cohortes, 954 personnes), la sensibilité variait de 0,00 à 0,23 (données probantes d’un niveau de confiance faible à très faible) et la spécificité variait de 0,90 à 1,00 (données probantes d’un niveau de confiance faible à modéré). Pour l'évaluation des symptômes combinée à la mesure directe de la température (2 cohortes, 779 personnes), la sensibilité allait de 0,12 à 0,69 (données probantes d’un niveau de confiance très faible) et la spécificité de 0,90 à 1,00 (données probantes d’un niveau de confiance faible). Pour le test PCR rapide (1 cohorte, 21 personnes), la sensibilité était de 0,80 (intervalle de confiance (IC) à 95% de 0,44 à 0,96 ; données probantes d’un niveau de confiance très faible) et la spécificité de 0,73 (IC à 95% de 0,39 à 0,94 ; données probantes d’un niveau de confiance très faible). Une cohorte (76 personnes) a fait état d'un dépistage répété avec évaluation des symptômes et présente une sensibilité de 0,44 (IC à 95% 0,29 à 0,59 ; données probantes d’un niveau de confiance très faible) et une spécificité de 0,62 (IC à 95% 0,42 à 0,79 ; données probantes d’un niveau de confiance faible). Trois études de modélisation ont évalué la précision du contrôle dans les aéroports. Les principaux critères de jugement mesurés étaient les cas manqués ou détectés par les contrôles d'entrée ou de sortie, ou les deux, dans les aéroports. Une étude suggère une très faible sensibilité à 0,30 (IC à 95% 0,1 à 0,53), manquant 70% des voyageurs infectés. Une autre étude a décrit un scénario irréaliste pour atteindre un taux de détection de 90%, nécessitant 0% d'infections asymptomatiques. L'étude finale fournit des données probantes très incertaines en raison de la faible qualité méthodologique.Les données probantes sur l'efficacité du dépistage proviennent de deux études de modélisation mathématique et sont limitées par leurs hypothèses. Des données probantes d’un niveau de confiance faible suggèrent que le dépistage dans les terminaux de voyage pourrait légèrement ralentir l'importation de cas infectés. Cette revue met en évidence l'incertitude et la variation de la précision des stratégies de dépistage. Une forte proportion de personnes infectées pourrait passer inaperçue et infecter d'autres personnes, et certaines personnes en bonne santé pourraient être faussement identifiées comme étant positives, ce qui nécessite des tests de confirmation et peut entraîner l'isolement inutile de ces personnes. D'autres études doivent évaluer l'utilité des tests rapides de laboratoire, du dépistage combiné et du dépistage répété. Il faut également poursuivre les recherches sur les standards de référence avec une plus grande précision que la RT‐PCR. Étant donné la faible sensibilité des approches existantes, nos conclusions soulignent la nécessité de mettre davantage l'accent sur d'autres moyens susceptibles de prévenir la transmission, tels que se couvrir le visage, la distanciation physique, la quarantaine et l'utilisation d'équipements de protection individuelle adéquats pour les travailleurs en première ligne.La enfermedad por coronavirus 2019 (covid‐19) está causada por el nuevo betacoronavirus: coronavirus‐2 del síndrome respiratorio agudo grave por coronavirus‐2 (SARS‐CoV‐2, del inglés). La mayoría de las personas contagiadas con el SARS‐CoV‐2 presenta una enfermedad leve con síntomas inespecíficos, pero alrededor del 5% se enferma gravemente con insuficiencia respiratoria, shock séptico e insuficiencia multiorgánica. Un porcentaje desconocido de individuos contagiados nunca experimenta síntomas de covid‐19 aunque son infecciosos, es decir, permanecen asintomáticos. Los que presentan la enfermedad, pasan por un período presintomático durante el cual son infecciosos. Por consiguiente, el cribado universal de las infecciones por SARS‐CoV‐2 para detectar a las personas contagiadas antes de que se presenten clínicamente, podría ser una medida importante para contener la propagación de la enfermedad.Se realizó una revisión rápida para evaluar (1) la efectividad del cribado universal de la infección por SARS‐CoV‐2 en comparación con la ausencia de cribado y (2) la precisión del cribado universal en las personas que no han solicitado atención clínica por síntomas de covid‐19. MÉTODOS DE BÚSQUEDA: Un documentalista buscó en Ovid MEDLINE y en la base de datos COVID‐19 Research Articles Downloadable Database de los Centers for Disease Control (CDC) hasta el 26 de mayo de 2020. Se hicieron búsquedas en Embase.com, CENTRAL y en el Registro Cochrane de estudios de covid‐19 el 14 de abril de 2020. Se buscaron estudios en LitCovid el 4 de abril de 2020. La Organización Mundial de la Salud (OMS) proporcionó entradas de búsquedas diarias en las bases de datos chinas y en PubMed hasta el 15 de abril de 2020. También se buscó en tres repositorios de modelos (Covid‐Analytics, Models of Infectious Disease Agent Study [MIDAS], y Society for Medical Decision Making) el 8 de abril de 2020. CRITERIOS DE SELECCIÓN: Ensayos, estudios observacionales o estudios de modelización matemática que evalúen la efectividad o la exactitud de los cribados en poblaciones generales en las que se desconoce la prevalencia del SARS‐CoV‐2. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Tras realizar pruebas piloto de formularios de revisión, un autor de la revisión examinó los títulos y resúmenes. Dos autores de la revisión identificaron el texto completo los estudios de forma independiente y resolvieron cualquier desacuerdo mediante discusión con un tercer autor de la revisión. Los resúmenes excluidos por un primer autor de revisión fueron revisados por un segundo autor de revisión antes de la exclusión. Un autor de la revisión extrajo de forma independiente datos, que fueron verificados por un segundo autor de la revisión en aras de su completitud y exactitud. Dos autores de la revisión de manera independiente calificaron la calidad de los estudios incluidos mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) para estudios de exactitud diagnóstica y un formulario modificado diseñado en origen para evaluaciones económicas de estudios de modelización. Las diferencias se resolvieron mediante consenso. Se resumió la evidencia en formatos narrativo y de tabla. Se evaluó la certeza de la evidencia de los días hasta el brote, la transmisión, los casos no detectados y detectados, la exactitud del diagnóstico (es decir, verdaderos positivos, falsos positivos, verdaderos negativos, falsos negativos) utilizando los criterios GRADE.Se incluyeron 22 publicaciones. Dos estudios de modelización informaron de la efectividad del cribado universal. Veintidós estudios (17 estudios de cohorte y tres de modelización) informaron acerca de la exactitud de las pruebas de detección. Efectividad del cribado Se incluyeron dos estudios de modelización. Un estudio sugiere que la detección de síntomas en los espacios de tránsito de viajeros, como los aeropuertos, puede ralentizar ligeramente pero no detener la importación de casos infectados (suponiendo que 10 o 100 viajeros infectados por semana reduzcan la demora en un brote local a ocho días o un día, respectivamente). Se evaluó el riesgo de sesgo como menor o sin preocupaciones, y la certeza de la evidencia fue baja, reducida por carácter indirecto muy grave. El segundo estudio de modelización proporciona evidencia de muy baja certeza de que el cribado de los trabajadores sanitarios en los servicios de urgencias mediante pruebas de laboratorio podría reducir la transmisión a los pacientes y a otros trabajadores sanitarios (suponiendo una constante de transmisión de 1,2 nuevas infecciones por cada 10 000 personas, el cribado semanal redujo las infecciones en un 5,1% en un plazo de 30 días). La certeza de la evidencia fue muy baja, disminuida debido al riesgo alto de sesgo, (preocupaciones importantes) y al carácter indirecto. Ningún estudio de modelización informó de los efectos perjudiciales del cribado. Exactitud de pruebas de detección Los 17 estudios de cohorte compararon una estrategia de cribado índice con la prueba de referencia de reacción en cadena de la polimerasa con transcriptasa inversa (de sus siglas en inglés, RT‐PCR). Todos los estudios, excepto uno, informaron sobre la exactitud del cribado en un solo punto temporal y variaron ampliamente en cuanto a la prevalencia de SARS‐CoV‐2, los entornos y los métodos de medición. Se evaluó el riesgo general de sesgo como poco claro en 16 de 17 estudios, debido principalmente a la información limitada sobre la prueba del índice y el patrón de referencia. Calificamos un estudio como de alto riesgo de sesgo debido a la inclusión de dos poblaciones separadas con prevalencias probablemente diferentes. En varias estrategias de cribado, las estimaciones de sensibilidad procedían de muestras pequeñas. En el caso de las estrategias de punto temporal único, para la evaluación de los síntomas, la sensibilidad de 12 cohortes (524 personas) osciló entre 0,00 y 0,60 (evidencia de certeza muy baja) y la especificidad de 12 cohortes (16 165 personas) osciló entre 0,66 y 1,00 (evidencia de certeza baja). En el caso del cribado mediante la medición directa de la temperatura (tres cohortes, 822 personas), los antecedentes de viajes internacionales (dos cohortes, 13 080 personas), o la exposición a personas contagiadas conocidas (tres cohortes, 13 205 personas) o sospechosas de estarlo (dos cohortes, 954 personas), la sensibilidad osciló entre 0,00 y 0,23 (evidencia de certeza muy baja a baja) y la especificidad entre 0,90 y 1,00 (evidencia de certeza moderada). Para la evaluación de los síntomas más medición de la temperatura (dos cohortes, 779 personas) la sensibilidad osciló entre 0,12 y 0,69 (evidencia de certeza muy baja) y la especificidad entre 0,90 y 1,00 (evidencia de certeza baja). Para la prueba PCR rápida (una cohorte, 21 personas), la sensibilidad fue de 0,80 (intervalo de confianza [IC] del 95%: 0,44 a 0,96; evidencia de certeza muy baja), y la especificidad fue del 0,73 (IC del 95%: 0,39 a 0,94; evidencia de certeza muy baja). Una cohorte (76 personas) informó de cribados repetidos con evaluación de síntomas y mostró una sensibilidad de 0,44 (IC del 95%: 0,29 a 0,59; evidencia de certeza muy baja) una especificidad de 0,62 (IC del 95%: 0,42 a 0,79; evidencia de certeza baja). Tres estudios de modelización evaluaron la exactitud del cribado en aeropuertos. Los principales desenlaces que se midieron fueron los casos detectados o no detectados por medio de cribados de entrada o salida, o ambos, en los aeropuertos. Un estudio sugiere una sensibilidad muy baja, de 0,30 (IC del 95%: 0,1 a 0,53), y un 70% de viajeros infectados no detectados. Otro estudio describió un escenario poco realista para lograr una tasa de detección del 90%, que requiere un 0% de infecciones asintomáticas. El estudio final proporciona evidencia muy incierta debido a la baja calidad metodológica.La base de la evidencia de la efectividad del cribado proviene de dos estudios de modelización matemática y está limitada por sus supuestos. Evidencia de certeza baja sugiere que el cribado en espacios de tránsito de viajeros podría ralentizar ligeramente la importación de casos infectados. Esta revisión pone de relieve la incertidumbre y la variación en la exactitud de las estrategias de cribado. Es posible que un elevado porcentaje de personas infectadas no se detecte y continúe contagiando a otras, y que algunas personas sanas sean identificadas falsamente como positivas, con la consiguiente realización de pruebas de confirmación y un posible aislamiento innecesario de esas personas. Es necesario realizar más estudios para evaluar la utilidad de las pruebas rápidas de laboratorio, el cribado combinado y el cribado repetido. También es necesario investigar más en patrones de referencia con mayor exactitud que la RT‐PCR. Dada la escasa sensibilidad de las técnicas existentes, estos hallazgos apuntan a la necesidad de hacer mayor hincapié en otras formas de prevención de la transmisión, como cubrirse el rostro, mantener la distancia física, imponer cuarentena y utilizar equipos de protección individual adecuados para los trabajadores de primera línea.

Importance Preterm delivery results in adverse outcomes; identifying and treating bacterial vaginosis may reduce its occurrence. Objective To update the evidence on screening and treatment of asymptomatic bacterial vaginosis in pregnancy for the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, and trial registries through May 29, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through December 31, 2019. Study Selection Fair- or good-quality English-language studies evaluating diagnostic accuracy of tests feasible within primary care; randomized clinical trials (RCTs); nonrandomized controlled intervention studies (for harms only); or meta-analyses of metronidazole or clindamycin. Data Extraction and Synthesis Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures Sensitivity, specificity, preterm delivery, maternal adverse effects, congenital birth defects, childhood cancer. Results Forty-four studies (48 publications) were included. No studies evaluated the benefits or harms of screening. Twenty-five studies (n = 15 785) evaluated the accuracy of screening tests; across individual studies and tests, sensitivity ranged from 0.36 to 1.0 and specificity ranged from 0.49 to 1.0. Among trials reporting findings from general obstetric populations (n = 7953), no significant association was observed between treatment and spontaneous delivery before 37 weeks (pooled absolute risk difference [ARD], –1.44% [95% CI, −3.31% to 0.43%]; 8 RCTs, n = 7571) or any delivery before 37 weeks (pooled ARD, 0.20% [95% CI, −1.13% to 1.53%]; 6 RCTs, n = 6307). Among 5 trials reporting findings among women with a prior preterm delivery, findings were inconsistent; 3 showed a significant beneficial effect, while 2 did not. Maternal adverse events from treatment were infrequent and minor (eg, candidiasis) but were slightly more common with active treatment compared with placebo across 8 RCTs. Two meta-analyses of observational studies reported no significant association between metronidazole exposure and congenital malformations (odds ratio, 0.96 [95% CI, 0.75 to 1.22]; odds ratio, 1.08 [95% CI, 0.90 to 1.29]). One cohort study reported no significantly increased incidence of childhood cancer among metronidazole-exposed children (adjusted relative risk, 0.81 [95% CI, 0.41 to 1.59]). However, studies of in utero exposure had important limitations. Conclusions and Relevance Accuracy of screening tests for bacterial vaginosis varies. The evidence suggests no difference in the incidence of preterm delivery and related outcomes from treatment for asymptomatic bacterial vaginosis in a general obstetric population but was inconclusive for women with a prior preterm delivery. Maternal adverse events from treatment appear to be infrequent and minor, but the evidence about harms from in utero exposure was inconclusive.

Of the nearly four million births that occur each year in the United States, almost one in three is a cesarean delivery. Despite the increasing C-section rate over the years, there is no evidence that the increase has caused a decrease in neonatal or maternal mortality or morbidity. Bayesian decision analysis is used to model the decision between classifying a patient as “failure-to-progress,” which is cause for a C-section, using current information (prior probability) or information gathered (posterior probability) as labor continues. The Bayesian decision models determine the conditions under which it is appropriate to gather additional information (i.e., take an observation) before deciding to end labor and perform a C-section based on the decision maker’s belief about successful labor. During an observation period, the decision maker learns more about the patient and her medical state and the likelihood of a successful vaginal delivery is updated. This study determines the conditional value of information (conditional on the decision maker’s prior belief) and determines the conditions under which information has positive value. This model can be used to facilitate shared decision making for labor and delivery through communicating beliefs, risk perceptions, and the associated actions. The online appendix is available at https://doi.org/10.1287/serv.2018.0205 .

Objectives Risk-of-bias assessment is a central component of systematic reviews, but little conclusive empirical evidence exists on the validity of such assessments. In the context of such uncertainty, we present pragmatic recommendations that promote transparency and reproducibility in processes, address methodological advances in the risk-of-bias assessment, and can be applied consistently across review topics. Study Design and Setting Epidemiological study design principles; available empirical evidence, risk-of-bias tools, and guidance; and workgroup consensus. Results We developed recommendations for assessing the risk of bias of studies of health-care interventions specific to framing the focus and scope of risk-of-bias assessment; selecting the risk-of-bias categories; choosing assessment instruments; and conducting, analyzing, and presenting results of risk-of-bias assessments. Key recommendations include transparency and reproducibility of judgments, separating risk of bias from other constructs such as applicability and precision, and evaluating the risk of bias per outcome. We recommend against certain past practices, such as focusing on reporting quality, relying solely on study design or numerical quality scores, and automatically downgrading for industry sponsorship. Conclusion Risk-of-bias assessment remains a challenging but essential step in systematic reviews. We presented standards to promote transparency of judgments.

Rapid review products are intended to synthesize available evidence in a timely fashion while still meeting the needs of healthcare decision makers. Various methods and products have been applied for rapid evidence syntheses, but no single approach has been uniformly adopted. Methods to gain efficiency and compress the review time period include focusing on a narrow clinical topic and key questions; limiting the literature search; performing single (versus dual) screening of abstracts and full-text articles for relevance; and limiting the analysis and synthesis. In order to maintain the scientific integrity, including transparency, of rapid evidence syntheses, it is imperative that procedures used to streamline standard systematic review methods are prespecified, based on sound review principles and empiric evidence when possible, and provide the end user with an accurate and comprehensive synthesis. The collection of clinical preventive service recommendations maintained by the U.S. Preventive Services Task Force, along with its commitment to rigorous methods development, provide a unique opportunity to refine, implement, and evaluate rapid evidence synthesis methods and add to an emerging evidence base on rapid review methods. This paper summarizes the U.S. Preventive Services Task Force's use of rapid review methodology, its criteria for selecting topics for rapid evidence syntheses, and proposed methods to streamline the review process.

Background: Systematic reviews of complex interventions can vary widely in purpose, data availability and heterogeneity, and stakeholder expectations. Rationale: This article addresses the uncertainty that systematic reviewers face in selecting methods for reviews of complex interventions. Specifically, it lays out parameters for systematic reviewers to consider when selecting analytic approaches that best answer the questions at hand and suggests analytic techniques that may be appropriate in different circumstances. Discussion: Systematic reviews of complex interventions comprising multiple questions may use multiple analytic approaches. Parameters to consider when choosing analytic methods for complex interventions include nature and timing of the decision (clinical practice guideline, policy, or other); purpose of the review; extent of existing evidence; logistic factors such as the timeline, process, and resources for deciding the scope of the review; and value of information to be obtained from choosing specific systematic review methods. Reviewers may elect to revise their analytic approach based on new or changing considerations during the course of the review but should guard against bias through transparency of reporting. (C) 2017 The Authors. Published by Elsevier Inc. Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services [HHSA290201200004C] This project was funded under contract no. HHSA290201200004C from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.

The project goal was to compare the effectiveness of strategies to prevent and de-escalate aggressive behaviors among psychiatric patients in acute care settings, including interventions for reducing use of seclusion and restraint.Relevant databases were systematically reviewed for comparative studies of violence prevention and de-escalation strategies involving adult psychiatric patients in acute care settings. Studies (trials and cohort studies) were required to report on aggression or seclusion or restraint outcomes. Both risk of bias, an indicator of quality of individual studies, and strength of evidence (SOE) for each outcome were independently assessed by two study personnel.Seventeen primary studies met inclusion criteria. Evidence was limited for benefits and harms; information about characteristics that might modify the interventions' effectiveness, such as race or ethnicity, was especially limited. All but one study had a medium or high risk of bias and thus presented worrisome limitations. For prevention, risk assessment reduced both aggression and use of seclusion and restraint (low SOE), and multimodal interventions reduced the use of seclusion and restraint (low SOE). SOE for all other interventions, whether aimed at preventing or de-escalating aggression, and for modifying characteristics was insufficient.Available evidence about strategies for preventing and de-escalating aggressive behavior among psychiatric patients is very limited. Two preventive strategies, risk assessment and multimodal interventions consistent with the Six Core Strategies principles, may effectively lower aggressive behavior and use of seclusion and restraint, but more research is needed on how best to prevent and de-escalate aggressive behavior in acute care settings.

Objective Obesity can contribute to urinary symptoms such as urgency, frequency, and incontinence. In addition to classic treatments, weight loss interventions offer a unique clinical opportunity to improve these symptoms. Study design The American Urogynecologic Society Systematic Review Group conducted a review of articles on the impact of surgical and behavioral weight loss (BWL) interventions on urinary symptoms in overweight and obese women. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. Results The review group identified 43 publications from 39 studies, including 10 reports that used data from 5 randomized trials. Overall, there is high-certainty evidence that BWL, such as diet and exercise, decreases the prevalence of stress urinary incontinence 15% to 18% and overall urinary incontinence (UI) by 12% to 17% at 1 to 2.9 years. The certainty of evidence on the long-term impact of these interventions was lower. The certainty of the evidence was moderate to low regarding the benefit of BWL on urgency UI and overactive bladder symptoms. No randomized trials evaluated the impact of surgical weight loss on urinary symptoms, and the certainty of evidence of other study types was very low. Conclusions There is high-certainty evidence that BWL results in modest improvements in stress and overall UI in overweight and obese women at 1 to 2.9 years after the intervention. Robust studies with low risk of bias are needed to assess whether these benefits are maintained over the long term and are associated with adverse events and to assess the impact of surgical weight loss interventions on urinary outcomes in overweight and obese women.

BackgroundWeb 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.MethodsWe 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.ResultsThe 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%).ConclusionsThe 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.

Background Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. Purpose Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. Data Sources English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. Study Selection Two persons independently selected studies based on predefined inclusion criteria. Data Extraction One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. Data Synthesis We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. Limitations Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. Conclusions Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. Registration PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260).

Background Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent. Methods We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019. Results We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used. Conclusions Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.

Importance Low serum vitamin D levels have been associated with adverse clinical outcomes; identifying and treating deficiency may improve outcomes. Objective To review the evidence about screening for vitamin D deficiency in adults. Data Sources PubMed, EMBASE, the Cochrane Library, and trial registries through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020. Study Selection Fair- or good-quality, English-language randomized clinical trials (RCTs) of screening with serum 25-hydroxyvitamin D (25[OH]D) compared with no screening, or treatment with vitamin D (with or without calcium) compared with placebo or no treatment conducted in nonpregnant adults; nonrandomized controlled intervention studies for harms only. Treatment was limited to studies enrolling or analyzing participants with low serum vitamin D levels. Data Extraction and Synthesis Two reviewers assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures Mortality, incident fractures, falls, diabetes, cardiovascular events, cancer, depression, physical functioning, and infection. Results Forty-six studies (N = 16 205) (77 publications) were included. No studies directly evaluated the health benefits or harms of screening. Among community-dwelling populations, treatment was not significantly associated with mortality (pooled absolute risk difference [ARD], 0.3% [95% CI, −0.6% to 1.1%]; 8 RCTs, n = 2006), any fractures (pooled ARD, −0.3% [95% CI, −2.1% to 1.6%]; 6 RCTs, n = 2186), incidence of diabetes (pooled ARD, 0.1% [95% CI, −1.3% to 1.6%]; 5 RCTs, n = 3356), incidence of cardiovascular disease (2 RCTs; hazard ratio, 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs; hazard ratio, 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58], or depression (3 RCTs, various measures reported). The pooled ARD for incidence of participants with 1 or more falls was −4.3% (95% CI, −11.6% to 2.9%; 6 RCTs). The evidence was mixed for the effect of treatment on physical functioning (2 RCTs) and limited for the effect on infection (1 RCT). The incidence of adverse events and kidney stones was similar between treatment and control groups. Conclusions and Relevance No studies evaluated the direct benefits or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the effect of treatment on physical functioning and infection.

AB Importance: Neural tube defects are among the most common congenital anomalies in the United States. Periconceptional folic acid supplementation is a primary care-relevant preventive intervention. Objective: To review the evidence on folic acid supplementation for preventing neural tube defects to inform the US Preventive Services Task Force for an updated Recommendation Statement. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts. Study Selection: English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries. Data Extraction and Synthesis: Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled. Main Outcomes and Measures: Neural tube defects, harms of treatment (twinning, respiratory outcomes). Results: A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from 0.93 to 1.4 and confidence intervals spanning the null (n > 13 990). Regarding harms, 1 trial (OR, 1.40 [95% CI, 0.89-2.21]; n = 4767) and 1 cohort study (OR, 1.04 [95% CI, 0.91-1.18]; n = 2620) found no statistically significant increased risk of twinning. Three systematic reviews found no consistent evidence of increased risk of asthma (OR, 1.06 [95% CI, 0.99-1.14]; n = 14 438), wheezing, or allergy. Conclusions and Relevance: In studies conducted before the initiation of food fortification in the United States in 1998, folic acid supplementation provided protection against neural tube defects. Newer postfortification studies have not demonstrated a protective association but have the potential for misclassification and recall bias, which can attenuate the measured association of folic acid supplementation with neural tube defects. Copyright 2017 by the American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use. American Medical Association, 515 N. State St, Chicago, IL 60610.

Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks.To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force.PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020.Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions.Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively.Sensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments.Forty-two studies from 43 publications were included (N12 400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were -4.38 mm Hg (95% CI, -7.27 to -2.16) for angiotensin-converting enzyme inhibitors and -3.07 mm Hg (95% CI, -4.99 to -1.44) for angiotensin receptor blockers. Candesartan reduced SBP by -6.56 mm Hg (P .001; n = 240). β-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (-4.9 mm Hg, P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (-2.2 mm Hg, P .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (-7.6 mm Hg; P .001; n = 95). Low-salt diet did not achieve reductions of blood pressure.Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.

Kokoro is a comprehensive term in Japanese religion, philosophy and aesthetics often translated as ‘heart’, whose range of meanings includes mind, wisdom, aspiration, essence, attention, sincerity and sensibility. In Buddhist texts and in philosophy, kokoro (or shin in its Sino-Japanese reading) denotes mind, heart or inner nature, the site of human sentience or delusion. By extension, in pre-modern theories of art, kokoro signifies simultaneously the emotional capacity of the artist to respond to the natural world, which ideally catalyzes the act of creation; the parallel ability of an audience to respond to such a work of art and thus indirectly to the experience of the artist; and finally the evaluation of such a work as possessing the ‘right conception’, kokoro ari or alternatively ushin.

While the terms ‘aesthetics’ and ‘philosophy’ were only introduced into Japan during the Meiji Period (post 1868), Japanese culture has nevertheless witnessed the proliferation of various arts and theories of art for over a millenium. Given that ‘aesthetics’ generally connotes a scientific, often taxonomic approach to the inquiry into beauty and art, it may be preferable to consider Japanese art and theories of art from the perspective of different ways of artistry, rather than impose on it alien categories and assumptions. Even our understanding about what constitutes art must alter when we consider such arts as the production of incense, the tea ceremony, the martial arts or flower arrangement, most of which do not have precise analogues in the West; or if they do, are not considered arts alongside poetry, drama, music and painting. One of the hallmarks of Japanese art is the emphasis on an awareness of nature. Not only is the natural world a rich storehouse of images and metaphors for use as subject matter, but it is also the means whereby the practices, values and aspirations of the art are defined. Significantly, art itself is seen to be catalysed directly by an encounter with the natural world. All living beings, we are told, are given to song. Yet the natural world also came to be a shibboleth in society among the members of the Japanese court, where a finely honed seasonal awareness came to attest to the refinement and sensibility of the individual. Of all the arts, poetry was seen as pre-eminent, in part because of poetry’s powers to influence the spirits inherent in the natural world. Even the emphasis on place and place-names in Japanese art may be traced to an understanding of the Japanese landscape and language as sacredly imbued. Another feature of Japanese art and theories of art is its orientation toward the human. In other words, we may define Japanese art as ‘expressive–affective’ in its configuration, stressing the experience of the artist as well as the response of the audience in encountering such a work. In fact, the two roles of artist and audience are related through the focus of the work of art, which usually frames a single moment and its quintessential significance, hon-i, which is unchanging. The quality which ideally characterizes both artist and audience is makoto or sincerity, underlining the point that the function of most Japanese art is to make us feel, rather than think. As in a number of other traditions, Japanese ways of art are bound up inextricably with issues of religion and religious practice. Not only did Shintō animatism have a profound impact on how Japanese viewed their landscape as well as their own lives, but other imported systems of belief also influenced the course of artistic development, especially Buddhism. Buddhism darkened the hues of classical Japanese art by introducing ideas such as mappō (Latter Days of the Law), which saw the present as degraded and corrupt with respect to the past, and mujō (inconstancy), or the awareness of the ephemerality of this phenomenal world. In Mahāyāna Buddhism, art was perceived as a means of religious awakening, both in the case of poetry viewed as a form of intense meditation (shikan) and as parables whereby the truth could be disseminated obliquely (hōben). This paved the way for the pursuit of various forms of art to become a path (michi) to spiritual awareness. The relation of teacher and student in an art form closely resembled the relation of spiritual master to disciple, a feature which is echoed in the various ‘secret’ artistic treatises whose form, approach and significance suggest esoteric Buddhist manuals setting forth precepts for future generations. Japanese theories of art also concerned themselves with various aesthetic ideals, distillations of the changing notion of beauty in each era. From aware (the beauty inherent in transience) and miyabi (courtly beauty) during the Heian Period (784–1185), to yūgen (the beauty of mystery and overtones) and sabi (the beauty of desolation and loneliness) in the medieval period, finally to wabi (the beauty of dearth and the humble) and karumi (the beauty of playful lightness) during the Edo Period (1600–1868), to mention only a few of the many ideals, we see an evolution of ideals as a response to cultural and historical change. What becomes evident in any survey is the assumption of an underlying unity, as in the notions that the impulse toward art is natural and universal; that art functions as a bridge mediating the experience of artist and audience; that sincerity and heart are to be privileged above all other qualities; and that the discipline of art can be a means of spiritual awakening. But we also discover that ideas, such as play, are critical to all forms of art in Japan. Other issues have surfaced periodically in various art forms in the course of Japanese history, such as the struggle between tradition and innovation or the debate about art as spontaneous versus art as the product of careful cultivation (that is, the question of artifice in art), or the question of the singularity of Japanese art.