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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hand cleaning with ash for reducing the spread of viral and bacterial infections: a rapid review.

BACKGROUND: Handwashing is important to reduce the spread and transmission of infectious disease. Ash, the residue from stoves and fires, is a material used for cleaning hands in settings where soap is not widely available. OBJECTIVES: To assess the benefits and harms of hand cleaning with ash compared with hand cleaning using soap or other materials for reducing the spread of viral and bacterial infections. SEARCH METHODS: On 26 March 2020 we searched CENTRAL, MEDLINE, Embase, WHO Global Index Medicus, and the WHO International Clinical Trials Registry Platform. SELECTION CRITERIA: We included all types of studies, in any population, that examined hand cleaning with ash compared to hand cleaning with any other material. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and full texts, and one review author extracted outcome data and assessed risk of bias, which another review author double-checked. We used the ROBINS-I tool for observational studies, we used RoB 2.0 for three interventional studies, and we used GRADE to assess the certainty of the evidence. We planned to synthesise data with random-effects meta-analyses. Our prespecified outcome measures were overall mortality, number of cases of infections (as defined in the individual studies), severity of infectious disease, harms (as reported in the individual studies), and adherence. MAIN RESULTS: We included 14 studies described in 19 records using eight different study designs, but only one randomised trial. The studies were primarily conducted in rural settings in low- and lower-middle-income countries. Six studies reported outcome data relevant to our review. A retrospective case-control study and a cohort study assessed diarrhoea in children under the age of five years and self-reported reproductive tract symptoms in women, respectively. It was very uncertain whether the rate of hospital contacts for moderate-to-severe diarrhoea in children differed between households that cleaned hands using ash compared with households cleaning hands using soap (RR 0.97, 95% CI 0.84 to 1.11; very low-certainty evidence). Similarly, it was very uncertain whether the rate of women experiencing symptoms of reproductive tract infection differed between women cleaning hands with ash compared with cleaning hands using soap (RR 0.48, 95% CI 0.12 to 1.86; very low-certainty evidence) or when compared with handwashing with water only or not washing hands (RR 0.50, 95% CI 0.13 to 1.96; very low-certainty evidence). Four studies reported on bacteriological counts after hand wash. We rated all four studies at high risk of bias, and we did not synthesise data due to methodological heterogeneity and unclear outcome reporting. AUTHORS' CONCLUSIONS: Based on the available evidence, the benefits and harms of hand cleaning with ash compared with soap or other materials for reducing the spread of viral or bacterial infections are uncertain.

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

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

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

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

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

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

Prevalence of mental disorders in young refugees and asylum seekers in European Countries: a systematic review.

The European Union member states received about 385,000 asylum applications from children and adolescents below 18 years in 2015, and 398,000 in 2016. The latest political crises and war have led to an upsurge in refugee movements into European countries, giving rise to a re-evaluation of the epidemiology of psychiatric disorders and mental health problems among young refugees and asylum seekers. We systematically searched five electronic databases and reference lists of pertinent review articles. We then screened the results of forward citation tracking of key articles for relevant studies in the field for the period from January 1990 to October 2017. We dually reviewed citations and assessed risk of bias. We reported the results narratively, as meta-analyses were impeded due to high heterogeneity. We included 47 studies covered in 53 articles. Overall, the point prevalence of the investigated psychiatric disorders and mental health problems varied widely among studies (presenting interquartile ranges): for posttraumatic stress disorder between 19.0 and 52.7%, for depression between 10.3 and 32.8%, for anxiety disorders between 8.7 and 31.6%, and for emotional and behavioural problems between 19.8 and 35.0%. The highly heterogeneous evidence base could be improved by international, methodologically comparable studies with sufficiently large sample sizes drawn randomly among specific refugee populations. The prevalence estimates suggest, nevertheless, that specialized mental health care services for the most vulnerable refugee and asylum-seeking populations are needed. REGISTRATION: The systematic review protocol was registered in PROSPERO on October 19th, 2017 with the number: CRD42017080039 and is available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=80039.

[Evidence-based recommendations for the revision of the Austrian periodic health examination]. / Evidenzbasierte Empfehlungen zur Überarbeitung der österreichischen Vorsorgeuntersuchung.

The Austrian periodic health examination (PHE) was introduced in 1974 as a health insurance benefit and was redesigned for the last time in 2005. Therefore, the aim of this work was to revise the scientific basis of the PHE using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We updated the scientific evidence of examinations and consultations that are currently part of the PHE and searched and integrated new examinations. We assessed the expectations of the population towards the PHE in three focus groups. A panel of experts developed evidence-based recommendations for the revised PHE. They formulated 26 recommendations on 20 target diseases or risk factors. In comparison to the previous PHE, the panel added screening for abdominal aortic aneurysm, osteoporotic fracture risk, and chronic kidney disease to the recommendations, while screening for asymptomatic bacteriuria, screening for iron deficiency/pernicious anaemia, and risk identification of glaucoma should no longer be included.

Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis.

BACKGROUND: Sunlight exposure and high vitamin D status have been hypothesised to reduce the risk of developing dementia. The objective of our research was to determine whether lack of sunlight and hypovitaminosis D over time are associated with dementia. METHODS: We systematically searched MEDLINE (via PubMed), Cochrane Library, EMBASE, SCOPUS, Web of Science, ICONDA, and reference lists of pertinent review articles from 1990 to October 2015. We conducted random effects meta-analyses of published and unpublished data to evaluate the influence of sunlight exposure or vitamin D as a surrogate marker on dementia risk. RESULTS: We could not identify a single study investigating the association between sunlight exposure and dementia risk. Six cohort studies provided data on the effect of serum vitamin D concentration on dementia risk. A meta-analysis of five studies showed a higher risk for persons with serious vitamin D deficiency (<25 nmol/L or 7-28 nmol/L) compared to persons with sufficient vitamin D supply (≥50 nmol/L or 54-159 nmol/L) (point estimate 1.54; 95% CI 1.19-1.99, I2 = 20%). The strength of evidence that serious vitamin D deficiency increases the risk of developing dementia, however, is very low due to the observational nature of included studies and their lack of adjustment for residual or important confounders (e.g. ApoE ε4 genotype), as well as the indirect relationship between Vitamin D concentrations as a surrogate for sunlight exposure and dementia risk. CONCLUSIONS: The results of this systematic review show that low vitamin D levels might contribute to the development of dementia. Further research examining the direct and indirect relationship between sunlight exposure and dementia risk is needed. Such research should involve large-scale cohort studies with homogeneous and repeated assessment of vitamin D concentrations or sunlight exposure and dementia outcomes.

Guidance on how to efficiently find, choose, and use available systematic reviews was developed.

OBJECTIVE: The aim of this paper is to provide clinicians and authors of clinical guidelines or patient information with practical guidance on searching and choosing systematic reviews(s) (SR[s]) and, where adequate, on making use of SR(s). STUDY DESIGN AND SETTING: At the German conference of the EBM-Network a workshop on the topic was held to identify the most important areas where guidance for practice appears necessary. After the workshop, we established working groups. These included SR users with different backgrounds (e. g. information specialists, epidemiologists) and working areas. Each working group developed and consented a draft guidance based on their expert knowledge and experiences. The results were presented to the entire group and finalized in an iterative process. RESULTS: We developed a practical guidance that answers questions that usually arise when choosing and using SR(s). 1: How to efficiently find high-quality SRs? 2: How to choose the most appropriate SR? 3: What to do if no SR of sufficient quality could be identified? In addition, we developed an algorithm that links these steps and accounts for their interaction. The resulting guidance is primarily directed at clinicians and developers of clinical practice guidelines or patient information resources. CONCLUSION: We suggest practical guidance for making the best use of SRs when answering a specific research question. The guidance may contribute to the efficient use of existing SRs. Potential benefits when using existing SRs should be always weighted against potential limitations.