Showing papers in "Cochrane Database of Systematic Reviews in 2020"

Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection.

Abstract: Background Accurate rapid diagnostic tests for SARS‐CoV‐2 infection could contribute to clinical and public health strategies to manage the COVID‐19 pandemic. Point‐of‐care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. Objectives To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Search methods Electronic searches of the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID‐19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. Selection criteria We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established diagnostic criteria). Data collection and analysis Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS‐2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular‐based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. Main results Seventy‐eight study cohorts were included (described in 64 study reports, including 20 pre‐prints), reporting results for 24,087 samples (7,415 with confirmed SARS‐CoV‐2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (37%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (37%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS‐CoV‐2 based on a single RT‐PCR result, and none included participants meeting case definitions for probable COVID‐19. Antigen tests Forty‐eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self‐testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer’s instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. Authors' conclusions Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID‐19 diagnostics (‘acceptable’ sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT‐PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self‐testing) are required.

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

Abstract: 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.

Antibody tests for identification of current and past infection with SARS‐CoV‐2

Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. Objectives To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. Search methods We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. Selection criteria We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). Data collection and analysis We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). Main results We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. Authors' conclusions The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

Abstract: BACKGROUND: The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%). AUTHORS' CONCLUSIONS: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions.

Barriers and facilitators to healthcare workers' adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis.

Abstract: Background This review is one of a series of rapid reviews that Cochrane contributors have prepared to inform the 2020 COVID‐19 pandemic. When new respiratory infectious diseases become widespread, such as during the COVID‐19 pandemic, healthcare workers’ adherence to infection prevention and control (IPC) guidelines becomes even more important. Strategies in these guidelines include the use of personal protective equipment (PPE) such as masks, face shields, gloves and gowns; the separation of patients with respiratory infections from others; and stricter cleaning routines. These strategies can be difficult and time‐consuming to adhere to in practice. Authorities and healthcare facilities therefore need to consider how best to support healthcare workers to implement them. Objectives To identify barriers and facilitators to healthcare workers’ adherence to IPC guidelines for respiratory infectious diseases. Search methods We searched OVID MEDLINE on 26 March 2020. As we searched only one database due to time constraints, we also undertook a rigorous and comprehensive scoping exercise and search of the reference lists of key papers. We did not apply any date limit or language limits. Selection criteria We included qualitative and mixed‐methods studies (with a distinct qualitative component) that focused on the experiences and perceptions of healthcare workers towards factors that impact on their ability to adhere to IPC guidelines for respiratory infectious diseases. We included studies of any type of healthcare worker with responsibility for patient care. We included studies that focused on IPC guidelines (local, national or international) for respiratory infectious diseases in any healthcare setting. These selection criteria were framed by an understanding of the needs of health workers during the COVID‐19 pandemic. Data collection and analysis Four review authors independently assessed the titles, abstracts and full texts identified by our search. We used a prespecified sampling frame to sample from the eligible studies, aiming to capture a range of respiratory infectious disease types, geographical spread and data‐rich studies. We extracted data using a data extraction form designed for this synthesis. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool. We used a ‘best fit framework approach’ to analyse and synthesise the evidence. This provided upfront analytical categories, with scope for further thematic analysis. We used the GRADE‐CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and developed implications for practice. Main results We found 36 relevant studies and sampled 20 of these studies for our analysis. Ten of these studies were from Asia, four from Africa, four from Central and North America and two from Australia. The studies explored the views and experiences of nurses, doctors and other healthcare workers when dealing with severe acute respiratory syndrome (SARS), H1N1, MERS (Middle East respiratory syndrome), tuberculosis (TB), or seasonal influenza. Most of these healthcare workers worked in hospitals; others worked in primary and community care settings. Our review points to several barriers and facilitators that influenced healthcare workers’ ability to adhere to IPC guidelines. The following factors are based on findings assessed as of moderate to high confidence. Healthcare workers felt unsure as to how to adhere to local guidelines when they were long and ambiguous or did not reflect national or international guidelines. They could feel overwhelmed because local guidelines were constantly changing. They also described how IPC strategies led to increased workloads and fatigue, for instance because they had to use PPE and take on additional cleaning. Healthcare workers described how their responses to IPC guidelines were influenced by the level of support they felt that they received from their management team. Clear communication about IPC guidelines was seen as vital. But healthcare workers pointed to a lack of training about the infection itself and about how to use PPE. They also thought it was a problem when training was not mandatory. Sufficient space to isolate patients was also seen as vital. A lack of isolation rooms, anterooms and shower facilities was a problem. Other important practical measures described by healthcare workers included minimising overcrowding, fast‐tracking infected patients, restricting visitors, and providing easy access to handwashing facilities. A lack of PPE, and equipment that was of poor quality, was a serious concern for healthcare workers and managers. They also pointed to the need to adjust the volume of supplies as infection outbreaks continued. Healthcare workers believed that they followed IPC guidance more closely when they saw the value of it. Some healthcare workers felt motivated to follow the guidance because of fear of infecting themselves or their families, or because they felt responsible for their patients. Some healthcare workers found it difficult to use masks and other equipment when it made patients feel isolated, frightened or stigmatised. Healthcare workers also found masks and other equipment uncomfortable to use. The workplace culture could also influence whether healthcare workers followed IPC guidelines or not. Across many of the findings, healthcare workers pointed to the importance of including all staff, including cleaning staff, porters, kitchen staff and other support staff when implementing IPC guidelines. Authors' conclusions Healthcare workers point to several factors that influence their ability and willingness to follow IPC guidelines when managing respiratory infectious diseases. These include factors tied to the guideline itself and how it is communicated, support from managers, workplace culture, training, physical space, access to and trust in personal protective equipment, and a desire to deliver good patient care. The review also highlights the importance of including all facility staff, including support staff, when implementing IPC guidelines.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.

Abstract: Background Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. Search methods We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 4 June 2020. Selection criteria We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. Data collection and analysis We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. MAIN RESULTS: This is the first living update of our review. We included 20 studies (1 RCT, 3 controlled NRSIs, 16 non-controlled NRSIs) with 5443 participants, of whom 5211 received convalescent plasma, and identified a further 98 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 50 are randomised. We did not identify any completed studies evaluating hyperimmune immunoglobulin. Overall risk of bias of included studies was high, due to study design, type of participants, and other previous or concurrent treatments. Effectiveness of convalescent plasma for people with COVID-19 We included results from four controlled studies (1 RCT (stopped early) with 103 participants, of whom 52 received convalescent plasma; and 3 controlled NRSIs with 236 participants, of whom 55 received convalescent plasma) to assess effectiveness of convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. All-cause mortality at hospital discharge (1 controlled NRSI, 21 participants) We are very uncertain whether convalescent plasma has any effect on all-cause mortality at hospital discharge (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.61 to 1.31; very low-certainty evidence). Time to death (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma prolongs time to death (RCT: hazard ratio (HR) 0.74, 95% CI 0.30 to 1.82; controlled NRSI: HR 0.46, 95% CI 0.22 to 0.96; very low-certainty evidence). Improvement of clinical symptoms, assessed by need for respiratory support (1 RCT, 103 participants; 1 controlled NRSI, 195 participants) We are very uncertain whether convalescent plasma has any effect on improvement of clinical symptoms at seven days (RCT: RR 0.98, 95% CI 0.30 to 3.19), 14 days (RCT: RR 1.85, 95% CI 0.91 to 3.77; controlled NRSI: RR 1.08, 95% CI 0.91 to 1.29), and 28 days (RCT: RR 1.20, 95% CI 0.80 to 1.81; very low-certainty evidence). Quality of life No studies reported this outcome. Safety of convalescent plasma for people with COVID-19 We included results from 1 RCT, 3 controlled NRSIs and 10 non-controlled NRSIs assessing safety of convalescent plasma. Reporting of adverse events and serious adverse events was variable. The controlled studies reported on adverse events and serious adverse events only in participants receiving convalescent plasma. The duration of follow-up varied. Some, but not all, studies included death as a serious adverse event. Grade 3 or 4 adverse events (13 studies, 201 participants) The studies did not report the grade of adverse events. Thirteen studies (201 participants) reported on adverse events of possible grade 3 or 4 severity. The majority of these adverse events were allergic or respiratory events. We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence). Serious adverse events (14 studies, 5201 participants) Fourteen studies (5201 participants) reported on serious adverse events. The majority of participants were from one non-controlled NRSI (5000 participants), which reported only on serious adverse events limited to the first four hours after convalescent plasma transfusion. This study included death as a serious adverse event; they reported 15 deaths, four of which they classified as potentially, probably or definitely related to transfusion. Other serious adverse events reported in all studies were predominantly allergic or respiratory in nature, including anaphylaxis, transfusion-associated dyspnoea, and transfusion-related acute lung injury (TRALI). We are very uncertain whether or not convalescent plasma affects the number of serious adverse events. Authors' conclusions We are very uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. For safety outcomes we also included non-controlled NRSIs. There was limited information regarding adverse events. Of the controlled studies, none reported on this outcome in the control group. There is only very low-certainty evidence for safety of convalescent plasma for COVID-19. While major efforts to conduct research on COVID-19 are being made, problems with recruiting the anticipated number of participants into these studies are conceivable. The early termination of the first RCT investigating convalescent plasma, and the multitude of studies registered in the past months illustrate this. It is therefore necessary to critically assess the design of these registered studies, and well-designed studies should be prioritised. Other considerations for these studies are the need to report outcomes for all study arms in the same way, and the importance of maintaining comparability in terms of co-interventions administered in all study arms. There are 98 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 50 are RCTs. This is the first living update of the review, and we will continue to update this review periodically. These updates may show different results to those reported here.

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review

Abstract: Background Evidence from disease epidemics shows that healthcare workers are at risk of developing short- and long-term mental health problems. The World Health Organization (WHO) has warned about the potential negative impact of the COVID-19 crisis on the mental well-being of health and social care professionals. Symptoms of mental health problems commonly include depression, anxiety, stress, and additional cognitive and social problems; these can impact on function in the workplace. The mental health and resilience (ability to cope with the negative effects of stress) of frontline health and social care professionals ('frontline workers' in this review) could be supported during disease epidemics by workplace interventions, interventions to support basic daily needs, psychological support interventions, pharmacological interventions, or a combination of any or all of these. Objectives Objective 1: to assess the effects of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Objective 2: to identify barriers and facilitators that may impact on the implementation of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Search methods On 28 May 2020 we searched the Cochrane Database of Systematic Reviews, CENTRAL, MEDLINE, Embase, Web of Science, PsycINFO, CINAHL, Global Index Medicus databases and WHO Institutional Repository for Information Sharing. We also searched ongoing trials registers and Google Scholar. We ran all searches from the year 2002 onwards, with no language restrictions. Selection criteria We included studies in which participants were health and social care professionals working at the front line during infectious disease outbreaks, categorised as epidemics or pandemics by WHO, from 2002 onwards. For objective 1 we included quantitative evidence from randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies, which investigated the effect of any intervention to support mental health or resilience, compared to no intervention, standard care, placebo or attention control intervention, or other active interventions. For objective 2 we included qualitative evidence from studies that described barriers and facilitators to the implementation of interventions. Outcomes critical to this review were general mental health and resilience. Additional outcomes included psychological symptoms of anxiety, depression or stress; burnout; other mental health disorders; workplace staffing; and adverse events arising from interventions. Data collection and analysis Pairs of review authors independently applied selection criteria to abstracts and full papers, with disagreements resolved through discussion. One review author systematically extracted data, cross-checked by a second review author. For objective 1, we assessed risk of bias of studies of effectiveness using the Cochrane 'Risk of bias' tool. For objective 2, we assessed methodological limitations using either the CASP (Critical Appraisal Skills Programme) qualitative study tool, for qualitative studies, or WEIRD (Ways of Evaluating Important and Relevant Data) tool, for descriptive studies. We planned meta-analyses of pairwise comparisons for outcomes if direct evidence were available. Two review authors extracted evidence relating to barriers and facilitators to implementation, organised these around the domains of the Consolidated Framework of Implementation Research, and used the GRADE-CERQual approach to assess confidence in each finding. We planned to produce an overarching synthesis, bringing quantitative and qualitative findings together. Main results We included 16 studies that reported implementation of an intervention aimed at supporting the resilience or mental health of frontline workers during disease outbreaks (severe acute respiratory syndrome (SARS): 2; Ebola: 9; Middle East respiratory syndrome (MERS): 1; COVID-19: 4). Interventions studied included workplace interventions, such as training, structure and communication (6 studies); psychological support interventions, such as counselling and psychology services (8 studies); and multifaceted interventions (2 studies). Objective 1: a mixed-methods study that incorporated a cluster-randomised trial, investigating the effect of a work-based intervention, provided very low-certainty evidence about the effect of training frontline healthcare workers to deliver psychological first aid on a measure of burnout. Objective 2: we included all 16 studies in our qualitative evidence synthesis; we classified seven as qualitative and nine as descriptive studies. We identified 17 key findings from multiple barriers and facilitators reported in studies. We did not have high confidence in any of the findings; we had moderate confidence in six findings and low to very low confidence in 11 findings. We are moderately confident that the following two factors were barriers to intervention implementation: frontline workers, or the organisations in which they worked, not being fully aware of what they needed to support their mental well-being; and a lack of equipment, staff time or skills needed for an intervention. We are moderately confident that the following three factors were facilitators of intervention implementation: interventions that could be adapted for local needs; having effective communication, both formally and socially; and having positive, safe and supportive learning environments for frontline workers. We are moderately confident that the knowledge or beliefs, or both, that people have about an intervention can act as either barriers or facilitators to implementation of the intervention. Authors' conclusions There is a lack of both quantitative and qualitative evidence from studies carried out during or after disease epidemics and pandemics that can inform the selection of interventions that are beneficial to the resilience and mental health of frontline workers. Alternative sources of evidence (e.g. from other healthcare crises, and general evidence about interventions that support mental well-being) could therefore be used to inform decision making. When selecting interventions aimed at supporting frontline workers' mental health, organisational, social, personal, and psychological factors may all be important. Research to determine the effectiveness of interventions is a high priority. The COVID-19 pandemic provides unique opportunities for robust evaluation of interventions. Future studies must be developed with appropriately rigorous planning, including development, peer review and transparent reporting of research protocols, following guidance and standards for best practice, and with appropriate length of follow-up. Factors that may act as barriers and facilitators to implementation of interventions should be considered during the planning of future research and when selecting interventions to deliver within local settings.

Laparoscopic surgery for endometriosis

Abstract: Background Endometriosis is the presence in inappropriate sites of tissue that normally lines the uterus It can cause pain and subfertility Different treatments for endometriosis are available, one of which is laparoscopic ('key hole') surgery, performed to remove visible areas of endometriosis Cochrane review authors assessed the evidence on the use of laparoscopic surgery to treat pain and fertility problems in women with endometriosis Laparoscopic surgical techniques include ablation, which means destruction of a lesion (for example by burning), and excision, which means cutting a lesion out Study characteristics We included 10 randomised controlled trials (involving 973 participants) They were conducted in Australia, Canada, Egypt, Iran and the United Kingdom Most compared laparoscopic ablation or excision versus diagnostic laparoscopy only Four of the 10 studies reported their source of funding The evidence was current to July 2013 Key results We found that laparoscopic surgery may be of benefit in treating overall pain and subfertility associated with mild to moderate endometriosis Laparoscopic excision and ablation were similarly effective in relieving pain, although this result came from a single study There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety

Thoracic imaging tests for the diagnosis of COVID-19.

Abstract: Background: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Our 2020 edition of this review showed thoracic (chest) imaging to be sensitive and moderately specific in the diagnosis of coronavirus disease 2019 (COVID-19). In this update, we include new relevant studies, and have removed studies with case-control designs, and those not intended to be diagnostic test accuracy studies. Objectives: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19. Search methods: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 30 September 2020. We did not apply any language restrictions. Selection criteria: We included studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19 and that reported estimates of test accuracy or provided data from which we could compute estimates. Data collection and analysis: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using the QUADAS-2 domain-list. We presented the results of estimated sensitivity and specificity using paired forest plots, and we summarised pooled estimates in tables. We used a bivariate meta-analysis model where appropriate. We presented the uncertainty of accuracy estimates using 95% confidence intervals (CIs). Main results: We included 51 studies with 19,775 participants suspected of having COVID-19, of whom 10,155 (51%) had a final diagnosis of COVID-19. Forty-seven studies evaluated one imaging modality each, and four studies evaluated two imaging modalities each. All studies used RT-PCR as the reference standard for the diagnosis of COVID-19, with 47 studies using only RT-PCR and four studies using a combination of RT-PCR and other criteria (such as clinical signs, imaging tests, positive contacts, and follow-up phone calls) as the reference standard. Studies were conducted in Europe (33), Asia (13), North America (3) and South America (2); including only adults (26), all ages (21), children only (1), adults over 70 years (1), and unclear (2); in inpatients (2), outpatients (32), and setting unclear (17). Risk of bias was high or unclear in thirty-two (63%) studies with respect to participant selection, 40 (78%) studies with respect to reference standard, 30 (59%) studies with respect to index test, and 24 (47%) studies with respect to participant flow. For chest CT (41 studies, 16,133 participants, 8110 (50%) cases), the sensitivity ranged from 56.3% to 100%, and specificity ranged from 25.4% to 97.4%. The pooled sensitivity of chest CT was 87.9% (95% CI 84.6 to 90.6) and the pooled specificity was 80.0% (95% CI 74.9 to 84.3). There was no statistical evidence indicating that reference standard conduct and definition for index test positivity were sources of heterogeneity for CT studies. Nine chest CT studies (2807 participants, 1139 (41%) cases) used the COVID-19 Reporting and Data System (CO-RADS) scoring system, which has five thresholds to define index test positivity. At a CO-RADS threshold of 5 (7 studies), the sensitivity ranged from 41.5% to 77.9% and the pooled sensitivity was 67.0% (95% CI 56.4 to 76.2); the specificity ranged from 83.5% to 96.2%; and the pooled specificity was 91.3% (95% CI 87.6 to 94.0). At a CO-RADS threshold of 4 (7 studies), the sensitivity ranged from 56.3% to 92.9% and the pooled sensitivity was 83.5% (95% CI 74.4 to 89.7); the specificity ranged from 77.2% to 90.4% and the pooled specificity was 83.6% (95% CI 80.5 to 86.4). For chest X-ray (9 studies, 3694 participants, 2111 (57%) cases) the sensitivity ranged from 51.9% to 94.4% and specificity ranged from 40.4% to 88.9%. The pooled sensitivity of chest X-ray was 80.6% (95% CI 69.1 to 88.6) and the pooled specificity was 71.5% (95% CI 59.8 to 80.8). For ultrasound of the lungs (5 studies, 446 participants, 211 (47%) cases) the sensitivity ranged from 68.2% to 96.8% and specificity ranged from 21.3% to 78.9%. The pooled sensitivity of ultrasound was 86.4% (95% CI 72.7 to 93.9) and the pooled specificity was 54.6% (95% CI 35.3 to 72.6). Based on an indirect comparison using all included studies, chest CT had a higher specificity than ultrasound. For indirect comparisons of chest CT and chest X-ray, or chest X-ray and ultrasound, the data did not show differences in specificity or sensitivity. Authors' conclusions: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19. Chest X-ray is moderately sensitive and moderately specific for the diagnosis of COVID-19. Ultrasound is sensitive but not specific for the diagnosis of COVID-19. Thus, chest CT and ultrasound may have more utility for excluding COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest in the same participant population, and implement improved reporting practices.

Negative pressure wound therapy for surgical wounds healing by primary closure

Abstract: Background Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). Existing evidence for the effectiveness of NPWT on postoperative wounds healing by primary closure remains uncertain. Objectives To assess the effects of NPWT for preventing SSI in wounds healing through primary closure, and to assess the cost-effectiveness of NPWT in wounds healing through primary closure. Search methods In June 2019, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries and references of included studies, systematic reviews and health technology reports. There were no restrictions on language, publication date or study setting. Selection criteria We included trials if they allocated participants to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with another type of NPWT. Data collection and analysis At least two review authors independently assessed trials using predetermined inclusion criteria. We carried out data extraction, assessment using the Cochrane 'Risk of bias' tool, and quality assessment according to Grading of Recommendations, Assessment, Development and Evaluations methodology. Main results In this third update, we added 15 new randomised controlled trials (RCTs) and three new economic studies, resulting in a total of 44 RCTs (7447 included participants) and five economic studies. Studies evaluated NPWT in the context of a wide range of surgeries including orthopaedic, obstetric, vascular and general procedures. Economic studies assessed NPWT in orthopaedic, obstetric and general surgical settings. All studies compared NPWT with standard dressings. Most studies had unclear or high risk of bias for at least one key domain. Primary outcomes Four studies (2107 participants) reported mortality. There is low-certainty evidence (downgraded twice for imprecision) showing no clear difference in the risk of death after surgery for people treated with NPWT (2.3%) compared with standard dressings (2.7%) (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.50 to 1.47; I2 = 0%). Thirty-nine studies reported SSI; 31 of these (6204 participants), were included in meta-analysis. There is moderate-certainty evidence (downgraded once for risk of bias) that NPWT probably results in fewer SSI (8.8% of participants) than treatment with standard dressings (13.0% of participants) after surgery; RR 0.66 (95% CI 0.55 to 0.80 ; I2 = 23%). Eighteen studies reported dehiscence; 14 of these (3809 participants) were included in meta-analysis. There is low-certainty evidence (downgraded once for risk of bias and once for imprecision) showing no clear difference in the risk of dehiscence after surgery for NPWT (5.3% of participants) compared with standard dressings (6.2% of participants) (RR 0.88, 95% CI 0.69 to 1.13; I2 = 0%). Secondary outcomes There is low-certainty evidence showing no clear difference between NPWT and standard treatment for the outcomes of reoperation and incidence of seroma. For reoperation, the RR was 1.04 (95% CI 0.78 to 1.41; I2 = 13%; 12 trials; 3523 participants); for seroma, the RR was 0.72 (95% CI 0.50 to 1.05; I2 = 0%; seven trials; 729 participants). The effect of NPWT on occurrence of haematoma or skin blisters is uncertain (very low-certainty evidence); for haematoma, the RR was 0.67 (95% CI 0.28 to 1.59; I2 = 0%; nine trials; 1202 participants) and for blisters the RR was 2.64 (95% CI 0.65 to 10.68; I2 = 69%; seven trials; 796 participants). The overall effect of NPWT on pain is uncertain (very low-certainty evidence from seven trials (2218 participants) which reported disparate measures of pain); but moderate-certainty evidence suggests there is probably little difference between the groups in pain after three or six months following surgery for lower limb fracture (one trial, 1549 participants). There is also moderate-certainty evidence for women undergoing caesarean sections (one trial, 876 participants) and people having surgery for lower limb fractures (one trial, 1549 participants) that there is probably little difference in quality of life scores at 30 days or 3 or 6 months, respectively. Cost-effectiveness Five economic studies, based wholly or partially on trials included in our review, assessed the cost-effectiveness of NPWT compared with standard care. They considered NPWT in four indications: caesarean sections in obese women; surgery for lower limb fracture; knee/hip arthroplasty and coronary artery bypass graft surgery. They calculated quality-adjusted life-years for treatment groups and produced estimates of the treatments' relative cost-effectiveness. The reporting quality was good but the grade of the evidence varied from moderate to very low. There is moderate-certainty evidence that NPWT in surgery for lower limb fracture was not cost-effective at any threshold of willingness-to-pay and that NPWT is probably cost-effective in obese women undergoing caesarean section. Other studies found low or very low-certainty evidence indicating that NPWT may be cost-effective for the indications assessed. Authors' conclusions People experiencing primary wound closure of their surgical wound and treated prophylactically with NPWT following surgery probably experience fewer SSI than people treated with standard dressings (moderate-certainty evidence). There is no clear difference in number of deaths or wound dehiscence between people treated with NPWT and standard dressings (low-certainty evidence). There are also no clear differences in secondary outcomes where all evidence was low or very low-certainty. In caesarean section in obese women and surgery for lower limb fracture, there is probably little difference in quality of life scores (moderate-certainty evidence). Most evidence on pain is very low-certainty, but there is probably no difference in pain between NPWT and standard dressings after surgery for lower limb fracture (moderate-certainty evidence). Assessments of cost-effectiveness of NPWT produced differing results in different indications. There is a large number of ongoing studies, the results of which may change the findings of this review. Decisions about use of NPWT should take into account surgical indication and setting and consider evidence for all outcomes.

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review.

Abstract: BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with respiratory virus diseases, and are currently being investigated in trials as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19. SEARCH METHODS: The protocol was pre-published with the Center for Open Science and can be accessed here: osf.io/dwf53 We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trials registries to identify ongoing studies and results of completed studies on 23 April 2020 for case-series, cohort, prospectively planned, and randomised controlled trials (RCTs). SELECTION CRITERIA: We followed standard Cochrane methodology and performed all steps regarding study selection in duplicate by two independent review authors (in contrast to the recommendations of the Cochrane Rapid Reviews Methods Group). We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulins. DATA COLLECTION AND ANALYSIS: We followed recommendations of the Cochrane Rapid Reviews Methods Group regarding data extraction and assessment. To assess bias in included studies, we used the assessment criteria tool for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events, and serious adverse events. MAIN RESULTS: We included eight studies (seven case-series, one prospectively planned, single-arm intervention study) with 32 participants, and identified a further 48 ongoing studies evaluating convalescent plasma (47 studies) or hyperimmune immunoglobulin (one study), of which 22 are randomised. Overall risk of bias of the eight included studies was high, due to: study design; small number of participants; poor reporting within studies; and varied type of participants with different severities of disease, comorbidities, and types of previous or concurrent treatments, including antivirals, antifungals or antibiotics, corticosteroids, hydroxychloroquine and respiratory support. We rated all outcomes as very low certainty, and we were unable to summarise numerical data in any meaningful way. As we identified case-series studies only, we reported results narratively. Effectiveness of convalescent plasma for people with COVID-19 The following reported outcomes could all be related to the underlying natural history of the disease or other concomitant treatment, rather than convalescent plasma. All-cause mortality at hospital discharge All studies reported mortality. All participants were alive at the end of the reporting period, but not all participants had been discharged from hospital by the end of the study (15 participants discharged, 6 still hospitalised, 11 unclear). Follow-up ranged from 3 days to 37 days post-transfusion. We do not know whether convalescent plasma therapy affects mortality (very low-certainty evidence). Improvement of clinical symptoms (assessed by respiratory support) Six studies, including 28 participants, reported the level of respiratory support required; most participants required respiratory support at baseline. All studies reported improvement in clinical symptoms in at least some participants. We do not know whether convalescent plasma improves clinical symptoms (very low-certainty evidence). Time to discharge from hospital Six studies reported time to discharge from hospital for at least some participants, which ranged from four to 35 days after convalescent plasma therapy. Admission on the intensive care unit (ICU) Six studies included patients who were critically ill. At final follow-up the majority of these patients were no longer on the ICU or no longer required mechanical ventilation. Length of stay on the ICU Only one study (1 participant) reported length of stay on the ICU. The individual was discharged from the ICU 11 days after plasma transfusion. Safety of convalescent plasma for people with COVID-19 Grade 3 or 4 adverse events The studies did not report the grade of adverse events after convalescent plasma transfusion. Two studies reported data relating to participants who had experienced adverse events, that were presumably grade 3 or 4. One case study reported a participant who had moderate fever (38.9 °C). Another study (3 participants) reported a case of severe anaphylactic shock. Four studies reported the absence of moderate or severe adverse events (19 participants). We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence). Serious adverse events One study (3 participants) reported one serious adverse event. As described above, this individual had severe anaphylactic shock after receiving convalescent plasma. Six studies reported that no serious adverse events occurred. We are very uncertain whether or not convalescent plasma therapy affects the risk of serious adverse events (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified eight studies (seven case-series and one prospectively planned single-arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID-19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low-certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID-19; all studies were at high risk of bias and reporting quality was low. No RCTs or controlled non-randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here.

Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19.

Abstract: Background The coronavirus disease 2019 (COVID‐19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. Objectives To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID‐19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS‐CoV‐2 exposure; 3) preventing infection in people exposed to SARS‐CoV‐2. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled‐trials.com), and the COVID‐19‐specific resources www.covid‐nma.com and covid‐19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. Selection criteria We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID‐19, people at risk of COVID‐19 exposure, and people exposed to COVID‐19. Adverse events (any, serious, and QT‐interval prolongation on electrocardiogram) were also extracted. Data collection and analysis Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane ‘Risk of bias’ tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta‐analysis using a random‐effects model for outcomes where pooling of effect estimates was appropriate.

Psychological interventions to foster resilience in healthcare professionals

Abstract: Background Resilience can be defined as the maintenance or quick recovery of mental health during or after periods of stressor exposure, which may result from a potentially traumatising event, challenging life circumstances, a critical life transition phase, or physical illness. Healthcare professionals, such as nurses, physicians, psychologists and social workers, are exposed to various work-related stressors (e.g. patient care, time pressure, administration) and are at increased risk of developing mental disorders. This population may benefit from resilience-promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthcare professionals, that is, healthcare staff delivering direct medical care (e.g. nurses, physicians, hospital personnel) and allied healthcare staff (e.g. social workers, psychologists). Search methods We searched CENTRAL, MEDLINE, Embase, 11 other databases and three trial registries from 1990 to June 2019. We checked reference lists and contacted researchers in the field. We updated this search in four key databases in June 2020, but we have not yet incorporated these results. Selection criteria Randomised controlled trials (RCTs) in adults aged 18 years and older who are employed as healthcare professionals, comparing any form of psychological intervention to foster resilience, hardiness or post-traumatic growth versus no intervention, wait-list, usual care, active or attention control. Primary outcomes were resilience, anxiety, depression, stress or stress perception and well-being or quality of life. Secondary outcomes were resilience factors. Data collection and analysis Two review authors independently selected studies, extracted data, assessed risks of bias, and rated the certainty of the evidence using the GRADE approach (at post-test only). Main results We included 44 RCTs (high-income countries: 36). Thirty-nine studies solely focused on healthcare professionals (6892 participants), including both healthcare staff delivering direct medical care and allied healthcare staff. Four studies investigated mixed samples (1000 participants) with healthcare professionals and participants working outside of the healthcare sector, and one study evaluated training for emergency personnel in general population volunteers (82 participants). The included studies were mainly conducted in a hospital setting and included physicians, nurses and different hospital personnel (37/44 studies). Participants mainly included women (68%) from young to middle adulthood (mean age range: 27 to 52.4 years). Most studies investigated group interventions (30 studies) of high training intensity (18 studies; > 12 hours/sessions), that were delivered face-to-face (29 studies). Of the included studies, 19 compared a resilience training based on combined theoretical foundation (e.g. mindfulness and cognitive-behavioural therapy) versus unspecific comparators (e.g. wait-list). The studies were funded by different sources (e.g. hospitals, universities), or a combination of different sources. Fifteen studies did not specify the source of their funding, and one study received no funding support. Risk of bias was high or unclear for most studies in performance, detection, and attrition bias domains. At post-intervention, very-low certainty evidence indicated that, compared to controls, healthcare professionals receiving resilience training may report higher levels of resilience (standardised mean difference (SMD) 0.45, 95% confidence interval (CI) 0.25 to 0.65; 12 studies, 690 participants), lower levels of depression (SMD -0.29, 95% CI -0.50 to -0.09; 14 studies, 788 participants), and lower levels of stress or stress perception (SMD -0.61, 95% CI -1.07 to -0.15; 17 studies, 997 participants). There was little or no evidence of any effect of resilience training on anxiety (SMD -0.06, 95% CI -0.35 to 0.23; 5 studies, 231 participants; very-low certainty evidence) or well-being or quality of life (SMD 0.14, 95% CI -0.01 to 0.30; 13 studies, 1494 participants; very-low certainty evidence). Effect sizes were small except for resilience and stress reduction (moderate). Data on adverse effects were available for three studies, with none reporting any adverse effects occurring during the study (very-low certainty evidence). Authors' conclusions For healthcare professionals, there is very-low certainty evidence that, compared to control, resilience training may result in higher levels of resilience, lower levels of depression, stress or stress perception, and higher levels of certain resilience factors at post-intervention. The paucity of medium- or long-term data, heterogeneous interventions and restricted geographical distribution limit the generalisability of our results. Conclusions should therefore be drawn cautiously. The findings suggest positive effects of resilience training for healthcare professionals, but the evidence is very uncertain. There is a clear need for high-quality replications and improved study designs.

Digital contact tracing technologies in epidemics: a rapid review

Abstract: Background Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in contact with an infected individual, in order to isolate them and reduce further transmission. Digital technology could be implemented to augment and accelerate manual contact tracing. Digital tools for contact tracing may be grouped into three areas: 1) outbreak response; 2) proximity tracing; and 3) symptom tracking. We conducted a rapid review on the effectiveness of digital solutions to contact tracing during infectious disease outbreaks. Objectives To assess the benefits, harms, and acceptability of personal digital contact tracing solutions for identifying contacts of an identified positive case of an infectious disease. Search methods An information specialist searched the literature from 1 January 2000 to 5 May 2020 in CENTRAL, MEDLINE, and Embase. Additionally, we screened the Cochrane COVID-19 Study Register. Selection criteria We included randomised controlled trials (RCTs), cluster-RCTs, quasi-RCTs, cohort studies, cross-sectional studies and modelling studies, in general populations. We preferentially included studies of contact tracing during infectious disease outbreaks (including COVID-19, Ebola, tuberculosis, severe acute respiratory syndrome virus, and Middle East respiratory syndrome) as direct evidence, but considered comparative studies of contact tracing outside an outbreak as indirect evidence. The digital solutions varied but typically included software (or firmware) for users to install on their devices or to be uploaded to devices provided by governments or third parties. Control measures included traditional or manual contact tracing, self-reported diaries and surveys, interviews, other standard methods for determining close contacts, and other technologies compared to digital solutions (e.g. electronic medical records). Data collection and analysis Two review authors independently screened records and all potentially relevant full-text publications. One review author extracted data for 50% of the included studies, another extracted data for the remaining 50%; the second review author checked all the extracted data. One review author assessed quality of included studies and a second checked the assessments. Our outcomes were identification of secondary cases and close contacts, time to complete contact tracing, acceptability and accessibility issues, privacy and safety concerns, and any other ethical issue identified. Though modelling studies will predict estimates of the effects of different contact tracing solutions on outcomes of interest, cohort studies provide empirically measured estimates of the effects of different contact tracing solutions on outcomes of interest. We used GRADE-CERQual to describe certainty of evidence from qualitative data and GRADE for modelling and cohort studies. Main results We identified six cohort studies reporting quantitative data and six modelling studies reporting simulations of digital solutions for contact tracing. Two cohort studies also provided qualitative data. Three cohort studies looked at contact tracing during an outbreak, whilst three emulated an outbreak in non-outbreak settings (schools). Of the six modelling studies, four evaluated digital solutions for contact tracing in simulated COVID-19 scenarios, while two simulated close contacts in non-specific outbreak settings. Modelling studies Two modelling studies provided low-certainty evidence of a reduction in secondary cases using digital contact tracing (measured as average number of secondary cases per index case - effective reproductive number (R eff)). One study estimated an 18% reduction in R eff with digital contact tracing compared to self-isolation alone, and a 35% reduction with manual contact-tracing. Another found a reduction in R eff for digital contact tracing compared to self-isolation alone (26% reduction) and a reduction in R eff for manual contact tracing compared to self-isolation alone (53% reduction). However, the certainty of evidence was reduced by unclear specifications of their models, and assumptions about the effectiveness of manual contact tracing (assumed 95% to 100% of contacts traced), and the proportion of the population who would have the app (53%). Cohort studies Two cohort studies provided very low-certainty evidence of a benefit of digital over manual contact tracing. During an Ebola outbreak, contact tracers using an app found twice as many close contacts per case on average than those using paper forms. Similarly, after a pertussis outbreak in a US hospital, researchers found that radio-frequency identification identified 45 close contacts but searches of electronic medical records found 13. The certainty of evidence was reduced by concerns about imprecision, and serious risk of bias due to the inability of contact tracing study designs to identify the true number of close contacts. One cohort study provided very low-certainty evidence that an app could reduce the time to complete a set of close contacts. The certainty of evidence for this outcome was affected by imprecision and serious risk of bias. Contact tracing teams reported that digital data entry and management systems were faster to use than paper systems and possibly less prone to data loss. Two studies from lower- or middle-income countries, reported that contact tracing teams found digital systems simpler to use and generally preferred them over paper systems; they saved personnel time, reportedly improved accuracy with large data sets, and were easier to transport compared with paper forms. However, personnel faced increased costs and internet access problems with digital compared to paper systems. Devices in the cohort studies appeared to have privacy from contacts regarding the exposed or diagnosed users. However, there were risks of privacy breaches from snoopers if linkage attacks occurred, particularly for wearable devices. Authors' conclusions The effectiveness of digital solutions is largely unproven as there are very few published data in real-world outbreak settings. Modelling studies provide low-certainty evidence of a reduction in secondary cases if digital contact tracing is used together with other public health measures such as self-isolation. Cohort studies provide very low-certainty evidence that digital contact tracing may produce more reliable counts of contacts and reduce time to complete contact tracing. Digital solutions may have equity implications for at-risk populations with poor internet access and poor access to digital technology. Stronger primary research on the effectiveness of contact tracing technologies is needed, including research into use of digital solutions in conjunction with manual systems, as digital solutions are unlikely to be used alone in real-world settings. Future studies should consider access to and acceptability of digital solutions, and the resultant impact on equity. Studies should also make acceptability and uptake a primary research question, as privacy concerns can prevent uptake and effectiveness of these technologies.

Helicobacter pylori eradication for the prevention of gastric neoplasia

Abstract: Background Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. Objectives To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. Search methods We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11), MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2013. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. Selection criteria We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. Data collection and analysis We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. Main results Six trials met all our eligibility criteria and provided extractable data. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported. Authors' conclusions We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants

Abstract: Background Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity. OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and mortality and morbidity in very preterm or very low birth weight infants. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library; MEDLINE Ovid (1946 to 17 Feb 2020), Embase Ovid (1974 to 17 Feb 2020), Maternity & Infant Care Database Ovid (1971 to 17 Feb 2020), the Cumulative Index to Nursing and Allied Health Literature (1982 to 18 Feb 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. Selection criteria We included RCTs and quasi-RCTs comparing probiotic supplementation with placebo or no probiotics in very preterm or very low birth weight infants. Data collection and analysis We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on NEC, all-cause mortality, late-onset infection, and severe neurodevelopmental impairment. Main results We included 56 trials in which 10,812 infants participated. Most trials were small (median sample size 149). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were the main potential sources of bias in about half of the trials. Trials varied by the formulation of the probiotics. The most commonly used preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus spp. alone or in combinations. Meta-analysis showed that probiotics may reduce the risk of NEC: RR 0.54, 95% CI 0.45 to 0.65 (54 trials, 10,604 infants; I² = 17%); RD -0.03, 95% CI -0.04 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 25 to 50. Evidence was assessed as low certainty because of the limitations in trials design, and the presence of funnel plot asymmetry consistent with publication bias. Sensitivity meta-analysis of trials at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55 to 0.89 (16 trials, 4597 infants; I² = 25%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100. Meta-analyses showed that probiotics probably reduce mortality (RR 0.76, 95% CI 0.65 to 0.89; (51 trials, 10,170 infants; I² = 0%); RD -0.02, 95% CI -0.02 to -0.01; NNTB 50, 95% CI 50 to 100), and late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; (47 trials, 9762 infants; I² = 19%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100). Evidence was assessed as moderate certainty for both these outcomes because of the limitations in trials design. Sensitivity meta-analyses of 16 trials (4597 infants) at low risk of bias did not show an effect on mortality or infection. Meta-analysis showed that probiotics may have little or no effect on severe neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26 (five trials, 1518 infants; I² = 0%). The certainty on this evidence is low because of limitations in trials design and serious imprecision of effect estimate. Few data (from seven of the trials) were available for extremely preterm or extremely low birth weight infants. Meta-analyses did not show effects on NEC, death, or infection (low-certainty evidence). Authors' conclusions Given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, and particularly for extremely preterm or extremely low birth weight infants, further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice.

Organised inpatient (stroke unit) care for stroke: network meta-analysis.

Abstract: BACKGROUND Organised inpatient (stroke unit) care is provided by multi-disciplinary teams that manage stroke patients. This can been provided in a ward dedicated to stroke patients (stroke ward), with a peripatetic stroke team (mobile stroke team), or within a generic disability service (mixed rehabilitation ward). Team members aim to provide co-ordinated multi-disciplinary care using standard approaches to manage common post-stroke problems. OBJECTIVES • To assess the effects of organised inpatient (stroke unit) care compared with an alternative service. • To use a network meta-analysis (NMA) approach to assess different types of organised inpatient (stroke unit) care for people admitted to hospital after a stroke (the standard comparator was care in a general ward). Originally, we conducted this systematic review to clarify: • The characteristic features of organised inpatient (stroke unit) care? • Whether organised inpatient (stroke unit) care provide better patient outcomes than alternative forms of care? • If benefits are apparent across a range of patient groups and across different approaches to delivering organised stroke unit care? Within the current version, we wished to establish whether previous conclusions were altered by the inclusion of new outcome data from recent trials and further analysis via NMA. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (2 April 2019); the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 4), in the Cochrane Library (searched 2 April 2019); MEDLINE Ovid (1946 to 1 April 2019); Embase Ovid (1974 to 1 April 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 2 April 2019). In an effort to identify further published, unpublished, and ongoing trials, we searched seven trial registries (2 April 2019). We also performed citation tracking of included studies, checked reference lists of relevant articles, and contacted trialists. SELECTION CRITERIA Randomised controlled clinical trials comparing organised inpatient stroke unit care with an alternative service (typically contemporary conventional care), including comparing different types of organised inpatient (stroke unit) care for people with stroke who are admitted to hospital. DATA COLLECTION AND ANALYSIS Two review authors assessed eligibility and trial quality. We checked descriptive details and trial data with co-ordinators of the original trials, assessed risk of bias, and applied GRADE. The primary outcome was poor outcome (death or dependency (Rankin score 3 to 5) or requiring institutional care) at the end of scheduled follow-up. Secondary outcomes included death, institutional care, dependency, subjective health status, satisfaction, and length of stay. We used direct (pairwise) comparisons to compare organised inpatient (stroke unit) care with an alternative service. We used an NMA to confirm the relative effects of different approaches. MAIN RESULTS We included 29 trials (5902 participants) that compared organised inpatient (stroke unit) care with an alternative service: 20 trials (4127 participants) compared organised (stroke unit) care with a general ward, six trials (982 participants) compared different forms of organised (stroke unit) care, and three trials (793 participants) incorporated more than one comparison. Compared with the alternative service, organised inpatient (stroke unit) care was associated with improved outcomes at the end of scheduled follow-up (median one year): poor outcome (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.69 to 0.87; moderate-quality evidence), death (OR 0.76, 95% CI 0.66 to 0.88; moderate-quality evidence), death or institutional care (OR 0.76, 95% CI 0.67 to 0.85; moderate-quality evidence), and death or dependency (OR 0.75, 95% CI 0.66 to 0.85; moderate-quality evidence). Evidence was of very low quality for subjective health status and was not available for patient satisfaction. Analysis of length of stay was complicated by variations in definition and measurement plus substantial statistical heterogeneity (I² = 85%). There was no indication that organised stroke unit care resulted in a longer hospital stay. Sensitivity analyses indicated that observed benefits remained when the analysis was restricted to securely randomised trials that used unequivocally blinded outcome assessment with a fixed period of follow-up. Outcomes appeared to be independent of patient age, sex, initial stroke severity, stroke type, and duration of follow-up. When calculated as the absolute risk difference for every 100 participants receiving stroke unit care, this equates to two extra survivors, six more living at home, and six more living independently. The analysis of different types of organised (stroke unit) care used both direct pairwise comparisons and NMA. Direct comparison of stroke ward versus general ward: 15 trials (3523 participants) compared care in a stroke ward with care in general wards. Stroke ward care showed a reduction in the odds of a poor outcome at the end of follow-up (OR 0.78, 95% CI 0.68 to 0.91; moderate-quality evidence). Direct comparison of mobile stroke team versus general ward: two trials (438 participants) compared care from a mobile stroke team with care in general wards. Stroke team care may result in little difference in the odds of a poor outcome at the end of follow-up (OR 0.80, 95% CI 0.52 to 1.22; low-quality evidence). Direct comparison of mixed rehabilitation ward versus general ward: six trials (630 participants) compared care in a mixed rehabilitation ward with care in general wards. Mixed rehabilitation ward care showed a reduction in the odds of a poor outcome at the end of follow-up (OR 0.65, 95% CI 0.47 to 0.90; moderate-quality evidence). In a NMA using care in a general ward as the comparator, the odds of a poor outcome were as follows: stroke ward - OR 0.74, 95% CI 0.62 to 0.89, moderate-quality evidence; mobile stroke team - OR 0.88, 95% CI 0.58 to 1.34, low-quality evidence; mixed rehabilitation ward - OR 0.70, 95% CI 0.52 to 0.95, low-quality evidence. AUTHORS' CONCLUSIONS We found moderate-quality evidence that stroke patients who receive organised inpatient (stroke unit) care are more likely to be alive, independent, and living at home one year after the stroke. The apparent benefits were independent of patient age, sex, initial stroke severity, or stroke type, and were most obvious in units based in a discrete stroke ward. We observed no systematic increase in the length of inpatient stay, but these findings had considerable uncertainty.

Video calls for reducing social isolation and loneliness in older people: a rapid review.

Abstract: Background The current COVID-19 pandemic has been identified as a possible trigger for increases in loneliness and social isolation among older people due to the restrictions on movement that many countries have put in place. Loneliness and social isolation are consistently identified as risk factors for poor mental and physical health in older people. Video calls may help older people stay connected during the current crisis by widening the participant's social circle or by increasing the frequency of contact with existing acquaintances. Objectives The primary objective of this rapid review is to assess the effectiveness of video calls for reducing social isolation and loneliness in older adults. The review also sought to address the effectiveness of video calls on reducing symptoms of depression and improving quality of life. Search methods We searched CENTRAL, MEDLINE, PsycINFO and CINAHL from 1 January 2004 to 7 April 2020. We also searched the references of relevant systematic reviews. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs (including cluster designs) were eligible for inclusion. We excluded all other study designs. The samples in included studies needed to have a mean age of at least 65 years. We included studies that included participants whether or not they were experiencing symptoms of loneliness or social isolation at baseline. Any intervention in which a core component involved the use of the internet to facilitate video calls or video conferencing through computers, smartphones or tablets with the intention of reducing loneliness or social isolation, or both, in older adults was eligible for inclusion. We included studies in the review if they reported self-report measures of loneliness, social isolation, symptoms of depression or quality of life. Two review authors screened 25% of abstracts; a third review author resolved conflicts. A single review author screened the remaining abstracts. The second review author screened all excluded abstracts and we resolved conflicts by consensus or by involving a third review author. We followed the same process for full-text articles. Data collection and analysis One review author extracted data, which another review author checked. The primary outcomes were loneliness and social isolation and the secondary outcomes were symptoms of depression and quality of life. One review author rated the certainty of evidence for the primary outcomes according to the GRADE approach and another review author checked the ratings. We conducted fixed-effect meta-analyses for the primary outcome, loneliness, and the secondary outcome, symptoms of depression. Main results We identified three cluster quasi-randomised trials, which together included 201 participants. The included studies compared video call interventions to usual care in nursing homes. None of these studies were conducted during the COVID-19 pandemic. Each study measured loneliness using the UCLA Loneliness Scale. Total scores range from 20 (least lonely) to 80 (most lonely). The evidence was very uncertain and suggests that video calls may result in little to no difference in scores on the UCLA Loneliness Scale compared to usual care at three months (mean difference (MD) -0.44, 95% confidence interval (CI) -3.28 to 2.41; 3 studies; 201 participants), at six months (MD -0.34, 95% CI -3.41 to 2.72; 2 studies; 152 participants) and at 12 months (MD -2.40, 95% CI -7.20 to 2.40; 1 study; 90 participants). We downgraded the certainty of this evidence by three levels for study limitations, imprecision and indirectness. None of the included studies reported social isolation as an outcome. Each study measured symptoms of depression using the Geriatric Depression Scale. Total scores range from 0 (better) to 30 (worse). The evidence was very uncertain and suggests that video calls may result in little to no difference in scores on the Geriatric Depression Scale compared to usual care at three months' follow-up (MD 0.41, 95% CI -0.90 to 1.72; 3 studies; 201 participants) or six months' follow-up (MD -0.83, 95% CI -2.43 to 0.76; 2 studies, 152 participants). The evidence suggests that video calls may have a small effect on symptoms of depression at one-year follow-up, though this finding is imprecise (MD -2.04, 95% CI -3.98 to -0.10; 1 study; 90 participants). We downgraded the certainty of this evidence by three levels for study limitations, imprecision and indirectness. Only one study, with 62 participants, reported quality of life. The study measured quality of life using a Taiwanese adaptation of the Short-Form 36-question health survey (SF-36), which consists of eight subscales that measure different aspects of quality of life: physical function; physical role; emotional role; social function; pain: vitality; mental health; and physical health. Each subscale is scored from 0 (poor health) to 100 (good health). The evidence is very uncertain and suggests that there may be little to no difference between people allocated to usual care and those allocated to video calls in three-month scores in physical function (MD 2.88, 95% CI -5.01 to 10.77), physical role (MD -7.66, 95% CI -24.08 to 8.76), emotional role (MD -7.18, 95% CI -16.23 to 1.87), social function (MD 2.77, 95% CI -8.87 to 14.41), pain scores (MD -3.25, 95% CI -15.11 to 8.61), vitality scores (MD -3.60, 95% CI -9.01 to 1.81), mental health (MD 9.19, 95% CI 0.36 to 18.02) and physical health (MD 5.16, 95% CI -2.48 to 12.80). We downgraded the certainty of this evidence by three levels for study limitations, imprecision and indirectness. Authors' conclusions Based on this review there is currently very uncertain evidence on the effectiveness of video call interventions to reduce loneliness in older adults. The review did not include any studies that reported evidence of the effectiveness of video call interventions to address social isolation in older adults. The evidence regarding the effectiveness of video calls for outcomes of symptoms of depression was very uncertain. Future research in this area needs to use more rigorous methods and more diverse and representative participants. Specifically, future studies should target older adults, who are demonstrably lonely or socially isolated, or both, across a range of settings to determine whether video call interventions are effective in a population in which these outcomes are in need of improvement.

Interventions for promoting physical activity in people with chronic obstructive pulmonary disease (COPD)

Abstract: Background Escalating awareness of the magnitude of the challenge posed by low levels of physical activity in people with chronic obstructive pulmonary disease (COPD) highlights the need for interventions to increase physical activity participation. The widely-accepted benefits of physical activity, coupled with the increasing availability of wearable monitoring devices to objectively measure participation, has led to a dramatic rise in the number and variety of studies that aimed to improve the physical activity of people with COPD. However, little was known about the relative efficacy of interventions tested so far. Objectives In people with COPD, which interventions are effective at improving objectively-assessed physical activity? Search methods We identified trials from the Cochrane Airways Trials Register Register, which contains records identified from bibliographic databases including the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and PsycINFO. We also searched PEDro, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform portal and the Australian New Zealand Clinical Trials Registry (from inception to June 2019). We checked reference lists of all primary studies and review articles for additional references, as well as respiratory journals and respiratory meeting abstracts, to identify relevant studies. Selection criteria We included randomised controlled trials of interventions that used objective measures for the assessment of physical activity in people with COPD. Trials compared an intervention with no intervention or a sham/placebo intervention, an intervention in addition to another standard intervention common to both groups, or two different interventions. Data collection and analysis We used standard methods recommended by Cochrane. Subgroup analyses were possible for supervised compared to unsupervised pulmonary rehabilitation programmes in clinically-stable COPD for a range of physical activity outcomes. Secondary outcomes were health-related quality of life, exercise capacity, adverse events and adherence. Insufficient data were available to perform prespecified subgroup analyses by duration of intervention or disease severity. We undertook sensitivity analyses by removing studies that were at high or unclear risk of bias for the domains of blinding and incomplete outcome data. Main results We included 76 studies with 8018 participants. Most studies were funded by government bodies, although some were sponsored by equipment or drug manufacturers. Only 38 studies had physical activity as a primary outcome. A diverse range of interventions have been assessed, primarily in single studies, but improvements have not been systematically demonstrated following any particular interventions. Where improvements were demonstrated, results were confined to single studies, or data for maintained improvement were not provided. Step count was the most frequently reported outcome, but it was commonly assessed using devices with documented inaccuracy for this variable. Compared to no intervention, the mean difference (MD) in time in moderate- to vigorous-intensity physical activity (MVPA) following pulmonary rehabilitation was four minutes per day (95% confidence interval (CI) -2 to 9; 3 studies, 190 participants; low-certainty evidence). An improvement was demonstrated following high-intensity interval exercise training (6 minutes per day, 95% CI 4 to 8; 2 studies, 275 participants; moderate-certainty evidence). One study demonstrated an improvement following six months of physical activity counselling (MD 11 minutes per day, 95% CI 7 to 15; 1 study, 280 participants; moderate-certainty evidence), but we found mixed results for the addition of physical activity counselling to pulmonary rehabilitation. There was an improvement following three to four weeks of pharmacological treatment with long-acting muscarinic antagonist and long-acting beta2-agonist (LAMA/LABA) compared to placebo (MD 10 minutes per day, 95% CI 4 to 15; 2 studies, 423 participants; high-certainty evidence). These interventions also demonstrated improvements in other measures of physical activity. Other interventions included self-management strategies, nutritional supplementation, supplemental oxygen, endobronchial valve surgery, non-invasive ventilation, neuromuscular electrical stimulation and inspiratory muscle training. Authors' conclusions A diverse range of interventions have been assessed, primarily in single studies. Improvements in physical activity have not been systematically demonstrated following any particular intervention. There was limited evidence for improvement in physical activity with strategies including exercise training, physical activity counselling and pharmacological management. The optimal timing, components, duration and models for interventions are still unclear. Assessment of quality was limited by a lack of methodological detail. There was scant evidence for a continued effect over time following completion of interventions, a likely requirement for meaningful health benefits for people with COPD.

Pelvic floor muscle training for preventing and treating urinary and faecal incontinence in antenatal and postnatal women

Abstract: Background: About one-third of women have urinary incontinence (UI) and up to one-tenth have faecal incontinence (FI) after childbirth. Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth for both preventing and treating incontinence. This is an update of a Cochrane Review previously published in 2017. Objectives: To assess the effects of PFMT for preventing or treating urinary and faecal incontinence in pregnant or postnatal women, and summarise the principal findings of relevant economic evaluations. Search Methods: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP, and handsearched journals and conference proceedings (searched 7 August 2019), and the reference lists of retrieved studies. Selection Criteria: We included randomised or quasi-randomised trials in which one arm included PFMT. Another arm was no PFMT, usual antenatal or postnatal care, another control condition, or an alternative PFMT intervention. Populations included women who, at randomisation, were continent (PFMT for prevention) or incontinent (PFMT for treatment), and a mixed population of women who were one or the other (PFMT for prevention or treatment). Data Collection and Analysis: We independently assessed trials for inclusion and risk of bias. We extracted data and assessed the quality of evidence using GRADE. Main Results: We included 46 trials involving 10,832 women from 21 countries. Overall, trials were small to moderately-sized. The PFMT programmes and control conditions varied considerably and were often poorly described. Many trials were at moderate to high risk of bias. Two participants in a study of 43 pregnant women performing PFMT for prevention of incontinence withdrew due to pelvic floor pain. No other trials reported any adverse effects of PFMT. Prevention of UI: compared with usual care, continent pregnant women performing antenatal PFMT probably have a lower risk of reporting UI in late pregnancy (62% less; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.20 to 0.72; 6 trials, 624 women; moderate-quality evidence). Antenatal PFMT slightly decreased the risk of UI in the mid-postnatal period (more than three to six months' postpartum) (29% less; RR 0.71, 95% CI 0.54 to 0.95; 5 trials, 673 women; high-quality evidence). There was insufficient information available for the late postnatal period (more than six to 12 months) to determine effects at this time point (RR 1.20, 95% CI 0.65 to 2.21; 1 trial, 44 women; low-quality evidence). Treatment of UI: compared with usual care, there is no evidence that antenatal PFMT in incontinent women decreases incontinence in late pregnancy (very low-quality evidence), or in the mid-(RR 0.94, 95% CI 0.70 to 1.24; 1 trial, 187 women; low-quality evidence), or late postnatal periods (very low-quality evidence). Similarly, in postnatal women with persistent UI, there is no evidence that PFMT results in a difference in UI at more than six to 12 months postpartum (RR 0.55, 95% CI 0.29 to 1.07; 3 trials; 696 women; low-quality evidence). Mixed prevention and treatment approach to UI: antenatal PFMT in women with or without UI probably decreases UI risk in late pregnancy (22% less; RR 0.78, 95% CI 0.64 to 0.94; 11 trials, 3307 women; moderate-quality evidence), and may reduce the risk slightly in the mid-postnatal period (RR 0.73, 95% CI 0.55 to 0.97; 5 trials, 1921 women; low-quality evidence). There was no evidence that antenatal PFMT reduces the risk of UI at late postpartum (RR 0.85, 95% CI 0.63 to 1.14; 2 trials, 244 women; moderate-quality evidence). For PFMT started after delivery, there was uncertainty about the effect on UI risk in the late postnatal period (RR 0.88, 95% CI 0.71 to 1.09; 3 trials, 826 women; moderate-quality evidence). Faecal incontinence: eight trials reported FI outcomes. In postnatal women with persistent FI, it was uncertain whether PFMT reduced incontinence in the late postnatal period compared to usual care (very low-quality evidence). In women with or without FI, there was no evidence that antenatal PFMT led to a difference in the prevalence of FI in late pregnancy (RR 0.64, 95% CI 0.36 to 1.14; 3 trials, 910 women; moderate-quality evidence). Similarly, for postnatal PFMT in a mixed population, there was no evidence that PFMT reduces the risk of FI in the late postnatal period (RR 0.73, 95% CI 0.13 to 4.21; 1 trial, 107 women, low-quality evidence). There was little evidence about effects on UI or FI beyond 12 months' postpartum. There were few incontinence-specific quality of life data and little consensus on how to measure it. Authors' Conclusions: This review provides evidence that early, structured PFMT in early pregnancy for continent women may prevent the onset of UI in late pregnancy and postpartum. Population approaches (recruiting antenatal women regardless of continence status) may have a smaller effect on UI, although the reasons for this are unclear. A population-based approach for delivering postnatal PFMT is not likely to reduce UI. Uncertainty surrounds the effects of PFMT as a treatment for UI in antenatal and postnatal women, which contrasts with the more established effectiveness in mid-life women. It is possible that the effects of PFMT might be greater with targeted rather than mixed prevention and treatment approaches, and in certain groups of women. Hypothetically, for instance, women with a high body mass index (BMI) are at risk of UI. Such uncertainties require further testing and data on duration of effect are also needed. The physiological and behavioural aspects of exercise programmes must be described for both PFMT and control groups, and how much PFMT women in both groups do, to increase understanding of what works and for whom. Few data exist on FI and it is important that this is included in any future trials. It is essential that future trials use valid measures of incontinence-specific quality of life for both urinary and faecal incontinence. In addition to further clinical studies, economic evaluations assessing the cost-effectiveness of different management strategies for FI and UI are needed.

Measures implemented in the school setting to contain the COVID-19 pandemic: a scoping review.

Abstract: Background In response to the spread of SARS-CoV-2 and the impact of COVID-19, national and subnational governments implemented a variety of measures in order to control the spread of the virus and the associated disease. While these measures were imposed with the intention of controlling the pandemic,they were also associated with severe psychosocial, societal, and economic implications on a societal level.One setting a ected heavily by these measures is the school setting. By mid-April 2020, 192 countries had closed schools, a ecting more than 90% ofthe world’s student population. In consideration ofthe adverse consequences of school closures, many countries around the world reopened their schools in the months aIer the initial closures. To safely reopen schools and keep them open, governments implemented a broad range of measures. The evidence with regards to these measures, however, is heterogeneous, with a multitude of study designs, populations, settings, interventions and outcomes being assessed. To make sense of this heterogeneity, we conducted a rapid scoping review (8 October to 5 November 2020). This rapid scoping review is intended to serve as a precursor to a systematic review of e ectiveness, which will inform guidelines issued by the WorldHealthOrganization (WHO). This review is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and was registered with the Open Science Framework. Objectives Toidentify andcomprehensivelymapthe evidence assessing the impactsofmeasures implementedinthe school setting toreopenschools, or keep schools open, or both, during the SARS-CoV-2/COVID-19 pandemic, with particular focus on the types of measures implemented in di erent school settings, the outcomes used to measure their impacts and the study types used to assess these. Search methods We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the CDC COVID-19 Research Articles Downloadable Database for preprints, and the WHO COVID-19 Global literature on coronavirus disease on 8 October 2020.

Induction of labour at or beyond 37 weeks' gestation

Abstract: Background Risks of stillbirth or neonatal death increase as gestation continues beyond term (around 40 weeks' gestation). It is unclear whether a policy of labour induction can reduce these risks. This Cochrane Review is an update of a review that was originally published in 2006 and subsequently updated in 2012 and 2018. Objectives To assess the effects of a policy of labour induction at or beyond 37 weeks' gestation compared with a policy of awaiting spontaneous labour indefinitely (or until a later gestational age, or until a maternal or fetal indication for induction of labour arises) on pregnancy outcomes for the infant and the mother. Search methods For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (17 July 2019), and reference lists of retrieved studies. Selection criteria Randomised controlled trials (RCTs) conducted in pregnant women at or beyond 37 weeks, comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour (expectant management). We also included trials published in abstract form only. Cluster-RCTs, quasi-RCTs and trials using a cross-over design were not eligible for inclusion in this review. We included pregnant women at or beyond 37 weeks' gestation. Since risk factors at this stage of pregnancy would normally require intervention, only trials including women at low risk for complications, as defined by trialists, were eligible. The trials of induction of labour in women with prelabour rupture of membranes at or beyond term were not considered in this review but are considered in a separate Cochrane Review. Data collection and analysis Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. We assessed the certainty of evidence using the GRADE approach. Main results In this updated review, we included 34 RCTs (reporting on over 21,000 women and infants) mostly conducted in high-income settings. The trials compared a policy to induce labour usually after 41 completed weeks of gestation (> 287 days) with waiting for labour to start and/or waiting for a period before inducing labour. The trials were generally at low to moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.15 to 0.64; 22 trials, 18,795 infants; high-certainty evidence). There were four perinatal deaths in the labour induction policy group compared with 25 perinatal deaths in the expectant management group. The number needed to treat for an additional beneficial outcome (NNTB) with induction of labour, in order to prevent one perinatal death, was 544 (95% CI 441 to 1042). There were also fewer stillbirths in the induction group (RR 0.30, 95% CI 0.12 to 0.75; 22 trials, 18,795 infants; high-certainty evidence); two in the induction policy group and 16 in the expectant management group. For women in the policy of induction arms of trials, there were probably fewer caesarean sections compared with expectant management (RR 0.90, 95% CI 0.85 to 0.95; 31 trials, 21,030 women; moderate-certainty evidence); and probably little or no difference in operative vaginal births with induction (RR 1.03, 95% CI 0.96 to 1.10; 22 trials, 18,584 women; moderate-certainty evidence). Induction may make little or difference to perineal trauma (severe perineal tear: RR 1.04, 95% CI 0.85 to 1.26; 5 trials; 11,589 women; low-certainty evidence). Induction probably makes little or no difference to postpartum haemorrhage (RR 1.02, 95% CI 0.91 to 1.15, 9 trials; 12,609 women; moderate-certainty evidence), or breastfeeding at discharge (RR 1.00, 95% CI 0.96 to 1.04; 2 trials, 7487 women; moderate-certainty evidence). Very low certainty evidence means that we are uncertain about the effect of induction or expectant management on the length of maternal hospital stay (average mean difference (MD) -0.19 days, 95% CI -0.56 to 0.18; 7 trials; 4120 women; Tau² = 0.20; I² = 94%). Rates of neonatal intensive care unit (NICU) admission were lower (RR 0.88, 95% CI 0.80 to 0.96; 17 trials, 17,826 infants; high-certainty evidence), and probably fewer babies had Apgar scores less than seven at five minutes in the induction groups compared with expectant management (RR 0.73, 95% CI 0.56 to 0.96; 20 trials, 18,345 infants; moderate-certainty evidence). Induction or expectant management may make little or no difference for neonatal encephalopathy (RR 0.69, 95% CI 0.37 to 1.31; 2 trials, 8851 infants; low-certainty evidence, and probably makes little or no difference for neonatal trauma (RR 0.97, 95% CI 0.63 to 1.49; 5 trials, 13,106 infants; moderate-certainty evidence) for induction compared with expectant management. Neurodevelopment at childhood follow-up and postnatal depression were not reported by any trials. In subgroup analyses, no differences were seen for timing of induction ( 41 weeks' gestation), by parity (primiparous versus multiparous) or state of cervix for any of the main outcomes (perinatal death, stillbirth, NICU admission, caesarean section, operative vaginal birth, or perineal trauma). Authors' conclusions There is a clear reduction in perinatal death with a policy of labour induction at or beyond 37 weeks compared with expectant management, though absolute rates are small (0.4 versus 3 deaths per 1000). There were also lower caesarean rates without increasing rates of operative vaginal births and there were fewer NICU admissions with a policy of induction. Most of the important outcomes assessed using GRADE had high- or moderate-certainty ratings. While existing trials have not yet reported on childhood neurodevelopment, this is an important area for future research. The optimal timing of offering induction of labour to women at or beyond 37 weeks' gestation needs further investigation, as does further exploration of risk profiles of women and their values and preferences. Offering women tailored counselling may help them make an informed choice between induction of labour for pregnancies, particularly those continuing beyond 41 weeks - or waiting for labour to start and/or waiting before inducing labour.

Travel-related control measures to contain the COVID-19 pandemic: a rapid review

Abstract: Background In late 2019, first cases of coronavirus disease 2019, or COVID‐19, caused by the novel coronavirus SARS‐CoV‐2, were reported in Wuhan, China. Subsequently COVID‐19 spread rapidly around the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers. Objectives To assess the effectiveness of travel‐related control measures during the COVID‐19 pandemic on infectious disease and screening‐related outcomes. Search methods We searched MEDLINE, Embase and COVID‐19‐specific databases, including the WHO Global Database on COVID‐19 Research, the Cochrane COVID‐19 Study Register, and the CDC COVID‐19 Research Database on 26 June 2020. We also conducted backward‐citation searches with existing reviews. Selection criteria We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across national borders during the COVID‐19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. Data collection and analysis One review author screened titles and abstracts; all excluded abstracts were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, ROBINS‐I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings. Main results We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID‐19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages. Most studies compared travel‐related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures. There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process.

Vaccines for measles, mumps, rubella, and varicella in children

Abstract: Background Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. Objectives To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). Selection criteria We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. Data collection and analysis Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. Main results We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.

Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment

Abstract: Background Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year. Objectives To assess the diagnostic accuracy of structural magnetic resonance imaging (MRI) for the early diagnosis of dementia due to Alzheimer's disease in people with MCI versus the clinical follow-up diagnosis of Alzheimer's disease dementia as a reference standard (delayed verification). To investigate sources of heterogeneity in accuracy, such as the use of qualitative visual assessment or quantitative volumetric measurements, including manual or automatic (MRI) techniques, or the length of follow-up, and age of participants. MRI was evaluated as an add-on test in addition to clinical diagnosis of MCI to improve early diagnosis of dementia due to Alzheimer's disease in people with MCI. Search methods On 29 January 2019 we searched Cochrane Dementia and Cognitive Improvement's Specialised Register and the databases, MEDLINE, Embase, BIOSIS Previews, Science Citation Index, PsycINFO, and LILACS. We also searched the reference lists of all eligible studies identified by the electronic searches. Selection criteria We considered cohort studies of any size that included prospectively recruited people of any age with a diagnosis of MCI. We included studies that compared the diagnostic test accuracy of baseline structural MRI versus the clinical follow-up diagnosis of Alzheimer's disease dementia (delayed verification). We did not exclude studies on the basis of length of follow-up. We included studies that used either qualitative visual assessment or quantitative volumetric measurements of MRI to detect atrophy in the whole brain or in specific brain regions, such as the hippocampus, medial temporal lobe, lateral ventricles, entorhinal cortex, medial temporal gyrus, lateral temporal lobe, amygdala, and cortical grey matter. Data collection and analysis Four teams of two review authors each independently reviewed titles and abstracts of articles identified by the search strategy. Two teams of two review authors each independently assessed the selected full-text articles for eligibility, extracted data and solved disagreements by consensus. Two review authors independently assessed the quality of studies using the QUADAS-2 tool. We used the hierarchical summary receiver operating characteristic (HSROC) model to fit summary ROC curves and to obtain overall measures of relative accuracy in subgroup analyses. We also used these models to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available. Main results We included 33 studies, published from 1999 to 2019, with 3935 participants of whom 1341 (34%) progressed to Alzheimer's disease dementia and 2594 (66%) did not. Of the participants who did not progress to Alzheimer's disease dementia, 2561 (99%) remained stable MCI and 33 (1%) progressed to other types of dementia. The median proportion of women was 53% and the mean age of participants ranged from 63 to 87 years (median 73 years). The mean length of clinical follow-up ranged from 1 to 7.6 years (median 2 years). Most studies were of poor methodological quality due to risk of bias for participant selection or the index test, or both. Most of the included studies reported data on the volume of the total hippocampus (pooled mean sensitivity 0.73 (95% confidence interval (CI) 0.64 to 0.80); pooled mean specificity 0.71 (95% CI 0.65 to 0.77); 22 studies, 2209 participants). This evidence was of low certainty due to risk of bias and inconsistency. Seven studies reported data on the atrophy of the medial temporal lobe (mean sensitivity 0.64 (95% CI 0.53 to 0.73); mean specificity 0.65 (95% CI 0.51 to 0.76); 1077 participants) and five studies on the volume of the lateral ventricles (mean sensitivity 0.57 (95% CI 0.49 to 0.65); mean specificity 0.64 (95% CI 0.59 to 0.70); 1077 participants). This evidence was of moderate certainty due to risk of bias. Four studies with 529 participants analysed the volume of the total entorhinal cortex and four studies with 424 participants analysed the volume of the whole brain. We did not estimate pooled sensitivity and specificity for the volume of these two regions because available data were sparse and heterogeneous. We could not statistically evaluate the volumes of the lateral temporal lobe, amygdala, medial temporal gyrus, or cortical grey matter assessed in small individual studies. We found no evidence of a difference between studies in the accuracy of the total hippocampal volume with regards to duration of follow-up or age of participants, but the manual MRI technique was superior to automatic techniques in mixed (mostly indirect) comparisons. We did not assess the relative accuracy of the volumes of different brain regions measured by MRI because only indirect comparisons were available, studies were heterogeneous, and the overall accuracy of all regions was moderate. Authors' conclusions The volume of hippocampus or medial temporal lobe, the most studied brain regions, showed low sensitivity and specificity and did not qualify structural MRI as a stand-alone add-on test for an early diagnosis of dementia due to Alzheimer's disease in people with MCI. This is consistent with international guidelines, which recommend imaging to exclude non-degenerative or surgical causes of cognitive impairment and not to diagnose dementia due to Alzheimer's disease. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future research should not focus on a single biomarker, but rather on combinations of biomarkers to improve an early diagnosis of Alzheimer's disease dementia.

Carotid artery stenting versus endarterectomy for treatment of carotid artery stenosis

Abstract: Background Carotid artery stenting is an alternative to carotid endarterectomy for the treatment of atherosclerotic carotid artery stenosis. This review updates a previous version first published in 1997 and subsequently updated in 2004, 2007, and 2012. Objectives To assess the benefits and risks of stenting compared with endarterectomy in people with symptomatic or asymptomatic carotid stenosis. Search methods We searched the Cochrane Stroke Group Trials Register (last searched August 2018) and the following databases: CENTRAL, MEDLINE, Embase, and Science Citation Index to August 2018. We also searched ongoing trials registers (August 2018) and reference lists, and contacted researchers in the field. Selection criteria Randomised controlled trials (RCTs) comparing stenting with endarterectomy for symptomatic or asymptomatic atherosclerotic carotid stenosis. In addition, we included RCTs comparing carotid artery stenting with medical therapy alone. Data collection and analysis One review author selected trials for inclusion, assessed trial quality and risk of bias, and extracted data. A second review author independently validated trial selection and a third review author independently validated data extraction. We calculated treatment effects as odds ratios (OR) and 95% confidence intervals (CI), with endarterectomy as the reference group. We quantified heterogeneity using the I² statistic and used GRADE to assess the overall certainty of evidence. Main results We included 22 trials involving 9753 participants. In participants with symptomatic carotid stenosis, compared with endarterectomy stenting was associated with a higher risk of periprocedural death or stroke (the primary safety outcome; OR 1.70, 95% CI 1.31 to 2.19; P < 0.0001, I² = 5%; 10 trials, 5396 participants; high‐certainty evidence); and periprocedural death, stroke, or myocardial infarction (OR 1.43, 95% CI 1.14 to 1.80; P = 0.002, I² = 0%; 6 trials, 4861 participants; high‐certainty evidence). The OR for the primary safety outcome was 1.11 (95% CI 0.74 to 1.64) in participants under 70 years old and 2.23 (95% CI 1.61 to 3.08) in participants 70 years old or more (interaction P = 0.007). There was a non‐significant increase in periprocedural death or major or disabling stroke with stenting (OR 1.36, 95% CI 0.97 to 1.91; P = 0.08, I² = 0%; 7 trials, 4983 participants; high‐certainty evidence). Compared with endarterectomy, stenting was associated with lower risks of myocardial infarction (OR 0.47, 95% CI 0.24 to 0.94; P = 0.03, I² = 0%), cranial nerve palsy (OR 0.09, 95% CI 0.06 to 0.16; P < 0.00001, I² = 0%), and access site haematoma (OR 0.32, 95% CI 0.15 to 0.68; P = 0.003, I² = 27%). The combination of periprocedural death or stroke or ipsilateral stroke during follow‐up (the primary combined safety and efficacy outcome) favoured endarterectomy (OR 1.51, 95% CI 1.24 to 1.85; P < 0.0001, I² = 0%; 8 trials, 5080 participants; high‐certainty evidence). The rate of ipsilateral stroke after the periprocedural period did not differ between treatments (OR 1.05, 95% CI 0.75 to 1.47; P = 0.77, I² = 0%). In participants with asymptomatic carotid stenosis, there was a non‐significant increase in periprocedural death or stroke with stenting compared with endarterectomy (OR 1.72, 95% CI 1.00 to 2.97; P = 0.05, I² = 0%; 7 trials, 3378 participants; moderate‐certainty evidence). The risk of periprocedural death or stroke or ipsilateral stroke during follow‐up did not differ significantly between treatments (OR 1.27, 95% CI 0.87 to 1.84; P = 0.22, I² = 0%; 6 trials, 3315 participants; moderate‐certainty evidence). Moderate or higher carotid artery restenosis (50% or greater) or occlusion during follow‐up was more common after stenting (OR 2.00, 95% CI 1.12 to 3.60; P = 0.02, I² = 44%), but the difference in risk of severe restenosis was not significant (70% or greater; OR 1.26, 95% CI 0.79 to 2.00; P = 0.33, I² = 58%; low‐certainty evidence). Authors' conclusions Stenting for symptomatic carotid stenosis is associated with a higher risk of periprocedural stroke or death than endarterectomy. This extra risk is mostly attributed to an increase in minor, non‐disabling strokes occurring in people older than 70 years. Beyond the periprocedural period, carotid stenting is as effective in preventing recurrent stroke as endarterectomy. However, combining procedural safety and long‐term efficacy in preventing recurrent stroke still favours endarterectomy. In people with asymptomatic carotid stenosis, there may be a small increase in the risk of periprocedural stroke or death with stenting compared with endarterectomy. However, CIs of treatment effects were wide and further data from randomised trials in people with asymptomatic stenosis are needed.

Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease

Abstract: Background Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. Objectives To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. Data collection and analysis Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. Main results Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. Authors' conclusions The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.

Psychological interventions to foster resilience in healthcare students

Abstract: Background Resilience can be defined as maintaining or regaining mental health during or after significant adversities such as a potentially traumatising event, challenging life circumstances, a critical life transition or physical illness. Healthcare students, such as medical, nursing, psychology and social work students, are exposed to various study- and work-related stressors, the latter particularly during later phases of health professional education. They are at increased risk of developing symptoms of burnout or mental disorders. This population may benefit from resilience-promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthcare students, that is, students in training for health professions delivering direct medical care (e.g. medical, nursing, midwifery or paramedic students), and those in training for allied health professions, as distinct from medical care (e.g. psychology, physical therapy or social work students). Search methods We searched CENTRAL, MEDLINE, Embase, 11 other databases and three trial registries from 1990 to June 2019. We checked reference lists and contacted researchers in the field. We updated this search in four key databases in June 2020, but we have not yet incorporated these results. Selection criteria Randomised controlled trials (RCTs) comparing any form of psychological intervention to foster resilience, hardiness or post-traumatic growth versus no intervention, waiting list, usual care, and active or attention control, in adults (18 years and older), who are healthcare students. Primary outcomes were resilience, anxiety, depression, stress or stress perception, and well-being or quality of life. Secondary outcomes were resilience factors. Data collection and analysis Two review authors independently selected studies, extracted data, assessed risks of bias, and rated the certainty of the evidence using the GRADE approach (at post-test only). Main results We included 30 RCTs, of which 24 were set in high-income countries and six in (upper- to lower-) middle-income countries. Twenty-two studies focused solely on healthcare students (1315 participants; number randomised not specified for two studies), including both students in health professions delivering direct medical care and those in allied health professions, such as psychology and physical therapy. Half of the studies were conducted in a university or school setting, including nursing/midwifery students or medical students. Eight studies investigated mixed samples (1365 participants), with healthcare students and participants outside of a health professional study field. Participants mainly included women (63.3% to 67.3% in mixed samples) from young adulthood (mean age range, if reported: 19.5 to 26.83 years; 19.35 to 38.14 years in mixed samples). Seventeen of the studies investigated group interventions of high training intensity (11 studies; > 12 hours/sessions), that were delivered face-to-face (17 studies). Of the included studies, eight compared a resilience training based on mindfulness versus unspecific comparators (e.g. wait-list). The studies were funded by different sources (e.g. universities, foundations), or a combination of various sources (four studies). Seven studies did not specify a potential funder, and three studies received no funding support. Risk of bias was high or unclear, with main flaws in performance, detection, attrition and reporting bias domains. At post-intervention, very-low certainty evidence indicated that, compared to controls, healthcare students receiving resilience training may report higher levels of resilience (standardised mean difference (SMD) 0.43, 95% confidence interval (CI) 0.07 to 0.78; 9 studies, 561 participants), lower levels of anxiety (SMD -0.45, 95% CI -0.84 to -0.06; 7 studies, 362 participants), and lower levels of stress or stress perception (SMD -0.28, 95% CI -0.48 to -0.09; 7 studies, 420 participants). Effect sizes varied between small and moderate. There was little or no evidence of any effect of resilience training on depression (SMD -0.20, 95% CI -0.52 to 0.11; 6 studies, 332 participants; very-low certainty evidence) or well-being or quality of life (SMD 0.15, 95% CI -0.14 to 0.43; 4 studies, 251 participants; very-low certainty evidence). Adverse effects were measured in four studies, but data were only reported for three of them. None of the three studies reported any adverse events occurring during the study (very-low certainty of evidence). Authors' conclusions For healthcare students, there is very-low certainty evidence for the effect of resilience training on resilience, anxiety, and stress or stress perception at post-intervention. The heterogeneous interventions, the paucity of short-, medium- or long-term data, and the geographical distribution restricted to high-income countries limit the generalisability of results. Conclusions should therefore be drawn cautiously. Since the findings suggest positive effects of resilience training for healthcare students with very-low certainty evidence, high-quality replications and improved study designs (e.g. a consensus on the definition of resilience, the assessment of individual stressor exposure, more attention controls, and longer follow-up periods) are clearly needed.

Electronic cigarettes for smoking cessation (Review)

Abstract: BACKGROUND Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. OBJECTIVES To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence. SEARCH METHODS We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors. SELECTION CRITERIA We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses. MAIN RESULTS We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. AUTHORS' CONCLUSIONS There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.

Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.

Abstract: Background Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. Objectives To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. Search methods Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. Selection criteria We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. Data collection and analysis Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. Main results We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). Authors' conclusions We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.