Measures implemented in the school setting to contain the COVID-19 pandemic.

BACKGROUND: More than 767 million coronavirus 2019 (COVID-19) cases and 6.9 million deaths with COVID-19 have been recorded as of August 2023. Several public health and social measures were implemented in schools to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent onward transmission. We built upon methods from a previous Cochrane review to capture current empirical evidence relating to the effectiveness of school measures to limit SARS-CoV-2 transmission. OBJECTIVES: To provide an updated assessment of the evidence on the effectiveness of measures implemented in the school setting to keep schools open safely during the COVID-19 pandemic. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Educational Resources Information Center, World Health Organization (WHO) COVID-19 Global literature on coronavirus disease database, and the US Department of Veterans Affairs Evidence Synthesis Program COVID-19 Evidence Reviews on 18 February 2022. SELECTION CRITERIA: Eligible studies focused on measures implemented in the school setting to contain the COVID-19 pandemic, among students (aged 4 to 18 years) or individuals relating to the school, or both. We categorized studies that reported quantitative measures of intervention effectiveness, and studies that assessed the performance of surveillance measures as either 'main' or 'supporting' studies based on design and approach to handling key confounders. We were interested in transmission-related outcomes and intended or unintended consequences. DATA COLLECTION AND ANALYSIS: Two review authors screened titles, abstracts and full texts. We extracted minimal data for supporting studies. For main studies, one review author extracted comprehensive data and assessed risk of bias, which a second author checked. We narratively synthesized findings for each intervention-comparator-outcome category (body of evidence). Two review authors assessed certainty of evidence. MAIN RESULTS: The 15 main studies consisted of measures to reduce contacts (4 studies), make contacts safer (7 studies), surveillance and response measures (6 studies; 1 assessed transmission outcomes, 5 assessed performance of surveillance measures), and multicomponent measures (1 study). These main studies assessed outcomes in the school population (12), general population (2), and adults living with a school-attending child (1). Settings included K-12 (kindergarten to grade 12; 9 studies), secondary (3 studies), and K-8 (kindergarten to grade 8; 1 study) schools. Two studies did not clearly report settings. Studies measured transmission-related outcomes (10), performance of surveillance measures (5), and intended and unintended consequences (4). The 15 main studies were based in the WHO Regions of the Americas (12), and the WHO European Region (3). Comparators were more versus less intense measures, single versus multicomponent measures, and measures versus no measures. We organized results into relevant bodies of evidence, or groups of studies relating to the same 'intervention-comparator-outcome' categories. Across all bodies of evidence, certainty of evidence ratings limit our confidence in findings. Where we describe an effect as 'beneficial', the direction of the point estimate of the effect favours the intervention; a 'harmful' effect does not favour the intervention and 'null' shows no effect either way. Measures to reduce contact (4 studies) We grouped studies into 21 bodies of evidence: moderate- (10 bodies), low- (3 bodies), or very low-certainty evidence (8 bodies). The evidence was very low to moderate certainty for beneficial effects of remote versus in-person or hybrid teaching on transmission in the general population. For students and staff, mostly harmful effects were observed when more students participated in remote teaching. Moderate-certainty evidence showed that in the general population there was probably no effect on deaths and a beneficial effect on hospitalizations for remote versus in-person teaching, but no effect for remote versus hybrid teaching. The effects of hybrid teaching, a combination of in-person and remote teaching, were mixed. Very low-certainty evidence showed that there may have been a harmful effect on risk of infection among adults living with a school student for closing playgrounds and cafeterias, a null effect for keeping the same teacher, and a beneficial effect for cancelling extracurricular activities, keeping the same students together and restricting entry for parents and caregivers. Measures to make contact safer (7 studies) We grouped studies into eight bodies of evidence: moderate- (5 bodies), and low-certainty evidence (3 bodies). Low-certainty evidence showed that there may have been a beneficial effect of mask mandates on transmission-related outcomes. Moderate-certainty evidence showed full mandates were probably more beneficial than partial or no mandates. Evidence of a beneficial effect of physical distancing on risk of infection among staff and students was mixed. Moderate-certainty evidence showed that ventilation measures probably reduce cases among staff and students. One study (very low-certainty evidence) found that there may be a beneficial effect of not sharing supplies and increasing desk space on risk of infection for adults living with a school student, but showed there may be a harmful effect of desk shields. Surveillance and response measures (6 studies) We grouped studies into seven bodies of evidence: moderate- (3 bodies), low- (1 body), and very low-certainty evidence (3 bodies). Daily testing strategies to replace or reduce quarantine probably helped to reduce missed school days and decrease the proportion of asymptomatic school contacts testing positive (moderate-certainty evidence). For studies that assessed the performance of surveillance measures, the proportion of cases detected by rapid antigen detection testing ranged from 28.6% to 95.8%, positive predictive value ranged from 24.0% to 100.0% (very low-certainty evidence). There was probably no onward transmission from contacts of a positive case (moderate-certainty evidence) and replacing or shortening quarantine with testing may have reduced missed school days (low-certainty evidence). Multicomponent measures (1 study) Combining multiple measures may have led to a reduction in risk of infection among adults living with a student (very low-certainty evidence). AUTHORS' CONCLUSIONS: A range of measures can have a beneficial effect on transmission-related outcomes, healthcare utilization and school attendance. We rated the current findings at a higher level of certainty than the original review. Further high-quality research into school measures to control SARS-CoV-2 in a wider variety of contexts is needed to develop a more evidence-based understanding of how to keep schools open safely during COVID-19 or a similar public health emergency.

A Bayesian hierarchical approach to account for evidence and uncertainty in the modeling of infectious diseases: An application to COVID-19.

Infectious disease models can serve as critical tools to predict the development of cases and associated healthcare demand and to determine the set of nonpharmaceutical interventions (NPIs) that is most effective in slowing the spread of an infectious agent. Current approaches to estimate NPI effects typically focus on relatively short time periods and either on the number of reported cases, deaths, intensive care occupancy, or hospital occupancy as a single indicator of disease transmission. In this work, we propose a Bayesian hierarchical model that integrates multiple outcomes and complementary sources of information in the estimation of the true and unknown number of infections while accounting for time-varying underreporting and weekday-specific delays in reported cases and deaths, allowing us to estimate the number of infections on a daily basis rather than having to smooth the data. To address dynamic changes occurring over long periods of time, we account for the spread of new variants, seasonality, and time-varying differences in host susceptibility. We implement a Markov chain Monte Carlo algorithm to conduct Bayesian inference and illustrate the proposed approach with data on COVID-19 from 20 European countries. The approach shows good performance on simulated data and produces posterior predictions that show a good fit to reported cases, deaths, hospital, and intensive care occupancy.

Effectiveness of international border control measures during the COVID-19 pandemic: a narrative synthesis of published systematic reviews.

The effectiveness of international border control measures during the COVID-19 pandemic is not well understood. Using a narrative synthesis approach to published systematic reviews, we synthesized the evidence from both modelling and observational studies on the effects of border control measures on domestic transmission of the virus. We find that symptomatic screening measures were not particularly effective, but that diagnostic-based screening methods were more effective at identifying infected travellers. Targeted travel restrictions levied against travellers from Wuhan were likely temporarily effective but insufficient to stop the exportation of the virus to the rest of the world. Quarantine of inbound travellers was also likely effective at reducing transmission, but only with relatively long quarantine periods, and came with important economic and social effects. There is little evidence that most travel restrictions, including border closure and those implemented to stop the introduction of new variants of concern, were particularly effective. Border control measures played an important role in former elimination locations but only when coupled with strong domestic public health measures. In future outbreaks, if border control measures are to be adopted, they should be seen as part of a broader strategy that includes other non-pharmaceutical interventions. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

Prognostic models for predicting clinical disease progression, worsening and activity in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly across individuals and many disease-modifying treatments with different safety and efficacy profiles have been developed recently. Prognostic models evaluated and shown to be valid in different settings have the potential to support people with MS and their physicians during the decision-making process for treatment or disease/life management, allow stratified and more precise interpretation of interventional trials, and provide insights into disease mechanisms. Many researchers have turned to prognostic models to help predict clinical outcomes in people with MS; however, to our knowledge, no widely accepted prognostic model for MS is being used in clinical practice yet. OBJECTIVES: To identify and summarise multivariable prognostic models, and their validation studies for quantifying the risk of clinical disease progression, worsening, and activity in adults with MS. SEARCH METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from January 1996 until July 2021. We also screened the reference lists of included studies and relevant reviews, and references citing the included studies. SELECTION CRITERIA: We included all statistically developed multivariable prognostic models aiming to predict clinical disease progression, worsening, and activity, as measured by disability, relapse, conversion to definite MS, conversion to progressive MS, or a composite of these in adult individuals with MS. We also included any studies evaluating the performance of (i.e. validating) these models. There were no restrictions based on language, data source, timing of prognostication, or timing of outcome. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently screened titles/abstracts and full texts, extracted data using a piloted form based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), assessed risk of bias using the Prediction Model Risk Of Bias Assessment Tool (PROBAST), and assessed reporting deficiencies based on the checklist items in Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD). The characteristics of the included models and their validations are described narratively. We planned to meta-analyse the discrimination and calibration of models with at least three external validations outside the model development study but no model met this criterion. We summarised between-study heterogeneity narratively but again could not perform the planned meta-regression. MAIN RESULTS: We included 57 studies, from which we identified 75 model developments, 15 external validations corresponding to only 12 (16%) of the models, and six author-reported validations. Only two models were externally validated multiple times. None of the identified external validations were performed by researchers independent of those that developed the model. The outcome was related to disease progression in 39 (41%), relapses in 8 (8%), conversion to definite MS in 17 (18%), and conversion to progressive MS in 27 (28%) of the 96 models or validations. The disease and treatment-related characteristics of included participants, and definitions of considered predictors and outcome, were highly heterogeneous amongst the studies. Based on the publication year, we observed an increase in the percent of participants on treatment, diversification of the diagnostic criteria used, an increase in consideration of biomarkers or treatment as predictors, and increased use of machine learning methods over time. Usability and reproducibility All identified models contained at least one predictor requiring the skills of a medical specialist for measurement or assessment. Most of the models (44; 59%) contained predictors that require specialist equipment likely to be absent from primary care or standard hospital settings. Over half (52%) of the developed models were not accompanied by model coefficients, tools, or instructions, which hinders their application, independent validation or reproduction. The data used in model developments were made publicly available or reported to be available on request only in a few studies (two and six, respectively). Risk of bias We rated all but one of the model developments or validations as having high overall risk of bias. The main reason for this was the statistical methods used for the development or evaluation of prognostic models; we rated all but two of the included model developments or validations as having high risk of bias in the analysis domain. None of the model developments that were externally validated or these models' external validations had low risk of bias. There were concerns related to applicability of the models to our research question in over one-third (38%) of the models or their validations. Reporting deficiencies Reporting was poor overall and there was no observable increase in the quality of reporting over time. The items that were unclearly reported or not reported at all for most of the included models or validations were related to sample size justification, blinding of outcome assessors, details of the full model or how to obtain predictions from it, amount of missing data, and treatments received by the participants. Reporting of preferred model performance measures of discrimination and calibration was suboptimal. AUTHORS' CONCLUSIONS: The current evidence is not sufficient for recommending the use of any of the published prognostic prediction models for people with MS in clinical routine today due to lack of independent external validations. The MS prognostic research community should adhere to the current reporting and methodological guidelines and conduct many more state-of-the-art external validation studies for the existing or newly developed models.

Interim Evaluation of Germany's Sugar Reduction Strategy for Soft Drinks: Commitments versus Actual Trends in Sugar Content and Sugar Sales from Soft Drinks.

INTRODUCTION: A high intake of sugar, in particular from sugar-sweetened soft drinks, increases the risk for obesity, type 2 diabetes mellitus, and dental caries. Germany has pursued a national strategy for sugar reduction in soft drinks based on voluntary commitments by industry since 2015, but its effects are unclear. METHODS: We use aggregated annual sales data from Euromonitor International to assess trends in mean sales-weighted sugar content of soft drinks and per capita sugar sales from soft drinks in Germany from 2015 to 2021. We compare these trends to the reduction path set by Germany's national sugar reduction strategy and to data for the United Kingdom, which adopted a soft drinks tax in 2017 and which we selected as best practice comparison country based on pre-defined criteria. RESULTS: Between 2015 and 2021, the mean sales-weighted sugar content of soft drinks sold in Germany decreased by 2% from 5.3 to 5.2 g/100 mL, falling short of an interim 9% reduction target and a 29% reduction observed in the United Kingdom over the same period. Sugar sales from soft drinks in Germany decreased from 22.4 to 21.6 g/capita/day (-4%) between 2015 and 2021 but remain high from a public health perspective. CONCLUSIONS: Reductions observed under Germany's sugar reduction strategy fall short of stated targets and trends observed internationally under best practice conditions. Additional policy measures may be needed to support sugar reduction in soft drinks in Germany.

Infrastructure, policy and regulatory interventions to increase physical activity to prevent cardiovascular diseases and diabetes: a systematic review.

BACKGROUND: Noncommunicable diseases are major contributors to morbidity and mortality worldwide. Modifying the risk factors for these conditions, such as physical inactivity, is thus essential. Addressing the context or circumstances in which physical activity occurs may promote physical activity at a population level. We assessed the effects of infrastructure, policy or regulatory interventions for increasing physical activity. METHODS: We searched PubMed, Embase and clinicaltrials.gov to identify randomised controlled trials (RCTs), controlled before-after (CBAs) studies, and interrupted time series (ITS) studies assessing population-level infrastructure or policy and regulatory interventions to increase physical activity. We were interested in the effects of these interventions on physical activity, body weight and related measures, blood pressure, and CVD and type 2 diabetes morbidity and mortality, and on other secondary outcomes. Screening and data extraction was done in duplicate, with risk of bias was using an adapted Cochrane risk of bias tool. Due to high levels of heterogeneity, we synthesised the evidence based on effect direction. RESULTS: We included 33 studies, mostly conducted in high-income countries. Of these, 13 assessed infrastructure changes to green or other spaces to promote physical activity and 18 infrastructure changes to promote active transport. The effects of identified interventions on physical activity, body weight and blood pressure varied across studies (very low certainty evidence); thus, we remain very uncertain about the effects of these interventions. Two studies assessed the effects of policy and regulatory interventions; one provided free access to physical activity facilities and showed that it may have beneficial effects on physical activity (low certainty evidence). The other provided free bus travel for youth, with intervention effects varying across studies (very low certainty evidence). CONCLUSIONS: Evidence from 33 studies assessing infrastructure, policy and regulatory interventions for increasing physical activity showed varying results. The certainty of the evidence was mostly very low, due to study designs included and inconsistent findings between studies. Despite this drawback, the evidence indicates that providing access to physical activity facilities may be beneficial; however this finding is based on only one study. Implementation of these interventions requires full consideration of contextual factors, especially in low resource settings. TRIAL REGISTRATION: PROSPERO 2018 CRD42018093429.

Ocean-atmosphere turbulent CO2 fluxes at Drake Passage and Bransfield Strait.

The oceans play an important role in mitigating climate change by acting as large carbon sinks, especially at high latitude regions. The Southern Ocean plays a major role in the global carbon dioxide (CO2) budget. This work aims to investigate the behavior of turbulent CO2 fluxes and quantify it under different atmospheric and oceanic conditions in the Drake Passage and Bransfield Strait regions on high spatiotemporal resolutions when compared with traditional CO2 fluxes estimations. The atmospheric stability condition was used to corroborate the description of CO2 fluxes. In situ, satellite, and reanalysis data from 08 to 22 November 2018, were used in this work. The Bransfield Strait uptaked 38.59% more CO2 than the Drake Passage due to the cold and fresh waters, allied to the influence of glacial meltwater dilution. Which increased the CO2 solubility, directing the CO2 fluxes to the ocean. The Bransfield Strait had predominantly stable atmospheric conditions, which contributed to this region acting as a CO2 sink. The Drake Passage, on average, behaved as a CO2 sink, mainly due to physical characteristics. This research contributes to a better understanding of the Southern Ocean's role in the global carbon balance on scales that are very difficult to monitor.

The effect of population-based blood pressure screening on long-term cardiometabolic morbidity and mortality in Germany: A regression discontinuity analysis.

BACKGROUND: Hypertension represents one of the major risk factors for cardiovascular morbidity and mortality globally. Early detection and treatment of this condition is vital to prevent complications. However, hypertension often goes undetected, and even if detected, not every patient receives adequate treatment. Identifying simple and effective interventions is therefore crucial to fight this problem and allow more patients to receive the treatment they need. Therefore, we aim at investigating the impact of a population-based blood pressure (BP) screening and the subsequent "low-threshold" information treatment on long-term cardiovascular disease (CVD) morbidity and mortality. METHODS AND FINDINGS: We examined the impact of a BP screening embedded in a population-based cohort study in Germany and subsequent personalized "light touch" information treatment, including a hypertension diagnosis and a recommendation to seek medical attention. We pooled four waves of the KORA study, carried out between 1984 and 1996 (N = 14,592). Using a sharp multivariate regression discontinuity (RD) design, we estimated the impact of the information treatment on CVD mortality and morbidity over 16.9 years. Additionally, we investigated potential intermediate outcomes, such as hypertension awareness, BP, and behavior after 7 years. No evidence of effect of BP screening was observed on CVD mortality (hazard ratio (HR) = 1.172 [95% confidence interval (CI): 0.725, 1.896]) or on any (fatal or nonfatal) long-term CVD event (HR = 1.022 [0.636, 1.641]) for individuals just above (versus below) the threshold for hypertension. Stratification for previous self-reported diagnosis of hypertension at baseline did not reveal any differential effect. The intermediate outcomes, including awareness of hypertension, were also unaffected by the information treatment. However, these results should be interpreted with caution since the analysis might not be sufficiently powered to detect a potential intervention effect. CONCLUSIONS: The study does not provide evidence of an effect of the assessed BP screening and subsequent information treatment on BP, health behavior, or long-term CVD mortality and morbidity. Future studies should consider larger datasets to detect possible effects and a shorter follow-up for the intermediate outcomes (i.e., BP and behavior) to detect short-, medium-, and long-term effects of the intervention along the causal pathway.

Interventions to improve water, sanitation, and hygiene for preventing soil-transmitted helminth infection.

BACKGROUND: It is estimated that 1.5 billion people are infected with soil-transmitted helminths (STHs) worldwide. Re-infection occurs rapidly following deworming, and interruption of transmission is unlikely without complementary control efforts such as improvements in water, sanitation, and hygiene (WASH) access and behaviours. OBJECTIVES: To assess the effectiveness of WASH interventions to prevent STH infection. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 19 October 2021. SELECTION CRITERIA: We included interventions to improve WASH access or practices in communities where STHs are endemic. We included randomized controlled trials (RCTs), as well as trials with an external control group where participants (or clusters) were allocated to different interventions using a non-random method (non-RCTs). We did not include observational study designs. Our primary outcome was prevalence of any STH infection. Prevalence of individual worms was a secondary outcome, including for Ascaris lumbricoides, Trichuris trichiura, hookworm (Ancylostoma duodenale or Necator americanus), or Strongyloides stercoralis. Intensity of infection, measured as a count of eggs per gram of faeces for each species, was another secondary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles and abstracts and full-text records for eligibility, performed data extraction, and assessed risk of bias using the Cochrane risk of bias assessment tool for RCTs and the EPOC tool for non-RCTs. We used a random-effects meta-analysis to pool study estimates. We used Moran's I² statistic to assess heterogeneity and conducted subgroup analyses to explore sources of heterogeneity. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 32 studies (16 RCTs and 16 non-RCTs) involving a total of 52,944 participants in the review. Twenty-two studies (14 RCTs (16 estimates) and eight non-RCTs (11 estimates)) reported on our primary outcome, prevalence of infection with at least one STH species. Twenty-one studies reported on the prevalence of A lumbricoides (12 RCTs and 9 non-RCTs); 17 on the prevalence of T trichiura (9 RCTs and 8 non-RCTs); 18 on the prevalence of hookworm (10 RCTs and 8 non-RCTs); and one on the prevalence of S stercoralis (1 non-RCT). Sixteen studies measured the intensity of infection for an individual STH type. Ten RCTs and five non-RCTs reported on the intensity of infection of A lumbricoides; eight RCTs and five non-RCTs measured the intensity of infection of T trichiura; and eight RCTs and five non-RCTs measured the intensity of hookworm infection. No studies reported on the intensity of infection of S stercoralis. The overall pooled effect estimates showed that the WASH interventions under study may result in a slight reduction of any STH infection, with an odds ratio (OR) of 0.86 amongst RCTs (95% confidence interval (CI) 0.74 to 1.01; moderate-certainty evidence) and an OR of 0.71 amongst non-RCTs (95% CI 0.54 to 0.94; low-certainty evidence). All six of the meta-analyses assessing individual worm infection amongst both RCTs and non-RCTs had pooled estimates in the preventive direction, although all CIs encapsulated the null, leaving the possibility of the null or even harmful effects; the certainty of the evidence ranged from very low to moderate. Individual studies assessing intensity of infection showed mixed evidence supporting WASH. Subgroup analyses focusing on narrow specific subsets of water, sanitation, and hygiene interventions did very little to elucidate which interventions might be better than others. Data on intensity of infection (e.g. faecal egg count) were reported in a variety of ways across studies, precluding the pooling of results for this outcome. We did not find any studies reporting adverse events resulting from the WASH interventions under study or from mass drug administration (MDA). AUTHORS' CONCLUSIONS: Whilst the available evidence suggests that the WASH interventions under study may slightly protect against STH infection, WASH also serves as a broad preventive measure for many other diseases that have a faecal oral transmission route of transmission. As many of the studies were done in addition to MDA/deworming (i.e. MDA was ongoing in both the intervention and control arm), our data support WHO recommendations for implementation of improvements to basic sanitation and adequate access to safe water alongside MDA. The biological plausibility for improved access to WASH to interrupt transmission of STHs is clear, but WASH interventions as currently delivered have shown impacts that were lower than expected. There is a need for more rigorous and targeted implementation research and process evaluations in order that future WASH interventions can better provide benefit to users. Inconsistent reporting of the intensity of infection underscores the need to define the minimal, standard data that should be collected globally on STHs to enable pooled analyses and comparisons.

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. OBJECTIVES: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022. SELECTION CRITERIA: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation. DATA COLLECTION AND ANALYSIS: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified no eligible studies for this review. AUTHORS' CONCLUSIONS: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.

Measures implemented in the school setting to contain the COVID-19 pandemic

BACKGROUND: In response to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the impact of coronavirus disease 2019 (COVID-19), governments have implemented a variety of measures to control the spread of the virus and the associated disease. Among these, have been measures to control the pandemic in primary and secondary school settings. OBJECTIVES: To assess the effectiveness of measures implemented in the school setting to safely reopen schools, or keep schools open, or both, during the COVID-19 pandemic, with particular focus on the different types of measures implemented in school settings and the outcomes used to measure their impacts on transmission-related outcomes, healthcare utilisation outcomes, other health outcomes as well as societal, economic, and ecological outcomes.  SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Educational Resources Information Center, as well as COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease (indexing preprints) on 9 December 2020. We conducted backward-citation searches with existing reviews. SELECTION CRITERIA: We considered experimental (i.e. randomised controlled trials; RCTs), quasi-experimental, observational and modelling studies assessing the effects of measures implemented in the school setting to safely reopen schools, or keep schools open, or both, during the COVID-19 pandemic. Outcome categories were (i) transmission-related outcomes (e.g. number or proportion of cases); (ii) healthcare utilisation outcomes (e.g. number or proportion of hospitalisations); (iii) other health outcomes (e.g. physical, social and mental health); and (iv) societal, economic and ecological outcomes (e.g. costs, human resources and education). We considered studies that included any population at risk of becoming infected with SARS-CoV-2 and/or developing COVID-19 disease including students, teachers, other school staff, or members of the wider community.  DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts. One review author extracted data and critically appraised each study. One additional review author validated the extracted data. To critically appraise included studies, we used the ROBINS-I tool for quasi-experimental and observational studies, the QUADAS-2 tool for observational screening studies, and a bespoke tool for modelling studies. We synthesised findings narratively. Three review authors made an initial assessment of the certainty of evidence with GRADE, and several review authors discussed and agreed on the ratings. MAIN RESULTS: We included 38 unique studies in the analysis, comprising 33 modelling studies, three observational studies, one quasi-experimental and one experimental study with modelling components. Measures fell into four broad categories: (i) measures reducing the opportunity for contacts; (ii) measures making contacts safer; (iii) surveillance and response measures; and (iv) multicomponent measures. As comparators, we encountered the operation of schools with no measures in place, less intense measures in place, single versus multicomponent measures in place, or closure of schools. Across all intervention categories and all study designs, very low- to low-certainty evidence ratings limit our confidence in the findings. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the model structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to deviations from intended interventions or missing data. Across all categories, few studies reported on implementation or described how measures were implemented. Where we describe effects as 'positive', the direction of the point estimate of the effect favours the intervention(s); 'negative' effects do not favour the intervention.  We found 23 modelling studies assessing measures reducing the opportunity for contacts (i.e. alternating attendance, reduced class size). Most of these studies assessed transmission and healthcare utilisation outcomes, and all of these studies showed a reduction in transmission (e.g. a reduction in the number or proportion of cases, reproduction number) and healthcare utilisation (i.e. fewer hospitalisations) and mixed or negative effects on societal, economic and ecological outcomes (i.e. fewer number of days spent in school). We identified 11 modelling studies and two observational studies assessing measures making contacts safer (i.e. mask wearing, cleaning, handwashing, ventilation). Five studies assessed the impact of combined measures to make contacts safer. They assessed transmission-related, healthcare utilisation, other health, and societal, economic and ecological outcomes. Most of these studies showed a reduction in transmission, and a reduction in hospitalisations; however, studies showed mixed or negative effects on societal, economic and ecological outcomes (i.e. fewer number of days spent in school). We identified 13 modelling studies and one observational study assessing surveillance and response measures, including testing and isolation, and symptomatic screening and isolation. Twelve studies focused on mass testing and isolation measures, while two looked specifically at symptom-based screening and isolation. Outcomes included transmission, healthcare utilisation, other health, and societal, economic and ecological outcomes. Most of these studies showed effects in favour of the intervention in terms of reductions in transmission and hospitalisations, however some showed mixed or negative effects on societal, economic and ecological outcomes (e.g. fewer number of days spent in school). We found three studies that reported outcomes relating to multicomponent measures, where it was not possible to disaggregate the effects of each individual intervention, including one modelling, one observational and one quasi-experimental study. These studies employed interventions, such as physical distancing, modification of school activities, testing, and exemption of high-risk students, using measures such as hand hygiene and mask wearing. Most of these studies showed a reduction in transmission, however some showed mixed or no effects.   As the majority of studies included in the review were modelling studies, there was a lack of empirical, real-world data, which meant that there were very little data on the actual implementation of interventions. AUTHORS' CONCLUSIONS: Our review suggests that a broad range of measures implemented in the school setting can have positive impacts on the transmission of SARS-CoV-2, and on healthcare utilisation outcomes related to COVID-19. The certainty of the evidence for most intervention-outcome combinations is very low, and the true effects of these measures are likely to be substantially different from those reported here. Measures implemented in the school setting may limit the number or proportion of cases and deaths, and may delay the progression of the pandemic. However, they may also lead to negative unintended consequences, such as fewer days spent in school (beyond those intended by the intervention). Further, most studies assessed the effects of a combination of interventions, which could not be disentangled to estimate their specific effects. Studies assessing measures to reduce contacts and to make contacts safer consistently predicted positive effects on transmission and healthcare utilisation, but may reduce the number of days students spent at school. Studies assessing surveillance and response measures predicted reductions in hospitalisations and school days missed due to infection or quarantine, however, there was mixed evidence on resources needed for surveillance. Evidence on multicomponent measures was mixed, mostly due to comparators. The magnitude of effects depends on multiple factors. New studies published since the original search date might heavily influence the overall conclusions and interpretation of findings for this review.

An Evaluation of Racial Diversity in Craniofacial Surgery Literature.

ABSTRACT: Implicit bias can lead to discrimination of certain populations within healthcare. Representation in medical literature is no exception and it is hypothesized that images with lighter skin tone are more prevalent than darker skin tones in craniofacial literature. Clinical photographs and figure graphics from 5 journals were examined for pre-defined years. Annals of Plastic Surgery, Aesthetic Surgery Journal, Journal of Craniofacial Surgery, Journal of Plastic, Reconstructive and Aesthetic Surgery, and Plastic and Reconstructive Surgery journals were reviewed. All craniofacial-focused articles containing at least one color image depicting human skin were included. 10,477 images and 627 graphics were evaluated using the Fitzpatrick scale as a guide. Most journals trended toward broader inclusion of nonwhite photographs and graphics over time. In 2016, 47% of articles published in Journal of Craniofacial Surgery included nonwhite images compared to Annals of Plastic Surgery (16%), Aesthetic Surgery Journal (40%), Journal of Plastic, Reconstructive and Aesthetic Surgery (25%), and Plastic and Reconstructive Surgery (7%). Comparison of domestic and international publications demonstrated that author's country of origin impacted the percentage of nonwhite clinical photographs for most journals. Comparisons of publications by country demonstrated increased diversity in Asia and the Middle East for clinical photographs but not graphics. The frequency of nonwhite figure graphics was staggeringly low, identified in only 18 articles across all journals and years. Craniofacial literature more commonly reflects white skin tones. The trend over time suggests increasing inclusion of racial diversity in clinical photographs; however, figure graphics remain less racially diverse. Time, country of origin, and publishing journal appear to play a role.

Underrepresentation of Racial Minorities in Breast Surgery Literature: A Call for Increased Diversity and Inclusion.

OBJECTIVE: In this study, the extent of racial diversity in images of breast-related plastic surgery published literature was investigated to better understand disparities that exist in breast surgery. BACKGROUND: The lack of racial diversity in images of skin color in surgery literature can perpetuate implicit bias and stereotypes. Implicit bias can affect the way patients are evaluated, diagnosed, and treated. The visual aspects of plastic surgery make a lack of diversity in imagery especially impactful on patient care and outcomes. METHODS: Published medical images and graphics depicting human skin were analyzed across 4 major plastic surgery journals. Up to 4 years were chosen a priori to evaluate from each journal and represented the initial year of color image publication, the year of study initiation (2016), and representative years for a given decade (2000 and 2010). Images and graphics were tabulated, rated by Fitzpatrick scale and categorized into "White" or "non-White." Data were evaluated with pair-wise and linear regression statistics. RESULTS: Of the 2774 images and 353 graphics that met inclusion criteria, only 184 (8.18%) images and 9 graphics (6.34%) depicted non-White skin. Temporal analysis showed that there is an increased diversity of images published since 2010 with 0% of images being non-White before and 7.3% to 10.3% after 2010. International and multi-national authors tended to publish more non-White images. CONCLUSIONS: There is insufficient racial diversity visually represented in the breast-related plastic surgery literature with a small degree of progress made towards more equitable imagery over time. Increasing awareness of image content, and the need for equitable visual representation may allow for improved racial diversity in surgical literature.

International travel-related control measures to contain the COVID-19 pandemic: a rapid review.

BACKGROUND: In late 2019, the first cases of coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of international travel-related control measures during the COVID-19 pandemic on infectious disease transmission and screening-related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO Global Database on COVID-19 Research to 13 November 2020. SELECTION CRITERIA: We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across international borders during the COVID-19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID-19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. 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: Two review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess 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, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements. MAIN RESULTS: Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission. Most studies compared travel-related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects. Below we outline the results for each intervention category by illustrating the findings from selected outcomes. Travel restrictions reducing or stopping cross-border travel (31 modelling studies) The studies assessed cases avoided and shift in epidemic development. We found very low-certainty evidence for a reduction in COVID-19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect. There was very low-certainty evidence that cross-border travel controls can slow the spread of COVID-19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure. Screening at borders (13 modelling studies; 13 observational studies) Screening measures covered symptom/exposure-based screening or test-based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely. For symptom/exposure-based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate-certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low-certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low-certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low-certainty evidence), although all but one study observed this proportion to be less than 54%. For test-based screening, one modelling study provided very low-certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low-certainty evidence). Quarantine (12 modelling studies) The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low- to low-certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low-certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance. Quarantine and screening at borders (7 modelling studies; 4 observational studies) The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low- to low-certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low-certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine. AUTHORS' CONCLUSIONS: With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross-border travel and quarantine of travellers, there is a lack of 'real-world' evidence. The certainty of the evidence for most travel-related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure-based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure-based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel-related control measures from a societal perspective.

Non-pharmacological measures implemented in the setting of long-term care facilities to prevent SARS-CoV-2 infections and their consequences: a rapid review.

BACKGROUND: Starting in late 2019, COVID-19, caused by the novel coronavirus SARS-CoV-2, spread around the world. Long-term care facilities are at particularly high risk of outbreaks, and the burden of morbidity and mortality is very high among residents living in these facilities. OBJECTIVES: To assess the effects of non-pharmacological measures implemented in long-term care facilities to prevent or reduce the transmission of SARS-CoV-2 infection among residents, staff, and visitors. SEARCH METHODS: On 22 January 2021, we searched the Cochrane COVID-19 Study Register, WHO COVID-19 Global literature on coronavirus disease, Web of Science, and CINAHL. We also conducted backward citation searches of existing reviews. SELECTION CRITERIA: We considered experimental, quasi-experimental, observational and modelling studies that assessed the effects of the measures implemented in long-term care facilities to protect residents and staff against SARS-CoV-2 infection. Primary outcomes were infections, hospitalisations and deaths due to COVID-19, contaminations of and outbreaks in long-term care facilities, and adverse health effects. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts. One review author performed data extractions, risk of bias assessments and quality appraisals, and at least one other author checked their accuracy. Risk of bias and quality assessments were conducted using the ROBINS-I tool for cohort and interrupted-time-series studies, the Joanna Briggs Institute (JBI) checklist for case-control studies, and a bespoke tool for modelling studies. We synthesised findings narratively, focusing on the direction of effect. One review author assessed certainty of evidence with GRADE, with the author team critically discussing the ratings. MAIN RESULTS: We included 11 observational studies and 11 modelling studies in the analysis. All studies were conducted in high-income countries. Most studies compared outcomes in long-term care facilities that implemented the measures with predicted or observed control scenarios without the measure (but often with baseline infection control measures also in place). Several modelling studies assessed additional comparator scenarios, such as comparing higher with lower rates of testing. There were serious concerns regarding risk of bias in almost all observational studies and major or critical concerns regarding the quality of many modelling studies. Most observational studies did not adequately control for confounding. Many modelling studies used inappropriate assumptions about the structure and input parameters of the models, and failed to adequately assess uncertainty. Overall, we identified five intervention domains, each including a number of specific measures. Entry regulation measures (4 observational studies; 4 modelling studies) Self-confinement of staff with residents may reduce the number of infections, probability of facility contamination, and number of deaths. Quarantine for new admissions may reduce the number of infections. Testing of new admissions and intensified testing of residents and of staff after holidays may reduce the number of infections, but the evidence is very uncertain. The evidence is very uncertain regarding whether restricting admissions of new residents reduces the number of infections, but the measure may reduce the probability of facility contamination. Visiting restrictions may reduce the number of infections and deaths. Furthermore, it may increase the probability of facility contamination, but the evidence is very uncertain. It is very uncertain how visiting restrictions may adversely affect the mental health of residents. Contact-regulating and transmission-reducing measures (6 observational studies; 2 modelling studies) Barrier nursing may increase the number of infections and the probability of outbreaks, but the evidence is very uncertain. Multicomponent cleaning and environmental hygiene measures may reduce the number of infections, but the evidence is very uncertain. It is unclear how contact reduction measures affect the probability of outbreaks. These measures may reduce the number of infections, but the evidence is very uncertain. Personal hygiene measures may reduce the probability of outbreaks, but the evidence is very uncertain.  Mask and personal protective equipment usage may reduce the number of infections, the probability of outbreaks, and the number of deaths, but the evidence is very uncertain. Cohorting residents and staff may reduce the number of infections, although evidence is very uncertain. Multicomponent contact -regulating and transmission -reducing measures may reduce the probability of outbreaks, but the evidence is very uncertain. Surveillance measures (2 observational studies; 6 modelling studies) Routine testing of residents and staff independent of symptoms may reduce the number of infections. It may reduce the probability of outbreaks, but the evidence is very uncertain. Evidence from one observational study suggests that the measure may reduce, while the evidence from one modelling study suggests that it probably reduces hospitalisations. The measure may reduce the number of deaths among residents, but the evidence on deaths among staff is unclear.  Symptom-based surveillance testing may reduce the number of infections and the probability of outbreaks, but the evidence is very uncertain. Outbreak control measures (4 observational studies; 3 modelling studies) Separating infected and non-infected residents or staff caring for them may reduce the number of infections. The measure may reduce the probability of outbreaks and may reduce the number of deaths, but the evidence for the latter is very uncertain. Isolation of cases may reduce the number of infections and the probability of outbreaks, but the evidence is very uncertain. Multicomponent measures (2 observational studies; 1 modelling study) A combination of multiple infection-control measures, including various combinations of the above categories, may reduce the number of infections and may reduce the number of deaths, but the evidence for the latter is very uncertain. AUTHORS' CONCLUSIONS: This review provides a comprehensive framework and synthesis of a range of non-pharmacological measures implemented in long-term care facilities. These may prevent SARS-CoV-2 infections and their consequences. However, the certainty of evidence is predominantly low to very low, due to the limited availability of evidence and the design and quality of available studies. Therefore, true effects may be substantially different from those reported here. Overall, more studies producing stronger evidence on the effects of non-pharmacological measures are needed, especially in low- and middle-income countries and on possible unintended consequences of these measures. Future research should explore the reasons behind the paucity of evidence to guide pandemic research priority setting in the future.

COVID-19 mitigation measures and nitrogen dioxide - A quasi-experimental study of air quality in Munich, Germany.

BACKGROUND: In response to the COVID-19 pandemic, the Bavarian State government announced several COVID-19 mitigation measures beginning on March 16, 2020, which likely led to a reduction in traffic and a subsequent improvement in air quality. In this study, we evaluated the short-term effect of COVID-19 mitigation measures on NO2 concentrations in Munich, Germany. METHODS: We applied two quasi-experimental approaches, a controlled interrupted time-series (c-ITS) approach and a synthetic control (SC) approach. Each approach compared changes occurring in 2020 to changes occurring in 2014-2019, and accounted for weather-related and other potential confounders. We hypothesized that the largest reductions in NO2 concentrations would be observed at traffic sites, with smaller reductions at urban background sites, and even small reductions, if any, at background sites. All hypotheses, as well as the main and additional analyses were defined a priori. We also conducted post-hoc analyses to ensure that observed effects were not due to factors other than the intervention. RESULTS: Main analyses largely supported our hypotheses. Specifically, at the two traffic sites, using the c-ITS approach we observed reductions of 9.34 µg/m3 (95% confidence interval: -23.58; 4.90) and 10.02 µg/m3 (-19.25; -0.79). Using the SC approach we observed reductions of 15.65 µg/m3 (-27.58; -4.09) and 15.1 µg/m3 (-24.82; -9.83) at these same sites. We observed effects ranging from smaller in magnitude to no effect at urban background and background sites. Additional analyses showed that the effect was largest in the first two weeks following introduction of measures, and that a 3-day lagged intervention time also showed a larger effect. Post-hoc analyses suggested that at least some of the observed effects may have been attributable to changes in air quality occurring before the intervention, as well as unusually high concentrations in January 2020. CONCLUSION: We applied two quasi-experimental approaches in assessing the impact of the COVID-19 mitigation measures on NO2 concentrations in Munich. Taking the 2020 pre-intervention average concentrations as a reference, we observed reductions in NO2 concentrations of approximately 15-25% and 24-36% at traffic sites, suggesting that reducing traffic may be an effective measure to reduce NO2 concentrations in heavily trafficked areas by margins which could translate to public health benefits.

Effectiveness of the German disease management programs: quasi-experimental analyses assessing the population-level health impact.

BACKGROUND: In 2002-2003 disease management programs (DMPs) for type 2 diabetes and coronary heart disease were introduced in Germany to improve the management of these conditions. Today around 6 million Germans aged 56 and older are enrolled in one of the DMPs; however, their effect on health remains unclear. METHODS: We estimated the impact of German DMPs on circulatory and all-cause mortality using a synthetic control study. Specifically, using routinely available data, we compared pre and post-intervention trends in mortality of individuals aged 56 and older for 1998-2014 in Germany to trends in other European countries. RESULTS: Average circulatory and all-cause mortality in Germany and the synthetic control was 1.63 and 3.24 deaths per 100 persons. Independent of model choice, circulatory and all-cause mortality decreased non-significantly less in Germany than in the synthetic control; for the model with a 3 year time lag, for example, by 0.12 (95%-CI: - 0.20; 0.44) and 0.22 (95%-CI: - 0.40; 0.66) deaths per 100 persons, respectively. Further main analyses, as well as sensitivity and subgroup analyses supported these results. CONCLUSIONS: We observed no effect on circulatory or all-cause mortality at the population-level. However, confidence intervals were wide, meaning we could not reject the possibility of a positive effect. Given the substantial costs for administration and operation of the programs, further comparative effectiveness research is needed to clarify the value of German DMPs for type 2 diabetes and CHD.

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

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 affected heavily by these measures is the school setting. By mid-April 2020, 192 countries had closed schools, affecting more than 90% of the world's student population. In consideration of the adverse consequences of school closures, many countries around the world reopened their schools in the months after 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 effectiveness, which will inform guidelines issued by the World Health Organization (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: To identify and comprehensively map the evidence assessing the impacts of measures implemented in the school setting to reopen schools, or keep schools open, or both, during the SARS-CoV-2/COVID-19 pandemic, with particular focus on the types of measures implemented in different 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. SELECTION CRITERIA: We included studies that assessed the impact of measures implemented in the school setting. Eligible populations were populations at risk of becoming infected with SARS-CoV-2, or developing COVID-19 disease, or both, and included people both directly and indirectly impacted by interventions, including students, teachers, other school staff, and contacts of these groups, as well as the broader community. We considered all types of empirical studies, which quantitatively assessed impact including epidemiological studies, modelling studies, mixed-methods studies, and diagnostic studies that assessed the impact of relevant interventions beyond diagnostic test accuracy. Broad outcome categories of interest included infectious disease transmission-related outcomes, other harmful or beneficial health-related outcomes, and societal, economic, and ecological implications. DATA COLLECTION AND ANALYSIS: We extracted data from included studies in a standardized manner, and mapped them to categories within our a priori logic model where possible. Where not possible, we inductively developed new categories. In line with standard expectations for scoping reviews, the review provides an overview of the existing evidence regardless of methodological quality or risk of bias, and was not designed to synthesize effectiveness data, assess risk of bias, or characterize strength of evidence (GRADE). MAIN RESULTS: We included 42 studies that assessed measures implemented in the school setting. The majority of studies used mathematical modelling designs (n = 31), while nine studies used observational designs, and two studies used experimental or quasi-experimental designs. Studies conducted in real-world contexts or using real data focused on the WHO European region (EUR; n = 20), the WHO region of the Americas (AMR; n = 13), the West Pacific region (WPR; n = 6), and the WHO Eastern Mediterranean Region (EMR; n = 1). One study conducted a global assessment and one did not report on data from, or that were applicable to, a specific country. Three broad intervention categories emerged from the included studies: organizational measures to reduce transmission of SARS-CoV-2 (n = 36), structural/environmental measures to reduce transmission of SARS-CoV-2 (n = 11), and surveillance and response measures to detect SARS-CoV-2 infections (n = 19). Most studies assessed SARS-CoV-2 transmission-related outcomes (n = 29), while others assessed healthcare utilization (n = 8), other health outcomes (n = 3), and societal, economic, and ecological outcomes (n = 5). Studies assessed both harmful and beneficial outcomes across all outcome categories. AUTHORS' CONCLUSIONS: We identified a heterogeneous and complex evidence base of measures implemented in the school setting. This review is an important first step in understanding the available evidence and will inform the development of rapid reviews on this topic.

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

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. Studies on COVID-19 Travel restrictions reducing cross-border travel Eleven studies employed models to simulate a reduction in travel volume; one observational ecological study assessed travel restrictions in response to the COVID-19 pandemic. Very low-certainty evidence from modelling studies suggests that when implemented at the beginning of the outbreak, cross-border travel restrictions may lead to a reduction in the number of new cases of between 26% to 90% (4 studies), the number of deaths (1 study), the time to outbreak of between 2 and 26 days (2 studies), the risk of outbreak of between 1% to 37% (2 studies), and the effective reproduction number (1 modelling and 1 observational ecological study). Low-certainty evidence from modelling studies suggests a reduction in the number of imported or exported cases of between 70% to 81% (5 studies), and in the growth acceleration of epidemic progression (1 study). Screening at borders with or without quarantine Evidence from three modelling studies of entry and exit symptom screening without quarantine suggests delays in the time to outbreak of between 1 to 183 days (very low-certainty evidence) and a detection rate of infected travellers of between 10% to 53% (low-certainty evidence). Six observational studies of entry and exit screening were conducted in specific settings such as evacuation flights and cruise ship outbreaks. Screening approaches varied but followed a similar structure, involving symptom screening of all individuals at departure or upon arrival, followed by quarantine, and different procedures for observation and PCR testing over a period of at least 14 days. The proportion of cases detected ranged from 0% to 91% (depending on the screening approach), and the positive predictive value ranged from 0% to 100% (very low-certainty evidence). The outcomes, however, should be interpreted in relation to both the screening approach used and the prevalence of infection among the travellers screened; for example, symptom-based screening alone generally performed worse than a combination of symptom-based and PCR screening with subsequent observation during quarantine. Quarantine of travellers Evidence from one modelling study simulating a 14-day quarantine suggests a reduction in the number of cases seeded by imported cases; larger reductions were seen with increasing levels of quarantine compliance ranging from 277 to 19 cases with rates of compliance modelled between 70% to 100% (very low-certainty evidence). AUTHORS' CONCLUSIONS: With much of the evidence deriving from modelling studies, notably for travel restrictions reducing cross-border travel and quarantine of travellers, there is a lack of 'real-life' evidence for many of these measures. The certainty of the evidence for most travel-related control measures is very low and the true effects may be substantially different from those reported here. Nevertheless, some travel-related control measures during the COVID-19 pandemic may have a positive impact on infectious disease outcomes. Broadly, travel restrictions may limit the spread of disease across national borders. Entry and exit symptom screening measures on their own are not likely to be effective in detecting a meaningful proportion of cases to prevent seeding new cases within the protected region; combined with subsequent quarantine, observation and PCR testing, the effectiveness is likely to improve. There was insufficient evidence to draw firm conclusions about the effectiveness of travel-related quarantine on its own. Some of the included studies suggest that effects are likely to depend on factors such as the stage of the epidemic, the interconnectedness of countries, local measures undertaken to contain community transmission, and the extent of implementation and adherence.

Inhibition of soluble TNFα prevents adverse atrial remodeling and atrial arrhythmia susceptibility induced in mice by endurance exercise.

Intense endurance exercise is linked to atrial fibrillation (AF). We established previously that interventions that simultaneously interfere with TNFα signaling, mediated via both the enzymatically liberated soluble and membrane-bound forms of TNFα, prevent atrial remodeling and AF vulnerability in exercised mice. To investigate which signaling modality underlies this protection, we treated exercised mice with XPRO®1595, a selective dominant-negative inhibitor of solTNFα. In male CD1 mice, 6 weeks of intense swim exercise induced reductions in heart rate, increased cardiac vagal tone, left ventricular (LV) dilation and enhanced LV function. By contrast, exercise induced hypertrophy, fibrosis, and increased inflammatory cell infiltrates in atria, and these changes were associated with increased AF susceptibility in isolated atria as well as mice, with and without parasympathetic nerve blockade. Although XPRO treatment had no effect on the beneficial physiological changes induced by exercise, it protected against adverse atrial changes as well as AF susceptibility. Our results establish that soluble TNFα is required for exercise-induced increases in AF vulnerability, which is linked to fibrosis, inflammation, and enlargement of the atria, but largely independent of changes in vagal tone.