Consideration of inequalities in effectiveness trials of mHealth applications - a systematic assessment of studies from an umbrella review.

BACKGROUND: The growing use of mobile health applications (apps) for managing diabetes and hypertension entails an increased need to understand their effectiveness among different population groups. It is unclear if efficacy and effectiveness trials currently provide evidence of differential effectiveness, and if they do, a summary of such evidence is missing. Our study identified to what extent sociocultural and socioeconomic inequalities were considered in effectiveness trials of mobile health apps in diabetic and hypertensive patients and if these inequalities moderated app effectiveness. METHODS: We built on our recent umbrella review that synthesized systematic reviews (SRs) of randomized controlled trials (RCTs) on the effectiveness of health apps. Using standard SR methodologies, we identified and assessed all primary RCTs from these SRs that focused on diabetes and/or hypertension and reported on health-related outcomes and inequality-related characteristics across intervention arms. We used the PROGRESS-Plus framework to define inequality-related characteristics that affect health opportunities and outcomes. We used harvest plots to summarize the subgroups (stratified analyses or interaction terms) on moderating effects of PROGRESS-Plus. We assessed study quality using the Risk of Bias 2 tool. RESULTS: We included 72 published articles of 65 unique RCTs. Gender, age, and education were the most frequently described PROGRESS-Plus characteristics at baseline in more than half of the studies. Ethnicity and occupation followed in 21 and 15 RCTs, respectively. Seven trials investigated the moderating effect of age, gender or ethnicity on app effectiveness through subgroup analyses. Results were equivocal and covered a heterogenous set of outcomes. Results showed some concerns for a high risk of bias, mostly because participants could not be blinded to their intervention allocation. CONCLUSIONS: Besides frequently available gender, age, and education descriptives, other relevant sociocultural or socioeconomic characteristics were neither sufficiently reported nor analyzed. We encourage researchers to investigate how these characteristics moderate the effectiveness of health apps to better understand how effect heterogeneity for apps across different sociocultural or socioeconomic groups affects inequalities, to support more equitable management of non-communicable diseases in increasingly digitalized systems. REGISTRATION: https://osf.io/89dhy/ .

Evaluation of implementation of evidence-based public health training in sub-Saharan Africa.

Background: The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA+) developed and offered a course on evidence-based public health (EBPH) in five sub-Saharan African (SSA) countries to enhance individual and institutional capacity. Aim: This study aims to assess, compare and learn from implementing the CEBHA+ EBPH course using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and Practical, Robust, Implementation and Sustainability Model (PRISM). Setting: This study involved CEHBA+ partner universities in five countries in SSA. Methods: We developed a framework that draws on signalling questions for RE-AIM and PRISM dimensions. Country teams reflected on, discussed and mapped unique experiences. Using this framework, we then elicited common themes across countries and distilled country-specific experiences through virtual discussions. Results: Across countries, 130 public health practitioners, researchers and students completed the course (Reach). The course increased EBPH knowledge and skills and the capacity to teach EBPH and resulted in immediate opportunities for applying skills (Effectiveness). Hybrid offering in two countries presented challenges regarding Internet connectivity and hybrid discussions. Facilitators had previous training in teaching EBPH. While learning material was the same across countries, the content was adapted to represent local public health priorities (Implementation, Adoption). Course materials have informed other related training leading to spin-offs (Maintenance). Institutionalisation is dependent on external funding. Conclusion: Strengthening EBPH capacity across contexts is feasible. Curricula containing both core and contextualised elements create an authentic learning environment. Formal evaluations should be embedded within capacity-strengthening initiatives. Contribution: This is the first study evaluating EBPH training in SSA using an implementation science lens, offering learning about context-relevant adaptations that assist with plans for sustainability and scale.

The effect of exposure to radiofrequency electromagnetic fields on cognitive performance in human experimental studies: Systematic review and meta-analyses.

BACKGROUND: The objective of this review is to evaluate the associations between short-term exposure to radiofrequency electromagnetic fields (RF-EMF) and cognitive performance in human experimental studies. METHODS: Online databases (PubMed, Embase, Scopus, Web of Science and EMF-Portal) were searched for studies that evaluated effects of exposure to RF-EMF on seven domains of cognitive performance in human experimental studies. The assessment of study quality was based on the Risk of Bias (RoB) tool developed by the Office of Health Assessment and Translation (OHAT). Random effects meta-analyses of Hedges's g were conducted separately for accuracy- and speed-related performance measures of various cognitive domains, for which data from at least two studies were available. Finally, the certainty of evidence for each identified outcome was assessed according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: 57,543 records were identified and 76 studies (80 reports) met the inclusion criteria. The included 76 studies with 3846 participants, consisting of humans of different age, sex and health status from 19 countries, were conducted between 1989 and 2021. Quantitative data from 50 studies (52 reports) with 2433 participants were included into the meta-analyses. These studies were performed in 15 countries between 2001 and 2021. The majority of the included studies used head exposure with GSM 900 uplink. None of the meta-analyses observed a statistically significant effect of RF-EMF exposure compared to sham on cognitive performance as measured by the confidence interval surrounding the Hedges's g or the significance of the z-statistic. For the domain Orientation and Attention, subclass Attention - Attentional Capacity RF-EMF exposure results in little to no difference in accuracy (Hedges's g 0.024, 95 % CI [-0.10; 0.15], I2 = 28 %, 473 participants). For the domain Orientation and Attention, subclass Attention - Concentration / Focused Attention RF-EMF exposure results in little to no difference in speed (Hedges's g 0.005, 95 % CI [-0.17; 0.18], I2 = 7 %, 132 participants) and probably results in little to no difference in accuracy; it does not reduce accuracy (Hedges's g 0.097, 95 % CI [-0.05; 0.24], I2 = 0 %, 217 participants). For the domain Orientation and Attention, subclass Attention - Vigilance RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.118, 95 % CI [-0.04; 0.28], I2 = 41 %, 247 participants) and results in little to no difference in accuracy (Hedges's g 0.042, 95 % CI, [-0.09; 0.18], I2 = 0 %, 199 participants). For the domain Orientation and Attention, subclass Attention - Selective Attention RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.080, 95 % CI [-0.09; 0.25], I2 = 63 %, 452 participants); it may result in little to no difference in accuracy, but it probably does not reduce accuracy (Hedges's g 0.178, 95 % CI [-0.02; 0.38], I2 = 68 %, 480 participants). For the domain Orientation and Attention, subclass Attention - Divided Attention RF-EMF exposure results in little to no difference in speed (Hedges's g -0.010, 95 % CI [-0.14; 0.12], I2 = 5 %, 307 participants) and may result in little to no difference in accuracy (Hedges's g -0.089, 95 % CI [-0.35; 0.18], I2 = 53 %, 167 participants). For the domain Orientation and Attention, subclass Processing Speed - Simple Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g 0.069, 95 % CI [-0.02; +0.16], I2 = 29 %, 820 participants). For the domain Orientation and Attention, subclass Processing Speed - 2-Choice Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g -0.023, 95 % CI [-0.13; 0.08], I2 = 0 %, 401 participants), and may result in little to no difference in accuracy (Hedges's g -0.063, 95 % CI [-0.38; 0.25], I2 = 63 %, 117 participants). For the domain Orientation and Attention, subclass Processing Speed - >2-Choice Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g -0.054, 95 % CI [-0.14; 0.03], I2 = 0 %, 544 participants) and probably results in little to no difference in accuracy (Hedges's g -0.129, 95 % CI [-0.30; 0.04], I2 = 0 %, 131 participants). For the domain Orientation and Attention, subclass Processing Speed - Other Tasks RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.067, 95 % CI [-0.12; 0.26], I2 = 38 %, 249 participants); it results in little to no difference in accuracy (Hedges's g 0.036, 95 % CI [-0.08; 0.15], I2 = 0 %, 354 participants). For the domain Orientation and Attention, subclass Working Memory - n-back Task (0-3-back) we found Hedges's g ranging from -0.090, 95 % CI [-0.18; 0.01] to 0.060, 95 % CI [-0.06; 0.18], all I2 = 0 %, 237 to 474 participants, and conclude that RF-EMF exposure results in little to no difference in both speed and accuracy. For the domain Orientation and Attention, subclass Working Memory - Mental Tracking RF-EMF exposure results in little to no difference in accuracy (Hedges's g -0.047, 95 % [CI -0.15; 0.05], I2 = 0 %, 438 participants). For the domain Perception, subclass Visual and Auditory Perception RF-EMF exposure may result in little to no difference in speed (Hedges's g -0.015, 95 % CI [-0.23; 0.195], I2 = 0 %, 84 participants) and probably results in little to no difference in accuracy (Hedges's g 0.035, 95 % CI [-0.13; 0.199], I2 = 0 %, 137 participants). For the domain Memory, subclass Verbal and Visual Memory RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.042, 95 % CI [-0.15; 0.23], I2 = 0 %, 102 participants); it may result in little to no difference in accuracy (Hedges's g -0.087, 95 % CI [-0.38; 0.20], I2 = 85 %, 625 participants). For the domain Verbal Functions and Language Skills, subclass Verbal Expression, a meta-analysis was not possible because one of the two included studies did not provide numerical values. Results of both studies did not indicate statistically significant effects of RF-EMF exposure on both speed and accuracy. For the domain Construction and Motor Performance, subclass Motor Skills RF-EMF exposure may reduce speed, but the evidence is very uncertain (Hedges's g -0.919, 95 % CI [-3.09; 1.26], I2 = 96 %, 42 participants); it probably results in little to no difference in accuracy and does not reduce accuracy (Hedges's g 0.228, 95 % CI [-0.01; 0.46], I2 = 0 %, 109 participants). For the domain Concept Formation and Reasoning, subclass Reasoning RF-EMF exposure results in little to no difference in speed (Hedges's g 0.010, 95 % CI [-0.11; 0.13], I2 = 0 %, 263 participants) and probably results in little to no difference in accuracy and does not reduce accuracy (Hedges's g 0.051, 95 % CI [-0.14; 0.25], I2 = 0 %, 100 participants). For the domain Concept Formation and Reasoning, subclass Mathematical Procedures RF-EMF exposure results in little to no difference in speed (Hedges's g 0.033, 95 % CI [-0.12; 0.18], I2 = 0 %, 168 participants) and may result in little to no difference in accuracy but probably does not reduce accuracy (Hedges's g 0.232, 95 % CI [-0.12; +0.59], I2 = 86 %, 253 participants). For the domain Executive Functions there were no studies. DISCUSSION: Overall, the results from all domains and subclasses across their speed- and accuracy-related outcome measures according to GRADE provide high to low certainty of evidence that short-term RF-EMF exposure does not reduce cognitive performance in human experimental studies. For 16 out of 35 subdomains some uncertainty remains, because of limitations in the study quality, inconsistency in the results or imprecision of the combined effect size estimate. Future research should focus on construction and motor performance, elderly, and consideration of both sexes. OTHER: This review was partially funded by the WHO radioprotection programme. The protocol for this review was registered in Prospero reg. no. CRD42021236168 and published in Environment International (Pophof et al. 2021).

Informing pandemic management in Germany with trustworthy living evidence syntheses and guideline development: lessons learned from the COVID-19 evidence ecosystem.

OBJECTIVES: We present the 'COVID-19 evidence ecosystem' (CEOsys) as a German network to inform pandemic management and to support clinical and public health decision-making. We discuss challenges faced when organizing the ecosystem and derive lessons learned for similar networks acting during pandemics or health-related crises. STUDY DESIGN AND SETTING: Bringing together 18 university hospitals and additional institutions, CEOsys key activities included research prioritization, conducting living systematic reviews (LSRs), supporting evidence-based (living) guidelines, knowledge translation (KT), detecting research gaps, and deriving recommendations, backed by technical infrastructure and capacity building. RESULTS: CEOsys rapidly produced 31 high-quality evidence syntheses and supported three living guidelines on COVID-19-related topics, while also developing methodological procedures. Challenges included CEOsys' late initiation in relation to the pandemic outbreak, the delayed prioritization of research questions, the continuously evolving COVID-19-related evidence, and establishing a technical infrastructure. Methodological-clinical tandems, the cooperation with national guideline groups and international collaborations were key for efficiency. CONCLUSION: CEOsys provided a proof-of-concept for a functioning evidence ecosystem at the national level. Lessons learned include that similar networks should, among others, involve methodological and clinical key stakeholders early on, aim for (inter)national collaborations, and systematically evaluate their value. We particularly call for a sustainable network.

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.

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.

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.

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'.

Public health and social measures during health emergencies such as the COVID-19 pandemic: An initial framework to conceptualize and classify measures.

Background: Public health and social measures (PHSM) intend to reduce the transmission of infectious diseases and to reduce the burden on health systems, economies and societies. During the COVID-19 pandemic, PHSM have been selected, combined and implemented in a variable manner and inconsistently categorized in policy trackers. This paper presents an initial conceptual framework depicting how PHSM operate in a complex system, enabling a wide-reaching description of these measures and their intended and unintended outcomes. Methods: In a multi-stage development process, we combined (i) a complexity perspective and systems thinking; (ii) literature on existing COVID-19 PHSM frameworks, taxonomies and policy trackers; (iii) expert input and (iv) application to school and international travel measures. Results: The initial framework reflects our current understanding of how PHSM are intended to achieve transmission-related outcomes in a complex system, offering visualizations, definitions and worked examples. First, PHSM operate through two basic mechanisms, that is, reducing contacts and/or making contacts safer. Second, PHSM are defined not only by the measures themselves but by their stringency and application to specific populations and settings. Third, PHSM are critically influenced by contextual factors. The framework provides a tool for structured thinking and further development, rather than a ready-to-use tool for practice. Conclusions: This conceptual framework seeks to facilitate coordinated, interdisciplinary research on PHSM effectiveness, impact and implementation; enable consistent, coherent PHSM monitoring and evaluation; and contribute to evidence-informed decision-making on PHSM implementation, adaptation and de-implementation. We expect this framework to be modified and refined over time.

Urban policy interventions to reduce traffic-related emissions and air pollution: A systematic evidence map.

BACKGROUND: Urban areas are hot spots for human exposure to air pollution, which originates in large part from traffic. As the urban population continues to grow, a greater number of people risk exposure to traffic-related air pollution (TRAP) and its adverse, costly health effects. In many cities, there is a need and scope for air quality improvements through targeted policy interventions, which continue to grow including rapidly changing technologies. OBJECTIVE: This systematic evidence map (SEM) examines and characterizes peer-reviewed evidence on urban-level policy interventions aimed at reducing traffic emissions and/or TRAP from on-road mobile sources, thus potentially reducing human exposures and adverse health effects and producing various co-benefits. METHODS: This SEM follows a previously peer-reviewed and published protocol with minor deviations, explicitly outlined here. Articles indexed in Public Affairs Index, TRID, Medline and Embase were searched, limited to English, published between January 1, 2000, and June 1, 2020. Covidence was used to screen articles based on previously developed eligibility criteria. Data for included articles was extracted and manually documented into an Excel database. Data visualizations were created in Tableau. RESULTS: We identified 7528 unique articles from database searches and included 376 unique articles in the final SEM. There were 58 unique policy interventions, and a total of 1,139 unique policy scenarios, comprising these interventions and different combinations thereof. The policy interventions fell under 6 overarching policy categories: 1) pricing, 2) land use, 3) infrastructure, 4) behavioral, 5) technology, and 6) management, standards, and services, with the latter being the most studied. For geographic location, 463 policy scenarios were studied in Europe, followed by 355 in Asia, 206 in North America, 57 in South America, 10 in Africa, and 7 in Australia. Alternative fuel technology was the most frequently studied intervention (271 times), followed by vehicle emission regulation (134 times). The least frequently studied interventions were vehicle ownership taxes, and studded tire regulations, studied once each. A mere 3 % of studies addressed all elements of the full-chain-traffic emissions, TRAP, exposures, and health. The evidence recorded for each unique policy scenario is hosted in an open-access, query-able Excel database, and a complementary interactive visualization tool. We showcase how users can find more about the effectiveness of the 1,139 included policy scenarios in reducing, increasing, having mixed or no effect on traffic emissions and/or TRAP. CONCLUSION: This is the first peer-reviewed SEM to compile international evidence on urban-level policy interventions to reduce traffic emissions and/or TRAP in the context of human exposure and health effects. We also documented reported enablers, barriers, and co-benefits. The open-access Excel database and interactive visualization tool can be valuable resources for practitioners, policymakers, and researchers. Future updates to this work are recommended. PROTOCOL REGISTRATION: Sanchez, K.A., Foster, M., Nieuwenhuijsen, M.J., May, A.D., Ramani, T., Zietsman, J. and Khreis, H., 2020. Urban policy interventions to reduce traffic emissions and traffic-related air pollution: Protocol for a systematic evidence map. Environment international, 142, p.105826.

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.

Mental Health Impact of Early Stages of the COVID-19 Pandemic on Individuals with Pre-Existing Mental Disorders: A Systematic Review of Longitudinal Research.

In view of disease-related threats, containment measures, and disrupted healthcare, individuals with pre-existing mental illness might be vulnerable to adverse effects of the COVID-19 pandemic. Previous reviews indicated increased mental distress, with limited information on peri-pandemic changes. In this systematic review, we aimed to identify longitudinal research investigating pre- to peri-pandemic and/or peri-pandemic changes of mental health in patients, focusing on the early phase and considering specific diagnoses. PsycINFO, Web of Science, the WHO Global literature on coronavirus disease database, and the Cochrane COVID-19 Study Register weresearched through 31 May 2021. Studies were synthesized using vote counting based on effect direction. We included 40 studies mostly from Western, high-income countries. Findings were heterogeneous, with improving and deteriorating mental health observed compared to pre-pandemic data, partly depending on underlying diagnoses. For peri-pandemic changes, evidence was limited, with some suggestion of recovery of mental distress. Study quality was heterogeneous; only few studies investigated potential moderators (e.g., chronicity of mental illness). Mental health effects on people with pre-existing conditions are heterogeneous within and across diagnoses for pre- to peri-pandemic and peri-pandemic comparisons. To improve mental health services amid future global crises, forthcoming research should understand medium- and long-term effects, controlling for containment measures.

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.

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.

Population-Level Interventions Targeting Risk Factors for Hypertension and Diabetes in Rwanda: A Situational Analysis.

Background: Eighty percent (80%) of global Non-Communicable Diseases attributed deaths occur in low- and middle-income countries (LMIC) with hypertension and diabetes being key contributors. The overall prevalence of hypertension was 15.3% the national prevalence of diabetes in rural and urban was 7.5 and 9.7%, respectively among 15-64 years. Hypertension represents a leading cause of death (43%) among hospitalized patients at the University teaching hospital of Kigali. This study aimed to identify ongoing population-level interventions targeting risk factors for diabetes and hypertension and to explore perceived barriers and facilitators for their implementation in Rwanda. Methods: This situational analysis comprised a desk review, key informant interviews, and stakeholders' consultation. Ongoing population-level interventions were identified through searches of government websites, complemented by one-on-one consultations with 60 individuals nominated by their respective organizations involved with prevention efforts. Semi-structured interviews with purposively selected key informants sought to identify perceived barriers and facilitators for the implementation of population-level interventions. A consultative workshop with stakeholders was organized to validate and consolidate the findings. Results: We identified a range of policies in the areas of food and nutrition, physical activity promotion, and tobacco control. Supporting program and environment interventions were mainly awareness campaigns to improve knowledge, attitudes, and practices toward healthy eating, physical activity, and alcohol and tobacco use reduction, healthy food production, physical activity infrastructure, smoke-free areas, limits on tobacco production and bans on non-standardized alcohol production. Perceived barriers included limited stakeholder involvement, misbeliefs about ongoing interventions, insufficient funding, inconsistency in intervention implementation, weak policy enforcement, and conflicts between commercial and public health interests. Perceived facilitators were strengthened multi-sectoral collaboration and involvement in ongoing interventions, enhanced community awareness of ongoing interventions, special attention paid to the elderly, and increased funds for population-level interventions and policy enforcement. Conclusion: There are many ongoing population-level interventions in Rwanda targeting risk factors for diabetes and hypertension. Identified gaps, perceived barriers, and facilitators provide a useful starting point for strengthening efforts to address the significant burden of disease attributable to diabetes and hypertension.

Lessons learnt: Undertaking rapid reviews on public health and social measures during a global pandemic.

Public health and social measures (PHSM) have been central to the COVID-19 response. Consequently, there has been much pressure on decision-makers to make evidence-informed decisions and on researchers to synthesize the evidence regarding these measures. This article describes our experiences, responses and lessons learnt regarding key challenges when planning and conducting rapid reviews of PHSM during the COVID-19 pandemic. Stakeholder consultations and scoping reviews to obtain an overview of the evidence inform the scope of reviews that are policy-relevant and feasible. Multiple complementary reviews serve to examine the benefits and harms of PHSM across different populations and contexts. Conceiving reviews of effectiveness as adaptable living reviews helps to respond to evolving evidence needs and an expanding evidence base. An appropriately skilled review team and good planning, coordination and communication ensures smooth and rigorous processes and efficient use of resources. Scientific rigor, the practical implications of PHSM-related complexity and likely time savings should be carefully weighed in deciding on methodological shortcuts. Making the best possible use of modeling studies represents a particular challenge, and methods should be carefully chosen, piloted and implemented. Our experience raises questions regarding the nature of rapid reviews and regarding how different types of evidence should be considered in making decisions about PHSM during a global pandemic. We highlight the need for readily available protocols for conducting studies on the effectiveness, unintended consequences and implementation of PHSM in a timely manner, as well as the need for rapid review standards tailored to "rapid" versus "emergency" mode reviewing.

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.

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.