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Objective: The objective of the study was to clarify how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept of certainty of evidence applies to certainty ratings of test accuracy. Study Design and Setting: After initial brainstorming with GRADE Working Group members, we iteratively refined and clarified the approaches for defining ranges when assessing the certainty of evidence for test accuracy within a systematic review, health technology assessment, or guideline. Results: Ranges can be defined both for single test accuracy and for comparative accuracy of multiple tests. For systematic reviews and health technology assessments, approaches for defining ranges include some that do not require value judgments regarding downstream health outcomes. Key challenges arise in the context of a guideline that requires ranges for sensitivity and specificity that are set considering possible effects on all critical outcomes. We illustrate possible approaches and provide an example from a systematic review of a direct comparison between two test strategies. Conclusions: This GRADE concept paper provides a framework for assessing, presenting, and making decisions based on the certainty of evidence for test accuracy. More empirical research is needed to support future GRADE guidance on how to best operationalize the candidate approaches.

Breakthrough invasive fungal infections (IFI) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed, and circulated to all members of the two organizations for comment and suggestions. The authors addressed comments received, and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment, and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.

This document is part of the “SHEA Neonatal Intensive Care Unit (NICU) White Paper Series.” It is intended to provide practical, expert opinion, and/or evidence-based answers to frequently asked questions about CLABSI detection and prevention in the NICU. This document serves as a companion to the CDC Healthcare Infection Control Practices Advisory Committee (HICPAC) Guideline for Prevention of Infections in Neonatal Intensive Care Unit Patients. Central line-associated bloodstream infections (CLABSIs) are among the most frequent invasive infections among infants in the NICU and contribute to substantial morbidity and mortality. Infants who survive CLABSIs have prolonged hospitalization resulting in increased healthcare costs and suffer greater comorbidities including worse neurodevelopmental and growth outcomes. A bundled approach to central line care practices in the NICU has reduced CLABSI rates, but challenges remain. This document was authored by pediatric infectious diseases specialists, neonatologists, advanced practice nurse practitioners, infection preventionists, members of the HICPAC guideline-writing panel, and members of the SHEA Pediatric Leadership Council. For the selected topic areas, the authors provide practical approaches in question-and-answer format, with answers based on consensus expert opinion within the context of the literature search conducted for the companion HICPAC document and supplemented by other published information retrieved by the authors. Two documents in the series precede this one: “Practical approaches to Clostridioides difficile prevention” published in August 2018 and “Practical approaches to Staphylococcus aureus prevention,” published in September 2020.

Contains fulltext : 237435.pdf (Publisher’s version ) (Open Access) Objective: We evaluated reporting completeness and transparency in randomised controlled trials (RCTs) conducted using administrative data based on 2021 CONSORT Extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study Design and Setting: MEDLINE and the Cochrane Methodology Register were searched (2011 and 2018). Eligible RCTs used administrative databases for identifying eligible participants or collecting outcomes. We evaluated reporting based on CONSORT-ROUTINE, which modified eight items from CONSORT 2010 and added five new items. Results: Of 33 included trials (76% used administrative databases for outcomes, 3% for identifying participants, 21% both), most were conducted in the United States (55%), Canada (18%), or the United Kingdom (12%). Of eight items modified in the extension; six were adequately reported in a majority (>50%) of trials. For the CONSORT-ROUTINE modification portion of those items, three items were reported adequately in >50% of trials, two in

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

Melioidosis is an uncommon, opportunistic disease caused by Burkholderia pseudomallei that lives freely in soil, water, and harsh environments. Transmission occurs from direct exposure of the bacteria to soil or contaminated water supplies. The case fatality rate (CFR) of Melioidosis is high and increases in children and underdeveloped countries. Unfortunately, the disease remains understudied around the world. We carried out an extensive literature review in a systematic approach. A detailed search strategy and PRISMA chart was used to select the relevant articles from reliable medical databases. Articles published from 2016 to 2020 that addressed the incidences, case fatality rates and epidemiology of Melioidosis are selected based on selection criteria. Finally, a total of 34 articles were included in this review. We identified 15,202 cases of Melioidosis globally from 1913-2018 with a total CFR of 33.9%. We calculated the global incidence of ~2607 per year and a CFR of ~814 (35.4%) per year. There are 80% (n = 2476) of adult cases and 20% (n = 620) of paediatric cases. The total (n = 12,413) male to female ratio of Melioidosis is 2.21:1. We also found that the male to female ratio of adult cases (n = 804) is 3.57:1, whereas that of paediatric cases (n = 318) is 1.39:1. The number of patients found working in the agricultural sector was 36.5% (n = 1068). We found a higher incidence and a lower total CFR which are consistent with previously reported studies. We also found that the percentage of paediatric cases was higher than in previous studies, and there is a considerable difference in male to female ratio between adult cases and paediatric cases. This review provides significant evidence to the public health policy makers to develop an effective preventable intervention to reduce the incidence and case fatality of this neglected tropical disease.

Background Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of ‘classical' S. aureus, while as yet no S. schweitzeri infections have been reported. Aim To provide decision support on whether and how to distinguish and report both species. Sources PubMed, searched for S. argenteus and S. schweitzeri. Content This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. Implications We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. ‘member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates.

OBJECTIVES: Most researchers who study the effects of hormonal contraception on menstrual bleeding rely on self-reported data via paper diaries, for which completeness and timeliness have been shown to be poor. The purpose of this exploratory study was to compare the completeness and timeliness of bleeding data collected via paper diaries, text messages or smartphone application (a.k.a “app”). METHODS: This was a sub-study of a double-blinded, placebo-controlled randomized trial comparing the effects of a non-steroidal anti-inflammatory drug, naproxen, with placebo when using a copper IUD. Participants tracked bleeding and symptoms over 112 days. Participants tracked bleeding daily using a paper diary as well as with either text messages or a smartphone app. Participants who used paper and the app were also able to record non-bleeding symptoms. RESULTS: Twenty-five participants submitted diaries. Of these participants, 10 completed both paper and app diaries, 7 completed both paper and text messages, 4 completed the paper diary only, 4 completed the app only. Text messages had the most complete data (108 days), followed by the app (96 days) and paper diaries (84 days). The lag time between a bleeding event and the date recording that event was 0.10 days for text, 1.0 days for app, and 4.73 days for paper diaries. Participants using the app reported a median of 33 other symptoms over the study period compared to 7 for the paper diaries DISCUSSION: Our findings suggest texts demonstrated more complete and timely bleeding data than either paper diaries, or the app. Compared to paper diaries, the app delivered more complete, timely data, and also collected a large set of symptoms.

Emergent tobacco products such as heated tobacco remain largely unregulated in many countries menacing the progress of tobacco control achieved in the last decades. They are being aggressively marketed by the industry as products of “reduced risk” and “smoking cessation tools” or smoke-free alternatives to smoking conventional cigarettes. WHO stresses that heated tobacco products are tobacco products and are therefore subject to the provisions of the WHO-FCTC. To date, there is growing independent research showing that these products are not harmless. However, a dangerous debate has re-launched harm reduction in the field of tobacco control and is splitting scientists, the public health community and society as large. Healthcare professional organizations have a crucial role to play in tobacco control. The European Respiratory Society (ERS), as a leading medical Society, has paved the way on tobacco control advocacy in Europe and worldwide. This presentation will present the ERS position on heated tobacco products, including the evidence regarding their toxicity, addictive potential and potential impact on public health.

Hydatidosis is a potential zoonotic helminthic disease affecting a broad spectrum of mammals, including humans, worldwide. The current review was conducted to investigate the genotypic status and prevalence of hydatid disease in camels across the world. For the purpose of the study, the articles addressing the worldwide prevalence of hydatidosis in camels were searched in several English language databases. The search process resulted in the inclusion of 122 papers. Based on the data presented in the reviewed articles, the pooled prevalence of hydatid disease in camels across the world was measured at 23.75% (95% CI 20.15–27.55). Moreover, the subgroup analysis demonstrated significant differences in the overall prevalence of hydatidosis among camels based on year, geographic area, climate parameters, camel population, gender, infected organ, fertility rate of the cyst and laboratory diagnostic technique. Furthermore, the Echinococcus granulosus genotypes identified in camels with hydatidosis included G1, G2, G3, G1–G3, G5, G6, G7, G6–G7 and G6–G10, with G6 being the most common genotype throughout the world. The data obtained from the current study are central to the better conceptualization of the biological and epidemiological characteristics of E. granulosus s.l. genotypes around the world, which can be helpful in the planning and adoption of more comprehensive control strategies.

ObjectiveTo describe characteristics of randomized controlled trials (RCTs) conducted using electronic health records (EHRs), including completeness and transparency of reporting assessed against the 2021 CONSORT Extension for RCTs Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria.Study DesignMEDLINE and Cochrane Methodology Register were searched for a sample of RCTs published from 2011–2018. Completeness of reporting was assessed in a random sample using a pre-defined coding form.ResultsOf the 183 RCT publications identified, 122 (67%) used EHRs to identify eligible participants, 139 (76%) used the EHR as part of the intervention and 137 (75%) to ascertain outcomes. When 60 publications were evaluated against the CONSORT 2010 item and the corresponding extension for the 8 modified items, four items were 'adequately reported' for most trials. Five new reporting items were identified for the CONSORT-ROUTINE extension; when evaluated, one was ‘adequately reported’, three were reported ‘inadequately or not at all’, the other ‘partially’. There were, however, some encouraging signs with adequate and partial reporting of many important items, including descriptions of trial design, the consent process, outcome ascertainment and interpretation.ConclusionAspects of RCTs using EHRs are sub-optimally reported. Uptake of the CONSORT-ROUTINE Extension may improve reporting.

Objective: We evaluated reporting completeness and transparency in randomized controlled trials (RCTs) conducted using administrative data based on 2021 CONSORT Extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study Design and Setting: MEDLINE and the Cochrane Methodology Register were searched (2011 and 2018). Eligible RCTs used administrative databases for identifying eligible participants or collecting outcomes. We evaluated reporting based on CONSORT-ROUTINE, which modified eight items from CONSORT 2010 and added five new items. Results: Of 33 included trials (76% used administrative databases for outcomes, 3% for identifying participants, 21% both), most were conducted in the United States (55%), Canada (18%), or the United Kingdom (12%). Of eight items modified in the extension; six were adequately reported in a majority (>50%) of trials. For the CONSORT-ROUTINE modification portion of those items, three items were reported adequately in >50% of trials, two in

Background: Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimination, is reproduced across settings. Systematic reviews and meta-analyses of studies evaluating prognostic models’ performance are a necessary step for selection of models for clinical practice and for testing the underlying assumption that their use will improve outcomes, including patient's reassurance and optimal future planning. Methods: In this paper, we highlight key concepts in evaluating the certainty of evidence regarding the calibration of prognostic models. Results and Conclusion: Four concepts are key to evaluating the certainty of evidence on prognostic models’ performance regarding calibration. The first concept is that the inference regarding calibration may take one of two forms: deciding whether one is rating certainty that a model's performance is satisfactory or, instead, unsatisfactory, in either case defining the threshold for satisfactory (or unsatisfactory) model performance. Second, inconsistency is the critical GRADE domain to deciding whether we are rating certainty in the model performance being satisfactory or unsatisfactory. Third, depending on whether one is rating certainty in satisfactory or unsatisfactory performance, different patterns of inconsistency of results across studies will inform ratings of certainty of evidence. Fourth, exploring the distribution of point estimates of observed to expected ratio across individual studies, and its determinants, will bear on the need for and direction of future research. © 2021

This article provides reflections on the 1962 paper by Sir Austin Bradford Hill, entitled “The Statistician in Medicine.” It discusses several key takeaways of this paper, including causal inference for big data, reproducibility and replicability in science, and integration of statistics and data science with domain science.

Evidence synthesis is critical in evidence-based healthcare and is a core program of JBI. JBI evidence synthesis is characterised by a pluralistic view of what constitutes evidence and is underpinned by a pragmatic ethos to facilitate the use of evidence to inform practice and policy. This second paper in this series provides a descriptive overview of the JBI evidence synthesis toolkit with reference to resources for 11 different types of reviews. Unique methodologies such as qualitative syntheses, mixed methods reviews, and scoping reviews are highlighted. Key features include standardised and collaborative processes for development of methodologies and a broad range of tailored resources to facilitate the conduct of a JBI evidence synthesis, including appraisal and data extraction tools, software to support the conduct of a systematic review and an intensive systematic review training program. JBI is one of the leading international protagonists for evidence synthesis, providing those who want to answer health-related questions with a toolkit of resources to synthesize the evidence.

Objective: Registries are important data sources for randomised controlled trials (RCTs), but reporting of how they are used may be inadequate. The objective was to describe the current adequacy of reporting of RCTs using registries. Study Design and Setting: We used a database of trials using registries from a scoping review supporting the development of the 2021 CONSORT extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE). Reporting completeness of 13 CONSORT-ROUTINE items was assessed. Results: We assessed reports of 47 RCTs that used a registry, published between 2011 and 2018. Of the 13 CONSORT-ROUTINE items, 6 were adequately reported in at least half of reports (2 in at least 80%). The 7 other items were related to routinely collected data source eligibility (32% adequate), data linkage (8% adequate), validation and completeness of data used for outcome assessment (8% adequate), validation and completeness of data used for participant recruitment (0% adequate), participant flow (9% adequate), registry funding (6% adequate) and interpretation of results in consideration of registry use (25% adequate). Conclusion: Reporting of trials using registries was often poor, particularly details on data linkage and quality. Better reporting is needed for appropriate interpretation of the results of these trials. Keywords: registries, CONSORT, CONSORT-ROUTINE, randomised controlled trials, reporting guideline, routinely collected data Running Title: Completeness and Transparency of Reporting of RCTs using Registries

BackgroundSmall bowel obstruction (SBO) is a common surgical emergency, causing high morbidity and healthcare costs. The majority of SBOs are caused by adhesions that result from previous surgeries. Bowel obstruction, however, also occurs in patients without previous operation or known pathology, a so called virgin abdomen. It is unknown if small bowel obstruction in the virgin abdomen (SBO-VA) can be managed according to the same principles as other cases of small bowel obstruction. The aim of this position paper is to evaluate the available evidence on etiology and management of small bowel obstruction in the virgin abdomen.MethodsThis is a narrative review with scoping aspects. Clinical topics covered in this review include epidemiology and etiology of SBO-VA, diagnosis and imaging, initial assessment, the role of surgical management in SBO-VA, and the role of non-operative management in SBO-VA.ResultsOur scoping search revealed seven original studies reporting original patient data related to SBO-VA. All the included studies are retrospective cohorts, with populations ranging between 44 and 103 patients with SBO-VA. Adhesions were found to be the cause of the obstruction in approximately half of the reported cases of SBO-VA. A relatively high number of cases of SBO-VA were managed surgically with studies reporting 39–83%. However, in cases where a trial of non-operative management was started, this was generally successful.ConclusionThe data available suggest that etiology and treatment results for patients with SBO-VA are largely comparable to the results in patients with SBO after previous abdominal surgery. We therefore propose that patients with a virgin abdomen could be treated according to existing guidelines for SBO and adhesive small bowel obstruction.

Objective : We compared methods used with current recommendations for synthesizing harms in systematic reviews and meta-analyses (SRMAs) of gabapentin. Study Design & Setting : We followed recommended systematic review practices. We selected reliable SRMAs of gabapentin (i.e., met a pre-defined list of methodological criteria) that assessed at least one harm. We extracted and compared methods in four areas: pre-specification, searching, analysis, and reporting. Whereas our focus in this paper is on the methods used, Part 2 examines the results for harms across reviews. Results : We screened 4320 records and identified 157 SRMAs of gabapentin, 70 of which were reliable. Most reliable reviews (51/70; 73%) reported following a general guideline for SRMA conduct or reporting, but none reported following recommendations specifically for synthesizing harms. Across all domains assessed, review methods were designed to address questions of benefit and rarely included the additional methods that are recommended for evaluating harms. Conclusion : Approaches to assessing harms in SRMAs we examined are tokenistic and unlikely to produce valid summaries of harms to guide decisions. A paradigm shift is needed. At a minimal, reviewers should describe any limitations to their assessment of harms and provide clearer descriptions of methods for synthesizing harms.

Funding Information: Work leading directly to this paper was not funded. The 10/66 DRG dementia prevalence study in Portugal was supported by FCT (Fundação para a Ciência e a Tecnologia; PTDC/SAU-EPI/113652/2009: “Prevalence of old age neuropsychiatric disorders: contribution to mental health policy in Portugal” – P.I. M. Xavier). Publisher Copyright: © 2021 The Author(s). Published by S. Karger AG, Basel on behalf of NOVA National School of Public Health. This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Dementia poses major public health challenges, and high-quality epidemiological data are needed for service planning. Published estimates of numbers of people with dementia in Portugal have been based, in most cases, on prevalence rates derived from international studies or expert consensus. As in many other countries, Portuguese community prevalence studies' results are nongeneralizable to a country level. Moreover, their prevalence estimates differ (not surprisingly, owing to different methodologies, e.g., design, sampling, and diagnostic criteria). Regardless, the Portuguese 10/66 Dementia Research Group (10/66 DRG) population-based survey fulfilled 10 out of 11 Alzheimer's Disease International quality criteria for prevalence studies. It relied on cross-culturally validated methods, fostering a wide comparability of results. Therefore, we can provide rough estimates of 217,549 community dwellers with dementia in Portugal according to the 10/66 DRG criteria (that would be only 85,162 according to DSM-IV criteria). This refers to people aged 65 years or older who are not institutionalized. Although broadly consistent with international projections, these estimates must be cautiously interpreted. Particularly in the context of scarce funding, which will probably last for years, we need more efficient, evidence-based dementia policies. Concerning further epidemiological studies, high-quality methods are needed but also their comparability potential should be improved at national and international levels. Most of all, fund allocation in Portugal should now privilege routine dementia information systems in both health and social services. publishersversion published

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden.

Background In cardiovascular prevention and rehabilitation, care activities are carried out by different professionals in coordination, each with their own specific competence. This GICR–IACPR position paper has analysed the interventions performed by the nurse, physiotherapist, dietician and psychologist in order to identify what constitutes minimal care, and it lists the activities that are fundamental and indispensable for each team member to perform in clinical practice. Results In analysing each type of intervention, the following dimensions were considered: the level of clinical care complexity, determined both by the disease and by environmental factors; the ‘area’ complexity, i.e. the specific level of competence required of the professional in each professional section; organisational factors, i.e. whether the care is performed in an inpatient or outpatient setting; duration of the rehabilitation intervention. The specific contents of minimal care have been identified for each professional area together with the specific goals, the assessment tools and the main essential interventions. For the assessments, only a few validated tools have been indicated, leaving the choice of which instrument to use to the individual professional based on experience and usual practice. Conclusion For the interventions, attention has been focused on conditions of major complexity requiring special care, taking into account the different care settings, the clinical conditions secondary to the disease event, and the distinct tasks of each area according to the operator's specific role. The final report performed by each professional has also been included.

Background Web-based surveys (WBS) are increasingly applied in epidemiological studies as an appealing alternative to traditional survey methods. Rapid data collection, reduced expenditure and ease of access to large populations are some of the clear advantages of online surveys. However, WBS are still subject to limitations in terms of sample size, response rate and other additional biases compared to traditional survey methods. In the present study, we seek to validate data on food allergy (FA) in two independent sample populations collected from a WBS, and compare it to a paper-based survey (PBS). Methods Data collected from two survey modes were compared by hypothesis testing for independent sample population. The WBS included 1185 respondents, while the PBS included 9039 respondents. Results Overall, the data from the WBS were comparable to the PBS conducted over the same period of time in Vietnamese adults. There were no effects of different survey modes on the lifetime prevalence of doctor-diagnosed FA (5.7%; P = 0.7795, β = 0.05) and IgE-mediated FA (5.8%; P = 0.9590, β = 0.05). Both surveys showed the dominance of seafood allergy in this population (up to 2.6%), followed by beef allergy. Close correlation was seen in the patterns of FAs and different clinical symptoms. The contribution of family history of allergic diseases and place of residence to FA were confirmed in both surveys. Conclusions The consistency of the WBS results with the PBS indicates a promising application of online surveys as an economic and validated model for future epidemiological studies, specifically in developing countries. Electronic supplementary material The online version of this article (10.1186/s40413-018-0195-2) contains supplementary material, which is available to authorized users.

The widespread availability of antiretroviral therapy (ART) for HIV infection in Sub-Saharan Africa (SSA) has resulted in decreased morbidity, mortality, and transmission of HIV. This region, however, still represents the majority of the global burden of HIV. Furthermore, levels of retention in care and medication adherence, critical determinants of ART effectiveness, are currently suboptimal, and, thus, continue to be the target of many interventions. This dissertation is comprised of three chapters related to understanding ART adherence and interventions to improve it.Chapter 1 quantitatively describes and examines the distribution of poor adherence to antiretroviral therapy in a study of HIV-positive patients in Zambia. In a novel application of the Lorenz curve, a tool used commonly in economics, this analysis characterized the concentration of medication non-possession in a network of clinics in order to identify “hotspots” and predictors of poor adherence. Results extend previous studies by revealing that even though average adherence is high, lapses in adherence are common and concentrated among a minority of patients, and also in certain clinics. This concentration and variability varies with time on ART. Furthermore, a small fraction of patients accounts for the majority of days of medication non-possession, with the size of this group increasing with time on ART. This suggests that targeted interventions may represent a preferable overall strategy as compared to those targeting all patients to improve adherence. Furthermore, there was high variability across clinics suggesting that interventions targeting clinic “hotspots” may also represent an efficient use of resources to improve ART adherence. Chapter 2 presents the results of the first qualitative study to examine conditional incentives for ART adherence and their potential pathways of action among people living with HIV. This study was conducted within a study of conditional food and cash transfers to increase retention in care and adherence to ART among HIV-positive food insecure recent adults in Shinyanga, Tanzania. Although financial and in-kind incentives have been shown to improve outcomes along the HIV care cascade, results are mixed, and there is little evidence about the pathways through which incentives work. Results of this qualitative study and analysis revealed that incentives acted through three primary pathways to potentially increase retention in care and adherence to ART: 1) addressing competing needs and offsetting opportunity costs associated with clinic attendance, 2) increasing motivation and 3) alleviating stress associated with attending clinic, worry about providing for oneself and one’s family, and providing hope for a better future. The first pathway was the strongest, which was consistent with field observations and discussions with local clinic staff, research staff, and Ministry of Health officials. Participants did not report any harmful events associated with the incentives, and reported a variety of beneficial spillover effects on household welfare. Understanding these pathways can help improve design and targeting of future food or cash incentive interventions. Chapter 3 focused on intrinsic motivation within the aforementioned study of food and cash transfers for ART adherence in Tanzania. Some critical of incentives argue that incentives can ‘crowd out’ intrinsic motivation, making the individual less likely to engage in the desired behavior after the incentive is removed, potentially leading to limited durability of effect and causing harm in the long term. This hypothesis was examined among recent antiretroviral treatment initiates in Tanzania by comparing participants’ level of intrinsic motivation before receiving transfers to the level once the transfer period ended. The analysis revealed that, not only did intrinsic motivation not decrease after the transfer period ended, but that the level of intrinsic motivation increased overall and within study arms. Furthermore, the change in motivation did not differ by study arms. As the first study to empirically examine the crowding out hypothesis regarding incentives in a real-world, resource-limited setting, these results suggest that incentive interventions in such settings should not be impeded by concerns of crowding out intrinsic motivation.Together these chapters contribute to improving our understanding of antiretroviral adherence and intervention response. The Lorenz curve and medication possession analysis provides a more comprehensive and detailed measurement and illustration of adherence and its variability across individuals and clinics in Zambia. Such information is critical to targeting and designing future interventions. Next, by examining an ongoing intervention to improve adherence in Tanzania, we were able to elucidate and examine the potential pathways of action of food and cash transfers. Furthermore, we found no evidence that these incentives decreased intrinsic motivation. Knowledge gleaned from this deep exploration of the incentives’ mechanism of action in a real-world setting not only informs refinement of the intervention, but also helps to fill the gap in understanding how and when these interventions may work.

This discussion paper addresses the safety of HIV cure studies, particularly those involving stopping antiretroviral therapy, known as an analytic treatment interruption (ATI) in the context of the SARS-CoV-2 pandemic. More than 30 studies listed on ClinicalTrials.gov include an ATI and many others were planned to begin over the next 12 months but most were halted due to the COVID-19 pandemic. We consider the ethics, risks and practical considerations to be taken into account before re-opening HIV cure clinical trials, noting the specific risks of ATI in the context of circulating SARS-CoV-2.

BACKGROUND AND OBJECTIVE: There is considerable actual and potential waste in research. Using evidence-based research (EBR) can ensure the value of a new study. The aim of this article, the third in a series, is to describe an EBR approach to putting research results into context.STUDY DESIGN AND SETTING: EBR is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this third and final article of a series, we describe how to use the context of existing evidence to reach and present a trustworthy and useful conclusion when reporting results from a new clinical study.RESULTS: We describe a method, the EBR approach, that by using a systematic and transparent consideration of earlier similar studies when interpreting and presenting results from a new original study will ensure usefulness of the conclusion.CONCLUSION: Using an EBR approach will improve the usefulness of a clinical study by providing the context to draw more valid conclusions and explicit information about new research needs.

ObjectiveTo evaluate the consistency of causal statements in observational studies published in The BMJ.DesignReview of observational studies published in a general medical journal.Data sourceCohort and other longitudinal studies describing an exposure-outcome relationship published in The BMJ in 2018. We also had access to the submitted papers and reviewer reports.Main outcome measuresProportion of published research papers with ‘inconsistent’ use of causal language. Papers where language was consistently causal or non-causal were classified as ‘consistently causal’ or ‘consistently not causal’, respectively. For the ‘inconsistent’ papers, we then compared the published and submitted version.ResultsOf 151 published research papers, 60 described eligible studies. Of these 60, we classified the causal language used as ‘consistently causal’ (48%), ‘inconsistent’ (20%) and ‘consistently not causal’(32%). Eleven out of 12 (92%) of the ‘inconsistent’ papers were already inconsistent on submission. The inconsistencies found in both submitted and published versions were mainly due to mismatches between objectives and conclusions. One section might be carefully phrased in terms of association while the other presented causal language. When identifying only an association, some authors jumped to recommending acting on the findings as if motivated by the evidence presented.ConclusionFurther guidance is necessary for authors on what constitutes a causal statement and how to justify or discuss assumptions involved. Based on screening these papers, we provide a list of expressions beyond the obvious ‘cause’ word which may inspire a useful more comprehensive compendium on causal language.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

Background and Objective We previously claimed that the credibility ceiling for meta-analyses is fundamentally flawed. We respond to Dr. Ioannidis' rebuttal of those claims. Methods We use statistical reasoning. Results We agree with Dr. Ioannidis on some general points about the limitations of statistical sensitivity analyses. But critically, his response has entirely sidestepped responding to the crux of our argument, namely a direct mathematical demonstration that the method simply does not do what it was claimed to do. We reiterate that if our claim were false, it could be persuasively refuted if Dr. Ioannidis were to identify inaccuracies in our mathematical argument, which he has not done. Dr. Ioannidis had also dismissed as “absurd” the thought experiments we had used to illustrate the method's misleading conclusion; we explain why these examples still stand. Conclusion Given that the crux of our argument remains unaddressed, we continue to recommend against use of the credibility ceiling method. We are, however, sympathetic to what seem to be the underlying aims of the method, if not the execution. Developing principled methods to address those aims would be useful.

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 104 GE/μL (1.2 × 105; 1 to 6.1 × 106 DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. © 2013 The Authors. Clinical Microbiology and Infection published by John Wiley and Sons Ltd on behalf of the European Society of Clinical Microbiology and Infectious Disease.

Worldwide, women struggle to control the timing and spacing of childbearing, resulting in a high number of pregnancies that are unintended. In order to achieve many of the United Nations Millennium Development goals related to maternal and child health, gender equality and HIV prevention, the incidence of unintended pregnancy and its consequences must be significantly reduced. The three papers comprising this dissertation represent distinct analyses related to the general theme of unintended pregnancy among disadvantaged women, with a particular focus on research that is responsive to and can directly inform pressing policy questions. Paper 1 synthesizes the observational evidence on the relationship between use of hormonal contraception (HC) and women's risk of HIV acquisition using quantitative meta-analysis. Given the central role of HC in preventing unintended pregnancy, policymakers and practitioners are struggling to translate an inconsistent body of observational evidence on this question into balanced contraceptive guidance for women, in particular in high prevalence HIV settings such as sub Saharan Africa. Pooled effect estimates from studies that use a comparable approach to identify the effect of use of various forms of HC on risk of HIV acquisition, and adequately address confounding and selection bias, suggest that use of certain forms of HC is associated with an elevated risk of HIV acquisition, but not of the magnitude that would merit complete withdrawal of these methods.Paper 2 capitalizes on a unique study design to examine the role of an unintended birth on women's educational attainment in the United States. Despite over three decades of research, there remains debate over the extent to which reduced educational attainment among women with an unintended pregnancy is a function of childbearing itself, or a consequence of common selection factors that predispose women to both early childbearing and poor socioeconomic outcomes. By exploiting a discontinuity in the timing of presentation for abortion care, this paper compares the incidence of graduation or drop out from school among exchangeable groups of women, half of whom had an unintended birth and half of whom received an abortion. Unlike previous research, this analysis finds no difference in the educational achievements of women who experience an unintended birth and those that experience an unintended pregnancy that they do not carry to term.Finally, paper 3 explores the extent to which minors seeking abortion in the U.S. involve parents and other important individuals in their decision-making process, and how these relationships influence their confidence in and projected coping with their abortion decision. Despite the fact that a majority of states require parental involvement in minors' abortion, little is known about the effect of involving a parent on minors' abortion decision-making and anticipated coping after abortion. This analysis reveals that in the absence of a law mandating involvement, a majority of minors involve parents, primarily mothers, and male partners in their abortion decisions. For a minority of minors, experiencing pressure or lack of support from mothers reduces confidence in their decision and increases their likelihood of anticipating poor coping after an abortion.

Atrial fibrillation (AF) is an important and highly prevalent arrhythmia, which is associated with significantly increased morbidity and mortality, including a four- to five-fold increased risk for stroke,1,2 a two-fold increased risk for dementia,3,4 a three-fold risk for heart failure,2 a two-fold increased risk for myocardial infarction,5,6 and a 40–90% increased risk for overall mortality.2,7 The constantly increasing number of AF patients and recognition of increased morbidity, mortality, impaired quality of life, safety issues, and side effects of rhythm control strategies with antiarrhythmic drugs, and high healthcare costs associated with AF have spurred numerous investigations to develop more effective treatments for AF and its complications.8 Although AF treatment has been studied extensively, AF prevention has received relatively little attention, while it has paramount importance in the prevention of morbidity and mortality, and complications associated with arrhythmia and its treatment. Current evidence shows a clear association between the presence of modifiable risk factors and the risk of developing AF. By implementing AF risk reduction strategies aiming at risk factors such as obesity, hypertension, diabetes, and obstructive sleep ap-noea (OSA), which are interrelated, we impact upon the escalating incidence of AF in the population and ultimately decrease the healthcare burden of associated co-morbidities of AF. To address this issue, a Task Force was convened by the European Heart Rhythm Association and the European Association of Cardiovascular Prevention and Rehabilitation, endorsed by the Heart Rhythm Society and Asia-Pacific Heart Rhythm Society, with the remit to comprehensively review the published evidence available, to publish a joint consensus document on the prevention of AF, and to provide up-to-date consensus recommendations for use in clinical practice. In this document, our aim is to summarize the current evidence on the association of each modifiable risk factor with AF and the available data on the impact of possible interventions directed at these factors in preventing or reducing the burden of AF. While the evidence on AF prevention is still emerging, the topic is not fully covered in current guidelines and some aspects are still controversial. Therefore, there is a need to provide expert recommendations for professionals participating in the care of at-risk patients and populations, with respect to addressing risk factors and lifestyle modifications. Health economic considerations Atrial fibrillation is a costly disease, both in terms of direct, and indirect costs, the former being reported by cost of illness studies as per-patient annual costs in the range of US $2000–14200 in North America and of €450–3000 in Europe.9 In individuals with AF or at risk of developing AF, any effective preventive measure, intervention on modifiable risk factors or comorbidities, as well as any effective pharmacological or non-pharmacological treatment has the aim to reduce AF occurrence, thromboembolic events and stroke, morbidity and, possibly, mortality related to this arrhythmia. Apart from the clinical endpoints, achievement of these goals has economic significance, in terms of positive impact on direct and indirect costs and favourable cost–effectiveness at mid- or long-term, in the perspective of healthcare systems.10–12 In view of the epidemiological profile of AF and progressive aging of the population,13 an impressive increase of patients at risk of AF or affected by AF,14 also in an asymptomatic stage, is expected in the next decades, inducing a growing financial burden on healthcare systems, not only in Europe and North America, but also worldwide.15,16 In consideration of this emerging epidemiological threat due to AF, it is worth considering a paradigm shift, going beyond the conventional approach of primary prevention based on treatment of AF risk factors, but, instead, considering the potential for ‘primordial’ prevention, defined as prevention of the development of risk factors predisposing to AF in the first place.17 This approach, aimed at avoiding the emergence and penetration of risk factors into the population, has been proposed in general terms for the prevention of cardiovascular diseases17 and should imply combined efforts of policymakers, regulatory and social service agencies, providers, physicians, community leaders, and consumers, in an attempt to improve social and environmental conditions, as well as individual behaviours, in the pursuit of adopting healthy lifestyle choices.16 Since a substantial proportion of incident AF events can be attributable to elevated or borderline levels of risk factors for AF,18 this approach could be an effective way to reduce the financial burden linked to AF epidemiology. In terms of individual behaviour and adoption of a ‘healthy lifestyle’, it is worth considering that availability of full healthcare coverage (through health insurance or the healthcare system) may in some cases facilitate the unwanted risk of reducing, at an individual level, the motivation to adopt all the preventive measures that are advisable, in line with the complex concept of ‘moral hazard effect’.19 Patient education and patient empowerment are the correct strategies for avoiding this undesirable effect.

Using a bacteriophage to represent microbial contamination, we investigated virus transmission to the hospital environment following hand drying. The use of paper towels resulted in lower rates of virus contamination on hands and clothing compared with a jet air dryer and, consequently, lower contamination of multiple hospital surfaces.