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Background: Active commuting benefits both individual and planetary health. Estimating commuting behavior is desirable, although very challenging in large and regionally relevant nations like Brazil. Methods: This review (CRD42023431054) included observational studies that estimated prevalence of active commuting in Brazil for adults (≥18 y). We searched terms related to physical activity, commuting, prevalence estimates, and Brazilian geographical regions in 5 databases (PubMed, EMBASE, LILACS, CINAHL, and SPORTDiscus). For the quantitative synthesis, 2 categories were used based on the strictness of case definition: "high-volume threshold" (HIGH), considering "active" individuals with ≥150 minutes per week; and "low-volume threshold" (LOW), considering "active" individuals with ≥10 minutes per week of active commuting or self-reporting this behavior. Results: There were 37 studies included in the main model, totaling 52 individual prevalence estimates and 1,266,862 units. Prevalence estimates were: 17.4% (15.1%–19.9%) for HIGH and 44.2% (36.9%–51.5%) for LOW. Subgroup analysis revealed a prevalence of 20.5% (16.7%–24.9%) for men and 13.8% (10.2%–17.9%) for women using HIGH, and 43.4% (27.2%–60.4%) for men and 47.6% (32.1%–63.4%) for women using LOW categories. Most studies had high risk of bias. Conclusions: We herein provided a panorama of active commuting in Brazil. Standardized active commuting definitions and objective measures of commuting activity are lacking. Studies specific to some regions of Brazil were few or inexistent. Considering the global importance of Brazil, sheltering ecologically relevant biomes, we encourage new, high-quality studies assessing commuting and its potential impacts on individual and planetary health. [ABSTRACT FROM AUTHOR]

In 1992, Wacholder and colleagues developed a theoretical framework for case-control studies to minimize bias in control selection. They described three comparability principles (study base, deconfounding, and comparable accuracy) to reduce the potential for selection bias, confounding, and information bias in case-control studies. Wacholder et al. explained how these principles apply to traditional sources of controls for case-control studies, including population controls, hospital controls, controls from a medical practice, friend or relative controls, and deceased controls. The goal of the current manuscript is to extend this seminal work on case-control studies by providing a modern perspective on sources of controls. Today, there are many more potential sources of controls for case-control studies than there were in the 1990s. This is due to technological advances in computing power, internet access, and availability of 'big data' resources. These advances have vastly expanded the quantity and diversity of data available for case-control studies. In this manuscript, we discuss control selection from electronic health records, health insurance claims databases, publicly available online data sources, and social media-based data. We focus on practical considerations for unbiased control selection, emphasizing the strengths and weaknesses of each modern source of controls for case-control studies.

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge.

Introduction: Pain is one of the most frequently reported symptoms in hemodialyzed (HD) patients, with prevalence rates between 33% and 82%. Risk factors for chronic pain in HD patients are older age, long-lasting dialysis history, several concomitant diseases, malnutrition, and others. However, chronic pain assessment in HD patients is rarely performed by specialists in pain medicine, with relevant consequences in terms of diagnostic and treatment accuracy. Furthermore, no study has used the recently introduced International Association for the Study of Pain (IASP) pathophysiological classification. Methods: In this observational, cross-sectional study in a tertiary HD center in Northern Italy, we analyzed data regarding HD patients, evaluated for 5 months in 2021 by specialists in pain medicine and aimed to identify and characterize chronic pain according to the IASP definition and the last 2019 classification of chronic pain for ICD-11. Pain severity was evaluated by the pain severity score of the brief pain inventory tool. Results: Among 213 patients, 65 (31%) suffered from chronic pain. The average age was 73.1 years; 55.5% of the patients were male; 53.7% had diabetes, and 39.2% had arterial hypertension. Of the 54 patients subjected to an in-depth evaluation, data regarding 113 pain diagnoses were extracted, particularly related to osteoarthritis, obliterating arterial disease, and low back pain with or without radiculopathy. On the basis of these diagnoses, the pain classification according to the IASP pathophysiological definition highlighted a predominant nociceptive pain type (53.9% of all the diagnoses), followed by neuropathic (22.1%), mixed (22.1%), nociplastic (2.6%), and idiopathic (2.6%) pain. According to the IASP classification for ICD-11, the clinical diagnosis of chronic pain secondary to obliterating arterial disease and diabetes-related foot ulcers could not be assigned to any diagnostic category as a result of the lack of a specific item in the aforementioned classification. Conclusion: This study confirmed that chronic pain is a common, burdening issue in hemodialysis patients and that it is of a prevalent nociceptive nature. Our study highlights some limitations of the last IASP ICD-11 classification, especially the lack of specific items for some pain features that are very frequent in hemodialysis patients, and not only in that population. Finally, this study underlines the importance of mutual collaboration between pain physicians and nephrologists for the well-being of patients of high clinical complexity, such as those undergoing chronic hemodialysis. [ABSTRACT FROM AUTHOR]

Context Iodine, combined with antithyroid drugs, is recommended as an initial pharmacologic treatment for thyroid storm according to some clinical guidelines. However, the clinical efficacy of iodine in managing thyroid storm remains unexplored. Objective This study aimed to determine whether early potassium iodide (KI) use is associated with mortality in patients hospitalized for thyroid storm. Methods Using the Japanese Diagnosis Procedure Combination database, we identified patients hospitalized with thyroid storm between July 2010 and March 2022. We compared in-hospital mortality, length of stay, and total hospitalization costs between patients who received KI within 2 days of admission (KI group) vs those who did not (non-KI group). Prespecified subgroup analyses were performed based on the presence of the diagnosis of Graves' disease. Results Among 3188 eligible patients, 2350 received KI within 2 days of admission. The crude in-hospital mortality was 6.1% (143/2350) in the KI group and 7.8% (65/838) in the non-KI group. After adjusting for potential confounders, KI use was not significantly associated with in-hospital mortality (odds ratio [OR] for KI use, 0.91; 95% CI, 0.62-1.34). In patients with the diagnosis of Graves' disease, in-hospital mortality was lower in the KI group than in the non-KI group (OR, 0.46; 95% CI, 0.25-0.88). No significant difference in in-hospital mortality was observed in patients without the diagnosis of Graves' disease (OR, 1.11; 95% CI, 0.67-1.85). Length of stay was shorter (subdistribution hazard ratio, 1.15; 95% CI, 1.05-1.27), and total hospitalization costs were lower (OR, 0.92; 95% CI, 0.85-1.00) in the KI group compared with the non-KI group. Conclusion Our findings suggest that KI may reduce in-hospital mortality among patients hospitalized for thyroid storm with Graves' disease. [ABSTRACT FROM AUTHOR]

We analyze the results to question 2 (individual preferences for cancelling or keeping the current clock regulations) from the 2018 Public Consultation on summertime arrangements (DST) conducted by the European Commission. We reveal correlations in the shares of population for cancelling the regulations and the winter sunrise time (SRW) [R2 = 0.177; p = 0.03; N = 25] and the onset of human activity [R2 = 0.677; p = 5 × 10−5; N = 17]. The results are in line with the rationale behind the regulations in the range of latitude 35 to 63: larger values of SRW (larger latitude) brought larger shares against the regulations; and earlier onset of human activity relative to SRW brought larger shares against the regulations. The shares for cancelling the regulation did not show correlations with time offset (position in time zone), thus challenging the current view within the circadian community. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to summarize the evidence on the teratogenic effects of dipyrone used during pregnancy. Methods: Databases (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science, Lilacs, SciELO, SCOPUS, OasisBR, and OpenGray) were reviewed until September 2023. We included studies that compared pregnant women who used dipyrone during any gestational period with those who used other analgesics or did not use any analgesics during the same gestational period. The outcome assessed was the presence of any congenital anomaly. Two reviewers independently conducted the review process, and a third reviewer resolved any disagreements. The risk of bias was assessed using the Joanna Briggs Institute tool for observational studies. The reviewed data synthesis is presented in narrative form. Results: The search retrieved 2045 results, of which seven studies were included in the review, four were case‒control studies, and three were cohort studies involving 153,562 participants. The congenital anomalies evaluated varied across studies, with unspecified congenital anomalies predominating. Five of seven studies found no association between dipyrone and congenital anomalies. In a case‒control study, a positive association was found between dipyrone use and isolated congenital cataracts compared to two control groups; in another study, a positive association for unspecified congenital anomalies was observed in only one of the two control groups analyzed. In all studies, a high risk of bias was identified, especially regarding measuring the exposure, outcome, and assessment of confounding factors. Conclusion: There is not enough evidence to define the risk of congenital anomalies associated with dipyrone use during pregnancy. Registration: CRD 42022333041. [ABSTRACT FROM AUTHOR]

The article focuses on the use of propensity score methods to control confounding in observational studies of therapeutics for COVID-19. Topics include the role of observational studies in clinical medicine, the need for statistical modeling to address confounding, and an overview of propensity score methods used in COVID-19 treatment studies.

Introduction: In the context of migraine preventive therapy, new therapeutic modalities such as monoclonal antibodies targeting the calcitonin gene-related peptide receptor (CGRP) or ligand offer potential advantages over traditional preventive treatments. Methods: This systematic literature review gathered recent real-world evidence from Spain on the use of galcanezumab, a CGRP-targeting treatment, in migraine patients. The review included observational studies in English or Spanish, published from August 2020 to August 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines. Results: A total of 29 publications involving 2,592 Spanish adult patients were identified, reporting relevant information on clinical outcomes (treatment effectiveness and safety), treatment persistence and patterns (switching from other therapies and time to discontinuation and restart), and patient-reported outcomes (including satisfaction with treatment). The most frequently reported variables were related to the clinical effectiveness of galcanezumab, demonstrating a significant reduction in monthly migraine days and monthly headache days. Additionally, adverse impact of headache per HIT-6 (Headache Impact Test-6) and disability per MIDAS (Migraine Disability Assessment) also improve. Studies also showed that up to 12-month persistence to galcanezumab ranged from 76.8 to 59.8%. Serious adverse events were rare. None of the publications included health-related quality of life data, either generic or migraine-specific. One study highlighted that galcanezumab treatment would offer high patient satisfaction for people with migraine. Conclusion: The real-world evidence on the use of galcanezumab treatment among the Spanish population shows that its effectiveness, persistence, safety, and impact on health burden align with findings from clinical trials and observational studies conducted in other countries. Future studies should incorporate health-related quality of life data to gain a more holistic understanding of this treatment's impact. [ABSTRACT FROM AUTHOR]

This review examines the relationship between long-term antipsychotic use and individual functioning, emphasizing clinical implications and the need for personalized care. The initial impression that antipsychotic medications may worsen long-term outcomes is critically assessed, highlighting the confounding effects of illness trajectory and individual patient characteristics. Moving beyond a focus on methodological limitations, the discussion centers on how these findings can inform clinical practice, keeping in consideration that a subset of patients with psychotic disorders are on a trajectory of long-term remission and that for a subset of patient the adverse effects of antipsychotics outweigh potential benefits. Key studies such as the OPUS study, Chicago Follow-up study, Mesifos trial, and RADAR trial are analyzed. While antipsychotics demonstrate efficacy in short-term symptom management, their long-term effects on functioning are less obvious and require careful interpretation. Research on long-term antipsychotic use and individual functioning isn't sufficient to favor antipsychotic discontinuation or dose reduction below standard doses for most patients, but it is sufficient to highlight the necessity of personalization of clinical treatment and the appropriateness of dose reduction/discontinuation in a considerable subset of patients. [ABSTRACT FROM AUTHOR]

An observational study might support a causal claim if the association found cannot be explained by bias due to unconsidered confounders. This bias depends on how strongly the common predisposition, a summary of unconsidered confounders, is related to the factor and the outcome. For a positive effect to be supported, the product of these two relations must be smaller than the left boundary of the confidence interval for, e.g., a standardised mean difference (d). We suggest means to derive heuristics for how large this product must be to serve as a confirmatory threshold. We also provide non-technical, visual means to express researchers' assumptions on the two relations to assess whether a finding on d is explainable by omitted confounders. The ViSe tool, available as an R package and Shiny application, allows users to choose between various effect sizes and apply it to their own data or published summary results. [ABSTRACT FROM AUTHOR]

Introduction: This exploratory review aimed to provide empirical evidence on the definitions of labor, the statistical approaches and measures reported in randomized controlled trials (RCTs) and observational studies measuring the duration of labor. Methods: A systematic electronic literature search was conducted using different databases. An extraction form was designed and used to extract relevant data. English, French, and German studies published between 1999 and 2019 have been included. Only RCTs and observational studies analyzing labor duration (or a phase of labor duration) as a primary outcome have been included. Results: Ninety‐two RCTs and 126 observational studies were eligible. No definition of the onset of labor was provided in 21.7% (n = 20) of the RCTs and 23.8% (n = 30) of the observational studies. Mean was the most frequently applied measure of labor duration in the RCTs (89.1%, n = 82), and median in the observational studies (54.8%, n = 69). Most RCTs (83%, n = 76) and observational studies (70.6%, n = 89) analyzed labor duration using a bivariate method, with the t‐test being the most frequently applied (45.7% and 27%, respectively). Only 10.8% (n = 10) of the RCTs and 52.4% (n = 66) of the observational studies conducted a multivariable regression: 3 (30%; out of 10) RCTs and 37 (56%; out of 66) observational studies used a time‐to‐event adapted model. Conclusion: This survey reports a lack of agreement with respect to how the onset of labor and phases of labor duration are presented. Concerning the statistical approaches, few studies used survival analysis, which is the appropriate statistical framework to analyze time‐to‐event data. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3–5 patients with heart failure (OR: 0.65, 95%CI: 0.54–0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68–0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73–0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60–0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79–2.17) and hypotension (OR:1.57, 95%CI:0.94–2.62) were increased in sacubitril/valsartan group among CKD stages 3–5 patients with heart failure. Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between statins and muscle problems in a highly diverse sample of Brazilian civil servants. Methods: We conducted a cross-sectional data analysis at baseline of the ELSA-Brasil MSK cohort. Pain was identified through self-reported symptoms in large muscle groups (lower back and/or hips/thighs). Muscle strength was assessed using the five-times-sit-to-stand (FTSTS) and handgrip tests, with weakness defined as the lowest and highest quintiles of age- and sex-stratified handgrip strength and FTSTS performance time, respectively. Multivariable logistic regression analyses were conducted to investigate the association between statin use and muscle pain and weakness. Secondary analyses explored the impact of different types of statins and their duration of use on the response variables. Results: A total of 2156 participants (mean age 55.6 ± SD 8.9, 52.8% women) were included, of whom 21.1% were taking statins and 25.1% reported muscle pain. We found no significant association between statin use and muscle problems. Secondary analysis on different types of statins revealed an association between atorvastatin and muscle weakness, as measured by the five-times-sit-to-stand test (OR 1.94, 95% CI 1.12–3.37), but not by the handgrip test (OR 0.75, 95% CI 0.29–1.42). No evidence was found to support a link between the duration of statin treatment and muscle problems. Conclusions: This study challenges previous claims of an efficacy-effectiveness gap between experimental and observational literature on statins. The findings indicate that statin use does not contribute to muscular problems. [ABSTRACT FROM AUTHOR]

Background: The relationship between dietary fiber intake and cancer outcomes, including incidence, recurrence, and mortality, is crucial for understanding cancer prevention strategies. Methods: An umbrella review was conducted, analyzing existing systematic reviews and meta-analyses from PubMed, Embase, and the Cochrane Database of Systematic Reviews. This included data from 26 meta-analyses based on 2,107 unique articles, covering 52 observational study outcomes. The quality of the studies was assessed using the AMSTAR 2 tool. Results: High fiber intake significantly lowers the risk of cancers affecting the digestive, reproductive, and urinary systems, including esophageal adenoma, squamous cell carcinoma, gastric, pancreatic, colon, rectal, colorectal adenoma, breast, ovarian, endometrial, prostate, renal cell, and bladder cancers. Findings estimated that the risk of Colon cancer between total dietary fiber (TDF) was 0.74 (95% confidence interval [CI]: 0.67–0.82), and the risk of Colorectal cancer between TDF was 0.88 (95% CI: 0.82–0.94). TDF was also found to be protective against Barrett’s esophagus and esophagus cancer, esophageal adenomas, and esophagus squamous cell carcinoma, with effect sizes of 0.52 (95% CI: 0.43–0.64), 0.50 (95% CI: 0.37–0.67), and 0.53 (95% CI: 0.31–0.90), respectively. Conversely, increased intake of cereal fiber was associated with a higher incidence of renal cell carcinoma and endometrial cancer. Dose–response analyses revealed that increments of 2.5, 5, or 10 g per day in dietary fiber could lead to different levels of risk reduction for these cancers. Meta-regression suggested an optimal fiber intake range of 7–36 g per day for colon cancer prevention. However, the overall study quality was predominantly rated as ‘very low’. Conclusions: Higher dietary fiber intake is linked to reduced cancer risk and improved outcomes. These findings highlight dietary fiber’s importance in cancer prevention and care.

Introduction There is no consensus on the questions that should be included in questionnaires to properly ascertain exposure to secondhand tobacco smoke (SHS). The objective of this study is to analyze the questions included in studies which have assessed SHS exposure in Spain. Methods A scoping review was performed, using PubMed, Embase and Web of Science databases, selecting original articles published in English and Spanish, across the period 2012–2021. We extracted data from each study regarding its design, target population, sample size or geographical scope; we also collected data regarding how studies dealt with exposure to SHS including assessment and intensity of SHS, exposure setting, geographical scope, and the verbatim questions used. Results Finally, 75 studies were identified. In the 23 studies carried out in children, verbatim questions were included in 8 studies, and the setting most studied was the home. SHS exposure was assessed during pregnancy and postnatally by 8 studies, the verbatim questions used were described in 2 studies, being exposure ascertained at home and workplace. In the adult population, 14 of 44 studies described the verbatim questions; the setting most studied was the home. Verbatim questions varied among studies. Conclusions Questionnaire-based assessment of SHS exposure is highly heterogeneous, hindering comparability between studies. Therefore, it is necessary to set a standard questionnaire to assess exposure to SHS.

Abstract Background Comprehensive summaries on real-world outcomes in pulmonary arterial hypertension (PAH)—a rare, incurable condition, are lacking. Main body of the abstract We conducted a systematic literature review to describe current survival, morbidity, and quality of life (QoL) outcomes in adult and pediatric PAH patients. We searched Medline and Embase electronic databases, clinicaltrials.gov, and encepp.eu entries, and grey literature to identify outcome estimates for right-heart catheterization-confirmed PAH patients from population-based observational studies (search date: 25 Nov 2021). Data were synthesized using a narrative approach and post-hoc subgroup meta-analyses were conducted to explore adult survival by region, disease severity, representativeness, and study period. The search yielded 7473 records. Following screening and full text review, 22 unique studies with 31 individual reports of outcomes were included. Studies were mostly national registries (n = 21), European (n = 13) and covering adults (n = 17); only six had systematic countrywide coverage of centers. Survival was the most frequently reported outcome (n = 22). Global adult 1-, 3-, and 5-year survival ranged from 85 to 99% (n = 15), 65 to 95% (n = 14), and 50 to 86% (n = 9), respectively. Subgroup meta-analysis showed that 1-, 3-, and 5-year survival in Europe was 90% (95% CI 86–94%; n = 8), 78% (95% CI 68–86%; n = 8), and 61% (95% CI 49–72%; n = 6), respectively; 1-year survival in North America was 88% (95% CI 83–93%; n = 3) and 3-year survival in Asia was 85% (95% CI 82–88%; n = 3). No difference in survival between regions was observed. Subgroup analysis suggested higher survival in patients with better baseline functional class; however, interpretation should be cautioned due to large subgroup heterogeneity and potential missingness of data. Short conclusion This review describes current disease outcomes based on well-defined and representative PAH populations. There is an overall lack of follow-up data for morbidity and QoL outcomes; survival estimates for pediatric patients are scarce and may not be generalizable to the current treatment era, although publications from large pediatric registries became available after our search date. This study demonstrated a remaining unmet need world-wide to improve long-term prognosis in PAH in the current era.

Objectives: The PROtein-enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing in older adults (PROMED-COG) is a European project that investigates the role of nutritional status on neurocognitive ageing. This methodological paper describes the harmonization process of dietary data from four Italian observational studies (Pro.V.A., ILSA, BEST-FU, and NutBrain). Methods: Portion sizes and food frequency consumption within different food frequency questionnaires were retrospectively harmonized across the datasets on daily food frequency, initially analyzing raw data using the original codebook and establishing a uniform food categorization system. Individual foods were then aggregated into 27 common food groups. Results: The pooled cohort consisted of 9326 individuals (40–101 years, 52.4% female). BEST-FU recruited younger participants who were more often smokers and less physically active than those of the other studies. Dietary instruments varied across the studies differing in the number of items and time intervals assessed, but all collected dietary intake through face-to-face interviews with a common subset of items. The average daily intakes of the 27 food groups across studies varied, with BEST-FU participants generally consuming more fruits, vegetables, red meat, and fish than the other studies. Conclusions: Harmonization of dietary data presents challenges but allows for the integration of information from diverse studies, leading to a more robust and statistically powerful dataset. The study highlights the feasibility and benefits of data harmonization, despite inherent limitations, and sets the stage for future research into the effects of diet on cognitive health and aging. [ABSTRACT FROM AUTHOR]

The results of observational studies using real-world data, known as real-world evidence, have gradually started to be used in drug development and decision-making by policymakers. A good quality management system—a comprehensive system of process, data, and documentation to ensure quality—is important in obtaining real-world evidence. A risk-based approach is a common quality management system used in interventional studies. We used a quality management system and risk-based approach in an observational study on a designated intractable disease. Our multidisciplinary team assessed the risks of the real-world data study comprehensively and systematically. When using real-world data and evidence to support regulatory decisions, both the quality of the database and the validity of the outcome are important. We followed the seven steps of the risk-based approach for both database selection and research planning. We scored the risk of two candidate databases and chose the Japanese National Database of designated intractable diseases for this study. We also conducted a quantitative assessment of risks associated with research planning. After prioritizing the risks, we revised the research plan and outcomes to reflect the risk-based approach. We concluded that implementing a risk-based approach is feasible for an observational study using real-world data. Evaluating both database selection and research planning is important. A risk-based approach can be essential to obtain robust real-world evidence. [ABSTRACT FROM AUTHOR]

Background: Comprehensive summaries on real-world outcomes in pulmonary arterial hypertension (PAH)—a rare, incurable condition, are lacking. We conducted a systematic literature review to describe current survival, morbidity, and quality of life (QoL) outcomes in adult and pediatric PAH patients. We searched Medline and Embase electronic databases, clinicaltrials.gov, and encepp.eu entries, and grey literature to identify outcome estimates for right-heart catheterization-confirmed PAH patients from population-based observational studies (search date: 25 Nov 2021). Data were synthesized using a narrative approach and post-hoc subgroup meta-analyses were conducted to explore adult survival by region, disease severity, representativeness, and study period. The search yielded 7473 records. Following screening and full text review, 22 unique studies with 31 individual reports of outcomes were included. Studies were mostly national registries (n = 21), European (n = 13) and covering adults (n = 17); only six had systematic countrywide coverage of centers. Survival was the most frequently reported outcome (n = 22). Global adult 1-, 3-, and 5-year survival ranged from 85 to 99% (n = 15), 65 to 95% (n = 14), and 50 to 86% (n = 9), respectively. Subgroup meta-analysis showed that 1-, 3-, and 5-year survival in Europe was 90% (95% CI 86–94%; n = 8), 78% (95% CI 68–86%; n = 8), and 61% (95% CI 49–72%; n = 6), respectively; 1-year survival in North America was 88% (95% CI 83–93%; n = 3) and 3-year survival in Asia was 85% (95% CI 82–88%; n = 3). No difference in survival between regions was observed. Subgroup analysis suggested higher survival in patients with better baseline functional class; however, interpretation should be cautioned due to large subgroup heterogeneity and potential missingness of data. Short conclusion: This review describes current disease outcomes based on well-defined and representative PAH populations. There is an overall lack of follow-up data for morbidity and QoL outcomes; survival estimates for pediatric patients are scarce and may not be generalizable to the current treatment era, although publications from large pediatric registries became available after our search date. This study demonstrated a remaining unmet need world-wide to improve long-term prognosis in PAH in the current era. [ABSTRACT FROM AUTHOR]

Medical research is costly and requires significant effort. While intracellular research hardly follows a formal design, most data-based studies require a structural approach for optimal utilization of resources. Depending on the study's objectives and available resources, as well as the aim to obtain valid and reliable results, the design may be descriptive, employing specific sampling strategies, or analytical, exploring antecedent-outcome relationships. Analytical studies often involve designs such as randomization and blinding in clinical trials, and may use prospective, retrospective, or cross-sectional designs in observational studies. This first article in the series on biostatistics methods specifies the essential features of each design and describes the contexts in which they are most appropriate. [ABSTRACT FROM AUTHOR]

Many Veterans receive Department of Veterans Affairs (VA)-purchased care from non-VA facilities but little is known about factors that Veterans consider for this choice. Between May 2020 and August 2021, we surveyed VA-purchased care-eligible VA patients about barriers and facilitators to choosing where to receive care. We examined the association between travel time to their VA facility and their choice of VA-purchased care (VA-paid health care received in non-VA settings) versus VA facility and whether this association was modified by distrust. We received 1,662 responses and 692 (42%) chose a VA facility. Eighty percent reported quality care was in their top three factors that influenced their decision. Respondents with the highest distrust and who lived >1 hr from the nearest VA facility had the lowest predicted probability (PP) of choosing VA (PP 15%; 95% confidence interval: 10%–20%). Veterans value quality of care. VA and other health care systems should consider patient-centered ways to improve and publicize quality and reduce distrust. [ABSTRACT FROM AUTHOR]

Valid inference of cause-and-effect relations in observational studies necessitates adjusting for common causes of the focal predictor (i.e., treatment) and the outcome. When such common causes, henceforth termed confounders, remain unadjusted for, they generate spurious correlations that lead to biased causal effect estimates. But routine adjustment for all available covariates, when only a subset are truly confounders, is known to yield potentially inefficient and unstable estimators. In this article, we introduce a data-driven confounder selection strategy that focuses on stable estimation of the treatment effect. The approach exploits the causal knowledge that after adjusting for confounders to eliminate all confounding biases, adding any remaining non-confounding covariates associated with only treatment or outcome, but not both, should not systematically change the effect estimator. The strategy proceeds in two steps. First, we prioritize covariates for adjustment by probing how strongly each covariate is associated with treatment and outcome. Next, we gauge the stability of the effect estimator by evaluating its trajectory adjusting for different covariate subsets. The smallest subset that yields a stable effect estimate is then selected. Thus, the strategy offers direct insight into the (in)sensitivity of the effect estimator to the chosen covariates for adjustment. The ability to correctly select confounders and yield valid causal inferences following data-driven covariate selection is evaluated empirically using extensive simulation studies. Furthermore, we compare the introduced method empirically with routine variable selection methods. Finally, we demonstrate the procedure using two publicly available real-world datasets. A step-by-step practical guide with user-friendly R functions is included. A central goal of psychological research is to understand cause-and-effect relations. Thoughtfully designed and meticulously conducted randomized experiments are the gold standard for examining the causal impact of an intervention, or treatment, on an outcome. But such randomized studies are often practically unfeasible for ethical and logistical reasons. In such contexts, observational or nonexperimental studies where individuals are exposed to nonrandomized treatments become the only viable option for causal inference. However, the statistical correlation between a nonrandomized treatment and an outcome can be due to noncausal (or "spurious") correlations generated by their mutual associations with common causes. Thus, adjusting, or controlling, for such common causes is necessary to eliminate the spurious correlations toward valid inference of the treatment effect. But correctly selecting covariates can be a challenging task. The common practice of routinely including all available (pretreatment) variables that covary with either treatment or outcome can result in effect estimators with poor statistical qualities. This article introduces a data-driven covariate (or confounder) selection strategy to help researchers avoid such concerns. It directly evaluates the impact of covariate selection on the quality of the effect estimator as part of the selection process. Covariates are first ordered by decreasing priority for confounding adjustment. The effect estimator adjusting for different covariate subsets is then calculated. Finally, the smallest subset that yields a stable estimator (visually or numerically), even as more covariates are included, is selected. The introduced strategy offers insight into the (in)sensitivity of the estimator to the covariates chosen and provides a resilient justification for valid causal inference. [ABSTRACT FROM AUTHOR]

Introduction: There is no consensus on the questions that should be included in questionnaires to properly ascertain exposure to secondhand tobacco smoke (SHS). The objective of this study is to analyze the questions included in studies which have assessed SHS exposure in Spain. Methods: A scoping review was performed, using PubMed, Embase and Web of Science databases, selecting original articles published in English and Spanish, across the period 2012–2021. We extracted data from each study regarding its design, target population, sample size or geographical scope; we also collected data regarding how studies dealt with exposure to SHS including assessment and intensity of SHS, exposure setting, geographical scope, and the verbatim questions used. Results: Finally, 75 studies were identified. In the 23 studies carried out in children, verbatim questions were included in 8 studies, and the setting most studied was the home. SHS exposure was assessed during pregnancy and postnatally by 8 studies, the verbatim questions used were described in 2 studies, being exposure ascertained at home and workplace. In the adult population, 14 of 44 studies described the verbatim questions; the setting most studied was the home. Verbatim questions varied among studies. Conclusions: Questionnaire-based assessment of SHS exposure is highly heterogeneous, hindering comparability between studies. Therefore, it is necessary to set a standard questionnaire to assess exposure to SHS. [ABSTRACT FROM AUTHOR]

ObjectivesMethodResultsConclusionWe conducted the current systematic review to investigate the association between dietary inflammatory index (DII) and severe headaches or migraine among adults via synthesizing observational evidence.We conducted a systematic literature search of observational studies through PubMed, Scopus, and Web of Science databases from inception until July 2024. The PECO framework was implemented to select eligible studies as follows: Population (adults with severe headache or migraine), Exposure (individuals with the highest adherence to a pro-inflammatory diet), Comparison (individuals with the lowest adherence to a pro-inflammatory diet), Outcome (risk of developing severe headache or migraine, headaches frequency, duration, severity, and migraine-related disability).After reviewing six studies involving 31,958 individuals, we found that following an anti-inflammatory diet is associated with a lower frequency and severity of migraine headaches. Additionally, our research revealed that individuals with migraines tend to have lower adherence to an anti-inflammatory diet when compared to people without migraines. Surprisingly, adherence to a pro-inflammatory diet was linked to a reduced risk of chronic daily headaches.Present findings imply a negative link between an inflammatory diet and severe headaches or migraine. However, further well-designed longitudinal studies are needed to interpret the causality and shed light on the underlying mechanisms. [ABSTRACT FROM AUTHOR]

In this work, we propose an approach for assessing sensitivity to unobserved confounding in studies with multiple outcomes. We demonstrate how prior knowledge unique to the multi-outcome setting can be leveraged to strengthen causal conclusions beyond what can be achieved from analyzing individual outcomes in isolation. We argue that it is often reasonable to make a shared confounding assumption, under which residual dependence amongst outcomes can be used to simplify and sharpen sensitivity analyses. We focus on a class of factor models for which we can bound the causal effects for all outcomes conditional on a single sensitivity parameter that represents the fraction of treatment variance explained by unobserved confounders. We characterize how causal ignorance regions shrink under additional prior assumptions about the presence of null control outcomes, and provide new approaches for quantifying the robustness of causal effect estimates. Finally, we illustrate our sensitivity analysis workflow in practice, in an analysis of both simulated data and a case study with data from the National Health and Nutrition Examination Survey (NHANES). for this article are available online. [ABSTRACT FROM AUTHOR]

What is the best way to split one stratum into two to maximally reduce the within-stratum imbalance in many covariates? We formulate this as an integer program and approximate the solution by randomized rounding of a linear program. A linear program may assign a fraction of a person to each refined stratum. Randomized rounding views fractional people as probabilities, assigning intact people to strata using biased coins. Randomized rounding is a well-studied theoretical technique for approximating the optimal solution of certain insoluble integer programs. When the number of people in a stratum is large relative to the number of covariates, we prove the following new results: (i) randomized rounding to split a stratum does very little randomizing, so it closely resembles the linear programming relaxation without splitting intact people; (ii) the linear relaxation and the randomly rounded solution place lower and upper bounds on the unattainable integer programming solution; and because of (i), these bounds are often close, thereby ratifying the usable randomly rounded solution. We illustrate using an observational study that balanced many covariates by forming matched pairs composed of 2016 patients selected from 5735 using a propensity score. Instead, we form 5 propensity score strata and refine them into 10 strata, obtaining excellent covariate balance while retaining all patients. An R package optrefine at CRAN implements the method. Supplementary materials are available online. [ABSTRACT FROM AUTHOR]

The combination of propensity score analysis and multiple imputation has been prominent in epidemiological research in recent years. However, studies on the evaluation of balance in this combination are limited. In this paper, we propose a new method for assessing balance in propensity score analysis following multiple imputation. A simulation study was conducted to evaluate the performance of balance assessment methods (Leyrat's, Leite's, and new method). Simulated scenarios varied regarding the presence of missing data in the control or treatment and control group, and the imputation model with/without outcome. Leyrat's method was more biased in all the studied scenarios. Leite's method and the combine method yielded balanced results with lower mean absolute difference, regardless of whether the outcome was included in the imputation model or not. Leyrat's method had a higher false positive ratio and Leite's and combine method had higher specificity and accuracy, especially when the outcome was not included in the imputation model. According to simulation results, most of time, Leyrat's method and Leite's method contradict with each other on appraising the balance. This discrepancy can be solved using new combine method. [ABSTRACT FROM AUTHOR]

When estimating treatment effects, the gold standard is to conduct a randomized experiment and then contrast outcomes associated with the treatment group and the control group. However, in many cases, randomized experiments are either conducted with a much smaller scale compared to the size of the target population or accompanied with certain ethical issues and thus hard to implement. Therefore, researchers usually rely on observational data to study causal connections. The downside is that the unconfoundedness assumption, which is the key to validating the use of observational data, is untestable and almost always violated. Hence, any conclusion drawn from observational data should be further analyzed with great care. Given the richness of observational data and usefulness of experimental data, researchers hope to develop credible methods to combine the strength of the two. In this paper, we consider a setting where the observational data contain the outcome of interest as well as a surrogate outcome, while the experimental data contain only the surrogate outcome. We propose an easy-to-implement estimator to estimate the average treatment effect of interest using both the observational data and the experimental data. [ABSTRACT FROM AUTHOR]

Immortal time bias is a well-recognized bias in clinical epidemiology but is rarely discussed in environmental epidemiology. Under the target trial framework, this bias is formally conceptualized as a misalignment between the start of study follow-up (time 0) and treatment assignment. This misalignment can occur when attained duration of follow-up is encoded into treatment assignment using minimums, maximums, or averages. The bias can be exacerbated in the presence of time trends commonly found in environmental exposures. Using lung cancer cases from the California Cancer Registry (2000-2010) linked with estimated concentrations of particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5), we replicated previous studies that averaged PM2.5 exposure over follow-up in a time-to-event model. We compared this approach with one that ensures alignment between time 0 and treatment assignment, a discrete-time approach. In the former approach, the estimated overall hazard ratio for a 5-μg/m3 increase in PM2.5 was 1.38 (95% confidence interval: 1.36, 1.40). Under the discrete-time approach, the estimated pooled odds ratio was 0.99 (95% confidence interval: 0.98, 1.00). We conclude that the strong estimated effect in the former approach was likely driven by immortal time bias, due to misalignment at time 0. Our findings highlight the importance of appropriately conceptualizing a time-varying environmental exposure under the target trial framework to avoid introducing preventable systematic errors.

Background Around one in three pregnant women undergoes induction of labour in the United Kingdom, usually preceded by in-hospital cervical ripening to soften and open the cervix. Objectives This study set out to determine whether cervical ripening at home is within an acceptable safety margin of cervical ripening in hospital, is effective, acceptable and cost-effective from both National Health Service and service user perspectives. Design The CHOICE study comprised a prospective multicentre observational cohort study using routinely collected data (CHOICE cohort), a process evaluation comprising a survey and nested case studies (qCHOICE) and a cost-effectiveness analysis. The CHOICE cohort set out to compare outcomes of cervical ripening using dinoprostone (a prostaglandin) at home with in-hospital cervical ripening from 39 weeks of gestation. Electronic maternity record data were collected from 26 maternity units. Following pilot analysis, the primary comparison was changed to ensure feasibility and to reflect current practice, comparing home cervical ripening using a balloon catheter with in-hospital cervical ripening using any prostaglandin from 37 weeks of gestation. Analysis involved multiple logistic regression for the primary outcome and descriptive statistics for all other outcomes. The qCHOICE study reported descriptive statistics of quantitative survey data and thematic analysis of focus group and interview data. The economic analysis involved a decision-analytic model from a National Health Service and Personal Social Services perspective, populated with CHOICE cohort and published data. Secondary analysis explored the patient perspective utilising cost estimates from qCHOICE data. Setting Twenty-six United Kingdom maternity units. Participants Women with singleton pregnancies at or beyond 37 weeks of gestation having induction with details of cervical ripening method and location recorded. Main outcome measures CHOICE cohort Neonatal unit admission within 48 hours of birth for 48 hours or more. qCHOICE Maternal and staff experience of cervical ripening. Economic analysis Incremental cost per neonatal unit admission within 48 hours of birth avoided. Data sources Electronic maternity records from 26 maternity units; survey and interviews with service users/maternity staff; focus groups with maternity staff; published literature on economic aspects. Results CHOICE cohort: A total of 515 women underwent balloon cervical ripening at home and 4332 underwent in-hospital cervical ripening using prostaglandin in hospitals that did not offer home cervical ripening. Neonatal unit admission within 48 hours of birth for 48 hours or more following home cervical ripening with balloon was not increased compared with in-hospital cervical ripening with prostaglandin. However, there was substantial uncertainty with the adjusted analysis consistent with a 74% decrease in the risk through to an 81% increase. qCHOICE Important aspects of service users’ experience of home cervical ripening were quality of information provided, support and perception of genuine choice. Economic analysis Home cervical ripening with balloon led to cost savings of £993 (−£1198, −£783) per woman and can be considered the dominant strategy. Limitations Circumstances relating to the COVID-19 pandemic limited the number of participating maternity units and the duration for which units participated. Low numbers of women having at-home cervical ripening limited the power to detect differences in safety, effectiveness, cost and acceptability between study groups. Conclusions Home cervical ripening using balloon catheter may be as safe for babies as using prostaglandins in hospital in low and moderate-risk groups, but there is substantial uncertainty. Home cervical ripening with balloon is likely to be cost saving. Impacts on workload, service user and staff experiences were complex. Future work Future research should focus on optimising experience and logistics of home cervical ripening within busy maternity services. Study registration Current Controlled Trials ISRCTN32652461. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127569) and is published in full in Health Technology Assessment; Vol. 28, No. 81. See the NIHR Funding and Awards website for further award information. Plain language summary Labour is often started artificially. This is called induction of labour. Induction of labour is usually planned when it is safer to end the pregnancy. The first stage of induction of labour – ‘cervical ripening’ – means using medication or a balloon to open the neck of the womb. Years ago, cervical ripening only happened in hospitals, but now many women are offered ‘home cervical ripening’. This means that induction of labour starts in hospital then women go home while the treatment starts working. This could mean that women spend less time in hospital. They may prefer to be at home. However, home cervical ripening may be less safe because problems may not be noticed as quickly. We looked at whether home cervical ripening is safe, acceptable to women and their partners, and good value for money. We used information about women and babies that is usually stored in electronic maternity notes. We studied women who had induction of labour in 26 United Kingdom maternity hospitals. Women were told about the study and could choose not to be included. Our main question was ‘does home cervical ripening increase the chance that a baby needs care in a neonatal unit, compared with cervical ripening in hospital?’ We surveyed women about their experience of induction of labour and any financial costs to them. We interviewed women, partners, doctors and midwives to hear what they thought about home cervical ripening. Fewer women than expected had home cervical ripening. We could not be certain that home cervical ripening with a balloon is as safe for babies as cervical ripening in hospital using medication. Home cervical ripening cost almost £1000 less per woman than in-hospital cervical ripening. Home cervical ripening was acceptable to women when they felt well looked after, when maternity staff communicated well with them, and when they felt they had a choice about going home. Scientific summary Background Around one in three pregnant women in the UK undergo induction of labour (IOL). The first step often involves cervical ripening (opening and shortening the cervix). Cervical ripening may be undertaken using either balloon catheters or administration of prostaglandin. Cervical ripening at home may reduce hospital stay during IOL and may be more acceptable to women than in-hospital cervical ripening. It is unclear whether it may increase risks to the unborn baby due to less monitoring of their well-being during the IOL process and whether it is acceptable to women and partners. It is also unclear whether home cervical ripening is cost-effective. Objective To assess whether it is safe, effective, cost-effective and acceptable to service users and providers to carry out home cervical ripening during IOL, the research questions asked were: Is home cervical ripening within an acceptable margin of in-hospital cervical ripening for safety, cost and acceptability outcomes? Is a strategy of home cervical ripening using a balloon as safe as in-hospital cervical ripening using prostaglandin for the primary outcome of neonatal unit (NINU) admission within 48 hours of birth for 48 hours or more? Is home cervical ripening as acceptable to service-users and health professionals as in-hospital cervical ripening? Are NHS and service user costs of home cervical ripening using a balloon comparable to costs of in-hospital cervical ripening using prostaglandin? Methods This project incorporated a prospective multicentre observational cohort study using real-world data from hospital electronic health records, a survey of service users and nested case studies involving interviews and focus groups, evaluating process and service user and provider experiences, and a health economic analysis. The original design was a comparison of home versus in-hospital cervical ripening using a non-inferiority design to determine whether home cervical ripening is within an acceptable margin (+ 4%) of in-hospital cervical ripening for the safety outcome of NNU admission, whether it is more acceptable to women and whether it is cost-effective. As insufficient home cervical ripening cases were identified at the pilot analysis stage, the statistical analysis was modified to a simple logistic regression on the primary outcome (NNU admission within 48 hours for 48 hours or more), unadjusted and adjusted by potential confounders. This was done because the limited sample size of the primary exposure variable (home vs. hospital) did not have enough power to answer the non-inferiority question as proposed. This had a knock-on effect on the other aspects of the project as well. Observational cohort A total of 26 maternity units in the UK contributed data to the observational cohort study, of whom 8 offered balloon home cervical ripening and 18 offered only in-hospital cervical ripening using prostaglandin. The sample included geographically and socially diverse populations. All units used the BadgerNet Maternity Notes (System C, Stratford-upon-Avon, UK) information system to record routine maternity care information. Deidentified data on all eligible women having IOL was extracted from the BadgerNet system using existing data fields. Data were securely transferred to the University of Edinburgh. Data were analysed using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). We used mixed-effects logistic regression for the comparison of NNU admission within 48 hours to control for treatment indication bias, with hospital/trust as a random effect. Further outcomes were reported descriptively as medians and interquartile ranges, proportions and percentages. Process evaluation A process evaluation was undertaken to identify contextual influences on implementation of cervical ripening protocols and outcomes and assess the acceptability of home cervical ripening and the experiences of women and their birth partners, professionals and other key stakeholders. The process evaluation comprised an online postnatal survey, five case study sites and qualitative interviews and focus groups with service users and staff. Overall, 309 women returned completed surveys. In the case study sites, interviews were undertaken with women (n = 43), partners (n = 17) and health professionals (n = 48) and four focus groups were conducted with health professionals (n = 28). Because the COVID-19 pandemic occurred during the study period, which had wide-reaching effects on maternity care, an additional survey of healthcare professionals at all UK NHS trusts and boards was conducted to determine whether aspects of practice and policy around IOL had altered in response to the pandemic. In total, surveys were returned from 92 of the UK NHS trusts and boards offering maternity services across the UK. Survey data were reported using descriptive statistics and qualitative data were analysed using a thematic framework. The original design involved audio recording of a sample of consultations where IOL is discussed to assess women’s involvement in the decision-making processes (analysed using the OPTION scale); however, COVID-19-related restrictions precluded this element. Health economic analysis An economic analysis was undertaken from the perspective of the NHS and Personal Social Services using a decision tree model, populated with data from the CHOICE study. Resource use data were combined with unit costs to calculate the within study cost for each strategy and outcomes were reported in terms of incremental cost per NNU admission avoided. A secondary analysis considered the patient perspective, including costs incurred by women and their families relating to IOL, gathered from the qCHOICE survey responses. Data sources Electronic patient records from 26 study sites (extracted via the BadgerNet maternity records data system): observational cohort study; economic analysis. Qualitative interviews and focus groups: process evaluation. Postnatal survey: process evaluation; economic analysis. Published literature: economic analysis. Results Observational cohort study The unanticipated context of the CHOICE study was an NHS under pressure to manage high IOL rates (range 31–49%) and long delays throughout the IOL process during the COVID-19 pandemic. Home cervical ripening using balloon was performed in women for a wide array of indications (low to moderate risk groups) and from 37 weeks of gestation. The main analysis population consisted of 17,350 women with singleton pregnancies having IOL at 37 weeks or later, of whom 515 underwent home cervical ripening using balloon, 4332 underwent in-hospital cervical ripening with prostaglandin in hospitals that only offered in-hospital cervical ripening, and 7397 women underwent in-hospital cervical ripening with prostaglandin in a hospital that also offered home cervical ripening. Compared with in-hospital cervical ripening with prostaglandin, the rate of NNU admission within 48 hours of birth for 48 hours or more following home cervical ripening with balloon was not increased. The event rate for this primary outcome was expected to be 6% for the in-hospital group. The rate was much lower than expected in both arms (3.1% after home cervical ripening vs. 4.8% after in-hospital cervical ripening) and there was no statistically significant difference between groups before or after adjusting for potential confounding variables. However, the odds ratio of 0.75 has a wide 95% confidence interval (CI) of 0.35 to 1.64 (0.81; 95% CI 0.36 to 1.81 in the adjusted analysis) signalling substantial uncertainty in this finding. Process evaluation Eligibility criteria for those offered the option of home cervical ripening varied between sites. Care was often planned around capacity rather than in line with guidance/policy. Of 230 survey respondents who underwent to in-hospital cervical ripening, the mean stay prior to transfer to labour ward was 31.5 hours (range 0–260 hours). Women reported physically and emotionally unsafe situations caused by these delays. Impact of COVID-19 Of responding sites, 23% reported a change in the method used for cervical ripening and 28% reported a change in criteria for offering home cervical ripening. Only 7% and 6%, respectively, reported changes in the professionals undertaking cervical ripening or the approach for post-dates IOL. The majority of respondents stated that there was no change (61%) or that more women (28%) were discharged home after cervical ripening. There was little consistency in policy changes during the pandemic – one study site expanded home cervical ripening eligibility while another completely suspended it. Acceptability to service users While attitudes towards home cervical ripening were positive, the experiences of those who actually went home were mixed. The positive experiences were most often associated with being in the comfort of one’s own environment. Safety appeared to be the biggest concern for those who said they would not want to return home for cervical ripening. Crucially, women and birth partners wanted the choice to go home or stay in hospital and lack of choice was evident both in survey responses and in case study site interviews. Women who had home cervical ripening were more likely to choose that option again (64%) and recommend it to others (61%) than those who stayed in hospital (55%, 54%). Women who had a balloon catheter inserted reported more discomfort than those who had a prostaglandin pessary or osmotic dilator, although ability to cope with discomfort was similar across all cervical ripening methods. Attentive care and access to pain relief were important to women and birth partners. Acceptability to clinicians and health professionals Attitudes were generally positive, and many healthcare professionals perceived mechanical methods to be the safest for home cervical ripening. Home cervical ripening was often seen as a potential solution to workload and capacity issues, but several professionals highlighted that it was not necessarily straightforward and that there could be unintended consequences for workload, including the management of re-admissions. Information Half of survey respondents did not feel they had enough information about what to expect during IOL, and over half (57%) felt that they had either had no choice or no alternative when deciding to have IOL. Psychological correlates Forty-one survey respondents described their experience of IOL as difficult or traumatic. Some maternity professionals also reported moral distress in relation to the process. Factors mediating experience The principal factors mediating experience of IOL were support from healthcare professionals, the presence of birth partners, information provision and having choice, privacy and having their own space, and delays. In the survey, the most important factor in a positive experience was support from kind, caring staff and feeling safe. Barriers and enablers of adoption Staff shortages was one of the key barriers to adoption of home cervical ripening. Delays during IOL were linked to unit capacity, staffing and workload. Enablers included cross-boundary collaboration, cross-trust/board knowledge sharing, consistent training and professional confidence. Health economic analysis The economic model found that home cervical ripening with balloon led to cost savings of £993 (−£1198, −£783) per woman, with no difference in NNU admissions avoided (mean 0.005; 95% CI −0.05 to 0.013). At willingness-to-pay thresholds above £3000, there is an 82% probability that home cervical ripening with balloon is the optimal option and in economic terms would be considered the dominant strategy compared with in-hospital cervical ripening with prostaglandin. Probabilistic sensitivity analysis indicates little uncertainty regarding the cost savings, however there was uncertainty regarding the impact on NNU admission. Any potential increase in NNU admissions between arms would be negligible. The cost savings in the home cervical ripening group are driven primarily by reduced time in an antenatal ward for the home cervical ripening group, with an average of 476 minutes (7.9 hours) compared with 2243 minutes (37.4 hours) in the in-hospital group. The resource use and cost data also indicate some of the ‘hidden’ or displaced costs of the home cervical ripening option, with an increased number and duration of phone calls from women and their partners to the hospital compared with those in the in-hospital group. Economic analysis of ‘spill over’ costs found that the average transport cost was higher among the mothers who had hospital cervical ripening (£23.10) than mothers who had home cervical ripening (£18.74). The total patient perspective cost was higher in the hospital arm (£954) compared with the home arm (£665), which was predominantly driven by the opportunity cost of partners’/other caregivers’ time supporting the mother either at home or in hospital ‘away from other activities’. Conclusions The CHOICE study provided multiple perspectives on the difference between home cervical ripening with balloon and in-hospital cervical ripening with prostaglandin during IOL, within a context of high IOL rates and multiple delays in the process. Home cervical ripening with balloon appears both safe and cost-effective when compared with in-hospital cervical ripening with prostaglandin for a range of indications, although safety conclusions are uncertain. Acceptance of home cervical ripening depends upon high-quality informed decision-making and consistent support for women throughout the IOL process, a reality that was often lacking in the study participants’ experience. Future research should focus on: Further exploration and implementation of system features that lead to positive experiences of home cervical ripening. Measuring rare but important safety outcomes of home cervical ripening. Practice implications of the CHOICE findings are that units should consider the practicalities of offering genuine choice around setting for IOL and ensure adequate staffing and support for women throughout their IOL experience regardless of setting for cervical ripening. Unless women feel supported to choose between home and in-hospital settings, and they have sufficient information to allow realistic expectations of the IOL process, women will not have positive birth experiences. Study registration Current Controlled Trials ISRCTN32652461. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127569) and is published in full in Health Technology Assessment; Vol. 28, No. 81. See the NIHR Funding and Awards website for further award information.

Against the background of low women's participation in farm decision making processes, Malawi's agriculture sector adapted and up- scaled Household Approach, a gender transformative tool known for its impact in enhancing participation of women in farm decision making processes. In this study, participation in farm decision making is defined as the involvement of women, men and youth in decision making process in relation to visioning, planning, implementation, monitoring and evaluation. The objective of this study was to determine level of participation of women under Household Approach in farm decision making processes. This was a cross- sectional study. Using a semi-structured interview, a quantification of the extent of participation of various gender categories in decision making in various areas was determined. Thirty- three households were purposively selected due to their participation in Household Approach. Analysis of women participation in decision making, was done by computing women's decision score. Decision score for men and youth was also computed so that a comparison is made to women's level of participation. Women took joint decisions in all farm decision making processes with a higher participation score in household visioning (0.91) compared to men (0.83) and youth (0.44). When it came to implementing production activities of an enterprise (maize) which is a major source of their livelihood determining fulfilment of their visions, there were significant variations among their participation score in decision making in relation to maize enterprise production ([chi]2 (2) = 40.282, p = 0.000) with a mean rank participation score of 25.00, 39.94 and 8.56 in men, women and youth, respectively. This implies that much as implementation of maize production activities are jointly done with men, women still do a greater part of maize production work. When it came to monitoring, women had a lower participation score (0.68) compared to men (0.81), but higher than the youth (0.33). The lower participation score in monitoring among women was due to multiple roles the women have. This study recommends that sharing of roles be encouraged among peer households. Key words: Level, Women, participation, Household Approach, Farm, Decision making, Pragmatic, Cross- sectional, INTRODUCTION Agriculture accounts for 30% of Gross Domestic Product (GDP), generates over 80% of national export earnings in Malawi [1] and employs 76% of the country's workforce [2]. In Malawi, [...]

Abstract Background Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. Results We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. Conclusions The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias.

Summary: Background: The human gut microbiome changes considerably over time. Previous studies have shown that gut microbiome profiles correlate with multiple metabolic traits. As disease development is likely a lifelong process, evidence gathered at different life stages would help gain a better understanding of this correlation. Therefore, we aim to investigate how the association of the gut microbiome and metabolic traits change over the lifespan. Methods: We identified microbiome patterns (clusters) within two population-based cohorts at different life stages, i.e., pre-adolescents of the Generation R Study (mean age 9.8 years; n = 1488) and older adults of the Rotterdam Study (RS, mean age 62.7 years; n = 1265) using K-Means clustering, and surveyed for host metabolic phenotypes, lifestyles and other factors driving these patterns. Analyses were replicated in the Lifelines-DEEP Study (mean age 45.0 years; n = 1117). The association between microbiome clusters and host metabolic health was evaluated as well as the link between microbiome clusters and incident atherosclerotic cardiovascular disease (ASCVD) in RS during follow-up (median 6.5 years). Findings: We identified two distinct microbiome clusters (U and H) within each study population presenting contrasting metabolic statuses. Cluster U was characterized by lower microbiome diversity, increased Streptococcus, Fusicatenibacter, and decreased Prevotella_9 and Christensenellaceae_R-7_group; wherein individuals showed higher fat percentage, triglycerides, use of medications, and lower socioeconomic status. Individuals in cluster U had increased odds (between 1.10 and 1.65) of being relatively metabolically unhealthy and presented a higher 5-year ASCVD risk (mean risk 0.059 ± 0.071 vs 0.047 ± 0.042, p

Background Aims Materials and Methods Results Discussion Conclusion The target trial framework was developed as a strategy to design and analyze observational epidemiologic studies with the aim of reducing bias due to analytic decisions. It involves designing a hypothetical randomized trial to answer a question of interest and systematically considering how to use observational data to emulate each trial component.The primary aim of this paper is to provide a detailed example of the application of the target trial framework to a research question in oral epidemiology.We describe the development of a hypothetical target trial and emulation protocol to evaluate the effect of preconception periodontitis treatment on time‐to‐pregnancy. We leverage data from Pregnancy Study Online (PRESTO), a preconception cohort, to ground our example in existing observational data. We discuss the decision‐making process for each trial component, as well as limitations encountered.Our target trial application revealed data limitations that precluded us from carrying out the proposed emulation. Implications for data quality are discussed and we provide recommendations for researchers interested in conducting trial emulations in the field of oral epidemiology.The target trial framework has the potential to improve the validity of observational research in oral health, when properly applied.We encourage the broad adoption of the target trial framework to the field of observational oral health research and demonstrate its value as a tool to identify directions for future research. [ABSTRACT FROM AUTHOR]

Background Methods Conclusion Practice‐Based Research Network (PBRN) studies typically assess the effectiveness of clinical interventions in settings that match real‐world conditions. Dental PBRNs have the capacity to amass, identify, and analyze vast amounts of data from patient populations that include diverse racial, ethnic, socio‐economic, and geographic backgrounds. These dental studies encompass a broad spectrum of healthcare aspects, including prevention, diagnosis, symptom and disease treatment, quality enhancement, and care coordination.An extensive range of research methodologies can be employed within dental PBRNs to investigate these topics, including randomized controlled trials. Dental PBRNs have evolved from primarily focusing on case observations to leveraging advanced network infrastructure and collaborating across multiple regional and national sites. In addition to producing numerous high‐impact peer‐reviewed publications, study results have led to improved clinical care. However, PBRNs encounter challenges, such as the sustainability of research capacity (relying heavily on ongoing support from funding agencies), diverse research cultures, and an imperative to design studies that are both feasible and relevant to everyday clinical practice. Recognizing the pivotal role of real‐world evidence, it is important to have sustained investment in dental PBRN infrastructure and feasible opportunities for practitioners to participate in network activities nationwide.Practice‐Based Research Network studies capitalize on an important research context within which to investigate a range of clinical topics that can employ multiple research methodologies. However, sustaining productive networks requires strategic effort, ongoing financial support, and customized organizational skills. [ABSTRACT FROM AUTHOR]

The debate about the characteristics and advantages of quantitative and qualitative methods is decades old. In their seminal monograph, A Tale of Two Cultures (2012, ATTC), Gary Goertz and James Mahoney argue that methods and research design practices for causal inference can be distinguished as two cultures that systematically differ from each other along 25 specific characteristics. ATTC's stated goal is a description of empirical patterns in quantitative and qualitative research. Yet, it does not include a systematic empirical evaluation as to whether the 25 are relevant and valid descriptors of applied research. In this paper, we derive five observable implications from ATTC and test the implications against a stratified random sample of 90 qualitative and 90 quantitative articles published in six journals between 1990–2012. Our analysis provides little support for the two-cultures hypothesis. Quantitative methods are largely implemented as described in ATTC, whereas qualitative methods are much more diverse than ATTC suggests. While some practices do indeed conform to the qualitative culture, many others are implemented in a manner that ATTC characterizes as constitutive of the quantitative culture. We find very little evidence for ATTC's anchoring of qualitative research with set-theoretic approaches to empirical social science research. The set-theoretic template only applies to a fraction of the qualitative research that we reviewed, with the majority of qualitative work incorporating different method choices. [ABSTRACT FROM AUTHOR]

Background: Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking. Objectives: To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS. Methods: Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab were identified in the global MSBase cohort and two additional UK centres. Patients were followed for ⩾6/12 and had ⩾3 in-person disability assessments. Patients were matched using propensity score. Four pairwise analyses compared annualised relapse rates (ARRs) and disability outcomes. Results: The eligible cohorts consisted of 853 (fingolimod), 464 (natalizumab), 1131 (ocrelizumab), 123 (alemtuzumab) or 493 (cladribine) patients. Cladribine was associated with a lower ARR than fingolimod (0.07 vs. 0.12, p = 0.006) and a higher ARR than natalizumab (0.10 vs. 0.06, p = 0.03), ocrelizumab (0.09 vs. 0.05, p = 0.008) and alemtuzumab (0.17 vs. 0.04, p < 0.001). Compared to cladribine, the risk of disability worsening did not differ in patients treated with fingolimod (hazard ratio (HR) 1.08, 95% confidence interval (CI) 0.47–2.47) or alemtuzumab (HR 0.73, 95% CI 0.26–2.07), but was lower for patients treated with natalizumab (HR 0.35, 95% CI 0.13–0.94) and ocrelizumab (HR 0.45, 95% CI 0.26–0.78). There was no evidence for a difference in disability improvement. Conclusion: Cladribine is an effective therapy that can be viewed as a step up in effectiveness from fingolimod, but is less effective than the most potent intravenous MS therapies. [ABSTRACT FROM AUTHOR]

The problems of generalization and transportation of treatment effect estimates from a study sample to a target population are central to empirical research and statistical methodology. In both randomized experiments and observational studies, weighting methods are often used with this objective. Traditional methods construct the weights by separately modeling the treatment assignment and study selection probabilities and then multiplying functions (e.g., inverses) of their estimates. In this work, we provide a justification and an implementation for weighting in a single step. We show a formal connection between this one-step method and inverse probability and inverse odds weighting. We demonstrate that the resulting estimator for the target average treatment effect is consistent, asymptotically Normal, multiply robust, and semiparametrically efficient. We evaluate the performance of the one-step estimator in a simulation study. We illustrate its use in a case study on the effects of physician racial diversity on preventive healthcare utilization among Black men in California. We provide R code implementing the methodology. [ABSTRACT FROM AUTHOR]

Background: Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. Results: We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. Conclusions: The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias. [ABSTRACT FROM AUTHOR]