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Objective: Farmworkers are at increased risk of adverse health outcomes related to occupational heat exposure and inadequate access to water, shade, or rest breaks. Presently, there is a dearth of studies examining the prevalence of dehydration and related factors in U.S. farmworkers. Our objectives were to characterize hydration status during typical workdays and to identify risk factors associated with increased dehydration in migrant farmworkers employed in Florida., Methods: Urine samples were collected and analyzed for urine specific gravity (USG) 2-3 times per person per day over five days in May 2021 and 2022. Data collection included demographic characteristics, wet-bulb-globe-temperature (WBGT), and information on working conditions (task type, duration, and crop units harvested), fluid intake, clothing worn, and heat safety behaviors. Multivariable mixed regression models were used to evaluate risk factors associated with change in USG levels (continuous) during a work shift., Results: A total of 111 farmworkers participated in this study providing 1020 cumulative USG measurements, of which 96.8% of end-of-shift USG samples were above 1.020 indicating potential dehydration. In multivariable models, dehydration assessed using change in USG levels significantly declined with age (β = -0.078; 95%CI: 0.150, -0.006) but showed significant increase with body mass index (β = 0.016; 95%CI: 0.003, 0.028), WGBT (β = 0.054; 95%CI:0.044, 0.064), mean shift duration, and state of primary residence. We did not find significant associations of dehydration with type of clothing worn, intake of employer-provided water, or crop units harvested during a shift in this sample of farmworkers., Conclusion: Our findings underscore the need for additional research to evaluate adverse outcomes related to dehydration and to better understand recovery patterns from chronic dehydration across workweeks and harvest seasons in migrant farmworkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Agriculture is a dangerous industry, with evidence indicating a disproportionate burden among Hispanic/Latinx workers. There is a need to expand the utilization of different data systems to improve the surveillance of precarious workers within agriculture. This analysis describes inclusion criteria to identify farm-related injuries and illnesses in hospital data utilizing ICD-10 codes to better assess health equity issues involving Hispanic/Latinx workers and their associated costs., Methods: Discharge data of agriculture-related injuries and illnesses treated in Illinois hospitals and emergency departments from 2018 to 2021 were extracted using ICD-10 diagnosis and location of injury codes. Injury cause, nature, severity, and course of clinical care are stratified by ethnicity. Multivariable models were developed to assess differences in injury severity, level of care required, and cost of care., Results: We identified 3,745 farm-related injuries and illnesses treated in Illinois hospitals between 2018 and 2021, of which 196 involved Hispanic/Latinx individuals. Hispanic/Latinx patients were substantially younger and disproportionately covered by workers' compensation insurance or uninsured. Compared to non-Hispanic/Latinx individuals, Hispanic/Latinx patients suffered injuries from different mechanisms, particularly involving animals and cutting/piercing instruments. While non-Hispanic/Latinx individuals demonstrated more severe injuries based on the descriptive statistics, after controlling for confounding (particularly age), we did not observe ethnic disparities in injury severity or level of care required. However, the cost of care was equivalent to or higher among Hispanic/Latinx persons., Conclusion: The case definition used for this analysis identified agriculture-related cases and provided insights on the course of clinical care by ethnicity. This strategy would likely yield valuable information in states with larger and more diverse agricultural workforces. More targeted research to appropriately scope the issue and inform interventions is needed to understand differential exposure and reduce agricultural workplace hazards and address the financial burden resulting from farm-related injuries.

Objective: This project compared student learning and satisfaction of an anatomy review delivered by a face-to-face lecture (F2FL) and an online learning module (OLM) for third-year doctor of chiropractic students., Methods: This cohort study compared student learning and satisfaction of a pediatric spinal anatomy review delivered via F2FL (cohort 1, n = 23) and OLM (cohort 2, n = 18) in 2 successive 2019 (pre-COVID) course offerings. Previously validated pre- and post-tests were given. Students completed a survey assessing delivery, comfort with online learning and online learning technology, and preference of F2FL vs OLM of review material. Pre- and post-test results were assessed using repeated-measures analysis of variance., Results: Testing results showed an improvement with both groups (F2FL 53.7%, p < .001 vs OLM 51.8%, p < .001), with no significant difference between the F2FL and OLM groups (p = .53; p = .82). The survey showed: 83.3% of OLM students felt the online method was effective, and 88.9% of the OLM students would prefer online reviews or have no preference between online or face-to-face; meanwhile, 80% of the F2FL group thought the lecture engaging/effective, whereas 60% of the F2FL group would have preferred to have the material presented online., Conclusion: The OLM was found to be as effective as the F2FL for the content assessed. The majority of students would prefer the online method for future anatomy review content presented in the course. This strategy could be applied to provide review materials in other clinical courses, allowing material to be developed and given by content experts while freeing valuable in-class time., (© 2024 Association of Chiropractic Colleges.)

Oxide-dispersion-strengthened (ODS) alloys have long been considered for high temperature turbine, spacecraft, and nuclear reactor components due to their high temperature strength and radiation resistance. Conventional synthesis approaches of ODS alloys involve ball milling of powders and consolidation. In this work, a process-synergistic approach is used to introduce oxide particles during laser powder bed fusion (LPBF). Chromium (III) oxide (Cr 2 O 3 ) powders are blended with a cobalt-based alloy, Mar-M 509, and exposed to laser irradiation, resulting in reduction-oxidation reactions involving metal (Ta, Ti, Zr) ions from the metal matrix to form mixed oxides of increased thermodynamic stability. A microstructure analysis indicates the formation of nanoscale spherical mixed oxide particles as well as large agglomerates with internal cracks. Chemical analyses confirm the presence of Ta, Ti, and Zr in agglomerated oxides, but primarily Zr in the nanoscale oxides. Mechanical testing reveals that agglomerate particle cracking is detrimental to tensile ductility compared to the base alloy, suggesting the need for improved processing methods to break up oxide particle clusters and promote their uniform dispersion during laser exposure.

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint-defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)-was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%-74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%-97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient., (Copyright © ASAIO 2022.)

Objective: Massage therapy involves pervasive ergonomic hazards with the majority of massage therapists (MTs) experiencing adverse musculoskeletal health issues. A variety of barriers and facilitators exist that can impact the efficacy of safety programs., Methods: A longitudinal study to characterize individual and organizational barriers and facilitators that influence the implementation of self-care techniques designed to reduce musculoskeletal health issues., Results: MTs who reported time as abarrier implemented 0.9 fewer selfcare items despite wanting to make these changes (P  = 0.003) and 1.4 fewer self-care items when management was identified as a barrier (P < 0.001). Almost 20% of the MTs reported switching jobs which was associated with implementing 1.1 fewer self-care items (P = 0.002)., Conclusions: Our findings show that organizational factors plays a critical role in workplace safety which can be used to improve working conditions faced by MTs., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

The burden of sports injury in soccer is high, and return to sport outcomes following injury are often poor. This is compounded by a current lack of understanding surrounding the factors that may optimize psychological readiness to return to sport. Consequently, in the present study, we aim to further our understanding of these issues by examining the role of perceived social support in predicting psychological readiness to return to sport. In doing so, we extend previous research by examining whether reinjury anxiety is a mediating factor in this relationship. A sample of 150 previously injured soccer players (mean age = 25.32 y) completed measures of perceived social support, reinjury anxiety during rehabilitation, and psychological readiness to return to sport. Mediation analyses showed that reinjury anxiety partly accounted for the positive relationship between perceived social support and psychological readiness to return to sport. These findings suggest that injured soccer players with higher perceptions of social support will experience less reinjury anxiety during rehabilitation and, as a consequence, will be more psychologically ready upon return to sport.

Studies of the effects of medical interventions increasingly take place in distributed research settings using data from multiple clinical data sources including electronic health records and administrative claims. In such settings, privacy concerns typically prohibit sharing of individual patient data, and instead, cross-network analyses can only utilize summary statistics from the individual databases such as hazard ratios and standard errors. In the specific but very common context of the Cox proportional hazards model, we show that combining such per site summary statistics into a single network-wide estimate using standard meta-analysis methods leads to substantial bias when outcome counts are small. This bias derives primarily from the normal approximations of the per site likelihood that the methods utilized. Here we propose and evaluate methods that eschew normal approximations in favor of three more flexible approximations: a skew-normal, a one-dimensional grid, and a custom parametric function that mimics the behavior of the Cox likelihood function. In extensive simulation studies, we demonstrate how these approximations impact bias in the context of both fixed-effects and (Bayesian) random-effects models. We then apply these approaches to three real-world studies of the comparative safety of antidepressants, each using data from four observational health care databases.

Estimating a treatment effect from observational data requires modeling treatment and outcome subject to uncertainty/misspecification. A previous research has shown that it is not possible to find a uniformly best strategy. In this article we propose a novel Frequentist Model Averaging (FMA) framework encompassing any estimation strategy and accounting for model uncertainty by computing a cross-validated estimate of Mean Squared Prediction Error (MSPE). We present a simulation study with data mimicking an observational database. Model averaging over 15+ strategies was compared with individual strategies as well as the best strategy selected by minimum MSPE. FMA showed robust performance (Bias, Mean Squared Error (MSE), and Confidence Interval (CI) coverage). Other strategies, such as linear regression, did well in simple scenarios but were inferior to the FMA in a scenario with complex confounding.

The expansion of urban landscapes has both negative and positive effects on wildlife. Understanding how different species respond to urbanization is key to assessing how urban landscapes influence regional wildlife behavior and ecosystem structure. Gulls are often described as strong urban adapters, but few studies have explored species-specific differences in habitat use. Here, we use GPS tracking in conjunction with stable isotope analysis (SIA) to quantify the habitat use and trophic ecology of great black-backed gulls (Larus marinus) and herring gulls (L. argentatus) in an urbanized area. Non-Metric Multidimensional Scaling (NMDS) of foraging locations revealed significant differences in the habitat use between species. Great black-backed gulls foraged primarily in marine habitats and herring gulls foraged primarily in specific urban habitats (e.g., landfills, dumpsters) and showed higher site fidelity in terms of the proportion of foraging sites revisited. Further, great black-backed gulls had significantly higher δ 15 N and δ 13 C than herring gulls, reflecting the use of marine, rather than urban, food sources. This study highlights the variability in urban habitat utilization among closely related species, assesses stable isotope signatures of urban diets in wild birds, and discusses ecological implications of the relative contribution of urban and marine foraging., (© 2021. The Author(s).)

Background: Employment is an important social determinant of health, and supporting individuals' return to the workforce is likely to have robust impacts on their health and well-being. The aim of this study was to identify (a) the self-perceived employment needs and expectations of users of community employment services; (b) the assets, needs, and barriers to reemployment among users of community employment services; and (c) areas of priority for programmatic development, including implications for patient-worker needs assessment and care coordination in clinical settings., Methods: We conducted structured interviews with 71 adults recruited from three workforce development programs located in the Chicago metropolitan area serving vulnerable workers. Topics of discussion included job histories, financial and social assets, and the respondents' motivation and expectations for their return to the workforce. We used descriptive statistics to analyze quantitative responses and performed content analysis for qualitative data., Findings: Users reported discrimination, legal barriers, family responsibilities, physical or mental health concerns, and needs related to transportation and housing as common challenges to reemployment. Concerns regarding navigating complex social support programs to meet individual and family needs, as well as uncertainty regarding what would qualify as sufficient employment in order to not be reliant on these programs in the future, were expressed., Conclusion/application to Practice: Health care providers have opportunities to identify those that may benefit from comprehensive referrals to reemployment programs and social services. Occupational health providers are also in a unique position to enhance workforce development programs through collaborations to better educate and support workers.

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Objective: The current observational research literature shows extensive publication bias and contradiction. The Observational Health Data Sciences and Informatics (OHDSI) initiative seeks to improve research reproducibility through open science., Methods: OHDSI has created an international federated data source of electronic health records and administrative claims that covers nearly 10% of the world's population. Using a common data model with a practical schema and extensive vocabulary mappings, data from around the world follow the identical format. OHDSI's research methods emphasize reproducibility, with a large-scale approach to addressing confounding using propensity score adjustment with extensive diagnostics; negative and positive control hypotheses to test for residual systematic error; a variety of data sources to assess consistency and generalizability; a completely open approach including protocol, software, models, parameters, and raw results so that studies can be externally verified; and the study of many hypotheses in parallel so that the operating characteristics of the methods can be assessed., Results: OHDSI has already produced findings in areas like hypertension treatment that are being incorporated into practice, and it has produced rigorous studies of COVID-19 that have aided government agencies in their treatment decisions, that have characterized the disease extensively, that have estimated the comparative effects of treatments, and that the predict likelihood of advancing to serious complications., Conclusions: OHDSI practices open science and incorporates a series of methods to address reproducibility. It has produced important results in several areas, including hypertension therapy and COVID-19 research., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (IMIA and Thieme. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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Objectives: To describe individuals coded as homeless in state-level data comprising of outpatient and inpatient cases over a multi-year period to provide public health surveillance data on the health care utilization and needs of this population., Research Design: In this cross-sectional study, outpatient and inpatient visits coded for homelessness were identified from the Illinois Hospital Discharge Database from January 1, 2011 through December 31, 2018. Demographic characteristics, primary diagnosis and comorbid conditions, and hospital course of treatment were described. Predictors of discharge to a health care facility versus routine discharge to home or self-care were evaluated using multivariable logistic regression., Results: There were 154,173 patient visits predominantly involving males, those aged 25-64 years, and non-Hispanic Whites and African Americans. The majority had comorbidities of depression, psychosis, and/or substance abuse (70.2%) and a routine discharge to home or self-care (81.9%). Discharge to home or self-care relative to another health care institution was associated with having charity coverage and being Black/African American., Conclusions: Those experiencing homelessness experience a high burden of health concerns. Hospital billing records can be used to prioritize the distribution of limited public health resources for health care programs and interventions among those experiencing homelessness., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study uses a pre- and post-training program evaluation of chiropractic interns to (1) describe changes in their frequency of occupational history taking before and after a 1-hour training and (2) to document the attitudes and beliefs regarding occupational health and history taking., Methods: All chiropractic interns at 1 clinic location completed questionnaires assessing their attitudes and perceptions regarding documenting the occupational history of their patients each trimester they were enrolled in the study. Each intern enrolled in the study for 2 or more trimesters participated in a 1-hour-long training session on taking an occupational history. The supervising clinician independently evaluated charting behaviors of interns for the duration of the study., Results: The supervising clinician assessed 20 interns' level of documenting occupational history for 202 new patient or reexamination visits. A majority of interns (85% at baseline) were interested in occupational health, and 80% believed that occupational history taking was "very important." Intern charting behaviors increased after training related to documentation of past occupation (62.9% from 32.4%) and relating the chief complaint to work (59.7% from 30.0%). Detailed occupational history taking remained low throughout the study but demonstrated a doubling in documentation after training (16.1% from 8.6%)., Conclusion: Chiropractic interns and clinicians should be adequately trained in occupational health history documentation practices as they are likely to care for work-related injuries. Short training modules appear to be effective in demonstrating small changes in documentation related to occupational history taking., (© 2021 Association of Chiropractic Colleges.)

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention., Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice., Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019., Exposures: Ticagrelor vs clopidogrel., Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis., Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group., Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.

Objectives: Sports coaches are influential in whether athletes dope, but receive very little antidoping education, particularly within entry-level coaching qualifications. We tested the feasibility of an antidoping intervention, delivered via a mobile application, which was designed to increase coaches' knowledge of doping and to reduce favourable doping attitudes., Methods: A two-arm randomised controlled trial, with grassroots coaches who coach young amateur athletes aged between 14 and 18 years of age, was conducted. The Anti-Doping Values in Coach Education (ADVICE) mobile application included modules on fair play, substances, nutritional supplements, rules and leadership. The primary outcome was the change in doping knowledge, 6 weeks after receiving the mobile application. The secondary outcome was changes in doping attitudes., Results: Grassroots coaches (n=200; aged between 18 and 71 years, with between 1 and 42 years of coaching experience) from 29 different countries completed baseline assessments, and 85 completed follow-up assessments, and were included in mixed analysis of variance analyses. The intervention increased coaches' knowledge about doping and also reduced favourable doping attitudes in the experimental arm., Conclusion: The ADVICE mobile application is a feasible method for delivering and increasing grassroots coaches' knowledge of banned substances and the potential side effects of doping. Mobile application-based resources could facilitate a much wider dissemination of antidoping education., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To demonstrate the application of the Large-scale Evidence Generation and Evaluation across a Network of Databases (LEGEND) principles described in our companion article to hypertension treatments and assess internal and external validity of the generated evidence., Materials and Methods: LEGEND defines a process for high-quality observational research based on 10 guiding principles. We demonstrate how this process, here implemented through large-scale propensity score modeling, negative and positive control questions, empirical calibration, and full transparency, can be applied to compare antihypertensive drug therapies. We assess internal validity through covariate balance, confidence-interval coverage, between-database heterogeneity, and transitivity of results. We assess external validity through comparison to direct meta-analyses of randomized controlled trials (RCTs)., Results: From 21.6 million unique antihypertensive new users, we generate 6 076 775 effect size estimates for 699 872 research questions on 12 946 treatment comparisons. Through propensity score matching, we achieve balance on all baseline patient characteristics for 75% of estimates, observe 95.7% coverage in our effect-estimate 95% confidence intervals, find high between-database consistency, and achieve transitivity in 84.8% of triplet hypotheses. Compared with meta-analyses of RCTs, our results are consistent with 28 of 30 comparisons while providing narrower confidence intervals., Conclusion: We find that these LEGEND results show high internal validity and are congruent with meta-analyses of RCTs. For these reasons we believe that evidence generated by LEGEND is of high quality and can inform medical decision-making where evidence is currently lacking. Subsequent publications will explore the clinical interpretations of this evidence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Evidence derived from existing health-care data, such as administrative claims and electronic health records, can fill evidence gaps in medicine. However, many claim such data cannot be used to estimate causal treatment effects because of the potential for observational study bias; for example, due to residual confounding. Other concerns include P hacking and publication bias. In response, the Observational Health Data Sciences and Informatics international collaborative launched the Large-scale Evidence Generation and Evaluation across a Network of Databases (LEGEND) research initiative. Its mission is to generate evidence on the effects of medical interventions using observational health-care databases while addressing the aforementioned concerns by following a recently proposed paradigm. We define 10 principles of LEGEND that enshrine this new paradigm, prescribing the generation and dissemination of evidence on many research questions at once; for example, comparing all treatments for a disease for many outcomes, thus preventing publication bias. These questions are answered using a prespecified and systematic approach, avoiding P hacking. Best-practice statistical methods address measured confounding, and control questions (research questions where the answer is known) quantify potential residual bias. Finally, the evidence is generated in a network of databases to assess consistency by sharing open-source analytics code to enhance transparency and reproducibility, but without sharing patient-level information. Here we detail the LEGEND principles and provide a generic overview of a LEGEND study. Our companion paper highlights an example study on the effects of hypertension treatments, and evaluates the internal and external validity of the evidence we generate., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Alendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporotic hip fracture, while secondary outcomes were vertebral fracture, atypical femoral fracture (AFF), osteonecrosis of the jaw (ONJ), and esophageal cancer. We used propensity score trimming and stratification based on an expansive propensity score model with all pre-treatment patient characteritistcs. We accounted for unmeasured confounding using negative control outcomes to estimate and adjust for residual systematic bias in each data source. We identified 283,586 alendronate patients and 40,463 raloxifene patients. There were 7.48 hip fracture, 8.18 vertebral fracture, 1.14 AFF, 0.21 esophageal cancer and 0.09 ONJ events per 1,000 person-years in the alendronate cohort and 6.62, 7.36, 0.69, 0.22 and 0.06 events per 1,000 person-years, respectively, in the raloxifene cohort. Alendronate and raloxifene have a similar hip fracture risk (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.94-1.13), but alendronate users are more likely to have vertebral fractures (HR 1.07, 95% CI 1.01-1.14). Alendronate has higher risk for AFF (HR 1.51, 95% CI 1.23-1.84) but similar risk for esophageal cancer (HR 0.95, 95% CI 0.53-1.70), and ONJ (HR 1.62, 95% CI 0.78-3.34). We demonstrated substantial control of measured confounding by propensity score adjustment, and minimal residual systematic bias through negative control experiments, lending credibility to our effect estimates. Raloxifene is as effective as alendronate and may remain an option in the prevention of osteoporotic fracture.

Importance: Chlorthalidone is currently recommended as the preferred thiazide diuretic to treat hypertension, but no trials have directly compared risks and benefits., Objective: To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide as first-line therapies for hypertension in real-world practice., Design, Setting, and Participants: This is a Large-Scale Evidence Generation and Evaluation in a Network of Databases (LEGEND) observational comparative cohort study with large-scale propensity score stratification and negative-control and synthetic positive-control calibration on databases spanning January 2001 through December 2018. Outpatient and inpatient care episodes of first-time users of antihypertensive monotherapy in the United States based on 2 administrative claims databases and 1 collection of electronic health records were analyzed. Analysis began June 2018., Exposures: Chlorthalidone and hydrochlorothiazide., Main Outcomes and Measures: The primary outcomes were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death. Fifty-one safety outcomes were measured., Results: Of 730 225 individuals (mean [SD] age, 51.5 [13.3] years; 450 100 women [61.6%]), 36 918 were dispensed or prescribed chlorthalidone and had 149 composite outcome events, and 693 337 were dispensed or prescribed hydrochlorothiazide and had 3089 composite outcome events. No significant difference was found in the associated risk of myocardial infarction, hospitalized heart failure, or stroke, with a calibrated hazard ratio for the composite cardiovascular outcome of 1.00 for chlorthalidone compared with hydrochlorothiazide (95% CI, 0.85-1.17). Chlorthalidone was associated with a significantly higher risk of hypokalemia (hazard ratio [HR], 2.72; 95% CI, 2.38-3.12), hyponatremia (HR, 1.31; 95% CI, 1.16-1.47), acute renal failure (HR, 1.37; 95% CI, 1.15-1.63), chronic kidney disease (HR, 1.24; 95% CI, 1.09-1.42), and type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12-1.30). Chlorthalidone was associated with a significantly lower risk of diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61-0.86)., Conclusions and Relevance: This study found that chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. These findings do not support current recommendations to prefer chlorthalidone vs hydrochlorothiazide for hypertension treatment in first-time users was found. We used advanced methods, sensitivity analyses, and diagnostics, but given the possibility of residual confounding and the limited length of observation periods, further study is warranted.

Objectives. To assess the value of hospital records in augmenting information on homelessness counts at a state level. Methods. We used data from the Illinois Hospital Discharge Database (2011-2018) to identify outpatients and inpatients identified as affected by homelessness. We used probabilistic linkage methodology to estimate unique individuals rather than visits and compared them with US Department of Housing and Urban Development annual estimates of homelessness based on point-in-time counts. Results. Department of Housing and Urban Development point-in-time estimates indicate a substantial decline of approximately 24% in homelessness in Illinois; however, estimates of unique individuals visiting the hospital with a code for homelessness more than doubled in this same period. Conclusions. Other data sources, such as hospital records, are increasingly able to identify and report information related to homelessness. Using these additional data sources may help to augment the Department of Housing and Urban Development point-in-time estimates to provide more accurate estimates of homelessness that are used to direct resources and assess policy and support services for those affected by homelessness.

Objective: Individuals in transitional housing programs often have a goal of reaching stable employment, but the unique needs and barriers for achieving this warrants further study., Methods: A structured interview guide was administered orally and descriptive data analysis was done for this exploratory mixed-methods study., Results: Commonly reported reemployment challenges included legal barriers and unmet transportation, housing, and financial needs. More than two-thirds of residents reported no place to live after the program regardless of if they had previous precarious housing. Emerging themes included challenges regarding sufficient time for the transition to being employed, fear of relapse, and lack of long-term goals and planning., Conclusions: Findings suggest that residential rehabilitation programs are an important resource. While these programs tend to focus on reemployment, their services could be enhanced by assessing individual needs and allowing for variation in reemployment preparation.

Healthcare professionals increasingly rely on observational healthcare data, such as administrative claims and electronic health records, to estimate the causal effects of interventions. However, limited prior studies raise concerns about the real-world performance of the statistical and epidemiological methods that are used. We present the "OHDSI Methods Benchmark" that aims to evaluate the performance of effect estimation methods on real data. The benchmark comprises a gold standard, a set of metrics, and a set of open source software tools. The gold standard is a collection of real negative controls (drug-outcome pairs where no causal effect appears to exist) and synthetic positive controls (drug-outcome pairs that augment negative controls with simulated causal effects). We apply the benchmark using four large healthcare databases to evaluate methods commonly used in practice: the new-user cohort, self-controlled cohort, case-control, case-crossover, and self-controlled case series designs. The results confirm the concerns about these methods, showing that for most methods the operating characteristics deviate considerably from nominal levels. For example, in most contexts, only half of the 95% confidence intervals we calculated contain the corresponding true effect size. We previously developed an "empirical calibration" procedure to restore these characteristics and we also evaluate this procedure. While no one method dominates, self-controlled methods such as the empirically calibrated self-controlled case series perform well across a wide range of scenarios.

Background: Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice., Methods: We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested., Findings: Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes., Interpretation: This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers., Funding: US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Predicting health outcomes from longitudinal health histories is of central importance to healthcare. Observational healthcare databases such as patient diary databases provide a rich resource for patient-level predictive modeling. In this paper, we propose a Bayesian hierarchical vector autoregressive (VAR) model to predict medical and psychological conditions using multivariate time series data. Compared to the existing patient-specific predictive VAR models, our model demonstrated higher accuracy in predicting future observations in terms of both point and interval estimates due to the pooling effect of the hierarchical model specification. In addition, by adopting an elastic-net prior, our model offers greater interpretability about the associations between variables of interest on both the population level and the patient level, as well as between-patient heterogeneity. We apply the model to two examples: 1) predicting substance use craving, negative affect and tobacco use among college students, and 2) predicting functional somatic symptoms and psychological discomforts., Competing Interests: The authors have declared that no competing interests exist.

Concerns over reproducibility in science extend to research using existing healthcare data; many observational studies investigating the same topic produce conflicting results, even when using the same data. To address this problem, we propose a paradigm shift. The current paradigm centres on generating one estimate at a time using a unique study design with unknown reliability and publishing (or not) one estimate at a time. The new paradigm advocates for high-throughput observational studies using consistent and standardized methods, allowing evaluation, calibration and unbiased dissemination to generate a more reliable and complete evidence base. We demonstrate this new paradigm by comparing all depression treatments for a set of outcomes, producing 17 718 hazard ratios, each using methodology on par with current best practice. We furthermore include control hypotheses to evaluate and calibrate our evidence generation process. Results show good transitivity and consistency between databases, and agree with four out of the five findings from clinical trials. The distribution of effect size estimates reported in the literature reveals an absence of small or null effects, with a sharp cut-off at p  = 0.05. No such phenomena were observed in our results, suggesting more complete and more reliable evidence.This article is part of a discussion meeting issue 'The growing ubiquity of algorithms in society: implications, impacts and innovations'., (© 2018 The Authors.)

Introduction: Substantial evidence suggests that drospirenone-containing oral contraceptives may cause a higher risk of venous thrombotic events than earlier-generation oral contraceptives., Methods: To gain insight into recent real-world implications, we conducted an analysis using the US Food and Drug Administration's Adverse Event Reporting System., Results: Venous thrombotic events continue to be reported at a much higher rate with drospirenone-containing oral contraceptives than the general background. The disproportionality has been rising since 2010. The same behavior is not seen with levonorgestrel-containing oral contraceptives., Conclusion: Our results are consistent with decreased physician and patient awareness of risks associated with drospirenone-containing oral contraceptives., Competing Interests: Disclosure Dr Madigan testified for plaintiffs in litigation related to Yaz in 2011. The authors report no other conflicts of interest in this work.

Observational healthcare data, such as electronic health records and administrative claims, offer potential to estimate effects of medical products at scale. Observational studies have often been found to be nonreproducible, however, generating conflicting results even when using the same database to answer the same question. One source of discrepancies is error, both random caused by sampling variability and systematic (for example, because of confounding, selection bias, and measurement error). Only random error is typically quantified but converges to zero as databases become larger, whereas systematic error persists independent from sample size and therefore, increases in relative importance. Negative controls are exposure-outcome pairs, where one believes no causal effect exists; they can be used to detect multiple sources of systematic error, but interpreting their results is not always straightforward. Previously, we have shown that an empirical null distribution can be derived from a sample of negative controls and used to calibrate P values, accounting for both random and systematic error. Here, we extend this work to calibration of confidence intervals (CIs). CIs require positive controls, which we synthesize by modifying negative controls. We show that our CI calibration restores nominal characteristics, such as 95% coverage of the true effect size by the 95% CI. We furthermore show that CI calibration reduces disagreement in replications of two pairs of conflicting observational studies: one related to dabigatran, warfarin, and gastrointestinal bleeding and one related to selective serotonin reuptake inhibitors and upper gastrointestinal bleeding. We recommend CI calibration to improve reproducibility of observational studies., Competing Interests: Conflict of interest statement: M.J.S. and P.B.R. are full-time employees and shareholders of Janssen Research & Development.

Purpose: Real-world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials. RWE studies aim to improve health care decision making., Methods: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) created a task force to make recommendations regarding good procedural practices that would enhance decision makers' confidence in evidence derived from RWD studies. Peer review by ISPOR/ISPE members and task force participants provided a consensus-building iterative process for the topics and framing of recommendations., Results: The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration, replicability, and stakeholder involvement in RWE studies. These recommendations, in concert with earlier recommendations about study methodology, provide a trustworthy foundation for the expanded use of RWE in health care decision making., Conclusion: The focus of these recommendations is good procedural practices for studies that test a specific hypothesis in a specific population. We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers, journal editors, and other key stakeholders., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: Real-world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials. RWE studies aim to improve health care decision making., Methods: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) created a task force to make recommendations regarding good procedural practices that would enhance decision makers' confidence in evidence derived from RWD studies. Peer review by ISPOR/ISPE members and task force participants provided a consensus-building iterative process for the topics and framing of recommendations., Results: The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration, replicability, and stakeholder involvement in RWE studies. These recommendations, in concert with earlier recommendations about study methodology, provide a trustworthy foundation for the expanded use of RWE in health care decision making., Conclusion: The focus of these recommendations is good procedural practices for studies that test a specific hypothesis in a specific population. We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers, journal editors, and other key stakeholders., (© 2017 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.)

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease., Competing Interests: Competing interests: DLB: Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St Jude Medical; Trustee: American College of Cardiology; Unfunded Research: FlowCo, PLx Pharma, Takeda. DB: This work was done while Dr. Bonds was an employee of the National Heart, Lung and Blood Institute. JSB: Personal fees from Cardiorentis (DSMB), AstraZeneca (event adjudication committee), Novartis (DSMB), ARMGO (advisory board), Celladon (DSMB), BioTRONIK (Trial Executive Committee), Boerhinger-Ingelheim (consultant), Abbott Laboratories (consultant), Sarepta (consultant), Amgen (consultant), Servier (Trial Executive Committee, consultant), GSK (DSMB), Pfizer (DSMB). LHL: Consultant to Bayer Pharma, Novartis, AstraZeneca, Vifor Pharma; Research grants from AstraZeneca, Boston Scientific; Honoraria for lectures or speaker's bureaus from Novartis, St Jude. DM: Within the past 4 years, DM has been a paid consultant to Endo, Jarvik Heart, Lilly, Merck and Pfizer. In addition he has testified on behalf of plaintiffs in litigation related to pharmaceutical products and medical devices. APM: Research grants from Novartis, Cardiorentis, Bayer; Honoraria for lectures from Servier. TS: Research grants from AstraZeneca, Daiichi-Sankyo, GSK, MSD, Novartis; Personal fees (board and consultancy) from AstraZeneca, Astellas, Bayer, BMS, Lilly, MSD, Novartis, Sanofi. WGS: Consultant to Overcome (travel expense reimbursement to attend CVCT and professional time related to preparation of this paper), European Society of Cardiology, Heart Failure Association of the European Society of Cardiology, Heart Failure Society of American, Relypsa, Stealth Peptides, Celyad and Respicardia. AZ: Employee of GSK. NZ: Employee of AstraZeneca., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We construct a framework for meta-analysis and other multi-level data structures that codifies the sources of heterogeneity between studies or settings in treatment effects and examines their implications for analyses. The key idea is to consider, for each of the treatments under investigation, the subject's potential outcome in each study or setting were he to receive that treatment. We consider four sources of heterogeneity: (1) response inconsistency, whereby a subject's response to a given treatment would vary across different studies or settings, (2) the grouping of nonequivalent treatments, where two or more treatments are grouped and treated as a single treatment under the incorrect assumption that a subject's responses to the different treatments would be identical, (3) nonignorable treatment assignment, and (4) response-related variability in the composition of subjects in different studies or settings. We then examine how these sources affect heterogeneity/homogeneity of conditional and unconditional treatment effects. To illustrate the utility of our approach, we re-analyze individual participant data from 29 randomized placebo-controlled studies on the cardiovascular risk of Vioxx, a Cox-2 selective nonsteroidal anti-inflammatory drug approved by the FDA in 1999 for the management of pain and withdrawn from the market in 2004.

Background: The physical and psychological risks of temporary employment are well documented but there are still many questions regarding the consequences of injuries among these workers., Methods: This analysis examines Illinois Workers' Compensation Commission filings from 2007 through 2012 to compare total cost of the decision, days of work missed, and percent disability of employees of temporary agencies with direct hire claims., Results: Total award median was $5,813.66 for direct hire employees and $2,625.00 for temporary workers. Of those employees claiming time off from work, median total time off was 1.3 weeks for direct hire employees compared to 1.2 weeks for temporary workers. Median total percent disability was 16.0% for direct hire and 10.0% for temporary employees., Conclusions: There are differences between temporary workers and direct hire employees in terms of total workers' compensation awards, total time off, and percent disability. Additional studies are needed to validate these findings. Am. J. Ind. Med. 60:11-19, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Most approaches used in postmarketing drug safety monitoring, including spontaneous reporting and statistical risk identification using electronic health care records, are primarily suited to pick up only acute adverse drug effects. With the availability of increasingly larger electronic health record and administrative claims databases comes the opportunity to monitor for potential adverse effects that occur only after prolonged exposure to a drug, but analysis methods are lacking. We propose an adaptation of the self-controlled case series design that uses the notion of accumulated exposure to capture long-term effects of drugs and evaluate extensions to correct for age and recurrent events. Several variations of the approach are tested on simulated data and two large insurance claims databases. To evaluate performance a set of positive and negative control drug-event pairs was created by medical experts based on drug product labels and review of the literature. Performance on the real data was measured using the area under the receiver operator characteristics curve. The best performing method achieved an area under the receiver operator characteristics curve of 0.86 in the largest database using a spline model, adjustment for age, and ignoring recurrent events, but it appears this performance can only be achieved with very large data sets., (© The Author(s) 2014.)

Clinical trials often lack power to identify rare adverse drug events (ADEs) and therefore cannot address the threat rare ADEs pose, motivating the need for new ADE detection techniques. Emerging national patient claims and electronic health record databases have inspired post-approval early detection methods like the Bayesian self-controlled case series (BSCCS) regression model. Existing BSCCS models do not account for multiple outcomes, where pathology may be shared across different ADEs. We integrate a pathology hierarchy into the BSCCS model by developing a novel informative hierarchical prior linking outcome-specific effects. Considering shared pathology drastically increases the dimensionality of the already massive models in this field. We develop an efficient method for coping with the dimensionality expansion by reducing the hierarchical model to a form amenable to existing tools. Through a synthetic study we demonstrate decreased bias in risk estimates for drugs when using conditions with different true risk and unequal prevalence. We also examine observational data from the MarketScan Lab Results dataset, exposing the bias that results from aggregating outcomes, as previously employed to estimate risk trends of warfarin and dabigatran for intracranial hemorrhage and gastrointestinal bleeding. We further investigate the limits of our approach by using extremely rare conditions. This research demonstrates that analyzing multiple outcomes simultaneously is feasible at scale and beneficial.

Importance: Although data obtained from regional trauma systems demonstrate improved outcomes for children treated at pediatric trauma centers (PTCs) compared with those treated at adult trauma centers (ATCs), differences in mortality have not been consistently observed for adolescents. Because trauma is the leading cause of death and acquired disability among adolescents, it is important to better define differences in outcomes among injured adolescents by using national data., Objectives: To use a national data set to compare mortality of injured adolescents treated at ATCs, PTCs, or mixed trauma centers (MTCs) that treat both pediatric and adult trauma patients and to determine the final discharge disposition of survivors at different center types., Design, Setting, and Participants: Data from level I and II trauma centers participating in the 2010 National Trauma Data Bank (January 1 to December 31, 2010) were used to create multilevel models accounting for center-specific effects to evaluate the association of center characteristics (PTC, ATC, or MTC) on mortality among patients aged 15 to 19 years who were treated for a blunt or penetrating injury. The models controlled for sex; mechanism of injury (blunt vs penetrating); injuries sustained, based on the Abbreviated Injury Scale scores (post-dot values <3 or ≥3 by body region); initial systolic blood pressure; and Glasgow Coma Scale scores. Missing data were managed using multiple imputation, accounting for multilevel data structure. Data analysis was conducted from January 15, 2013, to March 15, 2016., Exposures: Type of trauma center., Main Outcomes and Measures: Mortality at each center type., Results: Among 29 613 injured adolescents (mean [SD] age, 17.3 [1.4] years; 72.7% male), most were treated at ATCs (20 402 [68.9%]), with the remainder at MTCs (7572 [25.6%]) or PTCs (1639 [5.5%]). Adolescents treated at PTCs were more likely to be injured by a blunt than penetrating injury mechanism (91.4%) compared with those treated at ATCs (80.4%) or MTCs (84.6%). Mortality was higher among adolescents treated at ATCs and MTCs than those treated at PTCs (3.2% and 3.5% vs 0.4%; P < .001). The adjusted odds of mortality were higher at ATCs (odds ratio, 4.19; 95% CI, 1.30-13.51) and MTCs (odds ratio, 6.68; 95% CI, 2.03-21.99) compared with PTCs but was not different between level I and II centers (odds ratio, 0.76; 95% CI, 0.59-0.99)., Conclusion and Relevance: Mortality among injured adolescents was lower among those treated at PTCs, compared with those treated at ATCs and MTCs. Defining resource and patient features that account for these observed differences is needed to optimize adolescent outcomes after injury.

Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.

Background: The use of mechanism of injury as a predictor of injury outcome presents practical challenges because this variable may be missing or inaccurate in many databases. The purpose of this study was to determine the importance of mechanism of injury as a predictor of mortality among injured children., Methods: The records of children (<15-y-old) sustaining a blunt injury were obtained from the National Trauma Data Bank. Models predicting injury mortality were developed using mechanism of injury and injury coding using either abbreviated injury scale post-dot values (low-dimensional injury coding) or injury International Classification of Diseases, Ninth Revision codes and their two-way interactions (high-dimensional injury coding). Model performance with and without inclusion of mechanism of injury was compared for both coding schemes, and the relative importance of mechanism of injury as a variable in each model type was evaluated., Results: Among 62,569 records, a mortality rate of 0.9% was observed. Inclusion of mechanism of injury improved model performance when using low-dimensional injury coding but was associated with no improvement when using high-dimensional injury coding. Mechanism of injury contributed to 28% of model variance when using low-dimensional injury coding and <1% when high-dimensional injury coding was used., Conclusions: Although mechanism of injury may be an important predictor of injury mortality among children sustaining blunt trauma, its importance as a predictor of mortality depends on the approach used for injury coding. Mechanism of injury is not an essential predictor of outcome after injury when coding schemes are used that better characterize injuries sustained after blunt pediatric trauma., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: An individual's birth month has a significant impact on the diseases they develop during their lifetime. Previous studies reveal relationships between birth month and several diseases including atherothrombosis, asthma, attention deficit hyperactivity disorder, and myopia, leaving most diseases completely unexplored. This retrospective population study systematically explores the relationship between seasonal affects at birth and lifetime disease risk for 1688 conditions., Methods: We developed a hypothesis-free method that minimizes publication and disease selection biases by systematically investigating disease-birth month patterns across all conditions. Our dataset includes 1 749 400 individuals with records at New York-Presbyterian/Columbia University Medical Center born between 1900 and 2000 inclusive. We modeled associations between birth month and 1688 diseases using logistic regression. Significance was tested using a chi-squared test with multiplicity correction., Results: We found 55 diseases that were significantly dependent on birth month. Of these 19 were previously reported in the literature (P < .001), 20 were for conditions with close relationships to those reported, and 16 were previously unreported. We found distinct incidence patterns across disease categories., Conclusions: Lifetime disease risk is affected by birth month. Seasonally dependent early developmental mechanisms may play a role in increasing lifetime risk of disease., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Objectives: Using the social-ecological model, we hypothesized that the home residences of injured workers would be clustered predictably and geographically., Methods: We linked health care and publicly available datasets by home zip code for traumatically injured workers in Illinois from 2000 to 2009. We calculated numbers and rates of injuries, determined the spatial relationships, and developed 3 models., Results: Among the 23 200 occupational injuries, 80% of cases were located in 20% of zip codes and clustered in 10 locations. After component analysis, numbers and clusters of injuries correlated directly with immigrants; injury rates inversely correlated with urban poverty., Conclusions: Traumatic occupational injuries were clustered spatially by home location of the affected workers and in a predictable way. This put an inequitable burden on communities and provided evidence for the possible value of community-based interventions for prevention of occupational injuries. Work should be included in health disparities research. Stakeholders should determine whether and how to intervene at the community level to prevent occupational injuries.

In June 2013, a record-breaking female Isurus oxyrinchus (total length 373 cm, mass 600 kg) was captured by rod and reel off Huntington Beach, California, where it was subsequently donated to research and provided a rare opportunity to collect the first data for a female I. oxyrinchus of this size. Counts of vertebral band pairs estimate the shark to have been c. 22 years old, depending upon assumptions of band-pair deposition rates, and the distended uteri and spent ovaries indicated that this shark had recently given birth. The stomach contained a c. 4 year-old female California sea lion Zalophus californianus that confirmed the high trophic position of this large I. oxyrinchus, which was corroborated with the high levels of measured contaminants and tissue isotope analyses., (© 2015 The Fisheries Society of the British Isles.)

Background and Aim: The risk of local tumour progression (LTP) and factors predicting LTP following percutaneous thermal ablation (PTA) of early-stage hepatocellular carcinoma (HCC) have not been well studied in non-trial settings and may be underestimated. We aimed to assess these outcomes in a multicentre study., Patients and Methods: This was a retrospective review of consecutive patients with early-stage HCC treated with a curative intent across three tertiary Australian centres between 2006 and 2012 with either radiofrequency ablation or microwave ablation. The primary endpoint was LTP and multivariate analysis was carried out to identify the independent predictors of LTP., Results: In total 145 HCC nodules were treated in 126 patients (78% men, mean±SD age 62±10 years) with a mean±SD follow-up of 13.5±13 months. Local recurrence was observed in 23.4% (34/145). Mean±SD LTP-free survival was 46.9±3.6 months. For HCC nodules 2 cm or less, local recurrence rates were lower (15.9%), with a mean±SD LTP-free survival of 48.8±4.2 months. Poorly differentiated HCC [hazard ratio (95% confidence interval)=4.8 (1.1-20.4), P=0.032] and pretreatment α-fetoprotein more than 50 kIU/l [8.2 (1.7-39.0), P=0.008] were independent predictors of LTP. LTP rates were not significantly different between the radiofrequency ablation and the microwave ablation groups (22.8 vs. 25.8%, P=0.7). There were six (4.8%) procedure-related adverse events, but no deaths., Conclusion: Local recurrence after PTA for early-stage HCC is high in routine clinical practice. Poorly differentiated HCC and pretreatment α-fetoprotein are important, independent predictors of LTP. Further well-designed randomized controlled trials with larger sample sizes using adjuvant therapies in combination with PTA to decrease LTP rates are warranted.