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Background Evidence on the association between long-term exposure to air pollution and cardiovascular mortality is limited in Asian populations. Methods We conducted a cohort study on the association between fine particulate matter (PM 2.5 ) and cardiovascular mortality using 43,227 individuals in a civil servants health service in Taiwan. Each participant was assigned an exposure level of particulate matter based on their district of residence using air pollution data collected by the Taiwan Environmental Protection Agency and with modeling using geographic information systems. The participants were followed up from 1989 to 2008 and the vital status was ascertained from death records. Cox regression models were used to adjust for confounding factors. Results The district-level average of PM 2.5 ranged from 22.8 to 32.9 μg/m 3 in the study area. After a median follow-up of 18 years, 1992 deaths from all causes including 230 cardiovascular deaths occurred. After adjustment for potential confounders, PM 2.5 levels were not significantly associated with mortality from cardiovascular disease [Hazard Ratio (HR) 0.80; 95 % Confidence Interval (CI), 0.43 to 1.50 per 10 μg/m 3 increase in PM 2.5 ] or all causes (HR 0.92; 95 % CI, 0.72 to 1.17 per 10 μg/m 3 increase in PM 2.5 ). The results were similar when the analysis was restricted to the urban areas and when the PM 2.5 measurement was changed from the period average (2000–2008) to annual average. Discussion Our findings are different from those in prior cohort studies conducted in Asia where ambient air pollutionwas associated with an increased risk of cardiovascular mortality. The high background level of air pollutionin our study area and the small number of event cases limited the power of this study. Conclusions In this population-based cohort study in Taiwan, we found no evidence of increased risk for all-cause or cardiovascular mortality with long-term exposure to PM 2.5 .

Prediabetes affects 1 in 3 US adults. Most are not receiving evidence-based interventions, so understanding how providers discuss prediabetes with patients will inform how to improve their care. This study aimed to develop a natural language processing (NLP) algorithm using machine learning techniques to identify discussions of prediabetes in narrative documentation. We developed and applied a keyword search strategy to identify discussions of prediabetes in clinical documentation for patients with prediabetes. We manually reviewed matching notes to determine which represented actual prediabetes discussions. We applied 7 machine learning models against our manual annotation. Machine learning classifiers were able to achieve classification results that were close to human performance with up to 98% precision and recall to identify prediabetes discussions in clinical documentation. We demonstrated that prediabetes discussions can be accurately identified using an NLP algorithm. This approach can be used to understand and identify prediabetes management practices in primary care, thereby informing interventions to improve guideline-concordant care.

BackgroundPre-diabetes affects one-third of US adults and increases the risk of type 2 diabetes. Effective evidence-based interventions, such as the Diabetes Prevention Program, are available, but a gap remains in effectively translating and increasing uptake of these interventions into routine care.MethodsWe applied the Translating Research into Practice (TRiP) framework to guide three phases of intervention design and development for diabetes prevention: (1) summarise the evidence, (2) identify local barriers to implementation and (3) measure performance. In phase 1, we conducted a retrospective cohort analysis of linked electronic health record claims data to evaluate current practices in the management of pre-diabetes. In phase 2, we conducted in-depth interviews of 16 primary care physicians, 7 payor leaders and 31 patients to elicit common barriers and facilitators for diabetes prevention. In phase 3, using findings from phases 1 and 2, we developed the core elements of the intervention and performance measures to evaluate intervention uptake.ResultsIn phase 1 (retrospective cohort analysis), we found few patients with pre-diabetes received diabetes prevention interventions. In phase 2 (stakeholder engagement), we identified common barriers to include a lack of knowledge about pre-diabetes among patients and about the Diabetes Prevention Program among clinicians. In phase 3 (intervention development), we developed the START Diabetes Prevention Clinical Pathway as a systematic change package to address barriers and facilitators identified in phases 1 and 2, performance measures and a toolkit of resources to support the intervention components.ConclusionsThe TRiP framework supported the identification of evidence-based care practices for pre-diabetes and the development of a well-fitted, actionable intervention and implementation plan designed to increase treatment uptake for pre-diabetes in primary care settings. Our change package can be adapted and used by other health systems or clinics to target prevention of diabetes or other related chronic conditions.

Antibody class switching in activated B cells uses class switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart. To test postulated roles of S regions and AID in CSR, we generated mutant B cells in which donor Sμ and accepter Sγ1 regions were replaced with yeast I-SceI endonuclease sites. We found that site-specific I-SceI DSBs mediate recombinational IgH locus class switching from IgM to IgG₁ without S regions or AID. We propose that CSR evolved to exploit a general DNA repair process that promotes joining of widely separated DSBs within a chromosome.

Background Type 2 diabetes can be prevented through lifestyle programs like the Diabetes Prevention Programs (DPP), but few people with prediabetes participate in them, in part because their insurance does not reliably cover DPPs. Prior studies have not focused on payor-level barriers. Objective To understand barriers to DPP uptake that exist and intersect at different levels (patients, PCPs, and payors) to inform strategies to improve diabetes prevention in primary care settings through interviews with PCPs and payors. Design From May 2020 to October 2021, we conducted remote, semi-structured interviews with PCPs and payors. Participants PCPs were from primary care practices affiliated with one mid-Atlantic academic system. Payor leaders were from regional commercial, Medicare, and Medicaid plans. Approach Using a standardized interview guide focused on barriers, facilitators, and potential intervention components, interviews were audio-recorded using Zoom and professionally transcribed. Two reviewers double-coded transcripts using the framework analytic approach. Key Results We interviewed 16 PCPs from 13 primary care clinics and 7 payor leaders representing 6 insurance plans. Two themes emerged from PCP reports of patient-level barriers: (1) lack of programs and insurance coverage of resources to address nutrition and exercise and (2) inadequate resources to address social determinants of health that impact diabetes prevention. Among barriers PCPs faced, we identified two themes: (1) low PCP knowledge about DPPs and misperceptions of insurance coverage of DPPs and (2) inadequate clinical staff to address diabetes prevention. Barriers common to PCPs and payors included (1) absence of prediabetes quality measures and (2) inadequate engagement of PCPs and patients with payors. Conclusions Discussions with PCPs and payors revealed systemic barriers that suggest important priorities to improve prediabetes clinical care, including universal coverage of DPPs, clarity about coverage benefits, data reporting and outreach by payors to PCPs, and adoption of appropriate prediabetes quality measures.

BackgroundThe incidence of diabetes in the general US population (6.7 per 1000 adults in 2018) has not changed significantly since 2000, suggesting that individuals with prediabetes are not connecting to evidence-based interventions.ObjectiveWe sought to describe the clinical care of individuals with prediabetes, determine patient factors associated with this care, and evaluate risk for diabetes development.DesignRetrospective cohort study using linked claims and electronic health record data.ParticipantsWe created a cohort of adults with prediabetes based on laboratory measures. We excluded patients with a prior history of diabetes, pregnancy in prior 6 months, or recent steroid use.Main MeasuresWe measured ordering and completion of clinical services targeting prediabetes management and diabetes incidence within 12 months following cohort entry. We tested the strength of the association between individuals’ characteristics and outcomes of interest using bivariate and multiple logistic regression.ResultsOur cohort included 3888 patients with a laboratory diagnosis of prediabetes (incident or prevalent prediabetes). Within 12 months, 63.4% had repeat glycemic testing, yet only 10.4% had coded diagnoses of prediabetes, 1.0% were referred for nutrition services, and 5.4% were prescribed metformin. Most patients completed labs and nutrition visits when referred and filled metformin when prescribed. Individuals with a higher glycemic level or BMI were more likely to receive prediabetes clinical care. Six percent of individuals developed diabetes within 12 months of cohort entry and had higher glycemic levels and BMI ≥ 30 kg/m2. In the adjusted model, Black individuals had 1.4 times higher odds of developing diabetes than White individuals.ConclusionsRates of prediabetes clinical care activities are low and have not improved. Strategies are urgently needed to improve prediabetes care delivery thereby preventing or delaying incident diabetes.

BackgroundPrediabetes affects 86 million US adults, but primary care providers’ (PCPs') knowledge, practices, attitudes and beliefs toward prediabetes are unclear.ObjectiveAssess PCPs’ (1) knowledge of risk factors that should prompt prediabetes screening, laboratory criteria for diagnosing prediabetes and guidelines for management of prediabetes; (2) management practices around prediabetes; (3) attitudes and beliefs about prediabetes.DesignSelf-administered written survey of PCPs.ParticipantsOne hundred forty of 155 PCPs (90%) attending an annual provider retreat for academically affiliated multispecialty practices in the mid-Atlantic region.Main measuresDescriptive analyses of survey questions on knowledge, management, and attitudes and beliefs related to prediabetes. Multivariate logistic regression was used to determine the association between provider characteristics (gender, race/ethnicity, years since training, specialty and provider type) and knowledge, management, and attitudes and beliefs about prediabetes.Key resultsSix percent of PCPs correctly identified all of the risk factors that should prompt prediabetes screening. Only 17% of PCPs correctly identified the laboratory parameters for diagnosing prediabetes based on both fasting glucose and hemoglobin A1c. Nearly 90% of PCPs reported close follow-up (within 6 months) of patients with prediabetes. Few PCPs (11%) selected referral to a behavioral weight loss program as the recommended initial management approach to prediabetes. PCPs agreed that patient-related factors are important barriers to lifestyle change and metformin use. Provider characteristics were generally not associated with knowledge, management, attitudes and beliefs about prediabetes in multivariate analyses.ConclusionsAddressing gaps in knowledge and the underutilization of behavioral weight loss programs in prediabetes are two essential areas where PCPs could take a lead in curbing the diabetes epidemic.

Type 2 diabetes can be prevented through lifestyle programs like the Diabetes Prevention Programs (DPP), but few people with prediabetes participate in them, in part because their insurance does not reliably cover DPPs. Prior studies have not focused on payor-level barriers. To understand barriers to DPP uptake that exist and intersect at different levels (patients, PCPs, and payors) to inform strategies to improve diabetes prevention in primary care settings through interviews with PCPs and payors. From May 2020 to October 2021, we conducted remote, semi-structured interviews with PCPs and payors. PCPs were from primary care practices affiliated with one mid-Atlantic academic system. Payor leaders were from regional commercial, Medicare, and Medicaid plans. Using a standardized interview guide focused on barriers, facilitators, and potential intervention components, interviews were audio-recorded using Zoom and professionally transcribed. Two reviewers double-coded transcripts using the framework analytic approach. We interviewed 16 PCPs from 13 primary care clinics and 7 payor leaders representing 6 insurance plans. Two themes emerged from PCP reports of patient-level barriers: (1) lack of programs and insurance coverage of resources to address nutrition and exercise and (2) inadequate resources to address social determinants of health that impact diabetes prevention. Among barriers PCPs faced, we identified two themes: (1) low PCP knowledge about DPPs and misperceptions of insurance coverage of DPPs and (2) inadequate clinical staff to address diabetes prevention. Barriers common to PCPs and payors included (1) absence of prediabetes quality measures and (2) inadequate engagement of PCPs and patients with payors. Discussions with PCPs and payors revealed systemic barriers that suggest important priorities to improve prediabetes clinical care, including universal coverage of DPPs, clarity about coverage benefits, data reporting and outreach by payors to PCPs, and adoption of appropriate prediabetes quality measures.

BackgroundThe United States is facing a primary care physician shortage. Internal medicine (IM) primary care residency programs have expanded substantially in the past several decades, but there is a paucity of literature on their characteristics and graduate outcomes.ObjectiveWe aimed to characterize the current US IM primary care residency landscape, assess graduate outcomes, and identify unique programmatic or curricular factors that may be associated with a high proportion of graduates pursuing primary care careers.DesignCross-sectional studyParticipantsSeventy out of 100 (70%) IM primary care program directors completed the survey.Main MeasuresDescriptive analyses of program characteristics, educational curricula, clinical training experiences, and graduate outcomes were performed. Bivariate and multivariate logistic regression analyses were used to determine the association between ≥ 50% of graduates in 2016 and 2017 entering a primary care career and program characteristics, educational curricula, and clinical training experiences.Key ResultsOver half of IM primary care program graduates in 2016 and 2017 pursued a primary care career upon residency graduation. The majority of program, curricular, and clinical training factors assessed were not associated with programs that have a majority of their graduates pursuing a primary care career path. However, programs with a majority of program graduates entering a primary care career were less likely to have X + Y scheduling compared to the other programs.ConclusionsIM primary care residency programs are generally succeeding in their mission in that the majority of graduates are heading into primary care careers.

BackgroundDespite strong evidence and national policy supporting type 2 diabetes prevention, little is known about type 2 diabetes prevention in the primary care setting.ObjectiveOur objective was to assess primary care physicians’ knowledge and practice regarding perceived barriers and potential interventions to improving management of prediabetes.DesignCross-sectional mailed survey.ParticipantsNationally representative random sample of US primary care physicians (PCPs) identified from the American Medical Association Physician Masterfile.Main MeasuresWe assessed PCP knowledge, practice behaviors, and perceptions related to prediabetes. We performed chi-square and Fisher’s exact tests to evaluate the association between PCP characteristics and the main survey outcomes.Key ResultsIn total, 298 (33%) eligible participants returned the survey. PCPs had limited knowledge of risk factors for prediabetes screening, laboratory diagnostic criteria for prediabetes, and management recommendations for patients with prediabetes. Only 36% of PCPs refer patients to a diabetes prevention lifestyle change program as their initial management approach, while 43% discuss starting metformin for prediabetes. PCPs believed that barriers to type 2 diabetes prevention are both at the individual level (e.g., patients’ lack of motivation) and at the system level (e.g., lack of weight loss resources). PCPs reported that increased access to and insurance coverage of type 2 diabetes prevention programs and coordination of referral of patients to these resources would facilitate type 2 diabetes preventive efforts.ConclusionsAddressing gaps in PCP knowledge may improve the identification and management of people with prediabetes, but system-level changes are necessary to support type 2 diabetes prevention in the primary care setting.