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Context: Understanding mental health issues facing individuals with disorders/differences of sex development (DSD) is crucial for optimizing evidence-based practices in this population., Objectives: To compare the prevalence of psychiatric diagnoses among patients diagnosed with complete androgen insensitivity syndrome (CAIS) or Müllerian duct aplasia/agenesis (MA) to male and female reference groups., Design: Retrospective cohort study., Setting: Three large integrated health systems., Participants: All individuals with confirmed CAIS or MA enrolled in one of three Kaiser Permanente healthcare systems between January 1, 1988, and January 31, 2017. For each DSD patient, age-, race/ethnicity- and health system-matched male and female referents with typical sex development were randomly selected., Outcomes/measures: Mental health diagnoses and use of psychiatric medications., Results: The prevalence of anxiety and depressive disorders in the CAIS and MA cohorts was approximately twice as high as in male referents without DSD, but the corresponding differences relative to female referents were less evident. A subgroup of MA patients with uterine agenesis had higher prevalence of bipolar disorder than either reference group, but these results were accompanied by wide confidence intervals. Women with CAIS and MA more frequently filled psychiatric medications compared to male but not female referents., Conclusion: On balance, these findings are reassuring, albeit requiring confirmation in other settings. Future studies using longitudinal designs and patient-reported outcomes are needed to evaluate changes in mental health status of CAIS and MA patients at different ages and different intervals following initial diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: To examine anthropometric changes of patients with classic 46,XX congenital adrenal hyperplasia (CAH) and matched referents; and 2) To investigate the impact of improvements in diagnosis and care on growth patterns in these patients by comparing changes in anthropometric parameters before and after CAH consensus guidelines., Methods: This was a retrospective cohort study nested within 3 large integrated health-systems. Seventy-six patients with classic 46XX CAH and 1102 matched referents <21 years of age were identified. Anthropometric measurements including age-specific percentiles for height, weight, and body mass index were examined and compared between groups using linear mixed-effect models. Anthropometric trajectories were explored using latent class analyses., Results: CAH patients had lower height percentiles than referents at all time points. Differences ranged from 10.7% to 28.4%. After age 5, differences in height were only significant among study participants born before the publication of CAH consensus guidelines. Latent class analyses of height detected a "gradual growth increase" pattern in 28% of CAH cases and only 4% of referents, and a "growth stunting" pattern was observed in 13% of CAH cases and 6% of referents. Height percentile measures did not differ in CAH patients with or without evidence of hormonal interventions (growth hormone and/or puberty blockers) used to increase adult height., Conclusions: There is substantial heterogeneity in growth trajectories of CAH patients. Although stunting may affect CAH patients, advances in diagnosis and care improved anthropometric outcomes in this population. Understanding the disease- and therapy-related mechanisms that explain the different growth patterns requires additional research., Competing Interests: Disclosure Dr Goodman provides consulting services through Epidemiologic Research & Methods, LLC; his consulting services are not related to the topic of this publication., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Introduction: Obesity affects four in ten US adults. One of the most prevalent health-related social risk factors in the US is housing instability, which is also associated with cardiovascular health outcomes, including obesity. The objective of this research brief is to examine the association between housing instability with obesity status among a representative sample of insured adults across seven integrated health systems., Methods: Kaiser Permanente National Social Needs Survey used a multistage stratified sampling framework to administer a cross-sectional survey across seven integrated health systems (administered Jan.-Sept. 2020). Survey data were linked with electronic health records (EHR). Housing instability was categorized into levels of risk: (1) "No Risk"; (2) "Moderate Risk"; and (3) "Severe Risk." Based on established BMI thresholds, obesity, and severe obesity served as the primary outcome variables. In 2023, weighted multivariable logistic regression accounted for the complex sampling design and response probability and controlled for covariates., Results: The analytic cohort comprised 6,397 adults. Unadjusted weighted prevalence of obesity and severe obesity was 31.1% and 5.3%, respectively; and 15.5% reported housing instability. Adjusted regression models showed that the odds of severe obesity was nearly double among adults exposed to severe housing instability (Adjusted OR=1.93; 95% CI 1.14-3.26). Other BMI categories were not associated with housing instability., Conclusions: Among a representative cohort of insured adults, this study suggested increasing levels of housing instability are associated with increasing levels of obesity. Future research should further explore the temporal, longitudinal, and independent association of housing instability with obesity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To compare the associations of race, ethnicity, and socioeconomic status (SES) with visual impairment (VI) before surgical removal of cataracts across 2 health systems in the United States Mid-Atlantic region., Design: Multi-institutional cross-sectional study., Participants: Patients ≥ 65 years of age who underwent cataract surgery at Johns Hopkins Hospital (JHH) and Kaiser Permanente (KP) between January 1, 2017, and December 31, 2019., Methods: Covariates included patient age, sex, smoking status, surgery laterality, Charlson comorbidity index, and ocular comorbidities. Multivariable generalized estimating equation models were used to examine the association of race, ethnicity, and area deprivation index (ADI) with visual acuity., Main Outcome Measures: Visual acuity before cataract surgery was assessed using logarithm of minimum angle of resolution values. Race, ethnicity, and ADI were the main exposures of interest., Results: At JHH, 11 509 patients (17 731 eyes) were included, whereas KP included 7143 patients (10 542 eyes). After adjusting for covariates, Black patients (β = 0.49), Asian patients (β = 0.83), and Hispanic patients (β = 0.95) were more likely to have worse visual acuity at JHH (P < 0.001 for all) compared with White patients. Similarly, at KP, Black patients (β = 0.56), Asian patients (β = 0.70), and Hispanic patients (β = 0.89) were more likely to have worse visual acuity (P < 0.001 for all) compared with White patients. Compared with those living in the least disadvantaged neighborhoods at JHH, higher ADI quartiles (more deprived) were more likely to have worse visual acuity (β = 0.27 [P < 0.001] for quartile 2; β = 0.40 [P = 0.001] for quartile 3; β = 0.95 [P < 0.001] for quartile 4). No significant association was found between ADI and VI at KP., Conclusions: Among older adults, non-White race or ethnicity was associated independently with VI secondary to cataracts in 2 large health systems in the United States Mid-Atlantic region, after adjustment for ADI. Area deprivation also was associated with VI but only in the JHH system. Our study suggests that non-White patients and those with lower SES are at greater risk of VI secondary to cataracts possibly because of social, structural, and institutional barriers., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Context: The long-term effect of gender-affirming hormone therapy (GAHT) on glucose metabolism is an area of priority in transgender health research., Objectives: To evaluate the relation between GAHT and changes in fasting blood glucose (FG) and glycosylated hemoglobin (HbA1c) in transmasculine (TM) and transfeminine (TF) persons relative to the corresponding temporal changes in presumably cisgender persons (i.e. without any evidence of TGD status)., Design: Retrospective cohort study., Setting: Three large integrated health systems., Participants: 2,425 TF and 2,127 TM persons compared with 33,995 cisgender males (CM) and 38,913 cisgender females (CF) enrolled in the same health plans., Outcomes/measures: Temporal changes in FG and HbA1c levels examined using linear mixed models with main results expressed as ratios-of-ratios., Results: The pre- versus post-GAHT ratios-of-ratio (95% confidence interval) estimates adjusted for age, race/ethnicity, study site, and body mass index in the model comparing TF and CM groups were 1.05 (1.01, 1.09) for FG and 1.03 (0.99, 1.06) for HbA1c. By contrast, the corresponding results in the models contrasting TM and cisgender cohort members were in the 0.99-1.00 range. The ratio-of-ratios comparing post-GAHT changes among transgender and cisgender persons were close to the null and without a discernable pattern., Conclusion: Though the within-transgender cohort data suggest an increase in the levels of FG and HbA1c following feminizing GAHT initiation, these changes were no longer evident when compared with the corresponding changes in cisgender referents. Based on these results, clinically important effects of GAHT on routine laboratory markers of glucose metabolism appear unlikely., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: Heart failure risk is elevated in people with HIV (PWH). We investigated whether initial antiretroviral therapy (ART) regimens influenced heart failure risk., Design: Cohort study., Methods: PWH who initiated an ART regimen between 2000 and 2016 were identified from three integrated healthcare systems. We evaluated heart failure risk by protease inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTI), and integrase strand transfer inhibitor (INSTI)-based ART, and comparing two common nucleotide reverse transcriptase inhibitors: tenofovir disoproxil fumarate (tenofovir) and abacavir. Follow-up for each pairwise comparison varied (i.e. 7 years for protease inhibitor vs. NNRTI; 5 years for tenofovir vs. abacavir; 2 years for INSTIs vs. PIs or NNRTIs). Hazard ratios were from working logistic marginal structural models, fitted with inverse probability weighting to adjust for demographics, and traditional cardiovascular risk factors., Results: Thirteen thousand six hundred and thirty-four PWH were included (88% men, median 40 years of age; 34% non-Hispanic white, 24% non-Hispanic black, and 24% Hispanic). The hazard ratio (95% CI) were: 2.5 (1.5-4.3) for protease inhibitor vs. NNRTI-based ART (reference); 0.5 (0.2-1.8) for protease inhibitor vs. INSTI-based ART (reference); 0.1 (0.1-0.8) for NNRTI vs. INSTI-based ART (reference); and 1.7 (0.5-5.7) for tenofovir vs. abacavir (reference). In more complex models of cumulative incidence that accounted for possible nonproportional hazards over time, the only remaining finding was evidence of a higher risk of heart failure for protease inhibitor compared with NNRTI-based regimens (1.8 vs. 0.8%; P  = 0.002)., Conclusion: PWH initiating protease inhibitors may be at higher risk of heart failure compared with those initiating NNRTIs. Future studies with longer follow-up with INSTI-based and other specific ART are warranted., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Compare occurrence of self-inflicted injuries among transgender and gender diverse (TGD) youth to that of their cisgender peers while accounting for mental health diagnoses., Methods: Review of electronic health records from three integrated health care systems identified 1087 transfeminine and 1431 transmasculine adolescents and young adults. Poisson regression was used to calculate prevalence ratios comparing the proportion of TGD participants with at least one self-inflicted injury (a surrogate for suicide attempt) before index date (first evidence of TGD status) to the corresponding proportions in presumed cisgender male and female referents matched on age, race/ethnicity, and health plan. Interactions between gender identities and mental health diagnoses were assessed on multiplicative and additive scales., Results: TGD adolescents and young adults were more likely to have a self-inflicted injury, various mental health diagnoses, and multiple mental health diagnoses than their cisgender peers. The prevalence of self-inflicted injuries among TGD adolescents and young adults was high even in the absence of mental health diagnoses. Results were consistent with positive additive interaction and negative multiplicative interaction., Conclusions: Universal suicide prevention efforts for all youth, including those with no mental health diagnoses, and more intensive suicide prevention efforts for TGD adolescents and young adults and those with at least one mental health diagnosis are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The strategies patients use to organize medications (eg, pill dispenser) may be reflected in adherence measured at follow-up. We studied whether medication organization strategies patients use at home are associated with adherence measured using pharmacy-fills, self-report, and pill counts., Design: Secondary analysis of data from a prospective randomized clinical trial., Setting: Eleven US safety-net and community primary care clinics., Patients: Of the 960 enrolled self-identified non-Hispanic Black and White patients prescribed antihypertensive medications, 731 patients reported pill organization strategies and were included., Variable: Patients were asked if they use any of the following medication organization strategies: finish previous refills first; use a pill dispenser; combine same prescriptions; or combine dissimilar prescriptions., Outcomes: Adherence to antihypertensive medications using pill counts (range, 0.0-1.0% of the days covered), pharmacy-fill (proportion of days covered >90%), and self-report (adherent/non-adherent)., Results: Of the 731 participants, 38.3% were men, 51.7% were age ≥65, 52.9% self-identified as Black or African American. Of the strategies studied, 51.7% finished previous refills first, 46.5% used a pill dispenser, 38.2% combined same prescriptions and 6.0% combined dissimilar prescriptions. Median (IQR) pill count adherence was 0.65 (0.40-0.87), pharmacy-fill adherence was 75.7%, and self-reported adherence was 63.2%. Those who combined same prescriptions had significantly lower measured pill count adherence than those who did not (0.56 (0.26-0.82) vs 0.70 (0.46-0.90), p<0.01) with no significant difference in pharmacy-fill (78.1% vs 74%, p=0.22) or self-reported adherence (63.0% vs 63.3%, p=0.93)., Conclusion: Self-reported medication organization strategies were common. Combining same prescriptions was associated with lower adherence as measured using pill counts but not pharmacy-fills or self-report. Clinicians and researchers should identify the pill organization strategies used by their patients to understand how these strategies may influence measures of patient adherence., Trial Registration: ClinicalTrials.gov NCT03028597; https://clinicaltrials.gov/ct2/show/NCT03028597 (Archived by WebCite at http://www.webcitation.org/72vcZMzAB)., Competing Interests: Dr Stacie L. Daugherty is also supported by NIH grant DC0169065, NIH grant HL164106, a grant from PCORI and serves on a DSMB for another NHBLI funded trial; also reports royalties for review of cardiovascular risk factors in women from UpToDate. Dr John F. Steiner is supported by research funding from the National Institute of Diabetes, Digestive and Kidney Diseases (grant # P30DK092923) and by internal research funding from Kaiser Permanente. Dr Suma Vupputuri is supported by research funding from Sanofi, Inc. All other authors report no additional conflicts in relation to this manuscript., (© 2023 Genelin et al.)

In the United States, hypertension is more common among individuals from racial and ethnic minority groups. Hypertension control rates are also lower for minority group members compared with White Americans. However, little research has employed well-established theoretical perspectives on health behavior, such as the Theory of Planned Behavior (TPB) and the Model of Goal-Directed Behavior (MGB), to better understand racial differences in rates of hypertension control. The present study examines the psychological processes involved in efforts to control blood pressure, through the lens of the TPB augmented by the MGB, in hypertensive patients of three racial groups: American Indian/Alaska Native, Black/African American, and White. Participants completed measures of past efforts to control blood pressure, attitudes, norms, perceived behavioral control, intentions, and anticipated emotions. Analyses employed confirmatory factor analysis and cross-groups path analysis. Measurement of the theoretical constructs and core putative mediators of blood pressure control intentions were largely similar across racial groups. With regard to the patterns of relationships among the constructs, differences among the groups were most apparent in pathways from past efforts to both cognitive and affective theoretical antecedents of intentions. These findings contribute to the sparse literature on factors involved in racial differences in hypertension control rates and may inform future interventions aimed at increasing hypertension control behaviors. Trial Registration ClinicalTrials.gov, NCT03028597, registered 23 January 2017, https://clinicaltrials.gov/ct2/show/NCT03028597; ClinicalTrials.gov, NCT04414982, registered 4 June 2020 (retrospectively registered), https://www.clinicaltrials.gov/ct2/show/NCT04414982., Competing Interests: Conflict of interest The authors declare that they have no competing interests.

Background: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood., Setting: Integrated health care system., Methods: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex., Results: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively)., Conclusions: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS)., Participants: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation., Findings to Date: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS., Future Plans: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preemptive kidney transplant (PKT) is recognized as the most beneficial and cost-effective form of renal replacement therapy among patients with end-stage renal disease. Despite optimal outcomes and improved quality of life associated with PKT, its use as a first renal replacement therapy remains low among patients with end-stage renal disease. The goal of this retrospective cohort study was to compare, among adult kidney transplant recipients, characteristics across PKT status., Methods: We compared the characteristics of patients who did and did not have a PKT over 5 years, from 2010 to 2014, using the electronic health records of Kaiser Permanente Mid-Atlantic States., Results: A total of 233 patients received a kidney-alone transplant, and, of these, 44 patients (19%) were PKT and 189 patients (81%) were non-PKT. Of the patients in the PKT group, 43% received a kidney from a deceased donor. PKT recipients were more often White, had polycystic kidney disease or glomerulonephritis, received a living donor organ, and were transplanted at certain transplant centers. Estimated glomerular filtration rate on listing for those who received a deceased donor transplant was higher in PKT than non-PKT patients listed pre-dialysis., Conclusions: PKT was associated with having a living kidney donor and with having a higher estimated glomerular filtration rate at listing for deceased donor recipients., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Risk of type 2 diabetes mellitus (T2DM) in transgender and gender diverse (TGD) persons, especially those receiving gender-affirming hormone therapy (GAHT) is an area of clinical and research importance., Methods: We used data from an electronic health record-based cohort study of persons 18 years and older enrolled in 3 integrated health care systems. The cohort included 2869 transfeminine members matched to 28 300 cisgender women and 28 258 cisgender men on age, race/ethnicity, calendar year, and site, and 2133 transmasculine members similarly matched to 20 997 cisgender women and 20 964 cisgender men. Cohort ascertainment spanned 9 years from 2006 through 2014 and follow-up extended through 2016. Data on T2DM incidence and prevalence were analyzed using Cox proportional hazards and logistic regression models, respectively. All analyses controlled for body mass index., Results: Both prevalent and incident T2DM was more common in the transfeminine cohort relative to cisgender female referents with odds ratio and hazard ratio (95% CI) estimates of 1.3 (1.1-1.5) and 1.4 (1.1-1.8), respectively. No significant differences in prevalence or incidence of T2DM were observed across the remaining comparison groups, both overall and in TGD persons with evidence of GAHT receipt., Conclusion: Although transfeminine people may be at higher risk for T2DM compared with cisgender females, the corresponding difference relative to cisgender males is not discernable. Moreover, there is little evidence that T2DM occurrence in either transfeminine or transmasculine persons is attributable to GAHT use., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To evaluate the risk of heart failure (HF) linked to human immunodeficiency virus (HIV) infection, how risk varies by demographic characteristics, and whether it is explained by atherosclerotic disease or risk factor treatment., Patients and Methods: We performed a retrospective cohort study of persons with HIV (PWHs) from January 1, 2000, through December 31, 2016, frequency-matched 1:10 to persons without HIV on year of entry, age, sex, race/ethnicity, and treating facility. We evaluated the risk of incident HF associated with HIV infection, overall and by left ventricular systolic function, and whether HF risk varied by demographic characteristics., Results: Among 38,868 PWHs and 386,586 matched persons without HIV, mean ± SD age was 41.4±10.8 years, with 12.3% female, 21.1% Black, 20.5% Hispanic, and 3.9% Asian/Pacific Islander. During median follow-up of 3.8 years (interquartile range, 1.4-9.0 years), the rate (per 100 person-years) of incident HF was 0.23 in PWHs vs 0.15 in those without HIV (P<.001). The PWHs had a higher adjusted HF rate (adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.57 to 1.91), which was only modestly attenuated after accounting for interim acute coronary syndrome events. Results were similar by systolic function category. The adjusted risk of HF in PWHs was more prominent for those 40 years and younger (aHR, 2.45; 95% CI, 1.92 to 3.03), women (aHR, 2.48; 95% CI, 1.90 to 3.26), and Asian/Pacific Islanders (aHR, 2.46; 95% CI, 1.27 to 4.74)., Conclusion: HIV infection increases the risk of HF, which varied by demographic characteristics and was not primarily mediated through atherosclerotic disease pathways or differential use of cardiopreventive medications., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences subsequent morbidity and mortality remains unclear., Methods and Results: We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large US integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios (aHRs) by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3429 without HIV who developed HF from a frequency-matched source cohort of 38 868 PLWH and 386 586 without HIV. Mean age was 59.5 ± 11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization [aHR 1.01, 95% confidence interval (CI): 0.81-1.26] and of HF-related ED visits [aHR 1.22 (95% CI: 0.99-1.50)], but higher adjusted rates of all-cause death [aHR 1.31 (95% CI: 1.08-1.58)]. Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count <200 or 200-499 cells/μL., Conclusion: In a large, diverse cohort of adults with incident HF receiving care within integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Stereotype threat, or the fear of confirming a negative stereotype about one's social group, may contribute to racial differences in adherence to medications by decreasing patient activation to manage chronic conditions., Objective: To examine whether a values affirmation writing exercise improves medication adherence and whether the effect differs by patient race., Design, Setting, and Participants: The Hypertension and Values trial, a patient-level, blinded randomized clinical trial, compared an intervention and a control writing exercise delivered immediately prior to a clinic appointment. Of 20 777 eligible, self-identified non-Hispanic Black and White patients with uncontrolled hypertension who were taking blood pressure (BP) medications, 3891 were approached and 960 enrolled. Block randomization by self-identified race ensured balanced randomization. Patients enrolled between February 1, 2017, and December 31, 2019, at 11 US safety-net and community primary care clinics, with outcomes assessed at 3 and 6 months. Analysis was performed on an intention-to-treat basis., Interventions: From a list of 11 values, intervention patients wrote about their most important values and control patients wrote about their least important values., Main Outcomes and Measures: The primary outcome of adherence to BP medications was measured using pharmacy fill data (proportion of days covered >90%) at baseline, 3 months, and 6 months. The secondary outcome was systolic and diastolic BP. Patient activation to manage their health was also measured., Results: Of 960 patients, 474 (286 women [60.3%]; 256 Black patients [54.0%]; mean [SD] age, 63.4 [11.9] years) were randomly assigned to the intervention group and 486 (288 women [59.3%]; 272 Black patients [56.0%]; mean [SD] age, 62.8 [12.0] years) to the control group. Baseline medication adherence was lower (318 of 482 [66.0%] vs 331 of 412 [80.3%]) and mean (SE) BP higher among Black patients compared with White patients (systolic BP, 140.6 [18.5] vs 137.3 [17.8] mm Hg; diastolic BP, 83.9 [12.6] vs 79.7 [11.3] mm Hg). Compared with baseline, pharmacy fill adherence did not differ between intervention and control groups at 3 months (odds ratio [OR], 0.91 [95% CI, 0.57-1.43]) or at 6 months (OR, 0.86 [95% CI, 0.53-1.38]). There were also no treatment effect differences in pharmacy fill adherence by patient race (Black patients at 3 months: OR, 1.08 [95% CI, 0.61-1.92]; at 6 months: OR, 1.04 [95% CI, 0.58-1.87]; White patients at 3 months: OR, 0.68 [95% CI, 0.33-1.44]; at 6 months: OR, 0.55 [95% CI, 0.24-1.27]). Immediately after the intervention, the median patient activation was higher in intervention patients than in control patients, but this difference was not statistically significant in an unadjusted comparison (75.0 [IQR, 65.5-84.8] vs 72.5 [IQR, 63.1-80.9]; P = .06). In adjusted models, the Patient Activation Measure score immediately after the intervention was significantly higher in the intervention patients than in control patients (mean difference, 2.3 [95% CI, 0.1-4.5])., Conclusions and Relevance: A values affirmation intervention was associated with higher patient activation overall but did not improve adherence or blood pressure among Black and White patients with hypertension., Trial Registration: ClinicalTrials.gov Identifier: NCT03028597.

Introduction: Workplace violence is prevalent in the emergency department, putting patients and staff at risk for harm. An ED-specific standardized tool is needed to promote a consistent assessment process to strengthen documentation of escalating patient behaviors, give justification for de-escalating interventions, and reduce restraints. The purpose of this project was to design, implement, and evaluate feasibility of an ED-specific tool to help nurses proactively identify and intervene with patients' escalating behaviors, capture better documentation of aggressive/violent patient events, and reduce restraint usage., Methods: A quality improvement design was used. The Emergent Documentation Aggression Rating Tool was constructed by combining evidence-based behavioral cues for potential aggression/violence with observed behaviors and successfully implemented interventions in patients. Nurses were trained on how to use the tool to rate patients' behaviors and take necessary action. Chart data were collected from August 2018 to December 2019 at a Midwestern suburban hospital emergency department. Chart audits and just-in-time education were conducted after implementation. Survey data were collected to evaluate nurses' perception of the tool's usefulness., Results: Use of the novel Emergent Documentation Aggression Rating Tool increased over time (67.36% in Quarter 3 2018 to 97.55% in Quarter 4 2019). After Emergent Documentation Aggression Rating Tool implementation, visual inspection of the time series indicated a decrease in percent restraints, and there was an overall increase in documented escalations de-escalations over time. The patients that escalated most frequently had diagnoses of alcohol use, suicidal ideations, pain-related complaints, or mental health issues., Conclusion: The Emergent Documentation Aggression Rating Tool was feasible for emergency nurses to proactively identify and intervene with patients at risk for aggression/violence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health., Aim: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation., Methods: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs)., Outcomes: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents., Results: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity., Clinical Implications: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels., Strength and Limitations: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration., Conclusion: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The progression of gender-expansive behavior to gender dysphoria and to gender-affirming hormonal treatment (GAHT) in children and adolescents is poorly understood., Methods: A cohort of 958 gender-diverse (GD) children and adolescents who did not have a gender dysphoria-related diagnosis (GDRD) or GAHT at index were identified. Rates of first GDRD and first GAHT prescription were compared across demographic groups., Results: Overall, 29% of participants received a GDRD and 25% were prescribed GAHT during the average follow-up of 3.5 years (maximum 9 years). Compared with youth assigned male sex at birth, those assigned female sex at birth were more likely to receive a diagnosis and initiate GAHT with hazard ratio (95% confidence interval) estimates of 1.3 (1.0-1.7), and 2.5 (1.8-3.3), respectively. A progression to diagnosis was more common among those aged ≥15 years at initial presentation compared with those aged 10 to 14 years and those aged 3 to 9 years (37% vs 28% vs 16%, respectively). By using the youngest group as a reference, the adjusted hazard ratios (95% confidence interval) for a GDRD were 2.0 (1.3-3.0) for age 10 to 14 years and 2.7 (1.8-3.9) for age ≥15 years. Racial and ethnic minorities were less likely to receive a diagnosis or be prescribed GAHT., Conclusions: This study characterized the progression of GD behavior in children and adolescents. Less than one-third of GD youth receive an eventual GDRD, and approximately one-quarter receive GAHT. Female sex at birth, older age of initial GD presentation to medical care, and non-Hispanic white race and ethnicity increased the likelihood of receiving diagnosis and treatment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Transgender and gender nonconforming (TGNC) patients have been seeking medical care in higher numbers and have faced unique social, personal, and health issues that affect the quality of care they receive. The purpose of this study was to conduct a mixed-methods study to describe TGNC care at Kaiser Permanente Mid-Atlantic States, a large integrated health system. We used a transgender registry to describe a TGNC patient population and compared healthcare utilization between TGNC patients and non-TGNC patients. Four focus groups were also conducted among 28 patients. Atlas.ti software was used to code and analyze themes for the qualitative analysis. Among the 282 adults TGNC patients, the mean age was 32.6 years. Of the study sample, 59% were White, and 27% were Black. TGNC patients demonstrated an increased use of email/telephone visits and the online patient portal and more cancellations and no-shows compared to non-TGNC controls. Of the 28 TGNC patients who participated in the focus groups, 39% identified as female, 21% as a transman, and 18% as non-binary/genderqueer. Participants were predominantly White (68%), highly educated (74%), and reported use of hormones (89%). Themes that emerged from our qualitative analysis included: limited availability of TGNC information; positive and negative sentiments regarding patient-provider interactions; issues with case management; limited access to care; lack of coordination of care; negative staff experiences. We identified specific areas in a health system to improve the quality of care of TGNC patients, including specific TGNC training for providers and staff, a source of TGNC information/resources, and hiring and training TGNC-specific case managers.

Objective: To examine temporal changes in the number and demographic composition of transgender/gender non-binary (TGNB) population using data from integrated health care systems., Methods: Electronic health records from Kaiser Permanente health plans in Georgia and Northern and Southern California were used to identify TGNB individuals, who sought care from January 2006 to December 2014, and the data were analyzed by year, site, age, and sex assigned at birth., Results: In 2006, the number of TGNB people (and corresponding 95% CI) per 100 000 population were 3.5 (1.9, 6.3) in Georgia, 5.5 (4.8, 6.4) in Southern California, and 17 (16, 19) in Northern California. In 2014, these frequencies increased to 38 (32, 45), 44 (42, 46), and 75 (72, 78) per 100 000 population, respectively. When analyzed by age, the most rapid increase was observed among persons 18 to 25 years old, and this increase accelerated after 2010. The ratio of transmasculine to transfeminine persons also changed from 1:1.7 in 2006 to 1:1 in 2014 overall and from 1:1 in 2006 to 1.8:1 in 2014 among persons <18 years of age., Conclusion: This analysis confirms previous observations that the proportion of TGNB people is growing, especially among young adults. The composition of the TGNB population is also changing from predominantly transfeminine to roughly 1:1 overall and to predominantly transmasculine in children and adolescents., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Limited data exist that comprehensively describe the practical management, in-hospital outcomes, healthcare resource utilization, and rates of post-hospital readmission among patients with submassive and massive pulmonary embolism (PE). Consecutive discharges for acute PE were identified from a single health system over 3 years. Records were audited to confirm presence of acute PE, patient characteristics, disease severity, medical treatment, and PE-related invasive therapies. Rates of in-hospital major bleeding and death, hospital length of stay (LOS), direct costs, and hospital readmission are reported. From January 2016 to December 2018, 371 patients were hospitalized for acute massive or submassive PE. In-hospital major bleeding (12.1%) was common, despite low utilization of systemic thrombolysis (1.8%) or catheter-directed thrombolysis (3.0%). In-hospital death was 10-fold higher among massive PE compared to submassive PE (36.6% vs 3.3%, p < 0.001). Massive PE was more common during hospitalizations not primarily related to venous thromboembolism, including hospitalizations primarily for sepsis or infection (26.8% vs 8.2%, p = 0.001). Overall, the median LOS was 6.0 days (IQR, 3.0-11.0) and the median standardized direct cost of admissions was $10,032 (IQR, $4467-$20,330). Rates of all-cause readmission were relatively high throughout late follow-up but did not differ between PE subgroups. Despite low utilization of thrombolysis, in-hospital bleeding remains a common adverse event during hospitalizations for acute PE. Although massive PE is associated with high risk for in-hospital bleeding and death, those successfully discharged after a massive PE demonstrate similar rates of readmission compared to submassive PE into late follow-up.

Introduction: Despite the proven efficacy of plant-based diets in the management of cardiometabolic diseases, most healthcare providers do not incorporate them into treatment plans., Objective: Conduct a post-hoc evaluation of a novel plant-based nutrition program in a large integrated health care system, including the impact on health care outcomes., Methods: A large integrated health care system launched an innovative 12-week plant-based nutrition program that included weekly nutrition education, peer mentoring, and support. Plasma cholesterol levels, hemoglobin A1C, blood pressure, body weight, and healthcare utilization parameters were measured before and after the program. The current study is a pre- and post-descriptive analysis of the health metrics of individuals who participated in the program and a matched comparison group., Results: A total of 408 patients, across a wide range of weight categories, demographics, and co-morbidities, participated in a plant-based nutrition program, and program completers experienced mean reductions in total and LDL plasma cholesterol levels of 11.0 and 8.1 mg/dL, respectively, as well as reductions in medication usage, office visits, and body weight., Conclusion: Implementation of a novel plant-based, nutrition program in a large integrated health care system was associated with improvements in health outcomes.

Three-dimensional polyaniline (PANI) hydrogel was used as the conductive medium to improve the methane (CH 4 ) production from the anaerobic degradation of organics in wastewater. The porous structure and hydrophilic surface of the PANI hydrogel promoted the adhesion of the anaerobes. The PANI hydrogel existed as a conductive emeraldine base (EB) form with a conductivity of 0.42 S/cm, and had a good biocompatibility with the microorganisms in the anaerobic system. The conductive PANI hydrogel was added into the anaerobic sludge as the conductive medium of the direct interspecies electron transfer (DIET) between bacteria and archaea, accelerating CH 4 production during the biodegradation of organic pollutants. The results indicated that the CH 4 production rate was increased by 10.50%, 14.21%, 28.77% and 19.30% from the anaerobic system with adding 1000, 2000, 3000 and 4000 mg/L of PANI hydrogel. The proportion of Methanosaeta in the anaerobic sludge with the ability of DIET was increased to 64.74% after adding the PANI hydrogel. The conductive PANI hydrogel served as an electronic channel to enrich the microorganism with the DIET ability, which was responsible for PANI hydrogel improved CH 4 production., 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 © 2020 Elsevier Inc. All rights reserved.)

Background Direct-acting oral anticoagulants are now the preferred method of anticoagulation in patients with atrial fibrillation. Limited data on efficacy and safety of these fixed-dose regimens are available in severe obesity where drug pharmacokinetics and pharmacodynamics may be altered. The objectives of this study were to evaluate efficacy and safety in patients with atrial fibrillation taking direct-acting oral anticoagulants across body mass index (BMI) categories in a contemporary, real-world population. Methods and Results We performed a retrospective study of patients with atrial fibrillation at an integrated multisite healthcare system. Patients receiving a direct-acting oral anticoagulant prescription and ≥12 months of follow-up between 2010 and 2017 were included. The primary efficacy and safety outcomes were ischemic stroke or systemic embolism and intracranial hemorrhage. We performed Cox proportional hazards modeling to compute hazard ratios (HRs) adjusted for CHA 2 DS 2 -VASc score to examine differences by excess BMI categories relative to normal BMI. Of 7642 patients, mean±SD age was 69±12 years with a median (interquartile range) follow-up of 3.8 (2.2-6.0) years. Approximately 22% had class 1 obesity and 19% had class 2 or 3 obesity. Stroke risks were similar in patients with and without obesity (HR, 1.2; 95% CI, 0.5-2.9; and HR, 0.68; 95% CI, 0.23-2.0 for class 1 and class 2 or 3 obesity compared with normal BMI, respectively). Risk of intracranial hemorrhage was also similar in class 1 and class 2 or 3 obesity compared with normal BMI (HR, 0.64; 95% CI, 0.35-1.2; and HR, 0.66; 95% CI, 0.35-1.2, respectively). Conclusions Direct-acting oral anticoagulants demonstrated similar efficacy and safety across all BMI categories, even at high weight values.

Background: Transgender and gender-nonconforming (TGNC) patients have inadequate quality of care. Few studies have examined the issues related to quality of care from the perspective of providers. The purpose of this pilot study was to understand the barriers and facilitators of quality TGNC care and develop recommendations for health systems., Methods: We used phenomenological methods in the form of qualitative semistructured interviews to allow provider participants to elaborate about issues not covered in the script questions. Audio files from 11 provider interviews were transcribed and summarized by common themes. Thematic analysis was conducted in an iterative process to extract insights from the data., Results: Six main subthemes resulted from our qualitative review regarding "barriers to quality care": 1) provider training and knowledge of TGNC care, 2) provider and staff interactions with TGNC patients, 3) case management, 4) misgendering, 5) access and continuity of care, and 6) bias and discrimination. Four subthemes were identified as "facilitators of quality care" for TGNC patients: 1) skilled staff, 2) continuity of care and electronic health records, 3) organizational support, and 4) provider-patient interactions. Additional needs were also suggested., Conclusions: Findings were distilled into 3 recommendations to improve the quality of TGNC care: 1) establish a dedicated case-management team; 2) provide access to more in-depth and meaningful training for providers, clinic staff, and administrative staff (and mandate certain basic training); and 3) allocate financial resources and enforce a policy of nondiscrimination., (Copyright © 2020 The Permanente Press. All rights reserved.)

Background: Visual conformity with affirmed gender (VCAG) or "passing" is thought to be an important, but poorly understood, determinant of well-being in transgender people. VCAG is a subjective measure that is different from having an inner sense of being congruent with one's gender identity., Aim: We examined the frequency and determinants of VCAG and explored its association with mental health outcomes in a cohort of transgender adults., Methods: The "Study of Transition, Outcomes & Gender (STRONG)" is a cohort of transgender individuals recruited from 3 Kaiser Permanente health plans located in Georgia, Northern California and Southern California. A subset of cohort members completed a survey between 2015 and 2017. VCAG was assessed as the difference between 2 scales: scale 1 reflecting the person's sense of how they are perceived by others, and scale 2 reflecting the person's desire to be perceived. Participants were considered to have achieved VCAG when their scale 1 scores were equal to or exceeded their scale 2 scores. The frequency of VCAG and their independent associations with anxiety and depression symptoms were explored using data from 620 survey respondents including 309 transwomen and 311 transmen. Based on self-described gender identity, none of the participants identified as nonbinary or gender fluid., Outcomes: VCAG, depression, and anxiety., Results: VCAG was achieved in 28% of transwomen and 62% of transmen and was more common in persons who reported greater sense of acceptance and pride in their gender identity as measured on the Transgender Congruence Scale. Another factor associated with greater likelihood of VCAG was receipt of gender-affirming surgery, but the association was only evident among transmen. Participants who achieved VCAG had a lower likelihood of depression and anxiety with prevalence ratios (95% confidence intervals) of 0.79 (0.65, 0.96) and 0.67 (0.46, 0.98), respectively., Clinical Implications: VCAG may serve as an important outcome measure after gender-affirming therapy., Strengths and Limitations: Strengths of this study include a well-defined sampling frame and use of a novel patient-centered outcome of interest. Cross-sectional design and uncertain generalizability of results are the limitations., Conclusion: These results, once confirmed by prospective studies, may help better characterize the determinants of well-being in the transgender community, facilitating the design of interventions to improve the well-being and quality of life of this vulnerable population. To M, Zhang Q, Bradlyn A, et al. Visual Conformity With Affirmed Gender or "Passing": Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People. J Sex Med 2020;17:2084-2092., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Transgender and gender diverse people often face discrimination and may experience disproportionate emotional distress that leads to suicide attempts. Therefore, it is essential to estimate the frequency and potential determinants of suicide attempts among transgender and gender diverse individuals., Methods: Longitudinal data on 6,327 transgender and gender diverse individuals enrolled in 3 integrated healthcare systems were analyzed to assess suicide attempt rates. Incidence was compared between transmasculine and transfeminine people by age and race/ethnicity and according to mental health status at baseline. Cox proportional hazards models examined rates and predictors of suicide attempts during follow-up. Data were collected in 2016, and analyses were conducted in 2019., Results: During follow-up, 4.8% of transmasculine and 3.0% of transfeminine patients had at least 1 suicide attempt. Suicide attempt rates were more than 7 times higher among patients aged <18 years than among those aged >45 years, more than 3 times higher among patients with previous history of suicide ideation or suicide attempts than among those with no such history, and 2-5 times higher among those with 1-2 mental health diagnoses and more than 2 mental health diagnoses at baseline than among those with none., Conclusions: Among transgender and gender diverse individuals, younger people, people with previous suicidal ideation or attempts, and people with multiple mental health diagnoses are at a higher risk for suicide attempts. Future research should examine the impact of gender-affirming healthcare use on the risk of suicide attempts and identify targets for suicide prevention interventions among transgender and gender diverse people in clinical settings., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: The effect of gender-affirming hormone therapy (HT) on erythropoiesis is an area of priority in transgender health research., Objective: To compare changes in hematologic parameters and rates of erythrocytosis and anemia among transgender people to those of cisgender controls., Design: Longitudinal observational study., Participants and Setting: We compared 559 transfeminine (TF) and 424 transmasculine (TM) people enrolled in 3 integrated health care systems to matched cisgender referents., Interventions and Outcome: Hormone therapy receipt was ascertained from filled prescriptions. Hemoglobin (Hb) and hematocrit (Hct) levels were examined from the first blood test to HT initiation, and from the start of HT to the most recent blood test. Rates of erythrocytosis and anemia in transgender participants and referents were compared by calculating adjusted hazard ratios and 95% confidence intervals (CI)., Results: In the TF group, there was a downward trend for both Hb and Hct. The corresponding changes in the TM cohort were in the opposite direction. TM study participants experienced a 7-fold higher rate (95% CI: 4.1-13.4) of erythrocytosis relative to matched cisgender males, and an 83-fold higher rate (95% CI: 36.1-191.2) compared to cisgender females. The corresponding rates for anemia were elevated in TF subjects but primarily relative to cisgender males (hazard ratio 5.9; 95% CI: 4.6-7.5)., Conclusions: Our results support previous recommendations that hematological parameters of transgender people receiving HT should be interpreted based on their affirmed gender, rather than their sex documented at birth. The clinical significance of erythrocytosis following testosterone therapy, as well as anemia following feminizing HT, requires further investigation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

The 25th annual conference of the Health Care Systems Research Network (HCSRN) was held April 10-12 in Portland, Oregon, attracting 420 attendees. The HCSRN, a consortium of 18 community-based research organizations embedded in or affiliated with large health care delivery systems, has hosted annual research conferences since 1994. The primary objective of the conference is to convene researchers, project staff, funders, and other stakeholders to share latest scientific findings and cultivate new partnerships among research teams, patients, and clinicians. Collaboration is the cornerstone of the HCSRN's success; the conference serves as a catalyst for a variety of collaborative ventures as well as tactics and approaches to more effective and efficient research. This year's program included 70 distinct scientific presentations, plus nearly 100 posters, and spanned diverse content offerings that mirrored the diversity of the HCSRN and its collaborators. Plenary sessions imparted insights on ways that data science and approaches to collaborative design in health care can speed the translation of research into practice., Competing Interests: Conflicts of Interest None.

Aims: The aims of this study were to assess the impact of delays in treatment intensification (TI) on cardiovascular events, heart failure, and all-cause mortality at typical stages of anti-hyperglycaemic therapy., Materials and Methods: Using electronic health record data, we created three TI cohorts of diabetes patients who: 1) initiated metformin (MET) as their first anti-hyperglycaemic therapy; 2) added a sulfonylurea (SU) to MET; and 3) initiated insulin (INS) while using MET or SU, alone or in combination. Primary exposure variables were haemoglobin A1C value preceding cohort therapy (pre-TI A1C) and time to intensification, that is, the time between pre-TI A1C >7% and cohort index date. Cox regression models were used to analyse the associated risk of cardiovascular events, hospitalizations for heart failure and all-cause mortality., Results: In the MET cohort, each additional percentage point of pre-TI A1C was associated with a 10% increased risk of a CV event (HR, 1.10; 95% CI, 1.03-1.07; P = 0.004), a 7% increased risk of HF hospitalization (HR, 1.07; 95% CI, 1.01-1.14; P = 0.034) and a 7% increased risk of all-cause mortality (HR, 1.07; 95% CI, 1.01-1.14; P = 0.032). Pre-TI A1C was associated with a 9% increased risk of a CV event in the INS cohort (HR,1.09; 95% CI, 1.04-1.13; P < 0.001). Each month of delay in TI was significantly associated with a 6% increased risk of hospitalization for HF (HR, 1.06; 95% CI, 1.00-1.13; P = 0.040) and all-cause mortality (HR, 1.06; 95% CI, 1.00-1.13; P = 0.050) in the MET cohort., Conclusions: Delays in TI were associated with poor outcomes over a mean follow-up period of nearly five years. Earlier initiation and more rapid intensification of pharmacotherapy could reduce the risk of poor outcomes., (© 2019 John Wiley & Sons Ltd.)

Background: Racial/ethnic disparities in rates of influenza vaccinations in the US remain an issue even among those with access, no out-of-pocket costs, and after adjusting for confounders. We used an approach called the Oaxaca-Blinder (OB) decomposition method to ascertain the contribution of covariates individually and in aggregate to the racial disparity in influenza vaccination., Methods: We included members > = 18 years of age as of 05/01/2014 with continuous enrollment through 04/30/2015. Influenza vaccination was defined by diagnosis, procedure, or medication codes, or documentation in the immunization table. Characteristics were reported by race. Logistic regression models estimated the odds of vaccination associated with: (1) race; and (2) covariates stratified by race. The Oaxaca-Blinder (OB) method calculated the contribution of covariates to the difference or disparity in vaccination between Blacks and Whites., Results: We found that among adults, 44% were vaccinated; 55% were Black; and 45% were White. Black members have 42% lower odds of vaccination than White members. The contribution of the differences in the average value of the study covariates between Black and White members (the OB covariate effect) accounted for 29% of the racial disparity. The contributions to the total White-Black disparity in vaccination included: age (16%), neighborhood median income (11%), and registration on the online patient portal (13%). The contribution of the differences in how the covariates impact vaccination (OB coefficient effect) accounted for 71% of the disparity in vaccination between Blacks and Whites., Conclusion: In conclusion, equalizing average covariate values in Blacks and Whites could reduce the racial disparity in influenza vaccination by 29%. For health system vaccine campaigns, improving registration on the patient portal may be a target component of an effective system-level strategy to reduce racial disparities in vaccination. Additional information on patient-centered factors could further improve the value of the OB approach., Competing Interests: The authors have declared that no competing interests exist.

Background: Medication nonadherence is a significant, modifiable contributor to uncontrolled hypertension. Stereotype threat may contribute to racial disparities in adherence by hindering a patient's ability to actively engage during a clinical encounter, resulting in reduced activation to adhere to prescribed therapies., Objective: The Hypertension and Values (HYVALUE) trial aims to examine whether a values-affirmation intervention improves medication adherence (primary outcome) by targeting racial stereotype threat., Methods: The HYVALUE trial is a patient-level, blinded randomized controlled trial comparing a brief values-affirmation writing exercise with a control writing exercise among black and white patients with uncontrolled hypertension. We are recruiting patients from 3 large health systems in the United States. The primary outcome is patients' adherence to antihypertensive medications, with secondary outcomes of systolic and diastolic blood pressure over time, time for which blood pressure is under control, and treatment intensification. We are comparing the effects of the intervention among blacks and whites, exploring possible moderators (ie, patients' prior experiences of discrimination and clinician racial bias) and mediators (ie, patient activation) of intervention effects on outcomes., Results: This study was funded by the National Heart, Lung, and Blood Institute. Enrollment and follow-up are ongoing and data analysis is expected to begin in late 2020. Planned enrollment is 1130 patients. On the basis of evidence supporting the effectiveness of values affirmation in educational settings and our pilot work demonstrating improved patient-clinician communication, we hypothesize that values affirmation disrupts the negative effects of stereotype threat on the clinical interaction and can reduce racial disparities in medication adherence and subsequent health outcomes., Conclusions: The HYVALUE study moves beyond documentation of race-based health disparities toward testing an intervention. We focus on a medical condition-hypertension, which is arguably the greatest contributor to mortality disparities for black patients. If successful, this study will be the first to provide evidence for a low-resource intervention that has the potential to substantially reduce health care disparities across a wide range of health care conditions and populations., Trial Registration: ClinicalTrials.gov NCT03028597; https://clinicaltrials.gov/ct2/show/NCT03028597 (Archived by WebCite at http://www.webcitation.org/72vcZMzAB)., International Registered Report Identifier (irrid): DERR1-10.2196/12498., (©Stacie L Daugherty, Suma Vupputuri, Rebecca Hanratty, John F Steiner, Julie A Maertens, Irene V Blair, L Miriam Dickinson, Laura Helmkamp, Edward P Havranek. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.03.2019.)

Objective To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

A key priority of transgender health research is the evaluation of long-term effects of gender affirmation treatment. Thus, accurate assessment of treatment receipt is critical. The data for this analysis came from an electronic medical records (EMR) based cohort of transgender individuals. A subset of cohort members were also asked to complete a self-administered survey. Information from the EMR was compared with survey responses to assess the extent of agreement regarding transmasculine (TM)/transfeminine (TF) status, hormone therapy receipt, and type of surgery performed. Logistic regression models were used to assess whether participant characteristics were associated with disagreement between data sources. Agreement between EMR and survey-derived information was high regarding TM/TF status (99%) and hormone therapy receipt (97%). Lower agreement was observed for chest reconstruction surgery (72%) and genital reconstruction surgery (84%). Using survey responses as the "gold standard", both chest and genital reconstruction surgeries had high specificity (95 and 93%, respectively), but the corresponding sensitivities were low (49 and 68%, respectively). A lower proportion of TM had concordant results for chest reconstruction surgery (64% versus 79% for TF) while genital reconstruction surgery concordance was lower among TF (79% versus 89% for TM). For both surgery types, agreement was highest among the youngest participants. Our findings offer assurance that EMR-based data appropriately classify cohort participants with respect to their TM/TF status or hormone therapy receipt. However, current EMR data may not capture the complete history of gender affirmation surgeries. This information is useful in future studies of outcomes related to gender affirming therapy.

Objective: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy?, Methods: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses., Results: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome., (© 2017 by the American College of Cardiology Foundation and the American Heart Association, Inc.)

Objective: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy?, Methods: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses., Results: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (i.e., angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome., (Copyright © 2018 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.)

Reducing the promiscuous tropism of native adenovirus by using fiberless adenovirus is advantageous toward its use as a gene therapy vector or vaccine component. The removal of the fiber protein on native adenovirus abrogates several undesirable interactions; however, this approach decreases the particle's physical stability. To create stable fiberless adenovirus for pharmaceutical use, the effects of temperature and pH on the particle's stability profile must be addressed. Our results indicate that the stability of fiberless adenovirus is increased when it is stored in mildly acidic conditions around pH 6. The stability of fiberless adenovirus can be further enhanced by using excipients. Excipient screening results indicate that the nonionic surfactant Pluronic F-68 and the amino acid glycine are potential stabilizers because of their ability to increase the thermal transition temperature of the virus particle and promote retention of biological activity after exposure to prolonged thermal stress. Our data indicate that the instability of fiberless adenovirus can be ameliorated by storing the virus in the appropriate environment, and it should be possible to further optimize the virus so that it can be used as a biopharmaceutical., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations., Methods: We examined trends in hospitalized acute myocardial infarction incidence among adults aged ≥25 years in 13 US health plans in the Cardiovascular Research Network. The first hospitalization per member for acute myocardial infarction overall and for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge codes in each calendar year from 2000 through 2008. Age- and sex-adjusted incidence was calculated per 100,000 person-years using direct adjustment with 2000 US census data., Results: Between 2000 and 2008, we identified 125,435 acute myocardial infarction hospitalizations. Age- and sex-adjusted incidence rates (per 100,000 person-years) of acute myocardial infarction decreased an average 3.8%/y from 230.5 in 2000 to 168.6 in 2008. Incidence of ST-segment elevation myocardial infarction decreased 8.7%/y from 104.3 in 2000 to 51.7 in 2008, whereas incidence of non-ST-segment elevation myocardial infarction increased from 126.1 to 129.4 between 2000 and 2004 and then decreased thereafter to 116.8 in 2008. Age- and sex-specific incidence rates generally reflected similar patterns, with relatively larger decreases in ST-segment elevation myocardial infarction rates in women compared with men. As compared with 2000, the age-adjusted incidence of ST-segment elevation myocardial infarction in 2008 was 48% lower among men and 61% lower among women., Conclusions and Relevance: Among a large, diverse, multicenter community-based insured population, there were significant decreases in incidence of hospitalized acute myocardial infarction and the more serious ST-segment elevation myocardial infarctions between 2000 and 2008. Decreases in ST-segment elevation myocardial infarctions were most pronounced among women. While ecologic in nature, these secular decreases likely reflect, at least in part, results of improvement in primary prevention efforts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To describe the estimated prevalence and temporal trends of chronic kidney disease (CKD) treatment patterns, and the association between CKD and potential factors for type 2 diabetes mellitus (T2DM) in different demographic subgroups., Research Design and Methods: This was a cross-sectional analysis of adults with T2DM based on multiple US National Health and Nutrition Examination Survey (NHANES) datasets developed during 2007-2012. CKD severity was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines using the CKD Epidemiology Collaboration (CKD-EPI) equation: mild to moderate=stages 1-3a; moderate to kidney failure=stages 3b-5. Multivariable logistic regression analyses were performed to assess the associations between CKD and potential factors., Results: Of the adult individuals with T2DM (n=2006), age-adjusted CKD prevalence was 38.3% during 2007-2012; 77.5% were mild-to-moderate CKD. The overall age-adjusted prevalence of CKD was 40.2% in 2007-2008, 36.9% in 2009-2010, and 37.6% in 2011-2012. The prevalence of CKD in T2DM was 58.7% in patients aged ≥65 years, 25.7% in patients aged <65 years, 43.5% in African-Americans and Mexican-Americans, and 38.7% in non-Hispanic whites. The use of antidiabetes and antihypertensive medications generally followed treatment guideline recommendations. Older age, higher hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and having hypertension were significantly associated with CKD presence but not increasing severity of CKD., Conclusions: CKD continued to be prevalent in the T2DM population; prevalence remained fairly consistent over time, suggesting that current efforts to prevent CKD could be improved overall, especially by monitoring certain populations more closely.

Many alternative tobacco products (ATPs), such as hookahs, have grown in popularity and use beyond their locale of origin and are therefore becoming a significant global public health concern. This article provides an overview of an under-reported and understudied ATP, dokha, which is smoked in a midwakh pipe. It describes the state of tobacco control in the Arabian Gulf region where midwakh smoking appears to be most common, the history of midwakh and dokha use, and what is known about midwakh smoking from the published literature. On the basis of the stark lack of data on midwakh use, we suggest priority areas to focus future research. Preliminary data and observations from health providers and the public health sector suggest that midwakh smoking may pose challenges to the tobacco control efforts in the Arabian Gulf region. If it is emerging as a new ATP outside this region, there could be a significant impact on tobacco control strategies globally., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol treatment guideline recommends monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. We examined LDL-C reduction and statin adherence among high-risk patients initiating statins in a real-world setting., Study Design: Retrospective cohort study., Methods: The study population included Kaiser Permanente Georgia members (n = 1066) with a history of coronary heart disease or risk equivalent(s) initiating statins in 2011. Percent change in LDL-C was defined using measurements before and 60 to 450 days after statin initiation. Statin adherence was defined by proportion of days covered, categorized as high (≥80%), intermediate (50%-79%), and low (< 50%)., Results: Overall, 58.4% of patients failed to achieve a ≥ 30% LDL-C reduction after statin initiation. The prevalences of high, intermediate, and low statin adherence were 41.3%, 23.2%, and 35.6%, respectively. Of patients with high adherence, 42.3% did not achieve a ≥ 30% reduction in LDL-C compared with 54.7% and 79.7% of those with intermediate and low statin adherence, respectively. After multivariable adjustment, and compared with those with high adherence, the risk ratios for not achieving a ≥ 30% LDL-C reduction were 1.31 (95% CI, 1.13-1.52) and 1.88 (95% CI, 1.67-2.11), for those with intermediate and low adherence. Women and African Americans were less likely to have high adherence, whereas having cardiologist visits was associated with high adherence., Conclusions: In a real-world setting, many patients did not achieve a 30% or larger LDL-C reduction. These data support the ACC/AHA recommendation to monitor LDL-C response among patients initiating statins.

Objective: Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular medications (i.e., statins, angiotensin-converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs])., Methods: Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records., Results: Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls., Conclusions: We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker's willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline., (Copyright © 2016. Published by Elsevier Inc.)

Background: Whether there is a kidney function threshold to statin effectiveness in patients with acute myocardial infarction is poorly understood. Our study sought to help fill this gap in clinical knowledge., Methods: We undertook a new-user cohort study of the effectiveness of statin therapy by level of estimated glomerular filtration rate (eGFR) in adults who were hospitalized for myocardial infarction between 2000 and 2008. Data came from the Cardiovascular Research Network. The primary clinical outcomes were 1-year all-cause mortality and cardiovascular hospitalizations, with adverse outcomes of myopathy and development of diabetes mellitus. We calculated incidence rates, the number needed to treat, and used Cox proportional hazards regression with propensity score matching and adjustment to control for confounding, with testing for variation of effect by level of kidney function., Results: Compared with statin non-initiators (n = 5583), statin initiators (n = 5597) had a lower propensity score-adjusted risk for death (hazard ratio 0.79; 95% confidence interval [CI], 0.71-0.88) and cardiovascular hospitalizations (hazard ratio 0.90; 95% CI, 0.82-1.00). We found little evidence of variation in effect by level of eGFR (P = .86 for death; P = .77 for cardiovascular hospitalization). Adverse outcomes were similar for statin initiators and statin non-initiators. The number needed to treat to prevent 1 additional death over 1 year of follow-up ranged from 15 (95% CI, 11-28) for eGFR <30 mL/min/1.73 m(2) requiring statin treatment over 2 years to prevent 1 additional death, to 67 (95% CI, 49-118) for patients with eGFR >90 mL/min/1.73 m(2)., Conclusions: Our findings suggest that there is potential for important public health gains by increasing the routine use of statin therapy for patients with lower levels of kidney function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Adenovirus (Ad) is one of the viral vectors most widely used for gene delivery. The virus, however, has serious shortcomings such as immunogenicity, promiscuous tropism, and the inability to efficiently infect certain types of cells. The goal of this study was to improve the ability of an Ad-based vector to efficiently transform cells that lack the native coxsackie-adenovirus receptor (CAR(-)) by modifying the virus with CPP-PEG conjugates., Methods: The vector was produced by PEGylating Ad, which packages a lacZ reporter gene, and then conjugating CPPs to form CPP-PEG-Ad particles. The study compared the effectiveness of four different CPPs: Pen, Tat, Pep1, and pArg. The effects of CPP amount per virus, degree of PEGylation, and PEG molecular weight on transduction efficiency were studied on CAR(-) NIH/3T3 cells., Results: CPP-PEG-Ad particles transduced CAR(-) cells significantly better than unmodified Ad. Pen, the most effective CPP, produced an 80-fold improvement in transduction compared to the unmodified virus. The Pen peptide utilized a combination of electrostatic and hydrophobic interactions with the cell membrane to maximize cellular association while the other CPPs used only electrostatic or hydrophobic interactions but not both. Lastly, higher degrees of PEGylation, which prompted PEG to adopt a "brush" conformation, resulted in more efficient CPP-PEG-Ad particles because of both better conjugation of CPPs to the PEGylated virus and better exposure of the conjugated CPPs on the surface of the particle., Conclusions: CPP-PEG-Ad particles efficiently deliver genes to cells that Ad alone would not efficiently infect, thereby extending potential gene therapy treatments to a much broader range of cell types and diseases., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: Evaluate the utility of 2 electronic medical record (EMR)-linked, automated phone reminder interventions for improving adherence to cardiovascular disease medications., Study Design: A 1-year, parallel arm, pragmatic clinical trial in which 21,752 adults were randomized to receive either usual care (UC) or 1 of 2 interventions in the form of interactive voice recognition calls-regular (IVR) or enhanced (IVR+). The interventions used automated phone reminders to increase adherence to cardiovascular disease medications. The primary outcome was medication adherence; blood pressure and lipid levels were secondary outcomes., Methods: The study took place in 3 large health maintenance organizations. We enrolled participants who were 40 years or older, had diabetes mellitus or atherosclerotic cardiovascular disease, and were suboptimally adherent. IVR participants received automated phone calls when they were due or overdue for a refill. IVR+ participants received these phone calls, plus personalized reminder letters, live outreach calls, EMR-based feedback to their primary care providers, and additional mailed materials., Results: Both interventions significantly increased adherence to statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) compared with UC (1.6 to 3.7 percentage points). Adherence to ACEIs/ARBs was also significantly higher for IVR+ relative to IVR participants. These differences persisted across subgroups. Among statin users, IVR+ participants had significantly lower low-density lipoprotein (LDL) levels at follow-up compared with UC (Δ = -1.5; 95% CI, -2.7 to -0.2 mg/dL); this effect was seen mainly in those with baseline LDL levels ≥ 100 mg/dL (Δ = -3.6; 95% CI, -5.9 to -1.3 mg/dL)., Conclusions: Technology-based tools, in conjunction with an EMR, can improve adherence to chronic disease medications and measured cardiovascular disease risk factors.

Low statin adherence and discontinuation of statins are common in patients with coronary heart disease. We hypothesized that low antihypertensive medication adherence would be associated with future statin discontinuation and low adherence in patients initiating statins. Using a 5% national sample of Medicare beneficiaries, we conducted a cohort study of Medicare beneficiaries initiating statins after hospitalization for acute myocardial infarction or coronary revascularization in 2007, 2008, and 2009. Antihypertensive medication adherence, defined using the average proportion of days covered across 5 classes during the 365 days before hospitalization, was categorized as ≥80% (high), 50% to <80% (medium), and <50% (low). Statin discontinuation was defined as failure to refill a statin within 365 days of hospital discharge, and low adherence was defined as proportion of days covered for statins <80%. In 2,695 Medicare beneficiaries who initiated statins after hospital discharge, 6.0%, 8.4%, and 14.5% with high, medium, and low antihypertensive medication adherence discontinued statins. After multivariable adjustment, the risk ratios (95% confidence interval) for statin discontinuation were 1.38 (0.98 to 1.95) and 2.41 (1.51 to 3.87) for beneficiaries with medium and low versus high antihypertensive medication adherence, respectively. In beneficiaries who did not discontinue statins, 36.2% had low statin adherence. Compared with high adherence, medium and low antihypertensive medication adherences were associated with multivariable adjusted risk ratios (95% confidence interval) for low statin adherence of 1.33 (1.14 to 1.55) and 1.62 (1.25 to 2.10), respectively. In conclusion, low antihypertensive medication adherence before initiating statins is associated with future statin discontinuation and low statin adherence., (Copyright © 2014 Elsevier Inc. All rights reserved.)