Supplemental Nutrition Assistance Program and Adherence to Antihypertensive Medications.

Importance: Nonadherence to antihypertensive medications is associated with uncontrolled blood pressure, higher mortality rates, and increased health care costs, and food insecurity is one of the modifiable medication nonadherence risk factors. The Supplemental Nutrition Assistance Program (SNAP), a social intervention program for addressing food insecurity, may help improve adherence to antihypertensive medications. Objective: To evaluate whether receipt of SNAP benefits can modify the consequences of food insecurity on nonadherence to antihypertensive medications. Design, Setting, and Participants: A retrospective cohort study design was used to assemble a cohort of antihypertensive medication users from the linked Medical Expenditure Panel Survey (MEPS)-National Health Interview Survey (NHIS) dataset for 2016 to 2017. The MEPS is a national longitudinal survey on verified self-reported prescribed medication use and health care access measures, and the NHIS is an annual cross-sectional survey of US households that collects comprehensive health information, health behavior, and sociodemographic data, including receipt of SNAP benefits. Receipt of SNAP benefits in the past 12 months and food insecurity status in the past 30 days were assessed through standard questionnaires during the study period. Data analysis was performed from March to December 2021. Exposure: Status of SNAP benefit receipt. Main Outcomes and Measures: The main outcome, nonadherence to antihypertensive medication refill adherence (MRA), was defined using the MEPS data as the total days' supply divided by 365 days for each antihypertensive medication class. Patients were considered nonadherent if their overall MRA was less than 80%. Food insecurity status in the 30 days prior to the survey was modeled as the effect modifier. Inverse probability of treatment (IPT) weighting was used to control for measured confounding effects of baseline covariates. A probit model was used, weighted by the product of the computed IPT weights and MEPS weights, to estimate the population average treatment effects (PATEs) of SNAP benefit receipt on nonadherence. A stratified analysis approach was used to assess for potential effect modification by food insecurity status. Results: This analysis involved 6692 antihypertensive medication users, of whom 1203 (12.8%) reported receiving SNAP benefits and 1338 (14.8%) were considered as food insecure. The mean (SD) age was 63.0 (13.3) years; 3632 (51.3%) of the participants were women and 3060 (45.7%) were men. Although SNAP was not associated with nonadherence to antihypertensive medications in the overall population, it was associated with a 13.6-percentage point reduction in nonadherence (PATE, -13.6 [95% CI, -25.0 to -2.3]) among the food-insecure subgroup but not among their food-secure counterparts. Conclusions and Relevance: This analysis of a national observational dataset suggests that patients with hypertension who receive SNAP benefits may be less likely to become nonadherent to antihypertensive medication, especially if they are experiencing food insecurity. Further examination of the role of SNAP as a potential intervention for preventing nonadherence to antihypertensive medications through prospectively designed interventional studies or natural experiment study designs is needed.

Patient satisfaction with the quality of care received is associated with adherence to antidepressant medications.

BACKGROUND: There is a paucity of evidence on the association between satisfaction with quality of care and adherence to antidepressants. OBJECTIVES: To examine the association between patient satisfaction with healthcare and adherence to antidepressants. METHODS: A cohort study design was used to identify antidepressant users from the 2010-2016Medical Expenditure Panel Survey data, a national longitudinal complex survey study design on the cost and healthcare utilization of the noninstitutionalized population in the United States. The Consumer Assessment of Healthcare Providers and Systems were used to measure participants' satisfaction with access and quality of care, patient-provider communication and shared decision-making (SDM). Patients were considered satisfied if they ranked the quality of care at ≥9 (range: 0[worst]- 10[best]). Antidepressant adherence was measured based on medication refill and complete discontinuation. MEPS sampling survey-weighted multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between satisfaction and adherence to antidepressants. We tested for the potential presence of reverse associations by restricting the analysis to new users of antidepressants. The roles of patient-provider communication and SDM on the satisfaction-adherence association were examined through structural equation models (SEM). RESULTS: Among 4,990 (weighted counts = 8,661,953) antidepressant users, 36% were adherent while 39% discontinued antidepressants therapy. Half of antidepressant users were satisfied with the healthcare received. Satisfied patients were 26% (OR = 1.26, 95%CI: 1.08, 1.47) more likely to adhere and 17% (OR = 0.83, 95%CI: 0.71, 0.96) less likely to discontinue, compared to unsatisfied antidepressant users. Patient satisfaction was also associated with higher odds (OR = 1.41, 95%CI: 1.06, 1.88) of adherence among a subgroup of new users of antidepressants. The SEM analysis revealed that satisfaction was a manifestation of patient-provider communication (ß = 2.03, P-value<0.001) and SDM (ß = 1.14, P-value<0.001). CONCLUSIONS: Patient satisfaction is a potential predictor of antidepressant adherence. If our findings are confirmed through intervention studies, improving patient-provider communication and SDM could likely drive both patient satisfaction and adherence to antidepressants.

Seminar: Scalable Preprocessing Tools for Exposomic Data Analysis.

BACKGROUND: The exposome serves as a popular framework in which to study exposures from chemical and nonchemical stressors across the life course and the differing roles that these exposures can play in human health. As a result, data relevant to the exposome have been used as a resource in the quest to untangle complicated health trajectories and help connect the dots from exposures to adverse outcome pathways. OBJECTIVES: The primary aim of this methods seminar is to clarify and review preprocessing techniques critical for accurate and effective external exposomic data analysis. Scalability is emphasized through an application of highly innovative combinatorial techniques coupled with more traditional statistical strategies. The Public Health Exposome is used as an archetypical model. The novelty and innovation of this seminar's focus stem from its methodical, comprehensive treatment of preprocessing and its demonstration of the positive effects preprocessing can have on downstream analytics. DISCUSSION: State-of-the-art technologies are described for data harmonization and to mitigate noise, which can stymie downstream interpretation, and to select key exposomic features, without which analytics may lose focus. A main task is the reduction of multicollinearity, a particularly formidable problem that frequently arises from repeated measurements of similar events taken at various times and from multiple sources. Empirical results highlight the effectiveness of a carefully planned preprocessing workflow as demonstrated in the context of more highly concentrated variable lists, improved correlational distributions, and enhanced downstream analytics for latent relationship discovery. The nascent field of exposome science can be characterized by the need to analyze and interpret a complex confluence of highly inhomogeneous spatial and temporal data, which may present formidable challenges to even the most powerful analytical tools. A systematic approach to preprocessing can therefore provide an essential first step in the application of modern computer and data science methods. https://doi.org/10.1289/EHP12901.

Optimizing Medication Distribution in Automated Dispensing Cabinets: Dashboard Implementation and Evaluation.

Purpose: To determine the impact of a business intelligence dashboard tool to optimize automated dispensing cabinets (ADCs). Methods: A pre-post implementation design was used to evaluate key performance indicators (KPI) before and after the implementation of a dashboard tool to optimize ADCs. Eleven ADCs were optimized in 2 phases according to dashboard recommendations: (1) removal of unused medications over 90 days, (2) adjusting periodic automatic replenishment (PAR) levels, and (3) addition of commonly dispensed medications. The KPI measures that were assessed included inventory cost, no. of stocked medications, stockout percentage, vend to refill ratio, and missing dose messages from nursing. An interrupted-time-series regression was used to quantify the impact of ADCs on the means of measured KPIs. Results: Differences in mean distribution of all KPIs, except missing dose, between the pre- and post-ADC periods during the Phase 1 period were statistically significant: inventory cost (54.2 vs 56), stockout percentage (1.55 vs 1.12), vend to refill ratio (6.83 vs 6.14), and missing dose messages (221 vs 229). Only the mean ADC utilization (57.3 vs 64) and missing dose (228 vs 179) were statistically different between the pre- and post-ADC periods in Phase 2. The interrupted-time-series analysis showed that Phase 1 optimization significantly reduced the cost of inventory (ß = -$1.238.00, P < .01), no. Stocked medications (ß = -8.2, P < .01), percent stockout (ß = -.49%, P < .01), vend-to-refill ratio (ß = -1.29%, P<.01) and ADC utilization (ß = -.2, P < .01). Conclusion: Automated dispensing cabinets optimization, through the use of a dashboard tool, had a positive impact on almost all measured KPIs.

Predictors of Influenza and Pneumococcal Vaccination Among Participants in the Women's Health Initiative.

OBJECTIVE: Older adults typically experience higher rates of severe disease and mortality than the general population after contracting an infectious disease. Vaccination is critical for preventing disease and severe downstream outcomes; however, vaccination rates among older adults are suboptimal. We assessed predictors associated with pneumococcal and seasonal influenza vaccination among older women. METHODS: We used data from the Women's Health Initiative, a nationwide cohort of women. We ascertained seasonal influenza and pneumococcal vaccination status through a questionnaire administered in 2013. We limited analyses to women aged ≥65 years at questionnaire administration. We used logistic regression to estimate associations between demographic, lifestyle, and health-related factors and vaccination and explored stratification by race. RESULTS: Of participants who responded to each question, 84.3% (n = 60 578) reported being vaccinated for influenza and 85.5% (n = 59 015) for pneumonia. The odds of reporting influenza vaccination were significantly lower among non-Hispanic Black participants than among non-Hispanic White participants (odds ratio [OR] = 0.53; 95% CI, 0.49-0.58), women with no health insurance versus private health insurance (OR = 0.61; 95% CI, 0.54-0.68), and women living in rural versus urban settings (OR = 0.84; 95% CI, 0.73-0.96). Current smoking, lower education levels, and having comorbid conditions were associated with lower likelihood of being vaccinated for influenza (than not); past pneumonia diagnosis and being currently married were associated with a higher likelihood. We observed similar associations for pneumococcal vaccination coverage. CONCLUSIONS: These findings reinforce the need to enact policy and implement programs to improve access to, education and awareness about, and provider recommendations for these critical disease-prevention tools. Results from our study should guide strategies for SARS-CoV-2 vaccination.

A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

AIMS: The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. METHODS: A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. RESULTS: After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. CONCLUSION: We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.

More than treatment refusal: a National Cancer Database analysis of adjuvant treatment refusal and racial survival disparities among women with endometrial cancer.

BACKGROUND: Disparities in adjuvant treatment between Black and White women with endometrial cancer exist and contribute to worse outcomes among Black women. However, factors leading to disparate treatment receipt are understudied. OBJECTIVE: We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether treatment refusal mediated racial disparities in survival among women with endometrial cancer. STUDY DESIGN: We used the National Cancer Database, a hospital-based cancer registry, to identify non-Hispanic Black and non-Hispanic White women diagnosed with endometrial cancer from 2004 to 2016 who either received or refused recommended radiation or chemotherapy. We used logistic regression to estimate multivariable-adjusted odds ratios and 95% confidence intervals for associations between race and treatment refusal. We also examined predictors of treatment refusal in race-specific models. Accelerated failure time models were used to estimate absolute differences in overall survival by race. We used causal mediation analysis to estimate the proportion of racial differences in overall survival attributable to racial differences in adjuvant treatment refusal. We considered the overall study population and strata defined by histology, and adjusted for sociodemographic, tumor, and facility characteristics. RESULTS: Our analysis included 75,447 endometrial cancer patients recommended to receive radiation and 60,187 endometrial cancer patients recommended to receive chemotherapy, among which 6.4% and 11.4% refused treatment, respectively. Among Black women recommended for radiation or chemotherapy, 6.4% and 9.6% refused, respectively. Among White women recommended for radiation or chemotherapy, 6.4% and 11.8% refused, respectively. After adjusting for sociodemographic variables, facility characteristics, and tumor characteristics, Black women were more likely to refuse chemotherapy than White women (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.37), but no difference in radiation refusal was observed (adjusted odds ratio, 1.00; 95% confidence interval, 0.91-1.11). Some predictors of radiation refusal varied by race, namely income, education, histology, stage, and chemotherapy receipt (P interactions<.05), whereas predictors of chemotherapy refusal were generally similar between Black and White women. Among women recommended for radiation, Black women survived an average of 4.3 years shorter than White women, which did not seem attributable to differences in radiation refusal. Among women recommended for chemotherapy, Black women survived an average of 3.2 years shorter than White women of which 1.9 months (4.9%) could potentially be attributed to differences in chemotherapy refusal. CONCLUSION: We observed differences in chemotherapy refusal by race, and those differences may be responsible for up to about 2 months of the overall 3.2-year survival disparity between White and Black women. Radiation refusal did not explain any of the 4.3-year disparity among women recommended for radiation. Treatment refusal accounts for, at most, a small fraction of the total racial disparity in endometrial cancer survival. Although a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes, particularly those reflecting the social determinants of health, must be investigated.

Examining the Drivers of Racial/Ethnic Disparities in Non-Adherence to Antihypertensive Medications and Mortality Due to Heart Disease and Stroke: A County-Level Analysis.

Background: Prior research has identified disparities in anti-hypertensive medication (AHM) non-adherence between Black/African Americans (BAAs) and non-Hispanic Whites (nHWs) but the role of determinants of health in these gaps is unclear. Non-adherence to AHM may be associated with increased mortality (due to heart disease and stroke) and the extent to which such associations are modified by contextual determinants of health may inform future interventions. Methods: We linked the Centers for Disease Control and Prevention (CDC) Atlas of Heart Disease and Stroke (2014-2016) and the 2016 County Health Ranking (CHR) dataset to investigate the associations between AHM non-adherence, mortality, and determinants of health. A proportion of days covered (PDC) with AHM < 80%, was considered as non-adherence. We computed the prevalence rate ratio (PRR)-the ratio of the prevalence among BAAs to that among nHWs-as an index of BAA-nHW disparity. Hierarchical linear models (HLM) were used to assess the role of four pre-defined determinants of health domains-health behaviors, clinical care, social and economic and physical environment-as contributors to BAA-nHW disparities in AHM non-adherence. A Bayesian paradigm framework was used to quantify the associations between AHM non-adherence and mortality (heart disease and stroke) and to assess whether the determinants of health factors moderated these associations. Results: Overall, BAAs were significantly more likely to be non-adherent: PRR = 1.37, 95% Confidence Interval (CI):1.36, 1.37. The four county-level constructs of determinants of health accounted for 24% of the BAA-nHW variation in AHM non-adherence. The clinical care (ß = -0.21, p < 0.001) and social and economic (ß = -0.11, p < 0.01) domains were significantly inversely associated with the observed BAA-nHW disparity. AHM non-adherence was associated with both heart disease and stroke mortality among both BAAs and nHWs. We observed that the determinants of health, specifically clinical care and physical environment domains, moderated the effects of AHM non-adherence on heart disease mortality among BAAs but not among nHWs. For the AHM non-adherence-stroke mortality association, the determinants of health did not moderate this association among BAAs; the social and economic domain did moderate this association among nHWs. Conclusions: The socioeconomic, clinical care and physical environmental attributes of the places that patients live are significant contributors to BAA-nHW disparities in AHM non-adherence and mortality due to heart diseases and stroke.

Association Between Patient-Clinician Relationships and Adherence to Antihypertensive Medications Among Black Adults: An Observational Study Design.

Background We assessed the associations between patient-clinician relationships (communication and involvement in shared decision-making [SDM]) and adherence to antihypertensive medications. Methods and Results The 2010 to 2017 Medical Expenditure Panel Survey (MEPS) data were analyzed. A retrospective cohort study design was used to create a cohort of prevalent and new users of antihypertensive medications. We defined constructs of patient-clinician communication and involvement in SDM from patient responses to the standard questionnaires about satisfaction and access to care during the first year of surveys. Verified self-reported medication refill information collected during the second year of surveys was used to calculate medication refill adherence; adherence was defined as medication refill adherence ≥80%. Survey-weighted multivariable-adjusted logistic regression models were used to measure the odds ratio (OR) and 95% CI for the association between both patient-clinician constructs and adherence. Our analysis involved 2571 Black adult patients with hypertension (mean age of 58 years; SD, 14 years) who were either persistent (n=1788) or new users (n=783) of antihypertensive medications. Forty-five percent (n=1145) and 43% (n=1016) of the sample reported having high levels of communication and involvement in SDM, respectively. High, versus low, patient-clinician communication (OR, 1.38; 95% CI, 1.14-1.67) and involvement in SDM (OR, 1.32; 95% CI, 1.08-1.61) were both associated with adherence to antihypertensives after adjusting for multiple covariates. These associations persisted among a subgroup of new users of antihypertensive medications. Conclusions Patient-clinician communication and involvement in SDM are important predictors of optimal adherence to antihypertensive medication and should be targeted for improving adherence among Black adults with hypertension.

Prevalence and quality of antihypertensive therapy among hypertension patients enrolled in the Ghana National Health Insurance Scheme.

BACKGROUND: Hypertension is a leading cause of morbidity in Ghana. However, there is insufficient data on the prevalence and quality of antihypertensive therapy. OBJECTIVES: To describe the prevalence of use and quality of antihypertensive therapy. METHODS: A cross-sectional study design was used to analyze the 2015 Ghana National Health Insurance Scheme (NHIS) electronic claims data. Hypertension diagnosis was defined using ICD-10 codes. The primary outcomes assessed were the prevalence of use and quality of antihypertensive therapy. Quality of antihypertensive therapy was defined as the use of antihypertensive agents recommended for treating hypertension patients with comorbid heart failure, myocardial Infarction/Coronary Artery Disease, diabetes, chronic kidney disease or stroke. We used multivariable logistic regression models to identify predictors of antihypertensive use and quality of therapy. RESULTS: Antihypertensive medication use was very high (86%) among the 161 873 hypertension patients covered under the Ghana NHIS. Only a third (32%) of hypertension patients received guideline-concordant therapy. Angiotensin receptor blockers were consumed at the highest dosages of 120 (Interquartile Range [IQR]: 60, 180) daily defined doses over a year. Males (odds ratio [OR] = 0.60; 95% Confidence Interval [CI]:0.58, 0.61) and those with comorbid stroke (OR = 0.91, 95% CI:0.84, 0.99), diabetes (OR = 0.72; 95% CI:0.69, 0.74) and stroke (OR = 0.74, 95%CI:0.68, 0.80) were less likely to use antihypertensives, all other predictors were associated with higher use. CONCLUSION: Antihypertensive medication use was very high among hypertension patients covered under the Ghana NHIS. However, there was indication of suboptimal quality of the antihypertensive therapy provided.

Structural and Social Determinants of Health Factors Associated with County-Level Variation in Non-Adherence to Antihypertensive Medication Treatment.

BACKGROUND: Non-adherence to antihypertensive medication treatment (AHM) is a complex health behavior with determinants that extend beyond the individual patient. The structural and social determinants of health (SDH) that predispose populations to ill health and unhealthy behaviors could be potential barriers to long-term adherence to AHM. However, the role of SDH in AHM non-adherence has been understudied. Therefore, we aimed to define and identify the SDH factors associated with non-adherence to AHM and to quantify the variation in county-level non-adherence to AHM explained by these factors. METHODS: Two cross-sectional datasets, the Centers for Disease Control and Prevention (CDC) Atlas of Heart Disease and Stroke (2014-2016 cycle) and the 2016 County Health Rankings (CHR), were linked to create an analytic dataset. Contextual SDH variables were extracted from the CDC-CHR linked dataset. County-level prevalence of AHM non-adherence, based on Medicare fee-for-service beneficiaries' claims data, was extracted from the CDC Atlas dataset. The CDC measured AHM non-adherence as the proportion of days covered (PDC) with AHM during a 365 day period for Medicare Part D beneficiaries and aggregated these measures at the county level. We applied confirmatory factor analysis (CFA) to identify the constructs of social determinants of AHM non-adherence. AHM non-adherence variation and its social determinants were measured with structural equation models. RESULTS: Among 3000 counties in the U.S., the weighted mean prevalence of AHM non-adherence (PDC < 80%) in 2015 was 25.0%, with a standard deviation (SD) of 18.8%. AHM non-adherence was directly associated with poverty/food insecurity (ß = 0.31, P-value < 0.001) and weak social supports (ß = 0.27, P-value < 0.001), but inversely with healthy built environment (ß = -0.10, P-value = 0.02). These three constructs explained one-third (R2 = 30.0%) of the variation in county-level AHM non-adherence. CONCLUSION: AHM non-adherence varies by geographical location, one-third of which is explained by contextual SDH factors including poverty/food insecurity, weak social supports and healthy built environments.

The Effects of Social, Personal, and Behavioral Risk Factors and PM2.5 on Cardio-Metabolic Disparities in a Cohort of Community Health Center Patients.

(1) Background: Cardio-metabolic diseases (CMD), including cardiovascular disease, stroke, and diabetes, have numerous common individual and environmental risk factors. Yet, few studies to date have considered how these multiple risk factors together affect CMD disparities between Blacks and Whites. (2) Methods: We linked daily fine particulate matter (PM2.5) measures with survey responses of participants in the Southern Community Cohort Study (SCCS). Generalized linear mixed modeling (GLMM) was used to estimate the relationship between CMD risk and social-demographic characteristics, behavioral and personal risk factors, and exposure levels of PM2.5. (3) Results: The study resulted in four key findings: (1) PM2.5 concentration level was significantly associated with reported CMD, with risk rising by 2.6% for each µg/m3 increase in PM2.5; (2) race did not predict CMD risk when clinical, lifestyle, and environmental risk factors were accounted for; (3) a significant variation of CMD risk was found among participants across states; and (4) multiple personal, clinical, and social-demographic and environmental risk factors played a role in predicting CMD occurrence. (4) Conclusions: Disparities in CMD risk among low social status populations reflect the complex interactions of exposures and cumulative risks for CMD contributed by different personal and environmental factors from natural, built, and social environments.

The Women's Health Initiative Estrogen-alone Trial had differential disease and medical expenditure consequences across age groups.

OBJECTIVES: The Women's Health Initiative (WHI) randomized trial identified age differences in the benefit-risk profile of estrogen-alone (ET) use. The impact of WHI trial on disease-associated medical expenditures attributable to subsequent decreased ET utilization has, however, not been measured. Therefore, the objective of this analysis was to quantify the age-specific disease-associated medical expenditures attributable to reduced ET utilization after the WHI Hormone Therapy (HT) trials. METHODS: Population-level disease counts and associated expenditures between 2003 and 2015 were compared between an observed ET-user population versus a hypothetical ET-user population assuming absence of the WHI HT trials, constructed by extrapolating ET utilization rates from 1996 to 2002 assuming pre-WHI HT rates would have continued without publication of the WHI HT trial data (2002-2004). Analyses were stratified by age (50-59, 60-69, and 70-79 years). Input data were extracted from Medical Expenditure Panel Survey and the literature. The primary outcomes were: ET utilization, chronic diseases (breast cancer, stroke, coronary heart disease, colorectal cancer, pulmonary embolism, and hip fracture) and disease-associated direct medical expenditures. RESULTS: Over 13 years, the decline in ET utilization was associated with $4.1 billion expenditure for excess chronic diseases (37,549 excess events) among women in their 50s, compared to savings of $1.5 billion and $4.4 billion for diseases averted by lower ET utilization among women in their 60s (13,495 fewer events) and 70s (40,792 fewer events), respectively. CONCLUSION: The decline in ET utilization had differential disease and expenditure consequences by age groups in the United States. These results are limited by the lack of inclusion of vasomotor symptom benefit and costs of alternative medications for these symptoms in the analysis.

Cost-sharing payments for out-of-network care in commercially insured adults.

OBJECTIVES: Providers who do not contract with insurance plans are considered out-of-network (OON) providers. There were 2 objectives in this study: (1) to examine the variations of OON cost sharing, both at the state level and by care settings, and (2) to investigate the pattern of OON care use and cost sharing associated with OON care over time. STUDY DESIGN: Secondary data analysis using claims data of employer-sponsored insurance enrollees. METHODS: The study sample included adults aged 18 to 64 years who were continuously enrolled for at least a full calendar year with medical and prescription drug coverage and for whom OON care payment data were available. We examined levels and distributions of cost sharing for OON care from 2012 to 2017, in both emergency department (ED) and non-ED care settings. Outcome measures included annual use of health plan-covered OON care and total out-of-pocket (OOP) cost sharing for OON care. We also measured the use of and cost-sharing spending for OON care based on urgency and site of service. Logistic regression models were constructed to estimate the probability of OON care. Among those with each type of OON care, a generalized linear regression model was used to estimate the OOP spending on OON care. RESULTS: Slowly decreasing rates of OON care over time occurred in different care settings and at different urgency levels. The cost-sharing amounts for OON care rose rapidly from 2012 through 2016, before slowing slightly in 2017. The growth of cost sharing for OON care during nonemergent hospitalizations especially increased from $671 to $1286 during the study period. The amount enrollees spent on OON care grew in most states, but there were substantial variations. CONCLUSIONS: Cost-sharing payments for OON care represent a growing financial burden for some enrollees. Consumers should be held harmless from higher cost sharing for OON care when it occurs without their knowledge or consent. Further, health plan network adequacy may also merit closer scrutiny. Leveraging provider participation in narrow networks must be balanced with broader consumer protections.

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

BACKGROUND: The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. OBJECTIVE: The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. METHODS: We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. RESULTS: In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the first DSC. ITS analyses demonstrated variability but pointed to an increase in interest around the first DSC. Chow tests were significant (P<.0001) for both DSCs on Facebook and Twitter, but only the first DSC on Google Trends. Wikipedia edits occurred soon after each DSC release, citing news articles rather than the DSC itself and presenting content that needed subsequent revisions for accuracy. CONCLUSIONS: Social media offers challenges and opportunities for dissemination of the DSC messages. The FDA could consider strategies for more actively disseminating DSC safety information through social media platforms, particularly when announcements require updating. The FDA may also benefit from directly contributing content to websites like Wikipedia that are frequently accessed for drug-related information.

Trends and Patterns of Corticosteroid Use During Coronary Artery Bypass Grafting Surgery in the United States.

BACKGROUND: Several clinical trials have documented clinical benefits associated with prophylactic corticosteroid administration at the time of coronary artery bypass graft (CABG) surgery, including a reduction in the risk of atrial fibrillation and hospital length of stay. Despite the published data, the extent to which providers have adopted the perioperative use of corticosteroids remains unknown. OBJECTIVES: To assess temporal trends, between-hospital variation, and determinants of perioperative intravenous corticosteroid use during CABG surgery. METHODS: We identified all patients admitted for CABG surgery in the Premier Healthcare Database (2003-2014), a large US-based inpatient database. We determined the proportion of patients administered prophylactic corticosteroids on the day of CABG surgery. Linear time-series models were used to estimate the rate and trend of corticosteroid use over time. Separate multivariable generalized estimating equation models were used to quantify the variation in and determinants of perioperative corticosteroid use. RESULTS: Of 401 788 eligible patients who underwent a CABG surgery between 2003 and 2014, 20% (n = 80 681) were administered intravenous prophylactic perioperative corticosteroids (methylprednisolone, dexamethasone, or hydrocortisone). Corticosteroid use increased from 17.5% in 2003 to 22.6% in 2014 (annual rate = 0.42%; P < .001). Individual hospitals accounted for >50% of variation in corticosteroid use. High between-hospital variation was also observed, and the probability of utilization was ≥32.4% in the upper versus ≤3.4% in the bottom quartiles of hospitals. CONCLUSION: Prophylactic corticosteroid administration during CABG has increased gradually since 2003. To further evaluate the risk-benefit trade-off associated with their use, we believe a large-scale outcomes study is warranted to assess this highly variable practice.

Variation in adherence to medications across the healthcare system in two comparative effectiveness research cohorts.

AIM: To assess heterogeneity in adherence to medications in two example comparative effectiveness research studies. PATIENTS & METHODS: We analyzed data from commercially insured patients initiating a statin or anticoagulant during 2005-2012. We calculated the cross-validated R2 from a series of hierarchical linear models to assess variation in 1-year adherence. RESULTS: There was less heterogeneity in adherence in the statin cohort compared with the anticoagulant cohort, where patient characteristics explained 7.2% of variation in adherence, and adding therapy and provider characteristics increased the proportion of variation explained to 8.0 and 8.5%, cumulatively. Random effects provided essentially no explanatory power, even in the statin cohort with large numbers of patients clustered within each pharmacy, prescriber and provider. CONCLUSION: The dependence of adherence on the healthcare system was stronger when the healthcare system influenced treatment choice and patient access to medication and when indications for treatment were strong.

Time From Emergency Department Evaluation to Operation and Appendiceal Perforation.

BACKGROUND AND OBJECTIVES: In patients with appendicitis, the risk of perforation increases with time from onset of symptoms. We sought to determine if time from emergency department (ED) physician evaluation until operative intervention is independently associated with appendiceal perforation (AP) in children. METHODS: We conducted a planned secondary analysis of children aged 3 to 18 years with appendicitis enrolled in a prospective, multicenter, cross-sectional study of patients with abdominal pain (<96 hours). Time of initial physical examination and time of operation were recorded. The presence of AP was determined using operative reports. We analyzed whether duration of time from initial ED physician evaluation to operation impacted the odds of AP using multivariable logistic regression, adjusting for traditionally suggested risk factors that increase the risk of perforation. We also modeled the odds of perforation in a subpopulation of patients without perforation on computed tomography. RESULTS: Of 955 children with appendicitis, 25.9% (n = 247) had AP. The median time from ED physician evaluation to operation was 7.2 hours (interquartile range: 4.8-8.5). Adjusting for variables associated with perforation, duration of time (≤ 24 hours) between initial ED evaluation and operation did not significantly increase the odds of AP (odds ratio = 1.0, 95% confidence interval, 0.96-1.05), even among children without perforation on initial computed tomography (odds ratio = 0.95, 95% confidence interval, 0.89-1.02). CONCLUSIONS: Although duration of abdominal pain is associated with AP, short time delays from ED evaluation to operation did not independently increase the odds of perforation.

Clinical Outcomes of Concomitant Use of Warfarin and Selective Serotonin Reuptake Inhibitors: A Multidatabase Observational Cohort Study.

BACKGROUND: Patients treated with warfarin are often coprescribed selective serotonin reuptake inhibitors (SSRIs) for coexisting depression. Some SSRIs are potent CYP2C9 inhibitors that may increase warfarin plasma concentrations and the risk of bleeding. We aimed to examine the effect of the putative CYP2C9-mediated warfarin-SSRI interaction on clinical outcomes. METHODS: We conducted an observational cohort study among warfarin initiators who had a subsequent SSRI prescription in 5 US claims databases. Patients were followed for up to 180 days as long as they were exposed to both warfarin and their index SSRI groups. Cox regression models were used to estimate hazard ratios and 95% confidence intervals for bleeding events, ischemic or thromboembolic events, and mortality comparing patients treated with SSRIs that are potent CYP2C9 inhibitors (fluoxetine, fluvoxamine) with those treated with other SSRIs after propensity score matching. FINDINGS: The eligible cohort comprised 52,129 patients. Hazard ratios were 1.14 (95% confidence interval [CI], 0.94-1.38) for bleeding events, 1.03 (95% CI, 0.87-1.21) for ischemic or thromboembolic events, and 0.90 (95% CI, 0.72-1.14) for mortality. Results were consistent across individual component outcomes, different warfarin stabilization periods, and subgroup analyses. CONCLUSIONS: Patients concomitantly treated with warfarin and SSRIs that are potent CYP2C9 inhibitors had comparable rates of bleeding events, ischemic or thromboembolic events, and mortality as did patients cotreated with warfarin and other SSRIs, although small but potentially meaningful effects on bleeding cannot be completely excluded. SSRI inhibition of CYP2C9 does not appear to affect major safety or effectiveness outcomes of warfarin treatment in clinical practice, where patients may be closely monitored.

Impact of an Interaction Between Clopidogrel and Selective Serotonin Reuptake Inhibitors.

Clopidogrel is a pro-drug that requires activation by the cytochrome P450 (CYP) enzyme system. Patients receiving clopidogrel are often treated with selective serotonin reuptake inhibitors (SSRIs) for co-existing depression. SSRIs that inhibit the CYP2C19 enzyme have the potential to reduce the effectiveness of clopidogrel. Using 5 US databases (1998 to 2013), we conducted a cohort study of adults who initiated clopidogrel while being treated with either an SSRI that inhibits CYP2C19 (fluoxetine and fluvoxamine) or a noninhibiting SSRI. Patients were matched by propensity score and followed for as long as they were exposed to both clopidogrel and the index SSRI group (primary analysis) or for 180 days after clopidogrel initiation (sensitivity analysis). Outcomes included a composite ischemic event (myocardial infarction, ischemic stroke, or a revascularization procedure) and a composite major bleeding event (gastrointestinal bleed or hemorrhagic stroke). The final propensity score-matched cohort comprised 9,281 clopidogrel initiators on CYP2C19-inhibiting SSRIs and 44,278 clopidogrel initiators on a noninhibiting SSRIs. Compared with those treated with a noninhibiting SSRI, patients on a CYP2C19-inhibiting SSRI had an increased risk of ischemic events (hazard ratio [HR] 1.12; 95% confidence interval [CI] 1.01 to 1.24), which was more pronounced in patients ≥65 years (HR 1.22; 95% CI 1.00 to 1.48). The HR for major bleeding was 0.76 (95% CI 0.50 to 1.17). In conclusion, the findings from this large, population-based study suggest that being treated with a CYP2C19-inhibiting SSRI when initiating clopidogrel may be associated with slight decrease in effectiveness of clopidogrel.