Association Between Patient-Centered Medical Homes and Adherence to Chronic Disease Medications: A Cohort Study.

BACKGROUND: Despite the widespread adoption of patient-centered medical homes into primary care practice, the evidence supporting their effect on health care outcomes has come primarily from geographically localized and well-integrated health systems. OBJECTIVE: To assess the association between medication adherence and medical homes in a national patient and provider population, given the strong ties between adherence to chronic disease medications and health care quality and spending. DESIGN: Retrospective cohort study. SETTING: Claims from a large national health insurer. PATIENTS: Patients initiating therapy with common medications for chronic diseases (diabetes, hypertension, and hyperlipidemia) between 2011 and 2013. MEASUREMENTS: Medication adherence in the 12 months after treatment initiation was compared among patients cared for by providers practicing in National Committee for Quality Assurance-recognized patient-centered medical homes and propensity score-matched control practices in the same Primary Care Service Areas. Linear mixed models were used to examine the association between medical homes and adherence. RESULTS: Of 313 765 patients meeting study criteria, 18 611 (5.9%) received care in patient-centered medical homes. Mean rates of adherence were 64% among medical home patients and 59% among control patients. Among 4660 matched control and medical home practices, medication adherence was significantly higher in medical homes (2.2% [95% CI, 1.5% to 2.9%]). The association between medical homes and better adherence did not differ significantly by disease state (diabetes, 3.0% [CI, 1.5% to 4.6%]; hypertension, 3.2% [CI, 2.2% to 4.2%]; hyperlipidemia, 1.5% [CI, 0.6% to 2.5%]). LIMITATION: Clinical outcomes related to medication adherence were not assessed. CONCLUSION: Receipt of care in a patient-centered medical home is associated with better adherence, a vital measure of health care quality, among patients initiating treatment with medications for common high-cost chronic diseases. PRIMARY FUNDING SOURCE: CVS Health.

Longitudinal Patterns of Spending Enhance the Ability to Predict Costly Patients: A Novel Approach to Identify Patients for Cost Containment.

BACKGROUND: With rising health spending, predicting costs is essential to identify patients for interventions. Many of the existing approaches have moderate predictive ability, which may result, in part, from not considering potentially meaningful changes in spending over time. Group-based trajectory modeling could be used to classify patients into dynamic long-term spending patterns. OBJECTIVES: To classify patients by their spending patterns over a 1-year period and to assess the ability of models to predict patients in the highest spending trajectory and the top 5% of annual spending using prior-year predictors. SUBJECTS: We identified all fully insured adult members enrolled in a large US nationwide insurer and used medical and prescription data from 2009 to 2011. RESEARCH DESIGN: Group-based trajectory modeling was used to classify patients by their spending patterns over a 1-year period. We assessed the predictive ability of models that categorized patients in the top fifth percentile of annual spending and in the highest spending trajectory, using logistic regression and split-sample validation. Models were estimated using investigator-specified variables and a proprietary risk-adjustment method. RESULTS: Among 998,651 patients, in the best-performing model, prediction was strong for patients in the highest trajectory group (C-statistic: 0.86; R: 0.47). The C-statistic of being in the top fifth percentile of spending in the best-performing model was 0.82 (R: 0.26). Approaches using nonproprietary investigator-specified methods performed almost as well as other risk-adjustment methods (C-statistic: 0.81 vs. 0.82). CONCLUSIONS: Trajectory modeling may be a useful way to predict costly patients that could be implementable by payers to improve cost-containment efforts.

Evaluating Cardiovascular Health Disparities Using Estimated Race/Ethnicity: A Validation Study.

BACKGROUND: Methods of estimating race/ethnicity using administrative data are increasingly used to examine and target disparities; however, there has been no validation of these methods using clinically relevant outcomes. OBJECTIVE: To evaluate the validity of the indirect method of race/ethnicity identification based on place of residence and surname for assessing clinically relevant outcomes. DATA SOURCES: A total of 2387 participants in the Post-MI Free Rx Event and Economic Evaluation (MI FREEE) trial who had both self-reported and Bayesian Improved Surname Geocoding method (BISG)-estimated race/ethnicity information available. STUDY DESIGN: We used tests of interaction to compare differences in the effect of providing full drug coverage for post-MI medications on adherence and rates of major vascular events or revascularization for white and nonwhite patients based upon self-reported and indirect racial/ethnic assignment. RESULTS: The impact of full coverage on clinical events differed substantially when based upon self-identified race (HR=0.97 for whites, HR=0.65 for nonwhites; interaction P-value=0.05); however, it did not differ among race/ethnicity groups classified using indirect methods (HR=0.87 for white and nonwhites; interaction P-value=0.83). The impact on adherence was the same for self-reported and BISG-estimated race/ethnicity for 2 of the 3 medication classes studied. CONCLUSIONS: Quantitatively and qualitatively different results were obtained when indirectly estimated race/ethnicity was used, suggesting that these techniques may not accurately describe aspects of race/ethnicity related to actual health behaviors.

Full coverage for preventive medications after myocardial infarction.

BACKGROUND: Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. METHODS: We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. RESULTS: Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). CONCLUSIONS: The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774.).

Use and overuse of left ventriculography.

BACKGROUND: Left ventriculography provided the first imaging of left ventricular function and was historically performed as part of coronary angiography despite a small but significant risk of complications. Because modern noninvasive imaging techniques are more accurate and carry smaller risks, the routine use of left ventriculography is of questionable utility. We sought to analyze the frequency that left ventriculography was performed during coronary angiography in patients with and without a recent alternative assessment of left ventricular function. METHODS: We performed a retrospective analysis of insurance claims data from the Aetna health care benefits database including all adults who underwent coronary angiography in 2007. The primary outcome was the concomitant use of left ventriculography during coronary angiography. RESULTS: Of 96,235 patients who underwent coronary angiography, left ventriculography was performed in 78,705 (81.8%). Use of left ventriculography was high in all subgroups, with greatest use in younger patients, those with a diagnosis of coronary disease, and those in the Southern United States. In the population who had undergone a very recent ejection fraction assessment by another modality (within 30 days) and who had had no intervening diagnosis of new heart failure, myocardial infarction, hypotension, or shock (37,149 patients), left ventriculography was performed in 32,798 patients (88%)-a rate higher than in the overall cohort. CONCLUSIONS: Left ventriculography was performed in most coronary angiography cases and often when an alternative imaging modality had been recently completed. New clinical practice guidelines should be considered to decrease the overuse of this invasive test.

The incidence of gastrointestinal perforations among rheumatoid arthritis patients.

OBJECTIVE: Gastrointestinal (GI) perforation has emerged as a novel safety concern in relation to medications used to treat rheumatoid arthritis (RA). This study was undertaken to characterize the incidence and risk factors for GI perforation in RA patients. METHODS: Using administrative databases of a large US health plan, we identified RA patients treated with biologic agents, methotrexate (MTX), oral glucocorticoids, and nonsteroidal antiinflammatory drugs (NSAIDs). Additional risk factors we evaluated included diverticulitis. Hospitalization with GI perforation was identified using a validated algorithm. Incidence rates and risk factors were evaluated using Cox proportional hazards models. RESULTS: Among 40,841 RA patients, 37 hospitalizations with GI perforation were identified. The rate of GI perforation among patients currently being treated with biologic agents who were also receiving oral glucocorticoids was higher (1.12 per 1,000 person-years [95% confidence interval (95% CI) 0.50-2.49]) than for patients being treated with biologic agents who were not also receiving glucocorticoids (0.47 per 1,000 person-years [95% CI 0.22-0.98]) or for patients being treated with MTX who were also receiving glucocorticoids (0.87 per 1,000 person-years [95% CI 0.36-2.10]). Neither biologic agents nor MTX was significantly associated with GI perforation, in contrast to current treatment with glucocorticoids and NSAIDs together (hazard ratio 4.7 [95% CI 1.9-12.0]) or glucocorticoids alone (hazard ratio 2.8 [95% CI 1.3-6.1]). Diverticulitis also was a strong risk factor (hazard ratio 9.1 [95% CI 3.1-26.4]). Seventy percent of patients with GI perforation received glucocorticoids, had antecedent diverticulitis, or both. CONCLUSION: GI perforation is an uncommon but serious adverse event among RA patients. Because a majority of patients with GI perforation were being treated with glucocorticoids or had previously experienced diverticulitis, these individuals should be considered at higher risk.

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

PURPOSE: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. METHODS: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. RESULTS: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. CONCLUSIONS: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk.

The comparative risk of serious infections among rheumatoid arthritis patients starting or switching biological agents.

BACKGROUND: It is unclear whether anti-tumour necrosis factor alpha and biological agents with different mechanisms of action have similar safety. This study evaluated the incidence of hospitalised infections among rheumatoid arthritis (RA) patients starting or switching various biological agents. METHODS: Using a database from a large US healthcare organisation from January 2005 to August 2009, the authors identified enrollees with RA and their treatment episodes entailing the new use of a biological agent, stratified by no biological use in the previous year ('biological-free') or switching from a different biological agent ('switchers'). Outcomes were hospitalised infections identified using previously validated algorithms. Proportional hazards models estimated the hazard ratio of hospitalised infections, comparing each biological agent with infliximab. RESULTS: Among 7847 biological treatment episodes, 63% were for biological-free patients and 37% for switchers. There were 364 hospitalised infections. Rates of hospitalised infection among biological-free patients and switchers were 4.6 and 7.0 per 100 person-years, respectively (p<0.0001). After multivariable adjustment controlling for biological-free/switcher status and other infection-related factors and compared with infliximab, users of abatacept (HR 0.68, 95% CI 0.48 to 0.96), adalimumab (HR 0.52, 0.39 to 0.71), etanercept (HR 0.64, 0.49 to 0.84) and rituximab (HR 0.81, 0.55 to 1.20) had lower rates of hospitalised infection. Patient risk factors contributed more to the risk of infection than did the risk associated with specific biological therapies. CONCLUSION: The rate of hospitalised infections among RA patients was highest for infliximab. Most of the variability in patients' risk of infection was driven by factors other than biological agent exposure.

Utilization Patterns of Oral Disease-Modifying Drugs in Commercially Insured Patients with Multiple Sclerosis.

BACKGROUND: The approval of new oral disease-modifying drugs (DMDs), such as fingolimod, dimethyl fumarate (DMF), and teriflunamide, has considerably expanded treatment options for relapsing forms of multiple sclerosis (MS). However, data describing the use of these agents in routine clinical practice are limited. OBJECTIVE: To describe time trends and identify factors associated with oral DMD treatment initiation and switching among individuals with MS. METHODS: Using data from a large sample of commercially insured patients, we evaluated changes over time in the proportion of MS patients who initiated treatment with an oral DMD and who switched from an injectable DMD to an oral DMD between 2009 and 2014 in the United States. We evaluated predictors of oral DMD use using conditional logistic regression in 2 groups matched on calendar time: oral DMD initiators matched to injectable DMDs initiators and oral DMD switchers matched to those who switched to a second injectable DMD. RESULTS: Our cohort included 7,576 individuals who initiated a DMD and 1,342 who switched DMDs, of which oral DMDs accounted for 6% and 39%, respectively. Oral DMD initiation and switching steadily increased from 5% to 16% and 35% to 84%, respectively, between 2011 and 2014, with DMF being the most commonly used agent. Of the potential predictors with clinical significance, a recent neurologist consultation (OR = 1.60; 95% CI = 1.20-2.15) and emergency department visit (OR = 1.43; 95% CI = 1.01-2.01) were significantly associated with oral DMD initiation. History of depression was noted to be a potential predictor of oral DMD initiation; however, the estimate for this predictor did not reach statistical significance (OR = 1.35; 95% CI = 0.99-1.84). No clinically relevant factors measured in our data were associated with switching to an oral DMD. CONCLUSIONS: Oral DMDs were found to be routinely used as second-line treatment. However, we identified few factors predictive of oral DMD initiation or switching, which implies that their selection is driven by patient and/or physician preferences. DISCLOSURES: This study was funded by CVS Caremark through an unrestricted research grant to Brigham and Women's Hospital. Shrank and Matlin were employees of, and shareholders in, CVS Health at the time of the study; they report no financial interests in products or services that are related to the subject of this study. Spettell is an employee of, and shareholder in, Aetna. Chitnis serves on clinical trial advisory boards for Novartis and Genzyme-Sanofi; has consulted for Bayer, Biogen Idec, Celgene, Novartis, Merck-Serono, and Genentech-Roche; and has received research support from NIH, National Multiple Sclerosis Society, Peabody Foundation, Consortium for MS Centers, Guthy Jackson Charitable Foundation, EMD-Serono, Novartis Biogen, and Verily. Desai reports receiving a research grant from Merck for unrelated work. Gagne is principal investigator of a research grant from Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital and has received grant support from Eli Lilly, all for unrelated work. He is also a consultant to Aetion and Optum. Minden reports grants from Biogen and other fees from Genentech, EMD Serano, Avanir, and Novartis, unrelated to this study. The other authors have no conflicts to report. This study was presented as a poster at the International Society for Pharmacoepidemiology 32nd Annual Meeting; August 25-28, 2016; Dublin, Ireland.

Aetna's Compassionate Care Program: Sustained Value for Our Members with Advanced Illness.

Background: In 2004, Aetna, a national health insurer, launched the Aetna Compassionate Care Program (ACCP) targeting members diagnosed with an advanced illness with a view to increase access to palliative care and hospice services. Objective: The objective of this study is to evaluate the impact of ACCP on health care utilization and hospice enrollment among enrolled members. Methods: This was a retrospective cohort study comparing participants in ACCP to a matched control group using a propensity score method. The study group consisted of Aetna Medicare Advantage members who participated in the ACCP between January 2014 and June 2015. Potential control group members were those who were not identified by the predictive model nor were referred to the ACCP program through other means. The primary outcomes of interest were hospice use measured as percent of members electing hospice and median number of days in hospice; health care utilization and medical costs measured as rates and medical costs associated with acute inpatient admissions, emergency room, primary care, and specialty visits in the 30 and 90 days before death. Results: Participants in the ACCP program were 36% more likely to enroll in hospice (79% vs. 58%, p < 0.0001) and had reduced acute inpatient medical costs ($4169 vs. $5863, p < 0.0001) driven primarily by fewer inpatient admissions (860 vs. 1017, p < 0.0001) in the last 90 days of life. Conclusions: Advanced illness case management programs such as ACCP can improve access to hospice and improve patient outcomes while reducing unnecessary admissions in the last 90 days of life.

Rationale and design of the Post-MI FREEE trial: a randomized evaluation of first-dollar drug coverage for post-myocardial infarction secondary preventive therapies.

BACKGROUND: Medication nonadherence is a major public health problem, especially for patients with coronary artery disease. The cost of prescription drugs is a central reason for nonadherence, even for patients with drug insurance. Removing patient out-of-pocket drug costs may increase adherence, improve clinical outcomes, and even reduce overall health costs for high-risk patients. The existing data are inadequate to assess whether this strategy is effective. TRIAL DESIGN: The Post-Myocardial Infarction Free Rx and Economic Evaluation (Post-MI FREEE) trial aims to evaluate the effect of providing full prescription drug coverage (ie, no copays, coinsurance, or deductibles) for statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers to patients after being recently discharged from the hospital. Potentially eligible patients will be those individuals who receive their health and pharmacy benefits through Aetna, Inc. Patients enrolled in a Health Savings Account plan, who are > or =65 years of age, whose plan sponsor (ie, the employer, union, government, or association that sponsors the particular benefits package) has opted out of participating in the study, and who do not receive both medical services and pharmacy coverage through Aetna will be excluded. The plan sponsor of each eligible patient will be block randomized to either full drug coverage or current levels of pharmacy benefit, and all subsequently eligible patients of that same plan sponsor will be assigned to the same benefits group. The primary outcome of the trial is a composite clinical outcome of readmission for acute MI, unstable angina, stroke, congestive heart failure, revascularization, or inhospital cardiovascular death. Secondary outcomes include medication adherence and health care costs. All patients will be followed up for a minimum of 1 year. CONCLUSION: The Post-MI FREEE trial will be the first randomized study to evaluate the impact of reducing cost-sharing for essential cardiac medications in high-risk patients on clinical and economic outcomes.

A distributed research network model for post-marketing safety studies: the Meningococcal Vaccine Study.

PURPOSE: We describe a multi-center post-marketing safety study that uses distributed data methods to minimize the need for covered entities to share protected health information (PHI). Implementation has addressed several issues relevant to creation of a large scale post-marketing drug safety surveillance system envisioned by the FDA's Sentinel Initiative. METHODS: This retrospective cohort study of Guillain-Barré syndrome (GBS) following meningococcal conjugate vaccination incorporates the data and analytic expertise of five research organizations closely affiliated with US health insurers. The study uses administrative claims data, plus review of full text medical records to adjudicate the status of individuals with a diagnosis code for GBS (ICD9 357.0). A distributed network approach is used to create the analysis files and to perform most aspects of the analysis, allowing nearly all of the data to remain behind institutional firewalls. Pooled analysis files transferred to a central site will contain one record per person for approximately 0.2% of the study population, and contain PHI limited to the month and year of GBS onset for cases or the index date for matched controls. RESULTS: The first planned data extraction identified over 9 million eligible adolescents in the target age range of 11-21 years. They contributed an average of 14 months of eligible time on study over 27 months of calendar time. MCV4 vaccination coverage levels exceeded 20% among 17-18-year olds and 16% among 11-13 and 14-16-year-old age groups by the second quarter of 2007. CONCLUSION: This study demonstrates the feasibility of using a distributed data network approach to perform large scale post-marketing safety analyses and is scalable to include additional organizations and data sources. We believe these results can inform the development of a large national surveillance system.

Predicting Adherence to Chronic Disease Medications in Patients with Long-term Initial Medication Fills Using Indicators of Clinical Events and Health Behaviors.

BACKGROUND: Efforts at predicting long-term adherence to medications have been focused on patients filling typical month-long supplies of medication. However, prediction remains difficult for patients filling longer initial supplies, a practice that is becoming increasingly common as a method to enhance medication adherence. OBJECTIVES: To (a) extend methods involving short-term filling behaviors and (b) develop novel variables to predict adherence in a cohort of patients receiving longer initial prescriptions. METHODS: In this retrospective cohort study, we used claims from a large national insurer to identify patients initiating a 90-day supply of oral medications for diabetes, hypertension, and hyperlipidemia (i.e., statins). Patients were included in the cohort if they had continuous database enrollment in the 180 days before and 365 days after medication initiation. Adherence was measured in the subsequent 12 months using the proportion of days covered metric. In total, 125 demographic, clinical, and medication characteristics at baseline and in the first 30-120 days after initiation were used to predict adherence using logistic regression models. We used 10-fold cross-validation to assess predictive accuracy by discrimination (c-statistic) measures. RESULTS: In total, 32,249 patients met the inclusion criteria, including 14,930 patients initiating statins, 12,887 patients initiating antihypertensives, and 4,432 patients initiating oral hypoglycemics. Prediction using only baseline variables was relatively poor (cross-validated c-statistic = 0.644). Including indicators of acute clinical conditions, health resource utilization, and short-term medication filling in the first 120 days greatly improved predictive ability (0.823). A model that incorporated all baseline characteristics and predictors within the first 120 days after medication initiation more accurately predicted future adherence (0.832). The best performing model that included all 125 baseline and postbaseline characteristics had strong predictive ability (0.837), suggesting the utility of measuring these novel postbaseline variables in this population. CONCLUSIONS: We demonstrate that long-term, 12-month adherence in patients filling longer supplies of medication can be strongly predicted using a combination of clinical, health resource utilization, and medication filling characteristics before and after treatment initiation. DISCLOSURES: This work was supported by an unrestricted grant from CVS Health to Brigham and Women's Hospital. Shrank and Matlin were employees and shareholders at CVS Health at the time of this study; they report no financial interests in products or services that are related to this subject. Spettell is an employee of, and shareholder in, Aetna. This research was previously presented at the 2016 Annual Conference of the International Society for Pharmacoepidemiology; August 25-28, 2016; Dublin, Ireland.

Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings.

Importance: Autism spectrum disorder (ASD) is known to be more prevalent among males than females in the general population. Although overall risk of recurrence of ASD among siblings has been estimated to be between 6.1% and 24.7%, information on sex-specific recurrence patterns is lacking. Objective: To estimate high-confidence sex-specific recurrence rates of ASD among siblings. Design, Setting, and Participants: This observational study used an administrative database to measure the incidence of ASD among children in 1 583 271 families (37 507 with at least 1 diagnosis of ASD) enrolled in commercial health care insurance plans at a large US managed health care company from January 1, 2008, through February 29, 2016. Families in the study had 2 children who were observed for at least 12 months between 4 and 18 years of age. Main Outcomes and Measures: The primary measure of ASD recurrence was defined as the diagnosis of ASD in a younger sibling of an older sibling with an ASD diagnosis. Results: Among the 3 166 542 children (1 547 266 females and 1 619 174 males; mean [SD] age, 11.2 [4.7] years) in the study, the prevalence of ASD was 1.96% (95% CI, 1.94%-1.98%) among males and 0.50% (95% CI, 0.49%-0.51%) among females. When a male was associated with risk in the family, ASD was diagnosed in 4.2% (95% CI, 3.8%-4.7%) of female siblings and 12.9% (95% CI, 12.2%-13.6%) of male siblings. When a female was associated with risk in the family, ASD was diagnosed in 7.6% (95% CI, 6.5%-8.9%) of female siblings and 16.7% (95% CI, 15.2%-18.4%) of male siblings. Conclusions and Relevance: These findings are in agreement with the higher rates of ASD observed among males than among females in the general population. Our study provides more specific guidance for the screening and counseling of families and may help inform future investigations into the environmental and genetic factors that confer risk of ASD.

Predicting 1-Year Statin Adherence Among Prevalent Users: A Retrospective Cohort Study.

BACKGROUND: Attempts to predict who is at risk of future nonadherence have largely focused on predictions at the time of therapy initiation; however, these users are only a small proportion of all patients on therapy at any point in time. Methods to predict nonadherence for established medication users, which have not been previously described in the literature, would be helpful to guide efforts to enhance the use of evidence-based therapies. OBJECTIVE: To test approaches for adherence prediction among prevalent statin users, namely the use of short-term filling behavior, investigator-specified predictors from medical and pharmacy administrative claims, and the empirical selection of potential predictors using the high-dimensional propensity score variable selection algorithm. METHODS: Medical and prescription claims data from a large national health insurer were used to create a cohort of patients who filled statin medication prescriptions in January 2012. We defined 6 groups of adherence predictors and estimated 10 main models to predict medication adherence in the full cohort. The same was done for the population stratified based on the days supply of the index statin prescription (≤ 30 days vs. > 30 days). RESULTS: The study cohort consisted of 93,777 individuals, 58.4% of which were adherent to statins during follow-up. The use of 3 pre-index adherence predictors alone achieved a c-statistic of 0.70. Investigator-specified and empirically selected pharmacy, medical, and demographic variables did substantially worse (0.57-0.60). The use of 3 indicators of post-index adherence achieved a higher c-statistic than the best-performing model using pre-index information (0.74 vs. 0.72). The addition of 3 pre-index adherence predictors further improved discrimination (0.78). CONCLUSIONS: This analysis demonstrated the ability to predict adherence among medication users using filling behavior before and immediately after an index prescription fill. DISCLOSURES: This work was supported by an unrestricted grant from CVS Health to Brigham and Women's Hospital. Shrank, Brennan, and Matlin were employees and shareholders at CVS Health at the time of this manuscript preparation; they report no financial interests in products or services that are related to the subject of the manuscript. Franklin has received consulting fees from Aetion. Chourdry has received grants from the National Heart, Lung, and Blood Institute, PhRMA Foundation, Merck, Sanofi, AstraZeneca, and MediSafe. Spettell is an employee of, and shareholder in, Aetna. The other authors have nothing to disclose. Krumme, Choudhry, Tong, and Franklin contributed to the study design, interpretation of results, and manuscript drafting. Tong prepared and analyzed the data. Isaman, Spettell, Shrank, Brennan, and Matlin provided interpretation of results and critical manuscript revisions.

Effect of Electronic Reminders, Financial Incentives, and Social Support on Outcomes After Myocardial Infarction: The HeartStrong Randomized Clinical Trial.

Importance: Adherence to medications prescribed after acute myocardial infarction (AMI) is low. Wireless technology and behavioral economic approaches have shown promise in improving health behaviors. Objective: To determine whether a system of medication reminders using financial incentives and social support delays subsequent vascular events in patients following AMI compared with usual care. Design, Setting, and Participants: Two-arm, randomized clinical trial with a 12-month intervention conducted from 2013 through 2016. Investigators were blinded to study group, but participants were not. Design was a health plan-intermediated intervention for members of several health plans. We recruited 1509 participants from 7179 contacted AMI survivors (insured with 5 large US insurers nationally or with Medicare fee-for-service at the University of Pennsylvania Health System). Patients aged 18 to 80 years were eligible if currently prescribed at least 2 of 4 study medications (statin, aspirin, ß-blocker, antiplatelet agent), and were hospital inpatients for 1 to 180 days and discharged home with a principal diagnosis of AMI. Interventions: Patients were randomized 2:1 to an intervention using electronic pill bottles combined with lottery incentives and social support for medication adherence (1003 patients), or to usual care (506 patients). Main Outcomes and Measures: Primary outcome was time to first vascular rehospitalization or death. Secondary outcomes were time to first all-cause rehospitalization, total number of repeated hospitalizations, medication adherence, and total medical costs. Results: A total of 35.5% of participants were female (n = 536); mean (SD) age was 61.0 (10.3) years. There were no statistically significant differences between study arms in time to first rehospitalization for a vascular event or death (hazard ratio, 1.04; 95% CI, 0.71 to 1.52; P = .84), time to first all-cause rehospitalization (hazard ratio, 0.89; 95% CI, 0.73 to 1.09; P = .27), or total number of repeated hospitalizations (hazard ratio, 0.94; 95% CI, 0.60 to 1.48; P = .79). Mean (SD) medication adherence did not differ between control (0.42 [0.39]) and intervention (0.46 [0.39]) (difference, 0.04; 95% CI, -0.01 to 0.09; P = .10). Mean (SD) medical costs in 12 months following enrollment did not differ between control ($29 811 [$74 850]) and intervention ($24 038 [$66 915]) (difference, -$5773; 95% CI, -$13 682 to $2137; P = .15). Conclusions and Relevance: A compound intervention integrating wireless pill bottles, lottery-based incentives, and social support did not significantly improve medication adherence or vascular readmission outcomes for AMI survivors. Trial Registration: clinicaltrials.gov Identifier: NCT01800201.

Differences in self-management behaviors and use of preventive services among diabetes management enrollees by race and ethnicity.

We assessed the degree that managed care organization (MCO) enrollees used preventive services and engaged in diabetes self-management behaviors by race/ethnicity. A 40-item selfadministered survey was mailed to 19,483 diabetic MCO enrollees. The survey measured use of eight preventive services and engagement in four self-management behaviors among enrollees who self-identified as black, white, or Hispanic. Of the 6,035 surveys analyzed, 4,623 respondents (76.6%) were white, 984 (16.3%) were black, and 428 (7.0%) were Hispanic. Black and Hispanic respondents reported more healthcare visits (mean of 7.0 and 6.5, respectively) in the past year compared to whites (mean, 5.7; p < 0.0001). However, compared to whites, blacks had significantly lower utilization of five of the eight preventive services measured, and Hispanics had significantly lower utilization of seven of the eight preventive services (p < 0.005). With regard to self-management behaviors, blacks were significantly less likely than whites to monitor their diet (65.9% vs. 73.7%, p < 0.0001), exercise (46.4% vs. 52.8%; p = 0.0004) and not smoke (85.1% vs. 89.3%; p = 0.0002); while Hispanics were less likely to monitor their diet (67.3% vs. 73.7%, p = 0.0051). All racial/ethnic groups had low levels of selfmanagement behaviors. Further research is warranted to identify why disparities remain in settings where services are universally available, and to find practical ways to eliminate disparities in a group with routine healthcare encounters.

Assessing the Impact of Medication Adherence on Long-Term Cardiovascular Outcomes.

BACKGROUND: Although guideline-recommended therapies reduce major adverse cardiovascular events (MACE) in patients after myocardial infarction (MI) or those with atherosclerotic disease (ATH), adherence is poor. OBJECTIVES: The goal of this study was to determine the association between medication adherence levels and long-term MACE in these patients. METHODS: We queried the claims database of a large health insurer for patients hospitalized for MI or with ATH. The primary outcome measure was a composite of all-cause death, MI, stroke, or coronary revascularization. Using proportion of days covered for statins and angiotensin-converting enzyme inhibitors, patients were stratified as fully adherent (≥80%), partially adherent (≥40% to ≤79%), or nonadherent (<40%). Per-patient annual direct medical (ADM) costs were estimated by using unit costs from 2 national files. RESULTS: Data were analyzed for 4,015 post-MI patients and 12,976 patients with ATH. In the post-MI cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (18.9% vs. 26.3%; hazard ratio [HR]: 0.73; p = 0.0004) and partially adherent (18.9% vs. 24.7%; HR: 0.81; p = 0.02) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $369 and $440 compared with the partially adherent and nonadherent groups, respectively. In the ATH cohort, the fully adherent group had a significantly lower rate of MACE than the nonadherent (8.42% vs. 17.17%; HR: 0.56; p < 0.0001) and the partially adherent (8.42% vs. 12.18%; HR: 0.76; p < 0.0001) groups at 2 years. The fully adherent group had reduced per-patient ADM costs for MI hospitalizations of $371 and $907 compared with the partially adherent and nonadherent groups. CONCLUSIONS: Full adherence to guideline-recommended therapies was associated with a lower rate of MACE and cost savings, with a threshold effect at >80% adherence in the post-MI population; at least a 40% level of long-term adherence needs to be maintained to continue to accrue benefit. Novel approaches to improve adherence may significantly reduce cardiovascular events.

Multicomponent Internet continuing medical education to promote chlamydia screening.

BACKGROUND: Low Chlamydia trachomatis screening rates create an opportunity to test innovative continuing medical education (CME) programs. Few studies of Internet-based physician learning have been evaluated with objective data on practice patterns. DESIGN: This randomized controlled trial tested a multicomponent Internet CME (mCME) intervention for increasing chlamydia screening of at-risk women aged 16 to 26 years. SETTING: Eligible physician offices had > or =20 patients at risk for chlamydia as defined by the Health Plan Employer Data and Information Set (HEDIS), had at least one primary care physician (internal medicine, family medicine/general practice, pediatrics) with Internet access, and participated in the study managed care organization. The 191 randomized primary care offices represented 20 states. INTERVENTION: The intervention, available from February to December 2001, consisted of four case-based learning modules, was tailored in real time to each physician based on theory of behavior change, and included office-level feedback of chlamydia screening rates. MAIN OUTCOME MEASURE: HEDIS chlamydia screening rates for the pre-intervention (2000) and post-intervention (2002) periods. RESULTS: Pre-intervention screening rates for the intervention and comparison offices were 18.9% and 16.2% (p =0.135). Post-intervention screening rates for the intervention and comparison offices were 15.5% and 12.4%, respectively (p =0.044, adjusting for baseline performance). CONCLUSIONS: The substantial decline in chlamydia screening rates observed in the comparison offices was significantly attenuated for the intervention offices. The mCME favorably influenced chlamydia screening by primary care physicians.