IMPORTANCEThe association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006. OBJECTIVE To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy. DESIGN AND SETTING Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.PARTICIPANTS A total of 3 789 330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders.EXPOSURES FOR OBSERVATIONAL STUDIES SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use. MAIN OUTCOMES AND MEASURESRecorded diagnosis of PPHN during the first 30 days after delivery.RESULTS A total of 128 950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102 179 (2.7%) used an SSRI and 26 771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10 000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10 000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10 000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74). CONCLUSIONS AND RELEVANCEEvidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

IMPORTANCE Approximately half of patients with chronic conditions are nonadherent to prescribed medications, and interventions have been only modestly effective. OBJECTIVE To evaluate the effect of a remotely delivered multicomponent behaviorally tailored intervention on adherence to medications for hyperlipidemia, hypertension, and diabetes. DESIGN, SETTING, AND PARTICIPANTS Two-arm pragmatic cluster randomized controlled trial at a multispecialty group practice including participants 18 to 85 years old with suboptimal hyperlipidemia, hypertension, or diabetes disease control, and who were nonadherent to prescribed medications for these conditions. INTERVENTIONS Usual care or a multicomponent intervention using telephone-delivered behavioral interviewing by trained clinical pharmacists, text messaging, pillboxes, and mailed progress reports. The intervention was tailored to individual barriers and level of activation. MAIN OUTCOMES AND MEASURES The primary outcome was medication adherence from pharmacy claims data. Secondary outcomes were disease control based on achieved levels of low-density lipoprotein cholesterol, systolic blood pressure, and hemoglobin A 1c from electronic health records, and health care resource use from claims data. Outcomes were evaluated using intention-to-treat principles and multiple imputation for missing values. RESULTS Fourteen practice sites with 4078 participants had a mean (SD) age of 59.8 (11.6) years; 45.1% were female. Seven sites were each randomized to intervention or usual care. The intervention resulted in a 4.7% (95% CI, 3.0%-6.4%) improvement in adherence vs usual care but no difference in the odds of achieving good disease control for at least 1 (odds ratio [OR], 1.10; 95% CI, 0.94-1.28) or all eligible conditions (OR, 1.05; 95% CI, 0.91-1.22), hospitalization (OR, 1.02; 95% CI, 0.78-1.34), or having a physician office visit (OR, 1.11; 95% CI, 0.91-1.36). However, intervention participants were significantly less likely to have an emergency department visit (OR, 0.62; 95% CI, 0.45-0.85). In as-treated analyses, the intervention was associated with a 10.4% (95% CI, 8.2%-12.5%) increase in adherence, a significant increase in patients achieving disease control for at least 1 eligible condition (OR, 1.24; 95% CI, 1.03-1.50), and nonsignificantly improved disease control for all eligible conditions (OR, 1.18; 95% CI, 0.99-1.41). CONCLUSIONS AND RELEVANCE A remotely delivered multicomponent behaviorally tailored intervention resulted in a statistically significant increase in medication adherence but did not change clinical outcomes. Future work should focus on identifying which groups derive the most clinical benefit from adherence improvement efforts. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02512276

Background: Healthcare claims databases can provide information on the effects of type 2 diabetes (T2DM) medications as used in routine care, but often do not contain data on important clinical characteristics, which may be captured in electronic health records (EHR). Objectives: To evaluate the extent to which balance in unmeasured patient characteristics was achieved in claims data, by comparing against more detailed information from linked EHR data. Methods: Within a large US commercial insurance database and using a cohort design, we identified T2DM patients initiating linagliptin or a comparator agent within class (i.e., other DPP-4 inhibitors) or outside class (i.e., (pioglitazone or sulfonylureas) between 05/2011-12/2012. We focused on comparators used at a similar stage of diabetes as linagliptin. For each comparison, 1:1 propensity score (PS) matching was used to balance over 100 baseline claims-based characteristics, including proxies of diabetes severity and duration. Additional clinical data from EHRs was available for a subset of patients. We assessed representativeness of the claims-EHR linked subset, evaluated the balance of claims- and EHR-based covariates before and after PS-matching via standardized differences (SD), and quantified the potential bias associated with observed imbalances. Results: From a claims-based study population of 166,613 T2DM patients, 7,219 (4.3%) patients were linked to their EHR data. Claims-based characteristics between the EHR-linked and EHR-unlinked patients were comparable (SD<0.1), confirming representativeness of the EHR-linked subset. The balance of claims-based and EHR-based patient characteristics appeared to be reasonable before PS-matching and generally improved in the PS-matched population, to be SD<0.1 for most patient characteristics and SD<0.2 for select laboratory results and BMI categories, not large enough to cause meaningful confounding. Conclusion: In the context of pharmacoepidemiologic research on diabetes therapy, choosing appropriate comparison groups paired with a new user design and 1:1 PS matching on many proxies of diabetes severity and duration improves balance in covariates typically unmeasured in administrative claims datasets, to an extent that residual confounding is unlikely.