Chandrasekar Gopalakrishnan

Antidepressant Use Late in Pregnancy and Risk of Persistent Pulmonary Hypertension of the Newborn

IMPORTANCE The 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 MEASURES Recorded 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 RELEVANCE Evidence 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.

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review.

To systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).

Brief Report: Patterns and Secular Trends in Use of Immunomodulatory Agents During Pregnancy in Women With Rheumatic Conditions

To describe patterns and secular trends in the use of immunomodulatory agents in pregnant women with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS).

Comparative cardiovascular safety of glucagon‐like peptide‐1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study

To evaluate the comparative cardiovascular disease (CVD) safety of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in head‐to‐head comparisons with dipeptidyl peptidase‐4 (DPP‐4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in ‘real‐world’ patients with type 2 diabetes mellitus (T2DM).

Claims-based studies of oral glucose-lowering medications can achieve balance in critical clinical variables only observed in electronic health records

To evaluate the extent to which balance in unmeasured characteristics of patients with type 2 diabetes (T2DM) was achieved in claims data, by comparing against more detailed information from linked electronic health records (EHR) data.

Preferential prescribing and utilization trends of diabetes medications among patients with renal impairment: Emerging role of linagliptin and other dipeptidyl peptidase 4 inhibitors

Although many newer diabetes medications have become available in the last decade, most have not been widely studied in populations with chronic kidney disease under routine care. Linagliptin, a recently marketed dipeptidyl peptidase 4 (DPP‐4) inhibitor, is the only agent in the U.S. that does not require dose adjustment in patients with diabetes mellitus type 2 (T2DM) and renal impairment. We sought to describe baseline kidney function and other key characteristics among patients with diabetes mellitus type 2 (T2DM) initiating linagliptin and other diabetes medications, and to explore prescribing patterns among T2DM patients with moderate to severe renal impairment before and after the launch of linagliptin.

The relative benefits of claims and electronic health record data for predicting medication adherence trajectory

Background Healthcare providers are increasingly encouraged to improve their patients’ adherence to chronic disease medications. Prediction of adherence can identify patients in need of intervention, but most prediction efforts have focused on claims data, which may be unavailable to providers. Electronic health records (EHR) are readily available and may provide richer information with which to predict adherence than is currently available through claims. Methods In a linked database of complete Medicare Advantage claims and comprehensive EHR from a multi‐specialty outpatient practice, we identified patients who filled a prescription for a statin, antihypertensive, or oral antidiabetic during 2011 to 2012. We followed patients to identify subsequent medication filling patterns and used group‐based trajectory models to assign patients to adherence trajectories. We then identified potential predictors from both claims and EHR data and fit a series of models to evaluate the accuracy of each data source in predicting medication adherence. Results Claims were highly predictive of patients in the worst adherence trajectory (C = 0.78), but EHR data also provided good predictions (C = 0.72). Among claims predictors, presence of a prior gap in filling of at least 6 days was by far the most influential predictor. In contrast, good predictions from EHR data required complex models with many variables. Conclusion EHR data can provide good predictions of adherence trajectory and therefore may be useful for providers seeking to deploy resource‐intensive interventions. However, prior adherence information derived from claims is most predictive, and can supplement EHR data when it is available.

Effect of a Remotely Delivered Tailored Multicomponent Approach to Enhance Medication Taking for Patients With Hyperlipidemia, Hypertension, and Diabetes: The STIC2IT Cluster Randomized Clinical Trial

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 A1c 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

Claims data studies of direct oral anticoagulants can achieve balance in important clinical parameters only observable in electronic health records

Claims databases provide information on the effects of direct oral anticoagulants (DOACs) as used in routine care but may not contain important data on clinical characteristics, which may be captured in electronic health records (EHRs). Within a US claims database, we identified patients initiating a DOAC or warfarin between October 2010 and December 2014. Propensity score (PS) matching, 1:1, was used to balance 78 claims‐defined baseline characteristics. We evaluated whether balance was achieved in patient characteristics immeasurable in the claims data study by evaluating the balance in clinical information (using absolute standardized differences (aSDs)) from linked EHR data. From a claims data cohort study of 140,187 patients, 5,935 (4.2%) were linked to EHR data. After PS matching, almost all EHR‐defined patient characteristics were well balanced (aSD < 0.1). A new user active comparator design with 1:1 PS matching on many patient characteristics improved balance on clinical risk factors observed in EHRs but not in claims data.

Patterns and secular trends in use of immunomodulatory agents during pregnancy in women with rheumatologic conditions: Immunomodulatory agents in pregnancy

To describe patterns and secular trends in the use of immunomodulatory agents in pregnant women with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS).