Impact of Undertreatment of Depression on Suicide Risk Among Children and Adolescents With Major Depressive Disorder: A Microsimulation Study.

Undertreatment of depression is common among children and adolescents, but evidence of the impact of undertreatment of depression on risk of suicide is limited due to the low base rate of suicide in the population and lack of sufficient data sources. We developed a microsimulation model that uses evidence from multiple sources to study the impact of different durations of antidepressant treatment on suicide risk in a synthesized sample that is nationally representative of children and adolescents with major depressive disorder. Compared with receiving no treatment, suicide rate and risk of suicide attempt both decreased with increasing duration of antidepressant treatment (for 12 weeks, suicide rate ratios = 0.78 (95% credible interval (CrI): 0.58, 1.15), 36 weeks, 0.65 (95% CrI: 0.44, 0.90), and 52 weeks, 0.63 (95% CrI: 0.45, 0.72); for suicide attempt: 12 weeks, suicide risk ratios = 0.68 (95% CrI: 0.62, 0.69), 36 weeks, 0.56 (95% CrI: 0.52, 0.57), and 52 weeks, 0.55 (95% CrI: 0.51, 0.56). The suicide rate and risk of suicide attempt were lower in children than in adolescents. Males had a lower risk of suicide attempt but higher suicide rate than females. The findings from the microsimulation model show that completion of 12-36 weeks of antidepressant treatment may reduce suicide attempt and suicide among children and adolescents with major depressive disorder.

Attribute Development Using Continuous Stakeholder Engagement to Prioritize Treatment Decisions: A Framework for Patient-Centered Research.

OBJECTIVES: To develop a methodological approach for selecting, validating, and prioritizing attributes for health care decision making. METHODS: Participants (n = 48) were recruited from community support groups if they had a child aged 26 years or younger diagnosed with a coexisting mental health condition and cognitive impairment. Six in-depth interviews eliciting care management experiences were transcribed and coded into themes following the principles of grounded theory and the constant comparative method. Six focus groups involving 42 participants assessed the relevance, priority, and meaning and inter-relationship among the themes. The positive predictive value and sensitivity assessed agreement on thematic meaning. A final list was selected from the top priorities with good agreement as candidate attributes. Attribute levels reflecting the range of experiences in care management decisions emerged from the verbatim passages within each coded theme. RESULTS: Participants were the child's mother (73%), white (77%), married (69%), and on average 48 years old. The children were on average 14 years old; 44% had an intellectual disability, 25% had autism, and more than half had anxiety or attention-deficit/hyperactivity disorder. All 14 attributes identified from the in-depth interviews were deemed relevant. The positive predictive value exceeded 90%, and the sensitivity ranged from 64% to 89%. The final set of attributes formed the framework for care management decisions consisting of six attributes (medication, behavior, services, social, treatment effects, and school) each with three levels. CONCLUSIONS: A systematic approach grounded in qualitative methods produced a framework of relevant, important, and actionable attributes representing competing alternatives in clinical decisions.

Using claims data to predict dependency in activities of daily living as a proxy for frailty.

PURPOSE: Estimating drug effectiveness and safety among older adults in population-based studies using administrative health care claims can be hampered by unmeasured confounding as a result of frailty. A claims-based algorithm that identifies patients likely to be dependent, a proxy for frailty, may improve confounding control. Our objective was to develop an algorithm to predict dependency in activities of daily living (ADL) in a sample of Medicare beneficiaries. METHODS: Community-dwelling respondents to the 2006 Medicare Current Beneficiary Survey, >65 years old, with Medicare Part A, B, home health, and hospice claims were included. ADL dependency was defined as needing help with bathing, eating, walking, dressing, toileting, or transferring. Potential predictors were demographics, International Classification of Diseases, Ninth Revision Clinical Modification diagnosis/procedure and durable medical equipment codes for frailty-associated conditions. Multivariable logistic regression was used to predict ADL dependency. Cox models estimated hazard ratios for death as a function of observed and predicted ADL dependency. RESULTS: Of 6391 respondents, 57% were female, 88% white, and 38% were ≥80. The prevalence of ADL dependency was 9.5%. Strong predictors of ADL dependency were charges for a home hospital bed (OR = 5.44, 95%CI = 3.28-9.03) and wheelchair (OR = 3.91, 95%CI = 2.78-5.51). The c-statistic of the final model was 0.845. Model-predicted ADL dependency of 20% or greater was associated with a hazard ratio for death of 3.19 (95%CI: 2.78, 3.68). CONCLUSIONS: An algorithm for predicting ADL dependency using health care claims was developed to measure some aspects of frailty. Accounting for variation in frailty among older adults could lead to more valid conclusions about treatment use, safety, and effectiveness.

Metformin and the risk of endometrial cancer: a population-based cohort study.

OBJECTIVE: While some observational studies have suggested a protective effect of metformin on incident cancer, concerns about potential bias remain. We compared the incidence of endometrial cancer in metformin versus sulfonylurea initiators. Research design and methods We conducted a retrospective cohort analysis using US healthcare claims (MarketScan®), 2000-2011. We identified new users of metformin versus sulfonylureas with no prior cancer diagnoses and followed them until a diagnosis of endometrial cancer, hysterectomy, treatment change, or disenrollment. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards, using an as-treated analytic approach. Stabilized inverse probability of treatment weights were used to adjust for potential confounding at baseline. RESULTS: Of 541,128 eligible women, 456,838 (84%) initiated metformin and 84,290 (16%) initiated sulfonylurea. The treatment groups differed at baseline in terms of age and recent diagnosis codes for diabetes, polycystic ovarian syndrome, and endometrial hyperplasia. Over a median follow-up of 1.2 (IQR 0.4-2.3) years and a total of 2,030,914 person-years, 729 women developed endometrial cancer. Metformin initiation was associated with a lower risk of endometrial cancer in the unadjusted analysis (HR 0.81, 95% CI 0.67-0.97). However, after balancing baseline covariates across groups, metformin was not associated with a reduced risk of endometrial cancer (HR 1.09, 95% CI 0.88-1.35). This finding was consistent across multiple sensitivity analyses and subgroup analyses in diabetic patients and relevant age groups. CONCLUSIONS: In this population-based cohort of >500,000 women, initiating metformin compared with sulfonylureas was not associated with a reduced risk of developing endometrial cancer.