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.

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.

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.

Mediators of racial/ethnic inequities in clinical trial participation among patients with cancer, 2011-2023.

BACKGROUND: While minoritized populations are less likely to participate in cancer trials, it is unknown whether social determinants of health (SDOH) explain these inequities. Here we identify SDOH factors that contribute to racial/ethnic inequities in clinical trial participation among patients with 22 common cancers. METHODS: This retrospective cohort study used electronic health record data (2011-2023) linked to neighborhood (Census tract) data from multiple sources. Patients were followed from diagnosis to clinical study drug receipt (proxy for trial participation), death, or last recorded activity. Associations were assessed using Cox proportional hazards models adjusted for clinical factors (diagnosis year, age, sex, performance status, stage, cancer type). To elucidate which area-level SDOH underlie racial/ethnic inequities, mediation analysis was performed using nonlinear multiple additive regression tree models. RESULTS: This study included 250105 patients (64.7% non-Latinx White, 8.9% non-Latinx Black, 5.2% Latinx). Black and Latinx patients were more likely to live in economically/socially marginalized areas (eg, disproportionately minoritized [measure of segregation], limited English proficiency [LEP], low vehicle ownership) than White patients. Black (3.7%; HR = 0.55 [CI = 0.52-0.60]) and Latinx patients (4.4%; HR = 0.63 [CI = 0.58-0.69]) were less likely to participate in trials than White patients (6.3%). Fewer patients in economically/socially marginalized neighborhoods participated in trials. Mediators explained 62.2% (CI = 49.5%-74.8%) of participation inequities between Black and White patients; area-level SDOH-including segregation (29.9% [CI = 21.2%-38.6%]) and vehicle ownership (11.6% [CI = 7.0%-16.1%])-were the most important mediators. Similarly, Latinx-White participation inequities were mediated (65.1%, [CI = 49.8%-80.3%]) by area-level SDOH such as segregation (39.8% [CI = 28.3%-51.3%]), LEP (11.6%, [CI = 2.8%-20.4%]), and vehicle ownership (9.6% [CI = 5.8%-13.5%]). CONCLUSIONS: To improve racial/ethnic diversity in cancer trials, efforts to address barriers related to adverse neighborhood SDOH factors are necessary.

Cross-cultural adaptation of the awareness and beliefs about cancer measure for Hispanics/Latinos living in the United States.

Introduction: The purpose of this study is to culturally adapt the Awareness and Beliefs about Cancer (ABC) measure for use in the Hispanic/Latino population living in the United States (US). Methods: In accordance with Patient Reported Outcomes (PRO) Consortium guidelines for cross-cultural adaptation of measures for content and linguistic validity, we conducted: two forward-translations, reconciliation, two back-translations, revision and harmonization, six cognitive interviews, revision, external expert review, and finalization of the version. We used a mixed methods approach, conducting cognitive interviews with Hispanic/Latino community members while also convening an expert panel of six clinicians, health professionals, and community representatives and including the in the entire process. After cross-culturally adapting the ABC measure, we assessed the psychometric properties of the instrument using item response theory analysis. Item parameters, discrimination and category thresholds, and standard errors were calculated. For each of the adapted subdomains, we used item information curves to report the graphical profile of item effectiveness. Results: Twenty-two Hispanic/Latino community members were enrolled in cognitive interviews, and Hispanics/Latinos fluent in Spanish completed the measure to assess its psychometric properties. Cognitive interviews revealed opportunities to improve items. Key changes from the original measure include the inclusion of gender inclusive language and an inquiry into e-cigarette use on items related to smoking habits. Psychometric property analyses revealed that the anticipated delay in seeking medical help, general cancer beliefs, and cancer screening beliefs and behaviors subdomains had some slope parameters that were < 1; this implies that those items were not able to adequately discriminate the latent trait and had poor performance. Discussion: The adapted ABC measure for US Hispanics/Latinos meets content and linguistic validity standards, with construct validity confirmed for cancer symptom recognition and barriers to symptomatic presentation subdomains, but revisions are necessary for others, highlighting the need for ongoing refinement to ensure the cultural appropriateness of instruments.