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Background Prior studies have characterized distinct major depressive episode (MDE) subtypes among adults, yet limited evidence exists regarding variation in MDE during adolescence. Methods Using 2008-2016 National Survey of Drug Use and Health data, latent class analysis (LCA) was used to characterize depression subtypes (based on symptom presentation) among 9,896 youth ages 12-17 with recent first-onset MDE. Logistic regression was used to estimate associations of MDE subtype with functional outcomes and treatment utilization, adjusting for demographic characteristics and depression severity (i.e., number of MDE diagnostic criteria and recurrence status) Results A 5-class LCA model provided optimal fit. Three distinct categories of MDE symptoms generally clustered together, which we termed “somatic,” “cognitive,” and “self-worth;” classes were differentiated by distinct combinations of symptoms across these 3 categories. Subtypes were characterized as: Highly Symptomatic (39% of youth); Somatic & Cognitive (24%), Somatic (22%), Diffuse Symptoms (8%), and Somatic & Self-Worth (6%). The majority of youth reported at least moderate impairment across multiple domains; subtype was a significant predictor of functional impairment. Only 34% of youth received any past-year depression-related treatment; treatment utilization was significantly higher for MDE subtypes with the highest prevalences of suicidal ideation. Limitations Due to cross-sectional data, we cannot establish causal directionality. Conclusions Subtype was significantly predictive of functional impairment and treatment utilization, above and beyond number of MDE diagnostic criteria or recurrence status. Understanding distinct profiles of adolescent depression, as well as potential differential associations with impairment, can inform prevention, diagnosis, and treatment of depression among youth.

Introduction Prior studies have identified associations between specific health conditions and occupational impairments in the U.S. military, but little is known about the relative magnitude of impairments associated with different mental and physical health conditions among military service members. The goal of this study is to comparatively assess occupational impairment associated with mental and physical conditions among active duty military service members. Materials and Methods Data on 11,055 U.S. active duty service members were from the Department of Defense 2015 Health Related Behaviors Survey, an anonymous online health survey. Items assessed common mental and physical health conditions. Absenteeism was assessed as number of lost work days and presenteeism was assessed as number of work days with impaired functioning in the past 30 days. This research was approved by the RAND Human Subjects Protections Committee. Results Back pain (23%) and anxiety (14%) were the most prevalent conditions in the sample. Mental health conditions (anxiety, depression, and PTSD) were associated with more absentee and presentee days than physical conditions. Adjusting for physical health conditions, anxiety, depression, and PTSD showed robust associations with both absenteeism and presenteeism. Conclusions Common mental health conditions such as anxiety, depression, and PTSD showed robust associations with absenteeism and presenteeism among active duty U.S. military service members. Efforts to rigorously evaluate and improve existing military screening programs and reduce barriers to accessing and engaging in mental healthcare may help to reduce work absenteeism and presenteeism among active duty service members.

Opioid-related mortality increased by nearly 400% between 2000 and 2018. In response, federal, state, and local governments have enacted a heterogeneous collection of opioid-related policies in an effort to reverse the opioid crisis, producing a policy landscape that is both complex and dynamic. Correspondingly, there has been a rise in opioid-policy related evaluation studies, as policymakers and other stakeholders seek to understand which policies are most effective. In this paper, we provide an overview of methodological challenges facing opioid policy researchers when evaluating the effects of opioid policies using observational data, as well as some potential solutions to those challenges. In particular, we discuss the following key challenges: (1) Obtaining high-quality opioid policy data; (2) Appropriately operationalizing and specifying opioid policies; (3) Obtaining high-quality opioid outcome data; (4) Addressing confounding due to systematic differences between policy and non-policy states; (5) Identifying heterogeneous policy effects across states, population subgroups, and time; (6) Disentangling effects of concurrent policies; and (7) Overcoming limited statistical power to detect policy effects afforded by commonly-used methods. We discuss each of these challenges and propose some ways forward to address them. Increasing the methodological rigor of opioid evaluation studies is imperative to identifying and implementing opioid policies that are most effective at reducing opioid-related harms.

Purpose: Lesbian, gay, and bisexual (LGB) racial/ethnic minority individuals experience minority stress due to both their sexual identity and race/ethnicity and may be at elevated substance use risk (relative to heterosexuals) compared with their White LGB peers. We examined differences in the presence and magnitude of substance use disparities among LGB adults across race/ethnicity. Methods: Using data on 168,560 adults (including 11,389 LGB adults) from the 2015–2018 National Survey on Drug Use and Health, we examined disparities in cigarette smoking, heavy episodic drinking (HED), and marijuana use by race/ethnicity (White, Black, Hispanic, and other race/multiracial). Analyses compared lesbian/gay and bisexual adults, respectively, with heterosexual adults of the same gender and race/ethnicity. We also tested the magnitude of racial/ethnic minority disparities relative to the corresponding White disparity. Results: Significant disparities in smoking, HED, and marijuana use were observed for lesbian/gay and bisexual women across nearly all racial/ethnic groups. Disparities were consistently greater in magnitude for Black and Hispanic LGB women compared with White LGB women. Few disparities were observed among men; the magnitude of observed disparities did not differ by race/ethnicity. Conclusion: Disparities were most pronounced among racial/ethnic minority LGB women, which may reflect their unique experiences of discrimination at the intersection of multiple minority idenities. However, racial/ethnic minority gay and bisexual men were not at elevated risk relative to their White counterparts. Future research on substance use disparities among LGB individuals using an intersectional framework is warranted to elucidate differential minority stress processes that contribute to the observed heterogeneity across race/ethnicity, sexual identity, and gender.

Purpose: Lesbian, gay, and bisexual (LGB) adults have elevated rates of substance use (SU) relative to heterosexual adults, yet the extent to which these disparities vary across age groups is unknown. Using national survey data, we test for age group differences in lifetime and recent SU disparities among LGB adults. Methods: Using data on 67,354 adults (including 4868 LGB adults) from the 2015 and 2016 National Survey on Drug Use and Health (NSDUH), we examined LGB disparities in lifetime and recent use of cigarettes, marijuana, and illicit drugs. Analyses were stratified by age groups (18–25, 26–34, and 35–49 years) and compared lesbian/gay (L/G) and bisexual adults, respectively, with heterosexual adults of the same gender and age group. Results: Among L/G women, disparities (relative to same-age heterosexual women) were significantly larger in the youngest age group compared with the older age groups for numerous measures of lifetime and recent SU. Conversely, among bisexual men and bisexual women, multiple SU disparities (relative to heterosexual adults of the same age and gender) were significantly smaller among the youngest age group compared with the oldest age group. Conclusion: Contrary to hypotheses of decreased minority stress among more recent generations of LGB individuals, we found that SU disparities were not systematically smaller in younger age groups. Rather, disparities exhibited distinct trends across age groups. As NSDUH data are cross-sectional, differences by age group may reflect the influence of both age-varying developmental factors as well as time-varying social and contextual factors.

Purpose: We characterize disparities between lesbian, gay, and bisexual (LGB) adults and heterosexual adults across multiple health determinants in a nationally representative sample. Methods: Data on 153,939 adults (including 11,133 LGB adults) were from the 2015-2018 National Survey on Drug Use and Health. Separate Poisson regression models were used to estimate the relative risk (RR) that gay/lesbian and bisexual adults, respectively, experienced each health determinant, relative to heterosexual adults of the same gender and age group (ages 18-25, 26-34, 35-49, and 50-64). Statistically significant RR estimates were interpreted as a disparity. Results: Bisexual females exhibited disparities on all economic/health care access factors (no college degree, household poverty, means-tested assistance, unemployment, and lacking health insurance) across nearly all age groups; lesbian/gay females exhibited disparities in means-tested assistance and health insurance for some age groups. Notably fewer economic disparities were observed among gay and bisexual males. LGB adults (across identity, gender, and age group) were more likely to live alone, to have never been married, and to report low religious service attendance. Bisexual and lesbian/gay females, across age groups, had 1.7-2.2 times the risk of a lifetime arrest for a criminal offense, relative to same-age heterosexual females. Conclusions: Our results highlight that LGB females, particularly bisexual females, experience significant disparities in economic determinants of health, and all LGB subgroups exhibited disparities in some of the examined social determinants of health. The observed disparities, which spanned across age groups, likely contribute to disparities in physical and mental health observed among LGB adults.

Objective To assess whether per capita buprenorphine distribution varies by regional racial/ethnic composition, Medicaid expansion status, and time period. Methods Our unit of analysis -- three-digit ZIP codes (“ZIP3s”) -- was classified into quintiles based on percentage of White residents. A weighted linear regression model of buprenorphine distribution -- including White resident quintile, waivered prescriber rate, overdose rate, sociodemographic factors, and year fixed effects -- was estimated using national buprenorphine distribution data from 2007 to 2017. We report predictive margins of the buprenorphine distribution rate by quintile, as well as average marginal effects of waivered prescriber rate on buprenorphine distribution rate for each quintile. Analyses were stratified by Medicaid expansion status and time period (2007−2010, 2011−2014, 2015−2017). Results Buprenorphine distribution increased nationally during 2007–2017, yet growth was disproportionately greater for ZIP3s with higher percentages of White residents. Medicaid expansion states exhibited significant differences in buprenorphine distribution across ZIP3 quintiles during 2007−2010, the magnitude of which increased across time periods. Non-expansion states exhibited significant quintile differences during 2011−2014 and 2015−2017. The average marginal effect of increasing the waivered prescriber rate on the distribution rate was consistently smaller in ZIP3s with lower percentages of White residents, particularly in expansion states. Conclusions We find ecological evidence consistent with racial/ethnic disparities in buprenorphine distribution. Our finding that increasing the waivered prescriber rate had differential effects by ZIP3 racial/ethnic composition suggest that broad initiatives to increase the number of waivered prescribers are likely insufficient to achieve equitable buprenorphine access. Rather, targeted and tailored policy efforts are warranted.

Objective Characterize the state of the science in opioid policy research based on a literature review of opioid policy studies. Methods We conducted a scoping review of studies evaluating the impact of U.S. state-level and federal-level policies on opioid-related outcomes published in 2005−2018. We characterized: 1) state and federal policies evaluated, 2) opioid-related outcomes examined, and 3) study design and analytic methods (summarized overall and by policy category). Results In total, 145 studies were reviewed (79 % state-level policies, 21 % federal-level policies) and classified with respect to 8 distinct policy categories and 7 outcome categories. The majority of studies evaluated policies related to prescription opioids (prescription drug monitoring programs (PDMPs), opioid prescribing policies, federal regulation of prescription opioids, pain clinic laws) and considered policy impacts with respect to proximal outcomes (e.g., opioid prescribing behaviors). In total, only 29 (20 % of studies) met each of three key criteria for rigorous design: analysis of longitudinal data with a comparison group design, adjustment for difference between policy-enacting and comparison states, and adjustment for potentially confounding co-occurring policies. These more rigorous studies were predominately published in 2017–2018 and primarily evaluated PDMPs, marijuana laws, treatment-related policies, and overdose prevention policies. Conclusions Our results indicated that study design rigor varied notably across policy categories, highlighting the need for broader adoption of rigorous methods in the opioid policy field. More evaluation studies are needed regarding overdose prevention policies and policies related to treatment access. Greater examination of distal outcomes and potential unintended consequences are also warranted.

Characterizations of average end-of-life care for people with cancer can obscure important differences in patients’ experiences. Using Medicare claims data for 14,257 patients diagnosed with extensive-stage small-cell lung cancer in the period 1995–2009, we used latent class analysis to identify classes of people with different care patterns. We characterized care trajectories from diagnosis to death using time spent in five care settings—home, hospital inpatient unit (acute), hospital intensive care unit (ICU), postacute skilled nursing facility, and hospice—and transitions across these settings. We identified four classes of patients: 66 percent spent the time primarily at home, 11 percent were primarily in hospice, 17 percent were largely in an acute setting, and 6 percent were largely in an ICU. Patients in these classes differed significantly in terms of baseline clinical characteristics, survival length, time spent in hospice, site of death, and spending. The findings show substantial heterogeneity in patterns of care for patients with advanced cancer, which should be accounted for in efforts to improve end-of-life care.

We examined the effectiveness of human papillomavirus vaccination by dose number and spacing against incident genital warts in a cohort of 64,517 female health-plan enrollees in the United States during 2006-2012. Eligible recipients were classified into groups by regimen: 0, 1, 2 (

The impact of substance use on the life course of young adults can be substantial, yet few studies have examined to what extent early adult substance use behaviors are related to the timing of family formation, independent of confounding factors from adolescence. Using panel data from the Monitoring the Future study (N~20,000), the current study examined the associations between three substance use behaviors (i.e., cigarette use, binge drinking, and marijuana use) and the timing of family formation events in young adulthood. Survival analysis and propensity score weighting addressed pre-existing differences between substance users and non-users in the estimation of the timing of union formation (i.e., marriage, cohabitation) and parenthood. Results for young adult substance users showed general patterns of reduced rates of marriage and parenthood, and increased cohabitation during young adulthood. Variations were evident by substance and sex.

BACKGROUND: Prescription opioid misuse among older adults has received little attention to date. Potential age variation in characteristics of and motivations for prescription opioid misuse has not been fully characterized yet has important implications for preventing diversion and misuse. OBJECTIVE: To examine (1) age-specific patterns of source of misused prescription opioid pain relievers and motives for misuse and (2) age-specific and source-specific associations with opioid use disorder (OUD), heroin use, benzodiazepine misuse, and OUD treatment utilization. DESIGN: Cross-sectional study using 3 waves (2015–2017) of the National Survey on Drug Use and Health (68% average response rate) PARTICIPANTS: Respondents aged 12 and older with past-year prescription opioid pain reliever misuse (n = 8228) MAIN MEASURES: Source for the most-recently misused prescription pain reliever (categorized as medical, social, or illicit/other), motive for last episode of misuse, OUD, heroin use, benzodiazepine misuse, and OUD treatment. KEY RESULTS: Adults 50 and older comprised approximately 25% of all individuals reporting past-year prescription opioid misuse. A social source was most common for individuals under age 50 while a medical source was most common for individuals 50 and older. The most commonly reported motive for misuse was to “relieve physical pain”; the frequency of this response increased across age groups (47% aged 12–17 to 87% aged 65+). Among adults age 50 and older with prescription opioid misuse, 17% met criteria for OUD, 15% reported past-year benzodiazepine misuse, and 3% reported past-year heroin use. CONCLUSIONS: Physicians continue to be a direct source of prescription opioids for misuse, particularly for older adults. Ongoing clinical initiatives regarding optimal opioid prescribing practices are needed in addition to effective non-opioid strategies for pain management. Clinical initiatives should also include screening adult and adolescent patients for non-medical use of prescription opioids as well as improving access to OUD treatment for individuals of all ages.

Objectives Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA. Methods Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale Results Each disease severity measure exhibited a non-linear relationship concerning the probability of depression onset, with the higher quintiles generally being associated with a larger risk. The highest quintile (relative to the lowest) of joint space width and gait speed were both significantly associated with depression onset. By contrast, none of the higher pain quintiles compared with the lowest were significantly associated with the onset of depression. Conclusion Faster disease progression as measured by either worsening structural severity or decreasing physical performance corresponds to an increased risk of depression among individuals with radiographic knee OA.

Background Prior studies characterizing sexual minority substance use disparities have primarily compared lesbian/gay and bisexual individuals, respectively or in combination, to heterosexual individuals. In light of emerging evidence that bisexual individuals may have particularly elevated substance use risk, we examine differences in recent substance use between bisexual and lesbian/gay individuals using national survey data. Methods Data on 126,463 adults (including 8241 LGB adults) were from the 2015–2017 National Survey on Drug Use and Health. Substance use outcomes included binge drinking, cigarette smoking, cigar smoking, marijuana use, illicit drug use, opioid misuse, alcohol use disorder, nicotine dependence, and substance use disorder. Logistic regression was used to estimate sexual identity- and gender-specific odds ratios, controlling for demographic characteristics. Of particular interest were estimates comparing bisexual and lesbian/gay individuals of the same gender. Results Both male and female sexual minority adults had significantly elevated rates of substance use compared to heterosexual adults. Furthermore, relative to lesbian/gay women, bisexual women had significantly elevated odds of binge drinking (aOR = 1.29), marijuana use (aOR = 1.42), illicit drug use (aOR = 1.55), opioid misuse (aOR = 1.53), and alcohol use disorder (aOR = 1.48). Relative to gay men, bisexual men had significantly elevated cigar use (aOR = 1.64). Conclusions Bisexual women were at significantly greater risk for multiple substance use behaviors relative to lesbian/gay women. We did not observe any substance use behaviors for which bisexual individuals had significantly lower risk than their lesbian/gay peers. These disparities may be explained, in part, by unique risk factors for substance use experienced by bisexual individuals, particularly bisexual women.

Drawing on national retail pharmacy data, researchers identified and categorized clinicians who prescribed buprenorphine for OUD at least once between January 2017 and December 2018.

Patient-centered care involves patients in decision-making about their medical care. Effective shared decision-making requires relevant evidence on the expected health outcomes of treatment, assessment of patient preferences for possible health outcomes, and a method to synthesize this information. Few tools exist to help clinicians and patients synthesize clinical evidence and personal preferences. We develop a statistical framework that combines multiple data sources on expected treatment outcomes with individual preferences to produce a personalized preference-weighted outcome score (PWOS). The PWOS can be calculated for multiple treatments and compared to determine which will provide the best balance of risks and benefits given a patient’s preferences. We demonstrate our method by evaluating adjuvant chemotherapy regimens for colorectal cancer. We begin by identifying heterogeneity in patient preferences for health outcomes associated with colorectal cancer disease and treatment, finding classes of patients who value efficacy and side effects differently. Then we fit a hierarchical Bayesian model to randomized clinical trials and produce posterior distributions of expected outcomes under three chemotherapy regimens. We use the PWOS to combine distinct sets of patient preferences with these expected outcomes. Our method preserves estimation uncertainty and accounts for correlation among outcomes. In a simulation study of applying PWOS to make decisions at the population level, we find that our methods are most useful when there are large differences in individual preferences and small distinctions in treatment efficacy (i.e., preference-sensitive settings).

Introduction Little is known about how alcohol treatment rates vary across age or years since onset of an alcohol use disorder (AUD). We examined past-year treatment prevalence and associations across these important time metrics. Method Data on 22,278 adults ages 18–50 were from the National Epidemiologic Survey on Alcohol and Related Conditions-III (2012–2013). We examined the age-varying prevalence of alcohol treatment and associations of past-year AUD severity, MDD status, and DUD status with treatment. Additionally, for individuals with a lifetime AUD (N = 7089), we examined associations of severity, MDD, and DUD across years since AUD onset. Results Individuals with Moderate/Severe past-year AUD had significantly higher treatment rates at nearly all ages, compared to those with Mild or no AUD. For those with Moderate/Severe AUD, treatment rates were highest during late adolescence and middle adulthood and lowest during early adulthood. Mental health comorbidities were positively associated with treatment at certain age ranges in mid-adulthood. Among individuals with a lifetime AUD, those with Moderate/Severe past-year AUD had significantly higher past-year treatment rates across all years since onset. MDD and DUD were both positively associated with treatment at nearly all years since AUD onset. Conclusions Alcohol treatment rates varied notably by age and, to a lesser extent, by years since AUD onset. Greater AUD severity was consistently associated with higher rates of treatment, whereas Mild AUD had a much weaker relationship. MDD and DUD showed similar patterns of positive association with treatment. Our results highlight important subgroups where unmet treatment needs are highest.

Propensity score methods (e.g., matching, weighting, subclassification) provide a statistical approach for balancing dissimilar exposure groups on baseline covariates. These methods were developed in the context of data with no hierarchical structure or clustering. Yet in many applications the data have a clustered structure that is of substantive importance, such as when individuals are nested within healthcare providers or within schools. Recent work has extended propensity score methods to a multilevel setting, primarily focusing on binary exposures. In this paper, we focus on propensity score weighting for a continuous, rather than binary, exposure in a multilevel setting. Using simulations, we compare several specifications of the propensity score: a random effects model, a fixed effects model, and a single-level model. Additionally, our simulations compare the performance of marginal versus cluster-mean stabilized propensity score weights. In our results, regression specifications that accounted for the multilevel structure reduced bias, particularly when cluster-level confounders were omitted. Furthermore, cluster mean weights outperformed marginal weights.

Objective The present study was undertaken to identify depression subtypes in individuals with or at risk for symptomatic knee osteoarthritis (OA) and to evaluate differences in pain and disability trajectories between groups. Methods Participants (n = 4,486) were enrolled in the Osteoarthritis Initiative. Latent class analysis was applied to the 20-item Center for Epidemiologic Studies Depression Scale measured at baseline to identify groups with similar patterns of depressive symptoms, and subtypes were assigned using posterior probability estimates. The relationships between depression subtypes and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and disability subscales were modeled over 4 years and stratified by baseline knee OA status (symptomatic [n = 1,626] or at risk [n = 2,860]). Results Four subtypes were identified: asymptomatic (80.6%), catatonic (5.3%), anhedonic (10.6%), and melancholic (3.5%). Catatonic and anhedonic subtypes were differentiated by symptoms corresponding to psychomotor agitation and the inability to experience pleasure, respectively. The melancholic subtype expressed symptoms related to reduced energy and movement, anhedonia, and other somatic symptoms. Detectable mean differences in pain and disability compared to the asymptomatic group were observed for the anhedonic (1.5-2.3 WOMAC units) and melancholic (4.8-6.6 WOMAC units) subtypes, and associations were generally larger in individuals with symptomatic knee OA relative to those at risk. Conclusion Among individuals with or at risk for symptomatic knee OA, there is evidence of depression subtypes characterized by distinct clusters of depressive symptoms that have differential effects on reports of pain and disability over time. Our findings thus imply that depression interventions could be optimized by targeting the specific symptomology that these subtypes exhibit.

Purpose Substance use by peers and family may affect adolescent substance use, yet the relative influence may shift during adolescence as youth differentiate themselves from family and more closely affiliate with peers. This study examined trends in concordance of adolescent cigarette, alcohol and marijuana use and corresponding perceived use by friends and family members during middle and high school. Methods Data are from a longitudinal cohort of 12,038 youth who completed up to five surveys during grades 6–12. At each wave, adolescents reported past month use of cigarettes, alcohol and marijuana, as well as perceived use by their best friend, older sibling and most important adult figure. For each substance, we used time-varying effect models to estimate how associations between adolescent use and perceived use varied across grade. Results For all substances, concordance with best friend use was positive and stronger than concordance with older sibling or adult use at all grades. Concordance with both best friend and older sibling use of all substances was pronounced in 6th grade. Concordance peaked again during mid-high school for smoking (best friend, older sibling) and marijuana (best friend). Concordance with adult marijuana use peaked in middle school, yet associations with adult alcohol and cigarette use were relatively stable. Conclusions Substance use prevention efforts that seek to counter peer normative pressures should begin prior to middle school and span high school. Such efforts should address the role of peer and family environments, as both were found to be relevant during middle and high school.

OBJECTIVE: Young adult substance use is linked with the risk of substance use disorders (SUDs) later in adulthood. Marriage may be part of this pathway because of both selection effects (early substance use reducing marriage) and socialization effects (marriage reducing later substance use and disorder). We examine whether marital status mediates the association between young adult substance use and subsequent SUDs, using causal mediation methods to strengthen inferences. METHOD: Using panel data from high school seniors in 1990–1998, we examined whether the effects of two exposures (level of alcohol/marijuana use at age 19/20) on the outcomes (alcohol use disorder [AUD]/marijuana use disorder [MUD], nondisordered use, or abstinence at age 35) were mediated by marital status at age 29/30. Propensity score weights adjusted for potential confounding regarding both the exposures and the mediator. RESULTS: Moderate and heavy alcohol/marijuana use at age 19/20 were associated with higher odds of AUD/MUD and lower odds of abstinence, each relative to nondisordered use, at age 35. The association between heavy alcohol use at age 19/20 and subsequent AUD was partially mediated by being unmarried at age 29/30; the associations between moderate and heavy marijuana use at age 19/20 and subsequent marijuana abstinence were partially mediated by being unmarried at age 29/30. CONCLUSIONS: Both selection and socialization effects related to marriage explain the perpetuation of substance use behaviors across adulthood. Selection effects on marriage seem to occur at different thresholds for young adult alcohol and marijuana use.

Summary Objective Depressive symptoms in knee osteoarthritis (OA) are associated with increased pain severity and declines in physical performance. This study examined whether pain severity mediates the association between depressive symptoms and physical performance in persons with radiographic knee OA. Method Three years of annual data from participants (n = 1,463) with radiographic knee OA in the Osteoarthritis Initiative (OAI) were analyzed. Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D) scale. Pain severity was evaluated with the Western Ontario and McMaster Universities Arthritis Index. Physical performance was assessed via standardized gait speed. Marginal structural models were used to assess the direct (unmediated) effects of depressive symptoms on physical performance and indirect (mediated) effects through pain severity. Results Direct and indirect effects for a difference in CES-D score of 0–1 were −0.0051 (95% confidence intervals (CI): −0.0053, −0.0049) and −0.0016 (95% CI: −0.0024, −0.0007) standard deviations in gait speed, respectively. Higher depressive symptom severity exhibited diminishing, incremental, direct and indirect effects and for a difference in CES-D score of 15–16 were −0.0045 (95% CI: −0.0047, −0.0042) and −0.0009 (95% CI: −0.0014, −0.0004) standard deviations in gait speed, respectively. Therefore, the magnitude of the mediated, indirect effect, was never larger than 24%. Conclusion Pain severity mediated approximately one-fifth of the association between depressive symptoms and physical performance in persons with radiographic knee OA, and the diminishing incremental effects may explain why unimodal treatment strategies with a single disease target are often ineffective in depressed OA patients.

OBJECTIVES: The earned income tax credit (EITC), refundable monies for America’s working poor, is associated with improved child health. Yet, 20% of eligible families do not receive it. We provided free tax preparation services in clinics serving low-income families and assessed use, financial impact, and accuracy. METHODS: Free tax preparation services (“StreetCred”) were available at 4 clinics in Boston in 2016 and 2017. We surveyed a convenience sample of clients (n = 244) about experiences with StreetCred and previous tax services and of nonparticipants (n = 100; 69% response rate) and clinic staff (n = 41; 48% response rate) about acceptability and feasibility. RESULTS: A total of 753 clients received $1 619 650 in federal tax refunds. StreetCred was associated with significant improvement in tax filing rates. Of surveyed clients, 21% were new filers, 47% were new users of free tax preparation, 14% reported new receipt of the EITC, and 21% reported new knowledge of the EITC. StreetCred had high client acceptability; 96% would use StreetCred again. Families with children were significantly more likely to report StreetCred made them feel more connected to their doctor (P = .02). Clinic staff viewed the program favorably (97% approval). CONCLUSIONS: Free tax services in urban clinics are a promising, feasible financial intervention to increase tax filing and refunds, save fees, and link clients to the EITC. With future studies, we will assess scalability and measure impact on health. StreetCred offers an innovative approach to improving child health in primary care settings through a financial intervention.

Introduction Sensation seeking is associated with elevated risk for substance use among adolescents and young adults. However, whether these associations vary across age for young men and women is not well characterized. Methods Using data from the Monitoring the Future (MTF) panel study, we examine the age-varying associations of sensation seeking and three types of substance use behavior (binge drinking, cigarette use, and marijuana use) across ages 18 to 30 using time-varying effect modeling. Analyses include participants in the eleven most recent MTF cohorts (12th-graders in 1994–2004), who are eligible to respond through age 29/30 (N = 6338 people; 30,237 observations). Results While sensation seeking levels and substance use are lower among women, the magnitude of the association of sensation seeking with binge drinking and with marijuana use among women exceeds that of men in the later 20s. Differential age trends were observed; among men, the associations generally decreased or remained constant with age. Yet among women, the associations decayed more slowly or even increased with age. Specifically, the association of sensation seeking with marijuana use among women increased during the late 20s, such that the association at age 30 exceeded that in the early 20s. Conclusions The significantly stronger associations of sensation seeking with binge drinking and marijuana use observed among women compared to men during the mid- to late-20s suggests divergent risk factors across genders for substance use during young adulthood, with sensation seeking remaining a strong risk factor for women but not men.

Importance Depression during childhood and adolescence is heterogeneous. Treatment patterns are often examined in aggregate, yet there is substantial variability across individual treatment trajectories. Understanding this variability can help identify treatment gaps among youths with depression. Objective To characterize heterogeneity in 12-month trajectories of psychotherapy and antidepressant treatment in youths with depression. Design, Setting, and Participants This is a longitudinal-cohort study of youths 18 years or younger with a new diagnosis of depression and at least 12 months of follow-up following diagnosis, as determined from commercial insurance claims filed from 2007 to 2014. Latent class models were fit to summary measures of psychotherapy and antidepressant use in the 12 months following the index diagnosis. We examined variation in baseline health, health care utilization, and health outcomes across classes with similar patterns of psychotherapy and antidepressant use. Data analysis took place between June 2016 and March 2017. Main Outcomes and Measures Psychotherapy and antidepressant use. Results The cohort included 84 909 individuals with a mean (SD) age at index diagnosis of 15.0 (2.6) years, of whom 49 995 (59%) were female. Attention-deficit/hyperactivity disorder (n = 14 625; 17%) and anxiety (n = 12 358; 15%) were the most common comorbid diagnoses. During the assessment period, 59 023 individuals (70%) received psychotherapy at any point, and 33 997 individuals (40%) were dispensed antidepressants at any point. Eight classes with distinct treatment trajectories were identified, which we classified into 4 broad groups: 3 classes that received dual therapy (n = 18 710; 22%), 2 classes that received antidepressant monotherapy (n = 15 287; 18%), 2 classes that received psychotherapy monotherapy (n = 40 313; 48%) and 1 class that received no treatment (n = 10 599; 13%). The most common class received psychotherapy monotherapy (n = 35 243; 42%) and had the lowest incidence of attempted suicide (0.8 per 100 person-years [PY]) and inpatient hospitalization (3.5 per 100 PY) during the assessment period and postassessment period (0.5 per 100 PY and 1.3 per 100 PY, respectively). The group receiving dual therapy had the highest incidence of attempted suicide during the assessment period (4.7-7.1 per 100 PY, depending on the class) and postassessment period (1.5-1.7 per 100 PY). Conclusions and Relevance In our sample, 13% of youths received no treatment, and 18% received antidepressants without concomitant psychotherapy. Summary measures of treatment can mask informative patterns of psychotherapy and antidepressant use. Latent class analysis can be used to identify subgroups of individuals with similar treatment trajectories and help identify treatment gaps under current practice patterns.

Background Sexual minorities (SMs) experience elevated rates of substance use behaviors and disorders relative to heterosexuals; minority stress is theorized to contribute to these disparities. As SMs are not a homogenous group, analyses that aggregate SMs across sexual identity, age, or gender obscure important variation among this population. To date, age- and gender-specific disparities have not been rigorously examined using a large national sample. Methods Using data on 67,354 adults (ages 18–49) from the 2015 and 2016 National Survey of Drug Use and Health we examined age- and gender-specific disparities in smoking, heavy episodic drinking, marijuana use, illicit drug use, and alcohol/substance use disorder. Age groups were ages 18–25, 26–34, and 35–49. Using logistic regression, we estimated age- and gender-specific odds ratios for gay/lesbian and bisexual individuals, relative to heterosexuals; analyses adjusted for demographic characteristics. Results Bisexual women had significantly elevated odds of all outcomes at all ages, relative to heterosexual women. Gay/lesbian individuals had significantly elevated odds for nearly all outcomes compared to same-gender heterosexuals at ages 18–25, but not consistently at older ages. For bisexual men, significant disparities compared to heterosexual men were only observed at ages 35–49 for marijuana use and alcohol/substance use disorder. Conclusions We found notable within-group differences regarding SM disparities. While disparities were most pronounced in young adulthood for gay/lesbian individuals and mid-adulthood for bisexual men, bisexual women uniquely experienced disparities across all ages. Minority stress experiences may vary with respect to gender, age/cohort, and sexual identity, resulting in differential risk for substance use.

Background College attendance is a risk factor for frequent and heavy drinking and marijuana initiation but less is known about the extent to which risk varies by type of college attendance and across age. Methods Using panel data of young adults who were high school seniors in 1990–1998 from the Monitoring the Future study (n = 13,123), we examined the associations between college attendance at age 19/20 (4-year college full-time, other college, and non-attendance) and subsequent alcohol and marijuana use at age 21/22, 25/26, 29/30 and 35. Inverse propensity score weighting was used to balance the three college groups on pre-existing differences when examining associations with substance use outcomes. Results Compared to non-attendance, attending a 4-year college full-time was associated with significantly greater odds of binge drinking at age 21/22 (aOR = 1.20) and 25/26 (aOR = 1.12) and lower odds of alcohol abstinence at age 35 (aOR = 0.51). Similarly, other college attendance was associated with greater odds of binge drinking at age 21/22 (aOR = 1.08) and 25/26 (aOR = 1.04) and lower odds of abstinence at age 35 (aOR = 0.70). Four-year college full-time attendance was associated with greater odds of marijuana use at age 21/22 (aOR = 1.07) and 25/26 (aOR = 1.02) but lower odds at age 29/30 (aOR = 0.99). Other college attendance was associated with lower odds of marijuana use at age 25/26 (aOR = 0.98) and 29/30 (aOR = 0.97). Marijuana use at age 35 did not differ by college attendance. Conclusions College attendance may confer elevated risk of substance use post-college. The magnitude and duration of risk vary by type of college attendance and substance.

Estimation of causal effects using observational data continues to grow in popularity in the epidemiologic literature. While many applications of causal effect estimation use propensity score methods or G-computation, targeted maximum likelihood estimation (TMLE) is a well-established alternative method with desirable statistical properties. TMLE is a doubly robust maximum-likelihood-based approach that includes a secondary "targeting" step that optimizes the bias-variance tradeoff for the target parameter. Under standard causal assumptions, estimates can be interpreted as causal effects. Because TMLE has not been as widely implemented in epidemiologic research, we aim to provide an accessible presentation of TMLE for applied researchers. We give step-by-step instructions for using TMLE to estimate the average treatment effect in the context of an observational study. We discuss conceptual similarities and differences between TMLE and 2 common estimation approaches (G-computation and inverse probability weighting) and present findings on their relative performance using simulated data. Our simulation study compares methods under parametric regression misspecification; our results highlight TMLE's property of double robustness. Additionally, we discuss best practices for TMLE implementation, particularly the use of ensembled machine learning algorithms. Our simulation study demonstrates all methods using super learning, highlighting that incorporation of machine learning may outperform parametric regression in observational data settings.