Perspective on 'Harm' in Personalized Medicine.

Avoiding harm is an uncontroversial aim of personalized medicine and other epidemiologic initiatives. However, the precise mathematical translation of "harm" is disputable. Here we use a formal causal language to study common, but distinct, definitions of "harm". We clarify that commitment to a definition of harm has important practical and philosophical implications for decision making. We relate our practical and philosophical considerations to ideas from medical ethics and legal practice.

Cannabis use, cannabis use disorder and mental health disorders among pregnant and postpartum women in the US: A nationally representative study.

BACKGROUND: Cannabis use and cannabis use disorder (CUD) are associated with mental health disorders, however the extent of this matter among pregnant and recently postpartum (e.g., new moms) women in the US is unknown. Associations between cannabis use, DSM-5 CUD and DSM-5 mental health disorders (mood, anxiety, personality and post-traumatic stress disorders) were examined among a nationally representative sample of pregnant and postpartum women. METHODS: The 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III was used to examine associations between past-year cannabis use, CUD and mental health disorders. Weighted logistic regression models were used to estimate unadjusted and adjusted odds ratios (aORs). The sample (N=1316) included 414 pregnant and 902 postpartum women (pregnant in the past year), aged 18-44 years old. RESULTS: The prevalence of past-year cannabis use and CUD was 9.8% and 3.2%, respectively. The odds of cannabis use (aORs range 2.10-3.87, p-values<0.01) and CUD (aORs range 2.55-10.44, p-values< 0.01) were higher among women with versus without any past-year mood, anxiety or posttraumatic stress disorders or any lifetime personality disorder. aORs for the association of cannabis use with specific mood, anxiety or personality disorders ranged from 1.95 to 6.00 (p-values<0.05). aORs for the association of CUD with specific mood, anxiety or personality disorders ranged from 2.36 to 11.60 (p-values<0.05). CONCLUSIONS: From pregnancy up to one year postpartum is a critical period where women may be particularly vulnerable to mental health disorders, cannabis use and CUD. Treatment and prevention are essential.

Incidence and Outcomes of Non-Ventilator-Associated Hospital-Acquired Pneumonia in 284 US Hospitals Using Electronic Surveillance Criteria.

Importance: Non-ventilator-associated hospital-acquired pneumonia (NV-HAP) is a common and deadly hospital-acquired infection. However, inconsistent surveillance methods and unclear estimates of attributable mortality challenge prevention. Objective: To estimate the incidence, variability, outcomes, and population attributable mortality of NV-HAP. Design, Setting, and Participants: This cohort study retrospectively applied clinical surveillance criteria for NV-HAP to electronic health record data from 284 US hospitals. Adult patients admitted to the Veterans Health Administration hospital from 2015 to 2020 and HCA Healthcare hospitals from 2018 to 2020 were included. The medical records of 250 patients who met the surveillance criteria were reviewed for accuracy. Exposures: NV-HAP, defined as sustained deterioration in oxygenation for 2 or more days in a patient who was not ventilated concurrent with abnormal temperature or white blood cell count, performance of chest imaging, and 3 or more days of new antibiotics. Main Outcomes and Measures: NV-HAP incidence, length-of-stay, and crude inpatient mortality. Attributable inpatient mortality by 60 days follow-up was estimated using inverse probability weighting, accounting for both baseline and time-varying confounding. Results: Among 6 022 185 hospitalizations (median [IQR] age, 66 [54-75] years; 1 829 475 [26.1%] female), there were 32 797 NV-HAP events (0.55 per 100 admissions [95% CI, 0.54-0.55] per 100 admissions and 0.96 per 1000 patient-days [95% CI, 0.95-0.97] per 1000 patient-days). Patients with NV-HAP had multiple comorbidities (median [IQR], 6 [4-7]), including congestive heart failure (9680 [29.5%]), neurologic conditions (8255 [25.2%]), chronic lung disease (6439 [19.6%]), and cancer (5,467 [16.7%]); 24 568 cases (74.9%) occurred outside intensive care units. Crude inpatient mortality was 22.4% (7361 of 32 797) for NV-HAP vs 1.9% (115 530 of 6 022 185) for all hospitalizations; 12 449 (8.0%) were discharged to hospice. Median [IQR] length-of-stay was 16 (11-26) days vs 4 (3-6) days. On medical record review, pneumonia was confirmed by reviewers or bedside clinicians in 202 of 250 patients (81%). It was estimated that NV-HAP accounted for 7.3% (95% CI, 7.1%-7.5%) of all hospital deaths (total hospital population inpatient death risk of 1.87% with NV-HAP events included vs 1.73% with NV-HAP events excluded; risk ratio, 0.927; 95% CI, 0.925-0.929). Conclusions and Relevance: In this cohort study, NV-HAP, which was defined using electronic surveillance criteria, was present in approximately 1 in 200 hospitalizations, of whom 1 in 5 died in the hospital. NV-HAP may account for up to 7% of all hospital deaths. These findings underscore the need to systematically monitor NV-HAP, define best practices for prevention, and track their impact.

Longitudinal incremental propensity score interventions for limited resource settings.

Many real-life treatments are of limited supply and cannot be provided to all individuals in the population. For example, patients on the liver transplant waiting list usually cannot be assigned a liver transplant immediately at the time they reach highest priority because a suitable organ is not immediately available. In settings with limited supply, investigators are often interested in the effects of treatment strategies in which a limited proportion of patients receive an organ at a given time, that is, treatment regimes satisfying resource constraints. Here, we describe an estimand that allows us to define causal effects of treatment strategies that satisfy resource constraints: incremental propensity score interventions (IPSIs) for limited resources. IPSIs flexibly constrain time-varying resource utilization through proportional scaling of patients' natural propensities for treatment, thereby preserving existing propensity rank ordering compared to the status quo. We derive a simple class of inverse-probability-weighted estimators, and we apply one such estimator to evaluate the effect of restricting or expanding utilization of "increased risk" liver organs to treat patients with end-stage liver disease.

Comparison of Rates of Type 2 Diabetes in Adults and Children Treated With Anticonvulsant Mood Stabilizers.

Importance: Anticonvulsant mood stabilizer treatment is associated with an increased risk of weight gain, but little is known about the risk of developing type 2 diabetes (T2D). Objective: To evaluate the comparative safety of anticonvulsant mood stabilizers on risk of T2D in adults and children by emulating a target trial. Design, Setting, and Participants: This observational cohort study used data from IBM MarketScan (2010-2019), with a 5-year follow-up period. The nationwide sample of US commercially insured patients included children (aged 10-19 years) and adults (aged 20-65 years) who initiated anticonvulsant mood stabilizer treatment. Data were analyzed from August 2020 to May 2021. Exposures: Initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate. Main Outcomes and Measures: Onset of T2D during follow-up. Weighted pooled logistic regression was used to estimate the association of initiation and continuation of carbamazepine, lamotrigine, oxcarbazepine, or valproate with the risk of developing T2D. Inverse probability weights were used to control for confounding and loss to follow-up by measured baseline and time-varying covariates. Results: The analysis included 274 206 adults (159 428 women [58%]; mean [SD] age, 39.9 [13.2] years) and 74 005 children (38 672 girls [52%]; mean [SD] age, 15.6 [2.6] years) who initiated an anticonvulsant mood stabilizer. In adults, initiation of valproate was associated with an increased risk of developing T2D compared with initiation of lamotrigine (5-year risk difference [RD], 1.17%; 95% CI, 0.66% to 1.76%). The number needed to harm was 87 patients initiating valproate for 1 patient to develop T2D within 5 years compared with initiation of lamotrigine. Point estimates were similar when evaluating the association of treatment continuation (5-year RD, 1.99%; 95% CI, -0.64% to 5.31%). The estimated association was smaller and more variable comparing carbamazepine and oxcarbazepine to lamotrigine. In children, RDs were much smaller and more variable (5-year RD for initiation of oxcarbazepine vs lamotrigine, 0.29%; 95% CI, -0.12% to 0.69%; 5-year RD for initiation of valproate vs lamotrigine, 0.18%; 95% CI, -0.09% to 0.49%). Conclusions and Relevance: In this cohort study, valproate was associated with the highest risk of developing T2D in adults. The comparative safety was generally similar in children, but estimates were small and variable. In the absence of randomized trials, emulating target trials within health care databases can generate the age-specific drug safety data needed to inform treatment decision-making.

Association of Cannabis Use-Related Predictor Variables and Self-Reported Psychotic Disorders: U.S. Adults, 2001-2002 and 2012-2013.

OBJECTIVE: The authors sought to determine the association of cannabis indicators with self-reported psychotic disorders in the U.S. general population. METHODS: Participants were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309). Logistic regression was used to estimate standardized prevalences of past-year self-reported psychotic disorders within each survey and to evaluate the association of past-year self-reported psychotic disorders with indicators of nonmedical cannabis use (any use; frequent use [at least three times/week], daily/near-daily use, and DSM-IV cannabis use disorder) compared with those with no past-year nonmedical cannabis use. Whether the strength of associations differed between surveys was indicated by difference-in-difference tests (between-survey contrasts) and ratios of odds ratios between surveys. RESULTS: Self-reported psychotic disorders were significantly more prevalent among participants with any nonmedical cannabis use than those without (2001-2002: 1.65% compared with 0.27%; 2012-2013: 1.89% compared with 0.68%). In 2001-2002, self-reported psychotic disorders were unrelated to either frequent use or daily/near-daily use. However, in 2012 - 2013, compared with nonusers, self-reported psychotic disorders were more common among participants with frequent use and those with daily/near-daily nonmedical cannabis use (2012-2013: 2.79% and 2.52%, respectively, compared with 0.68% among nonusers). Self-reported psychotic disorders were significantly more prevalent among participants with cannabis use disorder than nonusers in both surveys (2001-2002: 2.55% compared with 0.27%; 2012 - 2013: 3.38% compared with 0.68%). The strength of these associations did not change over time. CONCLUSIONS: Data from the U.S. general population, especially more recent data, suggest associations between self-reported psychotic disorder and frequent nonmedical cannabis use and cannabis use disorder. Clinicians and policy makers should consider these relationships when monitoring patients and formulating programs.

Separating Algorithms From Questions and Causal Inference With Unmeasured Exposures: An Application to Birth Cohort Studies of Early Body Mass Index Rebound.

Observational studies reporting on adjusted associations between childhood body mass index (BMI; weight (kg)/height (m)2) rebound and subsequent cardiometabolic outcomes have often not paid explicit attention to causal inference, including definition of a target causal effect and assumptions for unbiased estimation of that effect. Using data from 649 children in a Boston, Massachusetts-area cohort recruited in 1999-2002, we considered effects of stochastic interventions on a chosen subset of modifiable yet unmeasured exposures expected to be associated with early (

Associations of intimate partner violence and financial adversity with familial homelessness in pregnant and postpartum women: A 7-year prospective study of the ALSPAC cohort.

OBJECTIVE: To determine whether emotional and physical intimate partner violence (IPV) and financial adversity increase risk of incident homelessness in pregnancy and the post-partum period. STUDY DESIGN: Data were drawn from the Avon Longitudinal Study of Parents and Children, which starting in 1990 mailed questionnaires to 14,735 mothers in the UK, over 7 years from pregnancy onwards. Marginal structural models and multiple imputation were used to address time-varying confounding of the primary variables, testing for interaction between concurrent emotional/physical IPV and financial adversity, and adjusted for baseline age, ethnicity, education, partner's alcohol use, parity, depression, and social class. RESULTS: Emotional IPV (HR 1.44 (1.13,1.84)), physical IPV (HR 2.05 (1.21,3.49)), and financial adversity (HR 1.59 (1.44,1.77)) each predicted a multiplicative increase in the discrete-time hazard of incident homelessness. We identified joint effects for concurrent emotional IPV and financial adversity (HR 2.09 (1.35,3.22)) and concurrent physical IPV and financial adversity (HR 2.79 (1.21,6.44)). We further identified a temporary decline in self-reported physical IPV among mothers during pregnancy and up to 8 months post-partum. CONCLUSIONS: Emotional and physical IPV and financial adversity independently and jointly increase the risk of incident homelessness. The effects of emotional and physical IPV are comparable to or greater than the risk of financial adversity. Homelessness prevention policies should consider IPV victims as high-risk, regardless of financial status. Furthermore, self-reported physical IPV declines temporarily during pregnancy and up to 8 months post-partum. Screening for IPV in this period may miss high-risk individuals.

Prevalence and Correlates of Sexual Assault Perpetration and Ambiguous Consent in a Representative Sample of College Students.

The primary aim of the current study was to examine the prevalence and correlates of self-reported sexual assault (SA) perpetration, defined as nonconsensual sexualized touching or attempted or completed oral, vaginal, or anal penetration since starting college among men, women, and gender nonconforming (GNC) students. A secondary aim was to examine the prevalence and correlates of self-reported sexual encounters when the respondent was unsure that their partner consented (ambiguous consent). In spring 2016, 1,671 randomly sampled students (67% response rate) at two interconnected urban undergraduate institutions participated in an online survey about sexual experiences and personal and social contextual correlates. Prevalence estimates for SA perpetration and ambiguous consent were estimated and logistic regression was used to test bivariate associations between these two outcomes and a range of potential correlates. Approximately 2% of students self-reported any SA perpetration and 9% reported any ambiguous consent experiences since starting college. Pre-college SA perpetration, past-year SA victimization, belief in and use of nonverbal consent strategies, binge drinking, and depression symptoms were associated with higher odds of both SA perpetration and ambiguous consent while at college. Hookups were associated with higher odds of ambiguous consent; family social support was associated with lower odds of ambiguous consent. Findings of similar correlates for SA perpetration and ambiguous consent point to prevention programming focused on verbal consent strategies, alcohol harm reduction approaches, and pre-college interventions.

A Graphical Description of Partial Exchangeability.

Partial exchangeability is sufficient for the identification of some causal effects of interest. Here we review the use of common graphical tools and the sufficient component cause model in the context of partial exchangeability. We illustrate the utility of single world intervention graphs (SWIGs) in depicting partial exchangeability and provide an illustrative example of when partial exchangeability might hold in the absence of complete exchangeability.

Medical marijuana laws and driving under the influence of marijuana and alcohol.

AIMS: Medical marijuana law (MML) enactment in the United States has been associated with increased cannabis use but lower traffic fatality rates. We assessed the possible association of MML and individual-level driving under the influence of cannabis (DUIC) and also under the influence of alcohol (DUIA). DESIGN AND SETTING: Three cross-sectional U.S. adult surveys: The National Longitudinal Alcohol Epidemiologic Survey (NLAES; 1991-1992), the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001-2002), and the NESARC-III (2012-2013). PARTICIPANTS: The total n was 118 497: 41 764, 41 184, and 35 549 from NLAES, NESARC, and NESARC-III, respectively. MEASUREMENTS: Across the three surveys, similar questions in the Alcohol Use Disorder and Associated Disabilities Interview Schedule assessed DUIC and DUIA. Ever-MML states enacted MML between 1991-1992 and 2012-2013 (overall period). Early-MML states enacted MML between 1991-1992 and 2001-2002 (early period). Late-MML states enacted MML between 2001-2002 and 2012-2013 (late period). MML effects on change in DUIC and DUIA prevalence were estimated using a difference-in-differences specification to compare changes in MML and other states. FINDINGS: From 1991-1992 to 2012-2013, DUIC prevalence nearly doubled (from 1.02% to 1.92%), increasing more in states that enacted MML than other states (difference-in-differences [DiD] = 0.59%; 95% CI = 0.06%-1.12%). Most change in DUIC prevalence occurred between 2001-2002 and 2012-2013. DUIC prevalence increased more in states that enacted MML 2001-2002 to 2012-2013 than in never-MML states (DiD = 0.77%; 95% CI = -0.05%-1.59%), and in two early-MML states, California (DiD = 0.82; 95% CI = 0.06-1.59) and Colorado (DiD = 1.32; 95% CI = 0.11-2.53). In contrast, DUIA prevalence appeared unrelated to MML enactment. CONCLUSIONS: Medical marijuana law enactment in US states appears to have been associated with increased prevalence of driving under the influence of cannabis, but not alcohol.

U.S. Adults With Pain, a Group Increasingly Vulnerable to Nonmedical Cannabis Use and Cannabis Use Disorder: 2001-2002 and 2012-2013.

OBJECTIVE: Given changes in U.S. marijuana laws, attitudes, and use patterns, individuals with pain may be an emerging group at risk for nonmedical cannabis use and cannabis use disorder. The authors examined differences in the prevalence of nonmedical cannabis use and cannabis use disorder among U.S. adults with and without pain, as well as whether these differences widened over time. METHODS: Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309) were analyzed using logistic regression. Risk differences of past-year nonmedical cannabis use, frequent (at least three times a week) nonmedical use, and DSM-IV cannabis use disorder were estimated for groups with and without moderate to severe pain, and these risk differences were tested for change over time. RESULTS: Any nonmedical cannabis use was more prevalent in respondents with than without pain (2001-2002: 5.15% compared with 3.74%; 2012-2013: 12.42% compared with 9.02%), a risk difference significantly greater in the 2012-2013 data than in the 2001-2002 data. The prevalence of frequent nonmedical cannabis use did not differ by pain status in the 2001-2002 survey, but was significantly more prevalent in those with than without pain in the 2012-2013 survey (5.03% compared with 3.45%). Cannabis use disorder was more prevalent in respondents with than without pain (2001-2002: 1.77% compared with 1.35%; 2012-2013: 4.18% compared with 2.74%), a significantly greater risk difference in the data from 2012-2013 than from 2001-2002. CONCLUSIONS: The results suggest that adults with pain are a group increasingly vulnerable to adverse cannabis use outcomes, warranting clinical and public health attention to this risk. Psychiatrists and other health care providers treating patients with pain should monitor such patients for signs and symptoms of cannabis use disorder.

Time trends in US cannabis use and cannabis use disorders overall and by sociodemographic subgroups: a narrative review and new findings.

Background: Due to significant comorbidity and impairment associated with cannabis use and cannabis use disorder, understanding time trends in cannabis use and cannabis use disorder is an important public health priority.Objectives: To identify trends in cannabis use and cannabis use disorder overall, and by sociodemographic subgroup.Methods: Narrative review of published findings on trends in cannabis use and cannabis use disorders in data from repeated cross-sectional US general population surveys. In addition, in National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2002-2002) and NESARC-III (2012-2013) data, logistic regression was used to examine whether trends differed between subgroups of adults.Results: The review showed that in adults, cannabis use increased over the past decade overall and within sociodemographic subgroups (gender, age, race/ethnicity, income, education, marital status, urbanicity, region, pregnancy status, disability status), with greater increases in men and disabled adults. Most sources also indicated significant increases in cannabis use disorders. New analysis showed significantly greater increases in adult cannabis use and cannabis use disorder in men (p ≤ .0001); young adults (p < .05); Blacks (vs. Whites, p < .01); low income groups (p < .001); never-married p ≤ .0001), and urban residents (p < .05). In adolescents, cannabis use generally decreased, although recent increases were observed in older and non-White adolescents.Conclusion: Cannabis use and cannabis use disorder are increasing in adults, with specific sociodemographic groups at higher risk, and may be increasing in some adolescent subgroups. Studies should determine mechanisms for differential trends to provide information to policymakers and enable informed decisions on cannabis legalization and service planning.

Situational Contexts and Risk Factors Associated with Incapacitated and Nonincapacitated Sexual Assaults Among College Women.

BACKGROUND: Research has documented multilevel risk factors associated with experiencing incapacitated sexual assault among undergraduate women. Less is known about multilevel risk factors associated with nonincapacitated sexual assault. This study examines and compares the different settings, coercion methods, and relationships in which incapacitated and nonincapacitated sexual assaults occur among undergraduate women. MATERIALS AND METHODS: Our sample included 253 undergraduate women who reported experiencing sexual assault during college on a population-based survey of randomly selected students at two colleges in New York City in 2016 (N = 1671, response rate = 67%). We examined event-level data on their most significant sexual assault incident since entering college. Using multivariable statistical analysis, we identified situational contexts associated with incapacitated and nonincapacitated assault incidents adjusting for binge drinking, illicit drug use, and other confounding sociodemographic and psychosocial variables. RESULTS: Almost half (47%) of women who experienced sexual assault reported being incapacitated due to alcohol or drugs during the most significant incident. Being at a party before the event and "acquaintance" perpetrators were associated with incapacitated sexual assault after adjusting for binge drinking and other confounders. Meeting a perpetrator through an Internet dating app or indicating the perpetrator was an intimate partner were each associated with nonincapacitated assault incidents. Perpetrator use of physical force and verbal coercion were also associated with nonincapacitated assault incident. CONCLUSIONS: The different situational contexts associated with incapacitated and nonincapacitated sexual assaults have important implications for the design of prevention strategies that will effectively target the diverse risk environments in which campus sexual assault occurs.

Age Differences in Daily and Nondaily Cannabis Use in the United States, 2002-2014.

OBJECTIVE: Adult cannabis use has increased in the United States since 2002, particularly after 2007, contrasting with stable/declining trends among youth. We investigated whether specific age groups disproportionately contributed to changes in daily and nondaily cannabis use trends. METHOD: Participants ages 12 and older (N = 722,653) from the 2002-2014 National Survey on Drug Use and Health reported past-year cannabis use frequency (i.e., daily = ≥300 days/year; nondaily = 1-299 days/year; none). Multinomial logistic regression was used to model change in past-year daily and nondaily cannabis use prevalence by age group (i.e., 12-17, 18-25, 26-34, 35-49, 50-64, ≥65), before and after 2007. Multinomial logistic regressions estimated change in relative odds of cannabis use frequency over time by age, adjusting for other sociodemographics. RESULTS: Daily cannabis use prevalence decreased in ages 12-17 before 2007 and increased significantly across adult age categories only after 2007. Increases did not differ significantly across adult ages 18-64 and ranged between 1 and 2 percentage points. Nondaily cannabis use decreased among respondents ages 12-25 and 35-49 before 2007 and increased across adult age categories after 2007, particularly among adults 26-34 (i.e., 4.5 percentage points). Adjusted odds of daily versus nondaily cannabis use increased after 2007 for ages 12-64. CONCLUSIONS: Increases in daily and nondaily cannabis use prevalence after 2007 were specific to adult age groups in the context of increasingly permissive cannabis legislation, attitudes, and lower risk perception. Although any cannabis use may be decreasing among teens, relative odds of more frequent use among users increased in ages 12-64 since 2007. Studies should assess not only any cannabis use, but also frequency of use, to target prevention efforts of adverse effects of cannabis that are especially likely among frequent users.

Recent rapid decrease in adolescents' perception that marijuana is harmful, but no concurrent increase in use.

BACKGROUND: National trends in adolescent's marijuana risk perceptions are traditionally used as a predictor of concurrent and future trends in adolescent marijuana use. We test the validity of this practice during a time of rapid marijuana policy change. METHODS: Two repeated cross-sectional U.S. nationally-representative surveys of 8th, 10th, and 12th-graders: Monitoring the Future (MTF) (1991-2015; N = 1,181,692) and National Survey on Drug Use and Health (NSDUH) (2002-2014; N = 113,317). We examined trends in the year-to-year prevalence of perceiving no risk of harm in using marijuana regularly, and prevalence of regular marijuana use within the previous month. A piecewise linear regression model tested for a change in the relationship between trends. Similar analyses examined any past-month use and controlled for demographic characteristics. RESULTS: Among MTF 12th-graders, the prevalence of regular marijuana use and risk perceptions changed similarly between 1991 and 2006 but diverged sharply afterward. The prevalence of regular marijuana use increased by ∼1 percentage point to 6.03% by 2015. In contrast, the proportion of 12th-graders that perceived marijuana as posing no risk increased over 11 percentage points to 21.39%. A similar divergence was found among NSDUH 12th-graders and other grades, for any past month marijuana use, and when controlling demographic characteristics. CONCLUSIONS: An increase in adolescent marijuana use has not accompanied recent rapid decreases in marijuana risk perceptions. Policy makers may consider broader prevention strategies in addition to targeting marijuana risk perceptions. Further monitoring of predictors of marijuana use trends is needed as states legalize recreational marijuana use.

Self-medication of mood and anxiety disorders with marijuana: Higher in states with medical marijuana laws.

BACKGROUND: Self-medication with drugs or alcohol is commonly reported among adults with mood or anxiety disorders, and increases the risk of developing substance use disorders. Medical marijuana laws (MML) may be associated with greater acceptance of the therapeutic value of marijuana, leading individuals to self-medicate. METHODS: The study utilized data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005). Participants were sampled from households in the general population and included adults with a mood or anxiety disorder in the past 12 months (n = 7418), and the subset of those who used marijuana and no other drug (n = 314). Weighted logistic regression models predicted the prevalence of self-medication with drugs in U.S. states with and without MML, adjusting for individual and state-level covariates. As a negative control, analyses were repeated for self-medication with alcohol. RESULTS: Overall, self-medication with drugs was 3.73 percentage points higher (95% confidence interval [CI]: 0.93-6.53) among those living in MML states (p = 0.01). For the subpopulation that only used marijuana, self-medication with drugs was 21.22 percentage points higher (95% CI: 3.91-38.53) among those living in MML states (p = 0.02). In contrast, self-medication with alcohol had nearly identical prevalence in MML and non-MML states, overall and for drinkers. CONCLUSIONS: Among adults with mood or anxiety disorders, living in a medical marijuana law state is associated with self-medication with marijuana. While additional research is needed to determine the reasons for this association, clinical screening for self-medication with marijuana may be particularly important in states with medical marijuana laws.

Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta-analysis.

AIMS: To conduct a systematic review and meta-analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past-month marijuana use prevalence among adolescents. METHODS: A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta-analyzed. Estimates of MML effects on any past-month marijuana use prevalence from included studies were obtained from comparisons of pre-post MML changes in MML states to changes in non-MML states over comparable time-periods. These estimates were standardized and entered into a meta-analysis model with fixed-effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F-test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: None of the 11 studies found significant estimates of pre-post MML changes compared with contemporaneous changes in non-MML states for marijuana use prevalence among adolescents. The meta-analysis yielded a non-significant pooled estimate (standardized mean difference) of -0.003 (95% confidence interval = -0.012, +0.007). Four studies compared MML with non-MML states on pre-MML differences and all found higher rates of past-month marijuana use in MML states pre-MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non-significant results, although limited heterogeneity may warrant further study. CONCLUSIONS: Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.

Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States.

Importance: No US national data are available on the prevalence and correlates of DSM-5-defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5. Objective: To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV. Design, Setting, and Participants: In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017. Main Outcomes and Measures: Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders. Results: Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality. Conclusions and Relevance: Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.