Brett Ewing

Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-analysis

CONTEXT Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder. OBJECTIVE To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration. DATA SOURCES AND STUDY SELECTION Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events. DATA EXTRACTION Independent article review and study quality assessment by 2 investigators. DATA SYNTHESIS Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms. CONCLUSIONS Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.

The Prevalence and Overlap of Interstitial Cystitis/Bladder Pain Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in Men: Results of the RAND Interstitial Cystitis Epidemiology Male Study

PURPOSE As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we developed validated case definitions to identify interstitial cystitis/bladder pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in men. Using population based screening methods, we applied these case definitions to determine the prevalence of these conditions in men. MATERIALS AND METHODS A total of 6,072 households were contacted by telephone to screen for men who had symptoms of interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive, of whom 149 met the inclusionary criteria and completed the telephone interview. For interstitial cystitis/bladder pain syndrome 2 case definitions were applied (1 with high sensitivity and 1 with high specificity), while for chronic prostatitis/chronic pelvic pain syndrome a single case definition (with high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. RESULTS The interstitial cystitis/bladder pain syndrome weighted prevalence estimates for the high sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1-2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI 966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and 2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition of interstitial cystitis/bladder pain syndrome in the United States. The overlap between men who met the high specificity interstitial cystitis/bladder pain syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome case definition was 17%. CONCLUSIONS Symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread among men in the United States. The prevalence of interstitial cystitis/bladder pain syndrome symptoms in men approaches that in women, suggesting that this condition may be underdiagnosed in the male population.

Group motivational interviewing for adolescents: change talk and alcohol and marijuana outcomes.

OBJECTIVE Little is known about what may distinguish effective and ineffective group interventions. Group motivational interviewing (MI) is a promising intervention for adolescent alcohol and other drug use; however, the mechanisms of change for group MI are unknown. One potential mechanism is change talk, which is client speech arguing for change. The present study describes the group process in adolescent group MI and effects of group-level change talk on individual alcohol and marijuana outcomes. METHOD We analyzed 129 group session audio recordings from a randomized clinical trial of adolescent group MI. Sequential coding was performed with the Motivational Interviewing Skill Code (MISC) and the CASAA Application for Coding Treatment Interactions software application. Outcomes included past-month intentions, frequency, and consequences of alcohol and marijuana use; motivation to change; and positive expectancies. RESULTS Sequential analysis indicated that facilitator open-ended questions and reflections of change talk increased group change talk. Group change talk was then followed by more change talk. Multilevel models accounting for rolling group enrollment revealed group change talk was associated with decreased alcohol intentions, alcohol use, and heavy drinking 3 months later; group sustain talk was associated with decreased motivation to change, increased intentions to use marijuana, and increased positive alcohol and marijuana expectancies. CONCLUSIONS Facilitator speech and peer responses each had effects on change and sustain talk in the group setting, which were then associated with individual changes. Selective reflection of change talk in adolescent group MI is suggested as a strategy to manage group dynamics and increase behavioral change.

Substance Use and Other Risk Factors for Unprotected Sex: Results From An Event-Based Study of Homeless Youth

This study used an event-based approach to understand condom use in a probability sample of 309 homeless youth recruited from service and street sites in Los Angeles County. Condom use was significantly less likely when hard drug use preceded sex, the relationship was serious, the partners talked about “pulling out”, or sex occurred in a non-private place (and marginally less likely when heavier drinking preceded sex, or the partnership was monogamous or abusive). Condom use was significantly more likely when the youth held positive condom attitudes or were concerned about pregnancy, the partners talked about condom use, and the partners met up by chance. This study extends previous work by simultaneously examining a broad range of individual, relationship, and contexual factors that may play a role in condom use. Results identify a number of actionable targets for programs aimed at reducing HIV/STI transmission and pregnancy risk among homeless youth.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis

BackgroundChronic pain patients increasingly seek treatment through mindfulness meditation.PurposeThis study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults.MethodWe conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use.ResultsThirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life.ConclusionsWhile mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Social Networks of Homeless Youth in Emerging Adulthood

Little is known about the social networks of homeless youth in emerging adulthood despite the importance of this information for interventions to reduce health risks. This study examined the composition of social networks, and the risks and supports present within them, in a random sample of 349 homeless youth (33.4% female, 23.9% African American, 17.7% Hispanic) between the ages of 18 and 24. Social network members who were met on the street were among the most likely to be perceived as engaging in risky sex, as well as to engage in substance use with the youth. Youth were more likely to count on relatives and sex partners for support compared to other network members, but they also were more likely to use substances with sex partners and perceived them as engaging in risky sex. Interventions may need to recognize the importance of intimate relationships during the developmental stage of emerging adulthood by enhancing supportive bonds and reducing substance use and risky sex in these relationships.

A randomized controlled trial of a group motivational interviewing intervention for adolescents with a first time alcohol or drug offense

Group motivational interviewing (MI) interventions that target youth at-risk for alcohol and other drug (AOD) use may prevent future negative consequences. Youth in a teen court setting [n=193; 67% male, 45% Hispanic; mean age 16.6 (SD=1.05)] were randomized to receive either a group MI intervention, Free Talk, or usual care (UC). We examined client acceptance, and intervention feasibility and conducted a preliminary outcome evaluation. Free Talk teens reported higher quality and satisfaction ratings, and MI integrity scores were higher for Free Talk groups. AOD use and delinquency decreased for both groups at 3 months, and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC. Results contribute to emerging literature on MI in a group setting. A longer term follow-up is warranted.

A longitudinal examination of alcohol, marijuana, and cigarette perceived norms among middle school adolescents

BACKGROUND Adolescents tend to overestimate the prevalence of substance use among their peers and these perceived norms are associated with their current and future use. However, little is known about how perceived norms change over time during middle school, a developmental period when adolescents are at-risk for initiating substance use. METHOD We examined changes in perceived norms of alcohol, marijuana, and cigarettes over a two-year period among a large and diverse sample of 6th and 7th grade youth (N=6097; 50.1% female; 54% Hispanic). Participants completed a baseline survey and two subsequent annual surveys. Participants estimated the percentage of their peers they believed used each substance, as well as indicated levels of personal use, offers to use from peers, and exposure to peers who were using each substance. RESULTS Perceived norms of all three substances increased over time. Increases were somewhat attenuated when controlling for demographic factors, personal use, and peer factors, but remained significant. Female adolescents and those reporting non-Hispanic White ethnicity experienced the greatest increase in perceived norms over time. CONCLUSION Normative perceptions of substance use increase greatly during the middle school years, an effect which cannot be fully explained by demographics, personal use, or peer factors. Given that perceived norms are often associated with personal use, early interventions with middle school youth are warranted to prevent the growth of these influential factors during this developmental period.

Alcohol and marijuana use trajectories in a diverse longitudinal sample of adolescents: examining use patterns from age 11 to 17 years

AIMS We tested race/ethnic differences in alcohol and marijuana (AM) trajectories (comprising an intercept term, reflecting overall probability of use, and a slope term, reflecting change in probability of use) during adolescence, whether AM use trajectories predicted high school outcomes, and whether outcomes differed by race/ethnicity after controlling for trajectory of AM use. DESIGN This longitudinal study involved 6509 youth from 16 middle schools in Southern California surveyed from age 11.5 (2008) to age 17 (2015) years; all surveys assessed AM use, and the final survey also examined high school outcomes. SETTING Youth completed five surveys in middle school and two on-line surveys in high school. PARTICIPANTS The sample was 50% male and 80% non-white. MEASUREMENTS Intercept (at 2.75 years post-baseline) and slope of AM use were examined as outcomes for race/ethnic differences. AM use trajectories were examined as predictors of academic performance and unpreparedness, social functioning, mental and physical health and delinquency. FINDINGS We found differences in trajectories of use by race/ethnicity, with white youth reporting a higher overall intercept of alcohol use compared to all other groups (versus Asian P < 0.001, black P = 0.001, multi-ethnic P = 0.008). Overall, examination of trajectories of use showed that adolescents with a higher alcohol use intercept term reported greater academic unpreparedness (P < 0.001) and delinquency (P < 0.001) at wave 7 in high school. In addition, youth with a higher intercept for marijuana use reported greater academic unpreparedness (P < 0.001) and delinquency (P < 0.001), and poorer academic performance (P = 0.032) and mental health (P = 0.002) in high school. At wave 7, compared to white youth, Hispanic and multi-ethnic youth reported poorer academic performance (P < 0.001 and P = 0.034, respectively); Asian, black and Hispanic youth reported higher academic unpreparedness (P < 0.001, P = 0.019, and P = 0.001); and Asian youth and multi-ethnic youth reported poorer physical health (P = 0.012 and P = 0.018) controlling for AM use. CONCLUSIONS Greater AM use was associated with worse functioning in high school for all youth. After controlling for AM use, non-white youth reported worse outcomes in high school for academics and health.

Alternative Tobacco Product Use and Smoking Cessation Among Homeless Youth in Los Angeles County

INTRODUCTION Approximately 70% of homeless youth smoke cigarettes, but their use of alternative tobacco products (ATPs) is unknown. This paper reports on ATP use among past-month smokers in Los Angeles County, including whether it differs by demographic characteristics, homelessness severity, past-year quit attempts, and readiness to quit smoking. Given the growing popularity of e-cigarettes, we also report on perceptions of harm and reasons for using this product. METHODS We surveyed 292 unaccompanied homeless youth who were randomly sampled from street sites. Participants had smoked at least 100 cigarettes during their lifetime and 1 cigarette during the past month. RESULTS Seventy-two percent of youth reported past-month ATP use (e-cigarettes = 51%; little cigars/cigarillos = 46%; hookah = 31%; other smokeless tobacco product = 24%; chewing tobacco/moist snuff = 19%). Current ATP use was unrelated to most demographic characteristics or having a past-year quit attempt. However, youth who planned to quit smoking in the next 30 days were significantly less likely to report current use of hookahs, other smokeless tobacco products, or e-cigarettes. Among lifetime e-cigarette users, the most common reasons for use included not having to go outside to smoke (38%) and being able to deal with situations or places where they cannot smoke (36%); it was less common to report using e-cigarettes to quit smoking (17%-18%). DISCUSSION Dual use of ATPs among homeless youth smokers is common and is more likely among those who have no immediate plans to quit smoking. Effective and easily disseminable strategies for reducing all forms of tobacco use among homeless youth are urgently needed.