Temporal dynamics of the relationship between change in depressive symptoms and cannabis use in adolescents receiving psychosocial treatment for cannabis use disorder.

AIMS: Cannabis use disorder (CUD) and depression frequently co-occur in youth. How depressive symptoms change over the course of CUD treatment and how they impact substance use treatment outcomes is unknown. In the current study, we examine the temporal relationships between cannabis use and depression in adolescents receiving evidence-based treatments for CUD as part of a multisite clinical trial. DESIGN: Six hundred adolescents (age 12-18) with a CUD were randomly assigned to substance use treatment from one of five evidence-based psychosocial interventions. We assessed self-reported cannabis use frequency and depressive symptoms at baseline (BL) and again at 3-, 6-, 9, and 12-months. A bivariate latent change model assessed bidirectional effects of baseline levels and time-lagged changes in depressive symptoms and cannabis use on depression and cannabis use outcomes. FINDINGS: Depressive symptoms (72%) and major depressive disorder (MDD) (18%) were common at BL. Both depression and cannabis use decreased over time and change in cannabis use was significantly associated with change in depressive symptoms (b = 1.22, p = .003). Time-lag analyses showed that within-subject change in depression (from one time point to the next) was predicted by previous depression (b = -0.71, p < .001) but not cannabis use (p = .068), and change (decrease) in cannabis use was predicted by previous (greater) depressive symptoms (b = -1.47, p < .001) but not cannabis use (p = .158), respectively. CONCLUSION: These findings indicate an enduring relationship between decreasing cannabis use and decreasing depression among adolescents lasting for 9-months after receiving psychosocial interventions for CUD. The presence of depressive symptoms did not appear to interfere with substance use treatment or attenuate improvements in cannabis use frequency. A decrease in cannabis use was not contingent upon a reduction in depressive symptoms. These findings are limited by the possibility of regression to the mean for both cannabis use and depressive symptoms, and the lack of a nonintervention control group.

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.

Effects of a health care provider intervention in reduction of sexual risk and related outcomes in economically marginal communities in Mumbai, India.

BACKGROUND: The present study assessed the effectiveness of a brief narrative intervention implemented by trained biomedical and Ayurveda, Yoga, Unani, Siddha, Homeopathy (AYUSH) providers from three low-income communities in Mumbai, India. METHODS: A quasi-experimental research design compared attitudinal and behavioural changes among a cohort of 554 patients presenting gupt rog ('secret sexual illnesses') to biomedical and AYUSH providers who were trained in the narrative intervention model (NIM; referred to as 'narrative prevention counseling' in the intervention manual) with those providing standard care (untrained in NIM). Data were analysed using multivariate and longitudinal statistical models. RESULTS: Patients who received treatment for gupt rog from trained providers reported receiving a significantly higher number of services than those receiving services from untrained providers (mean 8.9 vs 7.6 services, respectively; P<0.001). In addition, a higher number of patients seeing the trained providers no longer had gupt rog problems than those seeing untrained providers (42% vs 25%, respectively; P<0.001). Patient-reported sex with a partner who was not the wife decreased significantly from baseline to follow-up for the entire sample but was significantly greater among patients receiving treatment from trained AYUSH providers (from 27% at baseline to 2% at follow up) compared with untrained providers (from 18% at baseline to 5% at follow up; P<0.001). CONCLUSIONS: The results support the effectiveness of brief narrative intervention in primary care settings for reducing sexual risk and associated vulnerabilities among married men.

Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women.

OBJECTIVES: To investigate the effects of dehydroepiandrosterone (DHEA) combined with exercise on bone mass, strength, and physical function in older, frail women. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: A major medical institution. PARTICIPANTS: Ninety-nine women (mean age 76.6 ± 6.0) with low sulfated DHEA (DHEAS) levels, low bone mass, and frailty. INTERVENTION: Participants received 50 mg/d DHEA or placebo for 6 months; all received calcium and cholecalciferol. Women participated in 90-minute twice-weekly exercise regimens. MEASUREMENTS: Hormone levels, bone mineral density (BMD), bone turnover markers, body composition, upper and lower extremity strength, physical performance. RESULTS: Eighty-seven women (88%) completed 6 months. There were no significant changes in BMD or bone turnover markers. DHEA supplementation resulted in gains in lower extremity strength (from 459 ± 121 N to 484 ± 147 N; P=.01). There was also improvement in Short Physical Performance Battery score, a composite score that focuses on lower extremity function, in those taking DHEA (from 10.1 ± 1.8 to 10.7 ± 1.9; P=.02). There were significant changes in all hormone levels, including DHEAS, estradiol, estrone, and testosterone, and a decline in sex hormone-binding globulin levels in those taking DHEA. CONCLUSION: DHEA supplementation improved lower extremity strength and function in older, frail women involved in a gentle exercise program of chair aerobics or yoga. No changes were found in BMD either due to small sample size, short duration of study or no effect. The physical function findings are promising and require further evaluation as frail women are at high risk for falls and fracture.

Absence of iatrogenic or contagion effects in adolescent group therapy: findings from the Cannabis Youth Treatment (CYT) study.

Though widely used and presumed effective in practice, some scholars (Dishion et al., 1999) have raised the concern that group therapy for adolescents with substance use disorder and a range of deviancy has the potential for causing iatrogenic effects (e.g., increased substance use, behavior and legal problems) for those with low deviancy. Using data from 400 youth in the largest adolescent treatment experiment conducted to date (Dennis et al., 2004), this study shows that group composition in terms of conduct disorder symptoms is not associated with worse substance use, psychological, environmental or legal treatment outcomes. The results actually indicated that there was a slight advantage for youth with high conduct disorder to be included in the groups with less symptoms. The results appear consistent with recent meta-analyses of delinquency studies (Lipsey, 2006) which have found no evidence of iatrogenic effects. These results support the common clinical belief that group therapy for youths with substance use disorders is a safe and effective treatment modality.

Self-efficacy as a predictor of treatment outcome in adolescent substance use disorders.

Youth substance abuse relapse prevention was examined as a function of patients' situational self-efficacy (SE), their confidence to abstain from substance use in high-risk situations. An increase in SE has been shown to be enhanced by cognitive behavioral therapy (CBT) in adults. Eighty-eight adolescent substance abusers were randomly assigned to either CBT or psycho-education (PET) group therapy. Substance use and SE were assessed at end of treatment, 3- and 9-months after the end of planned treatment. Increased SE predicted subsequent abstinence independently from drug urinalysis and treatment condition only during treatment, while previous substance use predicted subsequent self-efficacy. CBT was not differentially effective than PET in promoting SE. It is recommended that potential mediators and moderators of SE in the treatment of adolescent substance abuse should be further explored.

Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women.

Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C-telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.

Correlation between ancillary community services with adolescent substance use disorders treatment outcome.

OBJECTIVE: This study explores whether participation in ancillary out-of-program services predicts outcomes of adolescents treated for substance use disorders. METHOD: Eighty-eight consenting adolescents, 13-18 years of age recruited at an outpatient program filled the Teen Treatment Services Review (T-TSR) during eight weekly sessions, and at 3-and 9-Month post-treatment. Outcome variables included urinalysis and three subscales of the Teen-Addiction Severity Index (T-ASI) during Treatment (DT) and at follow-ups. The predictor variable was the number of reported Out-of-Program service contact Days (OD). RESULTS: While DT OD did not correlate with DT urinalysis, high DT OD days showed a trend toward predicting negative 3-month (3-M) urinalysis. By contrast, high 3-M OD days-predicted positive 3-M urinalyses as well as high use on all three T-ASI subscales. Out-of-Program services between 3-and 9-M post-treatment were not correlated with 9-M objective or subjective outcomes. CONCLUSION: The more therapeutic services received during treatment, the better the short-term outcome. The more therapeutic services received post-treatment, however, the poorer the shortterm outcome. Use of outside services presented a response rather than a cause of substance use.

Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men.

OBJECTIVES: To study the effects of vitamin D supplementation in healthier populations of men. DESIGN: : Randomized, controlled trial. SETTING: General clinical research center. PARTICIPANTS: Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). INTERVENTION: Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. MEASUREMENTS: Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. RESULTS: The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. CONCLUSION: The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.

Treating juvenile offenders for marijuana problems.

AIMS: This study investigated the characteristics and substance abuse treatment experience of two differentially defined groups of juvenile offenders, those who were referred or otherwise involved with the legal system and those who reported recent criminal behavior. DESIGN: Six hundred adolescents from the Cannabis Youth Treatment (CYT) Project were classified by criminal justice system involvement and recent criminal behavior. Multivariate and repeated-measures techniques explored substance use frequency, substance use problems, psychological and social risk factors and treatment outcomes as functions of criminal status. FINDINGS: Adolescents reporting criminal justice system involvement were comparable to adolescents reporting no legal involvement. Adolescents reporting past crime presented with heavier substance use, more substance use problems and greater psychological and environmental risks. Criminally active adolescents had greater reductions in substance use frequency and substance use problems during the course of treatment. CONCLUSION: Juvenile offender status, whether defined by criminal justice system involvement or criminal behavior, does not seem to mitigate the potential for adolescents to benefit from manual-guided outpatient treatments.