A Randomized,Double-Blind,Placebo-Controlled,Trial of Lamotrigine Therapy in Bipolar Disorder,Depressed or Mixed Phase and Cocaine Dependence

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1–10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.     

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth

Background

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.

Methods

Opioid dependent adolescents and young adults (n = 152), aged 15–21, were randomized to 12 weeks (BUP, n = 74) or 2 weeks of detoxification (DETOX, n = 78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.

Results

In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.

Conclusions

Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.     

Donor transmission of malignant melanoma to a liver graft recipient: case report and literature review

Abstract:  Post-transplant malignancy of donor origin is a rare complication of organ transplantation, most likely transmitted as micrometastases within the parenchyma of the donor organ or from circulating tumor cells contained within the organ. Patient survival is dependent upon early diagnoses, and differentiation of the malignancy as of donor or recipient derivation is important in developing a treatment modality. The utilization of fluorescent in situ hybridization chromosome analysis and DNA sequence analysis of the tumor cells can assist in this determination. This case report describes the management of donor transmitted malignant melanoma in a liver graft recipient and a review of the current literature.     

Brief Report: Brain Activation to Social Words in a Sedated Child with Autism

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word ‘hello’, with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word ‘hello.’ These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.     

A psychometric evaluation of the CDRS and MADRS in assessing depressive symptoms in children

OBJECTIVE: This study compared the psychometric properties of the Children's Depression Rating Scale-Revised (CDRS-R) and the Montgomery-Asberg Depression Rating Scale (MADRS) in children with major depressive disorder. METHOD: Children (N = 96; ages 8 to 11 years inclusive) with nonpsychotic major depressive disorder were enrolled. Participants were part of a multisite, outpatient, randomized, placebo-controlled, 9-week trial of fluoxetine (10 mg/day for the first week and 20 mg/day thereafter). The CDRS-R and MADRS were completed based on clinician interviews with both parents and children. Classic test theory and item response theory analyses were conducted. RESULTS: The MADRS and CDRS-R total scores were correlated at baseline (r = 0.51) and at study exit (r = 0.85). Cronbach's alpha was .86 (CDRS-R) and .82 (MADRS) at exit. The effect sizes for change from baseline to exit between the fluoxetine and placebo groups were 0.78 (CDRS-R) and 0.61 (MADRS). There was agreement between the CDRS-R and MADRS in the declaration of treatment response (50% improvement from baseline to exit) in 84.2% of children. Test information function favored the CDRS-R. CONCLUSIONS: The CDRS-R showed greater effect size for differentiating drug and placebo and better test information than the MADRS in this study of depressed children.     

Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia

OBJECTIVE: This study evaluated the validity of prescriber, patient, and research assistant ratings of adherence to prescribed oral antipsychotic medication among outpatients with schizophrenia or schizoaffective disorder in comparison with electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or schizoaffective disorder (N=26) received adherence assessments via electronically monitored medication vial caps as well as by monthly prescriber, patient, and research assistant report for up to six months. RESULTS: Electronic monitoring detected greater nonadherence rates (57%) than either prescribers (7%) or patients (5%), though the research assistant ratings were 54%. No directional bias was found between electronic monitoring and assignment of adherence by research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS: Both patients and prescribers grossly overestimated medication adherence, which may interfere with or reduce the effectiveness of diligent medication management.     

Cyclooxygenase-2 expression is not associated with clinical outcome in synovial sarcoma

Several studies have identified cyclooxygenase-2 (COX-2) expression in a variety of sarcomas, including rhabdomyosarcoma, osteosarcoma and chondrosarcoma. Although overexpression of COX-2 has been associated with poor prognosis and decreased survival in chondrosarcoma and osteosarcoma, no relationship between COX-2 expression and patient outcome has been demonstrated in rhabdomyosarcoma or adult soft tissue sarcomas. Little is known concerning the expression of COX-2 in synovial sarcoma. Therefore, the aim of this study was to examine the expression of COX-2 in synovial sarcoma and if shown, to identify any association with tumor stage and oncologic outcome. Paraffin-embedded specimens from 27 patients with synovial sarcoma who were treated with surgical resection or biopsy were obtained. Specimens were evaluated for the degree of COX-2 expression after immunohistochemical staining. Specimens were assigned an immunoreactivity score (IS) based on the percent positivity of the specimen. A retrospective chart analysis was performed to determine the clinical stage at presentation, incidence of local recurrence, presence of metastatic disease and overall survival. Statistical analysis was then performed to determine whether there was a significant relationship between IS and stage at presentation or patient outcomes. COX-2 expression was detected in 18 of 27 (66.67%) of the pathological specimens. There was a statistically significant relationship between COX-2 expression and patient clinical stage at presentation; however, we were unable to identify a significant relationship between IS and patient survival. We also found no significant relationship between IS and development of metastases or local recurrence. COX-2 was expressed to some degree in 67% of the tumor specimens. There was a significant relationship between IS and patient stage at presentation, but no significant relationship between COX-2 expression and clinical outcome could be identified. The fact that these tumors do express COX-2, however, suggests the potential for an additional target for more effective therapy.     

Contemporary issues in dental education in Australia

Australia has witnessed a proliferation of dental workforce training opportunities over the last 15 years, including dentists, dental therapists, dental hygienists and prosthetists. The reasons for this have not been examined critically. Universities have welcomed the opportunities to increase the student base but do not seem to have examined the advisability of continued expansion or its impact on the delivery and costs of health services. Nor have they enquired expressly whether they have any responsibility in these matters. Public health benefits should constitute a significant element of curriculum design. There seems to have been a general acceptance of the premise that more is necessarily better. Ironically, these developments have occurred in the face of significant recurrent cost increments and serious academic staff shortages. The schools have responded with alterations to curriculum content. Student cohort composition, course structures, educational focus, postgraduate training and research have been affected. The primary purpose of this review is to highlight the issues which currently drive workforce training and curriculum content and to suggest that some current practices should be re-examined as a starting point for setting defined common objectives within the Australian dental educational spectrum. Salient issues which require examination include course standards and accreditation, workforce mix, dental health demands, public service obligations and staffing profiles.     

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

Background  

Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.