Effectiveness of structured patient-clinician communication with a solution focused approach (DIALOG+) in community treatment of patients with psychosis - a cluster randomised controlled trial

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Survival of Civilian and Prisoner Drug-Sensitive, Multi- and Extensive Drug- Resistant Tuberculosis Cohorts Prospectively Followed in Russia

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Microbicides Development Programme: design of a phase III trial to measure the efficacy of the vaginal microbicide PRO 2000/5 for HIV prevention.

BACKGROUND: With 2.5 million new HIV infections per year, effective preventive methods against HIV are urgently needed, especially in sub-Saharan Africa. MDP301 is an ongoing trial of the vaginal microbicide PRO 2000/5 being conducted by the Microbicides Development Programme. The main objective of the trial is to determine the efficacy and safety of 0.5% and 2% concentrations of PRO 2000/5 gel compared to placebo in preventing vaginally acquired HIV infection. METHODS/DESIGN: MDP301 is a multicentre randomised placebo-controlled Phase III trial. The design was informed by pre-trial feasibility and pilot studies. The choice of trial population, assessments and endpoints are discussed along with statistical and ethical considerations. Adaptations to the design were made during the conduct of the trial; these included closing a study arm and changing the timing of the primary endpoint. DISCUSSION: The development of effective microbicide products remains one of the strongest hopes for new biomedical prevention tools. MDP301 is the largest Phase III microbicide trial to date, with 9404 enrolments, and is scheduled for completion in September 2009. Results are expected towards the end of 2009

Prenatal alcohol exposure and childhood atopic disease:A Mendelian randomization approach

BACKGROUND: Alcohol consumption in western pregnant women is not uncommon and could be a risk factor for childhood atopic disease. However, reported alcohol intake may be unreliable, and associations are likely to be confounded. OBJECTIVE: We aimed to study the relation between prenatal alcohol exposure and atopic phenotypes in a large population-based birth cohort with the use of a Mendelian randomization approach to minimize bias and confounding. METHODS: In white mothers and children in the Avon Longitudinal Study of Parents and Children (ALSPAC) we first analyzed associations between reported maternal alcohol consumption during pregnancy and atopic outcomes in the offspring measured at 7 years of age (asthma, wheezing, hay fever, eczema, atopy, and total IgE). We then analyzed the relation of maternal alcohol dehydrogenase (ADH)1B genotype (rs1229984) with these outcomes (the A allele is associated with faster metabolism and reduced alcohol consumption and, among drinkers, would be expected to reduce fetal exposure to ethanol). RESULTS: After controlling for confounders, reported maternal drinking in late pregnancy was negatively associated with childhood asthma and hay fever (adjusted odds ratio [OR] per category increase in intake: 0.91 [95% CI, 0.82-1.01] and 0.87 [95% CI, 0.78-0.98], respectively). However, maternal ADH1B genotype was not associated with asthma comparing carriers of A allele with persons homozygous for G allele (OR, 0.98 [95% CI, 0.66-1.47]) or hay fever (OR, 1.11 [95% CI, 0.71-1.72]), nor with any other atopic outcome. CONCLUSION: We have found no evidence to suggest that prenatal alcohol exposure increases the risk of asthma or atopy in childhood

Core common clinical and demographic characteristics of patients from the 2002-3 TB Cohort and 2008 XDRTB Cohort^*.

<p>*Note: 3 people do not contribute any survival time data.</p

XDR strains molecular genotypes and proportions of common mutations associated with fluroquinolone resistance.

<p>*Clusters were identified using VNTR and spoligotyping.</p><p>**The VNTR types are given as 28-digit codes corresponding to the numbers of copies of minisatellites in respective loci (please see column heading).</p

Uni- and multivariate Cox regression models of predictors of death.

<p>*Three people died on the same date as diagnosis and hence do not contribute any time to the analysis.</p><p>**In the multivariate Cox model age was taken as a continuous variable.</p>∧<p>Patients without available DST results from 2002-3 TB Cohort are excluded from the analysis.</p>#<p>All variables from univariate analysis significant at 10% significance level are included into multivariate analysis (2002-3 TB Cohort); multivariate analysis was not performed for 2008 XDRTB Cohort as no significant variable were identified at univariate analysis in this group.</p>$<p>In 2002-3 Cohort re-treatment cases included relapses only; in 2008 XDRTB Cohort re-treatment cases include relapses, return after default, treatment after failure, chronic patients.</p

Kaplan-Meier survival curves for patients from (A) 2002-3 TB Cohort defined by MDR- vs non-MDR status and (B) 2008 XDRTB Cohort.

<p>Kaplan-Meier survival curves for patients from (A) 2002-3 TB Cohort defined by MDR- vs non-MDR status and (B) 2008 XDRTB Cohort.</p

High-dose vitamin D-3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis:a double-blind randomised controlled trial

Background: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. Methods: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D3 or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D3. This trial is registered with ClinicalTrials.gov number NCT00419068. Findings: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90–2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (pinteraction=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36–48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (pinteraction=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6–88·2; p&lt;0·0001). Interpretation: Administration of four doses of 2·5 mg vitamin D3 increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism