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Objective This paper presents the final analysis of once-daily darunavir/ritonavir ( DRV/r) vs. lopinavir/ritonavir ( LPV/r) in treatment-naïve HIV-1-infected adults. Methods ARTEMIS ( AntiRetroviral Therapy with TMC114 ExaMined In naïve Subjects; NCT00258557) was a randomized, open-label, phase- III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. Results Of 689 randomized patients receiving treatment ( DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response ( HIV-1 RNA < 50 copies/ mL) [ DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat ( ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint ( P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor ( PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor ( NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. Conclusion Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients. [ABSTRACT FROM AUTHOR]

Aims To determine if a low-intensity, clinic-integrated behavioural intervention reduced the incidence of hypoglycaemic events in children with Type 1 diabetes. Methods A total of 390 families with children with Type 1 diabetes were enrolled in a 2-year, randomized clinical trial of a behavioural intervention. The intervention was designed to improve diabetes management practices by targeting the family's diabetes problem-solving skills. Hypoglycaemic events were categorized in two groups: those treated by oral ingestion and those treated by parenteral therapy. Events were self-reported by participants at each clinic visit, which occurred approximately every 3-4 months. Analyses included two-sample t-tests, the mean cumulative function test, and the Cox proportional hazards model for recurrent events to compare the incidence between groups. Results Across the entire 2-year study period, the incidence of hypoglycaemic events treated by oral ingestion of glucose-rich foods and events requiring parenteral therapy did not significantly differ between study conditions; however, during the second year of participant enrolment, the incidence of events treated by oral ingestion in the intervention group was 13.6 per 100 person-years compared with 27.3 per 100 patient-years in the control group ( P = 0.02). The hazard ratio of these events during the second year was 0.49 (95% CI 0.27-0.90; P = 0.02). Conclusions Our findings suggest the need for a long-term (> 1 year) focus on the implementation of interventions targeting diabetes management in young people. Behavioural interventions targeting problem-solving skills could be considered as practical, non-pharmacological strategies to reduce hypoglycaemia in adolescents with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims To determine whether the provision of contingencymanagement using financial incentives to improve hepatitis B vaccine completion in people who inject drugs entering community treatment represents a cost-effective use of healthcare resources. Design A probabilistic cost-effectiveness analysis was conducted, using a decision-tree to estimate the short-term clinical and health-care cost impact of the vaccination strategies, followed by a Markov process to evaluate the long-term clinical consequences and costs associated with hepatitis B infection. Settings and participants Data on attendance to vaccination from a UK cluster randomized trial. Intervention Two contingency management options were examined in the trial: fixed versus escalating schedule financial incentives. Measurement Life-time health-care costs and quality-adjusted life years discounted at 3.5% annually; incremental cost-effectiveness ratios. Findings The resulting estimate for the incremental life-time health-care cost of the contingency management strategy versus usual care was £21.86 [95% confidence interval (CI) = -£12.20 to 39.86] per person offered the incentive. For 1000 people offered the incentive, the incremental reduction in numbers of hepatitis B infections avoided over their lifetime was estimated at 19 (95% CI = 8-30). The probabilistic incremental cost per quality adjusted life-year gained of the contingency management programmewas estimated to be £6738 (95% CI = £6297-7172),with an 89% probability of being considered cost-effective at a threshold of £20 000 per quality-adjusted life years gained (97.60% at £30 000). Conclusions Using financial incentives to increase hepatitis B vaccination completion in people who inject drugs could be a cost-effective use of health-care resources in the UK as long as the incidence remains above 1.2%. [ABSTRACT FROM AUTHOR]

Aims To characterize infections and compare obstetric outcomes in opioid-dependent pregnant women who participated in a randomized clinical trial comparing agonist medications, methadone and buprenorphine. Design Incidence of infections was identified as part of the screening medical assessment. As part of a planned secondary analysis, analysis of variance and polytomous logistic regressions were conducted on obstetric outcome variables using treatment randomization condition (maternal maintenance with either methadone or buprenorphine) as the predictor variable, controlling for differences between study sites. Setting Six United States sites and one European site that provided comprehensive treatment to opioid-dependent pregnant women. Participants Pregnant opioid-dependent women ( n = 131) who delivered while participating in the Maternal Opioid Treatment: Human Experimental Research ( MOTHER) study. Measurements Obstetric, infectious and other maternal medical complications captured by medical records, physical examination, blood tests and self-report. Neonatal medical complications captured by medical records. Findings Hepatitis C was the most common infection (32.3%), followed by hepatitis B (7.6%) and chlamydia (6.1%) among participants at study enrollment. Maternal methadone versus buprenorphine maintenance was associated with a higher incidence of preterm labor ( P = 0.04) and a significantly higher percentage of signs of respiratory distress in neonates at delivery ( P = 0.05). Other medical and obstetric complications were infrequent in the total sample, as well as in both methadone and buprenorphine conditions. Conclusions Buprenorphine appears to have an acceptable safety profile for use during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair. Design Pilot double-masked randomized placebo-controlled trial. Setting Large academic medical center. Participants Sixteen individuals aged 70 and older with hip fracture. Intervention Donepezil 5 mg or placebo was randomly allocated and initiated within 24 hours of surgery, preoperatively or postoperatively. Daily treatment was continued for 30 days or until side effects or the clinical situation required termination. Measurements All outcomes were ascertained masked to treatment status. Information on drug tolerability and safety was obtained from the participant, nurse, and medical record. Delirium presence and severity were measured during daily hospital interviews and at 2, 4, and 6 weeks after surgery after a standardized assessment using the Confusion Assessment Method ( CAM) and the Memorial Delirium Assessment Scale ( MDAS). Results Participants in the donepezil and placebo arms had similar baseline characteristics. Participants in the donepezil arm experienced significantly more side effects. In longitudinal models, there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time (odds ratio = 0.9, 95% confidence interval ( CI) = 0.4-2.3) or delirium severity over time (effect size = −0.2 on 30-point MDAS scale, 95% CI = −1.5-1.2). Conclusion Participants randomized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects. Overall, sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial. [ABSTRACT FROM AUTHOR]