Internet-Based Brief Intervention to Prevent Unhealthy Alcohol Use among Young Men: A Randomized Controlled Trial.

Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults. 2 parallel-group randomized controlled trial with follow-up at 1 and 6 months. Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013. Intervention: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. Intervention group participants received the IBI. Control group (CG) participants completed only an assessment. Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014-2015. Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months. We found protective short term effects of a primary prevention IBI. Controlled-Trials.com ISRCTN55991918.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Ability of physicians to diagnose influenza and usefulness of a rapid influenza antigen test in febrile returning travelers: A randomized controlled trial.

BACKGROUND: Fever is a frequent cause of medical consultation among returning travelers. The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test (iRDT) modified the clinical management of such patients. METHODS: Randomized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012. Inclusion criteria were 1) age ≥18 years, 2) documented fever of ≥38 °C or anamnestic fever + cough or sore throat within the last 4 days, 3) illness occurring within 14 days after returning from a trip abroad, 4) no definitive alternative diagnosis. Physicians were asked to estimate the likelihood of influenza on clinical grounds, and a single nasopharyngeal swab was taken. Thereafter patients were randomized into 2 groups: i) patients with iRDT (BD Directigen A + B) performed on the nasopharyngeal swab, ii) patients receiving usual care. A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period. Clinical management was evaluated on the basis of cost of medical care, number of X-rays requested and prescription of anti-infective drugs. RESULTS: 100 eligible patients were referred to the investigators. 93 patients had a naso-pharyngeal swab for a PCR and 28 (30%) swabs were positive for influenza. The median probability of influenza estimated by the physician was 70% for the PCR positive cases and 30% for the PCR negative cases (p < 0.001). The sensitivity of the iRDT was only 20%, and specificity 100%. Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 (95%CI 454-707) and USD 661 (95%CI 522-800) respectively. 14/60 (23%) of the patients managed with iRDT were prescribed antibiotics versus 13/33 (39%) in the control group (p = 0.15). No patient received antiviral treatment. CONCLUSION: Influenza was a frequent cause of fever among these febrile returning travelers. Based on their clinical assessment, physicians had a higher level of suspicion for influenza in PCR positive cases. The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00821626.

Sugar-and artificially sweetened beverages and intrahepatic fat : a randomized controlled trial.

OBJECTIVE: To test the hypothesis that substituting artificially sweetened beverages (ASB) for sugar-sweetened beverages (SSB) decreases intrahepatocellular lipid concentrations (IHCL) in overweight subjects with high SSB consumption. METHODS: About 31 healthy subjects with BMI greater than 25 kg/m(2) and a daily consumption of at least 660 ml SSB were randomized to a 12-week intervention in which they replaced SSBs with ASBs. Their IHCL (magnetic resonance spectroscopy), visceral adipose tissue volume (VAT; magnetic resonance imaging), food intake (2-day food records), and fasting blood concentrations of metabolic markers were measured after a 4-week run-in period and after a 12-week period with ASB or control (CTRL). RESULTS: About 27 subjects completed the study. IHCL was reduced to 74% of the initial values with ASB (N = 14; P < 0.05) but did not change with CTRL. The decrease in IHCL attained with ASB was more important in subjects with IHCL greater than 60 mmol/l than in subjects with low IHCL. ALT decreased significantly with SSB only in subjects with IHCL greater than 60 mmol/l. There was otherwise no significant effect of ASB on body weight, VAT, or metabolic markers. CONCLUSIONS: In subjects with overweight or obesity and a high SSB intake, replacing SSB with ASB decreased intrahepatic fat over a 12-week period.

Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24. RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)-a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group-a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006). CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study.

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Internet-Based Brief Intervention to Prevent Unhealthy Alcohol Use among Young Men: A Randomized Controlled Trial.

INTRODUCTION: Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults. STUDY DESIGN: 2 parallel-group randomized controlled trial with follow-up at 1 and 6 months. SETTING/PARTICIPANTS: Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013. INTERVENTION: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. INTERVENTION group participants received the IBI. Control group (CG) participants completed only an assessment. MAIN OUTCOME MEASURES: Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014-2015. RESULTS: Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months. CONCLUSION: We found protective short term effects of a primary prevention IBI. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55991918.

Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE: This multicenter phase III study evaluated the efficacy and safety of lapatinib, an epidermal growth factor receptor/ErbB2 inhibitor, administered concomitantly with chemoradiotherapy and as maintenance monotherapy in patients with high-risk surgically treated squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with resected stage II to IVA SCCHN, with a surgical margin ≤ 5 mm and/or extracapsular extension, were randomly assigned to chemoradiotherapy (66 Gy total radiation dose and cisplatin 100 mg/m(2) per day administered on days 1, 22, and 43) plus placebo or lapatinib (1,500 mg per day) before and during chemoradiotherapy, followed by 12 months of maintenance monotherapy. RESULTS: Six hundred eighty-eight patients were enrolled (lapatinib, n = 346; placebo, n = 342). With a median follow-up time of 35.3 months, the study ended early because of the apparent plateauing of disease-free survival (DFS) events. Median DFS assessed by an independent review committee was 53.6 months and not reached for lapatinib and placebo, respectively (hazard ratio, 1.10; 95% CI, 0.85 to 1.43). Investigator-assessed results confirmed the independent review committee assessment. No significant differences in DFS by human papillomavirus status or overall survival were observed between treatment arms. Similar numbers of patients in both treatment arms experienced adverse events (AEs), with more patients in the lapatinib arm than the placebo arm experiencing serious AEs (48% v 40%, respectively). The most commonly observed treatment-related AEs were diarrhea and rash, both predominantly in the lapatinib arm. CONCLUSION: Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk SCCHN.

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial?.

AIMS: Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. METHODS AND RESULTS: A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0.048). Major adverse events were rare in both treatment groups. CONCLUSION: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00765453 and EudraCT 2007-002144-16.