Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Bupivacaine 0.5 % versus articaine 4 % for the removal of lower third molars. A crossover randomized controlled trial

Objective: To compare the anesthetic action of 0.5% bupivacaine in relation to 4% articaine, both with 1:200,000 epinephrine, in the surgical removal of lower third molars. As a secondary objective hemodynamic changes using both anesthetics were analyzed. Study Design: Triple-blind crossover randomized clinical trial. Eighteen patients underwent bilateral removal of impacted lower third molars using 0.5% bupivacaine or 4% articaine in two different appointments. Preoperative, intraoperative and postoperative variables were recorded. Differences were assessed with McNemar tests and repeated measures ANOVA tests. Results: Both solutions exhibited similar latency times and intraoperative efficacy. Statistical significant lower pain levels were observed with bupivacaine between the fifth (p=0.011) and the ninth (p=0.007) postoperative hours. Bupivacaine provided significantly longer lasting soft tissue anesthesia (p<0.05). Systolic blood pressure and heart rate values were significantly higher with articaine. Conclusions: Bupivacaine could be a valid alternative to articaine especially due to its early postoperative pain prevention ability.

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.

Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial.

BACKGROUND: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. METHODS: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. RESULTS: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). CONCLUSION: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia.

A Randomized, Placebo-controlled Trial of Preemptive Antifungal Therapy for the Prevention of Invasive Candidiasis Following Gastrointestinal Surgery for Intra-abdominal Infections.

BACKGROUND: Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy. METHODS: This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression. RESULTS: The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result. CONCLUSIONS: This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC. CLINICAL TRIALS REGISTRATION: NCT01122368.

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.

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.

Randomized, crossover, double-blind, placebo-controlled trial to assess the lipid lowering effect of co-formulated TDF/FTC

Abstract INTRODUCTION: Previous studies have described improvements on lipid parameters when switching from other antiretroviral drugs to tenofovir (TDF) and impairments in lipid profile when discontinuing TDF. [1-3] It is unknown, however, if TDF has an intrinsic lipid-lowering effect or such findings are due to the addition or removal of other offending agents or other reasons. MATERIALS AND METHODS: RESULTS: 46 subjects with a median age of 43 (40-48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44% LPV/r. One subject withdrew the study voluntarily at week 4 and another one interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total, LDL and HDL-cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001) and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL-cholesterol levels remained stable during placebo exposure. Week 12 total cholesterol (p<0.001), LDL-cholesterol (p<0.001) and HDL-cholesterol (p=0.011) levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC reduced the fraction of subjects with abnormal fasting total-cholesterol (≥200 mg/dL) from 86.7% to 56.8% (p=0.001) and LDL-cholesterol (≥130 mg/dL) from 87.8% to 43.9% (p<0.001), which was not observed with placebo. There were no virological failures, and CD4 and triglyceride levels remained stable regardless of exposure. CONCLUSION: Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.

IV paracetamol versus IV ibuprofen for the treatment of PDA in LBW infants: a randomized controlled trial

Patent ductus arteriosus is a prevalent problem in low birth weight infants and it has an important morbidity and mortality in this group of patients. Classical treatment options include drugs (intravenous cyclooxygenase inhibitors: indomethacin and ibuprofen) and surgical ligation, but these treatments are associated with significant adverse effects. An alternative treatment with fewer side effects is needed. The role of oral paracetamol has gained importance in recent years, this new therapeutic option is being widely studied, and there are already many studies which support oral paracetamol as first line treatment for PDA, due to its better safety profile than classical drugs. In LBW infants is difficult to administer enteral treatment, since they are often multi pathological patients with several complications that preclude oral administration and they usually receive intravenous treatments. This multicenter, prospective, single blinded, randomized, controlled, parallel-group and noninferiority trial is designed to evaluate the efficacy and safety of intravenous paracetamol versus intravenous ibuprofen in the treatment of PDA in LBW infants. Sixty eight infants with echocardiography confirmed PDA will be randomly assigned to receive either intravenous paracetamol or intravenous ibuprofen. The main endpoints will be the rate of ductal closure of each drug and adverse events in each group of treatment

Percutaneous access versus standard femoral exposure for endovascular abdominal aortic aneurysm repair: a randomized, controlled trial

The treatment of abdominal aortic aneurysm (AAA) has shifted from the exposure of the aorta artery in an open repair technique to a small groin cut in an endovascular repair. Recently, a percutaneous access for endovascular repair has appeared. This new technique aims to minimize the complications of the common femoral artery exposure, the patient discomfort and the length of hospitalizationObjectives: To compare the proportion of discharged patients within the first 48 postoperative hours of two common femoral artery accesses for endovascular repair of AAA: the open exposure technique and the percutaneous technique. Secondary objectives include to evaluate the total procedure time, the femoral access complications, the need for extra analgesia and the patient satisfaction and groin discomfort of the two techniquesDesign: Randomized controlled trial conducted between 2014 and 2017Participants: Patients diagnosed with abdominal aortic aneurysm with elective endovascular repair indication

Induction of labor with titrated oral misoprostol solution versus oxytocin in term pregnancy: randomized controlled trial

PURPOSE: To evaluate the effectiveness and the safety of orally administered misoprostol in comparison to intravenously infused oxytocin for labor induction in term pregnant women. METHODS: Between 2008 and 2010, a total of 285 term pregnant women whom were candidate for vaginal delivery were assessed for eligibility to enter the study. Twenty five patients were excluded for different reasons; and 260 included women were randomly assigned to one of the two groups according to the method of treatment, misoprostol or oxytocin. The misoprostol group received 25 µg every 2 hours for up to 24 hours for induction. The oxytocin group received an infusion of 10 IU which was gradually increased. The time from induction to delivery and induction to the beginning of the active phase and successful inductions within 12, 18, and 24 hours were recorded. The trial is registered at irct.ir, number IRCT2012061910068N1. RESULTS: Failure of induction, leading to caesarean section was around 38.3% in the oxytocin group and significantly higher than that of the misoprostol group (20.3%) (p<0.001). Despite the more prevalent failure in the oxytocin group, the mean time intervals from induction to active phase and labor of this group were both significantly less than the misoprostol group (10.1±6.1 and 13.2±7.7 versus 12.9±5.4 and 15.6±5.1 hours respectively, both p-values were <0.05). Maternal and fetal complications were comparable between groups except gastrointestinal symptoms which were encountered more frequently in the misoprostol (10.9 versus 3.9%, p=0.03). CONCLUSIONS: Misoprostol is a safe and effective drug with low complications for the induction of labor. Failure is seen less with misoprostol and caesarean sections are less frequently indicated as compared to oxytocin.

Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.

Evaluating three self-help smoking cessation interventions for post-secondary smokers : a randomized controlled trial on six Ontario campuses

Objective. Smoking prevalence is highest among the young adult cohort. Postsecondary students are no exception. Although many students intend to quit smoking, no research has established what methods best promote reductions in, or complete abstinence from smoking. This randomized controlled trial examined the effectiveness of three self-help smoking cessation interventions. Method. On six post-secondary campuses, 483 smokers who voluntarily accessed Leave The Pack Behind (a tobacco control initiative) were randomly assigned to one of three smoking cessation interventions: One Step At A Time (a 2-booklet, *gold standard' program for adults); Smoke|Quit (a newly-developed 2-booklet program for young adult students); and usual care (a 'Quit Kit' containing a booklet on stress management, information about pharmacological quitting aides and novelty items). All participants also received one proactive telephone support call from a peer counsellor. During the study, 85 participants withdrew. The final sample of 216 students who completed baseline questionnaires and 12-week follow-up telephone interviews was representative of the initial sample in terms of demographic characteristics, and smokingquitting- related variables. Results. Whether participants quit smoking depended upon treatment condition, ^(2, N=2\6) = 6.34, p = .04, with Smoke|Quit producing more successfijl quitters (18.4%) than One Step At A Time (4.5%) or the Quit Kit (1 1.4%). On average, participants had quit 53.46 days, with no significant difference across treatments. Selfefficacy also increased. Use of the intervention or other quitting aides was not associated with treatment condition. Among the 191 participants who did not quit smoking, treatment condition did not influence outcomes. Overall, 46.2% had made a quit attempt. Significant decreases in weekly tobacco consumption and increases in self-efficacy to resist smoking were observed from baseline to follow-up. Conclusion. Post-secondary institutions represent a potentially final opportunity for age-targeted interventions. Self-help resources tailored to students' social and contextual characteristics will have considerable more impact than stage-only tailored interventions. Both reduction and abstinence outcomes should be emphasized to positively support students to stop smoking.