Datasets:

system-technologies

/

rct-labeled-1k

like 0

TITLE: Oral misoprostol for induction of labour at term: randomised controlled trial.ABSTRACT: To compare oral misoprostol solution with vaginal prostaglandin gel (dinoprostone) for induction of labour at term to determine whether misoprostol is superior.Randomised double blind placebo controlled trial.Maternity departments in three hospitals in Australia. Population Pregnant women with a singleton cephalic presentation at > or = 36+6 weeks' gestation, with an indication for prostaglandin induction of labour.20 mug oral misoprostol solution at ourly intervals and placebo vaginal gel or vaginal dinoprostone gel at six hourly intervals and placebo oral solution.Vaginal birth within 24 hours; uterine hyperstimulation with associated changes in fetal heart rate; caesarean section (all); and caesarean section for fetal distress.741 women were randomised, 365 to the misoprostol group and 376 to the vaginal dinoprostone group. There were no significant differences between the two treatment groups in the primary outcomes: vaginal birth not achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%); relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127), caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57 to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were differences in the process of labour induction, there were no significant differences in adverse maternal or neonatal outcomes.This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women.National Health and Medical Research Council, Perinatal Trials, PT0361.

TITLE: Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma.ABSTRACT: This double-blind, placebo-controlled, randomized, parallel-group, multicenter study was conducted in 302 children aged 6-11 years with asthma not optimally treated with inhaled corticosteroids alone. Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo, formoterol 4.5 microg or formoterol 9 microg b.i.d., for 12 weeks (all delivered via Turbuhaler). Terbutaline was available as reliever medication. The primary efficacy variable was change from baseline in morning peak expiratory flow (PEF); secondary efficacy variables included forced expiratory volume in 1 sec (FEV(1)), serial PEF measured over 12 hr, evening PEF, asthma symptom score, and quality of life. Compared with placebo, formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min (P = 0.035) and 11 l/min (P = 0.0045), respectively. Evening PEF and FEV(1) were also significantly increased compared with placebo, with no statistically significant difference between formoterol doses. Lung-function improvements compared with placebo were greater in the middle of the day. Twelve-hour average serial PEF after 3 months increased by 24 l/min (95% CI, 9, 39 l/min) in the formoterol 9-microg group, and by 14 l/min (95% CI, 0, 29 l/min) in the formoterol 4.5-microg group. The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group, indicating that formoterol may have the potential to improve exacerbation control in children. Both formoterol doses were well-tolerated, and tolerance to the drug's bronchodilator effect was not observed. Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone.

TITLE: Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.ABSTRACT: To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome.Randomised controlled trial.Secondary and tertiary hospitals in the Netherlands.168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone.Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone.Ongoing pregnancy within 12 months.. The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86).The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy.

TITLE: Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation.ABSTRACT: We examined risk factors of smoking and the association between smoking and pregnancy-related and 6-month infant mortality in rural Nepal, where 30% women reported smoking during pregnancy.Cross-sectional analysis of risk factors associated with smoking status and health consequences of smoking, using prospective data collected as part of a randomized community trial to examine the effect of maternal vitamin A or beta-carotene supplementation on maternal mortality.Rural, southeastern plains of Nepal.A total of 17 767 women contributed at least one pregnancy during 3.5 y of the study. Data on cigarette or bidi (rolled tobacco) smoking were collected using a 7-day recall, twice during pregnancy. Associations between smoking status and maternal diet, morbidity profile, household socioeconomic status and serum concentration of retinol, carotenoids and tocopherols were examined. Further, relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate supplement effects on pregnancy-related mortality, stratified by smoking status during pregnancy.Smokers were more likely to be older, illiterate and poor compared to nonsmokers. Fruit and vegetable consumption among smokers and nonsmokers did not vary. However, smokers were more likely to consume meat/fish/eggs and less likely to consume milk than nonsmokers. They were also more likely to report symptoms of vaginal bleeding, edema, severe headache and convulsions during pregnancy relative to nonsmokers. Mortality per 100,000 pregnancies appeared to be higher among smokers than nonsmokers in the placebo group (915 vs 584, RR=1.57, 95% CI: 0.80-3.08). beta-Carotene supplementation reduced pregnancy-related mortality both among smokers (RR=0.31 95% CI: 0.11-0.89) and nonsmokers (RR=0.41, 95% CI: 0.19-0.89). Similar results obtained with vitamin A supplementation were not statistically significant. Infant mortality up to 6 months was approximately 30% higher among smokers compared to nonsmokers in the placebo group both before and after adjusting for confounding factors. Neither supplement given to women reduced infant mortality.Cigarette smoking during pregnancy is associated with an increased risk of maternal and infant mortality in rural Nepal. beta-Carotene and to some extent vitamin A may reduce the risk of pregnancy-related mortality, but not infant mortality, among both smokers and nonsmokers.

TITLE: Effect of caudal epidural xylazine on intraoperative distress and post-operative pain in Holstein heifers.ABSTRACT: To compare the effects of caudal epidural xylazine versus saline on tolerance of paravertebral nerve block and flank surgery and on post-operative pain in heifers used for a veterinary student training laboratory.Randomized controlled prospective study.Fourteen one-year-old, nongravid, healthy Holstein heifers, weighing 360 +/- 5 kg.Xylazine (0.05 mg kg(-1)) or 0.9% saline (5 mL) was injected using a caudal epidural technique to seven heifers undergoing a flank surgery. Nerve block of the right paravertebral fossa was performed using equal parts of lidocaine 2% and bupivacaine 0.5%. Heart and respiratory rates, rectal temperature, rumination frequency, and appetite were recorded before and at 4, 8, and 24 hours after surgery. Scores were recorded for: tolerance of local anesthesia injections (pre-operatively), sedation, ataxia and distress (intraoperatively, every 30 minutes), and pain (4, 8, and 24 hours post-operatively).The animals reaction to local anesthetic injection was judged to be less in the xylazine group by both an experienced observer (p<0.001) and student surgeons (p<0.01). The xylazine group required less local anesthetic (82.9 +/- 13.8 mL) versus the saline group (108.4 +/- 19.6 mL, p=0.035). Intraoperatively, xylazine heifers were more sedated at all times (p-values from <0.001 to 0.017), were more ataxic for the first 1.5 hours (p-values from <0.001 to 0.026), and lower in distress at all times (p-values from <0.001 to 0.007). No difference in post-operative pain or physiologic variables was found, except immediately post-operatively, rectal temperature was higher in the xylazine group (39.5 +/- 0.3 degrees C) than in the saline group (38.6 +/- 0.2 degrees C, p<0.001).Compared with epidural saline, caudal epidural xylazine reduced distress of anesthetic injection and surgical manipulation in heifers and an improvement in animal well-being was apparent. This effect may have been as a result of sedation. Pre-operative epidural xylazine did not appear to improve post-surgical analgesia in our study.

TITLE: Repaglinide is more efficient than glimepiride on insulin secretion and post-prandial glucose excursions in patients with type 2 diabetes. A short term study.ABSTRACT: To compare the effect of Repaglinide vs Glimepiride on glucose- and meal-induced insulin secretion and on meal-test induced postprandial glucose excursions.After 2 weeks washout period, a 3-Month randomised, cross-over parallel group trial of R (1 mg x 2/die) vs G (2 mg/die) in 14 patients with type 2 diabetes "naive" in diet treatment was made.Both R and G significantly but similarly lowered fasting glucose levels and improved fasting plasma insulin levels vs baseline. Hyperglycemic clamp showed that both 1st (129.15 +/- 23.6 vs 106.90 +/- 18.6 pmol/L; p=0.01) and 2nd phase (189.42 +/- 34.4 vs 144.21 +/- 37.3 pmol/L; p=0.003) B-cell response to glucose as well as area under the curve (52.07 +/- 10.86 vs 39.54 +/- 10.27 micromol/L x 120'; p=0.005) were greater in R than G groups. Insulin action (4.0 +/- 1.1 vs 3.2 +/- 0.9 mg x Kg x 60'/microU/mL; p=0.046) was also improved by R than G administration. In the meal test, R therapy produced a more rapId induction of insulin secretion during the first part. In fact, the mean rise in insulin secretion peaked at 45 min in R (p=0.001 vs G) and at 60 min in G (p=0.001 vs R). Consequently, glucose spike at 60 min was higher in G group compared to glucose spike at 45 min in R group (p=0.002).Our study demonstrates that R is more efficient that G on improving glucose- and meal- induced insulin secretion as well as on controlling for postprandial glucose excursion.

TITLE: Perioperative topical nitrate and sphincter function in patients undergoing transanal stapled anastomosis: a randomized, placebo-controlled, double-blinded trial.ABSTRACT: The use of transanal stapling devices may impair continence because of digital dilatation and/or instrumentation. This study assessed the effect of pharmacological dilatation of the sphincter prior to stapler insertion.A randomized, placebo-controlled, double-blinded study of 60 patients undergoing transanal stapled anastomosis was undertaken. Consenting patients were randomly assigned to receive a single intraoperative dose of topical 0.2 percent nitroglycerin (glyceryl trinitrate) ointment or nitroglycerin-free placebo. All patients were assessed preoperatively and postoperatively by clinical methods (Wexner incontinence scores and examination), anorectal manometry by a station pull-through technique, and endoanal ultrasonography.Intraoperative mean (+/-SEM) resting pressures (mmHg) were significantly reduced by nitroglycerin compared with prenitroglycerin levels (9.9 +/- 0.9 vs. 50.5 +/- 2.7; P = 0.002) or controls (56.0 +/- 3.2; P = 0.001). Twenty-one of the 28 controls (75 percent) but only 4 of the 32 patients in the nitroglycerin group (12.5 percent) required digital dilatation to insert the stapling instrument ( P = 0.003). Squeeze pressures were unaltered by the intervention but mean resting pressures were higher in the nitroglycerin group postoperatively (52.9 +/- 3.2 - 31.6 +/- 1.3 = 21.3 mmHg; 95 percent confidence interval, 14-27). Incontinence scores were lower in the nitroglycerin group at the 3-month (1.1 +/- 0.2 vs. 4.6 +/- 0.3; P = 0.003) and 12-month (0.9 +/- 0.1 vs. 4.4 +/- 0.3; P = 0.002) clinic visits.Preoperative nitroglycerin dilatation protects sphincter function in patients undergoing transanal stapled anastomoses.

TITLE: A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.ABSTRACT: The aim of this study was to compare the efficacy and side effect profile of atosiban with hexoprenaline when used for intrauterine resuscitation of intrapartum fetal distress.Women in labour with acute intrapartum fetal distress detected by cardiotocography were randomly assigned to receive intravenous atosiban or hexoprenaline.Department of Obstetrics and Gynecology, Karl Franzens University of Graz and General Hospital Graz, Austria.One thousand and four hundred and thirty-one women with singleton pregnancy at term and cephalic presentation were enrolled in the study during October 2000 and May 2001.A prospective, randomised, pilot study with no a priori sample size calculation.Efficacy of treatment for stopping uterine contractions and the resumption of contractions determined by fetal heart rate monitoring.Tocolysis was achieved in 92% (12/13) of the women receiving atosiban and 100% (13/13) of those receiving hexoprenaline. Maternal tachycardia developed in 1/13 women, receiving atosiban and 10/13 women hexoprenaline. Hypertension occurred in 1/13 on atosiban and 3/13 women on hexoprenaline. Palpitations were only reported by 10/13 women receiving hexoprenaline. Uterine contractions resumed after 8 minutes (+/-3) in the atosiban group and 14 minutes (+/-4) in the hexoprenaline group (P < 0.001).Atosiban and hexoprenaline were similarly effective for stopping uterine contractions. Women receiving atosiban had significantly fewer adverse events than those receiving hexoprenaline. Uterine contractions resumed more promptly in the atosiban group. Considering the low incidence of mild maternal adverse events, atosiban may be an option for acute intrapartum tocolysis for fetal distress.

TITLE: Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants.ABSTRACT: This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.

TITLE: Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study.ABSTRACT: Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.

TITLE: Effect of ingested fluid composition on exercise-related transient abdominal pain.ABSTRACT: The present study investigated the effect of ingested fluid composition on the experience of exercise-related transient abdominal pain (ETAP). Forty subjects, susceptible to ETAP, completed 4 treadmill exercise trials: a no-fluid trial and flavored water (FW, no carbohydrate, osmolality = 48 mosmol/L, pH = 3.3), sports drink (SD, freshly mixed Gatorade, 6% total carbohydrate, 295 mosmol/L, pH = 3.3), and reconstituted fruit juice (FJ, BERRI trade mark orange, 10.4 % total carbohydrate, 489 mosmol/L, pH= 3.2) trials. Measures of the experience of ETAP and gastrointestinal disturbances, particularly bloating, were quantified. The FJ was significantly (p =.01) more provocative of both ETAP and bloating than all other trials. There was no difference among the no-fluid, FW, and SD in the severity of ETAP experienced, although the difference between the no-fluid and SD approached significance at the.05 level (p =.056). There was a significant relationship between both the mean (r = 0.40, p =.01) and peak (r= 0.44, p=.01) levels of ETAP and bloating. When the level of bloating was controlled for, the FJ remained significantly (p =.01) more provocative of ETAP than the other conditions, with no difference between the FW and SD (p =.37). The results indicate that in order to avoid ETAP, susceptible individuals should refrain from consuming reconstituted fruit juices and beverages similarly high in carbohydrate content and osmolality, shortly before and during exercise. Further, the mechanism responsible for the heightened experience of ETAP in the FJ trial extends beyond a gastric mass explanation.

TITLE: Five-year outcome of patients with acute myocardial infarction enrolled in a randomised trial assessing the value of abciximab during coronary artery stenting.ABSTRACT: The aim of the study was to investigate the long-term (five years) efficacy of glycoprotein IIb/IIIa inhibition with abciximab given as an adjunct therapy to coronary stenting in patients with acute myocardial infarction (MI) using the patient cohort of the Intracoronary Stenting and Antithrombotic Regimen-2 (ISAR-2) randomised trial.The patient cohort of ISAR-2 trial (401 patients) was followed up for 5 years after enrollment. There were 201 patients in the abciximab group (stenting plus abciximab) and 200 patients in the control group (stenting without abciximab). The primary end-point of the study was mortality at 5 years. Recurrent MI and target vessel re-vascularisation were also assessed at 5 years after enrollment. On the basis of the Kaplan-Meier analyses, the 5-year mortality was 17.8% (35 patients) in the group with abciximab and 14.6% (29 patients) in the control group (relative risk, 1.20 [95% confidence interval, 0.73-1.96]; P=0.47). The 5-year combined incidence of death, recurrent MI and target vessel re-vascularisation was 38.2% (76 patients) in the group of abciximab and 37.7% (75 patients) in the control group (relative risk, 0.97 [95% confidence interval, 0.70-1.33]; P=0.83). Multivariable analysis showed no significant independent association of abciximab with 5-year mortality (adjusted hazard ratio, 1.16 [95% confidence interval, 0.70-1.92]; P=0.55).These findings are not in support of a sustained clinical benefit at 5 years with the use of abciximab during coronary artery stenting in patients with acute MI.

TITLE: A randomised, double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis.ABSTRACT: To determine whether topical ketorolac (Acular) is more effective than artificial tears in treating the signs and symptoms of idiopathic episcleritis.In this prospective, randomised, double-blind study, 38 eyes of 37 patients presenting with idiopathic episcleritis were allocated to receive either topical ketorolac (0.5%) or artificial tears three times a day for 3 weeks. The severity of patients' signs (episcleral injection and the number of clock hours affected) were recorded at weekly intervals. Patients' symptoms (perceived redness and pain scores) were recorded using a daily diary.There was no significant difference in the ophthalmic signs between the two groups at each assessment, including intensity of episcleral injection and the number of clock hours affected. No significant difference was found in the time to halve the baseline redness intensity scores (4.4 vs 6.1 days, P=0.2) or pain scores (3.6 vs 4.3 days, P=0.55). Significantly more patients on ketorolac reported stinging at the first follow-up visit (P<0.001).Topical ketorolac is not significantly better than artificial tears in treating the signs or symptoms of idiopathic episcleritis.

TITLE: Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild.ABSTRACT: Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 h postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 min following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset.

TITLE: A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge.ABSTRACT: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction.A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4.Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels.In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction.

TITLE: Effect of methylprednisolone on return of sexual function after nerve-sparing radical retropubic prostatectomy.ABSTRACT: To determine whether postoperative methylprednisolone improves the recovery of sexual function after nerve-sparing radical retropubic prostatectomy.We randomized men undergoing bilateral nerve-sparing radical retropubic prostatectomy by a single surgeon to receive 6 days of placebo or methylprednisolone beginning on postoperative day 1. At 3, 6, and 12 months postoperatively, we assessed potency with the abbreviated International Index of Erectile Function questionnaire and urinary continence with participant-reported pad use. We used the chi-square test, Fisher's exact test, and the two-sample t test with equal variances for comparisons between study groups.No operative complications occurred and 70 (100%) of 70 participants experienced normal wound healing. The odds of being potent for participants who received methylprednisolone (n = 34) compared with those who received placebo (n = 36) did not significantly differ at 3 (odds ratio 0.29, 95% confidence interval 0.08 to 1.05), 6 (odds ratio 0.63, 95% confidence interval 0.17 to 2.4), or 12 (odds ratio 1.18, 95% confidence interval 0.29 to 4.8) months. The mean International Index of Erectile Function scores did not significantly differ at 3 (P = 0.08), 6 (P = 0.50), or 12 (P = 0.71) months. At 12 months, 74% of the methylprednisolone and 71% of the placebo participants were potent (P = 0.8). The proportions of participants who were continent did not differ significantly at 3 (P = 0.89), 6 (P = 0.25), or 12 (P = 0.49) months. At 12 months, 96% of the methylprednisolone and 100% of the placebo participants were continent.At doses sufficient to produce a systemic anti-inflammatory effect, postoperative methylprednisolone was not associated with improved potency at up to 12 months after bilateral nerve-sparing radical retropubic prostatectomy in men 40 to 60 years old.

TITLE: Efficacy and safety of lercanidipine versus hydrochlorothiazide as add-on to enalapril in diabetic populations with uncontrolled hypertension.ABSTRACT: Angiotensin-converting enzyme inhibitors plus dihydropyridine calcium channel blockers or low-dose thiazide diuretics are considered first-line therapies in hypertensive diabetic patients as glucose metabolism is not relevantly affected. Most diabetic patients require at least two different drug classes to achieve the recommended target blood pressure of 130/85 mmHg. This controlled clinical trial investigated the calcium channel blocker lercanidipine versus hydrochlorothiazide (HCTZ) as add-on in diabetic patients with uncontrolled hypertension on enalapril monotherapy.Overall, 174 patients (18-80 years old, well-controlled diabetes type 1 or 2, mild to moderate hypertension) were included in a 2-week placebo run-in followed by 4 weeks on enalapril 20 mg. Subsequently, 135 non-responders (90 mmHg < or = mean sitting diastolic blood pressure < or = 109 mmHg) were randomized to 20 weeks of double-blind add-on therapy to enalapril with either lercanidipine 10 mg (n = 69) or HCTZ 12.5 mg (n = 66). The primary study objective was to prove non-inferiority of lercanidipine add-on versus HCTZ add-on in reducing sitting diastolic blood pressure; response rates and tolerability data were also observed.Both add-on treatments clearly decreased diastolic blood pressure to a greater extent than enalapril monotherapy (mean +/- SD changes at study end: lercanidipine, -9.3 mmHg; HCTZ, -7.4 mmHg); non-inferiority of lercanidipine versus HCTZ was formally proven. Blood pressure response rates reached 69.6% on enalapril plus lercanidipine as compared with 53.6% on enalapril plus HCTZ (difference between treatments, P > 0.05). Blood pressure of 130/85 mmHg or less was achieved in 30.4% of patients on lercanidipine add-on and in 23.2% of those randomized to HCTZ add-on (P > 0.05). Both treatment regimens were well tolerated.Lercanidipine add-on showed comparable efficacy to HCTZ add-on in diabetic patients with hypertension badly controlled on angiotensin-converting enzyme inhibitor monotherapy. The blood pressure response rates seemed to be somewhat higher following enalapril plus lercanidipine than enalapril plus HCTZ.

TITLE: Symptoms of postpartum depression and breastfeeding.ABSTRACT: Despite important health benefits, the presence of depressive symptoms may decrease the prevalence of breastfeeding. The current study assessed the relationship between depressive symptoms and breastfeeding at 6 and 12 weeks postpartum. Participants were recruited from a cohort completing a clinical trial of calcium for prevention of preeclampsia. At 6 weeks postpartum, the Edinburgh Postnatal Depression Scale (EPDS) was completed by mail. At 12 weeks postpartum, the EPDS was completed at an outpatient visit. There was an inverse relationship between depressive symptoms and breastfeeding at 6 weeks postpartum (P<.001) but not at 12 weeks. This relationship persisted even after controlling for prior history of depression, increased life stress, and current psychoactive medication. The results suggest that depressive symptoms early in the postpartum period may lower the prevalence of breastfeeding.

TITLE: Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial.ABSTRACT: Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose-lowering drugs.To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.26-week multicenter, open-label, randomized, controlled trial.82 outpatient study centers in 13 countries.551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.Exenatide, 10 microg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL).Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, -0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, -4.1 kg [CI, -4.6 to -3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, -1.6 events/patient-year [CI, -2.3 to -0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%).The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL).Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine.

TITLE: Efficacy and tolerability of budesonide Clickhaler and Turbuhaler in adult asthma.ABSTRACT: New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler or Turbuhaler dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (<or=1600 microg/day) via either Clickhaler (n=110) or Turbuhaler (n=112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting beta2-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of--2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval--7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.

TITLE: Open right colectomy is still effective compared to laparoscopy: results of a randomized trial.ABSTRACT: The primary goal of this study was to clarify whether a laparoscopic (LPS) approach could be considered the dominant strategy in patients undergoing right colectomy.Because few nonrandomized or small sized studies have been carried out so far, definitive conclusions about the role of LPS right colectomy cannot be drawn.Two hundred twenty-six patients, candidates for right colectomy, were randomly assigned to LPS (n = 113) or open (n = 113) resection. The postoperative care protocol was the same for both groups. Trained members of the surgical staff who were not involved in the study registered postoperative morbidity. Follow-up was carried out for 30 days after hospital discharge. The following costs were calculated: surgical instruments, operative room occupation, routine care, postoperative morbidity, and hospitalization.Conversion rate in the LPS group was 2.6% (3 of 113). Operative time (in minutes) was longer in the LPS group (131 vs. 112, P = 0.01). Postoperative morbidity rate was 18.6% in the open group and 13.3% in the LPS group (P = 0.31). Postoperative stay was one day longer in the open group (P = 0.002). No difference was found in postoperative quality of life. The additional operative charge in the LPS group was euro980 per patient randomized (euro821 for surgical instruments and euro159 for longer operative time). The savings in the LPS group was euro390 per patient randomized (euro144 for shorter length of hospital stay and euro246 for the lower cost of postoperative morbidity). The net balance resulted in a euro590 extra charge per patient randomly allocated to the LPS group.LPS slightly improved postoperative recovery. This translated into a savings that covered only 40% of the extra operative charge. Therefore, open right colectomy could be still considered an effective procedure.

TITLE: Two-year follow-up of posterior capsule opacification after implantation of a hydrophilic or hydrophobic acrylic intraocular lens.ABSTRACT: To evaluate posterior capsule opacification (PCO) 2 years after cataract surgery following implantation of a hydrophilic or a hydrophobic single-piece acrylic intraocular lens (IOL) with a sharp edge.Phacoemulsification cataract surgery was performed in one eye of 120 patients with senile cataract in this prospective study. They were randomized to implantation of either a hydrophilic acrylic IOL (BL27; Bausch & Lomb, Rochester, NY, USA) or a hydrophobic acrylic IOL (AcrySof) SA60AT; Alcon Laboratories, Fort Worth, TX, USA). Two years after surgery, retroillumination images were obtained and PCO area and severity were evaluated using pocoman software. Best corrected visual acuity (VA) (both high-contrast [100%] and low-contrast [2.5%]), glare, laser flare and intraocular pressure were measured. Capsulotomy rates were recorded.Patients implanted with the hydrophilic IOL had a greater percentage area and severity of PCO compared with patients with the hydrophobic IOL (p < 0.001). There was no difference in PCO between men and women in the hydrophilic group. However, in the hydrophobic group, women had significantly more PCO than men (p < 0.05). Patients with the hydrophobic acrylic IOL had better high- and low-contrast visual activity (VA) (p < 0.01) and less glare (p < 0.001) than those with a hydrophilic acrylic IOL. Of the patients with the hydrophilic IOL, 42% underwent capsulotomy, compared with 10% in the hydrophobic group (p < 0.001).Two years after surgery, patients with the SA60AT hydrophobic acrylic IOL had less PCO and better high- and low-contrast VA than patients with the BL27 hydrophilic acrylic IOL.

TITLE: Five-year follow up of a randomised controlled trial comparing NovaSure and ThermaChoice endometrial ablation.ABSTRACT: We have previously reported that NovaSure was more effective than balloon ablation at 12 months follow up in the treatment of menorrhagia. In this paper, we report the 5-year outcome of this study. The objective was to evaluate amenorrhoea rates, hysterectomy rate, and quality of life associated with the bipolar impedance-controlled endometrial ablation technique (NovaSure) in comparison with balloon ablation technique (ThermaChoice) at 5 years after administration.Double-blind randomised controlled trial, 2:1 randomisation NovaSure versus ThermaChoice.A teaching hospital with 500 beds in The Netherlands.A total of 126 premenopausal women suffering from menorrhagia with a pictorial blood loss assessment count > or = 150 without intracavitary abnormalities.Women were randomly allocated to bipolar radio-frequency ablation and balloon ablation in a 2:1 ratio.The main outcome measures were amenorrhoea rate, hysterectomies, and health-related quality of life (HRQol) as reported at 5 year follow up.At 5 years of follow up, the total response rate was 96% in the bipolar group and 90% in the balloon group. Amenorrhoea was reported in the bipolar group by 48% of women and in the balloon arm by 32% (relative risk 1.6 [.93-2.6]). There were eight women in the bipolar group (9.8%) and five in the balloon group (12.9%) who had undergone a hysterectomy. Furthermore, there was a significant equal improvement of HRQoL over time in both groups.At 5 years follow up, bipolar thermal ablation was superior over balloon ablation in the treatment of menorrhagia.

TITLE: Leukocyte count and vascular risk in symptomatic intracranial atherosclerosis.ABSTRACT: Few data exist about the prognostic value of serum white blood cell (WBC) count among patients with symptomatic cerebrovascular disease. We investigated the relationship between WBC count and vascular risk in patients with symptomatic intracranial atherosclerotic disease enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease(WASID) study.The relationships between baseline serum WBC count (categorized into quartiles) and both ischemic stroke alone and the combined endpoint of ischemic stroke, myocardial infarction or vascular death were evaluated using the log-rank test and Cox proportional hazards regression.Compared with the quartile with the lowest WBC counts at baseline (< or =5.9 x 10(9)/l), WASID subjects in both upper WBC quartiles (7.3-8.8; > or =8.9 x 10(9)/l) were more likely to be younger (p = 0.022), diabetic (p = 0.013), on statin treatment (p = 0.015), or have higher mean body mass index (p = 0.015) and triglyceride (p = 0.0065) values. The rate of the primary endpoint was greater among WASID subjects in the upper two WBC quartiles compared with the lower two quartiles (28 vs. 16%, hazard ratio = 1.7; 95% CI = 1.2-2.5, p = 0.003). After adjusting for baseline factors found to be significantly related to the time of primary endpoint in multivariate analysis, both upper WBC quartiles (vs. lowest quartile) were independently associated with a greater risk for the primary endpoint (hazard ratio of 1.5; 95% CI = 1.06-2.2, p = 0.024).An elevated WBC count at study entry was associated with an increased risk of stroke and vascular death in patients with symptomatic intracranial atherosclerotic disease enrolled in the WASID trial.

TITLE: Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids.ABSTRACT: The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination (SFC) therapy have been well established in the treatment of adults and adolescents with asthma. Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma. This study aimed to investigate whether once-daily SFC 50 microg/100 microg was at least as effective as fluticasone propionate (FP) 100 microg twice daily, and more effective than twice-daily placebo, over 52 weeks as initial maintenance therapy in patients with mild persistent asthma.This was a randomized, double-blind, double-dummy, placebo-controlled, multicentre, parallel-group study carried out in primary and secondary care. Patients aged between 12 and 79 years with a documented clinical history of asthma for > or =6 months who were currently receiving inhaled short-acting beta(2)-adrenoceptor agonists only were enrolled. Patients were randomized to receive either once-daily inhaled SFC 50 microg/100 microg, twice-daily inhaled FP 100 microg (i.e. twice the dose of FP compared with SFC) or placebo for 52 weeks. The primary efficacy endpoints were mean morning peak expiratory flow (PEF), as recorded by patients prior to the use of bronchodilator or study medication, and the rate of investigator-recorded asthma exacerbations.Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo (FP, difference in means 20.1 L/min; 95% CI 14.7, 25.5; p < 0.001; SFC, difference in means 14.8 L/min; 95% CI 9.4, 20.2; p < 0.001). The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was -5.3 L/min (95% CI -9.1, -1.6). PEF results showed that once-daily SFC was non-inferior to twice-daily FP. Over 52 weeks, there was a 35% reduction in exacerbation rates with once-daily SFC, which in this respect demonstrated superiority over placebo (p < 0.001). Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown. Once-daily SFC significantly improved clinic forced expiratory flow between 25% and 75% of forced vital capacity (difference in means 0.129 L/s; p < 0.001) and clinic PEF (difference in means 10.8 L/min; p < 0.001) compared with twice-daily FP. Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo.In patients with mild persistent asthma not previously receiving maintenance therapy, once-daily SFC 50 microg/100 microg is an effective treatment compared with placebo, and was non-inferior to twice-daily FP 100 microg with respect to mean morning PEF. However, in this study, once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates. This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma.

TITLE: Infusion of albumin attenuates changes in serum protein binding of drugs in surgical patients compared with volume replacement with HAES.ABSTRACT: In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs.A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin.During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged.Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters.

TITLE: Community-based weight management in long-term heart transplant recipients: a pilot study.ABSTRACT: Heart transplant recipients often suffer from obesity, dyslipidemia, and hypertension thought to be related to triple-drug immunosuppression and poor adherence to diet and exercise. A lifestyle intervention that allows recipients to attend a community-based weight management program may improve health outcomes.To determine (1) the effects of attending a community-based weight management program on weight, systolic and diastolic blood pressure, and the lipid profile; and (2) the feasibility of a community-based program for weight management.Twenty-one patients (81% male; age 57 years, 99.7 months since transplantation) participated in a randomized clinical trial and received either weight management counseling (control) or a 6-month scholarship to a structured commercial program (treatment). Using simple analysis of covariance models, group differences were assessed and reported as marginal means.At baseline, there were no demographic differences between groups. There were no differences in outcome variables except weight (control, 102.1 kg vs treatment, 98.3 kg; P= .05). After 6 months, significant differences were found in weight (control, 100.5 kg vs treatment, 95.6 kg; P= .047) and high-density lipoprotein cholesterol (control, 40.6 mg/dL vs treatment, 49.1 mg/dL; P= .044). A marginally significant difference was found in systolic blood pressure (control, 138 mm Hg vs treatment, 121 mm Hg; P= .07). A decrease in diastolic blood pressure (6 mm Hg) was attributed to treatment effect (P = .16). No differences were noted in total cholesterol, triglycerides, or low-density lipoprotein cholesterol.The structured commercial program appears to be an effective, feasible alternative to usual care. Findings need to be confirmed in future research with a larger sample.

TITLE: Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.ABSTRACT: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass.The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin.These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

TITLE: Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.ABSTRACT: The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

TITLE: Predictors of sustained intraocular pressure elevation in eyes receiving intravitreal anti-vascular endothelial growth factor therapy.ABSTRACT: To determine the intravitreal anti-vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and to identify potential factors associated with the development of sustained intraocular pressure (IOP) elevation in patients treated with intravitreal anti-VEGF therapy for neovascular age-related macular degeneration (AMD).Cross-sectional physician survey.Five hundred and thirty retina specialists spanning both private and academic practices were surveyed regarding current anti-VEGF intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP.Two hundred ninety-two specialists (55%) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. Of these responses, the most common reported prevalence was 1%-2% (48%), followed by 3%-5% (34%). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. Physicians who injected greater than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation (P=.006, 95% CI 1.64-18.89).Based on physician survey data, serial anti-VEGF injections using higher injection volumes with a rapid injection technique may potentially lead to sustained IOP elevation. The underlying mechanism for this complication may be injury to the trabecular meshwork resulting from rapid elevations in IOP. Further investigation of the relationship between injection techniques and sustained IOP elevation in the form of retrospective or prospective clinical studies is warranted.

TITLE: Varenicline efficacy and safety among methadone maintained smokers: a randomized placebo-controlled trial.ABSTRACT: To test the efficacy and safety of varenicline as an aid to smoking cessation in methadone-maintained smokers.Multicenter, randomized, double-blind, placebo-controlled trial with random assignment to 12 weeks of varenicline 1 mg twice daily (n = 57) or matched placebo (n = 55), with in-person and telephone counseling.Urban methadone programs in the Bronx, New York City, New York, USA.Methadone maintenance patients, smoking ≥5 cigarettes/day, interested in quitting, stable in methadone treatment, without current Axis I psychiatric disorders, suicidal ideation or recent suicide attempts.Seven-day point prevalence abstinence verified by expired carbon monoxide (CO) < 8 parts per million at week 12 (primary outcome); carbon monoxide (CO)-verified abstinence, cigarettes/day, incident Axis I psychiatric illness, suicidal ideation or serious adverse events (SAEs) at weeks 2, 4, 8, 12 or 24 (secondary outcomes).Baseline demographic, smoking and clinical factors were similar between groups. Retention at 24 weeks was 90%. Subjects receiving varenicline were more likely than those receiving placebo to achieve abstinence (10.5 versus 0%, P = 0.03; effect size 10.5%, 95% confidence interval (CI) = 4.4-19.3%) and to reduce smoking (median five versus two cigarettes/day, P < 0.001) at 12 weeks. These effects were not maintained after drug treatment ceased. Incident psychiatric illness (OR= 0.84, 95% CI = 0.16, 4.4) and suicidality [odds ratio (OR) = 0.88, 95% CI 0.2, 3.9] were not different between groups. There were no psychiatric or cardiac SAEs.Varenicline can aid short-term smoking abstinence in methadone-maintained smokers.

TITLE: The optimum initial pediatric epidural bolus: a comparison of four local anesthetic solutions.ABSTRACT: There is no consensus on the concentration or type of local anesthetic used for initiation of epidural anesthesia. The aim of this randomized, double-blind, controlled trial was to compare the clinical effectiveness of epidural administration of both levobupivacaine and bupivacaine in 0.2% and 0.25% concentrations in pediatric patients undergoing abdominal and urological surgery.One hundred and forty-one children scheduled for lower abdominal and urological surgery were randomized to receive 0.4-0.6 ml.kg(-1) epidural, 0.25% bupivacaine, 0.2% bupivacaine, 0.25% levobupivacaine or 0.2% levobupivacaine. Initial epidural volumes, onset times; hemodynamic consequences, postoperative pain scores and degree of residual postoperative motor block were all recorded.There were no significant differences in the proportion of children with effective analgesia after incision [0.20% bupivacaine 97%, 0.25% bupivacaine 94%, 0.20% levobupivacaine 91%, 0.25% levobupivacaine 92% (P=0.73)] when a median volume of 0.55 ml.kg(-1) was used. There was no association between the volume used for thoracic, lumbar, or sacral epidural anesthesia and the effectiveness of the agents used. There was a significantly greater incidence of pain on awakening with the 0.2% solutions compared with the 0.25% solutions, but no differences in the incidence of residual motor block between groups.While there is no difference in the proportion of effective surgical anesthesia, the lower incidence of pain and distress with the 0.25% solutions suggests that this concentration has clinical advantages over the 0.2% solutions for pediatric epidural anesthesia.

TITLE: Randomized evaluation of atorvastatin in patients with coronary heart disease: a serial intravascular ultrasound study.ABSTRACT: It is unclear whether a marked reduction of low-density lipoprotein-cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild hypercholesterolemia leads to less progression of atherosclerosis.Patients with CHD and hypercholesterolemia (100<LDL-C<140 mg/dl) who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to the atorvastatin (10-20 mg/day) group or ;usual care' group. After 12 months 58 patients had follow-up CAG and IVUS studies that could be evaluated. Cross-sectional areas of the vessel, lumen, and plaque were measured at 1-mm intervals, and volumetric calculations were based on Simpson's rule. After 12 months, the mean reduction of LDL-C was 34% in the atorvastatin group and 0% in the usual care group (p<0.01). The mean absolute plaque volume showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin -1.4+/-11.6 mm3, usual care 7.6+/-10.3 mm3; p<0.01). Vessel volume also showed a larger increase in the usual care group than in the atorvastatin group (atorvastatin 2.2+/-10.9 mm3, usual care 10.9+/-17.7 mm3; p=0.03).Atorvastatin treatment prevented the further progression of atherosclerosis by maintaining LDL-C below 100 mg/dl in patients with CHD and hypercholesterolemia (100<LDL-C<140 mg/dl).

TITLE: Randomized comparison of the continuous vs point-by-point radiofrequency ablation of the cavotricuspid isthmus for atrial flutter.ABSTRACT: Achievement of complete conduction block in the cavotricuspid isthmus (CTI) is a curative ablation technique in patients with common atrial flutter (AFL). The present study was a prospective comparison of the efficacy of 2 ablation strategies in patients with common AFL: the continuous and point-by-point radiofrequency (RF) delivery techniques.Forty patients with common AFL were randomly assigned to either a group treated with a continuous RF delivery or to a group undergoing point-by-point RF ablation. In the first group, the RF energy was continuously delivered during a slow drag of the catheter tip from the tricuspid annulus to the inferior vena cava without stopping the application. In the second group, the RF ablation was performed using a point-by-point approach for 60 s at each point. All patients underwent ablation with an 8-mm-tip ablation catheter with a power limit of 50 W and a target temperature of 55 degrees C. Complete CTI conduction block was achieved in all patients. The patient characteristics, including the anatomy of the CTI estimated by 3-dimensional computed tomography, were no different between the 2 groups. The procedure time (time from the start of RF delivery to the completion of CTI block), fluoroscopic time and total RF energy required to create the CTI block between the continuous and point-by-point groups were 7.3+/-5.6 vs 21.2+/-22.2 min (p<0.01), 7.2+/-4.4 vs 16.2+/-14.1 min (p<0.05), and 15,631+/-6,001 vs 24,072+/-16,140 joules (p<0.05), respectively. There were no complications or recurrences of AFL during the follow-up period in any of the patients.In the curative treatment of common AFL, the continuous RF delivery approach could shorten the procedure and fluoroscopic time and reduce the total RF energy compared with the point-by-point RF ablation approach.

TITLE: Effects of strict blood pressure control by a long-acting calcium channel blocker on brain natriuretic peptide and urinary albumin excretion rate in Japanese hypertensive patients.ABSTRACT: Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level.

TITLE: Can validated wrist devices with position sensors replace arm devices for self-home blood pressure monitoring? A randomized crossover trial using ambulatory monitoring as reference.ABSTRACT: Electronic devices that measure blood pressure (BP) at the arm level are regarded as more accurate than wrist devices and are preferred for home BP (HBP) monitoring. Recently, wrist devices with position sensors have been successfully validated using established protocols. This study assessed whether HBP values measured with validated wrist devices are sufficiently reliable to be used for making patient-related decisions in clinical practice.This randomized crossover study compared HBP measurements taken using validated wrist devices (wrist-HBP, Omron R7 with position sensor) with those taken using arm devices (arm-HBP, Omron 705IT), and also with measurements of awake ambulatory BP (ABP, SpaceLabs), in 79 subjects (36 men and 43 women) with hypertension. The mean age of the study population was 56.7 +/- 11.8 years, and 33 of the subjects were not under treatment for hypertension.The average arm-HBP was higher than the average wrist-HBP (mean difference, systolic 5.2 +/- 9.1 mm Hg, P < 0.001, and diastolic 2.2 +/- 6.7, P < 0.01). Twenty-seven subjects (34%) had a > or =10 mm Hg difference between systolic wrist-HBP and arm-HBP and twelve subjects (15%) showed similar levels of disparity in diastolic HBP readings. Strong correlations were found between arm-HBP and wrist-HBP (r 0.74/0.74, systolic/diastolic, P < 0.0001). However, ABP was more strongly correlated with arm-HBP (r 0.73/0.76) than with wrist-HBP (0.55/0.69). The wrist-arm HBP difference was associated with systolic ABP (r 0.34) and pulse pressure (r 0.29), but not with diastolic ABP, sex, age, arm circumference, and wrist circumference.There might be important differences in HBP measured using validated wrist devices with position sensor vs. arm devices, and these could impact decisions relating to the patient in clinical practice. Measurements taken using arm devices are more closely related to ABP values than those recorded by wrist devices. More research is needed before recommending the widespread use of wrist monitors in clinical practice. American Journal of Hypertension doi:10.1038/ajh.2008.176American Journal of Hypertension (2008); 21, 7, 753-758. doi:10.1038/ajh.2008.176.

TITLE: Randomized, multicenter study comparing expanded polytetrafluoroethylene-covered endoprosthesis placement with percutaneous transluminal angioplasty in the treatment of superficial femoral artery occlusive disease.ABSTRACT: To compare the safety and effectiveness of the Viabahn endoprosthesis with that of percutaneous transluminal angioplasty (PTA) alone in the treatment of symptomatic peripheral arterial disease (PAD) affecting the superficial femoral artery (SFA).From 1998 to 1999, patients with symptomatic SFA PAD were enrolled in a prospective, multicenter randomized study and underwent either PTA alone (n = 100) or PTA followed by stent-graft placement (expanded polytetrafluoroethylene/nitinol self-expanding stent-graft) (n = 97) for stenoses or occlusions of the SFA that were 13 cm long or shorter. At baseline, there were no significant differences between the PTA and stent-graft treatment groups, including chronic limb ischemia status and treated lesion length.The stent-graft group had a significantly higher technical success rate (95% vs 66%, P < .0001) and 1-year primary vessel patency rate at duplex ultrasonography (65% vs 40%, P = .0003). A patency benefit was seen for lesions at least 3 cm long. At 12 months, chronic limb ischemia status was 15% further improved for the stent-graft group (P = .003). There were no significant differences between treatment groups with regard to the occurrence of early or late major adverse events.In this multicenter study, the patency, technical success, and clinical status results obtained with stent-grafts were superior to those obtained with PTA alone.

TITLE: Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults.ABSTRACT: Intermittent normobaric hypoxia training, an alternative to altitude training for athletes, may be beneficial to treat overweight and obesity. The purpose of this study is to investigate whether normobaric hypoxia training combined with low-caloric diet has the additive effect on weight loss compared with normoxia training in obese young adults.Twenty-two subjects (age 17-25 years, body mass index >27.5 kg/m(2)) were recruited for a 4-week residential camp of weight loss with low caloric intake, and trained at 60-70% maximal heart rate of aerobics and 40-50% of maximal strength of training. They were randomly assigned to either a normobaric hypoxia (HT, FiO2 = 16.4-14.5 %) or normoxia training group (NT, FiO2 = 21%), and subjects in HT and NT groups experienced weekly 16-h normoxia and 6-h hypoxia or 22-h normoxia training, respectively. Body composition, resting blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) were determined before and after the intervention.Weight loss was found in HT (-6.9 kg or -7.0%, p < 0.01) and NT groups (-4.3 kg or -4.2%, p < 0.01) significantly, and the former lost more weight than the latter (p < 0.01). Hypoxia training improved systolic BP (-7.6%) and mean BP (-7.1%) significantly (p < 0.05) despite having no effect on baPWV.Four weeks of normobaric hypoxia residential training with low caloric diet has an additive improvement on weight loss. It seems that normobaric hypoxia training might be a promising method to treat obesity.

TITLE: The Diet of Higher Insulinemic Potential Is Not Associated with Worse Survival in Patients with Stage III Colon Cancer (Alliance).ABSTRACT: Hyperinsulinemia is considered to be important in the development of colon cancer, but few studies have investigated the associations of hyperinsulinemia with colon cancer survival via dietary scores.Empirical dietary index for hyperinsulinemia (EDIH) was derived to assess the insulinemic potential of daily diets reflecting the long-term insulin exposure, with higher (more positive) scores indicating higher insulinemic diets. We prospectively estimated the HRs and 95% confidence intervals (CI) to investigate the association of EDIH with disease-free, recurrence-free, and overall survival among patients with stage III colon cancer (1999-2009) enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803).Of 1,024 patients (median follow-up: 7.3 years), 311 died, 350 had recurrences, and 394 had events for disease-free survival. Compared with patients in the lowest quintile of EDIH, the corresponding HRs of patients in the highest quintile for disease-free survival events, cancer recurrence, and overall mortality were 0.80 (95% CI, 0.56-1.15), 0.76 (95% CI, 0.51-1.11), and 0.77 (95% CI, 0.52-1.14).Higher EDIH was not associated with the risk of colon cancer recurrence or mortality in this population of patients with stage III colon cancer.EDIH, as a measure of dietary insulinemic potential, may be associated with colon cancer risk but not survival in patients with late-stage colon cancer.

TITLE: Comparison between shockpulse and pneumatic lithotripsy in percutaneous nephrolithotomy.ABSTRACT: To compare the effectiveness and safety of shockpulse with pneumatic lithotripsy in percutaneous nephrolithotomy.A prospective randomized comparative study was performed in Department of Urology, Bir Hospital for 1-year duration with 61 patients in shockpulse (Group 1) and 58 patients in pneumatic lithoclast (Group 2) groups, respectively. Patient's demographics, stone characteristics, hemoglobin drop, hospital stay, operative duration, stone fragmentation time and postoperative complications were compared.The two groups did not differ significantly in terms of patient's demographic and stone characteristics. The mean hemoglobin drop was 1.96 ± 1.48 g/dl in Group 1 and 2.32 ± 1.38 g/dl in Group 2 (p = 0.16) and hospital stay was 3.14 ± 1.42 days in Group 1 and 3.29 ± 1.82 days in Group 2 (p = 0.62). The number of cases that required multiple tracts were six (9.8%) in Group 1 and 12 (20.68%) in Group 2 (p = 0.12). The stone-free rates were 78.69% in Group 1 and 74.13% in Group 2 (p = 0.66). Mean total operation time was 43.23 ± 18.49 min in Group 1 as compared to 51.53 ± 19.48 min in Group 2 (p = 0.0188). Mean stone fragmentation time was 17.95 ± 15.25 min in Group 1 and 24.37 ± 11.12 min in Group 2 (p = 0.0096). Overall complications were not significant between the two Groups (p = 0.58). On sub-analysis of the patients with single tracts in both groups the results were comparable to patients with single and multiple tracts combined.Despite similar stone-free rates and complications between the two Groups, shockpulse has significantly lower stone fragmentation time and total operation time as compared to pneumatic lithotripsy.

TITLE: Comparison of nateglinide and gliclazide in combination with metformin, for treatment of patients with Type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone.ABSTRACT: To compare the effects of nateglinide plus metformin with gliclazide plus metformin on glycaemic control in patients with Type 2 diabetes.Double-blind, double-dummy, parallel group, randomized, multicentre study over 24 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to additionally receive nateglinide (n = 133) or gliclazide (n = 129). Changes from baseline in HbA1c, fasting plasma glucose (FPG) and mealtime glucose and insulin excursions were examined.HbA1c was significantly (P < 0.001) decreased from baseline in both treatment groups (mean changes: nateglinide -0.41%, gliclazide -0.57%), but with no significant difference between treatments. Proportions of patients achieving a reduction of HbA1c >or= 0.5% or an end point HbA1c < 7% were also similar (nateglinide 58.1%, gliclazide 60.2%). Changes from baseline in FPG were similarly significant in both treatment groups (nateglinide -0.63, gliclazide -0.82 mmol/l). Reduction from baseline in maximum postprandial glucose excursion were significant in the nateglinide group only (nateglinide -0.71, gliclazide -0.10 mmol/l; P = 0.037 for difference). Postprandial insulin levels were significantly higher with nateglinide compared with gliclazide. The overall rate of hypoglycaemia events was similar in the nateglinide group compared with the gliclazide group.No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA1c. However, the nateglinide combination demonstrated better postprandial glucose control.

TITLE: Does EVAR alter the rate of cardiovascular events in patients with abdominal aortic aneurysm considered unfit for open repair? Results from the randomised EVAR trial 2.ABSTRACT: To investigate whether endovascular aneurysm repair (EVAR) influences the rate of cardiovascular events (fatal or non-fatal myocardial infarction or stroke) in patients with abdominal aortic aneurysm (AAA) considered unfit for open repair.Randomised controlled trial.Between 1999 and 2004, 404 patients with large AAA considered unfit for open repair were randomised to EVAR or no surgical intervention across 33 UK hospitals and followed until July 2009.The Customised Probability Index was used to determine fitness for each patient and Cox regression was used to compare time to first cardiovascular event between randomised groups and levels of fitness.During an average of 2.8 years of follow-up, 67 first cardiovascular events occurred with a non-significantly higher event rate in the EVAR group compared to the no intervention group (6.6 versus 5.1 events per 100 person years); adjusted hazard ratio 1.42 [95% CI 0.87-2.34], p=0.156. There was no evidence to suggest that the hazard ratio between randomised groups changed with level of fitness (p=0.378).Cardiovascular event rates were high in these unfit patients and medical therapy was sub-optimal. Events rates were slightly higher in the EVAR group but this was not statistically significant.

TITLE: Effects of anaesthesia method and tourniquet use on recovery following total knee arthroplasty: a randomised controlled study.ABSTRACT: We investigated the effects of spinal and general anaesthesia and surgical tourniquet on acute pain and early recovery after total knee arthroplasty (TKA).Patients (n=413) were randomised to four parallel groups: spinal anaesthesia with or without tourniquet, and general anaesthesia with or without tourniquet. The primary outcome was patient-controlled i.v. oxycodone consumption over 24 postoperative hours.Results from 395 subjects were analysed. Median i.v. oxycodone consumption did not differ between the four groups (spinal anaesthesia without [36.6 mg] and with tourniquet [38.0 mg], general anaesthesia without [42.3 mg] and with tourniquet [42.5 mg], P=0.42), between spinal (37.7 mg) and general anaesthesia (42.5 mg) groups (median difference -3.1, 95% confidence interval [CI] -7.4 to 1.2, P=0.15) and between tourniquet and no-tourniquet groups (40.0 vs 40.0 mg, median difference -0.8, CI -5.1 to 3.5, P=0.72). Vomiting incidence was higher with spinal than with general anaesthesia (21% [42/200] vs 13% [25/194], CI 1.05 to 3.1, P=0.034). The mean haemoglobin decrease was greater without than with tourniquet (-3.0 vs -2.5 g dl, mean difference -0.48, CI -0.65 to -0.32, P<0.001). No differences were observed in pain, pain management, incidences of blood transfusions, in-hospital complications, or length of hospital stay.For TKA, spinal and general anaesthesia with or without tourniquet did not differ in 24-h postoperative opioid consumption, pain management, blood transfusions, in-hospital complications, and length of hospital stay. Vomiting incidence was higher in the spinal than in the general anaesthesia group. Tourniquet use caused smaller decreases in haemoglobin levels.EudraCT 2016-002035-15.

TITLE: Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program.ABSTRACT: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio.Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m to treatment with canagliflozin or placebo.Canagliflozin or matching placebo.The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes.Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04).Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m.Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin.This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical.The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.

TITLE: An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for treating erectile dysfunction in men naïve to treatment.ABSTRACT: Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.

TITLE: Regular vs prn nebulized treatment in wheeze preschool children.ABSTRACT: International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze.Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1-4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 microg beclomethasone bid plus 2500 microg salbutamol prn; (2) placebo bid plus 800 microg beclomethasone/1600 microg salbutamol combination prn; (3) placebo bid plus 2500 microg salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency.As compared with prn salbutamol (61.0 +/- 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes.Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study.

TITLE: Sildenafil citrate 100 mg starting dose in men with erectile dysfunction in an international, double-blind, placebo-controlled study: effect on the sexual experience and reducing feelings of anxiety about the next intercourse attempt.ABSTRACT: Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy.Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED.Men with ED (score < or =25 on the Erectile Function domain of the International Index of Erectile Function) who had received < or =6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg).Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg.Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose.Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

TITLE: OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.ABSTRACT: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study.PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported.Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials.This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.

TITLE: The Likelihood of Change in Fetal Presentation During the Third Trimester in Twin Pregnancies.ABSTRACT: To estimate the likelihood and identify predictors of spontaneous fetal version during the third trimester in twins using data from a multicenter randomized controlled trial on mode of delivery in twin pregnancies.Women with twin pregnancies after 32 weeks of gestation in which twin A was vertex were randomized to planned cesarean or planned vaginal delivery. In the current study we analyzed the likelihood of a spontaneous version of any of the twins between ultrasound assessment at the time of randomization and delivery.A total of 2,603 women were analyzed. Twin A tended to persist in the vertex presentation after 32 weeks of gestation with a spontaneous version rate to nonvertex presentation of 3.0% (95% confidence interval [CI] 2.3-3.7%). Twin B was less stable and underwent spontaneous version in 24.8% (95% CI 23.1-26.5%) of cases; the rate remained higher than 20% even after 34 weeks of gestation. On multivariable analysis, twin A was more likely to undergo version when twin B was smaller (adjusted odds ratio [OR] 2.0, 95% CI 1.04-3.3), when twin B was breech (adjusted OR 3.7, 95% CI 2.2-6.4) or transverse (adjusted OR 2.9, 95% CI 1.6-5.5), and when the interval to delivery exceeded 4 weeks (adjusted OR 2.5, 95% CI 1.3-5.0). Twin B was more likely to undergo version when it was in the breech presentation (adjusted OR 1.7, 95% CI 1.4-2.1) or transverse lie (adjusted OR 3.1, 95% CI 2.5-3.9) compared with vertex presentation, when it was smaller (adjusted OR 1.7, 95% CI 1.1-2.0), when the interval to delivery exceeded 4 weeks (adjusted OR 1.7, 95% CI 1.3-2.4), and in multiparous women (adjusted OR 1.3, 95% CI 1.04-1.5).The likelihood of spontaneous version of twin A after 32 weeks of gestation is low when twin A is in the vertex presentation but is much higher for twin B, even late during the third trimester.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187369.II.

TITLE: The use of mHealth to deliver tailored messages reduces reported energy and fat intake.ABSTRACT: Evidence supports the role of feedback in reinforcing motivation for behavior change. Feedback that provides reinforcement has the potential to increase dietary self-monitoring and enhance attainment of recommended dietary intake.The aim of this study was to examine the impact of daily feedback (DFB) messages, delivered remotely, on changes in dietary intake.This was a secondary analysis of the Self- Monitoring And Recording using Technology (SMART) Trial, a single-center, 24-month randomized clinical trial of behavioral treatment for weight loss. Participants included 210 obese adults (mean body mass index, 34.0 kg/m²) who were randomized to either a paper diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback messages (PDA + FB). To determine the role of daily tailored feedback in dietary intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with the self-monitoring without DFB group (no-DFB group, n = 140). All participants received a standard behavioral intervention for weight loss. Self-reported changes in dietary intake were compared between the DFB and no-DFB groups and were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling was used to examine percentage changes in dietary intake from baseline.Compared with the no-DFB group, the DFB group achieved a larger reduction in energy (-22.8% vs -14.0%; P = .02) and saturated fat (-11.3% vs -0.5%; P = .03) intake and a trend toward a greater decrease in total fat intake (-10.4% vs -4.7%; P = .09). There were significant improvements over time in carbohydrate intake and total fat intake for both groups (P values < .05).Daily tailored feedback messages designed to target energy and fat intake and delivered remotely in real time using mobile devices may play an important role in the reduction of energy and fat intake.

TITLE: Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study.ABSTRACT: To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause.A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 microg/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24).A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels < or = 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels < or = 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated.Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder.

TITLE: Diarrhoeal disease knowledge among diarrhoea patient housholds: findings from the randomised controlled trial of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) mobile health program.ABSTRACT: The objective of this study was to evaluate the impact of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7) handwashing with soap and water treatment mobile health (mHealth) program on diarrhoeal disease knowledge among diarrhoea patients and their household members in urban Dhaka, Bangladesh.A cluster-randomised controlled trial of the CHoBI7 mHealth program was conducted among diarrhoea patient households in Dhaka, Bangladesh. Patients were randomised to three arms: standard recommendation on oral rehydration solution use; health facility delivery of CHoBI7 plus mHealth (weekly voice and text messages) (no home visits); and health facility delivery of CHoBI7 plus two home visits and mHealth. An open-ended questionnaire was administered to 1468 participants 12 years of age or older on diarrhoeal disease transmission and prevention. These items were combined to form a diarrhoeal disease knowledge score measured at baseline and at a 1 week, 6 month and 12 month follow-up.At baseline, when participants were asked to report three ways diarrhoeal diseases were spread 37% (546/1468) of participants reported by water, 13% (187/1468) by lack of handwashing and 4% (53/1468) by food not being covered properly. At baseline when asked to name three ways diarrhoeal diseases could be prevented, 35% (515/1468) of participants reported safe water, and 16% (228/1468) reported handwashing with soap. At the 12-month follow-up, the overall diarrhoeal disease knowledge score was significantly higher in the mHealth with no home visits arm (score coefficient: 0.69, 95% Confidence Interval: 0.36, 1.01, P < 0.0001) and the mHealth with two home visits arm (score coefficient: 1.18, 95% CI: 0.87, 1.49, P < 0.0001) compared with the standard recommendation arm.The CHoBI7 mHealth program significantly increased knowledge of diarrhoeal disease transmission and prevention among diarrhoea patients and their household members 12 months after in-person visits for program delivery were conducted.

TITLE: Prospective randomized comparison of tongue base resection techniques: Robotic vs coblation.ABSTRACT: The objective of this study was to determine the effectiveness and morbidities of two different tongue base surgical approaches in patients with obstructive sleep apnoea (OSA).We carried out a prospective analysis in order to understand in detail the relative impact on apnoeas of the two different tongue base procedures. Seventy cases in 85 patients with OSA were divided into two operating groups and randomized. Altogether, 37 transoral robotic surgeries (TORS) and 33 coblations were performed. The patency of retrolingual passage was investigated by Muller's manoeuvere, polysomnography. Apnoea-hypopnea index (AHI) was the primary outcome measure with the Epworth Sleepiness Score (ESS). The final follow-up visit was at 6 months.The AHI index improved from 29.7 ± 9 to 10.7 ± 3.9 (P < .005) following TORS and from 27.2 ± 6.4 to 10.3 ± 4 in the coblation group. Selecting a threshold of a 50% reduction in AHI and AHI less than 20 events/h, the overall success rate was 75.6% in TORS compared with 78.7% in coblation (P = .785). Similar results were seen in AHI reduction rates (36%, 37.8%, respectively). ESS showed a significant improvement 6 months following surgery in both groups.Transoral robotic surgery technique showed higher complication rates than coblation. TORS and coblation of the tongue base represent a promising treatment option with a similar AHI improvement. However, coblation promises lower complication rates unlike TORS.

TITLE: Rigid Mini-Thoracoscopy Versus Semirigid Thoracoscopy in Undiagnosed Exudative Pleural Effusion: The MINT Randomized Controlled Trial.ABSTRACT: There is debate regarding the ideal instrument for medical thoracoscopy. The authors compared rigid mini-thoracoscopy with semirigid thoracoscopy for thoracoscopic pleural biopsy.Consecutive subjects with undiagnosed exudative pleural effusion were randomized (1:1 ratio) to mini-thoracoscopy or semirigid thoracoscopy groups. The primary objective was a comparison of the diagnostic yield of pleural biopsy. Key secondary outcomes were the comparison of sedative/analgesic dose, operator-rated and patient-rated pain on visual analog scale (VAS), operator-rated overall procedural satisfaction (VAS), pleural biopsy size, and complications between the groups.Of the 88 screened subjects, 73 were randomized: 36 to mini-thoracoscopy and 37 to semirigid thoracoscopy. Diagnostic yield of pleural biopsy in the mini-thoracoscopy (69.4%) and semirigid thoracoscopy groups (81.1%) was similar on intention-to-treat analysis (P=0.25). Although the operator-rated overall procedure satisfaction scores were similar between groups (P=0.87), operator-rated pain [VAS (mean±SD), 43.5±16.7 vs. 31.7±15.8; P<0.001] and patient-rated pain (VAS, 41.9±17.3 vs. 32.1±16.5; P=0.02) scores were greater in the mini-thoracoscopy group. Mean dose of fentanyl and midazolam received was similar between the 2 groups (P=0.28 and 0.68, respectively). Biopsy size was larger in the mini-thoracoscopy group (16.1±4.5 vs. 8.3±2.9 mm; P<0.001). Three minor complications occurred in the mini-thoracoscopy group and 6 in the semirigid thoracoscopy group (P=0.11). There were no serious adverse events or procedure-related mortality.Diagnostic yield of rigid mini-thoracoscopy is not superior to semirigid thoracoscopy. Use of semirigid thoracoscope may provide greater patient comfort.

TITLE: On-line haemodiafiltration versus haemodialysis: stable haematocrit with less erythropoietin and improvement of other relevant blood parameters.ABSTRACT: Controlled randomised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration (oHDF) are scarce.70 patients were treated with both haemodialysis (HD) and oHDF in a cross-over design during 2 x 24 weeks at a dialysis dose of eKt/V> or =1.2. Patients randomised into group A started on HD and switched over to oHDF, whereas patients in group B began with oHDF and were treated with HD afterwards. Intradialytic morbid events (IME), such as symptomatic hypotension or muscle cramps, were noted in case of appearance. Blood parameters reflecting anaemic status, phosphate status, lipid metabolism, oxidative stress, and accumulation of advanced glycation end products were recorded either monthly or at the end of each study phase.The mean incidence of IME was 0.15 IME per treatment, and there was no statistical difference between oHDF and HD. A higher haematocrit (oHDF 31.5% vs. HD 30.5%, p < 0.01) at a lower erythropoietin dose (oHDF 4,913 vs. HD 5,492 IU/week, p = 0.02) was found during oHDF, when the sequence of HD and oHDF had not been taken into account. For the study groups, the results were less distinct: in group A, a higher haematocrit (HD 30.4% vs. oHDF 32.0%, p < 0.01) at a comparable erythropoietin dose (HD 5,421 vs. oHDF 5,187 IU/week, ns) was observed during oHDF, whereas in group B an identical haematocrit (oHDF 30.8% vs. HD 30.7%, ns) was achieved at a reduced erythropoietin dose (oHDF 4,622 vs. HD 5,568 IU/week, p < 0.01). During oHDF, lower levels of free and protein-bound pentosidine and of serum phosphate were found.In contrast to other studies, no benefit regarding cardiovascular stability for oHDF was found, but oHDF could well offer a potential benefit regarding anaemia correction, inflammation, oxidative stress, lipid profiles, and calcium-phosphate product.

TITLE: Managing migraine headaches experienced by patients who self-report with menstrually related migraine: a prospective, placebo-controlled study with oral sumatriptan.ABSTRACT: The objective was to evaluate the efficacy and tolerability of oral sumatriptan (100 mg) in patients who self-reported with menstrually related migraine. A prospective, multicentre, randomised, double-blind, placebo-controlled, two-group crossover study was carried out in 20 UK primary and secondary care surgeries. Of 115 patients with a self-reported history of menstrually related migraine that entered the study, 93 patients completed it. Patients treated all migraine attacks for 2 months with sumatriptan (100 mg) and for 2 months with placebo. The primary endpoint was the proportion of patients reporting headache relief at 4 hours for the first treated attack. Only 11% of patients fulfilled the protocol definition of menstrually related migraine. Patients reported a variable pattern of migraine attacks occurring inside and outside the menstrual window. For the first attack, significantly more patients receiving sumatriptan than placebo reported headache relief for attacks occurring inside (67% vs. 33%, p=0.007) and outside (79% vs. 31%, p<0.001) the menstrual period. Sumatriptan was generally well tolerated. Oral sumatriptan (100 mg) is an effective and well tolerated acute treatment for patients who report menstrually related migraine.

TITLE: French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC).ABSTRACT: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002.Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1-->D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m2 (D1, D22, D43); 5FU, continuous infusion (D1-->D5), 750 mg/m2/day cycle 1; 430 mg/m2/day cycles 2 and 3.A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p = 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years.For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an "aggressive" dose-intensity radiotherapy schedule.

TITLE: Marine n-3 fatty acids in adipose tissue and development of atrial fibrillation: a Danish cohort study.ABSTRACT: Consumption of fish and marine n-3 polyunsaturated fatty acids (PUFA) may be associated with a lower risk of atrial fibrillation (AF), but results have been inconsistent. The aim was to investigate this further by measurements of marine n-3 PUFA in adipose tissue.Cohort study.A total of 57 053 Danish participants 50-64 years of age were enrolled into the Diet, Cancer and Health Cohort Study.A randomly drawn subcohort of 3440 participants with available data from baseline adipose tissue biopsies.Exposure was the adipose tissue content of marine n-3 PUFA, which reflects the endogenous exposure and is also an objective marker of the long-term dietary intake.Incident AF during follow-up.179 cases of AF occurred over 13.6 years. Multivariate, sex-stratified Cox proportional hazards regression analyses using cubic splines showed a monotonic, negative, dose-response trend, but not statistically significant association, between total marine n-3 PUFA in adipose tissue and incident AF. A similar trend towards a lower risk of AF was seen in the second (HR 0.87, 95% CI 0.60 to 1.24) and third tertiles (HR 0.77, 95% CI 0.53 to 1.10) of marine n-3 PUFA compared with the lowest tertile. Similar trends, but also not statistically significant, were found separately for eicosapentaenoic, docosahexaenoic and docosapentaenoic acids.There was no statistically significant association between the content of marine n-3 PUFA in adipose tissue and the development of AF; however, data showed a monotonic, negative dose-response trend suggestive of a negative association.

TITLE: Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147.ABSTRACT: Epidermal growth factor receptor inhibitors can result in a severe rash in 5-10% of patients and can detract from quality of life. The objective of this study was to identify clinical predictors of severe rash in the hope of utilizing such factors in the design of future rash palliative and prevention trials.933 cetuximab-treated patients enrolled on N0147, an adjuvant chemotherapy trial for colon cancer, were evaluated for clinical risk factors of severe rash.Within this cohort, 50 patients (5%) developed a severe rash (grade 3). More men compared to women developed such a rash: 34 (7%) versus 16 (3%) (multivariate odds ratio = 2.12; 95% confidence interval: 1.14-3.88; p = 0.017). A greater number of younger patients (<70 years of age) also developed a rash: 48 (6%) versus 2 (1%) (multivariate odds ratio = 0.21; 95% confidence interval: 0.05-0.88; p = 0.032). Race and performance score were not predictive.Men and younger patients are at greater risk for a severe cetuximab-induced rash although overall the risk is low. These observations are particularly important in designing future rash prevention and palliation trials.

TITLE: A comparative analysis between the effects of galactose and glucose supplementation on endurance performance.ABSTRACT: To determine beneficial effects of short-term galactose (GAL) supplementation over a 50:50 glucose-maltodextrin (GLUC) equivalent on self-paced endurance cycling performance.On 2 separate occasions, subjects performed a 100-km self-paced time trial (randomized and balanced order). This was interspersed with four 1-km and four 4-km maximal efforts reflecting the physical requirements of racing. Before each trial 38±3 g of GAL or GLUC was ingested in a 6% concentrate fluid form 1 hr preexercise and then during exercise at a rate of 37±3 g/hr. Performance variables were recorded for all 1- and 4-km efforts, all interspersed intervals, and the total 100-km distance. Noninvasive indicators of work intensity (heart rate [HR] and rating of perceived exertion) were also recorded.Times taken to complete the 100-km performance trial were 8,298±502 and 8,509±578 s (p=.132), with mean power outputs of 271±37 and 256±45 W (p=.200), for GAL and GLUC, respectively. Mean HR did not differ (GAL 157±7 and GLUC 157±7 beats/min, p=.886). A main effect of carbohydrate (CHO) type on time to complete 4-km efforts occurred, with no CHO Type×Effort Order interaction observed. No main effect of CHO type or interaction of CHO Type×Sequential Order occurred for 1-km efforts.A 6% GAL drink does not enhance performance time during a self-paced cycling performance trial in highly trained endurance cyclists compared with a formula typically used by endurance athletes but may improve the ability to produce intermediate self-paced efforts.

TITLE: Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD Treatment trial.ABSTRACT: Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤ 35% and serum creatinine level ≤ 2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)).Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74-0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73-1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69-0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66-0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70-0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dl in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mm Hg, both) and serum potassium (mean increase, 0. /L, both).Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.

TITLE: A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial.ABSTRACT: Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase.In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite.Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM.ClinicalTrials.gov NCT02246296.

TITLE: The impact of tranexamic acid on mortality in injured patients with hyperfibrinolysis.ABSTRACT: In 2011, supported by data from two separate trauma centers, we implemented a protocol to administer tranexamic acid (TXA) in trauma patients with evidence of hyperfibrinolysis (HF) on admission. The purpose of this study was to examine whether the use of TXA in patients with HF determined by admission rapid thrombelastography was associated with improved survival.Following institutional review board approval, we evaluated all trauma patients 16 years or older admitted between September 2009 and September 2013. HF was defined as LY-30 of 3% or greater. Patients with LY-30 less than 3.0% were excluded. Patients were divided into those who received TXA (TXA group) and those who did not (no-TXA group). After univariate analyses, a purposeful, logistic regression model was developed a priori to evaluate the impact of TXA on mortality (controlling for age, sex, Injury Severity Score (ISS), arrival physiology, and base deficit).A total of 1,032 patients met study criteria. Ninety-eight (10%) received TXA, and 934 (90%) did not. TXA patients were older (median age, 37 years vs. 32 years), were more severely injured (median ISS, 29 vs. 14), had a lower blood pressure (median systolic blood pressure 103 mm Hg vs. 125 mm Hg), and were more likely to be in shock (median, base excess, -5 mmol/dL vs. -2 mmol/dL), all p < 0.05. Twenty-three percent of the patients had a repeat thrombelastography within 6 hours; 8.8% of the TXA patients had LY-30 of 3% or greater on repeat rapid thrombelastography (vs. 10.1% in the no-TXA group, p = 0.679). Unadjusted in-hospital mortality was higher in the TXA group (40% vs. 17%, p < 0.001). There were no differences in venous thromboembolism (3.3% vs. 3.8%). Logistic regression failed to find a difference in in-hospital mortality among those receiving TXA (odds ratio, 0.74; 95% confidence interval, 0.38-1.40; p 0.80).In the current study, the use of TXA was not associated with a reduction in mortality. Further studies are needed to better define who will benefit from an administration of TXA.Therapeutic study, level IV.

TITLE: Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.ABSTRACT: Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD.We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life.An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life.Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

TITLE: Implications of ventricular arrhythmia "bursts" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury "downstream of downstream".ABSTRACT: Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR).Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015).Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive "biosignature" of optimal reperfusion than do single surrogate markers.

TITLE: A randomized control trial of bupivacaine and fentanyl versus fentanyl-only for epidural analgesia during the second stage of labor.ABSTRACT: The purpose of this prospective, double-blinded, parallel-arm, randomized trial was to examine the effects of epidural bupivacaine on the length of the second stage of labor in nulliparous women.The authors assessed length of second-stage labor, degree of motor blockade, mode of delivery, and visual analog scores in 310 nulliparous women with labor epidurals randomized to receive either: (1) 0.125% bupivacaine and fentanyl 2 μg/ml or (2) fentanyl 10 μg/ml alone via epidural using double blinding.The median duration of the second stage was 75 min (41, 128) in the bupivacaine/fentanyl group versus 73 min (42, 120) in the fentanyl-only group (P = 0.17) with a median difference of 6.0 (95% CI, -6.0 to 18.0). Furthermore, there was no difference in degree of motor blockade, incidence of operative delivery, visual analog scores, or neonatal outcomes between the two groups. No adverse events were reported.Use of epidural bupivacaine/fentanyl or a fentanyl-only infusion during the second stage of labor did not affect the duration of the second stage of labor, degree of motor blockade, mode of delivery, pain relief, and maternal or neonatal outcomes. However, in the fentanyl-only infusion group, there was a fivefold increase in opioid exposure to the fetus with unknown effects on neurobehavior, an outcome not assessed beyond the immediate postnatal period in this study.

TITLE: High-intensity statin therapy alters the natural history of diabetic coronary atherosclerosis: insights from SATURN.ABSTRACT: Although statins can induce coronary atheroma regression, this benefit has yet to be demonstrated in diabetic individuals. We tested the hypothesis that high-intensity statin therapy may promote coronary atheroma regression in patients with diabetes.The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. This analysis compared changes in biochemistry and coronary percent atheroma volume (PAV) in patients with (n = 159) and without (n = 880) diabetes.At baseline, patients with diabetes had lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels but higher triglyceride and CRP levels compared with patients without diabetes. At follow-up, diabetic patients had lower levels of LDL-C (61.0 ± 20.5 vs. 66.4 ± 22.9 mg/dL, P = 0.01) and HDL-C (46.3 ± 10.6 vs. 49.9 ± 12.0 mg/dL, P < 0.001) but higher levels of triglycerides (127.6 [98.8, 163.0] vs. 113.0 mg/dL [87.6, 151.9], P = 0.001) and CRP (1.4 [0.7, 3.3] vs. 1.0 [0.5, 2.1] mg/L, P = 0.001). Both patients with and without diabetes demonstrated regression of coronary atheroma as measured by change in PAV (-0.83 ± 0.13 vs. -1.15 ± 0.13%, P = 0.08). PAV regression was less in diabetic compared with nondiabetic patients when on-treatment LDL-C levels were >70 mg/dL (-0.31 ± 0.23 vs. -1.01 ± 0.21%, P = 0.03) but similar when LDL-C levels were ≤70 mg/dL (-1.09 ± 0.16 vs. -1.24 ± 0.16%, P = 0.50).High-intensity statin therapy alters the progressive nature of diabetic coronary atherosclerosis, yielding regression of disease in diabetic and nondiabetic patients.

TITLE: Gastrointestinal Tolerance, Growth and Safety of a Partly Fermented Formula with Specific Prebiotics in Healthy Infants: A Double-Blind, Randomized, Controlled Trial.ABSTRACT: This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS; 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants ≤28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%; < 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.

TITLE: Integrative analysis of the intestinal metabolome of childhood asthma.ABSTRACT: The intestinal metabolome reflects the biological consequences of diverse exposures and might provide insight into asthma pathophysiology.We sought to perform an untargeted integrative analysis of the intestinal metabolome of childhood asthma in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial.Metabolomic profiling was performed by using mass spectrometry on fecal samples collected from 361 three-year-old subjects. Adjusted logistic regression analyses identified metabolites and modules of highly correlated metabolites associated with asthma diagnosis by age 3 years. Sparse canonical correlation analysis identified associations relevant to asthma between the intestinal metabolome and other "omics": the intestinal microbiome as measured by using 16S rRNA sequencing, the plasma metabolome as measured by using mass spectrometry, and diet as measured by using food frequency questionnaires.Several intestinal metabolites were associated with asthma at age 3 years, including inverse associations between asthma and polyunsaturated fatty acids (adjusted logistic regression β = -6.3; 95% CI, -11.3 to -1.4; P = .01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breast-feeding for the first 4 months of life and asthma (P for indirect association = .04) and the positive association between a diet rich in meats and asthma (P = .03). Specific intestinal bacterial taxa, including the family Christensenellaceae, and plasma metabolites, including γ-tocopherol/β-tocopherol, were positively associated with asthma and asthma-associated intestinal metabolites.Integrative analyses revealed significant interrelationships between the intestinal metabolome and the intestinal microbiome, plasma metabolome, and diet in association with childhood asthma. These findings require replication in future studies.

TITLE: An open, randomized, controlled, phase II, single centre, two-period cross-over study to compare the quality of life and toxicity experienced on PEG interferon with interferon-alpha2b in patients with multiple myeloma maintained on a steady dose of interferon-alpha2b.ABSTRACT: To compare the effects of pegylated interferon-alpha2b (P-IFN) and interferon-alpha2b (IFN) on quality of life (QoL) and toxicity in patients with multiple myeloma maintained on a steady dose of IFN.Consenting, eligible myeloma patients on IFN maintenance therapy for at least 6 weeks were randomly (1:1) allocated to receive P-IFN for 3 months followed by IFN for 3 months, or to continue with IFN for 3 months followed by P-IFN for 3 months (cross-over design). Patients were assessed for toxicity and QoL. Dose of P-IFN was equivalent to IFN.The study enrolled 60 patients. At enrollment, 35 patients were in complete remission, 20 in partial remission and 5 were minimal responders. P-IFN was associated with significantly better global QoL score (mean difference 8.4; P = 0.0002). There was a significant improvement in functional scales--physical (P = 0.03), emotional (P = 0.04), social (P = 0.0008) with P-IFN. Fatigue (P = 0.0003), pain (P = 0.02) and appetite loss (P = 0.003) symptom scales were less in patients while on P-IFN. There were no statistically significant differences between treatment arms in QoL as measured by QLQ-MY24.These data suggest that patients on P-IFN have a better QoL. Dose escalation studies are warranted to investigate potential impact on survival.

TITLE: Preferences of adult patients with allergic rhinitis for the sensory attributes of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized, multicenter, double-blind, single-dose, crossover study.ABSTRACT: Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR).The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR.This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment.Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF.In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

TITLE: The Risk of Subclinical Breast Cancer-Related Lymphedema by the Extent of Axillary Surgery and Regional Node Irradiation: A Randomized Controlled Trial.ABSTRACT: To compare the risk of subclinical breast cancer-related lymphedema (sBCRL) using bioimpedance spectroscopy (BIS) or tape measure (TM) by the extent of axillary surgery and regional nodal irradiation (RNI).Patients were randomized to surveillance with TM or BIS. A BIS ≥6.5 L-Dex units or TM volume change ≥5 and <10% above presurgical baselines "triggered" sBCRL. The incidence of sBCRL by sentinel node biopsy or axillary lymph node dissection (ALND) with or without RNI was examined for 484 patients. Radiation was categorized as "limited RNI" (axilla level I/II only) or "extensive RNI" (axilla level III or supraclavicular fossa with or without level I/II).At a median follow-up of 20.5 months, 109 of 498 patients (21.9%) triggered sBCRL (BIS 13.5% vs TM 25.6%; P <.001). In patients not receiving RNI, BIS triggered 12.9% of patients undergoing SNB and 25.0% undergoing ALND (P = .18). Extensive RNI significantly increased triggering with BIS versus no RNI after sentinel node biopsy (SNB; 33.3% vs 12.9%; P = .03) but not ALND (30.8% vs 25.0%; P = .69). Triggering by TM was greater than 25% for most subgroups and was inferior to BIS in discriminating the risk of sBCRL by utilization of RNI or axillary surgery.The lower triggering rates with BIS and its better discrimination of the risk of sBCRL by receipt and type of RNI compared with TM support its use for posttreatment surveillance to detect sBCRL and to initiate early intervention. The risk of sBCRL increased with more extensive axillary treatment. Patients having ALND or extensive RNI require close surveillance for BCRL. Longer follow-up is required to determine rates of progression to clinical lymphedema.

TITLE: Food cravings and energy regulation: the characteristics of craved foods and their relationship with eating behaviors and weight change during 6 months of dietary energy restriction.ABSTRACT: To examine characteristics of craved foods in relation to dietary energy restriction (ER) with high (HG) and low glycemic load (LG) diets.Assessments of food cravings before and during a randomized controlled trial of HG and LG diets provided for 6 months.Thirty-two healthy, overweight women aged 20-42 years.Self-reported food cravings and dietary intake, body weight, weight history and measures of eating behaviors.Foods craved at baseline were more than twice as high in energy density as the habitual diet (3.7+/-1.5 vs 1.7+/-0.3 kcal/g; P<0.001), and on average were lower in protein (P<0.001) and fiber (P<0.001) and higher in fat (P=0.002). There were no statistically significant changes in nutritional characteristics of craved foods after 6 months of ER. There was a significant relationship between reported portion size of craved food consumed at baseline and lifetime high body mass index (r=0.49, P=0.005). Additionally, there was a significant association between susceptibility to hunger and craving frequency at baseline, and there were significant relationships between hunger score, craving frequency, strength and percentage of time that cravings are given in to after 6 months of ER. In multiple regression models, subjects who lost a greater percentage of weight craved higher energy-dense foods at month 6 of ER, but also reported giving in to food cravings less frequently (adjusted R (2)=0.31, P=0.009).High energy density and fat content, and low protein and fiber contents were identifying characteristics of craved foods. The relationships between craving variables and hunger score suggest that the relative influence of hunger susceptibility on cravings may be important before and especially after ER. Portion size of craved foods and frequency of giving in to food cravings appear to be important areas for focus in lifestyle modification programs for long-term weight loss.

TITLE: Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period.ABSTRACT: Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up.This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study.From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo.Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups.NCT02709486.

TITLE: Efficacy of a multifactorial intervention on therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): a randomized controlled trial.ABSTRACT: Therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is poor. This study evaluated the effectiveness of a multifactorial intervention on improving the therapeutic adherence in chronic obstructive pulmonary disease (COPD) patients with scheduled inhalation therapy.The study design consisted of a randomised controlled trial in a primary care setting. 146 patients diagnosed with COPD were randomly allocated into two groups using the block randomisation technique. One-year follow-ups with three visits were performed. The intervention consisted of motivational aspects related to adherence (beliefs and behaviour) in the form of group and individual interviews, cognitive aspects in the form of information about the illness and skills in the form of training in inhalation techniques. Cognitive-emotional aspects and training in inhalation techniques were reinforced during all visits of the intervention group. The main outcome measure was adherence to the medication regimen. Therapeutic adherence was determined by the percentage of patients classified as good adherent as evaluated by dose or pill count.Of the 146 participants (mean age 69.8 years, 91.8% males), 41.1% reported adherence (41.9% of the control group and 40.3% of the intervention group). When multifactorial intervention was applied, the reported adherence was 32.4% for the control group and 48.6% for the intervention group, which showed a statistically significant difference (p = 0.046). Number needed to treat is 6.37. In the intervention group, cognitive aspects increased by 23.7% and skilled performance of inhalation techniques increased by 66.4%. The factors related to adherence when multifactorial intervention was applied were the number of exacerbations (OR = 0.66), visits to health centre (OR = 0.93) and devices (OR = 2.4); illness severity (OR = 0.67), beta-2-adrenergic (OR = 0.16) and xantine (OR = 0.19) treatment; activity (OR = 1.03) and impact (OR = 1.03) scales of the Saint George Respiratory Questionnaire.Application of the multifactorial intervention designed for this study (COPD information, dose reminders, audio-visual material, motivational aspects and training in inhalation techniques) resulted in an improvement in therapeutic adherence in COPD patients with scheduled inhalation therapy.Current Controlled Trials ISRCTN18841601.

TITLE: Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real?ABSTRACT: Emerging literature suggests that obesity may be "protective" against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index [BMI] <22 kg/m(2) ) and smokers, neither obesity nor IFG was associated with all-cause mortality [corrected]. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22 kg/m(2) . The obesity paradox may result from confounding by a sicker, underweight referent population and smoking.

TITLE: Ginger for prevention of antiretroviral-induced nausea and vomiting: a randomized clinical trial.ABSTRACT: In this randomized clinical trial ginger efficacy for prevention of antiretroviral-induced nausea and vomiting (N/V) was investigated.From July 2011 until the end of June 2013, 102 HIV positive patients attending the HIV clinic of Imam Khomeini Hospital participated in the study. In a double blinded manner, participants randomly received either 500 mg ginger or placebo two times per day, 30 min before each dose of antiretroviral regimen for 14 days. The severity of nausea was assessed based on the visual analogue scale. The number of vomiting episodes were also recorded during the study period.A total of 46 (90.2%) and 29 (56.4%) of the patients in placebo and ginger groups experienced some degree of nausea during the first 2 weeks of antiretroviral therapy (ART), respectively (p = 0.001). Frequency of mild, moderate and severe nausea were significantly lower in the ginger than placebo group (p = 0. 001). Also, 24 (47.1%) and 5 (9.8%) of the patients in the placebo and ginger groups reported at least one episode of vomiting during their time on ART, respectively (p = 0.01).Ginger was effective in ameliorating of antiretroviral-induced N/V.

TITLE: Prospective comparison of the use of sirolimus and cyclosporine in recipients of a kidney from an expanded criteria donor.ABSTRACT: A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7+/-16.6 vs. 41.9+/-15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients.

TITLE: Electrocautery for cutaneous flap creation during thyroidectomy: a randomised, controlled study.ABSTRACT: Although electrocautery has been used widely in surgery, the fear of delayed wound healing and infection persists. We aimed to evaluate the risk factors for wound complications and the rate of wound complications, comparing the use of electrocautery or scissors in cutaneous flap creation during thyroidectomy.The study group comprised 239 consecutive patients scheduled for thyroidectomy.Patients were randomly assigned to cutaneous flap dissection by either electrocautery (group one, n = 126) or scissors (group two, n = 113). Age, gender, body mass index, American Society of Anesthesiology score, tissue weight, operating time, incision length, cutaneous tissue depth, thyroid function and surgeon experience were recorded and compared with the rate of post-operative wound complications in both groups.There were no significant differences between the overall rate of post-operative wound complications, comparing groups one and two (7.9 vs 10.6 per cent, respectively; p = 0.74). Significant positive correlations were found between wound complication and age (Spearman's rank coefficient (rs) = 0.135, p = 0.036), body mass index (rs = 0.379, p = 0.0001), cutaneous tissue depth (rs = 0.677, p = 0.0001) and tissue weight (rs = 0.643, p = 0.0001). According to logistic regression analysis, a body mass index of more than 27.5 kg/m2 was associated with a 13.7-fold increased rate of post-operative wound complications.When creating cutaneous flaps during thyroidectomy, the use of electrocautery is as safe as the use of scissors. Such electrocautery does not increase the risk of wound complications in thyroid surgery.

TITLE: Comparison of unilateral renal artery embolization versus bilateral for treatment of severe refractory hypertension in hemodialysis patients.ABSTRACT: Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bilateral renal embolization (BRE) is an alternative to nephrectomy in treating severe refractory hypertension in hemodialysis patients, but has drawbacks in residual renal function preservation and post-infarction syndrome. We evaluated the efficacy and safety of unilateral renal embolization (URE) for the treatment of severe refractory hypertension in hemodialysis patients.From January 2000 to May 2007, 16 hemodialysis patients with severe refractory hypertension were randomized to URE or BRE group, and received percutaneous transcatheter unilateral or bilateral renal embolization, respectively. The efficacy and complications of these two procedures were compared. The plasma renin activity (PRA), plasma angiotensin II, aldosterone and endothelin-1 (ET-1) were measured pre- and post-renal embolization in both groups.The procedures were completed successfully without severe immediate complications. The blood pressure decreased from 211/122 to 127/81 mmHg in URE group (P < 0.0001), and in BRE group from 208/117 to 124/76 mmHg (P < 0.0001) with significantly reduced need for antihypertensive medications. The residual renal function was reasonably kept and post-infarction syndrome was milder in URE group compared with BRE group. No activation of RAS was observed in this series and no RAS activity dynamic change occurred post-procedure. Decreased circulating ET-1 was accompanied with the lowering of blood pressure after the procedure (P < 0.0001).Unilateral renal embolization is as effective as BRE in treating severe refractory hypertension in hemodialysis patients, with advantages over BRE in residual renal function preservation and milder post-infarction syndrome.

TITLE: Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women.ABSTRACT: We determined if soy isoflavones have dose-related estrogenic and methylation effects. Thirty-four healthy premenopausal women were randomized to 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific and systemic estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, whereas methylation assessment of 5 cancer related genes (p16, RASSF1A, RARbeta2, ER, and CCND2) was performed on intraductal specimens. Serum genistein significantly increased after consuming both isoflavone doses. Cytology did not significantly change at either isoflavone dose. Serum C3 levels posttreatment were inversely related to change in serum genistein (r =-0.76, P = 0.0045) in women consuming low but not high dose isoflavones. The RAR beta 2 hypermethylation increase posttreatment correlated with the posttreatment genistein level considering the entire group (r = 0.67, P = 0.0017) and those receiving high-dose isoflavones (r = 0.68, P = 0.021). At the low but not the high isoflavone dose, CCND2 hypermethylation increase correlated with posttreatment genistein levels (r = 0.79, P = 0.011). In summary, the inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose-specific changes in RARbeta2 and CCND2 gene methylation, which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.

TITLE: Total Occlusive Ionic Silver-Containing Dressing vs Mupirocin Ointment Application vs Conventional Dressing in Elective Colorectal Surgery: Effect on Incisional Surgical Site Infection.ABSTRACT: Several pre- and intraoperative factors have been associated with incisional surgical site infection (SSI), but little is known about the influence of postoperative wound care and especially, the use of different dressings on incisional SSI. The aim of this study was to compare 3 methods of wound dressings (conventional dressing, silver-containing dressing, and mupirocin ointment dressing) for their ability to prevent SSI, as measured by SSI rates, in patients with colorectal cancer undergoing elective open surgery.A prospective, randomized study was performed. Inclusion criteria were diagnosis of colorectal neoplasms and plans to undergo elective surgery with curative aims. Patients were randomized using a 1:1:1 allocation into 3 groups: patients receiving an ionic silver-containing dressing (ISD) (group 1), a mupirocin ointment application (MOA) (group 2), and a conventional dressing (group 3 or standard dressing). The primary outcomes variable was occurrence of incisional SSI. Follow-up was 30 days postoperatively.A total of 147 patients were included, 49 in each group. Incisional SSI occurred in 9 patients (18.4%) in the ISD group, 2 (4.1%) in the MOA group, and 10 (20.4%) in the standard dressing group (p = 0.028). Adjusting for multiple comparisons, there were no significant differences between ISD and standard dressing groups; a significant difference was observed between ISD and MOA (relative risk [RR] 4.5; 95% CI (1.1 to 19.8); p = 0.046) and between the standard group and the MOA group (RR 5; 95% CI (1.2 to 21.7); p = 0.031).Topical application of mupirocin ointment achieves better results for the prevention of SSI than ionic silver-containing dressing or standard dressing in patients undergoing elective open colorectal surgery.

TITLE: Serum vitamin D, vitamin D binding protein, and risk of colorectal cancer.ABSTRACT: We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk.In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D.Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend  = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend  = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend  = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend  = 0.87), although the interaction was not statistically significant (p for interaction  = 0.24).Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers.

TITLE: Bystander fatigue and CPR quality by older bystanders: a randomized crossover trial comparing continuous chest compressions and 30:2 compressions to ventilations.ABSTRACT: This study sought to measure bystander fatigue and cardiopulmonary resuscitation (CPR) quality after five minutes of CPR using the continuous chest compression (CCC) versus the 30:2 chest compression to ventilation method in older lay persons, a population most likely to perform CPR on cardiac arrest victims.This randomized crossover trial took place at three tertiary care hospitals and a seniors' center. Participants were aged ≥55 years without significant physical limitations (frailty score ≤3/7). They completed two 5-minute CPR sessions (using 30:2 and CCC) on manikins; sessions were separated by a rest period. We used concealed block randomization to determine CPR method order. Metronome feedback maintained a compression rate of 100/minute. We measured heart rate (HR), mean arterial pressure (MAP), and Borg Exertion Scale. CPR quality measures included total number of compressions and number of adequate compressions (depth ≥5 cm).Sixty-three participants were enrolled: mean age 70.8 years, female 66.7%, past CPR training 60.3%. Bystander fatigue was similar between CPR methods: mean difference in HR -0.59 (95% CI -3.51-2.33), MAP 1.64 (95% CI -0.23-3.50), and Borg 0.46 (95% CI 0.07-0.84). Compared to 30:2, participants using CCC performed more chest compressions (480.0 v. 376.3, mean difference 107.7; p<0.0001) and more adequate chest compressions (381.5 v. 324.9, mean difference. 62.0; p=0.0001), although good compressions/minute declined significantly faster with the CCC method (p=0.0002).CPR quality decreased significantly faster when performing CCC compared to 30:2. However, performing CCC produced more adequate compressions overall with a similar level of fatigue compared to the 30:2 method.

TITLE: A prospective randomised controlled trial of the fibular nail versus standard open reduction and internal fixation for fixation of ankle fractures in elderly patients.ABSTRACT: The fundamental concept of open reduction and internal fixation (ORIF) of ankle fractures has not changed appreciably since the 1960s and, whilst widely used, is associated with complications including wound dehiscence and infection, prominent hardware and failure. Closed reduction and intramedullary fixation (CRIF) using a fibular nail, wires or screws is biomechanically stronger, requires minimal incisions, and has low-profile hardware. We hypothesised that fibular nailing in the elderly would have similar functional outcomes to standard fixation, with a reduced rate of wound and hardware problems.A total of 100 patients (25 men, 75 women) over the age of 65 years with unstable ankle fractures were randomised to undergo standard ORIF or fibular nailing (11 men and 39 women in the ORIF group, 14 men and 36 women in the fibular nail group). The mean age was 74 years (65 to 93) and all patients had at least one medical comorbidity. Complications, patient related outcome measures and cost-effectiveness were assessed over 12 months.Significantly fewer wound infections occurred in the fibular nail group (p = 0.002). At one year, there was no evidence of difference in mean functional scores (Olerud and Molander Scores 63; 30 to 85, versus 61; 10 to 35, p = 0.61) or scar satisfaction. The overall cost of treatment in the fibular nail group was £91 less than in the ORIF group despite the higher initial cost of the implant.We conclude that the fibular nail allows accurate reduction and secure fixation of ankle fractures, with a significantly lower rate of soft-tissue complications, and is more cost-effective than ORIF. Cite this article: Bone Joint J 2016;98-B:1248-52.

TITLE: Effect of evolocumab on cholesterol synthesis and absorption.ABSTRACT: The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in β-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering.

TITLE: Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial.ABSTRACT: Previously, our group has shown that topiramate, a sulfamate-substituted fructopyranose derivative, is an effective treatment for alcohol dependence. Herein, we extend that proof-of-concept study by determining whether cigarette-smoking, alcohol-dependent individuals from the earlier study also experienced improved smoking outcomes.As a subgroup analysis of a larger double-blind, randomized, controlled, 12-week study comparing topiramate vs placebo as treatment for alcohol dependence, a 12-week clinical trial compared topiramate vs placebo in 94 cigarette-smoking, alcohol-dependent individuals. Of these, 45 were assigned to receive topiramate (escalating dose from 25 to 300 mg/d) and the remaining 49 had placebo as an adjunct to weekly standardized medication compliance management. The primary outcome was smoking cessation ascertained by self-report and confirmed by the level of serum cotinine (nicotine's major metabolite).Topiramate recipients were significantly more likely than placebo recipients to abstain from smoking (odds ratio, 4.46; 95% confidence interval, 1.08-18.39; P = .04). Using a serum cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we found that the topiramate group had 4.97 times the odds of being nonsmokers (95% confidence interval, 1.1-23.4;P = .04). Smoking cessation rates for topiramate recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with 6.9% at both time points for placebo recipients.In this trial, topiramate (up to 300 mg/d) showed potential as a safe and promising medication for the treatment of cigarette smoking in alcohol-dependent individuals.

TITLE: Teleconferenced educational detailing: diabetes education for primary care physicians.ABSTRACT: Formal didactic continuing medical education (CME) is relatively ineffective for changing physician behaviour. Diabetes mellitus is an increasingly prevalent disease, and interventions to improve adherence to clinical practice guidelines (CPGs) are needed.A stratified, cluster-randomized, controlled trial design was used to evaluate the effects of a teleconferenced educational detailing (TED) CME on glycemic control (hemoglobin [Hb] A1c) and family physician adherence to national diabetes guidelines. TED employed sequential, small-group, case-based education using CPGs delivered by a diabetes specialist. Medical record audit data from baseline through the end of a 12-month postintervention period were compared for the control and intervention groups. Satisfaction with the intervention was evaluated.Sixty-one physicians provided 660 medical records. The intervention did not affect mean Hb A1c levels but did significantly (p = .04) alter the distribution of patients by category of glycemic control, with fewer in the intervention group in inadequate control (15.8% versus 23.9%). More patients took insulin (alone or with oral agents) in the intervention group (21.2% versus 12.0%, p = .03), and more took oral agents only in the control group (89.0% versus 82.9%, p = .005). More patients in the intervention group had documentation of body mass index (7.8% versus 1.9%, p < .02), eye exam (12.1% versus 5.1%, p = .02), and treatment plan (43.5% versus 23.6%, p = .01) and used a flow sheet (14.6% versus 7.7%, p < .03). Although there was general satisfaction with the teleconferencing format, specialist educators found the format more challenging than the family physicians.CME delivered by teleconference was feasible, well attended, well received by participants, and improved some key diabetes management practices and outcomes.

TITLE: Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT).ABSTRACT: The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear.The primary objective was to compare the efficacy of tadalafil 5mg once daily and tadalafil 20mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥ 22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length.Randomised, double-blind, double-dummy, placebo-controlled trial in men ≤ 68 yr of age with adenocarcinoma of the prostate (Gleason ≤ 7) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada.1:1:1 randomisation to 9 mo of treatment with tadalafil 5mg once daily, tadalafil 20mg on demand, or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily (all patients).Logistic regression, mixed-effects model for repeated measures, and analysis of covariance, adjusting for treatment, age, and country, were applied to IIEF-EF scores ≥ 22, SEP-3, and penile length.Four hundred twenty-three patients were randomised to tadalafil once daily (n=139), on demand (n=143), and placebo (n=141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores ≥ 22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6-2.1; p=0.675) and 0.9 (95% CI, 0.5-1.7; p=0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: ΔIIEF-EF ≥ 4) in both tadalafil groups; for SEP-3 (MCID ≥ 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p=0.016; SEP-3: p=0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1mm; 95% CI, 0.4-7.8; p=0.032).Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo.ClinicalTrials.gov identifier NCT01026818.

TITLE: Maintenance of elevated versus physiological iron indices in non-anaemic patients with chronic kidney disease: a randomized controlled trial.ABSTRACT: An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD).One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment.Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups.Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L.

TITLE: Immediate compared with delayed cord clamping in the preterm neonate: a randomized controlled trial.ABSTRACT: The comparative risks and benefits of early compared with delayed cord clamping in the preterm neonate remain unclear. Our objective was to evaluate the short-term effects of delayed clamping of the umbilical cord in preterm neonates.We conducted a randomized controlled trial comparing immediate with delayed cord clamping among preterm neonates born between 24 and 34 weeks of gestation. The primary study outcome was the need for blood transfusion. To detect a 33% reduction in this outcome (from 65 to 43.5%) with a two-tailed α of 0.5 and β of 0.8 required 178 patients equally divided into two groups.A total of 200 women were randomized, 99 to the delayed and 101 to the immediate clamp group. The groups were similar with respect to baseline characteristics. The mean gestational age at delivery was 30.8±3.1 weeks in the delayed compared with 30.7±2.8 weeks in the immediate clamp group (P=.64). There was no statistically significant difference between groups with regard to the need for blood transfusion: 25 of 99 (25.3%) in the delayed cord clamp group received one or more blood transfusion compared with 24 of 101 (23.7%) in the immediate clamp group (P=.8). The rates of various neonatal outcomes including respiratory distress syndrome, periventricular leukomalacia, necrotizing enterocolitis, anemia of prematurity, and neonatal morality did not differ significantly between the groups. However, the mean initial hemoglobin (17.4±2.5 compared with 16.3±2.3 g/dL, P=.001) and hematocrit (51.3±7.3 compared with 47.4±7.3, P=.001) was significantly higher in the delayed group. In the delayed clamp group, 11.1% (11/99) of neonates had intraventricular hemorrhage compared with 19.8% (20/101) in the immediate clamp group (P=.09).Delayed cord clamping for 30 seconds did not decrease the need for blood transfusion among preterm neonates.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00579839.

TITLE: Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: a Dutch TEAM trial analysis.ABSTRACT: Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC).Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score<50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p=0.25) or tamoxifen users (p=0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p=0.67], a DR (HR 1.02, 95% CI 0.77-1.35, p=0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p=0.48).The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy.

TITLE: Epoetin alpha improves the response to antiviral treatment in HCV-related chronic hepatitis.ABSTRACT: The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response.We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response.Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only.Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p<0.01).In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence.

TITLE: Addition of Exercise Increases Plasma Adiponectin and Release from Adipose Tissue.ABSTRACT: Adiponectin is an adipose tissue-derived anti-inflammatory protein that is down-regulated in obesity. The effects of caloric restriction and exercise-induced weight loss on adiponectin are not clear.To determine whether addition of aerobic exercise training to caloric restriction has additive effects over caloric restriction alone on circulating adiponectin concentrations and adiponectin release from abdominal and gluteal adipose tissue.Overweight or obese (body mass index, 25-40 kg·m(-2); waist >88 cm) postmenopausal women were randomized to 20-wk caloric restriction with and without aerobic exercise (CR + EX, n = 48; and CR, n = 22). Blood samples were collected for measuring plasma adiponectin concentration, and abdominal and gluteal subcutaneous adipose tissue biopsies were performed in a subgroup to determine in vitro adiponectin release, before and after the interventions.The interventions elicited similar amounts of weight loss (CR + EX, -11.3 ± 4.6 kg; CR,-11.2 ± 3.4 kg) and fat loss (CR + EX, -8.0 ± 3.5 kg; CR, -7.4 ± 2.7 kg). The two groups had differential changes in plasma adiponectin concentrations (for interaction, P = 0.014); CR + EX increased (6.9 ± 3.9 to 8.5 ± 4.9 μg·mL(-1); P = 0.0001), whereas CR did not alter (6.4 ± 4.4 to 6.5 ± 4.5 μg·mL(-1); P = 0.42) plasma adiponectin. Likewise, adiponectin release from abdominal and gluteal subcutaneous adipose tissue increased with CR + EX (P = 0.0076 and P = 0.089, respectively) but did not change with CR (P = 0.13 and P = 0.95, respectively).Despite similar reductions in body weight and fat mass, the addition of aerobic exercise to caloric restriction increased plasma adiponectin concentrations, which may be partly explained by increased adiponectin release from abdominal and gluteal subcutaneous adipose tissue.

TITLE: Multicenter Randomized Study of Obesity Treatment with Minimally Invasive Injection of Hyaluronic Acid Versus and Combined with Intragastric Balloon.ABSTRACT: Research into minimally invasive techniques is worthwhile for greater acceptance in bariatric surgery, a useful first step being to evaluate the combination of these with current procedures. We suggest that intragastric balloon (IGB) can be performed with hyaluronic acid (HA) injections at the level of the gastroesophageal junction.A submucosal restriction is created by circular injection of an absorbable material within a defined area based on endoscopic anatomy. We included 101 patients in a prospective multicenter randomized trial, with average body mass index (BMI) 33.4 (range 27-44), treated from April 2010 to April 2012 by IGB and/or HA injection, sequentially, and followed for two more years. Patients were divided into group 1 (IGB alone), group 2 (IGB followed by HA at IGB removal, at 6 months), and group 3 (HA and IGB at 6 months).BMI loss at 6 months was inferior in the HA group (32 patients) compared with the IGB groups (68 patients) (2.1 ± 0.4 versus 3.4 ± 0.3, p < 0.05). The efficacy of IGB alone compared with combined treatments (groups 2 and 3) was significantly inferior at 18 months only, but the impact of the treatment sequence (HA before or after IGB) on BMI loss was not statistically significant, although in favor of HA first.This study did not demonstrate the efficacy of HA injections as an obesity treatment.

TITLE: Promoting physical activity in older people in general practice: ProAct65+ cluster randomised controlled trial.ABSTRACT: Regular physical activity reduces falls, hip fractures, and all-cause mortality, but physical activity levels are low in older age groups.To evaluate two exercise programmes promoting physical activity among older people.Pragmatic three-arm, parallel-design cluster randomised controlled trial involving 1256 people aged ≥65 years (of 20 507 invited) recruited from 43 general practices in London, Nottingham, and Derby.Practices were randomised to the class-based Falls Management Exercise programme (FaME), the home-based Otago Exercise Program (OEP), or usual care. The primary outcome was the proportion reaching the recommended physical activity target 12 months post-intervention. Secondary outcomes included falls, quality of life, balance confidence, and costs.In total, 49% of FaME participants reached the physical activity target compared with 38% for usual care (adjusted odds ratio 1.78, 95% confidence interval [CI] =1.11 to 2.87, P = 0.02). Differences between FaME and usual care persisted 24 months after intervention. There was no significant difference comparing those in the OEP (43% reaching target at 12 months) and usual-care arms. Participants in the FaME arm added around 15 minutes of moderate-to-vigorous physical activity per day to their baseline level; this group also had a significantly lower rate of falls (incident rate ratio 0.74, 95% CI = 0.55 to 0.99, P = 0.042). Balance confidence was significantly improved in both intervention arms. The mean cost per extra person achieving the physical activity target was £1740. Attrition and rates of adverse reactions were similar.The FaME programme increases self-reported physical activity for at least 12 months post-intervention and reduces falls in people aged ≥65 years, but uptake is low. There was no statistically significant difference in reaching the target, or in falls, between the OEP and usual-care arms.

TITLE: Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial.ABSTRACT: The short stature homeobox-containing gene, SHOX, located on the distal ends of the X and Y chromosomes, encodes a homeodomain transcription factor responsible for a significant proportion of long-bone growth. Patients with mutations or deletions of SHOX, including those with Turner syndrome (TS) who are haplo-insufficient for SHOX, have variable degrees of growth impairment, with or without a spectrum of skeletal anomalies consistent with dyschondrosteosis.Our objective was to determine the efficacy of GH in treating short stature associated with short stature homeobox-containing gene deficiency (SHOX-D).Fifty-two prepubertal subjects (24 male, 28 female; age, 3.0-12.3 yr) with a molecularly proven SHOX gene defect and height below the third percentile for age and gender (or height below the 10th percentile and height velocity below the 25th percentile) were randomized to either a GH-treatment group (n = 27) or an untreated control group (n = 25) for 2 yr. To compare the GH treatment effect between subjects with SHOX-D and those with TS, a third study group, 26 patients with TS aged 4.5-11.8 yr, also received GH. Between-group comparisons of first-year and second-year height velocity, height sd score, and height gain (cm) were performed using analysis of covariance accounting for diagnosis, sex, and baseline age.The GH-treated SHOX-D group had a significantly greater first-year height velocity than the untreated control group (mean +/- se, 8.7 +/- 0.3 vs. 5.2 +/- 0.2 cm/yr; P < 0.001) and similar first-year height velocity to GH-treated subjects with TS (8.9 +/- 0.4 cm/yr; P = 0.592). GH-treated subjects also had significantly greater second-year height velocity (7.3 +/- 0.2 vs. 5.4 +/- 0.2 cm/yr; P < 0.001), second-year height sd score (-2.1 +/- 0.2 vs.-3.0 +/- 0.2; P < 0.001) and second-year height gain (16.4 +/- 0.4 vs. 10.5 +/- 0.4 cm; P < 0.001) than untreated subjects.This large-scale, randomized, multicenter clinical trial in subjects with SHOX-D demonstrates marked, highly significant, GH-stimulated increases in height velocity and height SDS during the 2-yr study period. The efficacy of GH treatment in subjects with SHOX-D was equivalent to that seen in subjects with TS. We conclude that GH is effective in improving the linear growth of patients with various forms of SHOX-D.

TITLE: Effectiveness of pelvic floor muscle training with and without electromyographic biofeedback for urinary incontinence in women: multicentre randomised controlled trial.ABSTRACT: To assess the effectiveness of pelvic floor muscle training (PFMT) plus electromyographic biofeedback or PFMT alone for stress or mixed urinary incontinence in women.Parallel group randomised controlled trial.23 community and secondary care centres providing continence care in Scotland and England.600 women aged 18 and older, newly presenting with stress or mixed urinary incontinence between February 2014 and July 2016: 300 were randomised to PFMT plus electromyographic biofeedback and 300 to PFMT alone.Participants in both groups were offered six appointments with a continence therapist over 16 weeks. Participants in the biofeedback PFMT group received supervised PFMT and a home PFMT programme, incorporating electromyographic biofeedback during clinic appointments and at home. The PFMT group received supervised PFMT and a home PFMT programme. PFMT programmes were progressed over the appointments.The primary outcome was self-reported severity of urinary incontinence (International Consultation on Incontinence Questionnaire-urinary incontinence short form (ICIQ-UI SF), range 0 to 21, higher scores indicating greater severity) at 24 months. Secondary outcomes were cure or improvement, other pelvic floor symptoms, condition specific quality of life, women's perception of improvement, pelvic floor muscle function, uptake of other urinary incontinence treatment, PFMT self-efficacy, adherence, intervention costs, and quality adjusted life years.Mean ICIQ-UI SF scores at 24 months were 8.2 (SD 5.1, n=225) in the biofeedback PFMT group and 8.5 (SD 4.9, n=235) in the PFMT group (mean difference -0.09, 95% confidence interval -0.92 to 0.75, P=0.84). Biofeedback PFMT had similar costs (mean difference £121 ($154; €133), -£409 to £651, P=0.64) and quality adjusted life years (-0.04, -0.12 to 0.04, P=0.28) to PFMT. 48 participants reported an adverse event: for 23 this was related or possibly related to the interventions.At 24 months no evidence was found of any important difference in severity of urinary incontinence between PFMT plus electromyographic biofeedback and PFMT alone groups. Routine use of electromyographic biofeedback with PFMT should not be recommended. Other ways of maximising the effects of PFMT should be investigated.ISRCTN57756448.

TITLE: Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema.ABSTRACT: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present.Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted.Change in optical coherence tomography measurements at 12-month follow-up.Among eyes with a baseline central subfield thickness of 250 microm or greater, central subfield thickening decreased by an average of 88 microm in the modified ETDRS group and by 49 microm in the MMG group at 12-month follow-up (adjusted mean difference, 33 microm; 95% confidence interval, 5-61 microm; P = .02). Weighted inner zone thickening by optical coherence tomography decreased by 42 microm in the modified ETDRS group and by 28 microm in the MMG group (adjusted mean difference, 14 microm; 95% confidence interval, 1-27 microm; P = .04); maximum retinal thickening (maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 microm, respectively (adjusted mean difference, 27 microm; 95% confidence interval, 6-47 microm; P = .01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference, 0.3 mm3; 95% confidence interval, 0.02-0.53 mm3; P = .03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P = .10).At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified.Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema.clinicaltrials.gov Identifier: NCT00071773.

TITLE: Once-daily cefepime versus ceftriaxone for nursing home-acquired pneumonia.ABSTRACT: To compare once-daily intramuscular cefepime with ceftriaxone controls.Double-blind study.Six skilled nursing facilities.Residents aged 60 and older with nursing home-acquired pneumonia.Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours.Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed.Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age+/-standard deviation of 85+/-6, with a mean 5.8+/-1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35+/-7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were 117+/-40 dollars for cefepime- and 215+/-68 dollars for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost 597 dollars and ceftriaxone 1,709 dollars per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust.Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization.