There is a large body of evidence for the involvement of the parietal cortex in orientation and navigation in space .


This has been supplemented by investigation of the contribution of a number of subregions using transcranial magnetic stimulation .


The role of the precuneus area , located in the medial plane of posterior parietal cortex ( PPC ) , in visuospatial functions is not well understood .


We investigated the contribution of this area using the landmark task .


Participants were asked to make forced-choice judgments of which side of prebisected line was longer for near and far viewing conditions ( 70 and 180cm , respectively ) .


Online 10Hz , repetitive transcranial magnetic stimulation ( rTMS ) was delivered for 500ms over the right precuneus , rPPC and vertex ( control ) , in separate blocks of trials .


The rPPC stimulation was used as a positive control , having previously resulted in `` neglect like '' spatial bias effects in a number of studies .


A no-TMS condition showed a leftward spatial bias ( pseudoneglect ) for near space judgments but not for far space and was used as the baseline .


Precuneus stimulation resulted in rightward spatial bias from the midpoint in near space similar to the rPPC neglect-like effect .


No significant effects were seen with vertex stimulation .


This study shows that precuneus , like other parietal areas , is involved in visuospatial functions .


Further work is required to clarify how the contribution of this area differs from other parietal regions .


To determine whether Care Navigation ( CN ) , a nurse-led hospital-based coordinated care intervention , reduced the use of hospital services and improved quality of life for patients with chronic illness .


Randomised controlled trial ; participants were allocated to CN or standard care .


Patients with chronic illness presenting to the emergency department of Nepean Hospital , Sydney , New South Wales .


High-risk status for an unplanned admission was defined as i ) three or more unplanned hospital admissions in 12 months for patients aged 70 or at least one admission for cardiac or respiratory disease in patients aged 16-69 years ; or ii ) judged by a CN nurse to be high risk and likely to benefit .


Numbers of re-presentations or readmissions , quality of life , time to re-presentation , readmission or death , length of stay , and access to hospital and community health services .


500 participants were randomised between May 2010 and February 2011 ; 359 by previous unplanned admission and 141 by clinical impression .


The CN group received more community health services ( rate ratio , 1.94 ; 95 % CI , 1.35-2 .81 ; P < 0.001 ) than participants receiving standard care ; however , this did not result in statistically significant differences in number of re-presentations ( rate ratio , 0.83 ; 95 % CI , 0.68-1 .01 ; P = 0.07 ) , number of readmissions ( rate ratio , 0.85 ; 95 % CI , 0.70-1 .04 ; P = 0.11 ) , quality of life at 24 months ( mean difference , 0 ; 95 % CI , -0.10 to 0.09 , P = 0.93 ) , or other measures .


CN did not improve quality of life or reduce unplanned hospital presentations or admissions despite community health services almost doubling .


Future service development should explore potential benefits of linking navigated intrahospital care to ongoing , proactive care planning and delivery in the community .


ACTRN12609000554268 .


For people with chronic low back pain , does Kinesio Taping , applied according to the treatment manual to create skin convolutions , reduce pain and disability more than a simple application without convolutions ?


Randomised trial with concealed allocation , intention-to-treat analysis and blinded assessment of some outcomes .


148 participants with chronic non-specific low back pain .


Experimental group participants received eight sessions ( over four weeks ) of Kinesio Taping applied according to the Kinesio Taping Method treatment manual ( ie , 10 to 15 % tension applied in flexion to create skin convolutions in neutral ) .


Control group participants received eight sessions ( over four weeks ) of Kinesio Taping with no tension , creating no convolutions .


The primary outcome measures were pain intensity and disability after the four-week intervention .


Secondary outcomes were pain intensity and disability 12 weeks after randomisation , and global perceived effect at both four and 12 weeks after randomisation .


Applying Kinesio Tape to create convolutions in the skin did not significantly change its effect on pain ( MD-0 .4 points , 95 % CI-1 .3 to 0.4 ) or disability ( MD-0 .3 points , 95 % CI-1 .9 to 1.3 ) at four weeks .


There was a small difference in favour of the experimental group for the secondary outcome of global perceived effect ( MD 1.4 points , 95 % CI 0.3 to 2.5 ) at four weeks .


No significant between-group differences were observed for the other secondary outcomes .


Kinesio Taping applied with stretch to generate convolutions in the skin was no more effective than simple application of the tape without tension for the outcomes measured .


These results challenge the proposed mechanism of action of this therapy .


Brazilian Registry of Clinical Trials , RBR-7ggfkv .


The estimation of effect size in clinical trials commonly disregards recurrent outcomes .


We investigated the effectiveness of a complex intervention on recurrent outcomes in patients with type 2 diabetes .


In the Diabetes Care in General Practice ( DCGP ) randomised controlled trial , 1,381 patients newly diagnosed with type 2 diabetes were randomised to 6 years of structured personal care or routine care ( ClinicalTrials.gov NCT01074762 ) .


The trial had 19 years of registry-based follow-up and was analysed with Cox regression models .


Repeated occurrences in the same patient of outcomes ( any diabetes-related endpoint , myocardial infarction [ MI ] , stroke , peripheral vascular disease and microvascular disease ) were accounted for with the Wei , Lin and Weissfeld method .


As previously shown , the intervention reduced the rates of first occurrence of both MI and any diabetes-related endpoint .


However , for all outcomes , the HR for a second event showed a statistically non-significant tendency to be increased .


We estimated a combined HR for all marginal failure times , regardless of whether they were first , second or later events .


This showed that the intervention had no effect on the rate of any of the outcomes , including MI ( HR 0.89 , 95 % CI 0.76 , 1.05 ) and any diabetes-related endpoint ( HR 0.98 , 95 % CI 0.87 , 1.09 ) .


In the DCGP study , a smaller proportion of patients who received structured care experienced a first occurrence of MI or any diabetes-related endpoint compared with patients who received routine care .


However , the patients who received structured care tended to experience more recurrent outcomes , so the total outcome rate was not affected by the intervention .


This study sought to report additional safety results from the ROCKET AF ( Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ) .


The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding ( principal safety endpoint ) with rivaroxaban and warfarin .


The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared , and factors associated with major bleeding were examined in a multivariable model .


The principal safety endpoint was similar in the rivaroxaban and warfarin groups ( 14.9 vs. 14.5 events/100 patient-years ; hazard ratio : 1.03 ; 95 % confidence interval : 0.96 to 1.11 ) .


Major bleeding risk increased with age , but there were no differences between treatments in each age category ( < 65 , 65 to 74,75 years ; pinteraction = 0.59 ) .


Compared with those without ( n = 13,455 ) , patients with a major bleed ( n = 781 ) were more likely to be older , current/prior smokers , have prior gastrointestinal ( GI ) bleeding , mild anemia , and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack .


Increasing age , baseline diastolic blood pressure ( DBP ) 90 mm Hg , history of chronic obstructive pulmonary disease or GI bleeding , prior acetylsalicylic acid use , and anemia were independently associated with major bleeding risk ; female sex and DBP < 90 mm Hg were associated with a decreased risk .


Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding .


Age , sex , DBP , prior GI bleeding , prior acetylsalicylic acid use , and anemia were associated with the risk of major bleeding .


( An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation : NCT00403767 ) .


To compare the efficacy of laryngeal mask airway-Supreme ( TM ) versus common laryngeal mask airway in children with general anesthesia .


With local research ethics committee 's approval and written informed parental consent , 100 children were randomly divided into groups L ( size 2.0 common laryngeal mask airway ) and S ( size 2.0 laryngeal mask airway-Supreme ( TM ) ) according to random number ( n = 50 each ) .


After anesthesia induction , a common laryngeal mask airway or laryngeal mask airway-Supreme ( TM ) was inserted and mechanically ventilated .


Time and ease for insertion , insertion success rate , airway leak pressure , success rate and ease of disposal sputum collecting tube insertion in group S , quality of airway during anesthetic maintenance , abdominal circumference changes and complications within 24 h post-operation were measured .


Compared with group L , abdominal circumference increased less in group S ( 0.90 0.35 vs 0.43 0.18 cm , n = 46 , P < 0.01 ) .


No significant inter-group differences existed for other measurements .


Disposal sputum collecting tube was successfully placed in group S ( 100 % ) .


In children with mechanical ventilation , laryngeal mask airway-Supreme ( TM ) can be effectively applied to maintain a good airway .


And the incidence of gastric insufflation is lower .


It is particularly useful for those requiring evacuation of gastric contents during general anesthesia .


The purpose of this trial was to evaluate crestal bone level changes radiographically in a standardized fashion over a period of 12 months in humans for implants with a 0.7-mm machined collar ( implant type A ) versus type B implants with a 1.5-mm machined collar .


Twenty-five patients with multiple missing teeth in posterior sectors were randomly assigned to one of the two groups : A ( 0.7-mm machined-collar implants ) or B ( 1.5-mm machined-collar implants ) .


Changes at crestal bone level were assessed by measuring the shoulder-crest distance ( SCD ) on the mesial and distal aspects of each implant on customized periapical radiographs , which were taken on the day of surgery and 3 , 6 , and 12 months after surgery .


Eighty-one implants were included in the study .


Mean SCD was 0.54 0.53 mm at baseline and 1.49 0.40 mm after 12 months .


For 0.7-mm-collar implants , mean SCD was 1.40 0.39 mm , while it was 1.56 0.40 mm for 1.5-mm-collar implants .


Statistically significant differences were found only between the two types of implants for distal measurements at 3 and 12 months after placement .


Both 0.7 - and 1.5-mm machined-collar implants can be used with predictable results , as changes in peri-implant crestal bone levels are similar for both implant types and do not seem to be significant from a clinical point of view .


The SCD may well depend more on the location of the abutment-implant interface than on machined-collar height .


To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development 's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial ( SUPPORT ) , using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure ( CPAP ) vs intubation/surfactant .


The Breathing Outcomes Study , a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial , assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age ( CA ) .


Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention .


One or more interviews were completed for 918 of the 922 eligible infants .


The incidences of wheezing and cough were 47.9 % and 31.0 % , respectively , and did not differ between the study arms of either randomized intervention .


Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity ( except for croup and treatment with oxygen or diuretics at home ) .


Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold ( 28.9 % vs 36.5 % ; P < .05 ) , respiratory illnesses diagnosed by a doctor ( 47.7 % vs 55.2 % ; P < .05 ) , and physician or emergency room visits for breathing problems ( 68.0 % vs 72.9 % ; P < .05 ) by 18-22 months CA .


Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA .


Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates .


To evaluate whether a polyethylene total body wrapping ( covering both the body and head ) is more effective than conventional treatment ( covering up to the shoulders ) in reducing perinatal thermal losses in very preterm infants .


This was a multicenter , prospective , randomized , parallel 1:1 , unblinded , controlled trial of infants < 29 weeks ' gestation age , comprising two study groups : experimental group ( total body group ; both the body and head covered with a polyethylene occlusive bag , with the face uncovered ) and control group ( only the body , up to the shoulders , covered with a polyethylene occlusive bag ) .


The primary outcome was axillary temperature on neonatal intensive care unit admission immediately after wrap removal .


One hundred randomly allocated infants ( 50 in the total body group and 50 controls ) completed the study .


Mean axillary temperature on neonatal intensive care unit admission was similar in the two groups ( 36.50.6 C total body vs 36.40.8 C controls ; P = .53 ) .


The rate of moderate hypothermia ( temperature < 36C ) was 12 % in the total body group and 20 % in the control group ( P = .41 ) .


Three subjects in each group ( 6.0 % ) had an axillary temperature > 37.5 C on admission , and one subject in control group had an axillary temperature > 38C .


Total body wrapping is comparable with covering the body up to the shoulders in preventing postnatal thermal losses in very preterm infants .


Available preclinical and phase 2 clinical data suggest that the addition of cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor ( EGFR ) , to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer ( NSCLC ) .


We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy .


In this unmasked , open-label randomised phase 3 trial we enrolled patients with metastatic , unresectable , or locally advanced NSCLC from 121 sites in Canada and the USA .


Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen .


Initially , patients were randomly assigned to receive either pemetrexed ( 500 mg/m ( 2 ) ) or docetaxel ( 75 mg/m ( 2 ) ) and then randomly assigned within each group to receive their chemotherapy with or without cetuximab ( 400 mg/m ( 2 ) at first dose and 250 mg/m ( 2 ) weekly thereafter ) until disease progression or unacceptable toxicity .


However , after a change in the standard of care , investigators chose whether to treat with pemetrexed or docetaxel on a patient-by-patient basis .


The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed , on an intention-to-treat basis .


This study is registered with ClinicalTrials.gov , number NCT00095199 .


Between Jan 10 , 2005 , and Feb 10 , 2010 , we enrolled 939 patients ; data for one patient was accidentally discarded .


Of the remaining 938 patients , 605 received pemetrexed ( 301 patients with cetuximab and 304 alone ) and 333 received docetaxel ( 167 in combination with cetuximab and 166 alone ) .


Median progression-free survival with cetuximab plus pemetrexed was 29 months ( 95 % CI 27-32 ) versus 28 months ( 25-33 ) with pemetrexed ( HR 103 , 95 % CI 087-121 ; p = 076 ) .


The most common grade 3-4 adverse events with cetuximab plus pemetrexed were fatigue ( 33 [ 11 % ] of 292 patients ) , acneiform rash ( 31 [ 11 % ] ) , dyspnoea ( 29 [ 10 % ] ) , and decreased neutrophil count ( 28 [ 10 % ] ) , and with pemetrexed alone were dyspnoea ( 35 [ 12 % ] of 289 patients ) , decreased neutrophil count ( 26 [ 9 % ] ) , and fatigue ( 23 [ 8 % ] ) .


A significantly higher proportion of patients in the cetuximab plus pemetrexed group ( 119 [ 41 % ] of 292 patients ) experienced at least one serious adverse event than those patients in the pemetrexed group ( 85 [ 29 % ] of 289 patients ; p = 00054 ) .


Nine ( 3 % ) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five ( 2 % ) of 289 treated patients in the pemetrexed alone group .


The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy .


Eli Lilly and Company and ImClone Systems LLC , a wholly owned subsidiary of Eli Lilly and Company .


Some studies suggest better overall outcomes when right unilateral electroconvulsive therapy ( RUL ECT ) is given with an ultrabrief , rather than brief , pulse width .


The aim of the study was to test if ultrabrief-pulse RUL ECT results in less cognitive side effects than brief - pulse RUL ECT , when given at doses which achieve comparable efficacy .


One hundred and two participants were assigned to receive ultrabrief ( at 8 times seizure threshold ) or brief ( at 5 times seizure threshold ) pulse RUL ECT in a double-blind , randomized controlled trial .


Blinded raters assessed mood and cognitive functioning over the ECT course .


Efficacy outcomes were not found to be significantly different .


The ultrabrief group showed less cognitive impairment immediately after a single session of ECT , and over the treatment course ( autobiographical memory , orientation ) .


In summary , when ultrabrief RUL ECT was given at a higher dosage than brief RUL ECT ( 8 versus 5 times seizure threshold ) , efficacy was comparable while cognitive impairment was less .


We compared the effects of intravenous lidocaine ( IVL ) with lumbar epidural lidocaine analgesia ( LEA ) on pain and ileus after open colonic surgery .


Between December 2011 and February 2013 , 60 patients were randomly allocated to IVL , LEA , or control group .


The IVL group received intraoperatively lidocaine 2 % intravenously ( 1.5 mg/kg bolus , 2 mg/kg/h infusion ) and normal saline ( NS ) epidurally .


The LEA group received lidocaine epidurally ( 1.5 mg/kg bolus , 2 mg/kg/h infusion ) and NS intravenously .


The control group received NS both intravenously and epidurally , as bolus and infusion .


All NS volumes were calculated as if containing lidocaine 2 % at the aforementioned doses .


We assessed pain intensity at rest/cough at 1 , 2 , 4 , 12 , 24 , and 48 h postoperatively ( numerical rating scale 0-10 ) , 48-h analgesic consumption , and time to first flatus passage .


Data from 60 patients ( 20 per group ) were analyzed .


The IVL group had significantly lower pain scores at rest and cough compared to LEA or control group only at 1 , 2 , and 4 h postoperatively ( P < 0.005 for all comparisons ) .


The 48-h analgesic requirements and time to first flatus passage did not differ significantly between IVL group and LEA or control group ( P > 0.05 ) .


Compared with LEA-lidocaine or placebo , intravenous lidocaine offered no clinically significant benefit in terms of analgesia and bowel function .


To compare patient satisfaction between telemedicine and in-person follow-up appointments for orthopedic trauma .


Prospective randomized controlled trial ( pilot study ) .


Level I trauma center .


Twenty-four patients were enrolled and randomized into 2 groups .


Eight patients who had telemedicine follow-up appointments and 9 who had in-person follow-up visits were included in a per-protocol analysis .


In the telemedicine group , 2 patients left the study because of nonadherence , 1 patient withdrew because of a weak Internet connection , and 1 patient sustained an open fracture .


Three control patients left the study because of nonadherence .


The patients had 4 follow-up appointments during a 6-month period .


Patients either had their 6-week and 6-month follow-ups through video calls or in the clinic .


After 6-week and 6-month follow-up appointments , the patients were given survey questions that were developed using literature-supported methods to compare follow-up experiences .


The patients were monitored for complications .


There was no significant difference in patient satisfaction between telemedicine and in-person clinic visits ( telemedicine : 89 % satisfied ; control : 100 % satisfied ; P = 0.74 ) .


Zero percent of patients in the telemedicine group took time off their work for their appointment compared with 55.6 % in the control ( P = 0.03 ) .


Telemedicine patients spent significantly less time on their visits ( P = 0.01 ) .


The majority of the patients in the telemedicine group reported clear visual ( 87.5 % ) and sound quality ( 100 % ) through and agreed to future follow-up visits through telemedicine ( 75.0 % ) .


One patient in each group developed complications .


Telemedicine may be a viable alternative to some in-person clinic visits because of similar measures of patient satisfaction but with significantly less time and distance traveled .


Therapeutic level II .


See Instructions for authors for a complete description of levels of evidence .


Chronic hepatitis B ( CHB ) is a major public health concern , particularly in endemic areas like Asia-Pacific .


Sustained virologic suppression correlates with regression of histologic fibrosis and cirrhosis .


This study evaluated efficacy and safety of tenofovir disoproxil fumarate ( TDF ) in Asian patients through 240 weeks of treatment .


Post hoc analysis of the Asian subpopulation from two phase 3 clinical studies was performed .


Following a 48-week randomized , double-blind evaluation of once-daily TDF versus once-daily adefovir dipivoxil , open-label TDF for up to 240 weeks was evaluated .


Patients with both baseline and week 240 liver biopsies were evaluated for histologic changes .


At baseline , 189/641 ( 29 % ) patients randomized were Asian .


Sixty-eight percent of Asian patients were male ; 50 % were hepatitis B e antigen ( HBeAg ) - positive .


At week 240 , similar proportions of Asian ( 88 % ) and non-Asian ( 87 % ) patients demonstrated improvement in liver histology , and 19/22 ( 86 % ) Asian patients with baseline cirrhosis were no longer cirrhotic .


By modified intent-to-treat analysis , 74 % of Asian patients and 76 % of non-Asian patients had HBV DNA < 400 copies/mL at the end of week 240 ( P = 0.602 ) .


No differences were seen in HBeAg loss or seroconversion in Asian versus non-Asian patients .


No Asian patient experienced hepatitis B surface antigen loss .


Safety and tolerability of TDF through week 240 , including changes in renal function and in hip/spine bone mineral density ( from weeks 192 to 240 ) , were comparable between Asian and non-Asian patients .


Long-term virologic and histologic efficacy and safety of TDF are comparable in Asian and non-Asian CHB patients .


To study the effect of exogenous i.m. glucagon on recovery from controlled insulin-induced hypoglycaemia in patients with type 2 diabetes treated with the novel glucokinase activator AZD1656 , in combination with metformin .


This was a single-centre randomized , open , two-way crossover phase I , automated glucose clamp ( Biostator ( ) ; Life Science Instruments , Elkhart , MD , USA ) study ( NCT00817271 ) in eight patients ( seven men and one woman , mean age 58.6 years , body mass index 28.1 kg/m ( 2 ) ) .


All patients received a stable dose of metformin twice daily , ranging from 1000 to 2250 mg .


A 2-day titration phase commenced with 40 mg AZD1656 twice daily , escalating to 80 mg twice daily if tolerated .


This was followed by a single dose of 80 or 160 mg AZD1656 , administered on days 5 and 8 when metabolic studies were performed .


After an overnight fast on days 5 and 8 , controlled hypoglycaemia was induced using an exogenous i.v. infusion of insulin .


Plasma glucose was lowered in a stepwise fashion over 3 h to attain a target nadir of 2.7 mmol/l .


This was sustained for 30 min , at the end of which the hypoglycaemic clamp was released .


In random sequence , patients either received an i.m. injection of 1 mg glucagon or were allowed to recover from hypoglycaemia by endogenous counter-regulation .


To avoid prolonged hypoglycaemia , a reverse glucose clamp was applied from 4 to 6 h post-dose .


Three patients received 40 mg AZD1656 twice daily and five patients 80 mg twice daily .


Mean plasma glucose at 20 min after release of the hypoglycaemic clamp was significantly lower ( 3.1 0.3 mmol/l ) for AZD1656 alone than for AZD1656 + glucagon ( 4.9 0.8 mmol/l ; p < 0.001 between the groups ) .


Catecholamine and cortisol responses were similar on the AZD1656 + glucagon and AZD alone study days .


Growth hormone response was 18 % lower for AZD1656 alone ( p = 0.01 ) , consistent with the effect of a pharmacological dose of glucagon on growth hormone secretion .


No safety or tolerability concerns were observed during treatment with AZ1656 .


Exogenous glucagon was effective as a rescue treatment for hypoglycaemia induced during treatment with AZD1656 , given in combination with metformin in patients with type 2 diabetes .


Retrograde intrarenal surgery ( RIRS ) involves a minimally invasive stone surgery , lending itself potential to combined spinal-epidural anesthesia ( CSEA ) , although it is performed preferably under general anesthesia ( GA ) .


This prospective randomized study was undertaken to evaluate the feasibility and efficacy of CSEA for patients undergoing RIRS .


Seventy consecutive patients who were scheduled for RIRS were randomized to receive CSEA ( n = 35 ) or GA ( n = 35 ) .


Operative time , stone clearance rate , visual analog scale ( VAS ) of pain , complication rate , anesthetic cost , and hospital stay were compared between the two groups .


A total of 65 patients randomized to CSEA ( 31 ) or GA ( 34 ) completed the study .


In the CSEA group , each procedure was completed and there was no anesthetic conversion .


Although based on the prospective randomized method , the GA group still had a little larger stone size ( p = 0.059 ) and more multiple caliceal stones ( p = 0.037 ) .


Overall , there were no statistically significant differences in operative time ( p = 0.088 ) , stone fragmentation time ( p = 0.074 ) , postoperative VAS pain score at 6 and 24 hours ( p = 0.156 , 0.146 ) , incidence of complications ( p = 0.870 ) , stone-free rate ( p = 0.804 ) , and hospital stays ( p = 0.907 ) between the two groups .


The patients in the GA group experienced a higher mean hemoglobin drop ( 6.53.2 vs 8.62.7 g/L , p = 0.012 ) .


In addition , the anesthetic cost was much cheaper in the CSEA group ( 183.831.4 vs 391.959.1 dollars , p < 0.001 ) .


RIRS with CSEA can be completed with no anesthetic conversions and with the same efficacy and safety compared with GA. .


When considering economical aspects , CSEA appears to be a preferable alternative to GA for the patient whose general health status permits it .


Progesterone is effective treatment for hot flushes/night sweats .


The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection .


We compared the effects of progesterone to placebo on endothelial function , weight , blood pressure , metabolism , lipids , inflammation and coagulation .


We conducted a randomized , double-blind , 3-month placebo-controlled trial of progesterone ( 300 mg daily ) among 133 healthy postmenopausal women in Vancouver , Canada from 2003-2009 .


Endothelial function by venous occlusion plethysmography was a planned primary outcome .


Enrolled women were 1-11 y since last menstruation , not using hormones ( for > 6 months ) , non-smoking , without diabetes , hypertension , heart disease or their medications .


Randomized ( 11 ) women ( 55 4 years , body mass index 25 3 ) initially had normal blood pressure , fasting lipid , glucose and electrocardiogram results .


Endothelial function ( % forearm blood flow above saline ) was not changed with progesterone ( 487 189 % , n = 18 ) compared with placebo ( 408 278 % , n = 16 ) ( 95 % CI diff [ -74 to 232 ] , P = 0.30 ) .


Progesterone ( n = 65 ) and placebo ( n = 47 ) groups had similar changes in systolic and diastolic blood pressure , resting heart rate , weight , body mass index , waist circumference , total cholesterol , low-density lipoprotein cholesterol and triglyceride levels .


High-density lipoprotein was lower ( -0.14 mmol/L , P = 0.001 ) on progesterone compared with placebo .


Fasting glucose , hs-C-reactive protein , albumin and D-dimer changes were all comparable to placebo .


Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo .


Results indicate that progesterone has short-term cardiovascular safety .


Endothelial function , weight , blood pressure , waist circumference , inflammation and coagulation were unchanged as were lipids except for HDL-C .


The statistically significant decrease in HDL-C levels was not clinically important ( based on lack of Cardiovascular Risk Profile change ) .


ClinicalTrials.gov NCT00152438 .


Fluralaner ( Bravecto ; Merck/MSD Animal Health ) is a novel systemic ectoparasiticide for dogs providing long-acting flea and tick control after a single oral dose .


Milbemycin oxime and praziquantel are routinely used to control Dirofilaria immitis and intestinal worm infections in dogs .


The safety of concurrent use of fluralaner and a commercially available milbemycin oxime plus praziquantel combination tablet , in particular with regard to gastrointestinal symptoms , was investigated using oral doses at or above the maximum recommended rates .


Some minor and transient clinical findings were observed during the study period ; however , none of these was considered to be related to concurrent treatment with fluralaner and milbemycin oxime plus praziquantel , or to the use of either product alone .


Concurrent treatment with fluralaner , milbemycin oxime and praziquantel is well tolerated in dogs .


Afterschool programs can be health-promoting environments for children .


Written policies positively influence nutrition and physical activity ( PA ) environments , but effective strategies for building staff capacity to write such policies have not been evaluated .


This study measures the comprehensiveness of written nutrition , PA , and screen time policies in afterschool programs and assesses impact of the Out of School Nutrition and Physical Activity ( OSNAP ) intervention on key policies .


Twenty afterschool programs in Boston , MA participated in a group-randomized , controlled trial from September 2010 to June 2011 .


Intervention program staff attended learning collaboratives focused on practice and policy change .


The Out-of-School Time ( OST ) Policy Assessment Index evaluated written policies .


Inter-rater reliability and construct validity of the measure and impact of the intervention on written policies were assessed .


The measure demonstrated moderate to excellent inter-rater reliability ( Spearman 's r = 0.53 to 0.97 ) and construct validity .


OSNAP was associated with significant increases in standards-based policy statements surrounding snacks ( +2.6 , p = 0.003 ) , beverages ( +2.3 , p = 0.008 ) , screen time ( +0.8 , p = 0.046 ) , family communication ( +2.2 , p = 0.002 ) , and a summary index of OSNAP goals ( +3.3 , p = 0.02 ) .


OSNAP demonstrated success in building staff capacity to write health-promoting policy statements .


Future research should focus on determining policy change impact on practices .


Nut consumption has been found to decrease risk of coronary heart disease and diabetes and to promote healthy body weights possibly related to their favorable macronutrient profile .


We therefore assessed the effect of pistachios on postprandial glucose and insulin levels , gut hormones related to satiety and endothelial function .


In this randomized crossover study , 20 subjects with metabolic syndrome consumed five study meals over 5-10 weeks .


The meals differed in fat type and quantity , but were matched according to available carbohydrates ( CHOs ) .


Three meals had 50 g available CHO : white bread ( WB50g ) , white bread , butter and cheese ( WB+B+C h ) and white bread and pistachios ( WB+P ) .


Two meals had 12 g available CHO : white bread ( WB12g ) and pistachios ( P ) .


Within each group of available CHO meals , postprandial glucose levels were the highest following the white bread-only meals , and glucose response was significantly attenuated when butter and cheese or pistachios were consumed ( P < 0.05 ) .


Postprandial insulin levels were highest after the WB+B+C h meal ( P < 0.05 ) , but did not differ between the white bread-only and pistachio meals .


Both endothelial function ( reactive hyperemia index ) and arterial stiffness ( augmentation index ) significantly increased after the white bread-only meals compared with the WB+B+C h meal ( all P < 0.05 ) .


Insulin secretagogue levels were higher when butter and cheese or pistachios were consumed than when white bread only was consumed ( P < 0.05 ) .


Compared with white bread , pistachio consumption reduced postprandial glycemia , increased glucagon-like-peptide levels and may have insulin-sparing properties .


These effects could be beneficial for individuals with diabetes and metabolic syndrome .


Bevacizumab prolongs progression-free survival ( PFS ) in patients with metastatic colorectal cancer .


We analysed the protein expression levels of vascular endothelial growth factor ( VEGF ) ligands and receptors to determine their prognostic and predictive effects .


We graded expression of VEGF-A , VEGF-B , VEGF-C , VEGF-D , VEGF-R1 , and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine ( C ) , capecitabine and bevacizumab ( CB ) , or CB and mitomycin ( CBM ) in the MAX trial and extended the analysis to the CAIRO-2 population .


Patients with low expression of VEGF-D ( 0 , 1 ) benefited from bevacizumab treatment ( PFS hazard ratio ( HR ) ( C vs CBCBM ) , 0.21 ; 95 % CI , 0.080.55 ; overall survival ( OS ) HR , 0.35 ; 95 % CI , 0.130.90 ) .


Patients with higher VEGF-D expression received less benefit ( VEGF-D 2 PFS HR , 0.67 ; 95 % CI , 0.451.00 ; OS HR , 0.82 ; 95 % CI , 0.521.30 ; VEGF-D 3 PFS HR , 0.77 ; 95 % CI , 0.501.17 ; OS HR , 1.28 ; 95 % CI , 0.792.09 ) ( P interaction o0 .05 ) .


In CAIRO-2 , there was no difference in PFS or OS according to VEGF-D expression .


The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used .


Further evaluation is required before clinical utilisation .


Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality .


Cardiac structure and function were assessed by echocardiography in a blinded core laboratory at baseline in 935 patients with heart failure with preserved ejection fraction ( left ventricular ejection fraction 45 % ) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist ( TOPCAT ) trial and related to the primary composite outcome of cardiovascular death , heart failure hospitalization , or aborted cardiac arrest , and its components .


At a median follow-up of 2.9 years , 244 patients experienced the primary outcome .


Left ventricular hypertrophy ( adjusted hazard ratio , 1.52 ; 95 % confidence interval , 1.16-2 .00 ) , elevated left ventricular filling pressure ( E/E ' ; adjusted hazard ratio 1.05 per 1 integer increase ; 95 % confidence interval , 1.02-1 .07 ) , and higher pulmonary artery pressure assessed by the tricuspid regurgitation velocity ( hazard ratio , 1.23 per 0.5 m/s increase ; 95 % confidence interval , 1.02-1 .49 ) were associated with the composite outcome and heart failure hospitalization alone after adjusting for clinical and laboratory variables .


The risk of adverse outcome associated with left ventricular hypertrophy was additive to the risk associated with elevated E/E ' .


Among heart failure with preserved ejection fraction patients enrolled in TOPCAT , left ventricular hypertrophy , higher left ventricular filling pressure , and higher pulmonary artery pressure were predictive of heart failure hospitalization , cardiovascular death , or aborted cardiac arrest independent of clinical and laboratory predictors .


These features , both alone and in combination , identify heart failure with preserved ejection fraction patients at particularly high risk for cardiovascular morbidity and mortality .


http://www.clinicaltrials.gov .


Unique identifier : NCT00094302 .


The clinical benefits of bioimpedance spectroscopy ( BIS ) - guided fluid management in patients on hemodialysis have been widely demonstrated .


However , no previous reports have evaluated the effect of regular and serial BIS-guided fluid management on the residual renal function ( RRF ) in patients on peritoneal dialysis ( PD ) .


Therefore , we will evaluate the clinical efficacy of BIS-guided fluid management for preserving RRF and protecting cardiovascular events in patients on PD .


This is a multicenter , prospective , randomized controlled trial .


A total of 138 participants on PD will be enrolled and randomly assigned to receive either BIS-guided fluid management or fluid management based only on the clinical information for 1 year .


The primary outcome is the change in the glomerular filtration rate ( GFR ) between months 0 and 12 after starting treatment .


The secondary outcomes will include GFR at month 12 , time to the anuric state ( urine volume < 100 ml/day ) , and fatal and nonfatal cardiovascular events during treatment .


This is the first clinical trial to investigate the effect of BIS-guided fluid management on RRF and for protecting against cardiovascular events in patients on PD .


Clinical Trials.gov number NCT01887262 , June 24 , 2013 .


This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate ( 5 mg ) and calcitriol ( 0.5 g ) combined drug ( Maxmarvil , Yuyu Co. ) .


The study population consisted of 33 postmenopausal healthy female volunteers , aged 50 to 70 years ( mean age , 58 5 ) without gastrointestinal symptoms and with normal baseline endoscopic findings .


Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil ( n = 17 subjects ) or alendronate only ( n = 16 subjects ) .


Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule .


Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group .


Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group ; this difference was statistically significant .


The mucosal damage scores for the alendronate group ( total score 24 ) were significantly higher than those for the Maxmarvil group ( total score 9 ) in the esophagus and stomach .


Therefore , this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate , and may improve the tolerability of osteoporosis medication in clinical practice .


Although antidepressant drugs are used as first-line intervention to treat patients with generalized anxiety disorder ( GAD ) , only one-third of patients respond positively to treatment .


In our study , we investigated whether functional genetic polymorphisms in the dopamine active transporter 1 ( DAT1 ) and dopamine receptor D2 ( DRD2 ) may play a role in antidepressant treatment response in GAD .


We examined 156 patients diagnosed with GAD who received venlafaxine Extended-Release ( XR ) treatment as part of an 18-month relapse-prevention study to determine whether variation in these genes had an effect on treatment response after 6months of open-label treatment .


Genotypes were obtained for rs1076560 ( DRD2 ) , rs1800497 ( DRD2 ) , rs2550948 ( DAT1 ) , and a variable number tandem repeat in the 3 ' untranslated region of the DAT1 gene using standard methods .


Results show that none of the tested variants were associated with treatment response to venlafaxine XR in GAD .


Genotype and allele frequencies did not differ statistically significantly between responders and non-responders using either the Hamilton Anxiety or Clinical Global Impressions of Improvement Scale at 6months .


Although we detected no association in our sample , future studies using larger samples and more comprehensive gene coverage are needed to evaluate potential effects of dopaminergic variants on antidepressant treatment response in anxiety disorders .


In non-small-cell lung cancer , an exon 19 deletion and an L858R point mutation in the epidermal growth factor receptor ( EGFR ) are predictors of a response to EGFR-tyrosine kinase inhibitors .


However , it is uncertain whether other uncommon EGFR mutations are associated with sensitivity to EGFR-tyrosine kinase inhibitors .


A post-hoc analysis to assess prognostic factors was performed with the use of patients with EGFR mutations ( exon 19 deletion , L858R , G719X , and L861Q ) who were treated with gefitinib in the NEJ002 study , which compared gefitinib with carboplatin-paclitaxel as the first-line therapy .


In the NEJ002 study , 225 patients with EGFR mutations received gefitinib at any treatment line .


The Cox proportional hazards model indicated that performance status , response to chemotherapy , response to gefitinib , and mutation types were significant prognostic factors .


Overall survival ( OS ) was significantly shorter among patients with uncommon EGFR mutations ( G719X or L861Q ) compared with OS of those with common EGFR mutations ( 12 versus 28.4 months ; p = 0.002 ) .


In the gefitinib group ( n = 114 ) , patients with uncommon EGFR mutations had a significantly shorter OS ( 11.9 versus 29.3 months ; p < 0.001 ) .


By contrast , OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group ( n = 111 ; 22.8 versus 28 months ; p = 0.358 ) .


The post-hoc analyses clearly demonstrated shorter survival for gefitinib-treated patients with uncommon EGFR mutations compared with the survival of those with common mutations and suggest that the first-line chemotherapy may be relatively effective for non-small-cell lung cancer with uncommon EGFR mutations .


To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea .


In a prospective , open , randomized case-control study conducted at the Department of Ophthalmology , Ume University Hospital , Sweden , sixty eyes of 43 patients with progressive keratoconus aged 18-28 years planned for corneal crosslinking and corresponding age - and sex-matched control subjects were included .


The patients were randomized to conventional corneal crosslinking ( CXL ; n = 30 ) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment ( CRXL ; n = 30 ) .


Subjective refraction and ETDRS best spectacle-corrected visual acuity ( BSCVA ) , axial length measurement , keratometry and pachymetry were performed before and 1 and 6 months after treatment .


The keratoconus patients had poorer BSCVA , higher refractive astigmatism and higher keratometry readings than the control subjects at baseline ( p < 0.01 ) .


In the CXL group , BSCVA increased from 0.19 0.26 to 0.14 0.18 logMar ( p = 0.03 ) , and the spherical equivalent improved from -1.9 2.8 D to -1.4 2.4 D ( p = 0.03 ) .


Maximum keratometry readings decreased after CXL from 53.1 4.9 D to 52.6 5.2 D ( p = 0.02 ) , and the axial length decreased in the CXL group , likely due to post-treatment corneal thinning ( p = 0.03 ) .


In the CRXL group , all the above variables were unaltered ( p > 0.05 ) .


At 6 months , the refractive results from CRXL did not surpass those of conventional CXL treatment .


Rather , some variables indicated a slightly inferior effect .


Possibly , stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens .


Although coexisting obstructive sleep apnea ( OSA ) and Cheyne-Stokes respiration ( CSR ) occur frequently in patients with heart diseases , optimal treatment remains unclear .


Positive airway pressure ( PAP ) effectively treats OSA and adaptive servo-ventilation ( ASV ) has been shown to improve CSR .


We compared a new treatment algorithm combining automatic continuous positive airway pressure ( APAP ) and ASV ( anticyclic modulated ventilation , ACMV ) versus continuous positive airway pressure ( CPAP ) .


Thirty-nine patients ( 35 male , four female ; aged 65.59.7 years ; body mass index , 31.05.9 kg/m2 ) with underlying heart disease and coexisting OSA and CSR were enrolled .


After diagnostic polysomnography ( PSG ) and CPAP titration , patients were randomized either to CPAP or to ACMV for four weeks of treatment in a crossover design .


Total apnea-hypopnea index ( AHI ) was 49.018.8 / h at baseline , 12.314.6 / h with CPAP ( P < 0.001 vs baseline ) , and 3.75.6 / h with ACMV ( P < 0.001 vs. baseline and vs. CPAP ) .


Obstructive AHI was 20.714.4 / h at baseline , 5.19.3 / h with CPAP ( P < 0.001 vs. baseline ) , and 0.40.4 / h with ACMV ( P < 0.001 vs. baseline and vs. CPAP ) .


Central AHI was 28.313.4 / h at baseline , 7.29.7 / h with CPAP ( P < 0.001 vs baseline ) and 3.35.4 / h with ACMV ( P < 0.001 vs. baseline and vs. CPAP ) .


Ejection fraction was increased significantly ( from 38.615.6 to 44.412.2 % ) only with ACMV .


Subjective sleepiness significantly improved only with CPAP whereas objective sleep quality and treatment adherence were not different between both treatment modalities .


ACMV is an effective treatment option in patients with coexisting OSA and CSR .


It is superior to CPAP in reducing total AHI as well as obstructive and central AHI .


HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization ( FISH ) .


However , FISH probes do not target only the annotated gene , while chromosome 17 ( chr17 ) is among the most unstable chromosomes in breast cancer .


Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients .


Copy numbers ( CN ) for 14 genes on chr17 , 4 of which were within and 10 outside the core HER2 amplicon ( HER2 - and non-HER2-genes , respectively ) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials .


HER2-genes CN strongly correlated to each other ( Spearman 's rho > 0.6 ) and were concordant with FISH HER2 status ( Kappa 0.6697 for ERBB2 CN ) .


TOP2A CN were not concordant with TOP2A FISH status ( Kappa 0.1154 ) .


CN hierarchical clustering revealed distinct patterns of gains , losses and complex alterations in HER2 - and non-HER2-genes associated with IHC4 breast cancer subtypes .


Upon multivariate analysis , non-HER2-gene gains independently predicted for shorter disease-free survival ( DFS ) and overall survival ( OS ) in patients with triple-negative cancer , as compared to luminal and HER2-positive tumors ( interaction p = 0.007 for DFS and p = 0.011 for OS ) .


Similarly , non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy ( p = 0.004 for both DFS and OS ) .


Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes , as compared to those with 4 or more nodes ( p = 0.017 for DFS and p = 0.001 for OS ) .


TOP2A FISH and qPCR may not identify the same pathology on chr17q .


Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis .


Heart failure ( HF ) and chronic obstructive pulmonary disease ( COPD ) frequently coexist , with undefined prognostic and therapeutic implications .


We investigated clinical profile and outcomes of patients with chronic HF and COPD , notably the efficacy and safety of ivabradine , a heart rate-reducing agent .


6505 ambulatory patients , in sinus rhythm , heart rate 70 bpm and stable systolic HF were randomised to placebo or ivabradine ( 2.5 to 7.5 mg bid ) .


Multivariate Cox model analyses were performed to compare the COPD ( n = 730 ) and non-COPD subgroups , and the ivabradine and placebo treatment effects .


COPD patients were older and had a poorer risk profile .


Beta-blockers were prescribed to 69 % of COPD patients and 92 % of non-COPD patients .


The primary endpoint ( PEP ) and its component , hospitalisation for worsening HF , were more frequent in COPD patients ( HRs f , 1.22 [ p = 0.006 ] ; and 1.34 [ p < 0.001 ] ) respectively , but relative risk was reduced similarly by ivabradine in both COPD ( 14 % , and 17 % ) and non-COPD ( 18 % and 27 % ) patients ( p interaction = 0.82 , and 0.53 , respectively ) .


Similar effect was noted also for cardiovascular death .


Adverse events were more common in COPD patients , but similar in treatment subgroups .


Bradycardia occurred more frequently in ivabradine subgroups , with similar incidence in patients with or without COPD .


The association of COPD and HF results in a worse prognosis , and COPD represents a barrier to optimisation of beta-blocker therapy .


Ivabradine is similarly effective and safe in chronic HF patients with or without COPD , and can be safely combined with beta-blockers in COPD .


Although several eating disorder prevention programs reduce eating disorder risk factors and symptoms for female high school and college students , few efficacious prevention programs exist for female middle school students , despite the fact that body image and eating disturbances often emerge then .


Two pilot trials evaluated a new dissonance-based eating disorder prevention program for middle school girls with body image concerns .


Female middle school students with body dissatisfaction from two sites [ Study 1 : N = 81 , M age = 12.1 , standard deviation ( SD ) = 0.9 ; Study 2 : N = 52 , M age = 12.5 , SD = 0.8 ] were randomized to a dissonance intervention ( MS Body Project ) or educational brochure control ; Study 2 included a 3-month follow-up .


Intervention participants showed significant post-test reductions in only one of the six variables with both Studies 1 and 2 ( i.e. , pressure to be thin and negative affect , respectively ) , though post-test effect sizes suggested medium reductions in eating disorder risk factors and symptoms ( Study 1 : M d = .40 ; Study 2 : M d = .65 ) ; reductions at 3-month follow-up in Study 2 were not evident ( M d = .19 ) .


Results suggest that this new middle school version of the Body Project is producing medium magnitude reductions in eating disorder risk factors at post-test but that effects are showing limited persistence .


Continued refinement and evaluation of this intervention appears warranted to develop more effective prevention programs for this age group .


The aim of this study is to evaluate the effect of oral glutamine ( GL ) supplementation on gut permeability and endotoxemia ( surrogate end point ) in patients with severe acute pancreatitis .


In a randomized controlled trial , patients were randomized to be given placebo or GL for 7 days .


The primary outcome measures include the effect on gut permeability ( assessed by lactulose/mannitol excretion in urine and endotoxemia assessed by endotoxin core antibodies type IgG and IgM ( EndoCab IgG and IgM ) .


The secondary outcome measures include infectious complications , mortality , total hospital/intensive care unit stay , C-reactive protein , and prealbumin levels .


Patients were assigned to GL ( n = 41 ) and placebo ( n = 39 ) groups .


There was no change in gut permeability after the intervention .


However , the EndoCab IgM levels increased significantly ( 33 [ 4 , 175 ] to 40 [ 8 , 350 ] GMU/mL ; P = 0.0164 ) and the C-reactive protein levels decreased significantly ( 133 [ 1 , 287 ] to 88 [ 1 , 267 ] ng/mL ; P = 0.0236 ) in the GL group .


No difference was observed in infectious complication , prealbumin value , hospital/intensive care unit stay , and mortality in both groups .


No significant trend was identified for an effect of GL on gut permeability .


Decreased inflammation and endotoxemia did not translate into reduced infectious complications in severe acute pancreatitis .


However , the study was underpowered to detect the aforementioned difference ( trial registration : CTRI/2009/000945 ) .


Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the - opioid receptor combined with inhibition of neuronal norepinephrine reuptake .


Both mechanisms are implicated in activation of descending inhibitory pain pathways .


In this study , we investigated the influence of tapentadol on conditioned pain modulation ( CPM , an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus ) and offset analgesia ( OA , a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation ) .


Twenty-four patients with diabetic polyneuropathy ( DPN ) were randomized to receive daily treatment with tapentadol sustained-release ( SR ) [ average daily dose 433 ( 31 ) mg ] or placebo for 4 weeks .


CPM and OA were measured before and on the last day of treatment .


Before treatment , none of the patients had significant CPM or OA responses .


At week 4 of treatment , CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses .


CPM increased from 9.1 ( 5.4 ) % ( baseline ) to 14.3 ( 7.2 ) % ( placebo ) and 24.2 ( 7.7 ) % ( tapentadol SR , P < 0.001 vs placebo ) ; relief of DPN pain was also greater in patients treated with tapentadol than placebo ( P = 0.028 ) .


Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses ( P = 0.78 ) .


Tapentadol 's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses .


The study was registered at trialregister.nl under number NTR2716 .


To characterize the safety , tolerability , pharmacokinetics ( PK ) and dose proportionality of mipomersen after single subcutaneous ( SC ) administration to Japanese healthy subjects ; and to compare the PK profiles of Japanese and Western subjects .


20 healthy first-generation Japanese male subjects were enrolled into one of three treatment cohorts ( 50 , 100 and 200 mg SC ) in a dose-escalation design .


Within each cohort , subjects were randomized in a 4 : 1 ratio to receive mipomersen or placebo .


Mipomersen was absorbed rapidly after SC administration ; median tmax varied between 2 and 3 hours .


After reaching peak levels , plasma concentrations of mipomersen decayed multiphasically with an initial distribution t1/2 in several hours and a terminal t1/2 of 261 - 393 hours .


Mean Cmax increased in a dose-linear manner while all mean AUC from time 0 to different cut points increased slightly more than dose proportionally .


Although mean terminal t1/2 varied in the dose range tested , it did not show dose-dependence .


The PK profiles of mipomersen in Japanese subjects are similar to those observed in Western subjects .


A single SC dose of 50 mg , 100 mg and 200 mg mipomersen was well tolerated by male Japanese subjects .


Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects .


Comparison of PK between Japanese and Western subjects does not support any need for dose adjustment in Japanese population in future clinical development .


The granisetron transdermal system ( GTS ) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting ( CINV ) during multiday chemotherapy .


We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy ( MEC ) .


A total of 276 patients were randomized into GTS ( n = 139 , one patch on days 1-4 ) or control group ( n = 137 , intravenous on day 1 and oral on days 2-4 ) .


The primary endpoint was the percentage of patients achieving complete response ( CR ) from chemotherapy initiation until 24 h after the final administration .


Out of 234 patients ( 112 in GTS and 122 in control group ) included in the per protocol analysis , 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy .


The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients ; 74.6 % of the patients in the control group achieved CR ( 95 % confidence interval -10.73 to 11.55 % ) .


The CR rate did not change after subgroup analyses by sex , age , and chemotherapy naivety and analysis per day and overall days of treatment .


The GTS group showed sustained CR from day 1 to day 4 .


Patients ' satisfaction , assessed using Functional Living Index-Emesis ( FLI-E ) , showed no difference .


Both treatments were well tolerated and safe .


The GTS showed non-inferior efficacy to intravenous and oral granisetron .


The safety , tolerability , and FLI-E scores of the GTS were comparable to those of control group .


The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC .


The Creighton Model FertilityCare System ( CrMS ) teaches women to identify days when intercourse is likely to result in pregnancy .


We sought to assess the impact of the CrMS on time to pregnancy ( TTP ) , via per-cycle pregnancy rates ( fecundability ) .


We conducted a parallel randomised trial at the University of Utah School of Medicine , 2003-06 .


Women ages 18-35 years , in a relationship of proven fertility , who desired to conceive , were block-randomised and stratified for age , with allocation concealment by opaque sequentially numbered sealed envelopes .


The control group received the advice to have intercourse 2-3 times per week , and the intervention group received CrMS instruction .


All women were asked to begin trying to conceive starting the second cycle in the study and were followed actively up to seven cycles , without blinding of research personnel .


We calculated descriptive statistics and fecundability , and estimated Cox models for TTP .


( Clinicaltrials.gov NCT00161395 ) .


There were 143 women randomised : 71 to the control group ( all analysed ) and 72 to the CrMS group ( 69 analysed ) .


The adjusted hazard ratio for the influence of CrMS on TTP was 0.86 [ 95 % confidence interval ( CI ) : 0.53 , 1.38 ] .


Fecundability in cycles with intent to conceive was 31 % in controls and 36 % with CrMS ( P = 0.32 ) .


By the first cycle , fecundability was 17 % in controls , and 4 % with CrMS ( P = 0.02 ) .


No adverse events were reported .


We found no significant impact of CrMS on TTP or fecundability , but fewer of the women receiving CrMS conceived by the first cycle .


Migraine is a highly disabling disease affecting a significant proportion of the Australian population .


The methylenetetrahydrofolate reductase ( MTHFR ) C677T variant has been associated with increased levels of homocysteine and risk of migraine with aura ( MA ) .


Folic acid ( FA ) , vitamin B6 , and B12 supplementation has been previously shown to reduce increased levels of homocysteine and decrease migraine symptoms .


However , the influence of dietary folate intake on migraine has been unclear .


The aim of the current study was to analyze the association of dietary folate intake in the form of dietary folate equivalent , FA , and total food folate ( TFF ) on migraine frequency , severity , and disability .


A cohort of 141 adult females of Caucasian descent with MA was genotyped for the MTHFR C677T variant using restriction enzyme digestion .


Dietary folate information was collected from all participants and analyzed using the `` FoodWorks '' 2009 package .


Folate consumption was compared with migraine frequency , severity , and disability using linear regression .


A significant inverse relation was observed between dietary folate equivalent ( R ( 2 ) = 0.201 , B = -0.002 , P = .045 , 95 % confidence interval [ CI ] [ -0.004 , -0.001 ] ) and FA ( R ( 2 ) = 0.255 , B = -0.005 , P = .036 , 95 % CI [ -0.009 , -0.002 ] ) consumption and migraine frequency .


It was also observed that in individuals with the CC genotype for the MTHFR C677T variant , migraine frequency was significantly linked to FA consumption ( R ( 2 ) = 0.106 , B = -0.004 , P = .029 , 95 % CI [ -0.007 , -0.004 ] ) .


The results from this study indicate that folate intake in the form of FA may influence migraine frequency in female MA sufferers .


Electronic monitoring is recommended for accurate measurement of medication adherence but a possible limitation is that it may influence adherence .


To test the reactive effect of electronic monitoring in a randomized controlled trial .


A total of 226 adults with type 2 diabetes and HbA1c 58mmol/mol were randomized to receiving their main oral glucose lowering medication in electronic containers or standard packaging .


The primary outcomes were self-reported adherence measured with the MARS ( Medication Adherence Report Scale ; range 5-25 ) and HbA1c at 8weeks .


Non-significantly higher adherence and lower HbA1c were observed in the electronic container group ( differences in means , adjusting for baseline value : MARS , 0.4 [ 95 % CI -0.1 to 0.8 , p = 0.11 ] ; HbA1c ( mmol/mol ) , -1.02 [ -2.73 to 0.71 , p = 0.25 ] ) .


Electronic containers may lead to a small increase in adherence but this potential limitation is outweighed by their advantages .


Our findings support electronic monitoring as the method of choice in research on medication adherence .


( Trial registration Current Controlled Trials ISRCT N30522359 ) .


High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD .


Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain .


A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial .


The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline , 124 of whom developed incident CKD during follow-up , and 520 additional patients with incident CKD outside the random subcohort .


The association between serum intact fibroblast growth factor 23 and incident CKD , defined as the new onset of eGFR < 60 ml/min per 1.73 m ( 2 ) that represented a 25 % decrease from baseline in an individual with eGFR60 ml/min per 1.73 m ( 2 ) and no microalbuminuria ( < 30 mg/g creatinine ) at baseline , was tested .


The mean baseline eGFR in the random subcohort was 90.922.7 ml/min per 1.73 m ( 2 ) .


During a median follow-up of 4.7 years , there was a total of 644 patients with incident CKD .


The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls ( 43.5 , interquartile range = 34.7-55 .1 versus 39.8 , interquartile range = 31.9-49 .5 pg/ml ; P < 0.001 ) .


Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models , but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR ( hazard ratio per SD of natural log fibroblast growth factor 23 , 1.09 ; 95 % confidence interval , 0.94 to 1.27 ) , which was the strongest predictor of incident CKD .


Consistent with the results of primary analyses , baseline fibroblast growth factor 23 was not associated with eGFR slope .


Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes .


Many commencing junior doctors worldwide feel ill-prepared to deal with their new responsibilities , particularly prescribing .


Simulation has been widely utilised in medical education , but the use of extended multi-method simulation to emulate the junior doctor experience has rarely been reported .


A randomised controlled trial compared students who underwent two , week-long , extended simulations , several months apart ( Intervention ) , with students who attended related workshops and seminars alone ( Control ) , for a range of outcome measures .


Eighty-four third year students in a graduate-entry medical program were randomised , and 82 completed the study .


At the end of the first week , Intervention students scored a mean of 75 % on a prescribing test , compared with 70 % for Control students ( P = 0.02 ) and Intervention teams initiated cardiac compressions a mean of 29.1 seconds into a resuscitation test scenario , compared with 70.1 seconds for Control teams ( P < 0.01 ) .


At the beginning of the second week , an average of nine months later , a significant difference was maintained in relation to the prescribing test only ( 78 % vs 70 % , P < 0.01 ) .


At the end of the second week , significant Intervention vs Control differences were seen on knowledge and reasoning tests , a further prescribing test ( 71 % vs 63 % [ P < 0.01 ] ) and a paediatric resuscitation scenario test ( 252 seconds to initiation of fluid resuscitation vs 339 seconds [ P = 0.05 ] ) .


The study demonstrated long-term retention of improved prescribing skills , and an immediate effect on knowledge acquisition , reasoning and resuscitation skills , from contextualising learning activities through extended multi-method simulation .


Identify predictors of non-compliance with first round screening exams in the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial .


The PLCO was conducted from 1993 to 2011 at 10 US institutions .


A total of 154,897 healthy men and women ages 55-74 years were randomized .


Intervention arm participants were invited to receive gender-appropriate screening exams for prostate , lung , colorectal and ovarian cancer .


Using intervention-arm data ( 73,036 participants ) , non-compliance percentages for 13 covariates were calculated , as were unadjusted and adjusted odds ratios ( ORs ) , and 95 % confidence intervals .


Covariates included demographic factors as well as factors specific to PLCO ( e.g. , method of consent , distance from screening center ) .


The rate of non-compliance was 11 % overall but varied by screening center .


Significant associations were observed for most covariates but indicated modest increases or decreases in odds .


An exception was the use of a two-step consent process ( consented intervention arm participants for exams after randomization ) relative to a one-step process ( consented all participants prior to randomization ) ( OR : 2.2 , 95 % CI : 2.0-2 .5 ) .


Non-compliance percentages increased with further distance from screening centers , but ORs were not significantly different from 1 .


Many factors modestly influenced compliance .


Consent process was the strongest predictor of compliance .


Regular exercise is an effective intervention to decrease blood pressure ( BP ) in hypertension , but no data are available concerning the effects of heated water-based exercise ( HEx ) .


This study examines the effects of HEx on BP in resistant hypertensive patients .


This is a parallel , randomized controlled trial .


125 nonconsecutive sedentary patients with resistant hypertension from a hypertension outpatient clinic in a university hospital were screened ; 32 patients fulfilled the study requirements .


The training was performed for 60-minute sessions in a heated pool ( 32C ) , three times a week for 12 weeks .


The HEx protocol consisted of callisthenic exercises and walking inside the pool .


The control group was asked to maintain habitual activities .


The main outcome measure was change in mean 24-hour ambulatory BP ( ABPM ) .


32 patients ( HEx n = 16 ; control n = 16 ) were randomized ; none were lost to follow-up .


Office BPs decreased significantly after heated water exercise ( 36/12 mmHg ) .


HEx decreased 24-hour systolic ( from 13723 to 12012 mmHg , p = 0.001 ) and diastolic BPs ( from 8113 to 7210 mmHg , p = 0.009 ) ; daytime systolic ( from 14124 to 12013 mmHg , p < 0.0001 ) and diastolic BPs ( from 8414 to 7311 mmHg , p = 0.003 ) ; and nighttime systolic ( from 12922 to 11412 mmHg , p = 0.006 ) and diastolic BPs ( from 7411 to 6610 mmHg , p < 0.0001 ) .


The control group after 12 weeks significantly increased in 24-hour systolic and diastolic BPs , and daytime and nighttime diastolic BPs .


HEx reduced office BPs and 24-hour ABPM levels in resistant hypertensive patients .


These effects suggest that HEx may be a potential new therapeutic approach in these patients .


Botulinum neurotoxin type A trials in aesthetic indications have used differing efficacy parameters and responder definitions .


To analyze the treatment efficacy and duration of incobotulinumtoxinA for glabellar frown lines using pooled data from 2 large , Phase 3 , placebo-controlled trials , and end points similar to those used in previous botulinum neurotoxin type A studies .


IncobotulinumtoxinA and placebo groups comprised 366 and 181 subjects , respectively .


The efficacy of a single 20-U treatment of incobotulinumtoxinA or placebo was evaluated by investigator-assessed and subject-assessed responder rates ( 1-point improvement from baseline ) , mean score , and mean change from the baseline glabellar frown line severity score .


At all follow-up visits , responder rates and mean change from the baseline score ( investigator-assessed and subject-assessed ) were significantly greater for incobotulinumtoxinA versus placebo ( p < .0001 ) .


The maximum investigator-assessed responder rate ( 93.1 % ) was achieved at Day 30 after treatment , when the mean improvement on the 4-point facial wrinkle scale peaked at 1.88 .


Treatment effect declined over time but the investigator-assessed responder rate was 45.7 % at the end of the study .


Superiority of incobotulinumtoxinA over placebo for treating glabellar frown lines was confirmed .


IncobotulinumtoxinA achieved a maximum responder rate of 93.1 % and a long duration of treatment effect : 45.7 % of subjects showed efficacy at 120 days .


To investigate whether standardised cigarette packaging increases the time spent looking at health warnings , regardless of the format of those warnings .


A factorial ( two pack styles x three warning types ) within-subject experiment , with participants randomised to different orders of conditions , completed at a university in London , UK .


Mock-ups of cigarette packets were presented to participants with their branded portion in either standardised ( plain ) or manufacturer-designed ( branded ) format .


Health warnings were present on all packets , representing all three types currently in use in the UK : black & white text , colour text , or colour images with accompanying text .


Gaze position was recorded using a specialised eye tracker , providing the main outcome measure , which was the mean proportion of a five-second viewing period spent gazing at the warning-label region of the packet .


An opportunity sample of 30 ( six male , mean age = 23 ) young adults met the following inclusion criteria : 1 ) not currently a smoker ; 2 ) < 100 lifetime cigarettes smoked ; 3 ) gaze position successfully tracked for > 50 % viewing time .


These participants spent a greater proportion of the available time gazing at the warning-label region when the branded section of the pack was standardised ( following current Australian guidelines ) rather than containing the manufacturer 's preferred design ( mean difference in proportions = 0.078 , 95 % confidence interval 0.049 to 0.106 , p < 0.001 ) .


There was no evidence that this effect varied based on the type of warning label ( black & white text vs. colour text vs. colour image & text ; interaction p = 0.295 ) .


During incidental viewing of cigarette packets , young adult never-smokers are likely to spend more time looking at health warnings if manufacturers are compelled to use standardised packaging , regardless of the warning design .


To provide the 4-week prevalence estimates of mental disorders in cancer populations .


We enrolled adult patients with cancer from in - and outpatient care facilities , using a proportional stratified random sample based on the nationwide cancer incidence in Germany .


Patients who scored 9 or above on the Patient Health Questionnaire ( PHQ-9 ) were administered to the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients ( CIDI-O ) .


A random sample of those with a PHQ-9 score that was less than 9 were selected for a CIDI-O .


A total of 5,889 patients were identified , which led to 4,020 participants ( a 68.3 % response rate ) ; of those , 2,141 patients were interviewed .


The 4-week total prevalence for any mental disorder was 31.8 % ( 95 % CI , 29.8 % to 33.8 % ) ; this included any anxiety disorder ( 11.5 % ; 95 % CI , 10.2 % to 12.9 % ) , any adjustment disorder ( 11.1 % ; 95 % CI , 9.7 % to 12.4 % ) , any mood disorder ( 6.5 % ; 95 % CI , 5.5 % to 7.5 % ) , any somatoform/conversion disorder ( 5.3 % ; 95 % CI , 4.3 % to 6.2 % ) , nicotine dependence ( 4.5 % ; 95 % CI , 3.6 % to 5.4 % ) , alcohol abuse/dependence ( 0.3 % ; 95 % CI , 0.1 % to 0.6 % ) , any mental disorder resulting from general medical condition ( 2.3 % ; 95 % CI , 1.7 % to 2.9 % ) , and any eating disorder ( 0 % ) .


The highest prevalence for any mental disorder was found in patients with breast cancer ( 41.6 % ; 95 % CI , 36.8 % to 46.4 % ) , followed by patients with head and neck cancer ( 40.8 % ; 95 % CI , 28.5 % to 53.0 % ) .


The lowest prevalence was found in patients with pancreatic cancer ( 20.3 % ; 95 % CI , 8.9 % to 31.6 % ) and stomach/esophagus cancers ( 21.2 % ; 95 % CI , 12.8 % to 29.6 % ) .


Our findings provide evidence for the strong need for psycho-oncological interventions .


Birt-Hogg-Dub syndrome ( BHD ) is a rare autosomal dominant disorder characterised by the occurrence of benign , mostly facial , skin tumours called fibrofolliculomas , multiple lung cysts , spontaneous pneumothorax and an increased renal cancer risk .


Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications .


It would be desirable to have a treatment that could prevent fibrofolliculomas from growing .


Animal models of BHD have previously shown deregulation of mammalian target of rapamycin ( mTOR ) .


Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours ( angiofibromas ) in tuberous sclerosis complex , which is also characterised by mTOR deregulation .


In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD. .


We performed a double blinded , randomised , facial left-right controlled trial of topical rapamycin 0.1 % versus placebo in 19 BHD patients .


Trial duration was 6 months .


The primary outcome was cosmetic improvement as measured by doctors and patients .


Changes in fibrofolliculoma number and size were also measured , as was occurrence of side effects .


No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated ( 79 % by doctors , 53 % by patients ) as well as the placebo treated facial sides ( both 74 % ) .


No significant differences between rapamycin and placebo treated facial halves were observed ( p = 1.000 for doctors opinion , p = 0.344 for patients opinion ) .


No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months .


Side effects occurred more often after rapamycin treatment ( 68 % of patients ) than after placebo ( 58 % of patients ; p = 0.625 ) .


A burning sensation , erythema , itching and dryness were most frequently reported .


This study provides no evidence that treatment of fibrofolliculomas with topical rapamycin in BHD results in cosmetic improvement .


ClinicalTrials.gov NCT00928798 .


Accurately estimating the period of time that individuals are exposed to online intervention content is important for understanding program engagement .


This can be calculated from time-stamped data reflecting navigation to and from individual webpages .


Prolonged periods of inactivity are commonly handled with a time-out feature and assigned a prespecified exposure duration .


Unfortunately , this practice can lead to biased results describing program exposure .


The aim of the study was to describe how multiple imputations can be used to better account for the time spent viewing webpages that result in a prolonged period of inactivity or a time-out .


To illustrate this method , we present data on time-outs collected from the Q ( 2 ) randomized smoking cessation trial .


For this analysis , we evaluate the effects on intervention exposure of receiving content written in a prescriptive versus motivational tone .


Using multiple imputations , we created five complete datasets in which the time spent viewing webpages that resulted in a time-out were replaced with values estimated with imputation models .


We calculated standard errors using Rubin 's formulas to account for the variability due to the imputations .


We also illustrate how current methods of accounting for time-outs ( excluding timed-out page views or assigning an arbitrary viewing time ) can influence conclusions about participant engagement .


A total of 63.00 % ( 1175/1865 ) of participants accessed the online intervention in the Q ( 2 ) trial .


Of the 6592 unique page views , 683 ( 10.36 % , 683/6592 ) resulted in a time-out .


The median time spent viewing webpages that did not result in a time-out was 1.07 minutes .


Assuming participants did not spend any time viewing a webpage that resulted in a time-out , no difference between the two message tones was observed ( ratio of mean time online : 0.87 , 95 % CI 0.75-1 .02 ) .


Assigning 30 minutes of viewing time to all page views that resulted in a time-out concludes that participants who received content in a motivational tone spent less time viewing content ( ratio of mean time online : 0.86 , 95 % CI 0.77-0 .98 ) than those participants who received content in a prescriptive tone .


Using multiple imputations to account for time-outs concludes that there is no difference in participant engagement between the two message tones ( ratio of mean time online : 0.87 ; 95 % CI 0.75-1 .01 ) .


The analytic technique chosen can significantly affect conclusions about online intervention engagement .


We propose a standardized methodology in which time spent viewing webpages that result in a time-out is treated as missing information and corrected with multiple imputations .


Clinicaltrials.gov NCT00992264 ; http://clinicaltrials.gov/ct2/show/NCT00992264 ( Archived by WebCite at http://www.webcitation.org/6Kw5m8EkP ) .


To evaluate the lung function and clinical outcome in severe chronic obstructive pulmonary disease in patients undergoing off-pump coronary artery bypass grafting with left internal thoracic artery graft , comparing the pleural drain insertion in the intercostal versus subxyphoid region .


A randomized controlled trial .


Chronic obstructive pulmonary disease patients were randomized into two groups according pleural drain site : II group ( n = 27 ) - pleural drain in intercostal space ; SI group ( n = 29 ) - pleural drain in the subxyphoid region .


Spirometry values ( Forced Vital Capacity - and Forced expiratory volume in 1 second ) were obtained on preoperative and 1 , 3 and 5 postoperative days .


Chest x-ray from preoperative until postoperative day 5 ( POD5 ) was performed for monitoring respiratory events , such as atelectasis and pleural effusion .


Pulmonary shunt fraction and pain score was evaluate preoperatively and on postoperative day 1 .


In both groups there was a significant decrease of the spirometry values ( Forced Vital Capacity and Forced expiratory volume in 1 second ) until POD5 ( P < 0.05 ) .


However , when compared , SI group presented less decrease in these parameters ( P < 0.05 ) .


Pulmonary shunt fraction was significantly lower in SI group ( P < 0.05 ) .


Respiratory events , pain score , orotracheal intubation time and postoperative length of hospital stay were lower in the SI group ( P < 0.05 ) .


Subxyphoid pleural drainage in severe Chronic obstructive pulmonary disease patients determined better preservation and recovery of pulmonary capacity and volumes with lower pulmonary shunt fraction and better clinical outcomes on early postoperative off-pump coronary artery bypass grafting .


Little is known about the effects of natural mineral water on constipation in adults .


We assessed the effect of a magnesium sulfate-rich natural mineral water ( Hpar ; Nestl Waters , Issy-les-Moulineaux , France ) on gastrointestinal transit in constipated women .


We performed a randomized , double-blind , placebo-controlled trial to evaluate the efficacy and safety of Hpar in outpatients with functional constipation ( based on the Rome III criteria ) .


The study included 244 female patients , age 18 to 60 years , identified by 62 general practitioners throughout France .


After a washout period , subjects drank 1.5 L natural low-mineral water daily ( control , n = 77 ) , 0.5 L Hpar and 1 L natural low-mineral water daily ( Hpar 0.5 group , n = 85 ) , or 1 L Hpar and 0.5 L natural low-mineral water daily ( Hpar 1 group , n = 82 ) for 4 weeks .


We collected information on the number and types of stools , abdominal pain , rescue medications , adverse events , and volume of water consumed .


We observed no significant effect at week 1 .


At week 2 , constipation was reduced in 21.1 % of patients in the control group , in 30.9 % in the Hpar 0.5 group ( P = .099 vs controls ) , and in 37.5 % in the Hpar 1 group ( P = .013 vs controls ) .


The Hpar 1 group also had a decreased number of hard or lumpy stools ( Bristol scale , P = .030 vs baseline ) and a substantial decrease in the use of rescue medication ( P = .034 vs controls ) .


Patient responses correlated with magnesium sulfate concentrations .


Safety was very good ; there were no serious adverse events among patients who drank Hpar .


In a controlled trial , daily consumption of 1 L Hpar reduced constipation and hard or lumpy stools in a greater percentage of women with functional constipation than natural low-mineral water , as early as the second week of treatment .


To evaluate the efficacy of adding nepafenac 0.1 % ophthalmic suspension to dexamethasone 0.1 % eyedrops in controlling macular swelling and other manifestations of inflammation after uneventful cataract surgery .


Ophthalmology Department , Mlndal Hospital , Gothenburg , and St. Erik Eye Hospital , Stockholm , Sweden .


Randomized double-masked clinical trial .


Patients at low risk for postoperative inflammation were recruited and randomized to the nepafenac group or to the control group .


Postoperative swelling of the macula was assessed with ocular coherence tomography .


Laser flare intensity , corrected distance visual acuity , ocular discomfort , and visual complaints were also recorded .


The analysis of intent-to-treat population comprised 75 patients in the nepafenac group and 77 patients in the control group .


Compared with the control regimen , add-on nepafenac resulted in statistically significant reductions in the following parameters : change in macular volume at 3 weeks and 6 weeks ( P < .001 ) , proportion of patients with more than 10 m of swelling in the central macula at 3 weeks ( P < .0001 ) and 6 weeks ( P = .02 ) , mean laser flare intensity at 1 day ( P = .029 ) , pain during the first 24 hours postoperatively ( P < .0001 ) , and ocular discomfort and photophobia during the first 3 postoperative weeks ( P = .0058 and P = .0052 , respectively ) .


The combination of topical nepafenac and steroid treatment reduced subclinical macular swelling and inflammation as well as subjective complaints , indicating it is an efficient antiinflammatory regimen after cataract surgery .


No author has a financial or proprietary interest in any material or method mentioned .


Cutaneous telangiectases are a characteristic and psychologically distressing feature of SSc .


Our aim was to assess the efficacy of two light-based treatments : pulsed dye laser ( PDL ) and intense pulsed light ( IPL ) .


Nineteen patients with facial or upper limb telangiectases underwent three treatments with PDL and IPL ( randomly assigned to left - and right-sided lesions ) .


Outcome measures were clinical photography ( assessed by two clinicians ) , dermoscopy ( assessed by two observers ) , laser Doppler imaging ( LDI ) and observer and patient opinion , including patient self-assessment psychological questionnaires [ Hospital Anxiety and Depression Scale ( HADS ) , Adapted Satisfaction with Appearance Scale ( ASWAP ) ] .


Comparison between 16-week follow-up and baseline photography scores ( from -2 to +2 on a Likert scale , with > 0 being improvement ) were a mean score for PDL of 1.7 ( 95 % CI 1.4 , 2.0 ) and for IPL 1.4 ( 0.9 , 1.8 ) , with a mean difference between PDL and IPL of -0.3 ( -0.5 , -0.1 ) ( P = 0.01 ) .


Dermoscopy scores also improved with both therapies : PDL 1.3 ( 1.1 , 1.5 ) and IPL 0.8 ( 0.5 , 1.1 ) , again greater with PDL ( P = 0.01 ) .


LDI showed decreases in blood flow at 16 weeks , indicating a response to both therapies .


All patients reported benefit from treatment ( more preferred PDL at 16 weeks ) .


Psychological questionnaires also indicated improvement after therapy with mean change in ASWAP of -13.9 ( 95 % CI -20.5 , -7.4 ) .


No side effects were reported for IPL ; PDL caused transient bruising in most cases .


Both PDL and IPL are effective treatments for SSc-related telangiectases .


Outcome measures indicate that PDL has better outcomes in terms of appearance , although IPL had fewer side effects .


To explore the roles of ribavirin aerosol in the prevention and treatment of hand-foot-mouth disease ( HFMD ) .


For this prospective , multicenter , randomized , double-blind and placebo-controlled trial , a total of 300 HFMD outpatients from 3 class 3A hospitals from July 2011 to June 2013 were divided into treatment ( ribavirin aerosol ) and control ( placebo ) groups ( n = 150 each ) .


The age range was 6 months to 6 years .


The proportion of male and female was 1.5 : 1 .


Temperature , herpes of mouth and skin rash were observed before and after treatments .


Before treatment and 6-7 days after , their specimens of throat swab were collected and the levels of EV71 and CA16 detected with reverse transcription ( RT ) - PCR .


The software SAS 9.2 was used for statistic data analyses .


Before treatment , no significant statistical difference existed in parameters between treatment and control groups ( all P > 0.05 ) .


After treatment , the degree of herpes of mouth and papulovesicle of skin in treatment group was better than that in control group ( 100.0 % ( 147/147 ) vs 83.9 % ( 120/143 ) , ( 2 ) = 109.21 , P < 0.01 ) ; ( 100.0 % ( 147/147 ) vs 95.9 % ( 139/145 ) , ( 2 ) = 6.38 , P < 0.05 ) .


The virus negative conversion rates had significant inter-group difference ( 80.0 % ( 102/110 ) vs 41.8 % ( 41/98 ) , ( 2 ) = 37.06 , P < 0.01 ) .


The temperature , compliance and differences were not significant ( all P > 0.05 ) .


The effective rate of comprehensive efficacy in treatment group was higher than that in control group ( 93.9 % ( 122/130 ) vs 52.0 % ( 64/123 ) , ( 2 ) = 111.08 , P < 0.01 ) .


No obvious adverse drug reaction was observed .


Ribavirin aerosol has multiple advantages of lower dose , quicker onset , higher local concentration , better clinical efficacy and fewer side-effects .


Its therapeutic effect for local lesion is better than that for systemic lesion .


Thus it may shorten the duration of oropharyngeal and skin lesions and lower the number and time of viral release .


Early combination antiretroviral therapy ( cART ) initiation at the time of primary HIV-1 infection could restrict the establishment of HIV reservoirs .


We aimed to assess the effect of a cART regimen intensified with raltegravir and maraviroc , compared with standard triple-drug cART , on HIV-DNA load .


In this randomised , open-label , phase 3 trial , we recruited patients from hospitals across France .


Inclusion criteria were primary HIV-1 infection ( an incomplete HIV-1 western blot and detectable plasma HIV-RNA ) , with either symptoms or a CD4 + cell count below 500 cells per L. Patients were randomly assigned ( 1:1 ) to an intensive , five-drug cART regimen ( raltegravir 400 mg and maraviroc 150 mg twice daily , and a fixed-dose combination of tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g , darunavir 800 g , and ritonavir 100 g once daily ) or a standard triple-drug cART regimen ( tenofovir disoproxil fumarate 300 g plus emtricitabine 200 g , darunavir 800 g , and ritonavir 100 g once daily ) using a predefined randomised list generated by randomly selected variable block sizes .


The primary endpoint was the median number of HIV-DNA copies per 10 ( 6 ) peripheral blood mononuclear cells ( PBMC ) at month 24 , analysed in the modified intention-to-treat population , defined as all patients who started their assigned treatment .


This study is registered with ClinicalTrials.gov , number NCT01033760 .


Between April 26 , 2010 , and July 13 , 2011 , 110 patients were enrolled , of whom 92 were randomly assigned and 90 started treatment ( 45 in each treatment group ) .


Six ( 13 % ) patients in the intensive cART group and two ( 4 % ) in the standard cART group discontinued before month 24 .


At month 24 , HIV-DNA loads were similar between groups ( 235 [ IQR 205-250 ] log per 10 ( 6 ) PBMC in the intensive cART group vs 225 [ 171-255 ] in the standard cART group ; p = 021 ) .


Eight grade 3-4 clinical adverse events were reported in seven patients in the intensive cART group and seven grade 3-4 clinical adverse events were reported in seven patients in the standard cART group .


Three serious clinical adverse events occurred : two ( pancreatitis and lipodystrophy ) in the standard cART group , which were regarded as treatment related , and one event ( suicide attempt ) in the intensive cART group that was unrelated to treatment .


After 24 months , cART intensified with raltegravir and maraviroc did not have a greater effect on HIV blood reservoirs than did standard cART .


These results should help to design future trials of treatments aiming to decrease the HIV reservoir in patients with primary HIV-1 infection .


Inserm-ANRS , Gilead Sciences , Janssen Pharmaceuticals , Merck , and ViiV Laboratories .


To test the effects of pregabalin on the induction of neurogenic claudication .


This study was a randomized , double-blind , active placebo-controlled , 2-period , crossover trial .


Twenty-nine subjects were randomized to receive pregabalin followed by active placebo ( i.e. , diphenhydramine ) or active placebo followed by pregabalin .


Each treatment period lasted 10 days , including a 2-step titration .


Periods were separated by a 10-day washout period , including a 3-day taper phase after the first period .


The primary outcome variable was the time to first moderate pain symptom ( Numeric Rating Scale score 4 ) during a 15-minute treadmill test ( Tfirst ) .


Secondary outcome measures included pain intensity at rest , pain intensity at the end of the treadmill test , distance walked , and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire , modified Brief Pain Inventory-Short Form , Oswestry Disability Index , and Swiss Spinal Stenosis Questionnaire .


No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom ( difference in median Tfirst = -1.08 [ 95 % confidence interval -2.25 to 0.08 ] , p = 0.61 ) .


In addition , none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo .


Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis .


This study provides Class I evidence that for patients with neurogenic claudication , compared with diphenhydramine , pregabalin does not increase the time to moderate pain during a treadmill test .


A phase 1 study was conducted to evaluate the bioavailability and food effect of a new veliparib formulation in subjects with solid tumors .


Subjects ( planned : Stage I , N = 20 ; Stage II , N = 16 ) received four regimens of a single oral dose of veliparib utilizing a group-sequential design .


Subjects were administered single doses of 40 mg veliparib supplied as four 10 mg current formulation , four 10 mg new formulation and one 40 mg new formulation under fasting conditions and under non-fasting conditions .


Serial blood samples were collected for the determination of veliparib pharmacokinetics .


At the end of Stage I , the relative bioavailability between each pair of regimens was assessed by a two one-sided tests procedure from the analyses of the natural logarithms of C ( max ) and AUC .


A 92.7 % confidence interval within the 0.80-1 .25 range between each regimen pair determined bioequivalence .


Four 10 mg current formulation capsules , four 10 mg new formulation and one 40 mg new formulation were bioequivalent with respect to C ( max ) and AUC under fasting conditions .


The administration of a high-fat meal did not have a significant effect on AUC and only caused a slight decrease in veliparib C ( max ) ( 17 % ) and a delay of approximately 1 h in T ( max ) .


The 40 mg new capsule was bioequivalent to currently used formulation .


Food had no effect on the extent of veliparib absorption and only a small ( 17 % ) decrease in peak exposure of veliparib .


Renin-angiotensin system inhibition ( RASI ) is frequently avoided in aortic stenosis ( AS ) patients because of fear of hypotension .


We evaluated if RASI with angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin receptor blocker ( ARB ) increased mortality in patients with mild to moderate AS .


All patients ( n = 1873 ) from the Simvastatin and Ezetimibe in Aortic Stenosis study : asymptomatic patients with AS and preserved left ventricular ( LV ) ejection fraction were included .


Risks of sudden cardiac death ( SCD ) , cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses .


769 ( 41 % ) patients received RASI .


During a median follow-up of 4.3 0.9 years , 678 patients were categorized as having severe AS , 545 underwent aortic valve replacement , 40 SCDs , 103 cardiovascular and 205 all-cause deaths occurred .


RASI was not associated with SCD ( HR : 1.19 [ 95 % CI : 0.50-2 .83 ] , p = 0.694 ) , cardiovascular ( HR : 1.05 [ 95 % CI : 0.62-1 .77 ] , p = 0.854 ) or all-cause mortality ( HR : 0.81 [ 95 % CI : 0.55-1 .20 ] , p = 0.281 ) .


This was confirmed in propensity matched analysis ( all p > 0.05 ) .


In separate analyses , RASI was associated with larger reduction in systolic blood pressure ( p = 0.001 ) and less progression of LV mass ( p = 0.040 ) .


RASI was not associated with SCD , cardiovascular or all-cause mortality in asymptomatic AS patients .


However , RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression .


Exercise capacity is a strong predictor of survival in patients with coronary artery disease ( CAD ) .


Exercise capacity improves after cardiac rehabilitation exercise training , but previous studies have demonstrated a decline in peak oxygen uptake after ending a formal rehabilitation program .


There is a lack of knowledge on how long-term exercise adherence can be achieved in CAD patients .


We therefore assessed if a 12-month maintenance program following cardiac rehabilitation would lead to increased adherence to exercise and increased exercise capacity compared to usual care .


Two-centre , open , parallel randomized controlled trial with 12 months follow-up comparing usual care to a maintenance program .