Depressive symptoms were negatively related to cortisol levels ( = -0.023 , p = .002 ) but were positively related to rate of change in cortisol ( = 0.003 , p = .003 ) .


Adrenocorticotropin hormone , epinephrine , and norepinephrine did not covary with depressive symptoms ( all p values > .05 ) .


When the CES-D and Perceived Stress Scale were both used to predict cortisol , only the CES-D was significantly related ( = -0.025 , p = .017 ) .


Depressive symptoms were negatively related to cortisol , but this relationship changed from the time of diagnosis/surgery through 12 months .


Cortisol may initially provide a buffering effect against depression during the stress of initial diagnosis and treatment , but this relationship seems to change over time .


Hematologic reference values vary by ethnicity .


We aimed to determine reference values of hemoglobin ( Hb ) for Korean adolescents .


Using data from the 5th Korean National Health and Nutrition Examination Survey ( KNHANES ) , we obtained reference values for Hb in adolescents aged 10-20 years .


Among 2,526 subjects recruited , 330 were excluded due to chronic diseases ( 9 congenital heart disease , 6 epilepsy , and 1 thyroid disease ) or abnormal laboratory values ( 253 subjects with Fe/TIBC < 16 % , 103 subjects with MCV < 80fl ) .


Accordingly , data from 2,196 subjects ( male = 1,196 and female = 1,000 ) were analyzed and age - and gender-stratified means and percentile values of Hb were obtained .


Pertinent findings observed in the current study were : ( i ) Hb levels in Korean male were similar to those of non-Hispanic Caucasians ; ( ii ) Hb values in females were similar to those of non-Hispanic Caucasians until age of 15 , and thereafter were slightly lower .


Prevalence of anemia according to WHO criteria and our own criteria ( Hb levels < 2 standard deviations of age - and gender-specific values ) in total sample was 3.5 % ( 88/2 ,526 ) and 3.8 % ( 97/2 ,526 ) , respectively .


Anemia was more prevalent in female in comparison with male ( 6.5 % vs. 1.0 % , P < 0.001 ) .


Our results could be used as a national reference standard to correctly classify a large population sample .


Further studies are necessary to determine reference Hb values for children younger than 10 years and identify genetic variations associated with distinctive characteristics observed in this study .


Most tobacco smokers who wish to quit fail to reach their goal .


One important , insufficiently emphasized aspect of addiction relates to the decision-making system , often characterized by dysfunctional cognitive control and a powerful drive for reward .


Recent proof-of-principle studies indicate that transcranial direct current stimulation ( tDCS ) over the dorsolateral prefrontal cortex ( DLPFC ) can transiently modulate processes involved in decision-making , and reduce substance intake and craving for various addictions .


We previously proposed that this beneficial effect of stimulation for reducing addictive behaviors is in part mediated by more reflective decision-making .


The goal of this study was to test whether nicotine intake and decision-making behaviors are modulated by tDCS over the DLPFC in tobacco smokers who wished to quit smoking .


Subjects received two five-day tDCS regimens ( active or sham ) .


Stimulation was delivered over the right DLPFC at a 2 mA during 30 min .


Nicotine cravings , cigarette consumption and decision-making were assessed before and after each session .


Main findings include a significant decrease in the number of cigarettes smoked when participants received active as compared to sham stimulation .


This effect lasted up to four days after the end of the stimulation regimen .


In regards to decision-making , smokers rejected more often offers of cigarettes , but not offers of money , after they received active as compared to sham stimulation at the Ultimatum Game .


No significant change was observed at the Risk Task with cigarettes or money as rewards .


Overall , these findings suggest that tDCS over the DLPFC may be beneficial for smoking reduction and induce reward sensitive effects .


Previous studies showed that noncoplanar intensity-modulated radiotherapy ( NC-IMRT ) for sinonasal cancer is superior to coplanar intensity-modulated radiotherapy ( IMRT ) .


Volumetric-modulated arc therapy ( VMAT ) is a newly introduced treatment modality , and the performance of noncoplanar VMAT for sinonasal cancer has not been well described to date .


To compare the dosimetry difference of noncoplanar VMAT ( NC-VMAT ) , coplanar VMAT ( co-VMAT ) , and NC-IMRT for sinonasal cancer .


Ten postoperative patients with sinonasal cancer were randomly selected for planning with NC-VMAT , co-VMAT , and NC-IMRT .


Two planning target volumes ( PTVs ) were contoured representing high-risk and low-risk regions set to receive a median absorbed dose ( D50 % ) of 68 Gy and 59 Gy , respectively .


The homogeneity index ( HI ) , conformity index ( CI ) , dose-volume histograms ( DVHs ) , and delivery efficiency were all evaluated .


Both NC-VMAT and co-VMAT showed superior dose homogeneity and conformity in PTVs compared with NC-IMRT .


There was no significant difference between NC-VMAT and co-VMAT in PTV coverage .


Both VMAT plans provided a better protection for organs at risk ( OARs ) than NC-IMRT plans , and NC-VMAT showed a small improvement over co-VMAT in sparing of OARs .


For peripheral doses , the doses to breast , thyroid , and larynx in the NC-IMRT plans were significantly higher than those in both VMAT plans .


Compared to NC-VMAT , co-VMAT significantly reduced peripheral doses .


NC-VMAT and co-VMAT reduced the average delivery time by 63.2 and 64.2 % , respectively , in comparison with NC-IMRT .


No differences in delivery efficiency were observed between the two VMAT plans .


Compared to NC-VMAT , co-VMAT showed similar PTV coverage and comparable OAR sparing but significantly reduced peripheral doses and positioning uncertainty .


We propose to give priority to coplanar VMAT in the treatment of sinonasal cancer .


There are no current pharmacological therapies for the prevention or treatment of acute respiratory distress syndrome .


Early dysregulated inflammation likely plays a role in acute respiratory distress syndrome development and possibly acute respiratory distress syndrome outcomes .


p38 mitogen-activated protein kinase is central to the regulation of multiple inflammatory mediators implicated in acute organ dysfunction and is the target for a novel class of cytokine-suppressive anti-inflammatory drugs .


In preclinical models , p38 inhibitors reduce lung injury following pancreatitis and burn injury .


We conducted a phase IIa , randomized , double-blind , placebo-controlled , parallel-group study to evaluate the safety and tolerability of dilmapimod , a novel p38 mitogen-activated protein kinase inhibitor , in patients at risk for developing acute respiratory distress syndrome admitted with an Injury Severity Score more than 16 , excluding head trauma .


Enrolled patients received 4 - or 24-hour IV dilmapimod infusions at different doses or placebo , daily for 3 days , in four separate cohorts .


Multicenter randomized clinical trial of large , academic trauma centers .


Seventy-seven patients were enrolled .


Although adverse events were common in this critically ill population , dilmapimod was well tolerated , with no clinically relevant safety findings .


Pharmacokinetic models indicated that the higher dose of 10mg given as continuous infusion over 24 hours had the most favorable plasma concentration profile .


Likewise , measures of soluble inflammatory markers including interleukin-6 , C-reactive peptide , interleukin-8 , and soluble tumor necrosis factor receptor 1 were most different between this dosing arm and placebo .


Although the study was not specifically designed with acute respiratory distress syndrome as an outcome , the number of patients who developed acute respiratory distress syndrome was small ( 2/77 ) .


The novel p38 mitogen-activated protein kinase inhibitor dilmapimod appears well tolerated and may merit further evaluation for prevention of acute respiratory distress syndrome and other organ injury in larger clinical trials .


Furthermore , results of this early-phase trial may aid in design of future studies aimed at prevention of acute respiratory distress syndrome and other organ injury .


To compare the effectiveness of two procedures increasing the botulinum toxin type A effect for wrist and finger flexor spasticity after stroke .


A single-blind randomized trial .


Seventy patients with upper limb post-stroke spasticity .


Adults with wrist and finger flexor muscles spasticity after stroke were submitted to botulinum toxin type A therapy .


After the treatment , the subjects injected were randomly divided into two groups and submitted to adhesive taping ( Group A ) or daily muscle manual stretching , passive articular mobilization of wrist and fingers , and palmar splint ( Group B ) for 10 days .


We measured spasticity with Modified Ashworth Scale , related disability with Disability Assessment Scale , and fingers position at rest .


The measurements were done at baseline , after two weeks , and after one month from the treatment session .


After two weeks , subjects in Group A reported a significantly greater decrease in spasticity scores ( Modified Ashworth Scale fingers : mean ( standard deviation ) 1.30.6 vs. 2.10.6 ; Modified Ashworth Scale wrist : 1.7 0.6 vs. 2.3 0.8 ) , and after one month in spasticity and disability scores ( Modified Ashworth Scale fingers : mean ( standard deviation ) 1.9 0.7 vs. 2.5 0.6 ; Modified Ashworth Scale wrist : 2.0 0.7 vs. 2.6 0.6 ; Disability Assessment Scale : 1.6 0.7 vs. 2.1 0.7 ) compared with Group B subjects .


Subjects in Group A reported also a significantly improved fingers position at rest compared with Group B subjects after two weeks ( 2.8 0.9 vs. 2.1 0.7 ) and one month ( 2.3 0.7 vs. 1.5 0.6 ) .


Adhesive taping of wrist and finger flexor muscles appeared to enhance the effect of botulinum toxin type A therapy more than daily manual muscle stretching combined with passive articular mobilization and palmar splint .


Research has shown that 6h after breeding is a critical time during the uterine innate immune response , and the failure to respond appropriately will result in persistent breeding-induced endometritis .


This presents a potential opportunity to modulate the course of inflammation towards a timely resolution .


To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6h after breeding .


The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares .


A randomised controlled study to evaluate the effects of mycobacterial cell wall extract and dexamethasone on endometrial gene expression after insemination in 6 mares susceptible to persistent breeding-induced endometritis .


Six susceptible mares were selected based on their uterine inflammatory response to insemination .


Mares were inseminated during 3 oestrous cycles with 1 10 ( 9 ) nonviable spermatozoa and 1 ) no additional treatment ( control ) , or in combination with 2 ) dexamethasone ( 50mg i.v. ) at the time of insemination , or 3 ) with mycobacterial cell wall extract ( 1.5 ml i.v. ) administered 24h prior to insemination .


Mares received one treatment per cycle in randomised order , and each mare served as her own control .


Endometrial biopsies were collected 6h after breeding , and quantitative polymerase chain reaction analysis for interleukin ( IL ) 1 , IL6 , interferon , IL10 and IL1RA was performed .


Relative quantification values reported fold changes in mRNA expression from the control .


Data were analysed using an ANOVA and significance was set at P < 0.05 .


Expression of IL1 mRNA was lower after treatment with dexamethasone ( P < 0.001 ) and mycobacterial cell wall extract ( P < 0.05 ) when compared with control .


No differences were detected in the mRNA expression of the other cytokines after any of the treatments .


Treatment with immune modulators alters endometrial mRNA expression of IL1 after insemination .


A better understanding of the mechanisms of immune modulation in the equine uterus can help to improve treatments for persistent breeding-induced endometritis .


Total knee arthroplasty ( TKA ) is often associated with severe pain .


Different regional anesthetic techniques exist , all with varying degrees of motor blockade .


We hypothesized that pain relief provided by the adductor canal block ( ACB ) could increase functional muscle strength .


We included 50 TKA patients with severe movement-related pain ; defined as having visual analog scale pain score of greater than 60 mm during active flexion of the knee .


The ACB group received an ACB with ropivacaine 0.2 % 30 mL and a femoral nerve block ( FNB ) with 30 mL saline .


The FNB group received an ACB with 30 mL saline and an FNB with ropivacaine 0.2 % 30 mL .


We compared the effect of the ACB versus FNB on maximum voluntary isometric contraction of the quadriceps muscle relative to a postoperative baseline value .


Secondary end points were differences between groups in ability to ambulate and changes in pain scores ( Clinicaltrials.gov identifier NCT01922596 ) .


After block , the quadriceps maximum voluntary isometric contraction increased to 193 % ( 95 % confidence interval [ CI ] , 143-288 ) of the baseline value in the ACB group and decreased to 16 % ( 95 % CI , 3-33 ) in the FNB group with an estimated difference of 178 % ( 95 % CI , 136-226 ) , P < 0.0001 .


Pain scores were similar between groups .


Before block , 2 of 25 patients in each group were unable to perform the Timed-Up-and-Go test ; after block , this number increased to 7 of 25 in the FNB group and decreased to 0 of 25 in the ACB group .


Adductor canal block provides a clinically relevant and statistically significant increase in quadriceps muscle strength for patients in severe pain after TKA .


To make a comprehensive evaluation of the efficiency of eradication therapy in patients with coronary heart disease ( CHD ) concurrent with peptic ulcer disease ( PUD ) .


The results of treatment were studied in 112 patients with CHD concurrent with PUD who were randomized into 3 groups : 1 ) adequate eradication therapy during treatment for CHD ; 2 ) antisecretory therapy ; 3 ) treatment for CHD only .


The trend in the clinical symptoms of the diseases and the results of an exercise test were assessed .


After eradication therapy , Group 1 patients displayed a reduction in the frequency of angina attacks by 62.6 % and weekly nitroglycerin needs by 70.4 % and an increase in exercise tolerance by 45.3 % .


In Group 2 patients on antisecretory therapy , the similar indicators changed by 30.7 , 21.2 , and 26.5 % , respectively .


Group 3 patients showed no significant change in the study indicators .


The findings suggest that eradication therapy has a positive impact on the course of CHD , which manifests itself as an antianginal effect and hence a change in the clinical picture .


This paper examines the relationship between race , religiousness , spiritual well-being , antitumor treatment and preference for aggressive care among Black and White patients with advanced stage lung cancer receiving ambulatory cancer care in an urban setting .


A cross-sectional exploration of patients enrolled in a Cleveland-based longitudinal study after initial diagnosis of advanced lung cancer were interviewed in Cleveland regarding religiousness , spiritual well-being , preferences for cardiopulmonary resuscitation ( CPR ) , goals of aggressive care , and willingness to tolerate adverse health states .


Receipt of antitumor treatment was identified from medical records .


We analyzed data from 67 Black and 129 White patients ( N = 196 ) .


Regression analysis for CPR showed that race was not associated with preference for CPR ( OR = 1.12 , CI 0.44-2 .85 ) .


The odds of choosing CPR were three times higher among patients receiving antitumor treatment ( OR = 3.26 , CI 1.12-9 .44 ) .


Greater willingness to endure adverse health states was associated with higher spiritual well-being scores ( b = 0.12 , CI 0.01-0 .25 ) .


Choosing goals to extend life versus relieve pain was higher among persons with higher spiritual well-being as well ( RRR = 1.08 , CI 1.01-1 .16 ) , yet the relationship with religiousness was negative ( RRR = 0.46 , CI 0.22-0 .98 ) .


After controlling for multiple factors , race was associated only with CPR , but not with other measures of preference for aggressive care .


In addition , receipt of active antitumor treatment was positively associated with preference for CPR and spiritual well-being was important to setting end-of-life care goals and perspectives .


Future directions for tailoring end-of-life care decision-making initiatives should move beyond race and discussions of CPR alone and focus on a full spectrum of patient beliefs and preferences at the end of life .


Continuous intraperitoneal insulin infusion ( CIPII ) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus ( T1DM ) .


Aim of the present study was to describe the long-term course of glycaemic control , complications , health related quality of life ( HRQOL ) and treatment satisfaction among T1DM patients treated with CIPII .


Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous ( SC ) therapy in 2006 were followed until 2012 .


Laboratory , continuous glucose monitoring , HRQOL and treatment satisfaction measurements were performed at the start of the study , the end of the SC - , the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012 .


Linear mixed models were used to calculate estimated values and to test differences between the moments in time .


In 2012 , more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006 : 37 % ( 95 % CI 29 , 44 ) vs. 55 % ( 95 % CI 48 , 63 ) , mean difference 19.8 % ( 95 % CI 3.0 , 36.6 ) .


HbA1c was 65mmol/mol ( 95 % CI 60 , 71 ) at the end of the SC treatment phase in 2006 , 58mmol/mol ( 95 % CI 53 , 64 ) at the end of the CIPII treatment phase and 65mmol/mol ( 95 % CI 60 , 71 ) in 2012 , respectively ( p > 0.05 ) .


In 2012 , the median number of grade 2 hypoglycaemic events per week ( 1 ( 95 % CI 0 , 2 ) ) was still significantly lower than during prior SC therapy ( 3 ( 95 % CI 2 , 4 ) ) : mean change -1.8 ( 95 % CI -3.4 , -0.4 ) .


Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable .


Pump or catheter dysfunction of the necessitated re-operation in 7 patients .


No mortality was reported .


After 6years of CIPII treatment , glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy .


Treatment satisfaction with CIPII is superior to SC insulin therapy , HRQOL is stable and complications are scarce .


CIPII is a safe and effective treatment option for selected patients with T1DM , also on longer term .


Atelectasis is common during and after general anaesthesia .


We hypothesized that a ventilation strategy , without recruitment manoeuvres , using a combination of continuous positive airway pressure ( CPAP ) or positive end-expiratory pressure ( PEEP ) and a reduced end-expiratory oxygen fraction ( FETO2 ) before ending mask ventilation with CPAP after extubation would reduce the area of postoperative atelectasis .


Thirty patients were randomized into three groups .


During induction and emergence , inspiratory oxygen fractions ( FIO2 ) were 1.0 in the control group and 1.0 or 0.8 in the intervention groups .


No CPAP/PEEP was used in the control group , whereas CPAP/PEEP of 6 cmH2O was used in the intervention groups .


After extubation , FIO2 was set to 0.30 in the intervention groups and CPAP was applied , aiming at FETO2 < 0.30 .


Atelectasis was studied by computed tomography 25 min postoperatively .


The median area of atelectasis was 5.2 cm ( 2 ) ( range 1.6-12 .2 cm ( 2 ) ) and 8.5 cm ( 2 ) ( 3-23 .1 cm ( 2 ) ) in the groups given FIO2 1.0 with or without CPAP/PEEP , respectively .


After correction for body mass index the difference between medians ( 2.9 cm ( 2 ) ) was statistically significant ( confidence interval 0.2-7 .6 cm ( 2 ) , p = 0.04 ) .


In the group given FIO2 0.8 , in which seven patients were ex - or current smokers , the median area of atelectasis was 8.2 cm ( 2 ) ( 1.8-14 .7 cm ( 2 ) ) .


Compared with conventional ventilation , after correction for obesity , this ventilation strategy reduced the area of postoperative atelectasis in one of the intervention groups but not in the other group , which included a higher proportion of smokers .


Androgen deprivation therapy ( ADT ) is a cornerstone in the treatment of advanced prostate cancer .


Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted .


The ` Football Club ( FC ) Prostate ' study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition , cardiovascular function , physical function parameters , glucose tolerance , bone health , and patient-reported outcomes in men undergoing ADT for prostate cancer .


Using a single-center randomized controlled design , 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6months or more at The Copenhagen University Hospital will be enrolled on this trial .


After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care .


The soccer intervention will consist of 12weeks of training 2-3 times/week for 45-60min after which the assessment protocol will be repeated .


Soccer training will then continue bi-weekly for an additional 20weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects .


The primary endpoint is changes in lean body mass from baseline to 12weeks assessed by dual X-ray absorptiometry scan .


Secondary endpoints include changes of cardiovascular , metabolic , and physical function parameters , as well as markers of bone metabolism and patient-reported outcomes .


The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT .


The results may pave the way for innovative , community-based interventions in the approach to treating prostate cancer .


ClinicalTrials.gov : NCT01711892 .


Thiazolidinediones reduce ectopic fat , increase adiponectin and reduce inflammatory adipokines , fatty acids and glucose in people with Type 2 diabetes .


We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance .


After approximately 3.5 years of exposure to rosiglitazone 8 mg ( n = 88 ) or placebo ( n = 102 ) , 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans .


Visceral and subcutaneous adipose tissue areas , estimated hepatic fat content , total fat and lean mass were calculated and changes in levels of fasting adipokines , free fatty acids , glucose and post-load glucose were assessed .


Compared with the placebo , participants on rosiglitazone had no difference in lean mass , had 4.1 kg more body fat ( P < 0.0001 ) and 31 cm ( 2 ) more subcutaneous abdominal adipose tissue area ( P = 0.007 ) .


Only after adjusting for total fat , participants on rosiglitazone had 23 cm less visceral adipose tissue area ( P = 0.01 ) and an 0.08-unit higher liver : spleen attenuation ratio ( i.e. less hepatic fat ; P = 0.02 ) than those on the placebo .


Adiponectin increased by 15.0 g/ml with rosiglitazone and by 0.4 g/ml with placebo ( P < 0.0001 ) .


Rosiglitazone 's effect on fat distribution was not independent of changes in adiponectin .


Rosiglitazone 's effects on fasting ( -0.36 mmol/l ; P = 0.0004 ) and 2-h post-load glucose ( -1.21 mmol/l ; P = 0.0008 ) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids .


In people with impaired fasting glucose/impaired glucose tolerance , rosiglitazone is associated with relatively less hepatic and visceral fat , increased subcutaneous fat and increased adiponectin levels .


These effects do not appear to explain the glucose-lowering effect of rosiglitazone .


The aim of this study was to compare the preperitoneal versus the preaponeurotic mesh positioning in open paraumbilical hernia repair .


During the period from January 2011 until July 2012 , 60 adult patients were randomly assigned to two equal groups .


The patients in group A were treated by preperitoneal mesh repair and those in group B underwent preaponeurotic mesh repair .


Both groups were assessed and compared .


There were no significant differences between the two groups in the demographics , hernia characteristics , risk factors , type of anesthesia , American Society of Anesthesiologists score or the mean follow-up period .


The length of the operation was significantly shorter in group B than in group A ( P value = 0.01 ) .


There were no significant differences in the early postoperative complications except for the development of a seroma , which developed only in group B ( P value = 0.044 ) .


The postoperative pain was significantly lower in group A than in group B ( P value = 0.01 ) .


The time of return to normal daily activities was significantly shorter in group A than in group B ( P value = 0.001 ) .


The preperitoneal mesh placement during the repair of paraumbilical hernias is superior to the preaponeurotic placement , because it is associated with fewer complications , less pain and a shorter time of return to normal daily activities .


Subphenotypes have been identified within heterogeneous diseases such as asthma and breast cancer , with important therapeutic implications .


We assessed whether subphenotypes exist within acute respiratory distress syndrome ( ARDS ) , another heterogeneous disorder .


We used data from two ARDS randomised controlled trials ( ARMA trial and ALVEOLI trial ) , sponsored by the National Heart , Lung , and Blood Institute .


We applied latent class modelling to identify subphenotypes using clinical and biological data .


We modelled data from both studies independently .


We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure ( PEEP ) in the ALVEOLI cohort .


We analysed data for 1022 patients : 473 in the ARMA cohort and 549 in the ALVEOLI cohort .


Independent latent class models indicated that a two-class ( ie , two subphenotype ) model was the best fit for both cohorts .


In both cohorts , we identified a hyperinflammatory subphenotype ( phenotype 2 ) that was characterised by higher plasma concentrations of inflammatory biomarkers , a higher prevalence of vasopressor use , lower serum bicarbonate concentrations , and a higher prevalence of sepsis than phenotype 1 .


Participants in phenotype 2 had higher mortality and fewer ventilator-free days and organ failure-free days in both cohorts than did those in phenotype 1 ( p < 0007 for all ) .


In the ALVEOLI cohort , the effects of ventilation strategy ( high PEEP vs low PEEP ) on mortality , ventilator-free days and organ failure-free days differed by phenotype ( p = 0049 for mortality , p = 0018 for ventilator-free days , p = 0003 for organ-failure-free days ) .


We have identified two subphenotypes within ARDS , one of which is categorised by more severe inflammation , shock , and metabolic acidosis and by worse clinical outcomes .


Response to treatment in a randomised trial of PEEP strategies differed on the basis of subphenotype .


Identification of ARDS subphenotypes might be useful in selecting patients for future clinical trials .


National Institutes of Health .


Influenza is an important cause of morbidity and mortality worldwide .


Treatment options are scarce , and new drugs with novel mechanisms of action are needed .


We aimed to assess the efficacy and safety of nitazoxanide , a thiazolide anti-infective , for treatment of acute uncomplicated influenza .


We did a double-blind , randomised , placebo-controlled , phase 2b/3 trial in 74 primary care clinics in the USA between Dec 27 , 2010 , and April 30 , 2011 .


We enrolled participants aged 12-65 years with fever , at least one respiratory symptom , and one constitutional symptom of influenza within 48 h of symptom onset .


We randomly assigned participants to receive either nitazoxanide 600 mg , nitazoxanide 300 mg , or placebo twice daily for 5 days , ( ratio 1:1:1 ) and followed them up for 28 days .


Randomisation lists were computer generated and done in blocks of three .


Sponsor , investigators , study monitors , patients , and laboratory personnel were all masked to treatment allocation in the study .


The primary endpoint was the time from first dose to alleviation of symptoms .


The primary analysis was by intention-to-treat for participants with influenza infection confirmed by RT-PCR or culture at baseline .


This trial is registered with ClinicalTrials.gov , number NCT01227421 .


Of 650 participants screened , 624 ( 96 % ) were enrolled .


Of these , 212 were randomly assigned to receive placebo twice a day , 201 to receive nitazoxanide 300 mg twice a day , and 211 to receive nitazoxanide 600 mg a day .


The median duration of symptoms for participants receiving placebo was 1167 h ( 95 % CI 1081-1221 ) compared with 955 h ( 840-1080 ; p = 00084 ) for those receiving 600 mg nitazoxanide and 1091 h ( 961-1295 , p = 052 ) for those receiving 300 mg nitazoxanide .


Adverse events were similar between the three groups , the most common being headache reported by 24 ( 11 % ) of 212 patients enrolled in placebo group , 12 ( 6 % ) of 201 patients in the low-dose group , and 17 ( 8 % ) of 211 patients in the high-dose group , or diarrhoea , reported by seven ( 3 % ) patients in the placebo group , four ( 2 % ) patients enrolled in the low-dose group , and 17 ( 8 % ) patients in the high-dose group .


Treatment with nitazoxanide 600 mg twice daily for 5 days was associated with a reduction of the duration of symptoms in participants with acute uncomplicated influenza .


Further studies are warranted to confirm these findings and to assess efficacy of the drug alone or in combination with existing drugs in seriously ill patients and those at risk of influenza complications .


Romark Laboratories LC .


The effects on plaque parameters of sugar free chewing-gums ( CG ) sweetened with either maltitol or xylitol were assessed to better understand the role polyols can play in dental caries prevention .


A double-blind , parallel , randomised , controlled study was conducted in China .


Subjects ( N = 258 , age = 13 to 15 years-old ) were divided into 4 groups : 2 receiving polyols CG , containing respectively maltitol or xylitol , a group receiving gum base ( placebo ) and a negative control group not receiving any gum .


CG were chewed for 30 days .


This corresponds to a 10 g consumption of polyol per day .


Plaque parameters ( growth , pH , bacteria and insoluble glucans ) were evaluated throughout the experimental period .


All parameters studied were significantly modified with gum base compared to no-gum : plaque pH increased ; plaque growth , bacteria ( S. mutans , S. sobrinus , A. viscosus and Lactobacillus ) and insoluble glucans decreased .


Maltitol and xylitol CG led similarly to a higher plaque pH ( AUC , p0 .05 ) on short ( at baseline after the first CG consumption ) and long term ( after 4 weeks of daily CG consumption ) , with or without saliva stimulation compared to both control and placebo groups .


They led to a decrease in plaque growth ( p = 0.02 ) over the experimental period compared to controls .


Moreover , they significantly reduced the concentration of 4 cariogenic bacteria species ( p0 .05 ) in dental plaque compared to gum base .


Sugar free CG sweetened with either maltitol or xylitol can similarly reduce plaque acidogenicity compared to gum base through a decrease in oral bacteria presence .


The use of a gum base placebo allowed to isolate effects on parameters involved in dental caries development specific to maltitol and xylitol , and to show these effects were similar .


The prevalence of non-alcoholic fatty liver disease is increasing worldwide and an effective and safe pharmacological treatment is needed .


We investigated whether inhibition of 11-hydroxysteroid dehydrogenase type 1 ( 11-HSD1 , also known as HSD11B1 ) by RO5093151 could safely and effectively decrease liver-fat content in patients with this disorder .


We did this phase 1b trial at four centres in Germany and Austria .


Participants with non-alcoholic fatty liver disease ( defined as ( 1 ) H magnetic resonance spectroscopy liver-fat content > 556 % ) , insulin resistance ( homoeostatic model assessment of insulin resistance [ HOMA-IR ] of at least 20 mmol/LmU/L ) , BMI greater than 27 kg/m ( 2 ) , and aged 35-65 years were randomly assigned by interactive voice response system in a 1:1 ratio , stratified for triglyceride concentration ( < 17 mmol/L or 17 mmol/L ) , to oral RO5093151 ( 200 mg twice daily ) or matching placebo for 12 weeks .


The main exclusion criteria were other liver diseases , aspartate aminotransferase or alanine aminotransferase concentrations of more than two and a half times the upper limit of normal , history of diabetes or bariatric surgery , and use of weight lowering drugs .


Participants and investigators were masked to assignment throughout the study .


The primary endpoint was change in liver-fat content from baseline to week 12 .


Efficacy analysis was by modified intention to treat , including all patients who received at least one dose of study drug and had a baseline and follow-up measurement of liver-fat content .


Safety analyses included all patients who received at least one dose of study drug .


This trial is registered with ClinicalTrials.gov , number NCT01277094 .


We did this trial between Jan 13 , 2011 , and March 28 , 2012.41 patients were randomly assigned to RO5093151 and 41 to placebo .


35 patients in the RO5093151 group and 39 in the placebo group were included in the efficacy analysis .


Mean liver-fat content decreased in the RO5093151 group ( from 1675 % [ SD 867 ] to 1428 % [ 889 ] ) , but not in the placebo group ( from 1853 % [ 1000 ] to 1846 % [ 1078 ] , p = 002 for between group difference ) .


26 participants ( 65 % ) in the RO5093151 group had adverse events , compared with 21 ( 53 % ) in the placebo group .


The most common adverse events were gastrointestinal disorders ( 12 patients [ 30 % ] in the RO5093151 group vs seven [ 18 % ] in the placebo group ) , and infections and infestations ( eight [ 20 % ] vs nine [ 23 % ] ) .


Nervous system disorders occurred in significantly more patients in the RO5093151 group than in the placebo group ( nine [ 23 % ] vs two [ 5 % ] ; p = 002 ) ; all other differences in adverse events were non-significant .


One participant ( 3 % ) in the placebo group and three participants ( 8 % ) in the RO5093151 group had serious adverse events .


All serious adverse events were deemed unrelated to study treatment .


Inhibition of 11-HSD1 by RO5093151 was effective and safe in reducing liver-fat content , suggesting that targeting of 11-HSD1 might be a promising approach for the treatment of non-alcoholic fatty liver disease .


F Hoffmann-La Roche .


Bone marrow mononuclear cell ( BMMC ) transplantation for heart failure has shown inconsistent therapeutic efficacy .


We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery ( CABG ) .


After 4 - to 12-week pharmacotherapy optimization , 39 patients with left ventricular ejection fraction ( LVEF ) of 45 % received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized , double-blind manner .


The median number of cells injected was 8.4 10 ( 8 ) ( interquartile range [ IQR ] : 5.2 10 ( 8 ) to 13.5 10 ( 8 ) ) .


We measured LV function and myocardial scar size by magnetic resonance imaging ( MRI ) , and viability by positron emission tomography ( PET ) and single-photon emission computed tomography ( SPECT ) , pre-operatively and after 1-year follow-up .


LVEF , the pre-defined primary end-point measure , improved by a median of 5.6 % in the control group ( IQR 0.2 to 10.1 ) and by 4.8 % in the BMMC group ( IQR -0.5 to 8.2 ) ( p = 0.59 ) .


Wall thickening in injected segments rose by a median of 4.5 % among controls ( IQR -18.1 to 23.9 ) and by 5.5 % in the BMMC group ( IQR -6.6 to 26.5 ) ( p = 0.68 ) .


Changes in viability by PET and SPECT did not differ between groups .


Myocardial scar size by MRI in injected segments rose by a median of 5.1 % among controls ( IQR -3.3 to 10.8 ) , but fell by 13.1 % in the BMMC group ( IQR -21.4 to -6.5 ) ( p = 0.0002 ) .


BMMC therapy combined with CABG failed to improve LV systolic function , or viability , despite reducing myocardial scar size .


To assess the efficacy of moxibustion ( heating of the acupuncture needle with an igniting charcoal moxa stick ) with acupuncture for version of breech presentations after 33 4/7 weeks of gestation to reduce their rate at 37 weeks of gestation and at delivery .


This was a randomized placebo-controlled single-blind trial including 328 pregnant women recruited in a university hospital center between 33 4/7 and 35 4/7 weeks of gestation .


Moxibustion with acupuncture or inactivated laser ( placebo ) treatment was applied to point BL 67 for six sessions .


The principal endpoint was the percentage of fetuses in breech presentation at 37 2/7 weeks of gestation .


The study included 328 women randomized into two groups : moxibustion with acupuncture ( n = 164 ) or placebo ( n = 164 ) .


The percentage of fetuses in breech presentation at 37 2/7 weeks of gestation was not significantly different in both groups ( 72.0 in the moxibustion with acupuncture group compared with 63.4 % in the placebo group , relative risk 1.13 , 95 % confidence interval 0.98-1 .32 , P = .10 ) .


Treatment by moxibustion with acupuncture was not effective in correcting breech presentation in the third trimester of pregnancy .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT01487590 .


To evaluate the effects of different dosing intervals on multiple-dose pharmacokinetics , and safety and tolerability of fentanyl pectin nasal spray ( FPNS ) .


This was an open-label study in healthy volunteers .


Five FPNS treatments ( 1 100 g ; 2 100 g at 4 - , 2 - , and 1-hour intervals , and 8 100 g consecutively ) were administered to the right nostril , with a 3-day washout period .


Blood samples were collected at predose and up to 1,440 minutes postdose .


Plasma fentanyl concentrations were determined .


Pharmacokinetic parameters-peak concentration ( C ( max ) ) , time to C ( max ) ( t ( max ) ) , and area under the concentration-time curve ( AUC ) - were derived using noncompartmental method .


For the two-dose regimens , pharmacokinetic parameters were compared between doses using a paired t-test with p < 0.05 as statistically significant .


Thirteen subjects were enrolled and 10 completed the study .


Median tmax was 10-15 minutes across five regimens .


Cmax post the second dose significantly increased for 1-hour ( p < 0.0001 ) and 2-hour ( p < 0.001 ) but not 4-hour intervals ( p = 0.462 ) .


C ( max ) and AUC ( 0-24 ) following 8 100 g were approximately fivefold of those following 1 100 g. Dizziness ( 11.9 percent ) and somnolence ( 4.9 percent ) were most common adverse events ( AEs ) .


12.9 percent of patients discontinued due to AEs .


FPNS exhibited consistently rapid t ( max ) .


When intervals between two doses were shorter , the difference in C ( max ) between the first and second dose was larger .


All regimens of FPNS were well tolerated .


Exposure reached a plateau after eight consecutive doses , suggesting potential limited absorption through the nasal mucosa .


Transcranial random noise stimulation ( tRNS ) is an innovative technique of non-invasive electrical stimulation .


tRNS over the parietal cortex has improved cognitive function in healthy controls and , applied to the auditory cortex , tRNS has shown beneficial effects on tinnitus .


Here we aimed to investigate the effects of tRNS over the auditory cortex on resting state and evoked activity in healthy subjects .


We used EEG to measure tRNS induced changes in resting state activity and in auditory steady state responses ( ASSRs ) .


Stimuli were 1000 Hz carrier frequency tones , amplitude modulated at 20 Hz and 40 Hz and applied in randomized order .


Fourteen subjects participated in a placebo-controlled randomized design study ; each received 20 min of tRNS applied over auditory cortices with 2 mA , with a one week interval between real and sham stimulation .


We found a significant increase in the ASSR in response to 40 Hz frequency modulated tone and a non-significant trend toward an increase in mean theta band power and variability of the theta band power for the resting state data .


Our finding of tRNS induced increased excitability in the auditory cortex parallels previous findings of tRNS effects on motor cortex excitability and is in line with current concepts of tRNS mechanisms such as increase of stochastic resonance .


The purpose of this study was assess the effect of evolocumab ( AMG 145 ) on lipoprotein ( Lp ) ( a ) from a pooled analysis of 4 phase II trials .


Lp ( a ) , a low-density lipoprotein ( LDL ) particle linked to the plasminogen-like glycoprotein apolipoprotein ( a ) , shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies .


Current therapeutic options to reduce Lp ( a ) are limited .


A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab , a fully human monoclonal antibody to PCSK9 , on Lp ( a ) , the relationship between Lp ( a ) and lowering of low-density lipoprotein cholesterol ( LDL-C ) and apolipoprotein B , and the influence of background statin therapy .


Lp ( a ) was measured using a standardized isoform-independent method .


Evolocumab treatment for 12 weeks resulted in significant ( p < 0.001 ) mean ( 95 % confidence interval ) dose-related reductions in Lp ( a ) compared to control : 29.5 % ( 23.3 % to 35.7 % ) and 24.5 % ( 20.4 % to 28.7 % ) with 140 mg and 420 mg , dosed every 2 and 4 weeks , respectively , with no plateau of effect .


Lp ( a ) reductions were significantly correlated with percentages of reductions in LDL-C ( Spearman correlation coefficient , 0.5134 ; p < 0.001 ) and apolipoprotein B ( Spearman correlation coefficient , 0.5203 ; p < 0.001 ) .


Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins .


Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp ( a ) .


While the mean percentage of reduction was significantly greater in those patients with baseline Lp ( a ) of 125 nmol/l , the absolute reduction was substantially larger in those with levels > 125 nmol/l .


The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation ( rTMS ) and venlafaxine ( 150-225 mg/day ) is effective and safe for treatment-resistant unipolar depression ( TRD ) .


In a multicenter ( 18 centers ) randomized double blind controlled trial with three arms , 170 patients were allocated to receive active rTMS combined with active venlafaxine ( n = 55 ) , active rTMS combined with placebo venlafaxine ( n = 60 ) or sham rTMS combined with active venlafaxine ( n = 55 ) .


The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex ( 360 pulses/day delivered at 120 % of the resting motor threshold ) for two to six weeks ; rTMS was combined with active or sham venlafaxine ( mean dose : 179.0 36.6 mg/day ) .


The primary outcome was the number of patients who achieved remission , which was defined as an HDRS17 score < 8 .


We reported a similar significant antidepressant effect in the 3 groups ( P < 10 ( -6 ) ) , with a comparable delay of action and a comparable number of remitters at the endpoint ( 28 % in the combination group , 41 % in the rTMS group and 43 % in the venlafaxine group ; P = 0.59 ) .


Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD .


Because of its short session duration ( the duration of one session was 8.5 min ) and its safety , slow rTMS might be a useful alternative treatment for patients with TRD .


Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate ( TDF ) , with or without emtricitabine ( FTC ) , as pre-exposure prophylaxis ( PrEP ) for reducing the risk of HIV acquisition .


Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women ( FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study ) , but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials .


We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites ( Bondo , Kenya ; Bloemfontein , South Africa ; and Pretoria , South Africa ) to examine adherence levels over time and to assess factors associated with adherence , based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals .


We observed drug concentrations consistent with good adherence in 28.5 % of all visit intervals when drug was available to use , but only 12 % of participants achieved good adherence throughout their study participation .


In multivariate analysis , the Bloemfontein site [ odds ratio ( OR ) : 2.43 ; 95 % confidence interval ( CI ) : 1.32 to 4.48 ] and liking the pill color ( OR : 2.93 ; 95 % CI : 1.18 to 7.27 ) were positively associated with good adherence , whereas using oral contraceptive pills at enrollment was negatively associated with good adherence ( OR : 0.37 ; 95 % CI : 0.18 to 0.74 ) .


Most participants did not regularly adhere to the study product throughout their trial participation , although a small minority did .


Few factors associated with good adherence to the study product were identified in FEM-PrEP .


Randomized crossover laboratory study .


To determine the effects of ankle destabilization devices on surface electromyography ( sEMG ) measures of selected lower extremity muscles during functional exercises in participants with chronic ankle instability .


Ankle destabilization devices are rehabilitation tools that can be worn as a boot or sandal to increase lower extremity muscle activation during walking in healthy individuals .


However , they have not been tested in a population with pathology .


Fifteen adults with chronic ankle instability participated .


Surface electromyography electrodes were located over the anterior tibialis , fibularis longus , lateral gastrocnemius , rectus femoris , biceps femoris , and gluteus medius .


The activity level of these muscles was recorded in a single testing session during unipedal stance with eyes closed , the Star Excursion Balance Test , lateral hops , and treadmill walking .


Each task was performed under 3 conditions : shod , ankle destabilization boot , and ankle destabilization sandal .


Surface electromyography signal amplitudes were measured for each muscle during each exercise for all 3 conditions .


Participants demonstrated a significant increase , with moderate to large effect sizes , in sEMG signal amplitude of the fibularis longus in the ankle destabilization boot and ankle destabilization sandal conditions during the unipedal eyes-closed balance test , the Star Excursion Balance Test in the anterior and posteromedial directions , lateral hops , and walking , when compared to the shod condition .


Both devices also resulted in an increase in sEMG signal amplitudes , with large effect sizes of the lateral gastrocnemius , rectus femoris , biceps femoris , and gluteus medius during the unipedal-stance-with-eyes-closed test , compared to the shod condition .


Wearing ankle destabilization devices caused greater muscle activation during functional exercises in individuals with chronic ankle instability .


Based on the magnitude of the effect , there were consistent increases in fibularis longus sEMG amplitudes during the unipedal eyes-closed balance test , the Star Excursion Balance Test in the anterior and posteromedial directions , and pre-initial contact and post-initial contact during lateral hops and walking .


Oxygen is commonly administered after extubation .


Although several devices are available , data about their clinical efficacy are scarce .


To compare the effects of the Venturi mask and the nasal high-flow ( NHF ) therapy on PaO2/FiO2SET ratio after extubation .


Secondary endpoints were to assess effects on patient discomfort , adverse events , and clinical outcomes .


Randomized , controlled , open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation .


The Venturi mask ( n = 52 ) or NHF ( n = 53 ) were applied for 48 hours postextubation .


PaO2/FiO2SET , patient discomfort caused by the interface and by symptoms of airways dryness ( on a 10-point numerical rating scale ) , interface displacements , oxygen desaturations , need for ventilator support , and reintubation were assessed up to 48 hours after extubation .


From the 24th hour , PaO2/FiO2SET was higher with the NHF ( 287 74 vs. 247 81 at 24 h ; P = 0.03 ) .


Discomfort related both to the interface and to airways dryness was better with NHF ( respectively , 2.6 2.2 vs. 5.1 3.3 at 24 h , P = 0.006 ; 2.2 1.8 vs. 3.7 2.4 at 24 h , P = 0.002 ) .


Fewer patients had interface displacements ( 32 % vs. 56 % ; P = 0.01 ) , oxygen desaturations ( 40 % vs. 75 % ; P < 0.001 ) , required reintubation ( 4 % vs. 21 % ; P = 0.01 ) , or any form of ventilator support ( 7 % vs. 35 % ; P < 0.001 ) in the NHF group .


Compared with the Venturi mask , NHF results in better oxygenation for the same set FiO2 after extubation .


Use of NHF is associated with better comfort , fewer desaturations and interface displacements , and a lower reintubation rate .


Clinical trial registered with www.clinicaltrials.gov ( NCT 01575353 ) .


To analysis the clinical characteristics of children with cough variation asthma ( CVA ) who received treatments with Carboxymethl starch sodium solution and inhaled Glucocorticoid budesonide .


A total of 96 children with CVA were divided into two group randomly .


The control group ( n = 49 ) received inhaled budesonide treatment ( 500 microg/times in 1-5 years old children , 1 mg/times and 2 times/day in 6-14 years old children over a 12 week period ) .


The children in treatment group ( n = 47 ) were given carboxymethl starch sodium solution ( 3 mL/times in 1-3 years old children , 5 mL/times in 4-7 years old children , 7 mL/times in 8-14 years old children , 3 times/day ) in addition to the inhaled budesonide treatment .


Observations were made on clinical therapeutic effects , cough score and the level of IgE 4 weeks , 8 weeks and 12 weeks after the treatments , respectively .


Recurrence rate and adverse reactions were investigated .


Compared with the control group , the treatment group had significantly improved clinical characteristics after 8 weeks and 12 weeks of treatments ( P < 0.05 ) , and reduced cough scores after 4 weeks , 8 weeks and 12 weeks of treatments ( P < 0.05 ) .


The IgE level of the children in the treatment group was significantly lower than the controls after 12 weeks of treatments ( P < 0.05 ) .


The treatment group also had significantly lower recurrence rate and adverse reactions than the controls ( P < 0.05 ) .


Carboxymethl starch sodium solution can boost the clinical efficiency of inhaled budesonide in the treatment of children with cough variant asthma .


It is safe and effectual .


To determine any differences between the prevalence of adolescent idiopathic scoliosis in ballet dancers who are girls compared with age-matched nondancers , and to establish if any relations exist between the presence of scoliosis and generalized joint hypermobility , age of menarche , body mass index ( BMI ) , and the number of hours of dance training per week .


Cross-sectional , matched pair study .


Dance school .


Dancers ( n = 30 ) between the ages of 9 and 16 years were recruited from a certified dance school in Western Australia ; each dancer provided a consenting age-matched nondancer ( n = 30 ) .


Not applicable .


Measurements were taken for angle of trunk rotation using a scoliometer ( presence of scoliosis ) and for height and weight to produce generalized joint hypermobility using Beighton criteria and an age-adjusted BMI , respectively .


A subjective questionnaire regarding age of menarche and participation in dance and other sports was completed .


Thirty percent of dancers tested positive for scoliosis compared with 3 % of nondancers .


Odds ratio calculations suggest that dancers were 12.4 times more likely to have scoliosis than nondancers of the same age .


There was a higher rate of hypermobility in the dancer group ( 70 % ) compared with the nondancers ( 3 % ) ; however , there were no statistically significant relations between scoliosis and hypermobility , age of menarche , BMI , or hours of dance per week .


Adolescent dancers , similar to adult dancers , are at significantly higher risk of developing scoliosis than nondancers of the same age .


Vigilant screening and improved education of dance teachers and parents of dance students may be beneficial in earlier detection and , consequently , reducing the risk of requiring surgical intervention .


The aim of this study was to evaluate the effect of working length determination methods , electronic apex locator and digital radiography , on postoperative pain .


Two hundred twenty patients with asymptomatic single-rooted vital teeth were randomly assigned to 2 groups according to the method used for working length determination , the radiographic group and the electronic apex locator group .


After working length determination , chemomechanical preparation was performed in a crown-down technique with ProTaper instruments .


A master cone radiograph was taken .


Canals were obturated with gutta-percha and sealer by using a lateral compaction technique .


Postoperative pain was assessed after 4 , 6 , 12 , 24 , and 48hours by using a 4-point pain intensity scale .


In addition , patients were asked to record the number of days necessary to achieve complete pain resolution .


Postoperative pain during the 4-hour to 48-hour interval studied was not significantly different ( P > .05 ) between groups .


The mean times for pain dissipation in the radiographic and electronic apex locator groups were 3.37 2.79 and 3.88 3.34 days , respectively .


The difference between groups was not statistically significant ( P > .05 ) .


There is no difference in postoperative pain between working length measurement methods by using an electronic apex locator or digital radiography .


The reduced exposure to radiation by using apex locator may be a factor that influences a dentist 's decision to choose the electronic apex locator over radiography .


Rehabilitation has been reported to improve pain and disability for patients after lumbar surgery .


However , studies to investigate the rehabilitation intervention for lumbar decompression surgery during hospitalization are scarce .


The aim of this study was to examine outcomes of perioperative rehabilitation intervention for patients who underwent lumbar decompression surgery ( LDS ) .


Patients aged 18-65 years old who received their first LDS were randomized into the perioperative rehabilitation group ( PG ) or control group ( CG ) .


The PG received rehabilitation intervention during hospitalization for lumbar decompression surgery .


Pain , functional capacity , Roland-Morris Disability Questionnaire ( RMDQ ) , and Short-Form Health Survey ( SF-12 ) were assessed on admission , at discharge , and at follow-ups one month , three months , and six months after surgery .


Two-way repeated measures ANOVAs were used for statistical analysis .


A total of 60 patients scheduled for decompression surgery for lumbar stenosis were enrolled into the study .


After surgery , the PG showed significant pain relief and improvement of disability as well as quality of life , but there were no significant functional improvements compared with the CG .


The findings of this study indicate that the rehabilitation intervention during hospitalization improves pain intensity as well as disability and quality of life , yet has limited effects on the functional performance over time up to six months post-surgery in patients who received LDS .


The study suggest that rehabilitation interventions during hospitalization must include regular support for patient adherence to the intervention program and focus on task-oriented programs for lower extremities such as closed-chain exercises in functional postures .


The 5-HT1B / D agonists ( triptans ) are specific headache medications that have no effect on pain as such .


Although they are routinely used in the treatment of acute migraine attacks , the underlying mechanisms of action are still a matter of debate .


Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a standardized fMRI paradigm .


Using a crossover , double-blind , placebo-controlled design , 21 participants ( 10 women , mean age 26.9 , range 20-37 years ) received sumatriptan and 22 participants ( 11 women , mean age 25.5 , range 22-32 years ) received acetylsalicylic acid ( ASA ) .


Administration of medication and saline was randomized between participants of each group resulting in half of the participants receiving saline and the other half receiving the respective medication during the first fMRI data acquisition .


While mean pain intensity ratings did not differ significantly between control and medication nor between medications , we found a significant blood oxygen level-dependent signal increase in the trigeminal nuclei and the thalamus after sumatriptan treatment compared with placebo or ASA .


In addition , we specifically looked for the pharmacologic modulation of functional coupling between trigeminal nuclei and higher brain areas , i.e. , trigemino-cortical pathways , and found a strong coupling during the saline condition , which was altered by sumatriptan but not after ASA administration .


These data suggest that a specific functional inhibition of trigemino-cortical projections is one of the reasons that triptans , unlike pain killers , act highly specifically on headache and migraine but not pain as such .


To compare dilutional effect of distilled water with saline solution as an irrigation fluid in percutaneous nephrolithotomy ( PCNL ) .


Three hundred twenty eight adult patients ( 191 men , 137 women ) who were candidates for PCNL were randomly assigned into two groups ( distilled water , n = 158 , group 1 ; saline solution , n = 162 , group 2 ) .


Stone size , operation time , irrigation fluid volume , blood hemoglobin level , urea nitrogen , creatinine , sodium and potassium levels were checked before and at 6 and 12 hours after operation .


The mean age of the patients was 37.8 years , and the mean stone diameter was 31.5 mm .


There was no clinical case of transurethral resection ( TUR ) syndrome .


Serum sodium depletion was significantly more in group 1 than group 2 ( P < .0001 ) .


Group 1 had significant decreased post-operative serum sodium levels ( P < .0003 ) .


Similarly in group 2 , postoperative serum sodium levels were significantly lower than the preoperative concentration ( P < .01 ) , but it was not the same 6 hours after the operation ( P = .23 ) .


Serum sodium concentrations remained within normal limits in all cases , without causing clinical signs and symptoms of hyponatremia .


We found that distilled water is safe irrigation fluid for PCNL in adults .


In addition , it is more available and cost effective .


To determine whether field photodynamic therapy ( PDT ) of actinic keratoses using a novel preparation of 5-aminolevulonic acid ( novel ALA ) results in fewer subsequent invasive skin cancers developing on the face of individuals with previous facial cutaneous malignancy in a prospective randomized controlled trial .


Intervention patients received two treatments of novel ALA 2 weeks apart .


Controls were observed .


Patients were followed up with biopsy of any suspicious lesions for 3 years .


The trial was suspended early because of problems with trial governance and the reporting of severe adverse events .


Sixty-four patients who were recruited at that time at one center were monitored .


Their average age was 71 , and 57 % were male .


Patients were randomized to intervention ( n = 34 ) or observation ( n = 29 ) .


Over the subsequent 3 years , 13 intervention patients ( 38 % ) developed 30 new cutaneous malignancies in the field treated , and 11 control patients ( 38 % ) developed 22 new malignancies .


Some intervention patients experienced prolonged adverse events , including permanent scarring .


Novel ALA made no difference in the likelihood of new malignancies developing .


The risks without benefit of this novel ALA are troubling .


Lack of efficacy and safety of novel ALA can not be extrapolated to other PDT products .


Nonmedical use of prescription opioids ( NM-POs ) has reached epidemic proportions in the United States .


Unintentional overdose deaths involving prescription opioids have quadrupled since 1999 .


Herein , we examine NM-POs and their associated risk factors among two cohorts of trauma patients with at-risk drinking .


This secondary analysis examines NM-PO from two separate randomized trials that delivered brief alcohol interventions to patients in urban Level I trauma centers .


In the first study , data were collected from 1,493 injured patients at a single trauma center , and in the second study , data were collected from 596 injured patients at two trauma centers .


All participants were considered at-risk drinkers because they were admitted for an alcohol related injury as indicated by a positive blood alcohol concentration and/or self-reported heavy drinking .


In Study 1 , NM-PO nearly doubled from 5.2 % before admission to 9.8 % at 6 months after discharge .


At 12 months after discharge , those who reported NM-PO ( odds ratio [ OR ] , 2.31 ; 95 % confidence interval [ CI ] , 1.28-4 .15 ) and drug use ( OR , 2.62 , 95 % CI , 1.70-4 .04 ) before admission had the highest odds for postdischarge NM-PO .


In Study 2 , NM-PO increased from 5.2 % before admission to 6.8 % at 12 months after discharge .


At 12 months after discharge , those who reported NM-PO ( OR , 2.71 ; 95 % CI , 1.10-6 .66 ) or drug use ( OR , 4.05 ; 95 % CI , 2.00-8 .21 ) before admission had the highest odds for postdischarge NM-PO .


The results suggest that there is an increased risk of postdischarge NM-PO among injured patients with at-risk drinking , particularly among those with a recent history of drug use or NM-PO .


Cautious , evidence-based opioid prescribing may reduce exposure to prescription opioids in high-risk patients , risk of subsequent misuse , and possible diversion .


Prognostic/epidemiologic study , level II .


To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids .


Double-blind , randomized administration of two 12-week courses of ulipristal acetate .


Gynecology centers .


A total of 451 patients with symptomatic uterine fibroid ( s ) and heavy bleeding .


Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate .


Amenorrhea , controlled bleeding , fibroid volume , quality of life ( QoL ) , pain .


In the 5 - and 10-mg treatment groups ( 62 % and 73 % of patients , respectively ) achieved amenorrhea during both treatment courses .


Proportions of patients achieving controlled bleeding during two treatment courses were > 80 % .


Menstruation resumed after each treatment course and was diminished compared with baseline .


After the second treatment course , median reductions from baseline in fibroid volume were 54 % and 58 % for the patients receiving 5 and 10 mg of ulipristal acetate , respectively .


Pain and QoL improved in both groups .


Ulipristal acetate was well tolerated with less than 5 % of patients discontinuing treatment due to adverse events .


Repeated 12-week courses of daily oral ulipristal acetate ( 5 and 10 mg ) effectively control bleeding and pain , reduce fibroid volume , and restore QoL in patients with symptomatic fibroids .


NCT01629563 ( PEARL IV ) .


The aim of this study is to assess the effectiveness of a very brief structured counseling for tobacco cessation in dentistry clinics .


A cluster randomized trial was conducted in Sweden in 2012-2013 .


Twenty-seven dentistry clinics in two Swedish counties were randomized to provide either a structured brief advice based on the 5 A 's model or usual care .


Participants were 467 patients currently using tobacco daily ( 225 in the intervention group and 242 in usual care ) , of which 97 % were retained at follow-up , six months after enrolment .


Study outcomes were : 7-day abstinence ( primary outcome ) ; 3-month sustained abstinence ; 50 % reduction of the amount tobacco used ; quit attempts lasting at least 24h .


Compared to usual care , brief counseling was not associated to statistically significant increase in the proportion abstinent from tobacco use after 6months .


However , there was a statistically significant association with reduction of tobacco consumption ( OR = 2.07 95 % CI 1.28-3 .35 ) .


Changes in the expected direction for all outcomes were more frequent in the intervention than in the usual care group , and larger among exclusive snus users than among smokers .


Very brief and structured counseling in dentistry may achieve positive behavioral modifications among tobacco users , with significant reduction of tobacco consumption , particularly among smokeless tobacco users .


To study whether high-dose versus usual-dose statin treatment reduces the incidence of peripheral artery disease ( PAD ) and what is the effect of high-dose statin treatment on cardiovascular disease ( CVD ) outcome in patients with PAD .


In the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial , 8888 post-myocardial infarction patients were randomised to high-dose or usual-dose statin therapy ( atorvastatin 80mg/day vs simvastatin 20-40mg / day ) .


We investigated the effect of high-dose versus usual-dose statins on the pre-specified outcome PAD incidence , and additionally performed a posthoc analysis of the efficacy of high-dose statins in reducing CVD risk among patients with PAD .


During a median follow-up of 4.8 years , 94 patients ( 2.2 % ) receiving atorvastatin and 135 patients ( 3.2 % ) receiving simvastatin developed PAD ( HR = 0.70 , 95 % CI 0.53 to 0.91 ; p = 0.007 ) .


The risk of major coronary events was almost twofold higher in patients with PAD at baseline , but was no longer significant after adjusting for the adverse cardiovascular risk profile .


In PAD patients , major coronary events occurred in fewer patients in the atorvastatin group ( 14.4 % ) than in the simvastatin group ( 20.1 % ) , but the difference did not reach statistical significance .


( HR = 0.68 , 95 % CI 0.41 to 1.11 ; p = 0.13 ) .


Atorvastatin treatment significantly reduced overall cardiovascular ( p = 0.046 ) and coronary events ( p = 0.004 ) , and coronary revascularisation ( p = 0.007 ) in these patients .


High-dose statin therapy with atorvastatin significantly reduced the incidence of PAD compared with usual-dose statin therapy with simvastatin .


Patients with a history of PAD at baseline were at higher risk of future coronary events and this risk was reduced by high-dose atorvastatin treatment .


NCT00159835 ( URL : http://clinicaltrials.gov/show/NCT00159835 ) .


To evaluate the effect of tube current limitation on contrast enhancement , image quality , and radiation dose in whole-body 64-detector CT with a high heat-capacity X-ray tube and automated tube current modulation .


One hundred eighteen patients were randomized into three whole-body CT protocols : tube current limitation at 210 mA , 450 mA , and no limitation .


Signal-to-noise ratio ( SNR ) , dose-length product ( DLP ) , estimated effective dose ( ED ) , and image quality were assessed .


Mean SNR of aorta was comparable among protocols , but that of liver was somewhat lower in 210-mA than in 450-mA and no-limitation protocols ( p < 0.05 ) .


Mean DLP with 210-mA ( 533.8 mGy cm ) was reduced by 31 % from that with 450-mA ( 768.4 mGy cm ) and by 38 % from that with no-limitation protocol ( 861.3 mGy cm ) , respectively .


Image quality was slightly degraded ( p < 0.017 ) with 210 mA relative to the others in thorax and pelvis , but no difference was found in diagnostic acceptability .


For whole-body CT using multidetector CT mounted with a high heat-capacity X-ray tube , an appropriate tube current limitation setting may help reduce excessive radiation dose without significant compromise in diagnostic acceptability .


To compare the efficacy and safety of long-term treatment ( 48 weeks ) with tiotropium bromide ( 5 g ) via Respimat ( ) with placebo in patients with chronic obstructive pulmonary disease ( COPD ) .


A total of 338 patients were randomized in this double-blind , placebo controlled , parallel study .


All patients received either tiotropium bromide or placebo .


Tiotropium bromide solution 5 g ( 22.5 g/puff ) or matching placebo was delivered via Respimat ( ) at a dosage of once daily for 48 weeks .


Co-primary endpoints were trough forced expiratory volume in one second ( FEV ( 1 ) ) and the time to first exacerbation .


Statistically significant improvements of both trough FEV ( 1 ) and trough forced vital capacity ( FVC ) in the tiotropium group were achieved at weeks 4 , 24 , and 48 compared with those in the placebo group ( P < 0.000 1 ) .


Tiotropium treatment delayed the time to first exacerbation .


The time was 157 days in the tiotropium group and 85 days in the placebo group .


A statistically significant difference ( P = 0.002 7 ) in favor of tiotropium was also observed .


The total numbers of exacerbation during treatment were 90 and 128 in the tiotropium and placebo groups , respectively .


The Poisson regression analysis gave a mean exacerbation rate per patient year exposure of 0.67 in the tiotropium group compared to 0.98 in the placebo group with a rate ratio of 0.69 ( 95 % CI 0.50-0 .93 , P = 0.016 4 ) .


A much larger improvement from baseline in St. George 's respiratory questionnaire ( SGRQ ) total score was observed for the tiotropium group than in the placebo group ( P = 0.036 7 ) , SGRQ symptom and activity scores of patients in the tiotropium group were also superior to those of patients receiving placebo .


The drugs-related adverse events in the tiotropium and placebo groups were 12 cases and 11 cases , respectively .


Tiotropium significantly improved lung function and quality of life , delayed the time to first exacerbation , reduced the number of exacerbation .


Overall , tiotropium was well tolerated .


According to the International Association for the Study of Pain ( IASP ) , the term temporomandibular disorder ( TMD ) regards a subgroup of orofacial pain , the symptoms of which include pain or discomfort in the temporomandibular joint , ears , masticatory muscles and neck on one or both sides , as well as joint sounds , limited mandibular movements or mandibular deviation and difficulties chewing .


Phototherapy , such as low-level laser therapy ( LLLT ) and light-emitting diode ( LED ) therapy , is one of the resources used to treatment muscle pain .


Thus , there is a need to investigate therapeutic resources that combine different wavelengths as well as different light sources ( LLLT and LED ) in the same apparatus .


The aim of the proposed study is to evaluate the effects of four different doses of phototherapy on pain , activity of the masticatory muscles ( masseter and bilateral anterior temporal ) and joint mobility in individuals with temporomandibular disorder .


A further aim is to determine the cumulative effect 24 and 48 hours after a single session .


A placebo-controlled , double-blind , randomized , clinical trial will be carried out involving 72 women between 18 and 40 years of age with a diagnosis of myogenous TMD .


The participants will then be randomly allocated to four groups totaling 18 individuals per group .


Three groups will be submitted to a single session of phototherapy with different light sources , and one group will receive placebo therapy : Group A ( 2.62 Joules ) ; Group B ( 5.24 Joules ) ; Group C ( 7.86 Joules ) ; and Group D ( 0 Joules ) .


The following assessment tools will be administered on four separate occasions ( baseline and immediately after , 24 h after and 48 h after phototherapy ) .


Pain intensity will be assessed using the visual analog scale for pain , while pain thresholds will be determined using algometer , and electromyographic ( EMG ) analysis on the masseter and anterior temporal muscles .


The study will contribute to the practice of the evidence-based use of phototherapy in individuals with a myogenous TMD .


Data will be published after the study is completed .


This study is registered with the Brazilian Registry of Clinical Trials , NCT02018770 , date of registration : 7 December 2013 .


Data relating to the impact of body mass index ( BMI ) on outcomes after isolated aortic valve replacement ( AVR ) are scarce and controversial .


The study aim was to investigate the predictive value of BMI for early and late mortality after isolated AVR .


Data obtained from patients who underwent isolated AVR between January 1998 and December 2010 at the authors ' institution were analyzed retrospectively .


Patients were allocated to five groups according to the preoperative BMI : underweight ( BMI < 20 kg/m2 ) ; normal weight ( BMI 20.0-24 .9 kg/m2 ) ; overweight ( BMI 25.0-29 .9 kg/m2 ) ; obese ( BMI 30.0-34 .9 kg/m2 ) ; and morbidly obese ( BMI > 34.9 kg/m2 ) .


Logistic and Cox regression analyses were performed to identify the independent predictors of early and late mortality , respectively .


After excluding 20 patients who were lost to follow up , and 30 patients with missing preoperative BMI data , a total of 1,758 patients was included in the analysis .


The mean follow up was 5.6 + / - 3.5 years ( range : 0-13 .4 years ) , and the mean BMI 26.8 + / - 4.3 kg/m2 ( range : 17-52 kg/m2 ) .


Multivariate logistic regression analyses showed no association between early mortality and the BMI groups .


Multivariate Cox regression analyses showed ` underweight ' to be an independent predictor for late mortality ( hazard ratio 2.89 ; 95 % confidence interval 1.63-5 .13 , p < 0.0001 ) .


` Underweight ' is an independent predictor for late mortality after AVR surgery .


Morbid obesity did not prove to be predictive of a worse late survival .


Patients with mild to moderate obstructive sleep apnoea ( OSA ) commonly suffer excessive daytime sleepiness .


Continuous positive airway pressure ( CPAP ) has limited effectiveness in reducing sleepiness in milder OSA .


Modafinil is a wake-promoting drug licensed to treat residual sleepiness in CPAP-treated OSA .


We hypothesised that modafinil may effectively treat sleepiness in untreated mild to moderate OSA .


Untreated sleepy men with mild to moderate OSA ( age 18-70 , apnoea-hypopnoea index ( AHI ) 5-30 / h , Epworth Sleepiness Scale ( ESS ) 10 ) were randomised to receive 200 mg modafinil or matching placebo daily for 2 weeks before crossing over to the alternative treatment after a minimum 2-week washout .


Mixed model analysis of variance was used to compare the changes on modafinil to placebo while classifying all randomised patients as random factors .


32 patients were randomised ( mean ( SD ) AHI 13 ( 6.4 ) / h , age 47 ( 10.7 ) years , ESS 13.6 ( 3.3 ) , body mass index 28.2 ( 3.6 ) kg/m ( 2 ) ) , 29 of whom ( 91 % ) completed the trial .


The primary outcome ( ESS ) improved more on modafinil than placebo ( 3.6 points , 95 % CI 1.3 to 5.8 , p = 0.003 ) and the secondary outcome ( 40-min driving simulator performance ) also improved more on modafinil than placebo ( steering deviation 4.7 cm , 95 % CI 0.8 to 8.5 , p = 0.018 ) .


Psychomotor Vigilance Task reciprocal reaction time improved significantly over placebo ( 0.15 ( 1/ms ) , 95 % CI 0.03 to 0.27 , p = 0.016 ) .


Improvements on the Functional Outcomes of Sleep Questionnaire were not significant ( 5.3 points over placebo , 95 % CI -1 to 11.6 , p = 0.093 ) .


Modafinil significantly improved subjective sleepiness in patients with untreated mild to moderate OSA .


The size of this effect is clinically relevant at 3-4 ESS points of improvement compared with only 1-2 points in CPAP clinical trials .


Driving simulator performance and reaction time also improved on modafinil .


ACTRN # 12608000128392 .


This study investigated the effects of irrigation solutions , administered at either 21 or 37C in percutaneous nephrolithotomy ( PCNL ) , on hypothermia and related postoperative complications such as late emergence and late recovery from anesthesia , shivering , lactic acidosis , and excess bleeding .


Sixty patients who were scheduled for PCNL were enrolled in this prospective randomized double-blind study .


Irrigation solutions at room temperature were administered to patients in group R ( 30 patients ) , and warmed irrigation solutions were administered to patients in group W ( 30 patients ) .


The two groups were compared for core and peripheral body temperature , incidence of hypothermia , duration of emergence from anesthesia , duration of recovery from anesthesia , shivering , lactic acidosis , and hemoglobin levels .


Hypothermia was incident in 19patients ( 63.3 % ) in group W and in 27 patients ( 90 % ) in group R at the end of surgery .


The difference between the initial and the final core body temperature was 0.90.6 C group W and 1.40.7 C in group R ( p = 0.003 ) .


The extubation time was 4.42.2 min in group W and 5.93 min in group R ( p = 0.032 ) .


Shivering was detected in seven patients ( 23.3 % ) in group W and in 15patients ( 50 % ) in group R ( p = 0.032 ) .


The recovery duration was 49.824.6 min in group W and 67.633.9 min in group R ( p = 0.023 ) .


Administration of irrigation solutions at room temperature in PCNL operations causes the body temperature to decrease significantly , which results in postoperative complications such as late emergence from anesthesia , late recovery from anesthesia , and shivering .


The aim of this study was to assess the effect of intraoral aging on the setting status of a resin composite and a glass ionomer adhesive , relative to control specimens stored in water .


Metallic brackets were bonded with resin composite orthodontic adhesive ( Transbond XT ; 3M Unitek , Monrovia , Calif ) or a glass ionomer cement ( Fuji I ; GC , Tokyo , Japan ) to recently extracted premolars and kept in water for 6 months .


The same materials were also bonded to the premolars of orthodontic patients .


After 6 months , the teeth were carefully extracted , with the brackets intact on their buccal surfaces .


All teeth were embedded in epoxy resin and sectioned buccolingually .


Fourier transform infrared microscopy and Raman microscopy were used for the estimation of the degree of cure in the composite and the salt yield in the glass ionomer adhesives .


The control samples of the composite showed significantly lower degrees of cure than did the retrieved specimens ( 52.40 % 3.21 % vs 57.62 % 1.32 % by Fourier transform infrared microscopy , and 61.40 % 2.61 % vs 67.40 % 3.44 % by Raman microscopy ) .


Raman microscopy significantly overestimated the degree of cure and failed to provide reliable information for the salt yield in the glass ionomer cement .


Fourier transform infrared microscopy showed increased , but no statistically significant difference in , aluminum-carboxylate salts in the retrieved specimens .


Enhanced oxidation of residual carbon-carbon bonds in the composite and slightly increased dissolution of the weaker calcium-salt phase in the glass ionomer cement were the main differences in the intraorally aged specimens in comparison with the specimens stored in water .


Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention ( PCI ) in patients with an acute coronary syndrome .


We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin .


Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion .


Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events ( a composite of death , myocardial infarction , or stroke ) and net adverse clinical events ( a composite of major bleeding or a major adverse cardiovascular event ) .


The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization , definite stent thrombosis , or net adverse clinical events .


The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin ( 10.3 % and 10.9 % , respectively ; relative risk , 0.94 ; 95 % confidence interval [ CI ] , 0.81 to 1.09 ; P = 0.44 ) , nor was the rate of net adverse clinical events ( 11.2 % and 12.4 % , respectively ; relative risk , 0.89 ; 95 % CI , 0.78 to 1.03 ; P = 0.12 ) .


Post-PCI bivalirudin infusion , as compared with no infusion , did not significantly decrease the rate of urgent target-vessel revascularization , definite stent thrombosis , or net adverse clinical events ( 11.0 % and 11.9 % , respectively ; relative risk , 0.91 ; 95 % CI , 0.74 to 1.11 ; P = 0.34 ) .


In patients with an acute coronary syndrome , the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin .


The rate of the composite of urgent target-vessel revascularization , definite stent thrombosis , or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion .


( Funded by the Medicines Company and Terumo Medical ; MATRIX ClinicalTrials.gov number , NCT01433627 . )


Afatinib is an oral , irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor ( EGFR ) - mutated lung cancer .


We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic ( R/M ) head and neck squamous cell carcinoma ( HNSCC ) patients , whose disease has progressed after platinum-containing therapy .


An open-label , randomized , phase II trial was conducted in 43 centers ; 124 patients were randomized ( 1 : 1 ) to either afatinib ( 50 mg/day ) or cetuximab ( 250 mg/m ( 2 ) / week ) until disease progression or intolerable adverse events ( AEs ) ( stage I ) , with optional crossover ( stage II ) .


The primary end point was tumor shrinkage before crossover assessed by investigator ( IR ) and independent central review ( ICR ) .


A total of 121 patients were treated ( 61 afatinib , 60 cetuximab ) and 68 crossed over to stage II ( 32 and 36 respectively ) .


In stage I , mean tumor shrinkage by IR/ICR was 10.4 % / 16.6 % with afatinib and 5.4 % / 10.1 % with cetuximab ( P = 0.46 / 0.30 ) .


Objective response rate was 16.1 % / 8.1 % with afatinib and 6.5 % / 9.7 % with cetuximab ( IR/ICR ) .


Comparable disease control rates were observed with afatinib ( 50 % ) and cetuximab ( 56.5 % ) by IR ; similar results were seen by ICR .


Most common grade 3 drug-related AEs ( DRAEs ) were rash/acne ( 18 % versus 8.3 % ) , diarrhea ( 14.8 % versus 0 % ) , and stomatitis/mucositis ( 11.5 % versus 0 % ) with afatinib and cetuximab , respectively .


Patients with DRAEs leading to treatment discontinuation were 23 % with afatinib and 5 % with cetuximab .


In stage II , disease control rate ( IR/ICR ) was 38.9 % / 33.3 % with afatinib and 18.8 % / 18.8 % with cetuximab .


Afatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial , although more patients on afatinib discontinued treatment due to AEs .


Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover , suggesting a lack of cross-resistance .


Exercise training may improve components of metabolic syndrome and obstructive sleep apnea syndrome ( OSAS ) .


The objective of our pilot randomized controlled study was to determine the benefits of a short intensive inpatient individualized exercise training ( IET ) program in sedentary untreated OSAS patients .


Twenty-two sedentary patients with moderate to severe OSAS were randomly assigned either to one-month education activity sessions ( n = 11 ; control group ) or to inpatient rehabilitation program ( n = 11 ) , including IET , education activities sessions , and dietary management .


Full polysomnography ( PSG ) , OSLER ( Oxford Sleep Resistance test ) , body composition , anthropometric measurements , metabolic syndrome components , and questionnaires were performed at baseline and at study end point .


No changes occurred in the control group in all variables .


Compared to controls , participants randomized to the IET group presented a significant decrease in apnea-hypopnea index ( AHI ) ( 40.619.4 vs. 28.019.3 ; P < 0.001 ) , oxygen desaturation index ( ODI ) , and arousal index , which occurred in conjunction with significant decrease in body mass index ( BMI ) , neck circumference , fat mass , fasting glucose , and diastolic blood pressure .


Increased sleep latency was found in participants in the IET group with altered values at baseline .


IET reduced OSAS severity with improvement of metabolic syndrome components with concomitant loss in body fat in sedentary adults .


If confirmed on a larger scale , a comprehensive rehabilitation program could constitute an additional or alternative treatment for moderate to severe OSAS patients .


The most appropriate means of capturing data from the Neuropsychiatric Inventory ( NPI ) must be understood to optimize use of this instrument in clinical trials .


The utility of the composite score ( frequency times severity ) was recently demonstrated in mild and moderate dementia .


Determination of frequency compared to composite scores in mild cognitive impairment ( MCI ) warrants investigation .


We used the NPI data from a randomized , placebo-controlled , multi-center , 24-week , clinical trial involving 160 patients who were diagnosed with amnestic MCI and had clinically significant neuropsychiatric symptoms ( NPS ) .


We calculated standardized changes for both frequency and composite scores .


There were improvements in NPI composite scores in both active drug - and placebo-treated patients , with significant superiority of active drug .


Standardized changes in severity and composite scores tended to be larger than those in the frequency scores , whereas discrimination between treatment groups was similar for all three scores .


Our findings support the hypothesis that in MCI , as in dementia , the NPI frequency score is not more sensitive to treatment-related change than the composite score .


As the severity score adds information , the use of the composite score has better performance characteristics .


Patients with type 2 diabetes mellitus ( T2DM ) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide ( GIP ) .


We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses of glucagon and insulin and glucose disposal in patients with T2DM .


We performed a single center , placebo-controlled , cross-over , experimental study .


We studied twelve patients with T2DM ( age : 62 1 years [ mean SEM ] , body mass index : 29 1 kg/m ( 2 ) ; glycosylated hemoglobin A1c : 6.5 0.1 % [ 48 2 mmol/mol ] ) .


We infused physiological amounts of GIP ( 2 pmol kg ( -1 ) min ( -1 ) ) or saline .


We measured plasma concentrations of glucagon , glucose , insulin , C-peptide , intact GIP , and amounts of glucose needed to maintain glucose clamps .


During fasting glycemia ( plasma glucose 8 mmol/L ) , GIP elicited significant increments in both insulin and glucagon levels , resulting in neutral effects on plasma glucose .


During insulin-induced hypoglycemia ( plasma glucose 3 mmol/L ) , GIP elicited a minor early-phase insulin response and increased glucagon levels during the initial 30 minutes , resulting in less glucose needed to be infused to maintain the clamp ( 29 8 vs 49 12 mg kg ( -1 ) , P < .03 ) .


During hyperglycemia ( 1.5 fasting plasma glucose 12 mmol/L ) , GIP augmented insulin secretion throughout the clamp , with slightly less glucagon suppression compared with saline , resulting in more glucose needed to maintain the clamp during GIP infusions ( 265 21 vs 213 13 mg kg ( -1 ) , P < .001 ) .


In patients with T2DM , GIP counteracts insulin-induced hypoglycemia , most likely through a predominant glucagonotropic effect .


In contrast , during hyperglycemia , GIP increases glucose disposal through a predominant effect on insulin release .


To determine the effect of fall-related concerns on physical , mental , and social function .


Community-based prospective cohort study ( secondary analysis using control group data from a randomized controlled trial ) .


Two municipalities in the south of the Netherlands .


Community-dwelling older adults ( N = 260 ) .


Two groups were created using Modified Falls Efficacy Scale scores ( high and low levels of fall-related concerns ) .


Five outcome measures representing physical , mental , and social function were included : activities of daily living ( ADLs ) , symptoms of depression , feelings of anxiety , social participation , and social support interactions .


Outcomes were measured at baseline and at 2 , 8 , and 14 months .


Data were analyzed using analysis of covariance and mixed-effect regression models for longitudinal data , adjusting for age , sex , living status ( alone or with another person ) , educational level , cognitive status , self-perceived health , and falls history at baseline .


At baseline , significantly more limitations in ADLs and social participation were found for older persons with high levels of fall-related concerns than for those with low levels of concern .


These differences persisted over 14 months of follow-up and were consistent over time .


No significant differences were found for symptoms of depression , feelings of anxiety , or social support interactions , except for feelings of anxiety at 14 months .


Older persons with higher levels of fall-related concerns reported up to 14 months poorer ADL and social participation for up to 14 months than those with lower levels of fall-related concerns .


From a clinical point of view , the clear relationship between fall-related concerns and ADL dysfunction and social participation may help to target groups who are at risk of developing adverse consequences of concerns about falls .


To determine whether an intensive lifestyle intervention ( ILI ) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up .


This randomized controlled trial of intensive weight loss compared an ILI with a diabetes support and education ( DSE ) group among 1,309 overweight or obese subjects .


Bone mineral density was assessed at baseline and after 1 year and 4 years of intervention .


ILI was effective in producing significant weight loss ( 5.3 % vs. 1.8 % in ILI and DSE , respectively ; P < 0.01 ) and increased fitness ( 6.4 % vs. -0.8 % ) at year 4 .


In men , ILI participants had a greater rate of bone loss during the first year ( -1.66 % vs. -0.09 % per year in ILI and DSE , respectively ) .


Differences between groups were diminished by one-half after 4 years ( -0.88 % vs. -0.05 % per year in ILI and DSE , respectively ) but remained significant ( P < 0.01 ) .


The difference in rate of hip bone loss between groups over 4 years was related to increased weight loss in ILI .


Among women , the rate of bone loss did not differ between ILI and DSE after 4 years .


A 4-year weight loss intervention was significantly associated with a modest increase in bone loss at the hip in men but not in women .


Epidemiological studies have found a U-shaped relationship between serum phosphorus and cardiovascular disease ( CVD ) .


The mechanism ( s ) behind such a relationship are poorly understood .


Phosphorus ( P ) is reported to improve insulin sensitivity , which is involved in lipid metabolism , and thus we were interested in determining the impact of phosphorus ingestion on postprandial lipemia , a recognized CVD risk factor .


A within-subject study design was conducted , whereby 8 healthy male subjects received a high fat meal ( 330 Kcal ; 69 % energy from fat ; 35 mg of phosphorus ) with placebo or phosphorus ( 500 mg ) in a random order .


Postprandial blood samples ( ~ 10 ml ) were collected every hour for 6 hours after meal ingestion .


Changes in different parameters were analyzed using a 2-factor repeated-measure ANOVA .


In the phosphorus ( P ) supplemented group , postprandial serum P increased ( p = 0.00 ) , while changes in insulin , non-esterified fatty acids ( NEFA ) and triglyceride ( TG ) were not significantly different than that of placebo .


Concurrently , phosphorus supplementation increased postprandial concentrations of apolipoprotein B48 ( ApoB48 ) ( p < 0.05 ) and decreased that of apolipoprotein B100 ( ApoB100 ) ( p < 0.05 ) .


Phosphorus supplementation ( 500 mg ) of the meal seems to alter the different components of postprandial lipemia .


These findings highlight the potential role of phosphorus in CVD .


To determine whether extracranial-intracranial ( EC-IC ) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery ( ICA ) occlusion and increased oxygen extraction fraction ( OEF ) on PET .


Patients underwent ( 15 ) O PET and were randomized if OEF ratio was > 1.13 on the occluded side .


Using blinded baseline and 2-year cognitive assessments , age-adjusted composite z scores were generated from subtests sensitive to right/left hemisphere plus global cognitive functioning .


Multiple regression predicted 2-year cognitive change .


Eighty-nine patients were enrolled ; 41 had increased OEF and were randomized .


Two died , 2 were lost to follow-up , and 2 refused 2-year testing .


Of the 35 remaining , 6 had ipsilateral stroke or death , leaving 13 surgical and 16 medical patients .


Controlling for age , education , and depression , there was no difference in 2-year cognitive change between the medical and surgical arms ( 95 % confidence interval -0.5 to 0.5 , p = 0.9 ) .


In post hoc analysis of 26 patients with no stroke in the follow-up period , cognitive improvement was associated with less impaired PET OEF at baseline ( p = 0.045 ) .


Cognitive improvement following bypass surgery was not superior to medical therapy among patients with recently symptomatic carotid occlusion and increased OEF .


Among those with no recurrent stroke , less hemodynamic impairment at baseline was associated with greater cognitive gain in both groups .


Reversing cognitive impairment in hemodynamic failure remains an open challenge .


This study provides Class II evidence that for patients with symptomatic ICA occlusion and increased OEF on PET , EC-IC bypass compared to no bypass does not improve cognitive function after 2 years .


To evaluate the safety , tolerability , and comparative pharmacokinetics ( PK ) of intravenous and oral carbamazepine .


In this phase 1 , open-label study , adult patients with epilepsy on a stable oral carbamazepine dosage ( 400-2 ,000 mg/day ) were converted to intravenous carbamazepine ( administered at 70 % of the oral dosage ) .


A 28-day outpatient period preceded an up to 10-day inpatient period and a 30-day follow-up period .


Intravenous carbamazepine was administered over 15 or 30 min every 6 h on days 1-7 ; some patients in the 15-min group were eligible to receive four 2 - to 5-min ( rapid ) infusions on day 8 .


Patients underwent blood sampling to determine the area under the concentration-time curve ( AUC ) for carbamazepine and metabolite carbamazepine-10 ,11 - epoxide following oral ( day 0 ) and intravenous carbamazepine administration ( days 1 , 7 , and 8 ) .


Bioequivalence was evaluated in patients with normal renal function ( creatinine clearance > 80 ml/min ) .


Safety assessments were conducted through day 38 .


Ninety-eight patients enrolled and 77 completed the PK component .


The mean daily oral and intravenous carbamazepine dosage for 64 PK-evaluable patients with normal renal function was 962.5 and 675.1 mg ( 70 % of oral dosage ) , respectively .


Steady-state minimum concentration ( C ( min ) ) and overall exposure ( AUC0-24 ) for intravenous carbamazepine infused over 30 , 15 , or 2-5 min were similar to oral carbamazepine .