Extensive ophthalmic examination was performed , including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity , applanation tonometry , slit-lamp examination , indirect ophthalmoscopy , digital color fundus photography , and optical coherence tomography ( OCT ) .


In selected cases , additional examinations were performed , including visual field testing and electro-oculography ( EOG ) .


Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium ( RPE ) proteins .


Visual symptoms , visual acuity , fundus appearance , characteristics on OCT , fundus autofluorescence ( FAF ) , and EOG .


Six CM patients ( 20 % ) and 2 UM patients ( 40 % ) reported visual symptoms during the study .


The median time to the onset of symptoms , which were all mild and transient , was 3.5 days ( range , < 1 hour to 3 weeks ) .


On OCT , subretinal fluid ( SRF ) was detected in 77 % of CM patients and 60 % of UM patients .


In the 26 patients with SRF , the fovea was affected in 85 % .


After the start of the medication , an EOG was performed in 19 eyes of 11 patients ; 16 of these eyes ( 84 % ) developed SRF on OCT. .


Fifteen of these eyes ( 94 % ) showed an abnormal Arden ratio ( < 1.65 ) .


A broad pattern of anti-retinal antibodies was found in 3 CM patients and 2 UM patients tested , whereas anti-RPE antibodies were detected in all 6 tested patients .


A time-dependent and reversible serous retinopathy can develop both in patients with metastatic CM and UM treated with binimetinib .


A minority of patients develop visual symptoms , which are generally mild and transient .


A cause of binimetinib-associated serous retinopathy may be toxicity of medication , but autoantibodies also may be involved .


Leukocytapheresis is an extracorporeal therapy for ulcerative colitis .


However , no large-scale study on leukocytapheresis has been reported .


This large-scale , prospective , observational study aimed to evaluate the treatment outcomes of leukocytapheresis for active ulcerative colitis in clinical practice .


Patients with active ulcerative colitis treated with leukocytapheresis using a Cellsorba E column between May 2010 and December 2012 were enrolled from 116 medical facilities in Japan .


A total of 847 patients were enrolled , and 623 were available for efficacy analysis .


Out of 847 patients , 80.3 % of the patients had moderate to severe disease activity , and 67.6 % were steroid refractory .


As concomitant medications , 5-aminosalicylic acids , corticosteroids , and thiopurines were administered to 94.8 % , 63.8 % , and 32.8 % of the patients , respectively .


In addition , infliximab and tacrolimus were concomitantly used in 5.8 % and 12.3 % , respectively .


Intensive leukocytapheresis ( 4 leukocytapheresis sessions within the first 2 weeks ) was used in > 70 % of the patients .


Adverse events were seen in 10.3 % ( 87/847 ) , which were severe in only 5 patients ( 0.6 % ) .


Any concomitant medications did not increase the incidence of adverse events .


Intensive leukocytapheresis was as safe as the conventional weekly procedure .


The overall clinical remission rate was 68.9 % ( 429/623 ) , and the mucosal healing rate was 62.5 % ( 145/232 ) .


Clinical remission was achieved more frequently and rapidly in the intensive group than in the weekly group .


This large-scale study indicates that leukocytapheresis , including intensive procedure , is a safe and effective therapeutic option for active ulcerative colitis .


The anaesthetic potency of intravenous propofol is quantified by its Cp50 value , which is defined as the plasma concentration required to prevent movement response in 50 % of patients to surgical stimuli .


We hypothesised that , in addition to propofol anaesthesia , an intravenous bolus of lidocaine 1.5 mg/kg will decrease the Cp50 value of propofol during anaesthesia .


We enrolled 54 elective surgical patients undergoing propofol-based anaesthesia , and randomised them to either lidocaine 1.5 mg/kg , lidocaine 0.5 mg/kg or placebo ( NaCl 0.9 % ) 3min before skin incision .


The propofol Cp50 value was then calculated using the ` up-and-down ' method of Dixon and Massey .


There was no significant reduction in propofol requirements after the administration of 0.5 mg/kg lidocaine from 8.5 g/ml [ confidence interval ( CI ) 6.0-11 .625 ] to 8.25 g/ml ( CI 6.75-9 .76 ) ; however , a bolus of 1.5 mg/kg lidocaine decreased the Cp50 value of propofol by 42 % from 8.5 g/ml ( CI 6.0-11 .625 ) to 4.92 g/ml ( CI 4.5-5 .78 ) ( P < 0.05 ) .


An intravenous bolus injection of 1.5 mg/kg lidocaine 2 % caused a significant reduction of the propofol Cp50 value .


The purpose of this study was to compare the success rate of monocanalicular versus that of bicanalicular silicone intubations of the nasolacrimal duct for nasolacrimal duct stenosis ( NLDS ) in adults ( patent nasolacrimal duct with resistance to positive-pressure irrigation ) .


In a prospective randomized clinical trial , 52 eyes of 38 patients with NLDS underwent either monocanalicular silicone intubation ( MCI ) ( n = 26 eyes ) or bicanalicular silicon intubation ( BCI ) ( n = 26 eyes ) .


All procedures were performed by 1 oculoplastic surgeon .


Tube removal was planned for 3 months postoperatively .


Treatment success was defined as the complete resolution of epiphora or intermittent epiphora with normal dye disappearance test at 6 months after tube removal .


The surgical outcome was assessed in 25 eyes with MCI and 21 eyes with BCI .


The mean ( SD ) age of treatment was 52.7 ( 18.6 ) years for MCI and 49 ( 18.8 ) years for BCI .


Treatment success was achieved in 19 of 25 eyes ( 76 % ) in the MCI group compared with 16 of 21 eyes ( 76.2 % ) in the BCI group .


Differences between the 2 groups proved to be not significant ( P = 0.9 ) .


The only complication was peripunctal pyogenic granuloma in 2 eyes with BCI .


Both MCI and BCI were successful in a similar percentage of patients with NLDS .


The main advantages of the former technique were simple insertion and easy removal of the tube .


Levobupivacaine use is progressively increased for intrathecal anesthesia in transurethral resections .


The aim was to determine ED ( 50 ) and ED ( 95 ) of intrathecal isobaric levobupivacaine by addition of 25mcg fentanyl for patients undergoing transurethral resections .


A total of 100 patients undergoing transurethral resections with ASA I-III , were randomized to groups receiving intrathecal 0.5 % isobaric levobupivacaine in doses of 6 , 8 , 10 , 12 or 14mg in equal volumes with 25mcg intrathecal fentanyl addition .


Sensorial block level was determined by pinprick and motor block by Bromage scale .


Mean onset time of sensorial block in 6mg group was significantly longer than that of sensorial block in 10mg , 12mg and 14mg groups ( p < 0.01 ) , 8mg was longer than 12mg and 14mg ( p < 0.01 ) , and 10mg onset time of sensorial block was significantly longer than 12mg and 14mg ( p < 0.01 ) .


Mean onset time of T10 sensory level in 6mg group was significantly longer than mean onset time of T10 sensory level in 10mg , 12mg and 14mg ( p < 0.01 ) , the mean onset time of T10 sensory level in 8mg group was also significantly longer than that of 12mg , 14mg groups ( p < 0.01 ) .


ED ( 50 ) and ED ( 95 ) of levobupivacaine coadministered with 25 mcg fentanyl were 7.32 mg and 10.88 mg , respectively .


Levobupivacaine with opioid co-administration can be used in doses considerably lower than doses proposed for routine use as it is a safe drug depending on its hemodynamic effects , side effects .


The aim of this study was to compare the effects of epidural analgesia with infiltration analgesia in postoperative pain control for total knee arthroplasty .


Thirty patients ( 28 female , 2 male ; mean age : 69.375.11 years , range : 61 to 80 years ) undergoing total knee arthroplasty between May 2011 and September 2011 were randomly divided into 2 groups .


All patients received spinal anesthesia with bupivacaine .


Postoperative analgesia of 72 ml 0.9 % NaCl + 48 ml bupivacaine ( 1 ml = 5 mg , total 120 ml ) was administered throughout 24 hours to Group 1 ( n = 15 ) by epidural catheter and to Group 2 ( n = 15 ) by ON-Q infiltration pump .


Groups were compared based on the Bromage scores and visual analog scale ( VAS ) , blood pressure , postoperative analgesia requirement and side effects .


Demographic data were similar in both groups .


Rates of additional analgesia requirement at the postoperative 60th minute and 2nd hour were significantly higher in Group 2 than Group 1 ( p < 0.05 ) .


Rates of nausea-vomiting at the postoperative 60th minute and 2nd hour were significantly higher in Group 1 than Group 2 ( p < 0.05 and p < 0.01 , respectively ) .


Bromage scores at 60 minutes and 2 hours was significantly higher in Group 1 than in Group 2 ( p < 0.01 ) .


Mean VAS scores at 60 minutes and 2 hours were significantly higher in Group 2 than Group 1 ( p < 0.05 ) .


While a statistically significant difference was found between systolic arterial pressure measurements at 60 minutes ( p < 0.05 ) , there was no significant difference in diastolic arterial pressure and peak heart rate .


Although the analgesic effect of local infiltration is provided later than by epidural analgesia , the same level of pain control can be achieved with initial additional analgesia .


Local infiltration is superior to epidural analgesia in respect of few side effects and early mobilization .


To evaluate whether implantation of an aspheric intraocular lens ( IOL ) results in reduced ocular aberrations and improved contrast sensitivity after cataract surgery and , therefore , changes on frequency-doubling technology ( FDT ) testing .


The present prospective clinical study enrolled 25 patients with bilateral cataract ( 50 eyes ) , who randomly received either an aspheric ( Akreos AO ) or a spherical ( Akreos Fit ) IOL in one eye and the other IOL in the second eye .


Assessment 12 months postoperatively included photopic and mesopic contrast sensitivity testing .


Higher-order aberrations ( HOAs ) were computed .


FDT testing was divided into four areas to evaluate the variation of the values at different points .


The median values of the local pattern thresholds ( median area contrast sensitivity [ MACS ] ) obtained with that division were calculated .


The Akreos AO group obtained statistically significantly lower values of HOAs and spherical aberration compared with the Akreos Fit group .


There was a statistically significant between-group difference in contrast sensitivity under mesopic conditions at all spatial frequencies .


No statistically significant differences were observed in mean deviation and pattern standard deviation .


The aspheric IOL exhibited higher MACS in all areas , although a statistically significant difference was reached only in the 20-degree field area ( P = 0.043 ) .


Aspheric IOLs significantly reduced spherical aberration and HOAs , improving mesopic contrast sensitivity .


Although there was a trend toward slightly improved FDT in the aspheric IOL group , it was not statistically significant .


Safety measures should be applied to reduce work-related fatal and non-fatal fall injuries .


However , according to the labor inspectorate , more than 80 % of Dutch construction sites violate safety regulations for working from heights .


To increase compliance with safety regulations , employers and workers have to select , implement and monitor safety measures .


To facilitate this behavioral change , stimulating knowledge awareness and personalized feedback are frequently advocated behavior change techniques .


For this study , two behavior change strategies have been developed in addition to the announcement of safety inspections by the labor inspectorate .


These strategies consist of 1 ) face-to-face contacts with safety consultants and 2 ) direct mail with access to internet facilities .


The objective of this study is to evaluate the effectiveness of these two strategies on the safety violations for working from heights , the process and the cost measures .


This study is a block randomized intervention trial in 27 cities to establish the effects of the face-to-face guidance strategy ( N = 9 ) , a direct mailing strategy ( N = 9 ) and a control condition of no guidance ( N = 9 ) on safety violations to record by labor inspectors after three months .


A process evaluation for both strategies will be performed to determine program implementation ( reach , dose delivered and dose received ) , satisfaction , knowledge and perceived safety behavior .


A cost analysis will be performed to establish the financial costs for both strategies .


The present study is in accordance with the CONSORT statement .


This study increases insight into performing practice-based randomized controlled trials .


The outcome will help to evaluate the effect of two guidance strategies on safety violations .


If these strategies are effective , implementation of these strategies through the national institute of safety and health or labor inspectorate can take place to guide construction companies in complying with safety regulations .


NTR 4298 on 29-nov-2013 .


Understanding mechanisms linking neighborhood context to health behaviors may provide targets for increasing lifestyle intervention effectiveness .


Although associations between home neighborhood and obesogenic behaviors have been studied , less is known about the role of worksite neighborhood .


To evaluate associations between worksite neighborhood context at baseline ( 2006 ) and change in obesogenic behaviors of adult employees at follow-up ( 2007-2009 ) in a worksite randomized trial to prevent weight gain .


Worksite property values were used as an indicator of worksite neighborhood SES ( NSES ) .


Worksite neighborhood built environment attributes associated with walkability were evaluated as explanatory factors in relationships among worksite NSES , diet , and physical activity behaviors of employees .


Behavioral data were collected at baseline ( 2005-2007 ) and follow-up ( 2007-2009 ) .


Multilevel linear and logistic models were constructed adjusting for covariates and accounting for clustering within worksites .


Product-of-coefficients methods were used to assess mediation .


Analyses were performed after study completion ( 2011-2012 ) .


Higher worksite NSES was associated with more walking ( OR = 1.16 , 95 % CI = 1.03 , 1.30 , p = 0.01 ) .


Higher density of residential units surrounding worksites was associated with more walking and eating five or more daily servings of fruits and vegetables , independent of worksite NSES .


Residential density partially explained relationships among worksite NSES , fruit and vegetable consumption , and walking .


Worksite neighborhood context may influence employees ' obesogenic behaviors .


Furthermore , residential density around worksites could be an indicator of access to dietary and physical activity-related infrastructure in urban areas .


This may be important given the popularity of worksites as venues for obesity prevention efforts .


To analyze the differences between biodegradable and nondegradable nasal dressings with regard to their effects on wound healing in the short and medium term and on surgical outcomes in the long term , after endoscopic sinus surgery ( ESS ) .


A prospective , randomized , partly blinded , controlled trial .


A total of 56 patients undergoing bilateral ESS for chronic rhinosinusitis with polyposis were enrolled and randomized to receive biodegradable ( Nasopore ; Stryker , Hamilton , ON , Canada ) on one side and nondegradable packing ( Merocel ; Medtronic Xomed , Minneapolis , MN ) on the opposite side .


Postoperative morbidities ( pain , bleeding , facial edema , nasal blockage ) related to dressings were assessed on postoperative day 6 .


Wound healing ( edema , crusting , secretions , synechia , granulation tissue formation , and percentage re-epithelialization ) were evaluated at 2 weeks , 1 month , 3 months , and 6 months using modified Lund-Kennedy scores .


Long-term assessment at 12 months was done using validated Lund-Kennedy scores .


Morbidities related to nondegradable packing were significantly higher than with degradable packing ( Wilcoxon signed rank test , P < .01 ) .


Pain , bleeding , nasal blockage , and facial edema were significantly less with absorbable packing .


No statistically significant difference was found between sinonasal cavities packed with biodegradable or nondegradable materials with regard to healing scores and percentage of re-epithelialization at 2 weeks , 1 month , 3 months , 6 months , and surgical outcomes at 1 year ( P > .05 ) .


However , healing at 6 months was correlated with the preoperative Lund-Mackay radiology and surgery scores ( Spearman 's rho correlation test , P < .05 and P < .01 , respectively ) .


No significant healing or surgical outcome differences were found between biodegradable and nondegradable packing .


However pain , bleeding , nasal blockage , and facial edema were lower with biodegradable packing .


1b .


Even after quitting illicit drugs , tobacco abuse remains a major cause of morbidity and mortality in former injection drug users .


An important unmet need in this population is to have effective interventions that can be used in the context of community based care .


Contingency management , where a patient receives a monetary incentive for healthy behavior choices , and incorporation of individual counseling regarding spirometric `` lung age '' ( the age of an average healthy individual with similar spirometry ) have been shown to improve cessation rates in some populations .


The efficacy of these interventions on improving smoking cessation rates has not been studied among current and former injection drug users .


In a randomized , factorial design study , we recruited 100 active smokers from an ongoing cohort study of current and former injection drug users to assess the impact of contingency management and spirometric lung age on smoking cessation .


The primary outcome was 6-month biologically-confirmed smoking cessation comparing contingency management , spirometric lung age or both to usual care .


Secondary outcomes included differences in self-reported and biologically-confirmed cessation at interim visits , number of visits attended and quit attempts , smoking rates at interim visits , and changes in Fagerstrom score and self-efficacy .


Six-month biologically-confirmed smoking cessations rates were 4 % usual care , 0 % lung age , 14 % contingency management and 0 % for combined lung age and contingency management ( p = 0.13 ) .


There were no differences in secondary endpoints comparing the four interventions or when pooling the lung age groups .


Comparing contingency management to non-contingency management , 6-month cessation rates were not different ( 7 % vs. 2 % ; p = 0.36 ) , but total number of visits with exhaled carbon monoxide-confirmed abstinence were higher for contingency management than non-contingency management participants ( 0.38 vs. 0.06 ; p = 0.03 ) , and more contingency management participants showed reduction in their Fagerstrom score from baseline to follow-up ( 39 % vs. 18 % ; p = 0.03 ) .


While lung age appeared ineffective , contingency management was associated with more short-term abstinence and lowered nicotine addiction .


Contingency management may be a useful tool in development of effective tobacco cessation strategies among current and former injection drug users .


Clinicaltrials.gov NCT01334736 ( April 12 , 2011 ) .


Obese women have poorer in vitro fertilization outcomes , but underlying mechanisms remain unclear .


The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin ( hCG ) and ovarian steroid hormone production , after subcutaneous ( s.c. ) and intramuscular ( i.m. ) injection of hCG in obese and normal-weight women .


This was a randomized , experimental study .


Twenty-two women aged 18-42 years with body mass index of 18.5-24 .9 ( normal ) or 30-40 kg/m ( 2 ) ( obese ) .


Participants received im urinary hCG or s.c. recombinant hCG and returned for a second injection type after a 4-week washout .


Intramuscular injections were performed under ultrasound guidance .


Blood was taken 0 , 0.5 , 1 , 2 , 4 , 6 , 8 , 12 , 24 , and 36 hours after injection .


hCG was measured at each time point ; estradiol , progesterone , 17-hydroxyprogesterone ( 17-OHP ) , testosterone ( T ) , dehydroepiandrosterone , and SHBG were measured at 0 and 36 hours .


Twenty-two women completed the study .


In both normal-weight and obese women , peak serum concentration ( Cmax ) , area under the curve ( AUC ) , and average hCG concentration were higher after i.m. injection as compared with s.c. injection ( all P < .003 ) .


Obese women had markedly lower Cmax , AUC , and average hCG concentration after s.c. injection as compared with normal-weight women ( P = .02 , P = .009 , and P = .008 , respectively ) .


After i.m. injection , Cmax , AUC , and average concentration were similar for normal-weight and obese women ( P = .31 , P = .25 , and P = .18 , respectively ) .


Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle .


hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an increase in T in obese but not normal-weight women ( all P < .04 ) .


Subcutaneous injection yields lower hCG levels in obese women .


Standard-length needles are insufficient to administer i.m. injections in many obese women .


The use of 24-h ambulatory blood pressure monitoring ( ABPM ) in clinical practice and observational epidemiological studies has grown considerably in the past 25 years .


ABPM is a very effective technique for assessing biological , environmental , and drug effects on blood pressure .


In order to enhance the effectiveness of ABPM for clinical and observational research studies using analytical and graphical results , developing alternative data analysis approaches using modern statistical techniques are important .


The linear mixed model for the analysis of longitudinal data is particularly well suited for the estimation of , inference about , and interpretation of both population ( mean ) and subject-specific trajectories for ABPM data .


We propose using a linear mixed model with orthonormal polynomials across time in both the fixed and random effects to analyze ABPM data .


We demonstrate the proposed analysis technique using data from the Dietary Approaches to Stop Hypertension ( DASH ) study , a multicenter , randomized , parallel arm feeding study that tested the effects of dietary patterns on blood pressure .


The linear mixed model is relatively easy to implement ( given the complexity of the technique ) using available software , allows for straightforward testing of multiple hypotheses , and the results can be presented to research clinicians using both graphical and tabular displays .


Using orthonormal polynomials provides the ability to model the nonlinear trajectories of each subject with the same complexity as the mean model ( fixed effects ) .


Anterior knee pain may occur after total knee arthroplasty ( TKA ) .


Patellar resurfacing , which is considered to lower the incidence of anterior knee pain after TKA , remains controversial .


In the present study clinical and radiological outcomes after TKA performed on patients with clinical and radiological signs of femorotibial and patellofemoral osteoarthritis ( OA ) with and without patellar resurfacing will be compared .


Fifty patients will be included in a randomized controlled trial .


Patients scheduled for TKA with clinical and radiological signs of femorotibial and patellofemoral OA will be included .


Arthritis of the patellofemoral joint was determined based on the preoperative Baldini and Merchant X-ray views , which is assessed by the orthopaedic surgeon who treats the patient .


Exclusion criteria are rheumatoid arthritis , history of patellar fracture , tuberosity transposition , high tibial osteotomy ( HTO ) , hip arthroplasty and posterior cruciate ligament insufficiency .


Patients will be randomized to undergo TKA either with or without patellar resurfacing .


Outcomes will be assessed preoperatively , at 6 weeks and at 6 , 12 , 18 and 24 months postoperatively .


Primary outcome measure is the patellofemoral scoring system according to Baldini .


Secondary outcome measures are the Knee Society clinical rating system ( KSS ) and the Knee Osteoarthritis Outcome Scale ( KOOS ) scores .


Conventional weight-bearing radiographs , and views according to Baldini will be used to asses component loosening , wear , and patellofemoral problems including fracture or loosening of resurfaced patellae , subluxation and wear of non-resurfaced patellae .


There is no consensus regarding patellar resurfacing during primary TKA .


Current prospective studies fail to determine any differences in clinical outcome among patients after TKA with or without patellar resurfacing .


This randomized controlled trial has been designed to determine the effectiveness of patellar resurfacing during TKA in patients undergoing TKA who have clinical and radiological signs of tibiofemoral and patellofemoral OA , using a specific patellofemoral outcome measurement .


Netherlands Trial Registry NTR3108 .


Symptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect .


To assess the ability of exhaled breath temperature ( EBT ) , a putative marker of airway inflammation , to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study .


This was a double-blinded , placebo-controlled clinical trial in 56 subjects ( mean SD 30 12 years old , 33 men ) sensitized to grass pollen .


The objective measurements were EBT , spirometry , and periostin and high-sensitivity C-reactive protein in blood .


Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms .


Evaluations were performed before , during , and after the grass pollen season .


Fifty-one subjects ( 25 and 26 in the active treatment and placebo groups , respectively ) were assessed before and during the pollen season .


The mean pre - vs in-season increase in EBT was significantly smaller ( by 59.1 % ) in the active treatment than in the placebo group ( P = .030 ) .


Of the other objective markers , only the blood periostin level increased significantly during the pollen season ( P = .047 ) , but without intergroup differences .


Subjectively , the mean pre - vs in-season increase in the visual analog scale score was 32.3 % smaller in the active treatment than in the placebo group , although this difference did not reach statistical significance ( P = .116 ) .


These results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT , a putative quantitative measurement of airway inflammation , which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale .


clinicaltrials.gov Identifier : NCT01785394 .


Decreased movement ability , one of the hallmarks of Parkinson disease ( PD ) , may lead to inadequate physical activity ( PA ) and excessive time spent in sedentary behaviors-2 factors associated with an elevated risk for lifestyle-related diseases , poor management of PD , and premature death .


To identify the extent to which people with PD are physically active , a comprehensive characterization of PA in this population is needed .


The study objective was to describe levels and patterns of PA and sedentary behaviors in elderly people with PD .


This cross-sectional study involved a free-living setting and 53 men and 42 women ( mean age = 73.4 years ) with mild to moderate idiopathic PD .


Time spent in PA and sedentary behaviors was assessed for 1 week with accelerometers .


Mean daily step counts were 4,765 ; participants spent 589 minutes in sedentary behaviors , 141 minutes in low-intensity activities , 30 minutes in moderate-intensity lifestyle activities , and 16 minutes in moderate - to vigorous-intensity ambulatory activities .


No differences were found between weekdays and weekend days .


Patterns were characterized by a rise in total PA in the morning , peaking between 10 am and 3 pm , and a gradual decline toward the late evening .


The proportion achieving 150 minutes of moderate - to vigorous-intensity PA per week was 27 % , and 16 % achieved 7,000 or more steps per day .


Nonrandomized selection of participants may limit the generalizability of the results .


Physical activity levels were generally low , in terms of both total volume and intensity , with only minor variations over the course of a day or between days .


These results emphasize the need to develop strategies to increase PA and reduce time spent in sedentary behaviors in elderly people with mild to moderate PD .


Chronic pancreatitis is a chronic inflammatory disorder characterized by progressive fibrosis of pancreatic tissue .


The principal symptom is chronic pain resulting in reduced quality of life and inability to work .


Short-term follow-up has shown that duodenum-preserving pancreatic head resections ( DPPHRs ) are superior in outcomes to pancreaticoduodenectomy .


Therefore , these organ-sparing procedures have gained wide acceptance .


This trial was conducted to compare patient outcomes 16 years after treatment for chronic pancreatitis by means of the Beger or the Frey procedure .


Seventy-four patients suffering from chronic pancreatitis were randomly assigned to 2 treatment groups ( Beger n = 38 ) and Frey ( n = 36 ) .


The perioperative courses in the randomized controlled trial and the 8-year follow-up have been reported previously .


All participating patients were contacted with a standardized , validated questionnaire to evaluate long-term survival , quality of life , pain , and exocrine and endocrine function .


No significant differences between the 2 groups in terms of quality of life , pain control , or other somatic parameters were detected after a median of 16 years postoperatively .


Mortality was comparable after Beger and Frey procedures at 39 % vs 34 % , respectively , with postoperative survivals of 13.0 1.1 years and 13.3 0.9 years , respectively ( p = 0.660 ) .


No statistically significant differences were found in rates of endocrine insufficiency ( Beger 87 % vs Frey 86 % ; p = 0.953 ) or exocrine insufficiency ( Beger 77 % vs Frey 83 % ; p = 0.655 ) .


Duodenum-preserving resections of the pancreatic head offered good and permanent pain relief and substantially increased quality of life in chronic pancreatitis .


Overall , a 16-year long-term follow-up found comparable outcomes for the Beger and Frey procedures .


To evaluate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin plus metformin ( A+M ) initial combination therapy versus either as monotherapy in drug-nave T2DM patients .


This international , randomized , double-blind , placebo-controlled , 26-week study involved T2DM patients with hyperglycaemia ( HbA1c 7.5-10 .0 % ) following diet/exercise therapy .


Patients ( N = 784 ) received placebo , alogliptin ( A , 12.5 mg BID or 25mg QD ) , metformin ( M , 500 or 1000mg BID ) or A+M ( 12.5 / 500 or 12.5 / 1000mg BID ) ; placebo , A25 for secondary analyses only .


week26 changes from baseline in HbA1c ( primary ) , fasting plasma glucose ( FPG ) and 2-h postprandial glucose ( PPG ) ; incidences of clinical response and hyperglycaemic rescue .


Week 26 mean HbA1c reductions from baseline ( 8.45 % ) were -1.22 and -1.55 % with A+M 12.5 / 500 and 12.5 / 1000 versus -0.56 , -0.65 , and -1.11 % with A12 .5 , M500 and M1000 ( p < 0.001 , A+M vs. component monotherapies ) .


FPG reductions were -1.76 and -2.55 mmol/L with 12.5 / 500 and 12.5 / 1000 versus -0.54 , -0.64 and -1.78 mmol/L with A12 .5 , M500 and M1000 ( p < 0.05 , A+M vs. component monotherapies ) .


Significantly more A+M - treated patients achieved HbA1c < 7 % ( 47.1-59 .5 % vs. 20.2-34 .3 % with monotherapy ) , significantly fewer required hyperglycaemic rescue ( 2.6-12 .3 % vs. 10.8-22 .9 % with monotherapy ) .


A+M caused only mild/moderate hypoglycaemia ( 1.9-5 .3 % ) and weight loss ( 0.6-1 .2 kg ) .


Alogliptin plus metformin initial combination therapy was well tolerated yet more efficacious in controlling glycaemia in drug-nave T2DM patients than either as monotherapy .


To clinically and histopathologically evaluate the anti-inflammatory effect of 0.2 % hyaluronan gel alone and with mechanical therapy on gingivitis .


The argyrophilic nucleolar organizer region staining technique was attempted to routinely determine its diagnostic and prognostic dependability for periodontal lesions .


In each of the 28 gingivitis patients , the four quadrants were subjected to different treatments : scaling , scaling + topical hyaluronan gel , only topical hyaluronan gel , and topical + intrasulcular hyaluronan gel .


Clinical parameters were recorded at baseline , and on days 7 , 14 , and 21 .


Biopsies were taken from each quadrant , inflammatory infiltrates were graded , and the argyrophilic nucleolar organizer region count was measured before and after treatment .


A significant reduction was seen in clinical parameters , inflammatory infiltrates , and the argyrophilic nucleolar organizer region count within the groups .


The effect of topical + intrasulcular gel was equivalent to scaling ( P > 0.05 ) .


Topical + intrasulcular hyaluronan gel application demonstrated a better reduction than topical hyaluronan gel alone .


Hyaluronan gel is an effective topical agent for treating gingivitis , along with scaling and intrasulcular application .


The argyrophilic nucleolar organizer region count can be used as a histopathological indicator in cases of non-responsive gingivitis to assess the severity of gingival inflammation .


We aimed to assess the dyadic validity of the Decisional Conflict Scale ( DCS ) for assessing shared decision making in clinical consultations .


We applied dyadic criteria , which consider the patient and physician as an interactive dyad instead of as independent individuals , to identify common patient/physician measures of patient uncertainty .


Patients and their physicians , participating in a randomized clustered trial , completed separately an adapted version of the DCS with five subscales .


We performed factor analysis on the full DCS and each subscale independently .


We defined a measure as dyadic when measurement invariance across patients and physicians was supported .


We analyzed 332 paired responses ( physicians with adults or with parents and children ) at study entry and 339 at exit .


Factor analysis showed that the full DCS is not a valid dyadic measure .


However , independent analysis of each subscale showed measurement invariance for values clarity , support , and effective decision ( comparative fit index range , 0.93-1 ; root mean square error of approximation range , 0-0 .07 ; and P-value > 0.05 ) .


Application of our dyadic validation criterion indicated that the full DCS can not be considered a dyadic measure .


However , three of its subscales , values clarity , support and effective decision , are valid dyadic measures .


Research has shown that orthodontic patients are more likely to retain information presented in an audiovisual format .


However , there has been little research on the effectiveness of audiovisual information provided through different routes such as the Internet .


This parallel-group randomized controlled trial assessed whether provision of audiovisual information on the YouTube ( Google , San Bruno , Calif ) Web site to orthodontic patients undergoing fixed appliance treatment results in improved patient knowledge when compared with conventional methods of information provision .


The effects of sex and ethnicity were also investigated .


Participants were recruited from the Department of Orthodontics of the Eastman Dental Hospital , University College London Hospitals NHS Foundation Trust , United Kingdom .


The patients were 13 years of age and over , with no history of orthodontic treatment , and patient and parental ( where appropriate ) consent were obtained .


The participants were randomized into control ( n = 34 ) and intervention ( n = 33 ) groups using a random number table ; there was stratification based on age group , with permuted blocks of 10 patients .


Both groups were given routine verbal and written patient information related to fixed appliances , and the participants in the intervention group were sent 3 e-mails over 6 weeks requesting that they view a 6-minute YouTube video containing similar information but in audiovisual format .


Patient knowledge was measured using identical questionnaires answered on the day of recruitment ( baseline ) and again 6 to 8 weeks later .


The researchers were unaware of group allocations when enrolling patients and scoring questionnaires .


Sixty participants ( 89.55 % ) completed the study .


Those who completed the trial in the intervention group ( n = 30 ) demonstrated significantly greater improvements in knowledge than did those in the control group ( n = 30 ) , scoring , on average , almost 1 point more ( 95 % CI for the difference , 0.305-1 .602 ; P = 0.005 ) on the final questionnaire .


Ethnicity had a statistically significant effect on improvement in knowledge , but sex did not .


No harm to any patient was noted during the trial .


Presenting audiovisual information through the YouTube Web site to orthodontic patients resulted in a significant improvement in patient knowledge .


Supplementation of verbal and written patient information with audiovisual information via the Internet is therefore worthy of consideration .


National Research and Ethics Service ( REC number 12/LO/0863 ) , United Kingdom .


The protocol was not published before trial commencement .


No funding or conflict of interest to be declared .


Gamithromycin is active in vitro against the bacterial agents most commonly associated with bronchopneumonia in older foals .


However , the clinical efficacy and safety of this drug have not been investigated .


Gamithromycin is effective for the treatment of bronchopneumonia in foals .


One hundred and twenty-one foals on a farm endemic for infections caused by Rhodococcus equi .


In a controlled , randomized , and double blinded clinical trial , foals with ultrasonographic evidence of pulmonary abscesses ( abscess score 8.0-20 cm ) were randomly allocated in 3 treatment groups : ( 1 ) gamithromycin IM q7 days ( n = 40 ) ; ( 2 ) azithromycin with rifampin , PO q24h ( n = 40 ) ; or ( 3 ) no antimicrobial treatment ( controls ; n = 41 ) .


Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment .


Foals that worsened were removed from the study .


The proportion of foals that recovered without the need to be removed from the study was significantly higher for foals treated with gamithromycin ( 38 of 40 ) or azithromycin with rifampin ( 39 of 40 ) than for controls ( 32 of 41 ) .


Treatment with gamithromycin or with azithromycin-rifampin resulted in a significantly faster decrease in the clinical score and abscess score compared to the controls .


Adverse reactions characterized by colic ( n = 18 ) and hind limb lameness ( n = 14 ) were observed only in foals treated with gamithromycin .


Gamithromycin was noninferior to azithromycin with rifampin for the treatment of bronchopneumonia in the study population but had a higher frequency of adverse reactions .


Diabetes mellitus is a rising non-communicable disease in Malaysia .


Insulin therapy refusal is a great challenge for healthcare providers , as it results in delayed insulin initiation .


This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors .


This cross sectional study was conducted at seven public health clinics in Kubang Pasu district , Malaysia , from March to October 2012 .


A newly developed and validated questionnaire was used and participants were selected via systematic random sampling .


Only patients diagnosed with type II diabetes mellitus ( T2DM ) and under the public health clinic care in Kubang Pasu were included in the study .


Multiple logistic regressions were used to study the association between insulin therapy refusal and its associated factors .


There were 461 respondents and the response rate was 100 % .


Among these 461 patients with T2DM , 74.2 % refused insulin therapy .


The most common reason given for refusal was a lack of confidence in insulin injection ( 85.4 % ) .


Multiple logistic regression revealed that respondents who had secondary education were 55.0 % less likely to refuse insulin therapy than those who had primary or no formal education ( p = 0.009 , adjusted odds ratio [ OR ] = 0.45 , 95 % confidence interval [ CI ] = 0.25-0 .82 ) .


There was also a significant inverse association between glycated haemoglobin ( HbA1c ) and insulin therapy refusal ( p = 0.047 , adjusted OR = 0.87 , 95 % CI = 0.76-1 .00 ) .


Insulin therapy refusal is common in Kubang Pasu .


Education status and HbA1c should be taken into consideration when counselling patients on insulin therapy initiation .


The present study evaluated the effects of creatine monohydrate ( CrM ) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program .


In a double-blind , randomized trial , 20 males aged between 55 and 70 years were randomly assigned to consume either CrM-carbohydrate ( CHO ) [ 20 g days ( -1 ) CrM + 5 g days ( -1 ) CHO 7 days , then 0.1 g kg ( -1 ) CrM + 5 g CHO on training days ( average dosage of ~ 8.8 g ) ] or placebo CHO ( 20 g days ( -1 ) CHO 7 days , then 5 g CHO on training days ) while participating in a high intensity resistance training program [ 3 sets 10 repetitions at 75 % of 1 repetition maximum ( 1RM ) ] , 3 days weeks ( -1 ) for 12 weeks .


Following the initial 7-day `` loading '' phase , participants were instructed to ingest their supplement within 60 min post-exercise .


Body composition and muscle strength measurements , blood collection and vastus lateralis muscle biopsy were completed at 0 , 4 , 8 and 12 weeks of the supplement and resistance training program .


A significant time effect was observed for 1RM bench press ( p = 0.016 ) , leg press ( p = 0.012 ) , body mass ( p = 0.03 ) , fat-free mass ( p = 0.005 ) and total myofibrillar protein ( p = 0.005 ) .


A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training ( p = 0.08 ) .


No supplement interaction effects were observed .


Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males .


The purpose of routine alcohol screening is to identify patients who may benefit from brief intervention , but patients who also have alcohol and other substance use disorders ( AUD/SUD ) likely require more intensive interventions .


This study sought to determine the prevalence of clinically documented AUD/SUD among VA outpatients with unhealthy alcohol use identified by routine screening .


VA patients 18-90 years who screened positive for unhealthy alcohol use ( AUDIT-C 3 women ; 4 men ) and were randomly selected for quality improvement standardized medical record review ( 6/06 -6 / 10 ) were included .


Gender-stratified prevalences of clinically documented AUD/SUD ( diagnosis of AUD , SUD , or alcohol-specific medical conditions , or VA specialty addictions treatment on the date of or 365 days prior to screening ) were estimated and compared across AUDIT-C risk groups , and then repeated across groups further stratified by age .


Among 63,397 eligible patients with unhealthy alcohol use , 25 % ( n = 2109 ) women and 28 % ( n = 15,199 ) men had documented AUD/SUD ( p < 0.001 ) .


The prevalence of AUD/SUD increased with increasing AUDIT-C risk , ranging from 13 % ( 95 % CI 13-14 % ) to 82 % ( 79-85 % ) for women and 12 % ( 11-12 % ) to 69 % ( 68-71 % ) for men in the lowest and highest AUDIT-C risk groups , respectively .


Patterns were similar across age groups .


One-quarter of all patients with unhealthy alcohol use , and a majority of those with the highest alcohol screening scores , had clinically recognized AUD/SUD .


Healthcare systems implementing evidence-based alcohol-related care should be prepared to offer more intensive interventions and/or effective pharmacotherapies for these patients .


Iniparib is a novel anticancer agent initially considered a poly ( ADP-ribose ) polymerase ( PARP ) inhibitor , but subsequently shown to act via non-selective protein modification through cysteine adducts .


This randomized phase II study investigated the addition of iniparib to gemcitabine-cisplatin in metastatic non-small-cell lung cancer ( NSCLC ) patients .


Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to receive gemcitabine ( 1250 mg/m ( 2 ) , days 1/8 ) and cisplatin ( 75 mg/m ( 2 ) , day 1 ) with [ gemcitabine/cisplatin/iniparib ( GCI ) ] or without [ gemcitabine/cisplatin ( GC ) ] iniparib ( 5.6 mg/kg , days 1/4/8 / 11 ) every 3 weeks for six cycles .


The primary end point was the overall response rate ( ORR ) .


Secondary objectives included progression-free survival ( PFS ) , overall survival ( OS ) , and safety .


The study was not designed for formal efficacy comparison , the control arm being to benchmark results against the literature .


One hundred and nineteen patients were randomized ( 39 GC and 80 GCI ) .


More GCI patients were male ( 80 % GCI and 67 % GC ) and had PS 0 ( 61 % GCI and 49 % GC ) .


The ORR was 25.6 % [ 95 % confidence interval ( CI ) 13.0 % -42.1 % ] with GC versus 20.0 % ( 95 % CI 11.9 % -30.4 % ) with GCI , which did not allow rejection of the null hypothesis ( ORR with GCI 20 % ; P = 0.545 ) .


Median PFS was 4.3 ( 95 % CI 2.8-5 .6 ) months with GC and 5.7 ( 95 % CI 4.6-6 .6 ) months with GCI ( hazard ratio 0.89 , 95 % CI 0.56-1 .40 ) .


Median OS was 8.5 ( 95 % CI 5.5 to not reached ) months with GC , and 12.0 ( 95 % CI 8.9-17 .1 ) months with GCI ( hazard ratio 0.78 , 95 % CI 0.48-1 .27 ) .


More GCI patients received second-line treatment ( 51 % GC and 68 % GCI ) .


Toxicity was similar in the two arms .


Grade 3-4 toxicities included asthenia ( 28 % GC and 8 % GCI ) , nausea ( 3 % GC and 14 % GCI ) , and decreased appetite ( 10 % in each ) .


Addition of iniparib to GC did not improve ORR over GC alone .


The GCI safety profile was comparable to GC alone .


Imbalances in PS and gender distribution may have impacted study results regarding PFS and OS .


ClinicalTrial.gov Identifier NCT01086254 .


Polysorbate 80 ( P80 ) , a nonionic detergent used to solubilize proteins , is used in both oral and injectable medications including vaccines .


Development studies with 13-valent pneumococcal conjugate vaccine ( PCV13 ) showed that adding P80 resulted in a more robust manufacturing process .


Before adding P80 to the formulation of PCV13 , we investigated the immunogenicity and safety of PCV13 with and without P80 .


Phase 3 , parallel-group , randomized , active-controlled , double-blind multicenter trial was conducted at 15 sites in Poland .


Healthy infants were randomized ( 1:1 ) to receive PCV13 + P80 or PCV13 without P80 given at ages 2 , 3 , 4 and 12 months concomitantly with DTaP-IPV-Hib at 2 , 3 and 4 months ; hepatitis B at 2 months and measles , mumps , and rubella at 12 months .


Serotype-specific antipneumococcal immune responses were evaluated using antipolysaccharide capsular immunoglobulin ( Ig ) G responses and opsonophagocytic activity ( OPA ) assay .


Safety data were also collected .


The 2 treatment groups were demographically similar .


Following the infant immunization series , anticapsular IgG antibody geometric mean concentrations and OPA geometric mean titers for each serotype were within 2-fold between the 2 groups .


Formal noninferiority criteria for comparison of proportion of responders ( subjects with IgG titers 0.35 g/mL ) were met for 11 of the 13 serotypes .


Overall population responses were highly similar .


Anticapsular IgG responses were also within 2-fold following the toddler dose .


Safety profiles were similar between the 2 groups .


Addition of P80 to PCV13 did not adversely affect PCV13 immunogenicity or safety when compared with vaccine formulated without P80 .


We investigated with 1HNMR-spectroscopy the effects of habitual fatty fish intake on serum lipiprotein profiles in persons with features of metabolic syndrome .


The participants ( n = 105 ) were randomized into three diet intervention groups .


The groups were given different dietary instructions .


Increased intake of fatty fish had a significant ( p < 0.05 ) increasing effect on the amount of large HDL-lipoprotein subclasses and their lipids .


Frequent intake of fatty fish may have beneficial effects on HDL-metabolism beyond that assumed to be related to its serum concentrations .


To assess , in a randomized , phase 2 trial , the efficacy and safety of chemoradiotherapy with or without induction chemotherapy ( ICT ) of S1 and oxaliplatin for esophageal cancer .


Patients with stage II , III , or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT ( oxaliplatin 130 mg/m ( 2 ) on day 1 and S1 at 40 mg/m ( 2 ) twice daily on days 1-14 , every 3 weeks ) followed by concurrent chemoradiotherapy ( CCRT ) ( 46 Gy , 2 Gy/d with oxaliplatin 130 mg/m ( 2 ) on days 1 and 21 and S1 30 mg/m ( 2 ) twice daily , 5 days per week during radiation therapy ) and esophagectomy ( arm A ) , or the same CCRT followed by esophagectomy without ICT ( arm B ) .


The primary endpoint was the pathologic complete response ( pCR ) rate .


A total of 97 patients were randomized ( arm A/B , 47/50 ) , 70 of whom underwent esophagectomy ( arm A/B , 34/36 ) .


The intention-to-treat pCR rate was 23.4 % ( 95 % confidence interval [ CI ] 11.2-35 .6 % ) in arm A and 38 % ( 95 % CI 24.5 % to 51.5 % ) in arm B. With a median follow-up duration of 30.3 months , the 2-year progression-free survival rate was 58.4 % in arm A and 58.6 % in arm B , whereas the 2-year overall survival rate was 60.7 % and 63.7 % , respectively .


Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B ( 35.4 % vs 4.1 % ) .


The relative dose intensity of S1 ( 89.5 % 20.6 % vs 98.3 % 5.2 % , P = .005 ) and oxaliplatin ( 91.4 % 16.8 % vs 99.0 % 4.2 % , P = .007 ) during CCRT was lower in arm A compared with arm B. Three patients in arm A , compared with none in arm B , died within 90 days after surgery .


Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer .


However , we failed to show that the addition of ICT to the regimen can improve the pCR rate .


There is a growing interest for the use of probiotics for chronic constipation .


A recent randomized controlled trial ( RCT ) showed a positive effect of Lactobacillus reuteri ( L. reuteri ) on bowel movement frequency in infants with chronic constipation .


The aim of the present study was to evaluate the effects of L. reuteri in adult patients with functional constipation .


A double-blind , placebo RCT was conducted in 40 adults ( 18M/22F , 35 + / -15 years ) affected by functional constipation according to the Rome III criteria .


Patients were randomly assigned to receive a supplementation of L. reuteri ( DSM 17938 ) , or matching placebo for 4 weeks .


The increase of bowel movements/week was the primary outcome , while the improvement of stool consistency was the secondary outcome .


At week 4 , the mean increase in bowel movements/week was 2.6 ( SD + / -1.14 , 95 % CI :1.6 -3.6 ) in the L. reuteri group and 1.0 ( SD + / -1.95 % CI :0.12 -1.88 ) in the placebo group ( p = 0.046 ) .


At the end of the treatment , the mean bowel movements/week was 5.28 + / -1.93 in the L. reuteri group and 3.89 + / -1.79 in the placebo group .


There was a not significant difference in the stool consistency between the two groups .


L. reuteri is more effective than the placebo in improving bowel movement frequency in adult patients with functional constipation as previously demonstrated in children , even if it seems to have no effect on stool consistency .


The extent of heterogeneity in response to the psychopharmacological treatment of negative symptoms is unknown .


To examine the extent of heterogeneity in response to the treatment of predominantly negative symptoms of schizophrenia .


Data were analyzed from three clinical trials that compared placebo or amisulpride for up to 60days .


Trial participants had predominantly negative symptoms of schizophrenia ( n = 485 ) .


Heterogeneity of percentage reduction on the Scale for the Assessment of Negative Symptoms ( SANS ) was examined with trajectory-group based modeling followed by descriptive statistics and the prediction of trajectory group membership with logistic regression modeling .


Analyses were repeated separately for the placebo and amisulpride groups .


Trajectory group-based modeling identified groups of non - ( n = 297 , 61.2 % ) , gradual-moderate ( n = 135 , 27.8 % ) and rapid - ( n = 53 , 10.9 % ) responders .


At baseline compared to non-responders , rapid-responders had consistently significantly ( p < .05 ) higher SANS total and subscale scores .


Percent SANS improvement at endpoint was greatest for the rapid-responders group , a finding that replicated stratifying by placebo and amisulpride treatment groups .


Similarly , in the total sample and stratifying by placebo and amisulpride groups , dropout was not significantly associated with trajectory group membership .


Trajectories of treatment response to the psychopharmacological medication of the negative symptoms of schizophrenia demonstrate substantial heterogeneity .


Approximately half of the patients included in our analysis showed little improvement , and the most severely ill at baseline responded the most .


Fetuin-A may mediate cross-talk between the liver and adipose tissue .


We studied the physiologic regulation of fetuin-A and explored its potential regulation by leptin .


Fetuin-A levels were measured in three interventional studies as well as in in vitro experiments .


Study 1 : 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin ( metreleptin ) following short term complete caloric deprivation to induce severe hypoleptinemia ; Study 2 : 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin ; Study 3 : 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months .


In study 4 human hepatoma Hep G2 cells were treated with leptin .


Fetuin-A mRNA expression and secretion were measured .


Complete caloric deprivation significantly decreased leptin but had no effect on fetuin-A levels .


Normalizing leptin levels with metreleptin in hypoleptinemic subjects had no effect on circulating fetuin-A levels .


Leptin treatment had no effect on fetuin-A mRNA expression and secretion in vitro .


Circulating fetuin-A levels are not affected by short and long-term energy deprivation .


Furthermore , both in vivo and in vitro experiments confirm that fetuin-A is not regulated by leptin .


Unexplained fatigue is often left untreated or treated with antidepressants .


This randomized , placebo-controlled , single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose ( FCM ) in iron-deficient , premenopausal women with symptomatic , unexplained fatigue .


Fatigued women ( Piper Fatigue Scale [ PFS ] score 5 ) with iron deficiency ( ferritin < 50 g/L and transferrin saturation < 20 % , or ferritin < 15 g/L ) and normal or borderline hemoglobin ( 115 g/L ) were enrolled in 21 sites in Austria , Germany , Sweden and Switzerland , blinded to the study drug and randomized ( computer-generated randomization sequence ) to a single FCM ( 1000 mg iron ) or saline ( placebo ) infusion .


Primary endpoint was the proportion of patients with reduced fatigue ( 1 point decrease in PFS score from baseline to Day 56 ) .


The full analysis included 290 women ( FCM 144 , placebo 146 ) .


Fatigue was reduced in 65.3 % ( FCM ) and 52.7 % ( placebo ) of patients ( OR 1.68 , 95 % CI 1.05-2 .70 ; p = 0.03 ) .


A 50 % reduction of PFS score was achieved in 33.3 % FCM - vs. 16.4 % placebo-treated patients ( p < 0.001 ) .


At Day 56 , all FCM-treated patients had hemoglobin levels 120 g/L ( vs. 87 % at baseline ) ; with placebo , the proportion decreased from 86 % to 81 % .


Mental quality-of-life ( SF-12 ) and the cognitive function scores improved better with FCM .


` Power of attention ' improved better in FCM-treated patients with ferritin < 15 g/L .


Treatment-emergent adverse events ( placebo 114 , FCM 209 ; most frequently headache , nasopharyngitis , pyrexia and nausea ) were mainly mild or moderate .


A single infusion of FCM improved fatigue , mental quality-of-life , cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin .


Although more side effects were reported compared to placebo , FCM can be an effective alternative in patients who can not tolerate or use oral iron , the common treatment of iron deficiency .


Overall , the results support the hypothesis that iron deficiency can affect women 's health , and a normal iron status should be maintained independent of hemoglobin levels .


ClinicalTrials.gov NCT01110356 .


This study compared wireless Contralateral Routing of Signals ( CROS ) hearing aid and bone-anchored hearing device ( BAHD ) in patients with single-sided deafness .


Eight adults with single-sided deafness previously implanted with a BAHD were given a 2-week trial with a CROS hearing aid and tested in unaided and aided conditions .


Both devices were compared on head shadow effect reduction , speech perception measures in quiet and in noise , self-assessment questionnaires , and daily diaries .


Both the CROS and BAHD significantly reduced the head shadow effect .


QuickSIN scores were significantly better with noise presented to the poorer ear , as compared to the better ear , for the unaided condition , the BAHD , and the CROS .


Scores showed no significant differences between the CROS and BAHD with noise presented to the better ear , but scores with the CROS were significantly poorer than in the unaided condition with noise presented to the poorer ear .


There were no significant differences between BAHD and CROS for the ratings on the Bern Benefit in Single-Sided Deafness and Speech Spatial Qualities questionnaires .


Both devices were worn an average of 10 hours per day .


Four participants preferred the CROS for sound quality ; three preferred the BAHD for comfort .


Comparisons of CROS and BAHD need to be re-evaluated as both technologies have evolved .


In our pilot study , both devices seem comparable , with the CROS avoiding the risks of surgery , and we recommend a trial of CROS in our center for first line treatment of single-sided deafness .


To evaluate the outcomes of the combination of red light or intense pulsed laser ( IPL ) with 5-aminolevulinic acid ( ALA ) - mediated photodynamic therapy ( PDT ) in the treatment of photodamaged neck skin .


The anterior of the neck was divided into four 2 cm 2 cm sections and randomly assigned to red-light , red-light-PDT , IPL or IPL-PDT group .


ALA cream of 5 % was applied to PDT regions for 2h prior to light irradiation .


Treatment was repeated once .


The stratum corneum ( SC ) hydration , transepidermal water loss ( TEWL ) , L ( * ) , a ( * ) , b ( * ) values , melanin index ( MI ) , erythema index ( EI ) , skin elasticity and skin thickness were examined by a blinded investigator .


The function and volume of thyroid were also measured .


After red-light-PDT , IPL-PDT and IPL treatment , the appearance of photoaging lesion was improved .


The SC hydration , L ( * ) value , elasticity and thickness increased , whereas the TEWL and MI value decreased .


These changes in red-light-PDT and IPL-PDT group were more obvious than IPL group .


The a ( * ) and EI value increased in red-light-PDT group .


No significant change was noticed in red-light group .


Partial irradiation of the thyroid did not affect the function and volume of the thyroid .


IPL-PDT and red-light-PDT showed better rejuvenation effect than IPL or red light alone on the neck skin .


Disordered eating behavior and body dissatisfaction affect a large proportion of the Dutch population and account for severe psychological , physical and social morbidity .


Yet , the threshold for seeking professional care is still high .


In the Netherlands , only 7.5 % of patients with bulimia nervosa and 33 % of patients with anorexia nervosa are treated within the mental health care system .


Easily accessible and low-threshold interventions , therefore , are needed urgently .


The internet has great potential to offer such interventions .


The aim of this study is to determine whether a web-based treatment program for patients with eating disorders can improve eating disorder psychopathology among female patients with bulimia nervosa , binge eating disorder and eating disorders not otherwise specified .


This randomized controlled trial will compare the outcomes of an experimental treatment group to a waiting list control group .


In the web-based treatment program , participants will communicate personally and asynchronously with their therapists exclusively via the internet .


The first part of the program will focus on analyzing eating attitudes and behaviors .


In the second part of the program participants will learn how to change their attitudes and behaviors .


Participants assigned to the waiting list control group will receive no-reply email messages once every two weeks during the waiting period of 15 weeks , after which they can start the program .


The primary outcome measure is an improvement in eating disorder psychopathology as determined by the Eating Disorder Examination Questionnaire .


Secondary outcomes include improvements in body image , physical and mental health , body weight , self-esteem , quality of life , and social contacts .


In addition , the participants ' motivation for treatment and their acceptability of the program and the therapeutic alliance will be measured .


The study will follow the recommendations in the CONSORT statement relating to designing and reporting on RCTs .


This study protocol presents the design of a RCT for evaluating the effectiveness of a web-based treatment program using intensive therapeutic support for female patients with bulimia nervosa , binge eating disorder and eating disorders not otherwise specified .


The protocol for this study is registered with the Netherlands Trial Registry NTR2415 .


To compare the anaesthetic and convulsive effects of sevoflurane/remifentanil versus propofol/remifentanil combination in electroconvulsive therapy ( ECT ) .


In this prospective , randomized double-blind study , patients diagnosed with treatment-resistant depression were included for ECT .


Prior to treatment , 1g/kg remifentanil was intravenously administered to all patients , followed by anaesthetic induction with either 0.5 mg/kg propofol or 8 % sevoflurane .


Following muscular paralysis with succinylcholine and hypnosis , bitemporal ECT was applied .


Vital signs , depth of sedation , recovery parameters , motor and electroencephalography ( EEG ) convulsion activity and postictal suppression index scores were recorded .


A total of 120 sessions of ECT were administered to 12 patients .


Heart rate was higher in the sevoflurane group than the propofol group .


Compared with the sevoflurane group , bispectral index level was lower in the propofol group during the induction period and higher during the recovery period .


Anaesthetic induction and recovery times were lower , and average motor and EEG convulsion activity was longer , in the propofol group than in the sevoflurane group .


Propofol/remifentanil is more successful compared with sevoflurane/remifentanil in anaesthesia management during ECT since it provides quick induction and recovery , longer seizure activity and stable haemodynamics .


The objective was to determine the separate and combined effects of hypoxia and inactivity/unloading on sleep architecture during a 10-day period of confinement .


Ten subjects participated in three 10-day trials in random order : hypoxic ambulatory ( HAMB ) , hypoxic bedrest ( HBR ) , and normoxic bedrest ( NBR ) .


During the HAMB and HBR trials , subjects were confined to a hypoxic facility .


The hypoxia profile was : simulated altitude of 2,990 m on day 1 , 3,380 m on day 2 , and 3,881 m on day 3 .


In the NBR and HBR trials , subjects maintained a horizontal position throughout the confinement period .


During each trial , sleep polysomnography was conducted one night prior to ( baseline ; altitude of facility is 940 m ) and on the first ( NT1 , altitude 2,990 m ) and tenth ( NT10 , altitude 3,881 m ) night of the 10-day intervention .


Average time in sleep stage 1 decreased from NT1 to NT10 irrespective of trial .


Overall incidence and time spent in periodic breathing increased from NT1 to NT10 in both HAMB and HBR .


During NT1 , both HAMB and HBR reduced slow-wave sleep and increased light sleep , whereas NBR and HBR increased the number of awakenings/night .


There were fewer awakenings during HAMB than NBR .


Acute exposure to both hypoxia and bedrest ( HBR ) results in greater sleep fragmentation due to more awakenings attributed to bedrest , and lighter sleep as a result of reduced slow wave sleep caused by the hypoxic environment .


Peripheral opioid receptor targeting has been well established as a novel target in clinical pain management for acute and chronic peripheral inflammatory pain .


The physiochemical properties of the peripheral mu-opioid receptor agonist , loperamide HCl , limit the use of the free drug as an analgesic or anti-inflammatory agent , particularly for dermal delivery across intact skin .


Our objective was to manufacture an effective topical formulation containing loperamide using liposomal delivery that would allow loperamide to produce analgesia and anti-inflammatory effects , by penetrating the epidermis to reach peripheral opioid receptors within the dermis of intact skin .


A randomized , double blind , controlled animal trial .


Thirty-five adult male Wistar rats ( 200 - 250 g ) were randomly divided into 5 groups : loperamide HCl-encapsulated liposomal gel , naloxone methiodide + loperamide HCl-encapsulated liposomal gel , free loperamide gel , empty liposomal gel , and 1 % diclofenac gel ( Voltaren ) .


Diclofenac gel was used as a positive control as it is clinically used as a topical analgesic and anti-inflammatory drug .


Animals received an intraplantar injection of 150 l Complete Freund 's Adjuvant ( CFA ) into the right hindpaw and experiments were performed 5 days post-CFA injection , which corresponded to the peak inflammatory response .


All manufactured formulations were applied topically on both hind paws twice daily , whereas Voltaren gel was applied 3 times a day in accordance with the manufacturer 's instructions .


The dose administered was 50 l , which equated to 0.4 mg of loperamide HCl for the loperamide HCl treatment groups ( low dose ) .


Naloxone methiodide ( 1 mg/kg ) was administered via intraplantar injection , 15 minutes prior to application of loperamide HCl-encapsulated liposomal gel to determine opioid receptor dependent activity .


An investigator blinded to the treatment administered assessed time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer , respectively .


Application of loperamide HCl in a liposomal gel formulation exerted analgesic and anti-inflammatory effects exclusively in peripheral painful inflamed tissue .


This formulation produced highly significant analgesic and anti-inflammatory effects over the 48-hour time course studied following topical administration in rats with CFA-induced inflammation of the paw .


As expected , the diclofenac gel group showed significant antinociception over the duration of the study ; however , this effect was lower in comparison to the loperamide HCl liposomal gel formulation .


All other control groups showed no significant antinociceptive effects .


In addition , all control groups ( 1 % diclofenac gel , free loperamide gel , and empty liposomal gel ) did not demonstrate a significant change in paw volume over 48 hours .


In vivo studies were performed in the well-established rodent model of acute inflammatory pain .


We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response .


The study demonstrates that topically applied loperamide encapsulated within liposomal systems has improved therapeutic efficacy over conventional formulations for the local treatment of acute peripheral inflammatory pain conditions where the skin has remained intact .


Once in the inflamed peripheral tissue , loperamide provides analgesic and anti-inflammatory effects in a similar manner to peripheral endogenous opioids .


This preparation optimises the retention of drug at the site where action is required .


Remote ischemic preconditioning ( RIPC ) induced by transient limb ischemia confers multi-organ protection and improves exercise performance in the setting of tissue hypoxia .


We aimed to evaluate the effect of RIPC on exercise capacity in heart failure patients .


We performed a randomized crossover trial of RIPC ( 45-minutes limb ischemia ) compared to sham control in heart failure patients undergoing exercise testing .


Patients were randomly allocated to either RIPC or sham prior to exercise , then crossed over and completed the alternate intervention with repeat testing .


The primary outcome was peak VO2 , RIPC versus sham .


A mechanistic substudy was performed using dialysate from study patient blood samples obtained after sham and RIPC .


This dialysate was used to test for a protective effect of RIPC in a mouse heart Langendorff model of infarction .


Mouse heart infarct size with RIPC or sham dialysate exposure was also compared with historical control data .


Twenty patients completed the study .


RIPC was not associated with improvements in peak VO2 ( 15.6 + / -4.2 vs 15.3 + / -4.6 mL/kg/min ; p = 0.53 , sham and RIPC , respectively ) .


In our Langendorff sub-study , infarct size was similar between RIPC and sham dialysate groups from our study patients , but was smaller than expected compared to healthy controls ( 29.0 % , 27.9 % [ sham , RIPC ] vs 51.2 % [ controls ] .


We observed less preconditioning among the subgroup of patients with increased exercise performance following RIPC ( p < 0.04 ) .


In this pilot study of RIPC in heart failure patients , RIPC was not associated with improvements in exercise capacity overall .


However , the degree of effect of RIPC may be inversely related to the degree of baseline preconditioning .


These data provide the basis for a larger randomized trial to test the potential benefits of RIPC in patients with heart failure .


ClinicalTrials.gov + + + + + NCT01128790 .


The minimal clinically important difference ( MCID ) is the smallest outcome change that has clinical significance .


Its use has not been established in the study of myasthenia gravis ( MG ) .


Patients from a published intravenous immunoglobulin ( IVIg ) vs. placebo study were studied .


One anchor-based and 3 distribution-based techniques were used to identify quantitative myasthenia gravis score ( QMGS ) , repetitive nerve stimulation ( RNS ) , and single-fiber electromyography ( SFEMG ) MCID cut-offs .


Patients with a change-score exceeding MCID cut-offs were compared .


MCID cut-offs were below a QMGS change of 3.0 .


Anchor-based and 1 SEM cut-offs showed 58.3 % vs. 30.7 % responders ( P = 0.017 ) , SD 54.2 % vs. 19.2 % responders ( P = 0.018 ) , and effect size 0.519 vs. 0.164 ( P = 0.011 ) in IVIg vs. placebo .


Anchor-based ( P = 0.73 ) and effect-size ( P = 0.41 ) MCID cut-offs did not show a difference between IVIg and placebo .


MCID methods did not produce meaningful RNS cut-offs .


QMGS MCID values provide clinically relevant information and are recommended in MG trials .


MCID analysis shows that improvement in MG patients treated with IVIg reflects clinically meaningful changes .


Nonalcoholic fatty liver disease is associated with hepatic inflammation .


An emerging technique to image inflammation is PET using the glucose tracer , ( 18 ) F-FDG .


The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte .


Hepatic FDG uptake , as SUV = [ voxel counts / administered activity ] body weight ) , and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT .


Maximum SUV ( region voxel with the highest count rate , SUVmax ) and average SUV ( SUVave ) were measured .


Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity ( SUVLV ) .


SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density .


Patients were divided in subgroups on the basis of blood glucose ( < 4 , 4 to < 5 , 5 to < 6 , 6 to < 8 , 8 to < 10 , and > 10 mmol/L ) .


Hepatic steatosis was defined as CT density less than 40 HU ( n = 71 ) .


The percentage of hepatic fat increased exponentially with blood glucose .


SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose .


Fat-adjusted SUVave was higher in patients with hepatic steatosis ( p < 0.001 ) by ~ 0.4 in all blood glucose groups .


There was a similar difference ( ~ 0.3 ) in SUVmax ( p < 0.005 ) but no difference in SUVave .


SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without .


SUVave / SUVLV correlated with blood glucose in neither group .


FDG uptake is increased in hepatic steatosis , probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake .


Actinic keratosis ( AK ) may progress to squamous cell carcinoma .


In the case of normal or mildly photodamaged skin , lesion-directed treatments are considered valuable options despite poor published evidence of their therapeutic activity .


The aim of this single-centre , open-label , prospective , nonsponsored , randomized , controlled clinical trial was to compare CO2 laser ablation with cryotherapy in the treatment of isolated AKs of the face and scalp .


Patients with isolated ( 4 ) AKs of the face and scalp were randomized to receive CO2 laser ablation or cryotherapy .


After 90days , the overall complete remission ( CR ) rates of patients and lesions were assessed and correlated with thickness grade .


Two hundred patients with a total number of 543 AKs were enrolled .


The CR rates of lesions after 3months were 782 % with cryotherapy and 724 % with CO2 laser ablation .


Thicker lesions were significantly more responsive to cryotherapy ( P = 0034 ) .


Seventy-three patients ( 716 % ) had CR of all lesions 3months after cryotherapy and 64 ( 653 % ) after laser ablation .


At 12months after treatment the number of patients with CR was reduced to 53 with cryotherapy and 14 with laser ablation .


The rate of patients and lesions with CR is similar after 3months , but more patients remain in stable remission for 12months after cryotherapy .


Cryotherapy is more effective for thick lesions .


The cosmetic outcome was good or excellent in almost all patients .


To investigate changes in student food selection and consumption in response to the new National School Lunch Program meal patterns during fall 2011 .


Eight elementary and four intermediate schools in one Houston area school district were matched on free/reduced-price meal eligibility and randomized into control or intervention conditions .


Both intervention and control school cafeterias served the same menu .


The intervention school cafeterias posted the new meal pattern daily ; students could select one fruit and two vegetable servings per reimbursable meal .


Control school students could only select the previous meal pattern : a total of two fruit and vegetable servings per meal .


Students were observed during lunch : student sex and foods selected/consumed were recorded .


Diet analysis software was used to calculate energy/food groups selected/consumed .


Cochran-Mantel-Haenszel tests examined differences in the percent of students selecting each meal component by condition , controlling for sex , grade , and school free/reduced-price meal eligibility .


Analysis of covariance assessed differences in amount of energy/food groups selected and consumed , and differences in percent of food groups consumed .


Observations were conducted for 1,149 elementary and 427 intermediate students .


Compared with students in the control schools , significantly more intervention elementary and intermediate school students selected total ( P < 0.001 , P < 0.05 ) and starchy vegetables ( P < 0.001 , P < 0.01 ) ; more intervention intermediate school students selected fruit ( P < 0.001 ) , legumes ( P < 0.05 ) , and protein foods ( P < 0.01 ) .


There were significantly greater amounts of these foods selected and consumed , but no differences in the proportion of the foods consumed by condition .


Fewer calories were consumed by elementary and intermediate school intervention students .


More intervention students selected fruit and vegetables at lunch and consumed them compared with control condition students .


Future studies with larger and more diverse student populations are warranted .


Cigarette smoking is a well-known risk factor for development of coronary artery disease ( CAD ) .


However , some studies have suggested a `` smoker 's paradox , '' meaning neutral or favorable outcomes in smokers who have developed CAD , especially myocardial infarction ( MI ) .


The study aimed to examine the association of smoking status with clinical outcomes in the randomized controlled SYNTAX ( SYNergy Between PCI With TAXUS and Cardiac Surgery ) trial at 5-year follow-up .


Detailed smoking history was collected at baseline , 6-month , 1-year , 3-year , and 5-year follow-up .


The composite endpoints included death/MI/stroke ( primary endpoint ) plus major adverse cardiac and cerebrovascular events ( MACCE ) ( combination of death/MI/stroke and target lesion revascularization ) according to patient smoking status .


The comparison of 5-year clinical outcomes between the groups according to smoking status was performed with Cox regression using smoking status at baseline or smoking as a time-dependent covariate .


A sizeable proportion ( n = 322 , 17.9 % ) of patients had changing smoking status during 5-year follow-up .


One in 5 patients with complex CAD was smoking at baseline .


However , 60 % stopped after revascularization while others continued to smoke .


Smokers had worse clinical outcomes due to a higher incidence of recurrent MI in both revascularization arms .


Smoking was an independent predictor of the composite endpoint of death/MI/stroke ( hazard ratio [ HR ] : 1.8 ; 95 % confidence interval [ CI ] : 1.3 to 2.5 ; p = 0.001 ) and MACCE ( HR : 1.4 ; 95 % CI : 1.1 to 1.7 ; p = 0.02 ) .


Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD .


This places further emphasis on efforts at smoking cessation to improve revascularization benefits .


( SYNTAX Study : TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries ; NCT00114972 ) .


Tasisulam sodium ( hereafter referred to as tasisulam ) is a novel , highly albumin-bound agent that demonstrated activity in a phase 2 melanoma study .


In this open-label phase 3 study , patients with AJCC stage IV melanoma received tasisulam ( targeting an albumin-corrected exposure of 1200-6400 h ( hour ) .


g/mL on day 1 ) or paclitaxel ( 80 mg/m ( 2 ) on days 1 , 8 , and 15 ) every 28 days as second-line treatment .


The study was placed on clinical hold after randomization of 336 patients when a safety review indicated an imbalance of possibly drug-related deaths in the tasisulam arm .


Efficacy results for tasisulam versus paclitaxel revealed a response rate of 3.0 % versus 4.8 % , a median progression-free survival of 1.94 months versus 2.14 months ( P = .048 ) , and a median overall survival of 6.77 months versus 9.36 months ( P = .121 ) .


The most common drug-related grade 3 laboratory toxicities ( graded according to Common Terminology for Adverse Events [ version 3.0 ] ) were thrombocytopenia ( 18.9 % ) for patients treated with tasisulam and neutropenia/leukopenia ( 8.7 % ) among those receiving paclitaxel .


There were 13 possibly related deaths reported to occur on the study , with the majority occurring during cycle 2 in the setting of grade 4 myelosuppression , all in the tasisulam arm .


Investigation of the unexpectedly high rate of hematologic toxicity revealed a subset of patients with low tasisulam clearance , leading to drug accumulation and high albumin-corrected exposure in cycle 2 .


Although the study was stopped early because of safety issues in the tasisulam arm , tasisulam was considered unlikely to be superior to paclitaxel , and paclitaxel activity in the second-line treatment of melanoma was much lower than expected .


The toxicity imbalance was attributed to an unexpectedly low tasisulam clearance in a subset of patients , underscoring the importance of pharmacokinetic monitoring of compounds with complex dosing , even in late-phase studies .


To study the effect of transcutaneous acupoint electrical stimulation ( TAES ) on stress who received propofol target controlled infusion ( TCI ) general anesthesia in brain surgery .


Totally 40 neurosurgical patients of I-II grade ( ASA grading ) in our hospital were randomly divided into the TAES group ( T group ) and the control group ( C group ) , 20 in each group .


All patients received intravenous anesthesia by propofol TCI .


The TAES intervention was adopted in those of C group .


Electrodes were only applied to corresponding acupoints without electric stimulation .


The arterial blood was withdrawn before TAES ( T0 ) , before anesthesia ( T1 ) , before cutting ( T2 ) , at 60 min after encephalic incision ( T3 ) , immediately after incisions suture ( T4 ) , at about 10 min after removing tracheal catheters ( T5 ) to detect beta-endorphin ( beta-EP ) , cortisol ( COR ) , adrenalin ( E ) , blood sugar ( Glu ) .


The heart rate ( HR ) and mean arterial pressure ( MAP ) were recorded .


The total time of surgery , anesthesia , total infusion amount , blood lost amount , and urine amount were recorded .


In both groups , HR , MAP , COR , and E at T2 were lower than at T0 significantly ( P < 0.05 ) .


beta-EP in group C at T2 was lower than at T0 significantly ( P < 0.05 ) .


HR , MAP , COR in group C at T3 were higher than at T0 significantly ( P < 0.05 ) .


HR , MAP , E , and Glu in group C at T4 and T5 were higher than at T0 significantly ( P < 0.05 ) .


beta-EP in group T at T1 and T3 were higher than at T0 significantly ( P < 0.05 ) .


HR , COR , E , Glu , and beta-EP in group T at T4 and T5 were higher than at T0 significantly ( P < 0.05 ) .


Between groups , comparing with the time point T0 , the amplitude of variation of MAP , COR , and E at T2 in group C were significantly less ( P < 0.05 ) ; the amplitude of variation of HR , MAP , and COR at T3 in group C were less significantly , when compared with the time point T0 ( P < 0.05 ) ; the amplitude of variation of HR , MAP , COR , E , and Glu at T4 and T5 in group C were less significantly , when compared with the time point T0 ( P < 0.05 ) .


When comparing the two groups , the amplitude of variation of beta-EP at time points of T1 , T3 , T4 , and T5 in group T were larger than at T0 in group C ( P < 0.05 ) .


TAES could reduce stress and stabilize the internal environment when used in brain surgery with propofol TCI general anesthesia .


Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer , it may no longer be necessary either as treatment or as a guide to adjuvant treatment .


The authors conducted a single-center randomized trial ( INT09/98 ) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control .


From June 1998 to June 2003 , 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with ( QUAD ) or without ( QU ) axillary lymph node dissection ; a total of 517 patients finally were evaluated .


All patients received radiotherapy to the residual breast only .


Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status , estrogen receptor status , and tumor grade .


Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status , tumor grade , and human epidermal growth factor receptor 2 and laminin receptor status .


Overall survival ( OS ) was the primary endpoint .


Disease-free survival ( DFS ) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints .


After a median follow-up of > 10 years , the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 ( 95 % confidence interval , 0.59-2 .00 ; P = .783 ) and was 1.04 ( 95 % confidence interval , 0.56-1 .94 ; P = .898 ) for DFS .


Of the 245 patients in the QU treatment arm , 22 ( 9.0 % ) experienced axillary lymph node recurrence .


The median time to axillary lymph node recurrence from breast surgery was 30.0 months ( interquartile range , 24.2 months-73 .4 months ) .


Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial .


The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment .


Apha-2 agonists are combined with local anesthetics to extend the duration of regional anesthesia .


We evaluated the effect of combining dexmedetomidine with levobupivacine with respect to duration of motor and sensory block and duration of analgesia .


Sixty patients scheduled for elective forearm and hand surgery were divided into two equal groups in a randomized double blind fashion .


The patients received brachial plexus block via supraclavicular route with the help of nerve stimulator .


In group L ( n = 30 ) 35cc of levobupivacaine with 1ml of isotonic saline and in group LD ( n = 30 ) 35cc of levobupivacine with 1 ml of ( 100 microgram ) of dexmedetomidine was given .


Duration of motor and sensory block and time to first rescue analgesia were recorded .


Data analysis was done by SPSS version 16.0 [ SPSS Inc ILLINOIS , USA , 2008 ] .


Categorical variables were analyzed using Pearson `` s Chi-square test .


Normally distributed numerical variables were analyzed using unpaired `` t '' test .


Skewed numerical variables within the group were analyzed using Man-Whitney `` U '' test .


All tests were two tailed .


Statistical significance was defined as P < 0.05 .


Sensory and motor block durations were longer in group LD as compared to L ( P < 0.01 ) .


Duration of analgesia was significantly longer in group LD as compared to group L ( p < 0.05 ) .


Dexmedetomidine added to levobupivacaine in supraclavicular brachial plexus block prolongs the duration of block and the duration of postoperative analgesia .


To investigate the correlation between regulatory T ( Treg ) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [ 1,25 ( OH ) D ] in relation to Treg cells .


Fifty female BALB/c mice were randomly divided into five groups : the basal control ( BAS ) , Sham , ovariectomy ( OVX ) , OVX + diethylstilbestrol ( OVX+DES ) , and OVX +1,25 ( OH ) D. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry .


Femurs were stained by immunohistochemistry to detect Foxp3 protein expression .


Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR , respectively .


In comparison with the Sham group , a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area ( BV/TV ) , trabecular number ( Tb.N ) and trabecular thickness ( Tb.Th ) .


1,25 ( OH ) Dand DES partly prevented the decrease in BV/TV , Tb.N , Tb.Th in OVX mice .


Treg cell number , Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group .


1,25 ( OH ) 2Dand DES significantly increased Treg cell number and Foxp3 expression .


Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters .


The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis .


The antiosteoporosis of 1,25 ( OH ) Dis related to regulatory T cells .


Dexmedetomidine-induced bradycardia or hypotension has recently attracted considerable attention because of potentially grave consequences , including sinus arrest and refractory cardiogenic shock .


A route other than intravenous injection or a low dose may help minimize cardiovascular risks associated with dexmedetomidine .


However , few studies have addressed the clinical effects of low-dose intramuscular dexmedetomidine as premedication .


Forty American Society of Anesthesiologists physical status I adult patients undergoing suspension laryngoscopic surgery were randomized to receive intramuscular dexmedetomidine ( 1 gkg-1 ) or midazolam ( 0.02 mgkg-1 ) 30 minutes prior to anaesthesia induction .


The sedative , hemodynamic , and adjuvant anaesthetic effects of both premedications were assessed .


The levels of sedation ( Observer 's Assessment of Alertness/Sedation scales ) and anxiety ( visual analog score ) at pre-induction , and the times to eye-opening and extubation , were not different between the groups .


The heart rate response following tracheal intubation and extubation , and mean arterial pressure responses after extubation , were attenuated in the dexmedetomidine group compared to the midazolam group .


No bradycardia or hypotension was noted in any patients .


Propofol target concentrations at intubation and at start and completion of surgery were decreased in the dexmedetomidine group , whereas no difference in respective remifentanil levels was detected .


This study provides further evidence that dexmedetomidine premedication in low dose ( 1 gkg-1 ) by intramuscular route can induce preoperative sedation and adjuvant anaesthetic effects without clinically significant bradycardia or hypotension .


To determine which nostril is more suitable for nasotracheal intubation in patients with normal patency of both nostrils .


Prospective , randomized clinical trial .


Operating room of a university medical center .


191 ASA physical status 1 and 2 patients scheduled for elective oral surgery requiring general anesthesia with nasotracheal intubation .


Patients were randomized to two groups to undergo nasotracheal intubation through the right nostril ( Group R ; n = 96 ) or the left nostril ( n = 95 ) .


Standard traditional nasotracheal intubation was performed using the Macintosh laryngoscope .


Tube rotation was attempted for alignment toward the glottis , and Magill forceps were then used to assist intubation , as necessary .


Epistaxis was inspected in the pharynx after the tube tip was passed through the nasal cavity and 15 minutes after nasotracheal intubation was completed .


Intubation time was the interval between when the anesthesiologist opened the patient 's mouth with the cross finger maneuver and when the tube was connected to the anesthetic circuit after nasotracheal completion .


The frequency of epistaxis was significantly lower in Group R than Group L ( P = 0.0006 ) .


Although there was no significant difference in nasal passage time between two groups , the intubation time in Group R ( 24.5 9.4 sec ) was shorter than in Group L ( 30.5 15.6 sec ; P = 0.0015 ) .


Nasal intubation via the right nostril is more safely performed than with the left nostril .


Because of less epistaxis and faster intubation .


Many patients with high blood pressure ( BP ) do not have antihypertensive medications appropriately intensified at clinician visits .


We investigated whether an online spaced-education ( SE ) game among primary care clinicians can decrease time to BP target among their hypertensive patients .


A 2-arm randomized trial was conducted over 52 weeks among primary care clinicians at 8 hospitals .


Educational content consisted of 32 validated multiple-choice questions with explanations on hypertension management .


Providers were randomized into 2 groups : SE clinicians were enrolled in the game , whereas control clinicians received identical educational content in an online posting .


SE game clinicians were e-mailed 1 question every 3 days .


Adaptive game mechanics resent questions in 12 or 24 days if answered incorrectly or correctly , respectively .


Clinicians retired questions by answering each correctly twice consecutively .


Posting of relative performance among peers fostered competition .


Primary outcome measure was time to BP target ( < 140/90 mm Hg ) .


One hundred eleven clinicians enrolled .


The SE game was completed by 87 % of clinicians ( 48/55 ) , whereas 84 % of control clinicians ( 47/56 ) read the online posting .


In multivariable analysis of 17 866 hypertensive periods among 14 336 patients , the hazard ratio for time to BP target in the SE game cohort was 1.043 ( 95 % confidence interval , 1.007-1 .081 ; P = 0.018 ) .


The number of hypertensive episodes needed to treat to normalize one additional patient 's BP was 67.8 .


The number of clinicians needed to teach to achieve this was 0.43 .


An online SE game among clinicians generated a modest but significant reduction in the time to BP target among their hypertensive patients .


http://www.clinicaltrials.gov .


Unique identifier : NCT00904007 .


Understanding attitudes to mental health issues can inform public health interventions .


However , low response rates may contribute to nonresponse bias .


In a randomized controlled trial we examined the effect of sending a prenotification postcard before the questionnaire and the placement of a short message on the survey envelope ( teaser ) on response rates to a mailed questionnaire about bulimia nervosa `` mental health literacy '' .


Questionnaires were mailed to 3,010 adults ( 50.6 % female and 49.4 % male ) aged 18-65years .


In a 2 ( pre-notification-present ; absent ) by 2 ( teaser-present ; absent ) design , questionnaire recipients were randomly allocated to the experimental strategies .


Outcomes considered were response rate , response time , and cost .


The overall response rate was 22.0 % .


Significant main effects showed higher response rates for the use of prenotification ( present = 23.6 % ; absent = 20.3 % ) , among female participants , and older participants .


A significant interaction of teaser by gender indicated lower response rates for men who received the teaser but not for women .


Older participants returned the questionnaire more promptly than younger participants .


Females-but not males-who received the teaser were slower to return the questionnaire .


Higher response rates for participants receiving the postcard compensated for increased costs , particularly for males and older participants .


Response rates to a mental health postal survey can be increased through the use of prenotification .


Endothelial function is an independent predictor of prognosis in heart failure ( HF ) subjects .


Statins , beyond their lipid lowering role , exert beneficial effect in patients with atherosclerosis .


In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function , bone marrow-derived endothelial progenitor cells ( EPC ) mobilization and inflammatory status according to HF patient status .


We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF .


The study was carried out on two separate arms , one with atorvastatin 40mg/d and one with atorvastatin 10mg/d ( randomized , double-blind , cross-over design ) .


The number of circulating CD34 ( + ) / CD133 ( + ) / KDR ( + ) EPCs was evaluated by flow cytometry .


Endothelial function was evaluated by flow mediated dilation ( FMD ) in the brachial artery .


Serum levels of tumor necrosis factor alpha ( TNF - ) were measured by ELISA .


Treatment with atorvastatin 40mg/d significantly increased circulating EPC ( p = 0.002 ) , FMD ( p = 0.001 ) and reduced TNF - ( p = 0.01 ) compared to baseline .


Similarly , treatment with atorvastatin 10mg/day increased circulating EPC ( p = 0.01 ) , FMD ( p = 0.08 ) and reduced TNF - ( p = 0.01 ) compared to baseline .


Interestingly , with 40mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III ( p = 0.03 ) .


Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects .


Moreover , these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects .