; BMI , 243kg/m ( 2 ) ; fasting plasma glucose , 5.10.2 mmol/l and HbA1c , 341mmol/mol ( 5.30.1 % ) ) were randomised to two-paired study days comprising a 4-h 50g oral glucose tolerance test ( OGTT ) with paracetamol ( A ) and an isoglycaemic intravenous ( i.v. ) glucose infusion ( B ) , with ( A1 + B1 ) and without ( A2 + B2 ) preceding administration of the DPP4 inhibitor sitagliptin .


Isoglycaemia was obtained in all subjects on the paired study days .


Significant increases in fasting levels and OGTT-induced responses of active GLP1 and GIP were seen after DPP4 inhibition .


No significant impact of DPP4 inhibition on fasting plasma glucose ( 5.10.1 vs 4.90.1 mmol/l , P = 0.3 ) , glucose tolerance ( area under the curve ( AUC ) for plasma glucose , 15135 vs 13726mmol/lmin , P = 0.7 ) or peak plasma glucose during OGTT ( 8.50.4 vs 8.10.3 mmol/l , P = 0.3 ) was observed .


Neither incretin effect ( 409 % ( without DPP4 inhibitor ) vs 407 % ( with DPP4 inhibitor ) , P = 1.0 ) , glucagon responses ( 1395165 vs 1223195pmol/lmin , P = 0.41 ) , GIGD ( 524 vs 565 % , P = 0.40 ) nor gastric emptying ( Tmax for plasma paracetamol : 869 vs 8012min , P = 0.60 ) changed following DPP4 inhibition .


These results suggest that acute increases in active incretin hormone levels do not affect glucose tolerance , GIGD , incretin effect , glucagon responses or gastric emptying in healthy subjects .


Patients 65 years old ( `` older '' ) are often not included in randomized clinical trials ( RCT ) , but when they are , care in an RCT might improve quality of life ( QoL ) .


We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study ( `` off-trial '' ) .


Older women with invasive , non-metastatic breast cancer ( n = 150 RCT ; 530 off-trial ) were included .


Linear mixed-effects models tested associations between chemotherapy on - vs. off-trial and changes in EORTC ( European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire ) QoL scores over 24 months , controlling for pre-treatment QoL , age , education , tumor factors , comorbidity , and other covariates .


Anthracycline regimens were used by 58 % of women treated on-trial vs. 54 % of those treated off-trial .


Women in the RCT reported an adjusted mean increase of 13.7 points ( 95 % CI 10.2 , 17.1 ) in global QoL at 24 months ( vs. mid-treatment ) , while women treated off-trial had only an adjusted improvement of 7.0 points ( 95 % CI 3.5 , 10.4 ; p = .007 for difference in mean changes ) .


Women in the RCT had significantly greater improvement in emotional function than those treated off-trial , controlling for baseline ; they also had greater reductions in therapy side effects and fatigue at 24 months than women off-trial , controlling for covariates .


There may be different QoL trajectories for older women undergoing breast cancer chemotherapy on - vs. off-trial .


If confirmed , the results suggest that the extra monitoring and communication within an RCT could provide the infrastructure for interventions to address symptoms and improve QoL for the growing older cancer population .


Acute cellular rejection ( AR ) after lung transplantation may result in significant morbidity and mortality both on the short and long term .


Transbronchial biopsy through flexible bronchoscopy is highly sensitive for the diagnosis of AR , but reproducibility of histopathologic interpretation is less convincing .


Probe-based confocal laser endomicroscopy ( pCLE ) , a novel imaging tool in the field of respiratory medicine , enables real-time imaging of the pulmonary acini .


We performed 105 bronchoscopies in lung transplant recipients , combining both transbronchial biopsies and pCLE .


We conducted an observational survey for pCLE findings in AR .


Calculations for cellularity showed a median cell count ( ACA ) of 50 ( IQR 18 to 120 ) cells per microscopic field for AR and 10 ( IQR 0 to 15 ) cells per microscopic field for matched controls ( p = 0.0004 ) .


Cellular autofluorescence in the AR group was 1,163 ( 157 ) units and 489 ( 101 ) units for the matched controls ( p = 0.0009 ) .


Autofluorescent cells were present in 73 % ( 10 ) of the recorded frames in the AR group and in only 42 % ( 9 ) of the recorded frames in the control group ( p = 0.03 ) .


Contingency analysis for the presence/absence of ACA in the AR group versus the control group showed a sensitivity of 0.93 and a specificity of 0.46 ( relative risk = 6.5 [ 95 % CI 0.94 to 44.8 ] , p = 0.01 ) .


The consecutive application of 3 pCLE criteria resulted in a sensitivity of 0.93 and a specificity of 0.83 for detection of AR .


Our observational survey suggests the existence of specific pCLE characteristics in patients with AR .


Further efforts are necessary to validate these findings prospectively .


Noroviruses are the most common cause of gastroenteritis in the United States .


An understanding of the infectious dose of these viruses is important for risk assessment studies .


Healthy adults were enrolled in a randomized , double-blind , placebo-controlled evaluation of different dosages of Norwalk virus .


Eligible subjects were monitored for clinical gastroenteritis , and infection status was determined .


The presence of virus in vomitus was also assessed .


Fifty-seven persons were enrolled ; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative .


Twenty-one persons were infected ( all blood group O or A ) , and 67 % of those infected developed viral gastroenteritis .


The 50 % human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units ( approximately 1320 genomic equivalents [ gEq ] ) for secretor-positive blood group O or A persons and 7.0 ( approximately 2800 gEq ) for all secretor-positive persons .


The time of illness onset was inversely correlated with inoculum dose .


The maximal concentration of virus shedding was higher for persons with gastroenteritis .


Norwalk virus was identified in 15 of 27 ( 56 % ) vomitus samples at a median concentration of 41 000 gEq/mL .


The 50 % human infectious dose measured is higher than previous estimates and similar to that of other RNA viruses .


Clinical Trials RegistrationNCT00138476 .


Hospital readmissions for acute exacerbations of COPD ( AECOPDs ) pose burdens to the health-care system and patients .


A current gap in knowledge is whether a predischarge screening and educational tool administered to patients with COPD reduces readmissions and ED visits .


A single-center , randomized trial of admitted patients with AECOPDs was conducted at Henry Ford Hospital between February 2010 and April 2013 .


One hundred seventy-two patients were randomized to either the control ( standard care ) or the bundle group in which patients received smoking cessation counseling , screening for gastroesophageal reflux disease and depression or anxiety , standardized inhaler education , and a 48-h postdischarge telephone call .


The primary end point was the difference in the composite risk of hospitalizations or ED visits for AECOPD between the two groups in the 30 days following discharge .


A secondary end point was 90-day readmission rate .


Of the 172 patients , 18 of 79 in the control group ( 22.78 % ) and 18 of 93 in the bundle group ( 19.35 % ) were readmitted within 30 days .


The risk of ED visits or hospitalizations within 30 days was not different between the groups ( risk difference , -3.43 % ; 95 % CI , -15.68 % to 8.82 % ; P = .58 ) .


Overall , the time to readmission in 30 and 90 days was similar between groups ( log-rank test P = .71 and .88 , respectively ) .


A predischarge bundle intervention in AECOPD is not sufficient to reduce the 30-day risk of hospitalizations or ED visits .


More resources may be needed to generate a measurable effect on readmission rates .


ClinicalTrials.gov ; No. : NCT02135744 ; URL : www.clinicaltrials.gov .


Opioid-induced constipation is common and debilitating .


We investigated the efficacy and safety of naloxegol , an oral , peripherally acting , - opioid receptor antagonist , for the treatment of opioid-induced constipation .


In two identical phase 3 , double-blind studies ( study 04 , 652 participants ; study 05 , 700 participants ) , outpatients with noncancer pain and opioid-induced constipation were randomly assigned to receive a daily dose of 12.5 or 25 mg of naloxegol or placebo .


The primary end point was the 12-week response rate ( 3 spontaneous bowel movements per week and an increase from baseline of 1 spontaneous bowel movements for 9 of 12 weeks and for 3 of the final 4 weeks ) in the intention-to-treat population .


The key secondary end points were the response rate in the subpopulation of patients with an inadequate response to laxatives before enrollment , time to first postdose spontaneous bowel movement , and mean number of days per week with one or more spontaneous bowel movements .


Response rates were significantly higher with 25 mg of naloxegol than with placebo ( intention-to-treat population : study 04 , 44.4 % vs. 29.4 % , P = 0.001 ; study 05 , 39.7 % vs. 29.3 % , P = 0.02 ; patients with an inadequate response to laxatives : study 04 , 48.7 % vs. 28.8 % , P = 0.002 ; study 05 , 46.8 % vs. 31.4 % , P = 0.01 ) ; in study 04 , response rates were also higher in the group treated with 12.5 mg of naloxegol ( intention-to-treat population , 40.8 % vs. 29.4 % , P = 0.02 ; patients with an inadequate response to laxatives , 42.6 % vs. 28.8 % , P = 0.03 ) .


A shorter time to the first postdose spontaneous bowel movement and a higher mean number of days per week with one or more spontaneous bowel movements were observed with 25 mg of naloxegol versus placebo in both studies ( P < 0.001 ) and with 12.5 mg of naloxegol in study 04 ( P < 0.001 ) .


Pain scores and daily opioid dose were similar among the three groups .


Adverse events ( primarily gastrointestinal ) occurred most frequently in the groups treated with 25 mg of naloxegol .


Treatment with naloxegol , as compared with placebo , resulted in a significantly higher rate of treatment response , without reducing opioid-mediated analgesia .


( Funded by AstraZeneca ; KODIAC-04 and KODIAC-05 ClinicalTrials.gov numbers , NCT01309841 and NCT01323790 , respectively . )


Patients with a pacing indication and first-degree atrioventricular ( AV ) - block pose a clinical challenge .


The prognostic impact of first-degree AV-block in patients with sinus node dysfunction and the impact of pacing in this setting are not known .


In the Mode Selection Trial ( MOST ) , 2,010 patients with sinus node dysfunction were randomized to either dual-chamber ( DDD-R ) or ventricular ( VVI-R ) pacing and followed for a median of 33 months .


We report on clinical outcomes in patients with first-degree AV-block ( PR interval > 200 ms ) compared with patients who had a normal PR interval at baseline .


Patients with first-degree AV-block ( n = 378 ) were older ( median [ Q1 , Q3 ] ; 76 [ 70 , 82 ] years vs 73 [ 66 , 79 ] years , P < 0.0001 ) , more often male ( 57 % vs 49 % , P = 0.0049 ) , and had more comorbidity , such as hypertension ( 66 % vs 60 % , P = 0.034 ) and heart failure ( 24 % vs 17 % , P = 0.0050 ) than patients with normal AV-conduction ( n = 1,159 ) .


In multivariable analyses , patients with first-degree AV-block were at greater risk of death , stroke , or heart failure hospitalization ( hazard ratio [ HR ] 1.31 , 95 % confidence interval [ CI ] 1.06-1 .61 , P = 0.013 ) .


A trend towards a higher incidence of atrial fibrillation was seen ( HR 1.24 , 95 % CI 0.98-1 .55 , P = 0.069 ) .


No significant interactions between pacing arm and prolonged versus normal PR were found for any endpoint , and hazard ratios were consistent across subgroups .


First-degree AV-block is associated with more advanced disease but is still an independent predictor of poor clinical outcome .


Neither DDD-R nor VVI-R pacing , as employed in MOST , eliminate the negative effects associated with first-degree AV-block .


This study evaluated the pharmacokinetics of a granule formulation of dolutegravir developed as an alternative to tablets for use in paediatric populations .


A randomized , open-label study in healthy adults was carried out .


Subjects received five treatments in a crossover design : a single dose of dolutegravir 50 mg as a tablet and dolutegravir 50 mg in 10 g of granule administered directly to mouth or mixed with purified water , water containing high cation concentrations or milk-based infant formula .


Study treatments were separated by 7 days .


Safety evaluations and serial pharmacokinetic sampling were done during each treatment period .


A non-compartmental pharmacokinetic analysis was performed ; geometric least-squares mean ratios and 90 % CIs were generated for treatment comparison .


Palatability was assessed by questionnaire .


Plasma dolutegravir exposures in all granule treatment arms exceeded those of tablet formulation .


The mean area under the curve from time 0 to infinity ( AUC ( 0 - ) ) and maximum concentrations were 55-83 % and 62-102 % higher , respectively .


Pharmacokinetics were similar when dolutegravir was mixed with purified or cation-containing water .


Dolutegravir was well tolerated , with no withdrawals due to adverse events .


Taste was rated acceptable for all treatments .


The exposure of dolutegravir after administration of granule formulation alone , with different types of water and with milk formula , exceeded that of the tablet .


The similarity of dolutegravir exposure seen with the granule formulation demonstrates that dolutegravir granule can be given without restriction on the type of liquid or can be administered directly to the mouth ( for example , when potable water is not available ) .


To establish during late gestation and early lactation the effects of supplementing silymarin , a natural hepatoprotective substance , combined with a powerful antioxidant , lycopene , on milk production and on serum biomarkers of oxidative status .


Italian Friesian dairy cows were given individually a supplement containing a mixture of silymarin ( 7.77 g/day/cow ) and lycopene ( 1.27 g/day/cow ) ( n = 10 ) or no supplement ( control ; n = 10 ) .


Treatment was administered from 7 days before the expected calving date to the first 14 days in milk .


At 7 days before the expected calving date , at calving , and 7 days postpartum , body condition score ( BCS ) and concentrations in serum of reactive oxygen metabolites ( ROM ) , total antioxidant capacity ( OXY ) and thiobarbituric acid reactive substances ( TBARS ) were evaluated .


Bodyweight , milk production , and somatic cell count ( SCC ) were determined at 7 , 14 and 21 days postpartum .


The mean time of treatment prior to calving was 6.3 ( min 4 , max 11 ) days .


Compared with control cows , treatment increased energy corrected milk yield ( 33.3 vs. 37.8 ( SEM 1.10 ) kg/day ; p = 0.006 ) and milk fat yield ( 1.14 vs. 1.32 ( SEM 0.06 ) kg/day ; p = 0.05 ) over the first 21 days of lactation .


Treated cows had lower mean log10 SCC compared to control cows ( 4.9 vs. 5.24 ( SEM 0.11 ) log10 cells/mL ) and had lower overall concentration of TBARS ( 1.47 vs. 1.59 ( SEM 0.016 ) nM/mL ; p < 0.001 ) , but similar concentrations of ROM and OXY in serum .


However there was a treatment by time interaction ( p = 0.09 ) for OXY , and at calving mean OXY was higher in treated cows compared with pre-calving values ( p < 0.001 ) .


Despite the acknowledged limitation of the study , i.e. the small number of animals , our results suggest that silymarin and lycopene , as health-beneficial feed supplements , may help dairy cows in metabolic adaptation during the first stages of lactation .


During the peripartum period dairy cows suffer moderate-to-severe fatty liver and from an overproduction of free radicals .


The supplementation of a mixture of silymarin and lycopene during these stressful days may be useful to mitigate these metabolic disorders with beneficial effects on the subsequent lactation .


Part 1 of this phase III study was a randomized , double-blind , parallel-group , placebo-controlled , multicenter study of caregiver administered diazepam auto-injector ( AI ) in subjects with acute repetitive seizures ( ARS ) and demonstrated that diazepam AI was well-tolerated and significantly more effective than placebo AI in delaying the time to next seizure or rescue .


Part 2 of this study , presented herein , was an open-label continuation to assess the long-term safety and effectiveness of diazepam AI for the treatment of ARS .


Of the 234 subjects randomized in part 1 , 161 continued into part 2 and were provided open-label diazepam AI .


Effectiveness measures were time to next seizure or rescue , number of subsequent rescues by type ( rescue medication , emergency room visit , or other medical care ) , and number of subsequent seizures during the 12-h follow-up period .


Safety data ( adverse events and respirations < 8/min ) were also collected .


During the open-label part 2 study , 129 subjects were administered a total of 1,380 diazepam AI treatments ( median 4.5 ; range 1-118 ) , of which 1,071 ( 77.6 % ) were effective with no subsequent seizure or rescue during the 12-h follow-up period .


Median number of subsequent seizures experienced by subjects was one ( range 0-20 ) .


Of the 1,380 administrations , 79 ( 5.7 % ) required use of rescue medication , 18 ( 1.3 % ) required a visit to an emergency room , and 6 ( 0.4 % ) required other rescue medical care .


In most ( 75 % ) of subjects with treatment-emergent adverse events ( TEAEs ) , TEAEs were mild or moderate in severity .


Commonly reported treatment-related TEAEs were injection-site pain ( 10.9 % ) , injection-site hemorrhage ( 7 % ) , and injection-site bruising ( 6.3 % ) .


Although three subjects met the predefined respiratory rate threshold , none were considered clinically significant or reported as AEs .


Long-term treatment with diazepam AI administered by trained caregivers in an outpatient setting to treat ARS is a safe and effective option .


A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .


The prognostic importance of the speed of early hematoma growth in acute intracerebral hemorrhage ( ICH ) has not been well established .


We aimed to determine the association between the rate of increase in hematoma volume and major clinical outcomes in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial ( INTERACT ) studies .


The effects of early intensive blood pressure ( BP ) lowering according to the speed of hematoma growth were also investigated .


Pooled analyses of the INTERACT1 ( n = 404 ) and INTERACT2 ( n = 2,839 ) studies-randomized controlled trials of patients with spontaneous ICH with elevated systolic BP , randomly assigned to intensive ( target systolic BP < 140 mm Hg ) or guideline-based ( < 180 mm Hg ) BP management .


The speed of ultraearly hematoma growth ( UHG ) was defined as hematoma volume ( mL ) / onset-to-CT time ( hours ) .


Primary outcome was death or major disability ( modified Rankin Scale score of 3-6 ) at 90 days .


Among a total of 2,909 patients ( 90 % ) with information on UHG and outcome , median speed of UHG was 6.2 mL/h .


There was a linear association between UHG and outcome : multivariable-adjusted odd ratios 1.90 ( 95 % confidence interval 1.50-2 .39 ) for 5-10 mL/h and 2.96 ( 2.36-3 .71 ) for > 10 mL/h vs the < 5 mL/h group .


There were no clear differences in the effects of intensive BP lowering according to 3 speeds of UHG on outcome ( p = 0.75 for homogeneity ) .


The speed of UHG in patients with ICH was continuously associated with increased risks of death or major disability , and from lower levels than previously reported ( 5 mL/h ) .


The benefits of intensive BP lowering appear to be independent of the speed of bleeding .


Photodynamic therapy is an effective tool in the management of some forms of skin cancer and generalized solar dermopathy and can be beneficial in the management of acne vulgaris .


When used as an area treatment one of the main limiters is the quite severe burning pain that patients feel during the illumination phase of the treatment .


To examine the effectiveness of a plant derived anti-nociceptive spray applied prior to and during large area photodynamic therapy .


A split face or left arm versus right arm , placebo controlled trial was performed on 60 patients to assess the effectiveness of the spray in reducing pain perception .


There was a statistically significant reduction in pain at all illumination points during the illumination phase but no significant difference in discomfort levels in the first 72 h post illumination .


Only large area photodynamic therapy treatment was performed during the study .


No conclusions can be drawn for small area treatments .


Use of a simple , plant derived anti-nociceptive spray can reduce the discomfort experienced by patients undergoing photodynamic therapy to large areas .


To compare the effectiveness of the traditional center of tibial plateau as the entry point and digital technology in the design of intramedullary tibial nail point positioning method in total knee arthroplasty ( TKA ) .


Between October 2011 and October 2012 , 60 cases undergoing unilateral TKA and meeting the selection criteria were randomly divided into 2 groups : in group A ( 30 cases ) , the tibial plateau center as the entry point of tibial intramedullary positioning was used ; in group B ( 30 cases ) , Mimics 10.01 software to simulate the guide rod point of tibial intramedullary positioning was used .


There was no significant difference in gender , age , etiology , disease duration , sides , and preoperative knee range of motion , Hospital for Special Surgery ( HSS ) score , and Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) between 2 groups ( P > 0.05 ) .


Postoperative X-ray films were taken to measure the tibiofemoral angle and tibial angle ; knee range of motion , and HSS and WOMAC scores were used to assess the activity of knee .


The entry point of group B was located in front of the center of tibial plateau , which was inconsistent with the traditional entry point .


The incision healed by first intention in all patients of 2 groups .


The patients were followed up 6 to 12 months ( mean , 8.6 months ) .


The X-ray measurement at 1 week after operation showed no significant difference in tibiofemoral angle between 2 groups ( t = -6.65 , P = 0.72 ) , but the anteroposterior and lateral tibial angles of group A were significantly lower than those of group B ( P < 0.05 ) .


The knee range of motion , HSS score , and WOMAC score of 2 groups were significantly higher at 3 and 6 months after operation when compared with preoperative values ( P < 0.05 ) , and the values at 6 months were significantly increased than those at 3 months after operation ( P < 0.05 ) .


HSS score and WOMAC score had no significant difference between 2 groups at 3 months after operation ( P > 0.05 ) , but the scores of group B were significantly higher than those of group A at 6 months ( P < 0.05 ) .


The knee range of motion of group B was significantly better than that of group A at 3 months after operation ( t = 2.13 , P = 0.04 ) , but no significant difference was found between 2 groups at 6 months ( t = 0.58 , P = 0.56 ) .


Compared with the traditional intramedullary guide rod insertion point positioning , digital individualized design of entry point positioning has the advantages of more accurate lower limb force line , better recovery of knee function , and earlier 90 degrees activities , but the long-term effectiveness needs further observation .


Chronic alcohol abuse has been traditionally associated with impaired cognitive abilities .


The deficits are most evident in higher order cognitive functions , such as abstract reasoning , problem solving and visuospatial processing .


The present study sought to increase current understanding of the neuropsychological basis of poor abstract reasoning abilities in alcohol-dependent subjects using functional magnetic resonance imaging ( fMRI ) .


An abstract reasoning task-based fMRI study was carried out on alcohol-dependent subjects ( n = 18 ) and healthy controls ( n = 18 ) to examine neural activation pattern .


The study was carried out using a 3-T whole-body magnetic resonance scanner .


Preprocessing and post processing was performed using SPM 8 software .


Behavioral data indicated that alcohol-dependent subjects took more time than controls for performing the task but there was no significant difference in their response accuracy .


Analysis of the fMRI data indicated that for solving abstract reasoning-based problems , alcohol-dependent subjects showed enhanced right frontoparietal neural activation involving inferior frontal gyrus , post central gyrus , superior parietal lobule , and occipito-temporal gyrus .


The extensive activation observed in alcohol dependents as compared to controls suggests that alcohol dependents recruit additional brain areas to meet the behavioral demands for equivalent task performance .


The results are consistent with previous fMRI studies suggesting decreased neural efficiency of relevant brain networks or compensatory mechanisms for the execution of task for showing an equivalent performance .


To evaluate efficacy , safety , and tolerability efinaconazole topical solution , 10 % in diabetic patients with onychomycosis .


A post-hoc analysis of 112 patients , aged 29-70 years , randomized to receive efinaconazole topical solution , 10 % or vehicle from two identical multicenter , double-blind , vehicle-controlled 48-week studies evaluating safety and efficacy .


The primary end point was complete cure rate ( 0 % clinical involvement of target toenail , and both negative potassium hydroxide examination and fungal culture ) at week 52 .


Mycologic cure rates ( OC ) were significantly greater with efinaconazole ( 56.5 % and 56.3 % in diabetic and non-diabetic patients respectively ) compared to vehicle ( P = 0.016 and P < 0.001 , respectively ) .


The primary end point , complete cure , was also greater for efinaconazole ( 13.0 % and 18.8 % , respectively vs 3.7 % and 4.7 % ) .


Treatment success ( percent affected target toenail 10 % ) for efinaconazole was 40.8 % and 47.7 % , respectively vs 18.5 % and 18.2 % with vehicle .


There was no statistically significant difference between the diabetic and non-diabetic populations for any efficacy endpoint .


Adverse events associated with efinaconazole were local site reactions and clinically similar to vehicle .


Once daily efinaconazole topical solution , 10 % may provide a useful topical option in the treatment of diabetic patients with onychomycosis .


Allergic rhinitis is a chronic illness , affecting 10 to 40 % of the worldwide population .


Chinese herbal medicines , the treatment of allergic rhinitis , adopted thousands of years in ancient China , has recently raised much attention among researchers globally .


This study evaluates the effects of two Chinese herbal formulae [ Cure-allergic-rhinitis Syrup ( CS ) and Yu-ping-feng San ( YS ) ] in treating undergraduate nursing students with allergic rhinitis over a 3-month follow-up , when compared to a placebo control group .


A double-blind , randomised controlled trial with repeated-measures , three-parallel-groups design was conducted in a random sample of 249 participants recruited from one university in Hong Kong .


After baseline measurements , participants were randomly assigned to CS , YS , or placebo groups ( n = 83 per group ) .


The main outcomes , including symptom severity , quality of life , and body constitution , were measured with self-administered questionnaires at baseline and immediately , 1 and 3 months after the 4-week interventions .


240 participants completed the trial , with 9 ( 3.6 % ) drop-outs .


The results of Generalised Estimating Equations test followed by pairwise contrasts tests indicated that the participants who received CS showed significantly greater reduction of symptoms ( mean difference of CS vs. placebo = 26.13-34 .55 , P < 0.0005 ) and improvements in quality of life ( mean difference of CS vs. placebo = 12.81-16 .76 , P < 0.001 ) , and body constitution in ` Qi-deficiency ' , ` Yang-deficiency ' , and ` Inherited Special ' ( mean difference of CS vs. placebo = 7.05-8 .12 , 7.56-8 .92 , and 4.48-8 .10 , P = 0.01 - < 0.0005 , 0.001-0 .004 , and 0.01 - < 0.0005 , accordingly , at three post-tests ) .


The participants who received YS also indicated significant greater improvements in symptom severity , quality of life , and a few patterns of body constitution when compared to the placebo group .


However , its effects were lesser in strength ( i.e. , smaller effect sizes ) , varieties of symptoms , and body constitution and sustainability over the 3 months .


The herbal formula CS was found effective to reduce symptoms and enhance quality of life in young adults ( nursing students ) with allergic rhinitis in ` Yang - and/or Qi-deficiency ' body constitution .


Further controlled trials of its effects in Chinese and/or Asians with allergic rhinitis in terms of socio-demographic , ethnic and illness characteristics and a longer-term follow-up are recommended .


The trial has registered at ClinicalTrials.gov with an ID : NCT02027194 ( 3 January 2014 ) .


To determine the impact of educational materials ( EMs ) on the treatment compliance of postmenopausal women with hormone receptor-positive ( HR + ) early-stage breast cancer .


Patients ( n = 2757 ) were randomized to standard aromatase inhibitors ( AI ) alone ( group A ) or with EMs ( group B ) in a global , real-world setting .


The 2-year results ( n = 2242 ) showed EMs had no impact on compliance ( 82 vs. 82 % , group A vs. B ) , compliance with initial AI ( 82 vs. 81 % ) or persistence ( 90 vs. 88 % ) , confirming the 1-year interim analysis ( n = 2567 ) .


Of the 2082 patients considered compliant at 1 year , 77 % remained compliant at 2 years .


Discontinuations ( 9 % ) were mainly attributed to AI-related side effects ( 68 % of discontinuations ) .


Exploratory analyses suggest a relationship between patient characteristics and compliance behaviors .


EMs do not improve compliance in this patient population .


Compliance and persistence are complex end points influenced by multiple variables .


Side effects were the main reasons for discontinuations .


To determine whether the method of specimen preparation after transrectal ultrasound-guided biopsy of the prostate affected core fragmentation , and secondly to determine whether such fragmentation was influenced by the presence of malignancy in the biopsy specimen .


A prospective randomized study comparing 2 different mechanisms of specimen preparation , wash vs swipe of biopsy cores , with blinded assessment by a specific uropathologist was undertaken .


For those cores in which prostate cancer was present , the wash method of specimen preparation resulted in fewer and longer core fragments ( P = .005 ) .


Those patients in whom cancer was present on biopsy also had a greater degree of biopsy core fragmentation in those cores in which only benign tissue was identified ( P = .017 ) .


Gleason score did not appear to influence the extent of fragmentation .


The method of specimen preparation at prostate biopsy influences the degree of fragmentation seen at histologic evaluation .


This has the potential to affect the interpretation of biopsy results , including suitability of patients for inclusion in active surveillance protocols .


Core fragmentation might be minimized by modification of technique .


With aging , the detrimental effects of stress can impair a person 's ability to learn and sustain memory .


Humor and its associated mirthful laughter can reduce stress by decreasing the hormone cortisol .


Chronic release of cortisol can damage hippocampal neurons , leading to impairment of learning and memory .


Objectives The study intended to examine the effect of watching a humor video on short-term memory in older adults .


Design The research team designed a randomized , controlled trial .


The study took place at Loma Linda University in Loma Linda , CA , USA .


The study included 30 participants : 20 normal , healthy , older adults-11 males and 9 females-and 10 older adults with type 2 diabetes mellitus ( T2DM ) -6 males and 4 females .


The study included 2 intervention groups of older adults who viewed humorous videos , a healthy group ( humor group ) , aged 69.9 3.7 y , and the diabetic group , aged 67.1 3.8 y. Each participant selected 1 of 2 humorous videos that were 20 min in length , either a Red Skeleton comedy or a montage of America 's Funniest Home Videos .


The control group , aged 68.7 5.5 y , did not watch a humor video and sat in quiescence .


A standardized , neuropsychological , memory-assessment tool , the Rey Auditory Verbal Learning Test ( RAVLT ) , was used to assess the following abilities : ( 1 ) learning , ( 2 ) recall , and ( 3 ) visual recognition .


The testing occurred twice , once before ( RAVLT1 ) and once after ( RAVLT2 ) the humorous video for the humor and diabetic groups , and once before ( RAVLT1 ) and once after ( RAVLT2 ) the period of quiescence for the control group .


At 5 time points , measurements of salivary cortisol were also obtained .


The Kruskal-Wallis test was used to measure significance of the data based on the 3 groups .


In the humor , diabetic , and control groups , ( 1 ) learning ability improved by 38.5 % , 33.4 % , and 24.0 % , respectively ( P = .025 ) ; ( 2 ) delayed recall improved by 43.6 % , 48.1 % , and 20.3 % , respectively ( P = .064 ) ; and ( 3 ) visual recognition increased by 12.6 % , 16.7 % , and 8.3 % , respectively ( P = .321 ) .


For levels of salivary cortisol , the research team found significant and borderline decreases for the humor group between baseline and ( 1 ) post-RAVLT1 ( P = .047 ) , ( 2 ) postvideo ( P = .046 ) , and ( 3 ) post-RAVLT2 ( P = .062 ) .


The diabetic group showed significant decreases between baseline and ( 1 ) post-RAVLT1 ( P = .047 ) , ( 2 ) postvideo ( P = .025 ) , and ( 3 ) post-RAVLT2 ( P = .034 ) .


The study found no significant changes for the control group .


The research findings supported potential clinical and rehabilitative benefits for humor that can be applied to whole-person wellness programs for older adults .


The cognitive components-learning ability and delayed recall-become more challenging as individuals age and are essential to older adults for providing a high quality of life : mind , body , and spirit .


Because older adults can experience age-related memory deficits , complementary , enjoyable , and beneficial humor therapies should be implemented for them .


Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol .


In patients with type 2 diabetes and nephropathy , chronic kidney disease stage II-III , we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide ( NO ) availability using L-NMMA as an inhibitor of NO production .


We performed a randomized , placebo-controlled , crossover study , using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake .


We measured brachial BP ( bBP ) , central BP ( cBP ) , GFR , urinary output ( OU ) , free water clearance ( CH2O ) , fractional excretion of sodium ( FENa ) , urinary excretion of albumin ( UAER and UACR ) , AQP2 ( u-AQP2 ) and ENaC ( u-ENaC ) and plasma concentrations of vasoactive hormones : renin , angiotensin II , aldosterone , arginine vasopressin , endothelin-1 and brain natriuretic peptide .


During atorvastatin and placebo treatment , L-NMMA infusion , changed the effect variables significantly , but to the same extent , i.e. an increase in bBP and cBP , and a decrease in GFR , OU , CH2O , FENa , u-AQP2 and u-ENaC .


In addition , renin and angiotensin II was reduced , aldosterone increased , and vasopressin , endothelin-1 and brain natriuretic hormone unchanged .


During , atorvastatin and placebo treatment , inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure , GFR , renal tubular function and vasoactive hormones .


Thus , atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy .


Despite scientific advances in typing of C. difficile strains very little is known about how hospital staff use typing results during periods of increased incidence ( PIIs ) .


This qualitative study , undertaken alongside a randomised controlled trial ( RCT ) , explored this issue .


The trial compared ribotyping versus more rapid genotyping ( MLVA or multilocus variable repeat analysis ) and found no significant difference in post 48 hour cases ( C difficile transmissions ) .


In-depth qualitative interviews with senior staff in 11/16 hospital trusts in the trial ( 5 MLVA and 6 Ribotyping ) .


Semi-structured interviews were conducted at end of the trial period .


Transcripts were content analysed using framework analysis supported by NVivo-8 software .


Common sub-themes were extracted by two researchers independently .


These were compared and organised into over-arching categories or ` super-ordinate themes ' .


The trial recorded that 45 % of typing tests had some impact on infection control ( IC ) activities .


Interviews indicated that tests had little impact on initial IC decisions .


These were driven by hospital protocols and automatically triggered when a PII was identified .


To influence decision-making , a laboratory turnaround time < 3 days ( ideally 24 hours ) was suggested ; MLVA turnaround time was 5.3 days .


Typing results were predominantly used to modify initiated IC activities such as ward cleaning , audits of practice or staff training ; major decisions ( e.g. ward closure ) were unaffected .


Organisational factors could limit utilisation of MLVA results .


Results were twice as likely to be reported as ` aiding management ' ( indirect benefit ) than impacting on IC activities ( direct effect ) .


Some interviewees considered test results provided reassurance about earlier IC decisions ; others identified secondary benefits on organisational culture .


An underlying benefit of improved discrimination provided by MLVA typing was the ability to explore epidemiology associated with CDI cases in a hospital more thoroughly .


Ribotyping and MLVA are both valued by users .


MLVA had little additional direct impact on initial infection control decisions .


This would require reduced turnaround time .


The major impact is adjustments to earlier IC measures and retrospective reassurance .


For this , turnaround time is less important than discriminatory power .


The potential remains for wider use of genotyping to examine transmission routes .


To test whether red blood cell ( RBC ) levels of marine omega-3 fatty acids measured in the Women 's Health Initiative Memory Study were related to MRI brain volumes measured 8 years later .


RBC eicosapentaenoic acid ( EPA ) , docosahexaenoic acid ( DHA ) , and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women 's Health Initiative Memory Study .


The endpoints were total brain volume and anatomical regions .


Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy , time since randomization , demographics , intracranial volume , and cardiovascular disease risk factors .


In fully adjusted models , a 1 SD greater RBC EPA + DHA ( omega-3 index ) level was correlated with 2.1 cm ( 3 ) larger brain volume ( p = 0.048 ) .


DHA was marginally correlated ( p = 0.063 ) with total brain volume while EPA was less so ( p = 0.11 ) .


There were no correlations between ischemic lesion volumes and EPA , DHA , or EPA + DHA .


A 1 SD greater omega-3 index was correlated with greater hippocampal volume ( 50 mm ( 3 ) , p = 0.036 ) in fully adjusted models .


Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume ( 159 mm ( 3 ) , p = 0.034 ) .


A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later .


While normal aging results in overall brain atrophy , lower omega-3 index may signal increased risk of hippocampal atrophy .


Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy .


To evaluate the analgesic and physiological effects of epidural morphine administered at the sixth and seventh lumbar or the fifth and sixth thoracic vertebrae in dogs undergoing thoracotomy .


Prospective , randomized , blinded trial .


Fourteen mixed-breed dogs , weighing 8.6 1.4 kg .


The animals received acepromazine ( 0.1 mg kg ) IM and anesthesia was induced with propofol ( 4 mg kg ) IV .


The lumbosacral space was punctured and an epidural catheter was inserted up to the region between the sixth and seventh lumbar vertebrae ( L , n = 6 ) or up to the fifth or sixth intercostal space ( T , n = 8 ) .


The dogs were allowed to recover and after radiographic confirmation of correct catheter position , anesthesia was reinduced with propofol IV and maintained with 1.7 % isoflurane .


Following stabilization of monitored parameters , animals received morphine ( 0.1 mg kg ) diluted in 0.9 % NaCl to a final volume of 0.25 mL kg via the epidural catheter , and after 40 minutes , thoracotomy was initiated .


Heart rate and rhythm , systolic , mean and diastolic arterial pressures , respiratory rate , arterial hemoglobin oxygen saturation , partial pressure of expired CO and body temperature were measured immediately before the epidural administration of morphine ( 0 minute ) and every 10 minutes during the anesthetic period .


The Melbourne pain scale and the visual analog scale were used to assess postoperative pain .


The evaluation began 3 hours after the epidural administration of morphine and occurred each hour until rescue analgesia .


There were no important variations in the physiological parameters during the anesthetic period .


The post-operative analgesic period differed between the groups , being longer in T ( 9.9 01.6 hours ) compared with L ( 5.8 0.8 hours ) .


The use of morphine , at a volume of 0.25 mL kg 0.1 , administered epidurally over the thoracic vertebrae provided longer lasting analgesia than when deposited over the lumbar vertebrae .


There are no randomized studies that compare outcomes after single-incision ( SLC ) and conventional multi-incision ( MLC ) laparoscopic cholecystectomy under an optimized perioperative analgesic regimen .


This patient - and assessor-blinded randomized three-centre clinical trial compared SLC and MLC in women admitted electively with cholecystolithiasis .


Outcomes were registered on the day of operation ( day 0 ) , on postoperative days 1 , 2 , 3 and 30 , and 12months after surgery .


Blinding of the patients was maintained until day 3 .


The primary endpoint was pain on movement measured on a visual analogue scale , reported repeatedly by the patient until day 3 .


The intention-to-treat population comprised 59 patients in the SLC and 58 in the MLC group .


There was no significant difference between the groups with regard to any of the pain-related outcomes , on-demand administration of opioids or general discomfort .


Median duration of surgery was 325min longer in the SLC group ( P < 0001 ) .


SLC was associated with a reduced incidence of vomiting on day 0 ( 7 versus 22 per cent ; P = 0019 ) .


The incidences of wound-related problems were comparable .


One patient in the SLC group experienced a biliary leak requiring endoscopic retrograde cholangiopancreatography .


The rates of incisional hernia at 12-month follow-up were 2 per cent in both groups .


Cosmetic rating was significantly improved after SLC at 1 and 12months ( P < 0001 ) .


SLC did not significantly diminish early pain in a setting with optimized perioperative analgesic patient care .


SLC may reduce postoperative vomiting .


NCT01268748 ( http://www.clinicaltrials.gov ) .


The efficacy of artemisinin-based combination therapy ( ACT ) has been established .


The objective of the present study was to compare the efficacy and safety in the Central African Republic ( CAR ) of three commercially available artemisinin-based combinations , artemether + lumefantrine ( AL ) , artesunate + sulphamethoxypyrazine-pyrimethamine ( AS-SMP ) and artesunate + amodiaquine ( AS-AQ ) , with those of sulphadoxine-pyrimethamine + amodiaquine ( SP-AQ ) , which was the first-line reference treatment in the country from 2004 , until it was replaced by ACT in 2006 in accordance with changes in international recommendations based on resistance identified in other regions .


Children aged six to 59 months with uncomplicated Plasmodium falciparum malaria were recruited in Bangui , the capital of the CAR .


The 251 patients selected were randomly assigned to receive AL ( n = 60 ) , AS-SMP ( n = 58 ) , AS-AQ ( n = 68 ) or SP-AQ ( n = 65 ) and were followed up for 28 days .


Clinical outcome was classified according to the standard 2003 World Health Organization protocol .


At day 28 , the cure rates in a per-protocol analysis were 92 % ( 48/52 ) with AL , 93 % ( 50/54 ) with AS-SMP , 93 % ( 55/59 ) with AS-AQ and 100 % ( 57/57 ) with SP-AQ , with no statistically significant difference between the four treatments .


Defervescence was significantly faster with AS-AQ than with AL ( p < 0.035 ) .


Fatigue was reported significantly more frequently by patients receiving AQ than by those treated with AS-SMP or AL ( p = 0.006 ) .


All the other adverse events reported were mild , and no significant difference was noted by treatment .


The three artemisinin-bsed combinations show similar , satisfactory results , comparable to that with SP-AQ .


This evaluation is the first conducted in CAR since the official introduction of ACT .


It should guide the National Malaria Control Programme in choosing the appropriate ACT for treatment of uncomplicated P. falciparum malaria in the future .


The control of body lice in homeless persons remains a challenge .


To determine whether the use of long-lasting insecticide-treated underwear provides effective long-term protection against body lice in homeless persons .


A randomized , double-blind , placebo-controlled trial was conducted in February and December 2011 in 2 homeless shelters ( Madrague Ville and Forbin ) in Marseille , France .


Of the 125 homeless persons screened for eligibility , 73 body lice-infested homeless persons , 18 years or older , were enrolled .


Body lice-infested homeless persons were randomly assigned to receive 0.4 % permethrin-impregnated underwear or an identical-appearing placebo for 45 days , in a 1:1 ratio , with a permuted block size of 10 .


Visits were scheduled at days 14 and 45 .


Data regarding the presence or absence of live body lice were collected .


The primary and secondary end points were the proportions of homeless persons free of body lice on days 14 and 45 , respectively .


Mutations associated with permethrin resistance in the body lice were also identified .


Significantly more homeless persons receiving permethrin-impregnated underwear than homeless persons receiving the placebo were free of body lice on day 14 in the intent-to-treat population ( 28 % vs 9 % ; P = .04 ) , with a between-group difference of 18.4 percentage points ( 95 % CI , 1.4-35 .4 ) , and in the per-protocol population ( 34 % vs 11 % ; P = .03 ) , with a between-group difference of 23.7 percentage points ( 95 % CI , 3.6-43 .7 ) .


This difference was not sustained on day 45 .


At baseline , the prevalence of the permethrin-resistant haplotype was 51 % in the permethrin group and 44 % in the placebo group .


On day 45 , the permethrin-resistant haplotype was significantly more frequent in the permethrin group than in the placebo group ( 73 % vs 45 % , P < .001 ) .


Permethrin-impregnated underwear is more efficient than placebo at eliminating body louse infestations by day 14 ; however , this difference was not sustained on day 45 .


The use of permethrin may have increased the resistance to permethrin in body lice and thus must be avoided .


clinicaltrials.gov Identifier : NCT01287663 .


Animal studies have shown that methylphenidate ( MPH ) and fluoxetine ( FLX ) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain .


The effects of Psychotropic drugs On the Developing brain ( ePOD ) study is a combination of different approaches to determine whether there are related findings in humans .


Animal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques .


In addition , we set up two double-blind placebo controlled clinical trials with MPH in 50 boys ( 10-12 years ) and 50 young men ( 23-40 years ) suffering from ADHD ( ePOD-MPH ) and with FLX in 40 girls ( 12-14 years ) and 40 young women ( 23-40 years ) suffering from depression and anxiety disorders ( ePOD-SSRI ) .


Trial registration numbers are : Nederlands Trial Register NTR3103 and NTR2111 .


A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX ( ePOD-Pharmo ) is also ongoing .


The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition , behavior and emotion .


All assessments take place before , during ( only in case of MPH ) and after chronic treatment .


The combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development .


Cigarette demand , or the change in cigarette consumption as a function of price , is a measure of reinforcement that is associated with level of tobacco dependence and other clinically relevant measures , but the effects of experimentally controlled income on real-world cigarette consumption have not been examined .


In this study , income available for cigarette purchases was manipulated to assess the effect on cigarette demand .


Tobacco-dependent cigarette smokers ( n = 15 ) who smoked 10-40 cigarettes per day completed a series of cigarette purchasing tasks under a variety of income conditions meant to mimic different weekly cigarette budgets : $ 280 , approximately $ 127 , $ 70 , or approximately $ 32 per week .


Prices of $ 0.12 , $ 0.25 , $ 0.50 , and $ 1.00 per cigarette were assessed in each income condition .


Participants were instructed to purchase as many cigarettes as they would like for the next week and to only consume cigarettes purchased in the context of the study .


One price in 1 income condition was randomly chosen to be `` real , '' and the cigarettes and the excess money in the budget for that condition were given to the participant .


Results indicate that demand elasticity was negatively correlated with income .


Demand intensity ( consumption at low prices ) was unrelated to income condition and remained high across incomes .


These results indicate that the amount of income that is available for cigarette purchases has a large effect on cigarette consumption , but only at high prices .


Fibrates were found to reduce cytokine release and low-grade inflammation in patients with impaired glucose tolerance .


The aim of this study was to investigate whether these effects of fibrates may be potentiated by metformin treatment .


The study included 43 patients with isolated impaired glucose tolerance and normal plasma lipids who had been treated for at least 6 months with micronized fenofibrate ( 200 mg daily ) .


These subjects were randomly assigned to 12 weeks ' treatment with either high dose metformin ( 3 g daily in three divided doses ) or placebo .


Plasma lipids , glucose homeostasis markers , monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment .


Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor - and interleukin-6 , as well as tended to reduce monocyte release of interleukin-1 and monocyte chemoattractant protein-1 , which was accompanied by an improvement in insulin sensitivity .


Our results show that high-dose metformin produces monocyte-suppressing and systemic anti-inflammatory effects in fibrate-treated patients with isolated impaired glucose tolerance .


This suggests that fibrate-metformin combination therapy may bring clinical benefits to impaired glucose tolerance patients at high cardiovascular risk .


New models of health care delivery for dermatological care have the potential to increase access and improve patient-centered outcomes .


To compare effectiveness of a direct-access , online model for follow-up dermatologic care in pediatric and adult patients with atopic dermatitis with that of in-person office visits .


This was a 1-year , randomized controlled equivalency clinical trial in medically underserved areas , outpatient clinics , and the general community .


Participants included children and adults with atopic dermatitis with access to the Internet , computers , and digital cameras .


After an initial in-person visit , patients were randomized 1:1 to direct-access online or usual in-person care for follow-up management of atopic dermatitis .


In the direct-access online group , patients captured and transmitted clinical images and history asynchronously to dermatologists online ; dermatologists evaluated the clinical information , provided recommendations and education , and prescribed medications online asynchronously .


In the in-person group , patients visited dermatologists in their offices for follow-up care .


Atopic dermatitis disease severity as assessed by patient-oriented eczema measure ( POEM ) and investigator global assessment ( IGA ) .


A total of 156 children and adults were randomized .


Between baseline and 12 months , the mean ( SD ) within-group difference in POEM score in patients in the direct-access online group was -5.1 ( 5.48 ) ( 95 % CI , -6.32 to -3.88 ) ; in the in-person group , the within-group difference was -4.86 ( 4.87 ) ( 95 % CI , -6.27 to -3.46 ) .


The difference in the change in POEM scores between the 2 groups was 0.24 ( 6.59 ) ( 90 % CI , -1.70 to 1.23 ) , which was contained within the predetermined 2.5 equivalence margin .


The percentage of patients achieving clearance or near-clearance of their disease ( IGA score of 0 or 1 ) was 38.4 % ( 95 % CI , 27.7 % to 49.3 % ) in the direct-access online group and 43.6 % ( 95 % CI , 32.6 % -54.6 % ) in the in-person group .


The difference in the percent of patients achieving clearance or near-clearance between the 2 groups was 5.1 % ( 90 % CI , 1.7 % -8.6 % ) , which was contained within the predetermined 10 % equivalence margin .


The direct-access online model results in equivalent improvements in atopic dermatitis clinical outcomes as in-person care .


Direct-access online care may represent an innovative model of delivering dermatological services to patients with chronic skin diseases .


clinicaltrials.gov Identifier : NCT00985894 .


We report the results of the investigation of safety and efficacy of venous angioplasty in patients with multiple sclerosis ( MS ) with findings of extracranial venous anomalies , considered hallmarks of chronic cerebrospinal venous insufficiency ( CCSVI ) , in a 2-phase study ( ClinicalTrials.gov NCT01450072 ) .


Phase 1 was an open-label safety study ( 10 patients ) ; phase 2 was sham-controlled , randomized , and double-blind ( 10 sham procedure , 9 treated ) .


All study patients fulfilled venous hemodynamic screening criteria indicative of CCSVI .


Assessment was at 1 , 3 , and 6 months postprocedure with MRI , clinical , and hemodynamic outcomes .


Primary endpoints were safety at 24 hours and 1 month , venous outflow restoration > 75 % at 1 month , and effect of angioplasty on new lesion activity and relapse rate over 6 months .


Secondary endpoints included changes in disability , brain volume , cognitive tests , and quality of life .


No perioperative complications were noted ; however , one patient with history of syncope was diagnosed with episodic bradycardia requiring placement of a pacemaker before discharge .


Doppler evidence-based venous hemodynamic insufficiency severity score ( VHISS ) was reduced > 75 % compared to baseline in phase 1 ( at 1 month ) but not phase 2 .


In phase 2 , higher MRI activity ( cumulative number of new contrast-enhancing lesions [ 19 vs 3 , p = 0.062 ] and new T2 lesions [ 17 vs 3 , p = 0.066 ] ) and relapse activity ( 4 vs 1 , p = 0.389 ) were identified as nonsignificant trends in the treated vs sham arm over 6 months .


Using analysis of covariance , significant cumulative new T2 lesions were related to larger VHISS decrease ( p = 0.028 ) and angioplasty ( p = 0.01 ) over the follow-up .


No differences in other endpoints were detected .


Venous angioplasty is not an effective treatment for MS over the short term and may exacerbate underlying disease activity .


This is a Class I study demonstrating that clinical and imaging outcomes are no better or worse in patients with MS identified with venous outflow restriction who receive venous angioplasty compared to sham controls who do not receive angioplasty .


This study also includes a Class IV phase 1 study of safety in 10 patients receiving the angioplasty procedure .


Previous efforts such as Assessing Care of Vulnerable Elders ( ACOVE ) provide quality indicators for assessing the care of elderly patients , but thus far little has been done to leverage this knowledge to improve care for these patients .


We describe a clinical decision support system to improve general practitioner ( GP ) adherence to ACOVE quality indicators and a protocol for investigating impact on GPs ' adherence to the rules .


We propose two randomized controlled trials among a group of Dutch GP teams on adherence to ACOVE quality indicators .


In both trials a clinical decision support system provides un-intrusive feedback appearing as a color-coded , dynamically updated , list of items needing attention .


The first trial pertains to real-time automatically verifiable rules .


The second trial concerns non-automatically verifiable rules ( adherence can not be established by the clinical decision support system itself , but the GPs report whether they will adhere to the rules ) .


In both trials we will randomize teams of GPs caring for the same patients into two groups , A and B. For the automatically verifiable rules , group A GPs receive support only for a specific inter-related subset of rules , and group B GPs receive support only for the remainder of the rules .


For non-automatically verifiable rules , group A GPs receive feedback framed as actions with positive consequences , and group B GPs receive feedback framed as inaction with negative consequences .


GPs indicate whether they adhere to non-automatically verifiable rules .


In both trials , the main outcome measure is mean adherence , automatically derived or self-reported , to the rules .


We relied on active end-user involvement in selecting the rules to support , and on a model for providing feedback displayed as color-coded real-time messages concerning the patient visiting the GP at that time , without interrupting the GP 's workflow with pop-ups .


While these aspects are believed to increase clinical decision support system acceptance and its impact on adherence to the selected clinical rules , systems with these properties have not yet been evaluated .


Controlled Trials NTR3566 .


To evaluate whether preterm very low birth weight ( VLBW ) infants receiving early iron ( EI ) supplementation ( 2 mg/kg/day elemental iron ) at 2 weeks postnatal age have improved serum ferritin levels compared with late iron ( LI ) supplementation at 6 weeks postnatal age .


Single-blinded parallel-group interventional randomised controlled trial .


Tertiary care centre in southern India .


Randomised at 2 weeks postnatal age to EI and LI groups and evaluated at 2 , 6 and 12 weeks postnatal age .


The primary outcome was serum ferritin level at 12 weeks , and the secondary outcomes were the incidence of neonatal morbidities , haemoglobin level , anthropometric parameters and blood transfusion requirements .


Of the 104 babies randomised , outcomes were analysed in 46 and 47 babies in EI and LI groups , respectively .


Serum ferritin level was significantly higher ( p < 0.001 ) at 12 weeks ( 825 vs 633 ng/mL ) in the EI group .


Haemoglobin ( 10.10.4 vs 9.20.4 g/dL ) and mean corpuscular haemoglobin concentration ( 310.5 vs 29.40.5 g/dL ) were also significantly ( p < 0.001 ) higher at 12 weeks in the EI group .


There was a significant decrease of ferritin in the LI group and significant increase in ferritin in the EI group at 6 weeks compared with 2 weeks .


There were no significant differences in the incidences of neonatal morbidities ( necrotising enterocolitis , periventricular leukomalacia , retinopathy of prematurity ) , anthropometric parameters and blood transfusion requirements between the two groups .


EI supplementation in preterm VLBW infants improves serum ferritin and haemoglobin levels .


CTRI/2013/01 / 003277 .


To investigate whether providing sonographic ( US ) / MRI fusion images will enhance the ability of medical students and radiology residents to identify MSK anatomy on sonograms alone .


Medical students ( n = 31 ) and radiology residents ( n = 23 ) were each randomly divided into two groups : Group A and Group B. Subjects in Group A were shown 10 MSK sonograms with arrows pointing to a specific anatomic structure or anatomic region .


Subjects in Group B were shown the exact same 10 annotated sonograms as Group A as well as an additional fusion image consisting of an MRI of the same anatomy in the same plane fused with the sonogram without arrows .


Sonograms and MRI were obtained from adult patients who consented to have their images used .


The anatomic regions included the shoulder , hip , and pelvis .


Both groups were given the same 10-question multiple choice examination to identify the anatomic structure that the arrow was marking on the sonogram .


The transducer 's location was given for every question .


One minute was allowed to answer each question .


The Wilcoxon rank sum test was used to assess if there was a difference between Group A and Group B in both the medical student and the radiology resident cohorts .


Medical students : subjects in Group A ( n = 16 ) gave the correct answers in 33.8 % of the cases ( 54/160 ) .


Subjects in Group B ( n = 15 ) gave correct answers in 26.0 % of the cases ( 39/150 ) ( p value < 0.110 ) .


Radiology residents : subjects in Group A ( n = 11 ) gave correct answers in 40.9 % of the cases ( 45/110 ) .


Subjects in Group B ( n = 12 ) gave correct answers in 72.5 % of the cases ( 87/120 ) ( p value < 0.001 ) .


The addition of a fusion MRI/US image enhances radiology residents ' ability to identify MSK US anatomy accurately compared with the sonogram alone .


The medical students , however , did not show improvement with the addition of the fusion MRI/sonogram .


2014 .


Penetrating keratoplasty can commonly restore vision in corneal blindness .


However , immunological graft reactions may induce irreversible graft failure in a substantial percentage .


Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness .


Topical as well as systemic immunosuppressants are administered for prophylaxis .


However , severe adverse effects limit long-term usage .


By contrast , matching for transplantation antigens might be effective for a long time .


FANCY is a prospective , controlled , randomised , double-blind , multi-centre clinical trial with two parallel arms .


The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint ` time to first endothelial graft rejection ' .


Relevant inclusion criteria are age over 18years and waiting for penetrating or endothelial lamellar keratoplasty .


The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6months .


After randomisation , patients either receive a HLA-matched graft ( experimental intervention ) or a random graft ( control intervention ) .


The calculated sample size is 620 patients .


The trial started in 2009 with a recruitment period of 24months .


A total of 654 patients were included during this time .


The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine .


However , during the course of the trial , the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty ( DMEK ) .


Nowadays , immune reactions are confined mostly to the ` high-risk ' subgroups .


If we would design FANCY in 2014 , we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here .


The unique identifying number of the FANCY trial is NCT00810472 .


We tested the impact of banning tobacco displays and posting graphic health warning signs at the point of sale ( POS ) .


We designed 3 variations of the tobacco product display ( open , enclosed [ not visible ] , enclosed with pro-tobacco ads ) and 2 variations of the warning sign ( present vs absent ) with virtual store software .


In December 2011 and January 2012 , we randomized a national convenience sample of 1216 adult smokers and recent quitters to 1 of 6 store conditions and gave them a shopping task .


We tested for the main effects of the enclosed display , the sign , and their interaction on urge to smoke and tobacco purchase attempts .


The enclosed display significantly lowered current smokers ' ( B = -7.05 ; 95 % confidence interval [ CI ] = -13.20 , -0.91 ; P < .05 ) and recent quitters ' ( = -6.00 , 95 % CI = -11.00 , -1.00 ; P < .01 ) urge to smoke and current smokers ' purchase attempts ( adjusted odds ratio = 0.06 ; 95 % CI = 0.03 , 0.11 ; P < .01 ) .


The warning sign had no significant main effect on study outcomes or interaction with enclosed display .


These data show that POS tobacco displays influence purchase behavior .


Banning them may reduce cues to smoke and unplanned tobacco purchases .


Topical corticosteroids are the most common first-line treatment for psoriasis .


Tachyphylaxis , a decreased response to treatment with repetitive application of the drug , is a controversial phenomenon associated with topical corticosteroid treatment .


We sought to prove or disprove tachyphylaxis to occluded halobetasol 0.05 % versus vehicle .


Patients with plaque psoriasis were recruited to this study .


The study involved 3 phases ( 1 , 2A , and 2B ) with each phase being separated by a treatment vacation period .


In phases 1 and 2A , 2 plaques were randomized to either halobetasol 0.05 % or vehicle ointment application .


In phase 2B , halobetasol 0.05 % was applied to both .


Target Lesion Severity Scale was used for clinical assessment .


Twenty patients were enrolled .


No difference in time to clearance ( P = .88 ) or time to recurrence ( P = .92 ) of the treated plaques was found between phases 1 and 2A .


Percentage of improvement was higher in phase 2A compared with phase 1 ( 89.4 % , P < .05 vs 71 % , P < .05 ) , as a result of reduction of vehicle effect .


In phase 2B , a greater improvement was found for previously corticosteroid-treated plaques .


Limitations are small sample size and 1 corticosteroid tested .


No evidence of tachyphylaxis to the topical corticosteroid halobetasol 0.05 % ointment treatment in patients with plaque psoriasis was found .


A new , highly filled primer is currently marketed as a fluoride delivery system effective in reducing white spot lesions in orthodontic patients .


However , no studies in the literature support this claim .


The purpose of this in-vivo study was to investigate the retention and the efficacy of this primer in reducing the formation of white spot lesions .


In each patient for whom premolar extractions were planned ( n = 22 ) , 1 premolar was randomly chosen as the experimental tooth for the application of the fluoride delivery system ( Opal Seal ; Ultradent Products , South Jordan , Utah ) , and the contralateral tooth was assigned as the control to receive the standard treatment ( Transbond XT ; 3M Unitek , Monrovia , Calif ) .


After the bonding procedures , separators were placed around the premolar brackets to encourage plaque retention over 8 weeks .


After the extractions , the tooth surfaces were evaluated visually and with microhardness techniques for demineralization .


Primer retention was also investigated .


There were no statistically significant differences in the numbers of white spot lesions between the 2 groups .


The primer retention was calculated as 50 % .


The results indicated no significant difference between the efficacies of the fluoride-releasing primer and the control primer in reducing demineralization over the duration of the study .


We compared the outcomes of patients treated with everolimus-eluting stents ( EES ) versus paclitaxel-eluting stents ( PES ) at 3 years from the large-scale randomized SPIRIT IV trial .


SPIRIT IV is the largest randomized trial comparing the outcomes of EES and PES .


The present report represents the final long-term follow-up analysis from this study .


A total of 3,687 patients were randomized 2:1 to EES or PES , stratified by presence of diabetes mellitus and lesion characteristics .


Prespecified subgroups were compared for interaction with stent allocation .


The primary end point was target lesion failure ( TLF ) ( the composite of cardiac death , target vessel-related myocardial infarction [ MI ] , or ischemia-driven target lesion revascularization ) .


At 3 years , TLF occurred in 9.2 % versus 11.7 % of EES - and PES-treated patients ( hazard ratio [ HR ] 0.78 [ 0.63-0 .97 ] , P = .02 ) .


The incidence of death or MI was 5.9 % versus 9.1 % , respectively ( HR 0.67 [ 0.52-0 .85 ] , P = .001 ) , and there was a 64 % reduction in stent thrombosis ( Academic Research Consortium definite or probable definition ) with EES ( 0.59 % vs 1.60 % , HR 0.36 [ 0.18-0 .72 ] , P = .003 ) .


The difference in target lesion revascularization at 3 years did not reach statistical significance ( 6.2 % vs 7.8 % , respectively , HR 0.78 [ 0.60-1 .01 ] , P = .06 ) .


There was no significant interaction between treatment allocation and any of the subgroups , including diabetes .


When compared with PES , EES provides durable and significant reduction in TLF , especially due to its enhanced safety profile , with lower rates of death or MI and stent thrombosis up to 3 years .


The development of minimally invasive surgical techniques is driven by the quest for better patient outcomes .


There is some evidence for the use of minimally invasive surgery for degenerative lumbar spine stenosis ( LSS ) , but there are currently no studies comparing outcomes with matched controls .


The object of this study was to compare outcomes following minimally invasive unilateral laminectomy for bilateral decompression ( ULBD ) to a standard `` open '' laminectomy for LSS .


The authors conducted a prospective , 1:1 randomized trial comparing ULBD to open laminectomy for degenerative LSS .


The study enrolled 79 patients between 2007 and 2009 , and adequate data for analysis were available in 54 patients ( 27 in each arm of the study ) .


Patient demographic characteristics and clinical characteristics were recorded and clinical outcomes were obtained using pre - and postoperative Oswestry Disability Index ( ODI ) scores , visual analog scale ( VAS ) scores for leg pain , patient satisfaction index scores , and postoperative 12-Item Short Form Health Survey ( SF-12 ) scores .


Significant improvements were observed in ODI and VAS scores for both open and ULBD interventions ( p < 0.001 for both groups using either score ) .


In addition , the ULBD-treated patients had a significantly better mean improvement in the VAS scores ( p = 0.013 ) but not the ODI scores ( p = 0.055 ) compared with patients in the open-surgery group .


ULBD-treated patients had a significantly shorter length of postoperative hospital stay ( 55.1 vs. 100.8 hours , p = 0.0041 ) and time to mobilization ( 15.6 vs. 33.3 hours , p < 0.001 ) and were more likely to not use opioids for postoperative pain ( 51.9 % vs. 15.4 % , p = 0.046 ) .


Based on short-term follow-up , microscopic ULBD is as effective as open decompression in improving function ( ODI score ) , with the additional benefits of a significantly greater decrease in pain ( VAS score ) , postoperative recovery time , time to mobilization , and opioid use .


The benefit of adding sciatic nerve block ( SNB ) to femoral nerve block to improve analgesia after total knee arthroplasty ( TKA ) is uncertain .


We hypothesized that the effective duration of single-injection SNB is too short to improve postoperative analgesia and that this contributes to conflicting results on the efficacy of SNB after TKA .


We evaluated this hypothesis in a prospective double-blind randomized controlled trial .


Sixty patients undergoing TKA were randomly allocated to a continuous SNB group or a single-injection SNB group .


All patients received femoral nerve block ( 0.5 % ropivacaine 20 mL ) and SNB ( 0.2 % ropivacaine 20 mL ) and catheters were inserted into both peripheral nerve block sites before surgery .


Both groups received continuous femoral nerve block and patient-controlled intravenous analgesia with morphine .


Continuous SNB ( 0.2 % ropivacaine 5 mL/h ; continuous SNB group ) or sham continuous SNB ( 0.9 % normal saline 5 mL/h ; single-injection SNB group ) was provided after surgery .


The primary outcome was total morphine consumption for 48 hours after surgery .


Total morphine consumption in the 48-hour period after surgery was significantly lower in the continuous SNB group compared with the single-injection SNB group [ 4.9 ( 5.9 ) vs 9.7 ( 9.5 ) mg , P = 0.002 ] .


Visual analog scale pain scores at rest were also significantly lower in the continuous SNB group ( P = 0.035 ) .


The combination of continuous femoral and SNB provides a superior opioid sparing effect and improves analgesia after TKA .


Direct evidence for the effects of vegetable intake on weight loss is qualified .


The study aimed to assess the effect of higher vegetable consumption on weight loss .


A single blind parallel controlled trial was conducted with 120 overweight adults ( mean body mass index = 29.98 kg/m ( 2 ) ) randomised to two energy deficit healthy diet advice groups differing only by doubling the serving ( portion ) sizes of vegetables in the comparator group .


Data were analysed as intention-to-treat using a linear mixed model .


Spearmans rho bivariate was used to explore relationships between percentage energy from vegetables and weight loss .


After 12 months , the study sample lost 6.55.2 kg ( P < 0.001 time ) with no difference between groups ( P > 0.05 interaction ) .


Both groups increased vegetable intake and lost weight in the first 3 months , and the change in weight was significantly correlated with higher proportions of energy consumed as vegetables ( rho = -0.217 , P = 0.024 ) .


Fasting glucose , insulin and triglyceride levels decreased ( P < 0.001 time ) and high-density lipoprotein cholesterol levels increased ( P < 0.001 time ) , with no difference between groups .


Weight loss was sustained for 12 months by both groups , but the comparator group reported greater hunger satisfaction ( P = 0.005 ) .


Advice to consume a healthy low-energy diet leads to sustained weight loss , with reductions in cardiovascular disease risk factors regardless of an emphasis on more vegetables .


In the short term , consuming a higher proportion of the dietary energy as vegetables may support a greater weight loss and the dietary pattern appears sustainable .


To study the effectiveness of yoga intervention on oxidative stress , glycemic status , blood pressure and anthropometry in prediabetes .


Randomized-controlled trial .


Twenty nine prediabetes subjects aged 30-75 years .


Yoga was conducted at 4 different community diabetes clinics in Mangalore , India .


Participants were randomized to either 3-month yoga or wait-list control groups .


Malondialdehyde , glutathione , vitamin C , vitamin E , superoxide dismutase , plasma glucose , glycated haemoglobin , BMI , waist circumference , waist-to-hip ratio and blood pressure .


Yoga intervention resulted in a significant decline in malondialdehyde ( p < 0.001 ) , relative to the control group .


In comparison with the control , there was a significant improvement in BMI , waist circumference , systolic blood pressure and fasting glucose levels at follow-up .


No significant improvement in glycated haemoglobin , waist-to-hip ratio or any of the antioxidants was observed .


Yoga intervention may be helpful in control of oxidative stress in prediabetes subjects .


Yoga can also be beneficial in reduction in BMI , waist circumference , systolic blood pressure and fasting glucose .


Effect of yoga on antioxidant parameters was not evident in this study .


The findings of this study need to be confirmed in larger trials involving active control groups .


Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition , making it an attractive candidate for depressed patients at imminent risk of suicide .


In the first randomized controlled trial of ketamine using an anesthetic control condition , we tested ketamine 's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition ( Implicit Association Test ; IAT ) previously linked to suicidal behavior .


Symptomatic patients with treatment-resistant unipolar major depression ( inadequate response to 3 antidepressants ) were assessed using a composite index of explicit suicidal ideation ( Beck Scale for Suicidal Ideation , Montgomery-Asberg Rating Scale suicide item , Quick Inventory of Depressive Symptoms suicide item ) and the IAT to assess suicidality implicitly .


Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine ( n = 36 ) or midazolam ( n = 21 ) , a psychoactive placebo agent selected for its similar , rapid anesthetic effects .


Twenty four hours postinfusion , explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group .


Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr , compared with 24 % of the midazolam group ( ( 2 ) = 4.6 ; P = .03 ) .


Implicit associations between self - and escape-related words were reduced following ketamine ( P = .01 ; d = .58 ) but not midazolam ( P = .68 ; d = .09 ) .


Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline , and were mediated by decreases in nonsuicide-related depressive symptoms .


Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo .


Further study is warranted to test ketamine 's antisuicidal effects in higher-risk samples .


To evaluate the efficacy and safety of twice-daily dosing of dapagliflozin and metformin , exploring the feasibility of a fixed-dose combination .


In this 16-week , phase III , randomized , double-blind placebo-controlled study , adults who were receiving metformin administered twice daily ( 1500mg/day ) and had inadequate glycaemic control were randomized 1:1:1:1 to receive dapagliflozin twice daily ( 2.5 or 5mg ) , placebo or dapagliflozin 10mg once daily ( which was included as a benchmark ) .


The primary endpoint was change from baseline glycated haemoglobin ( HbA1c ) level .


Secondary endpoints included changes in fasting plasma glucose ( FPG ) level and body weight .


Four hundred adults were randomized to dapagliflozin ( 2.5 mg twice daily , 5mg twice daily , 10mg once daily ) or placebo co-administered with metformin twice daily .


At 16 weeks , the adjusted mean change in HbA1c from baseline was significantly reduced in the dapagliflozin 2.5 mg twice daily and 5mg twice daily groups versus placebo ( -0.52 vs. -0.30 % , p = 0.0106 and -0.65 % vs. -0.30 % , p < 0.0001 ) .


There were also significantly greater improvements for dapagliflozin twice daily groups versus placebo in FPG body weight and achievement of HbA1c level of < 7 % .


Efficacy outcomes for dapagliflozin twice daily were numerically similar to those for dapagliflozin once daily .


Dapagliflozin twice daily was well tolerated .


Dapagliflozin 2.5 or 5mg twice daily added to metformin was effective in reducing glycaemic levels in patients with type 2 diabetes inadequately controlled with metformin alone .


This study supports the development of a fixed-dose combination regimen .


The commonly used therapeutic approach , the contemporary Bobath approach ( CBA ) , is not sufficient to restore independent locomotion for individuals with severe motor deficit ( SMD ) after stroke .


Therefore , we propose that the early sitting , standing , and walking in conjunction with the CBA ( ECBA ) be used to treat individuals with SMD after stroke .


To investigate whether ECBA may enhance mobility and balance in subjects with SMD after stroke .


Thirty-three men and 15 women , aged 60 to 74 years , with SMD after stroke were recruited for the study .


CBA or ECBA was performed with the subjects 5 times per week in 50-minute sessions for 8 weeks .


The Stroke Rehabilitation Assessment of Movement ( STREAM ) and the Berg Balance Scale were implemented before treatment and at 4 and 8 weeks after treatment , respectively .


The STREAM scores indicated that ECBA was more efficient than the CBA intervention for lower extremity mobility , F ( 1 , 46 ) = 24.0 , P < .001 , and basic mobility , F ( 1 , 46 ) = 102.6 , P < .001 .


Overall STREAM scores were higher in the ECBA group , F ( 1 , 46 ) = 24.1 , P < .001 , after 8 weeks of therapy .


Balance scores of the ECBA subjects were higher than those of the CBA subjects after 8 weeks of therapy , F ( 1 , 46 ) = 73.1 , P < .001 .


However , there was no difference in upper extremity mobility between the 2 groups .


ECBA is a valuable intervention to improve lower extremity mobility , basic mobility , and balance ability for individuals with SMD after stroke .


Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome , but aromatase inhibitors , including letrozole , might result in better pregnancy outcomes .


In this double-blind , multicenter trial , we randomly assigned 750 women , in a 1:1 ratio , to receive letrozole or clomiphene for up to five treatment cycles , with visits to determine ovulation and pregnancy , followed by tracking of pregnancies .


The polycystic ovary syndrome was defined according to modified Rotterdam criteria ( anovulation with either hyperandrogenism or polycystic ovaries ) .


Participants were 18 to 40 years of age , had at least one patent fallopian tube and a normal uterine cavity , and had a male partner with a sperm concentration of at least 14 million per milliliter ; the women and their partners agreed to have regular intercourse with the intent of conception during the study .


The primary outcome was live birth during the treatment period .


Women who received letrozole had more cumulative live births than those who received clomiphene ( 103 of 374 [ 27.5 % ] vs. 72 of 376 [ 19.1 % ] , P = 0.007 ; rate ratio for live birth , 1.44 ; 95 % confidence interval , 1.10 to 1.87 ) without significant differences in overall congenital anomalies , though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group ( P = 0.65 ) .


The cumulative ovulation rate was higher with letrozole than with clomiphene ( 834 of 1352 treatment cycles [ 61.7 % ] vs. 688 of 1425 treatment cycles [ 48.3 % ] , P < 0.001 ) .


There were no significant between-group differences in pregnancy loss ( 49 of 154 pregnancies in the letrozole group [ 31.8 % ] and 30 of 103 pregnancies in the clomiphene group [ 29.1 % ] ) or twin pregnancy ( 3.4 % and 7.4 % , respectively ) .


Clomiphene was associated with a higher incidence of hot flushes , and letrozole was associated with higher incidences of fatigue and dizziness .


Rates of other adverse events were similar in the two treatment groups .


As compared with clomiphene , letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome .


( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others ; ClinicalTrials.gov number , NCT00719186 . )


Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival ( OS ) in the East Asian subgroup were consistent with those observed in the entire JMDB study population .


This bridging study ( JMIL ) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin ( PC ) versus gemcitabine/cisplatin ( GC ) in Chinese patients with nonsquamous non-small cell lung cancer ( NSCLC ) .


The primary endpoint of this local registration trial was designed to compare OS in the combined dataset , consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB .


Chinese patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned ( 1:1 ) to 6 cycles maximum ( 21 days/cycle ) of pemetrexed 500mg/m ( 2 ) + cisplatin 75mg/m ( 2 ) ( day 1 ) , or gemcitabine 1250mg/m ( 2 ) ( days 1 and 8 ) + cisplatin 75mg/m ( 2 ) ( day 1 ) .


In JMIL , 256 Chinese patients were randomized ( PC , n = 126 ; GC , n = 130 ) .


Patient baseline characteristics were balanced between treatment arms .


In the combined dataset , PC was superior to GC in prolonging OS , with adjusted hazard ratio ( HR ) of 0.87 ( 95 % CI : 0.77-0 .98 , p = 0.023 ) and median OS of 11.76 versus 10.94 months .


In the JMIL-only population , no significant OS difference observed between treatment arms ( adjusted HR = 1.03 [ 95 % CI : 0.77-1 .39 , p = 0.822 ] ; unadjusted HR = 0.996 [ 95 % CI : 0.74-1 .33 , p = 0.980 ] ) , nor for other secondary efficacy endpoints .


Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities , 54 ( 43.2 % ) versus 71 ( 55.9 % ) for GC ( p = 0.045 ) , with significantly lower rates of leukocytopenia , thrombocytopenia , and fatigue .


This study showed that in the combined population , OS of PC was superior to GC , while in the Chinese-only population , no significant difference was observed ; a better safety and risk/benefit profile was found in the PC arm .


A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLC patients in a first-line setting .


Physical inactivity is a major , potentially modifiable , risk factor for cardiovascular disease , cancer , and other chronic diseases .


Effective , simple , and generalisable interventions that will increase physical activity in populations are needed .


To evaluate the effectiveness of a smartphone application ( app ) to increase physical activity in primary care .


An 8-week , open-label , randomised controlled trial in rural , primary care in the west of Ireland .


Android smartphone users > 16 years of age were recruited .


All participants were provided with similar physical activity goals and information on the benefits of exercise .


The intervention group was provided with a smartphone app and detailed instructions on how to use it to achieve these goals .


The primary outcome was change in physical activity , as measured by a daily step count between baseline and follow-up .


A total of 139 patients were referred by their primary care health professional or self-referred .


In total , 37 ( 27 % ) were screened out and 12 ( 9 % ) declined to participate , leaving 90 ( 65 % ) patients who were randomised .


Of these , 78 provided baseline data ( intervention = 37 ; control = 41 ) and 77 provided outcome data ( intervention = 37 ; control = 40 ) .


The mean daily step count at baseline for intervention and control groups was 4365 and 5138 steps per day respectively .


After adjusting , there was evidence of a significant treatment effect ( P = 0.009 ) ; the difference in mean improvement in daily step count from week 1 to week 8 inclusive was 1029 ( 95 % confidence interval 214 to 1843 ) steps per day , favouring the intervention .


Improvements in physical activity in the intervention group were sustained until the end of the trial .


A simple smartphone app significantly increased physical activity over 8 weeks in a primary care population .


To observe the therapeutic effect of cervical paravertebral block plus acupuncture treatment for cervicogenic headache .


Sixty cases of cervicogenic headache were randomly and equally divided into cervical paravertebral block ( control ) group and acupuncture plus cervical paravertebral block ( acupuncture ) group .


Paravertebral block was performed by injection of 5 mL of 0.3 % lidocaine solution containing triamcinolone ( 10 mg ) into the 2nd cervical paravertebral tissue from the cross point between the posterior border of the sternomastoid muscle and the angle of jaw , once every week for three weeks .


Manual acupuncture stimulation was applied to Baihui ( GV 20 ) , unilateral Fengchi ( GB 20 ) and Jiaosun ( SJ 20 ) , once daily for 3 weeks .


The patients ' headache severity was assessed by visual analogue scale ( VAS ) and their cervical vertebral activity assessed by range of motion ( ROM ) before and after the treatment .


Compared with pre-treatment in the same one group , the scores of both VAS and ROM at time points of one , two and three weeks after the treatment were significantly decreased in the control and acupuncture groups ( P < 0.05 ) , suggesting a marked improvement of both headache and cervical motion after the treatment .


Comparison between the two groups showed that the VAS and ROM scores of the acupuncture group were evidently lower than those of the control group at each time point after the treatment ( P < 0.05 ) , displaying a better therapeutic effect of acupuncture plus paravertebral block for cervicogenic headache .


Acupuncture combined with cervical paravertebral block is effective in relieving cervicogenic headache and improving cervical vertebral activity in cervicogenic headache patients , and can strengthen the therapeutic effect of simple paravertebral block .


Anatomy education on embalmed specimens is presumed to have added educational value .


However , although embalmed specimens have been used for anatomy education for years , there is little evidence on the added educational value of dissection-based teaching .


The objective of this randomized study is to examine the added value of dissection-based teaching , using models of the inguinal region in embalmed specimens .


In 2011 , medical students at Erasmus Medical Center , The Netherlands , were randomly assigned to three groups .


Group I attended lectures , group II attended dissection-based training using laparoscopic dissection models , and group III attended lectures as well as dissection-based laparoscopic training .


To assess the improvement of anatomical knowledge , all students had to complete a practical test before , immediately after , and two weeks after training .


Data were analyzed with mixed modeling .


Forty-six students participated in this study .


No significant difference in results was observed among the three groups before the start of training .


Immediately after the course , groups II and III scored significantly higher than group I ( P < .001 ; P < .001 ) , and group II scored higher than group III ( P = .009 ) .


The difference between group I and groups II and III persisted during follow-up ( P = 012 ; P = .001 ) .


The difference between groups II and III disappeared .


Three-dimensional anatomy education with dissection models enhances anatomy learning by medical students .


Students who received dissection-based training scored higher in the short - and long term compared with students who did not receive this type of education .


Active immunotherapy is a promising antitumoral strategy ; however its use in combination with chemotherapy in dogs with large B-cell lymphoma ( DLBCL ) remains largely untested .


Heat shock proteins ( HSP ) bind the small peptides they chaperone ( HSPPC ) , allowing for immunization of the host against a large repertoire of tumor-associated antigens .


Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant .


The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL .


Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone .


Endpoints included time to progression ( TTP ) , lymphoma-specific survival ( LSS ) , and incidence of toxicoses .


Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm ( P = 0.0004 ) .


There was also a statistically significant difference in duration of second remission between the two groups ( P = 0.02 ) .


Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs ( P = 0.0018 ) .


Six vaccinated dogs achieved molecular remission , as shown by clonal immunoglobulin H ( IgH ) rearrangement .


Toxicoses were comparable between the two treatment arms .


The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy .


On the basis of these results , additional evaluation of this novel therapeutic strategy is warranted in human DLBCL .


Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis .


This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk .


Adolescents and young adults ( mean age 17.4 4.1 years ) with attenuated positive psychotic symptoms , brief and intermittent psychosis , or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk ( FFT-CHR ) in 6 months or 3 sessions of family psychoeducation ( enhanced care [ EC ] ) .


FFT-CHR included psychoeducation about early signs of psychosis , stress management , communication training , and problem-solving skills training , whereas EC focused on symptom prevention .


Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms andsocial-role functioning .


Of 129 participants , 102 ( 79.1 % ) were followed up at 6months .


Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC ( F1 ,97 = 5.49 , p = .02 ) .


Negative symptoms improved independently of psychosocial treatments .


Changes in psychosocial functioning depended on age : participants more than 19 years of age showed more role improvement inFFT-CHR , whereas participants between 16 and 19 years of age showed more role improvement in EC .


The results were independent of concurrent pharmacotherapy .


Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis .


Future studies should examine the specificity of effects of family intervention compared to individual therapy of the sameduration and frequency .


Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis ; http://clinicaltrials.gov/; NCT01907282 .


Cancer anorexia-cachexia syndrome ( CACS ) is common in advanced cancer patients and associated with weight loss , fatigue , impaired quality of life ( QoL ) , and poor prognosis .


The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 ( NCT01387282 ) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer ( NSCLC ) cachexia : the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) and the Functional Assessment of Anorexia/Cachexia Therapy ( FAACT ) .


In the ROMANA 2 trial , 477 patients with unresectable stage III or IV NSCLC and cachexia were to be enrolled and randomized ( 2:1 ) to receive anamorelin HCl or placebo once daily for 12weeks .


All 203 patients who reached the week 12 visit at the time of data analysis were included .


Co-primary endpoints were change from baseline in lean body mass and handgrip strength .


QoL was a secondary outcome with FACIT-F and FAACT questionnaires administered at baseline and at weeks 3 , 6 , 9 , and 12 .


Two 4-item scales ( fatigue/activity and appetite/eating ) from the FACIT-F and FAACT questionnaires , respectively , demonstrated good internal consistency reliability , validity , and responsiveness ( also referred to as the Simplified Evaluation of Fatigue ( SEF ) and Simplified Evaluation of Appetite ( SEA ) , respectively ) .


The estimated important difference for each scale was 1-2 points .


These brief scales provide the psychometric properties necessary to promote future research in NSCLC patients with CACS .


Additional work should examine the clinical utility of these scales and their impact on treatment decision-making .