At the ideal screw trajectory , pars fixation by intralaminar screw is uniformly feasible at L3 to L5 laminae , where most patients can accommodate a 4.5-mm screw .


2 .


Female sexual dysfunction is a side effect of selective serotonin reuptake inhibitor ( SSRI ) / serotonin noradrenalin reuptake inhibitor ( SNRI ) therapy .


The aim of this study is to investigate the efficacy of transdermal testosterone ( TT ) as a treatment for SSRI/SNRI-emergent loss of libido .


This was a double-blind , randomized , placebo-controlled study .


Forty-four women , aged 35-55 years , on a stable dose of SSRI or SNRI with treatment-emergent loss of libido were randomly allocated to treatment with a TT patch delivering 300 mcg of testosterone/day or an identical placebo patch ( Pl ) for 12 weeks .


The primary outcome measure was the change in the Sabbatsberg Sexual Self-rating Scale ( SSS ) total score over 12 weeks .


The 4-week frequency of Satisfactory Sexual Events ( SSEs ) and the Female Sexual Distress Scale-Revised ( FSDS-R ) were also measured .


At baseline , there were no differences between the treatment groups .


At week 12 , the change in the SSS score did not differ between the two groups .


The increase in the 4-week frequency of SSEs was significantly greater for the TT group than for the Pl group ( an increase of 2.3 events vs. 0.1 , P = 0.02 ) .


The between-group difference in the change in the FSDS-R score approached statistical significance ( P = 0.06 ) .


The mean total serum testosterone level at 12 weeks in the TT group was 2.1 nmol/L .


No women withdrew because of androgenic adverse events .


TT therapy resulted in a significant increase in the number of SSEs compared with Pl therapy in women with SSRI/SNRI-emergent loss of libido .


The lack of improvement in the SSS total score may reflect lack of sensitivity of this instrument for the measurement of change in sexual function .


This provides the first evidence that TT therapy may be a treatment option for women with SSRI/SNRI-emergent loss of libido who need to remain on their antidepressant therapy .


The best treatment strategy for a patient with type 2 diabetes who shows pronounced weight gain after the introduction of insulin treatment is unclear .


We determined whether addition of a glucagon-like peptide-1 ( GLP-1 ) analogue could reverse pronounced insulin-associated weight gain while maintaining glycaemic control , and compared this with the most practised strategy , continuation and intensification of standard insulin therapy .


In a 26-week , randomised controlled trial ( ELEGANT ) , conducted in the outpatient departments of one academic and one large non-academic teaching hospital in the Netherlands , adult patients with type 2 diabetes with 4 % weight gain during short-term ( 16 months ) insulin therapy received either open-label addition of liraglutide 1.8 mg/day ( n = 26 ) or continued standard therapy ( n = 24 ) .


A computer-generated random number list was used to allocate treatments .


Participants were evaluated every 4-6 weeks for weight , glycaemic control and adverse events .


The primary endpoint was between-group weight difference after 26 weeks of treatment ( intention to treat ) .


Of 50 randomised patients ( mean age 58 years , BMI 33 kg/m ( 2 ) , HbA1c 7.4 % [ 57 mmol/mol ] ) , 47 ( 94 % ) completed the study ; all patients were analysed .


Body weight decreased by 4.5 kg with liraglutide and increased by 0.9 kg with standard therapy ( mean difference -5.2 kg [ 95 % CI -6.7 , -3.6 kg ] ; p < 0.001 ) .


The respective changes in HbA1c were -0.77 % ( -8.4 mmol/mol ) and +0.01 % ( +0.1 mmol/mol ) ( difference -0.74 % [ -8.1 mmol/mol ] ) ( [ 95 % CI -1.08 % , -0.41 % ] [ -11.8 , -4.5 mmol/mol ] ; p < 0.001 ) ; respective changes in insulin dose were -29 U/day and +5 U/day ( difference -33 U/day [ 95 % CI -41 , -25 U/day ] ; p < 0.001 ) .


In five patients ( 19 % ) , insulin could be completely discontinued .


Liraglutide was well tolerated ; no severe adverse events or severe hypoglycaemia occurred .


In patients with pronounced insulin-associated weight gain , addition of liraglutide to their treatment regimen reverses weight , decreases insulin dose and improves glycaemic control , and hence seems a valuable therapeutic option compared with continuation of standard insulin treatment .


Trial registration ClinicalTrials.gov NCT01392898 .


Funding The study was funded by Novo Nordisk .


To compare the effectiveness of body weight-supported treadmill training and body weight-supported overground training for improving gait and strength in people with traumatic incomplete tetraplegia .


Assessor blinded randomized trial .


Rehabilitation institute of a tertiary care teaching hospital in India .


Sixteen participants with traumatic motor incomplete tetraplegia and within two years of injury .


Participants were randomised to one of two groups : body weight-supported overground training on level ground and body weight-supported treadmill training .


Both groups received 30 minutes of gait training per day , five days a week for eight weeks .


In addition , both groups received regular rehabilitation which included flexibility , strength , balance , self care and functional training .


The primary outcome measure was the Walking Index for Spinal Cord Injury ( / 20 points ) and the secondary outcome was the Lower Extremity Muscle Score ( / 50 points ) .


There was no statistically significant between group differences in the Walking Index for Spinal Cord Injury [ mean difference = 0.3 points ; 95 % CI ( -4.8 to 5.4 ) ; p = 0.748 ] or the Lower Extremity Muscle Score [ mean difference = 0.2 points ; 95 % CI ( -3.8 to 5.1 ) ; p = 0.749 ] .


Gait training with body weight-supported overground training is comparable to treadmill training for improving locomotion in people with traumatic incomplete tetraplegia .


Although exercise training is known to promote post-exercise hypotension , there is currently no consistent argument about the effects of manipulating its various components ( intensity , duration , rest periods , types of exercise , training methods ) on the magnitude and duration of hypotensive response .


To compare the effect of continuous and interval exercises on hypotensive response magnitude and duration in hypertensive patients by using ambulatory blood pressure monitoring ( ABPM ) .


The sample consisted of 20 elderly hypertensives .


Each participant underwent three ABPM sessions : one control ABPM , without exercise ; one ABPM after continuous exercise ; and one ABPM after interval exercise .


Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , heart rate ( HR ) and double product ( DP ) were monitored to check post-exercise hypotension and for comparison between each ABPM .


ABPM after continuous exercise and after interval exercise showed post-exercise hypotension and a significant reduction ( p < 0.05 ) in SBP , DBP , MAP and DP for 20 hours as compared with control ABPM .


Comparing ABPM after continuous and ABPM after interval exercise , a significant reduction ( p < 0.05 ) in SBP , DBP , MAP and DP was observed in the latter .


Continuous and interval exercise trainings promote post-exercise hypotension with reduction in SBP , DBP , MAP and DP in the 20 hours following exercise .


Interval exercise training causes greater post-exercise hypotension and lower cardiovascular overload as compared with continuous exercise .


Both epidemiological and randomized clinical studies suggest that supplementation with very-long-chain marine polyunsaturated n-3 fatty acids ( n-3 PUFA ) have cardioprotective effects , however these results are not without controversy .


Study population , sample-size , type of supplementation and type of endpoint have all varied widely accross different studies.Therefore , the aims of the present study are to evaluate the effect of 2 years supplementation with capsules of very-long chain marine n-3 PUFA on top of standard therapy in elderly patients after acute myocardial infarction ( AMI ) .


In addition , special characteristics of this population with regard to prediction of clinical outcome will be investigated .


The hypothesis is that this supplementation on top of modern therapy will reduce the occurence of major cardiovascular events ( MACE ) .


We present the design of the OMEMI ( OMega-3 fatty acids in Elderly patients with Myocardial Infarction ) study .


The OMEMI study is designed as a randomized , placebo-controlled double-blind multicenter trial.Included are patients 70-82 years of age who have sustained AMI .


Patients of either gender are eligible .


Sample size calculation based on existing literature has resulted in the need for 1400 patients followed for 2 years , based on the assumption that the n-3 PUFA supplementation will reduce MACE with 30 % .


The study medication is Pikasol Axellus AS , Norway , 3 capsules ( 1.8 g eicosapentaenoic acid ( EPA ) + docohexaenoic acid ( DHA ) ) per day , and matching placebo is corn oil .


The Primary end-point is the composite of total mortality , first non-fatal recurring AMI , stroke and revascularization .


Secondary end-point is the occurrence of new onset atrial fibrillation .


Extensive biobanking will be performed , including adipose tissue biopsies .


Compliance will be assessed by measurements of the fatty acid profile in serum , sampled at inclusion , after 12 months and at the end of study .


The OMEMI study is scheduled to terminate when the last included patient has been followed for 2 years .


To the best of our knowledge , the OMEMI study is the first to evaluate the effect of n-3 PUFAs on CVDs and mortality in a high risk elderly population having suffered an acute myocardial infarction .


ClinicalTrials.gov , NCT01841944 .


A review of all the adjuncts for intravenous regional anaesthesia concluded that there is good evidence to recommend NonSteroidal Anti-Inflammatory agents and pethidine in the dose of 30mg dose as adjuncts to intravenous regional anaesthesia .


But there are no studies to compare pethidine of 30mg dose to any of the NonSteroidal Anti-Inflammatory agents .


In a prospective , randomized , double blind study , 45 patients were given intravenous regional anaesthesia with either lignocaine alone or lignocaine with pethidine 30mg or lignocaine with ketprofen 100mg .


Fentanyl was used as rescue analgesic during surgery .


For the first 6h of postoperative period analgesia was provided by fentanyl injection and between 6 and 24h analgesia was provided by diclofenac tablets .


Visual analogue scores for pain and consumption of fentanyl and diclofenac were compared .


The block was inadequate for one case each in lignocaine group and pethidine group , so general anaesthesia was provided .


Time for the first dose of fentanyl required for postoperative analgesia was significantly more in pethidine and ketoprofen groups compared to lignocaine group ( 156.7148.8 and 153.0106.0 vs. 52.152.4 min respectively ) .


Total fentanyl consumption in first 6h of postoperative period was less in pethidine and ketoprofen groups compared to lignocaine group ( 37.529.0 mcg , 38.320.8 mcg vs. 64.227.2 mcg respectively ) .


Consumption of diclofenac tablets was 2.40.7 , 2.50.5 and 2.00.7 in the control , pethidine and ketoprofen group respectively , which was statistically not significant .


Side effects were not significantly different between the groups .


Both pethidine and ketoprofen are equally effective in providing postoperative analgesia up to 6h , without significant difference in the side effects and none of the adjuncts provide significant analgesia after 6h .


Contingency management ( CM ) is an efficacious intervention for reducing cigarette smoking .


However , CM is rarely adopted as a smoking cessation treatment in the community .


This study analyzed the effectiveness of a CM procedure in combination with a cognitive-behavioral treatment ( CBT ) for smoking cessation among treatment-seeking patients from the general population .


A total of 92 patients were randomly assigned to one of two treatment conditions : CBT ( N = 49 ) or CBT+CM ( N = 43 ) .


The CM procedure included a voucher program through which nicotine abstinence was reinforced on a schedule of escalating magnitude of reinforcement with a reset contingency .


Self-reported smoking status was confirmed with both carbon monoxide ( CO ) level in expired air and cotinine levels in urine .


Of the patients who received CBT+CM 97.7 % , completed 6 weeks of treatment , versus 81.6 % of those who received CBT ( p = .03 ) .


At the post-treatment assessment , 95.3 % of the patients assigned to the CBT+CM condition achieved abstinence in comparison to the 59.2 % in the CBT group ( p = .000 ) .


At the one-month follow-up , 72.1 % of the patients who received CBT+CM maintained smoking abstinence , versus 34.7 % in the CBT group ( p = .001 ) .


At the six-month follow-up , 51.2 % of the patients who received CBT+CM maintained smoking abstinence in comparison to the 28.6 % in the CBT group ( p = .04 ) .


Results from this randomized clinical trial showed that adding CM to a CBT is effective , and is feasible as an intervention approach with treatment-seeking patients in a community setting .


To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer .


A 2 2 factorial design was used to test two hypotheses : ( 1 ) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and ( 2 ) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer .


With 3,250 patients , a disease-free survival ( DFS ) hazard ratio of 0.82 for each randomization could be detected with 90 % power with two-sided = .05 .


Overall survival ( OS ) was a secondary outcome .


Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens .


After a median follow-up of 6 years , a significant interaction developed between the two randomization factors ( DFS P = .024 ; OS P = .010 ) in the 2,716 patients randomly assigned in the original design , which precluded interpretation of the two factors separately .


Comparing all four arms showed a significant difference in OS ( P = .040 ) but not in DFS ( P = .11 ) , with all treatments given once every 2 weeks associated with the highest OS .


This difference in OS seemed confined to patients with hormone receptor-negative/human epidermal growth factor receptor 2 ( HER2 ) - negative tumors ( P = .067 ) , with no differences seen with hormone receptor-positive/HER2-negative ( P = .90 ) or HER2-positive tumors ( P = .40 ) .


Patients achieved a similar DFS with any of these regimens .


Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor-negative/HER2-negative tumors .


To evaluate the effectiveness of resin-based sealants and glass ionomer sealants on caries prevention in the first permanent molars .


A randomized controlled , examiner-blinded , 2-year clinical trial with parallel groups was conducted .


A total of 419 children ( 664 first molars ) who had at least one sound first permanent molar with deep fissures or fissures with signs of non-cavitated lesions were recruited .


They were randomly allocated into three groups.Helioseal F , a light-cured resin-based sealants was used in group R ( 136 children with 219 first molars ) .


FUJI VII , a light-cured glass ionomer sealants was used in group G ( 130 children with 218 first molars ) and group N ( 153 children with 227 first molars ) was blank control.Follow-up examinations were conducted at 6 , 12 , and 24 month after sealing to examine the sealants retention and caries incidence .


Chi-square test was used to compare the differences of caries incidence among the 3 groups.Generalized estimating equations ( GEE ) was used to analyze the effective factors of caries incidence .


During the 2-year follow-up period , 3.0 % ( 6/197 ) of the teeth in group R , 6.7 % ( 13/193 ) of the teeth in group G , and 14.7 % ( 29/197 ) of the teeth in group N were diagnosed as having developed a cavitated lesion .


The difference in the incidence of caries among the three groups was significant ( P < 0.05 ) .


No significant difference in caries incidence was found between group R and group G ( P > 0.05 ) .


The tooth-level preventive fractions were 79.6 % for resin-based sealants and 54.4 % for glass ionomer sealants , respectively .


Both resin-based sealants and glass ionomer sealants can effectively prevent the incidence of caries in the first permanent molars .


The two sealants have similar caries prevention effect .


In the Single Ventricle Reconstruction ( SVR ) trial , 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt ( RVPAS ) compared with a modified Blalock-Taussig shunt ( MBTS ) .


At 3 years , we compared transplantation-free survival , echocardiographic right ventricular ejection fraction , and unplanned interventions in the treatment groups .


Vital status and medical history were ascertained from annual medical records , death indexes , and phone interviews .


The cohort included 549 patients randomized and treated in the SVR trial .


Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years ( 67 % versus 61 % ; P = 0.15 ) or with all available follow-up of 4.81.1 years ( log-rank P = 0.14 ) .


Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group ( 41.75.1 % versus 44.76.0 % ; P = 0.007 ) , and right ventricular ejection fraction deteriorated in RVPAS ( P = 0.004 ) but not MBTS ( P = 0.40 ) subjects ( pre-Fontan minus 14-month mean , -3.258.24 % versus 0.998.80 % ; P = 0.009 ) .


The RVPAS versus MBTS treatment effect had nonproportional hazards ( P = 0.004 ) ; the hazard ratio favored the RVPAS before 5 months ( hazard ratio = 0.63 ; 95 % confidence interval , 0.45-0 .88 ) but the MBTS beyond 1 year ( hazard ratio = 2.22 ; 95 % confidence interval , 1.07-4 .62 ) .


By 3 years , RVPAS subjects had a higher incidence of catheter interventions ( P < 0.001 ) with an increasing HR over time ( P = 0.005 ) : < 5 months , 1.14 ( 95 % confidence interval , 0.81-1 .60 ) ; from 5 months to 1 year , 1.94 ( 95 % confidence interval , 1.02-3 .69 ) ; and > 1 year , 2.48 ( 95 % confidence interval , 1.28-4 .80 ) .


By 3 years , the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival .


Moreover , RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time .


http://www.clinicaltrials.gov .


Unique identifier : NCT00115934 .


The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia ( CAP ) and acute otitis media ( AOM ) is unclear .


This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) on these end points .


The primary objective was to demonstrate vaccine efficacy ( VE ) in a per-protocol analysis against likely bacterial CAP ( B-CAP : radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray , or non-alveolar infiltrates and C-reactive protein 40 g/ml ) ; other protocol-specified outcomes were also assessed .


This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine , Panamanian , and Colombian populations with good access to health care .


Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine ( hepatitis B for primary vaccination , hepatitis A at booster ) at 2 , 4 , 6 , and 15-18 mo of age .


Interim analysis of the primary end point was planned when 535 first B-CAP episodes , occurring 2 wk after dose 3 , were identified in the per-protocol cohort .


After a mean follow-up of 23 mo ( PHiD-CV , n = 10,295 ; control , n = 10,201 ) , per-protocol VE was 22.0 % ( 95 % CI : 7.7 , 34.2 ; one-sided p = 0.002 ) against B-CAP ( conclusive for primary objective ) and 25.7 % ( 95 % CI : 8.4 % , 39.6 % ) against World Health Organization-defined consolidated CAP .


Intent-to-treat VE was 18.2 % ( 95 % CI : 5.5 % , 29.1 % ) against B-CAP and 23.4 % ( 95 % CI : 8.8 % , 35.7 % ) against consolidated CAP .


End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease ( IPD ) ( PHiD-CV , n = 10,211 ; control , n = 10,140 ) and AOM ( n = 3,010 and 2,979 , respectively ) .


Per-protocol VE was 16.1 % ( 95 % CI : -1.1 % , 30.4 % ; one-sided p = 0.032 ) against clinically confirmed AOM , 67.1 % ( 95 % CI : 17.0 % , 86.9 % ) against vaccine serotype clinically confirmed AOM , 100 % ( 95 % CI : 74.3 % , 100 % ) against vaccine serotype IPD , and 65.0 % ( 95 % CI : 11.1 % , 86.2 % ) against any IPD .


Results were consistent between intent-to-treat and per-protocol analyses .


Serious adverse events were reported for 21.5 % ( 95 % CI : 20.7 % , 22.2 % ) and 22.6 % ( 95 % CI : 21.9 % , 23.4 % ) of PHiD-CV and control recipients , respectively .


There were 19 deaths ( n = 11,798 ; 0.16 % ) in the PHiD-CV group and 26 deaths ( n = 11,799 ; 0.22 % ) in the control group .


A significant study limitation was the lower than expected number of captured AOM cases .


Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice .


www.ClinicalTrials.gov NCT00466947 .


Optimization of chemotherapy effectiveness in metastatic colorectal cancers ( mCRC ) is a major endpoint to enhance the possibility of curative intent surgery .


FOLFIRI3 has shown promising results as second-line chemotherapy for mCRC patients previously exposed to oxaliplatin .


The clinical efficacy of FOLFIRI3 was never determined in association with bevacizumab in non-previously treated mCRC patients .


We conducted a phase II clinical trial to characterize the response rate and toxicity profile of FOLFIRI3-bevacizumab as initial treatment for mCRC .


Sixty-one patients enrolled in 3 investigation centers were treated with FOLFIRI3-bevacizumab ( median of 10cycles ) followed by a maintenance therapy combining bevacizumab and capecitabine .


Levels of plasma angiopoietin-2 ( Ang-2 ) were measured by enzyme-linked immunosorbent assay at baseline .


Overall response rate ( ORR ) was 66.7 % ( 8 % of complete and 58 % of partial responses ) .


The disease control rate was 91.7 % .


After a median time of follow-up of 46.7 months , 56 patients ( 92 % ) had progressed or died .


The median progression free survival ( PFS ) was 12.7 months ( 95 % confidence interval ( CI ) 9.7-15 .8 months ) .


The median overall survival ( OS ) was 24.5 months ( 95 % CI : 10.6-38 .3 months ) .


Twenty-one patients underwent curative intent-surgery including 4 patients with disease initially classified as unresectable .


Most common grade III-IV toxicities were diarrhea ( 15 % ) , neutropenia ( 13 % ) , asthenia ( 10 % ) , and infections ( 4 % ) .


Hypertension-related medications needed to be increased in 3 patients .


In multivariate analysis , surgery of metastases and Ang-2 levels were the only independent prognostic factors for PFS and OS .


Indeed , baseline level of Ang-2 above 5ng/mL was confirmed as an independent prognostic factor for progression free survival ( HR = 0.357 ; 95 % CI : 0.168-0 .76 , p = 0.005 ) and overall survival ( HR = 0.226 ; 95 % CI : 0.098-0 .53 , p = 0.0002 ) .


As front-line therapy , FOLFIRI-3-bevacizumab is associated with an acceptable toxicity and induced promising objective response rates .


However , unfavorable clinical outcomes were observed in patients with high levels of angiopoietin-2 .


Despite considerable evidence supporting cognitive behavioral therapy for insomnia ( CBT-I ) for chronic insomnia , it remains untested within the context of acute insomnia .


This study examined the efficacy of a single session of CBT-I , with an accompanying self-help pamphlet , for individuals with acute insomnia .


A pragmatic parallel group randomized controlled trial .


Community .


Forty adults ( mean age 32.9 13.72 y ) with Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition ( DSM-5 ) defined insomnia disorder , except a self-reported duration of less than 3 mo ( i.e. , acute insomnia ) , who reported no previous exposure to CBT-I and were not currently taking medication for sleep .


A single 60 - to 70-min session of CBT-I ( n = 20 ) , with an accompanying self-help pamphlet , or wait list control group ( n = 20 ) .


All subjects were offered a full individual course of CBT-I on completion of the study , regardless of group allocation .


Subjects completed sleep diaries and the Insomnia Severity Index ( ISI ) pretreatment and 1 mo following treatment .


There were no between-group differences on baseline ISI scores or subjective sleep continuity .


The intervention group reported significantly lower ISI scores than controls ( t ( 38 ) 2.24 , P < 0.05 ) at follow-up .


Further , using proposed ISI scores for identifying insomnia caseness ( i.e. , 10 ) , 60 % of those in the CBT-I group had remitted by 1 mo compared to 15 % of those in the control group .


This single session of cognitive behavioral therapy for insomnia ( CBT-I ) is sufficiently efficacious for a significant proportion of those with acute insomnia .


The results are discussed in terms of integrating this brief form of CBT-I into the `` stepped care '' model of insomnia .


Testing the efficacy of an early intervention for acute insomnia ( SRCTN05891695 ) http://www.controlled-trials.com/ISRCTN05891695 .


Dietary triacylglycerols containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose .


We used a cross-over designed feeding trial in 53 healthy Asian men and women ( 20-50 years ) to test this hypothesis by exchanging 20 % energy of palm olein ( PO ; control ) with randomly interesterified PO ( IPO ) or high oleic acid sunflower oil ( HOS ) .


After a 2-week run-in period on PO , participants were fed PO , IPO and HOS for 6 week consecutively in randomly allocated sequences .


Fasting ( midpoint and endpoint ) and postprandial blood at the endpoint following a test meal ( 3.54 MJ , 14g protein , 85g carbohydrate and 50g fat as PO ) were collected for the measurement of C-peptide , insulin , glucose , plasma glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 , lipids and apolipoproteins ; pre-specified primary and secondary outcomes were postprandial changes in C-peptide and plasma glucose .


Low density lipoprotein cholesterol was 0.3 mmol/l ( 95 % confidence interval ( 95 % CI ) ) 0.1 , 0.5 ; P < 0.001 ) lower on HOS than on PO or IPO as predicted , indicating good compliance to the dietary intervention .


There were no significant differences ( P = 0.58 ) between diets among the 10 male and 31 female completers in the incremental area under the curve ( 0-2h ) for C-peptide in nmol .120 min/l : GM ( 95 % CI ) were PO 220 ( 196 , 245 ) , IPO 212 ( 190 , 235 ) and HOS 224 ( 204 , 244 ) .


Plasma glucose was 8 % lower at 2h on IPO vs PO and HOS ( both P < 0.05 ) .


Palmitic acid in the sn-2 position does not adversely impair insulin secretion and glucose homeostasis .


Morquio A syndrome ( mucopolysaccharidosis IVA ; MPS IVA ) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase , an enzyme required for degradation of the glycosaminoglycan keratan sulfate .


Enzyme replacement therapy with elosulfase alfa provides a potential therapy for Morquio A syndrome .


We analyzed the pharmacokinetics and pharmacodynamics of elosulfase alfa in Morquio A patients from a phase III clinical trial .


In a randomized double-blind study , elosulfase alfa at 2.0 mg/kg was administrated weekly or every other week for 24 weeks .


Pharmacokinetic parameters of elosulfase alfa were determined at weeks 0 and 22 by non-compartmental analysis .


Safety was assessed throughout the study .


The relationship of pharmacokinetic parameters to patient demographics , pharmacodynamic assessments , immunogenicity , and efficacy and safety outcomes were assessed graphically by treatment group .


Elosulfase alfa exposure and half-life ( t ( ) ) increased for both dose regimens during the study .


There appeared to be no consistent trend between drug clearance ( CL ) and patient 's sex , race , body weight , or age .


All patients developed anti-drug antibodies , but no association was noted between total antibody titer and CL .


In contrast , positive neutralizing antibody ( NAb ) status appeared to associate with decreased CL and prolonged t ( ) for patients in the cohort dosed weekly .


NAb may interfere with receptor-mediated cellular uptake and lead to increased circulation time of elosulfase alfa .


Despite the association between NAb and decreased drug clearance , neither dosing cohort showed associations between drug exposure and change in urinary keratan sulfate , 6-min walk test distances , or the occurrence of adverse events .


Benign paroxysmal positional vertigo ( BPPV ) is a common presenting problem .


Our aim was to compare the efficacy of vestibular rehabilitation ( maneuver ) vs. conventional therapy ( medications ) in patients presenting to the emergency department ( ED ) with BPPV .


This was a prospective , single-blinded physician , randomized pilot study comparing two groups of patients who presented to the ED with a diagnosis of BPPV at a Level 1 trauma center with an annual census of approximately 75,000 .


The first group received standard medications and the second group received a canalith repositioning maneuver .


The Dizziness Handicap Inventory was used to measure symptom resolution .


Twenty-six patients were randomized ; 11 to the standard treatment arm and 15 to the interventional arm .


Mean age standard deviation of subjects randomized to receive maneuver and medication were 59 12.6 years and 64 11.2 years , respectively .


There was no significant difference in mean ages between the two treatment arms ( p = 0.310 ) .


Two hours after treatment , the symptoms between the groups showed no difference in measures of nausea ( p = 0.548 ) or dizziness ( p = 0.659 ) .


Both groups reported a high level of satisfaction , measured on a 0-10 scale .


Satisfaction in subjects randomized to receive maneuver and medication was 9 1.5 and 9 1.0 , respectively ; there was no significant difference in satisfaction between the two arms ( p = 0.889 ) .


Length of stay during the ED visit did not differ between the treatment groups ( p = 0.873 ) .


None of the patients returned to an ED for similar symptoms .


This pilot study shows promise , and would suggest that there is no difference in symptomatic resolution , ED length of stay , or patient satisfaction between standard medical care and canalith repositioning maneuver .


Physicians should consider the canalith repositioning maneuver as a treatment option .


To study the therapeutic efficacy and safety of Ginkgo special extract EGb 761 in the treatment of cognitive and non-cognitive symptoms ( anxiety , depression , sleep disorders , activity ) in patients with discirculatory encephalopathy ( DE ) and cognitive impairment .


The study enrolled 45 patients with DE ( mean age 60,85,9 years ) .


Patients were randomized to treatment with EGb 761 ( 30 patients ) or other drugs ( 15 patients ) .


Patients underwent neurological examinations , along with cognitive and neuropsychological testing ( FAB , MMSE , HADS and other tests ) .


EGb 761 was used in dose 240 mg per day during 24 weeks .


By the end of the study , the levels of anxiety and depression decreased ( p < 0,05 ) to the 12th and 24th week , respectively .


The results indicate the efficacy and good tolerability of EGb 761 in the treatment of mental disorders in DE patients with cognitive impairment .


The best effect was observed in relation to anxiety .


This prospective , randomized , controlled clinical trial compared changes in primary outcome measures of claudication onset time ( COT ) and peak walking time ( PWT ) , and secondary outcomes of submaximal exercise performance , daily ambulatory activity , vascular function , inflammation , and calf muscle hemoglobin oxygen saturation ( StO2 ) in patients with symptomatic peripheral artery disease ( PAD ) following new exercise training using a step watch ( NEXT Step ) home-exercise program , a supervised exercise program , and an attention-control group .


One hundred eighty patients were randomized .


The NEXT Step program and the supervised exercise program consisted of intermittent walking to mild-to-moderate claudication pain for 12 weeks , whereas the controls performed light resistance training .


Change scores for COT ( P < 0.001 ) , PWT ( P < 0.001 ) , 6-minute walk distance ( P = 0.028 ) , daily average cadence ( P = 0.011 ) , time to minimum calf muscle StO2 during exercise ( P = 0.025 ) , large-artery elasticity index ( LAEI ) ( P = 0.012 ) , and high-sensitivity C-reactive protein ( hsCRP ) ( P = 0.041 ) were significantly different among the 3 groups .


Both the NEXT Step home program and the supervised exercise program demonstrated a significant increase from baseline in COT , PWT , 6-minute walk distance , daily average cadence , and time to minimum calf StO2 .


Only the NEXT Step home group had improvements from baseline in LAEI , and hsCRP ( P < 0.05 ) .


NEXT Step home exercise utilizing minimal staff supervision has low attrition , high adherence , and is efficacious in improving COT and PWT , as well as secondary outcomes of submaximal exercise performance , daily ambulatory activity , vascular function , inflammation , and calf muscle StO2 in symptomatic patients with PAD .


ClinicalTrials.gov .


Unique Identifier : NCT00618670 .


One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery .


We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes .


We enrolled patients in 23 centres in Switzerland , Germany and Serbia .


Eligible patients had pathologically proven , stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio .


Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy ( 100 mg/m ( 2 ) cisplatin and 85 mg/m ( 2 ) docetaxel ) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks , and those in the control group received neoadjuvant chemotherapy alone .


All patients were scheduled to undergo surgery .


Randomisation was stratified by centre , mediastinal bulk ( less than 5 cm vs 5 cm or more ) , and weight loss ( 5 % or more vs less than 5 % in the previous 6 months ) .


The primary endpoint was event-free survival .


Analyses were done by intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT00030771 .


From 2001 to 2012 , 232 patients were enrolled , of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group .


Median event-free survival was similar in the two groups at 128 months ( 95 % CI 97-229 ) in the chemoradiotherapy group and 116 months ( 84-152 ) in the chemotherapy group ( p = 067 ) .


Median overall survival was 371 months ( 95 % CI 226-500 ) with radiotherapy , compared with 262 months ( 199-521 ) in the control group .


Chemotherapy-related toxic effects were reported in most patients , but 91 % of patients completed three cycles of chemotherapy .


Radiotherapy-induced grade 3 dysphagia was seen in seven ( 7 % ) patients .


Three patients died in the control group within 30 days after surgery .


Radiotherapy did not add any benefit to induction chemotherapy followed by surgery .


We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer .


Swiss State Secretariat for Education , Research and Innovation ( SERI ) , Swiss Cancer League , and Sanofi .


To observe the therapeutic effect of Chishaodanpi decoction ( CSDPD ) on chronic viral cholestatic hepatitis .


A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007 to November 2012 .


Patients were randomly divided into treatment ( 54 cases ) and control groups ( 53 cases ) .


The control group was treated with potassium magnesium aspartate , diammonium glycyrrhizinate , glucurolactone , vitamin C , and lamivudine , once a day .


The treatment group was treated with modified CSDPD , 100 mL a time , twice a day , in addition to the treatment given to the control group .


The patients in both groups were treated for 8 weeks .


The main symptoms and signs were recorded every day throughout the clinical trial .


Before and after the trial , changes in liver function including total bilirubin ( TBil ) , direct bilirubin ( DBil ) , total bile acid ( TBA ) , and the activities of alkaline phosphatase ( ALP ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , and - glutamyl transferase ( - GT ) , were all detected .


Adverse reactions were also recorded .


There were no differences in gender , age , disease duration , symptoms , signs , or laboratory findings between the two groups ( P > 0.05 ) .


After an 8-week treatment , improvements in jaundice , weakness , poor appetite , abdominal distention , and skin itching were significantly better in the treatment group than in the control group ( P < 0.05 ) .


In the treatment group , 43 patients had a significant response to the treatment , seven patients had a response , and four patients had no response , with 21 , 12 , and 20 patients in the control group , respectively .


The total effective rate was 92.6 % in the treatment group and 62.3 % in the control group , which was a significant difference ( P < 0.05 ) .


The levels of TBil , DBil , TBA , ALP , ALT , AST , and - GT in both groups were significantly lower after treatment , and were significantly different between the two groups ( P < 0.05 ) .


A few patients in the treatment group had mild adverse effects such as increased bowel movement frequency and mild stomach-ache .


No other adverse reactions were observed in either group .


Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease .


A previous study found an effect of sleep on - amyloid ( A ) , which is a key protein in Alzheimer disease pathology .


To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid A42 protein levels in healthy middle-aged men .


The Alzheimer , Wakefulness , and Amyloid Kinetics ( AWAKE ) study at the Radboud Alzheimer Center , a randomized clinical trial that took place between June 1 , 2012 , and October 1 , 2012 .


Participants were cognitively normal middle-aged men ( 40-60 years of age ) with normal sleep ( n = 26 ) recruited from the local population .


Participants were randomized to 1 night with unrestricted sleep ( n = 13 ) or 1 night of total sleep deprivation ( 24 hours of wakefulness ) ( n = 13 ) .


Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am .


Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral A42 concentrations between evening and morning .


A night of unrestricted sleep led to a 6 % decrease in A42 levels of 25.3 pg/mL ( 95 % CI [ 0.94 , 49.6 ] , P = .04 ) , whereas sleep deprivation counteracted this decrease .


When accounting for the individual trajectories of A42 over time , a difference of 75.8 pg/mL of A42 was shown between the unrestricted sleep and sleep deprivation group ( 95 % CI [ 3.4 , 148.4 ] , P = .04 ) .


The individual trajectories of evening and morning A42 concentrations differed between the unrestricted sleep and sleep deprivation groups ( P = .04 ) in contrast to stable A40 , tau , and total protein levels .


Sleep deprivation , or prolonged wakefulness , interferes with a physiological morning decrease in A42 .


We hypothesize that chronic sleep deprivation increases cerebral A42 levels , which elevates the risk of Alzheimer disease .


clinicaltrials.gov Identifier : NCT01194713 .


This 12-week randomized placebo controlled clinical trial investigated the effect of Coenzyme Q10 ( CoQ10 ) on diabetic neuropathy , oxidative stress , blood glucose and lipid profile of patients with type 2 diabetes .


Diabetic patients with neuropathic signs ( n = 70 ) were randomly assigned to CoQ10 ( 200 mg/d ) or placebo for 12 weeks .


Blood samples were collected for biochemical analysis and neuropathy tests before and after the trial .


There were no significant differences between the two groups in terms of mean fasting blood glucose , HbA1c and the lipid profile after the trial .


The mean insulin sensitivity and total antioxidant capacity ( TAC ) concentration significantly increased in the Q10 group compared to the placebo after the trial ( P < 0.05 ) .


C-reactive protein ( hsCRP ) significantly decreased in the intervention group compared to placebo after the trial ( P < 0.05 ) .


In the control group , insulin sensitivity decreased and HOMA-IR increased , which revealed a significant difference between groups after the trial .


Neuropathic symptoms and electromyography measurements did not differ between two groups after the trial .


According to the present study , CoQ10 , when given at a dose of 200 mg/d for 12 weeks to a group of neuropathic diabetic patients , did not improve the neuropathy signs compared to placebo , although it had some beneficial effects on TAC and hsCRP and probably a protective effect on insulin resistance .


Pneumonia is a major cause of mortality and morbidity in patients with stroke fed via nasogastric tubes and may be because of vomiting and gastro-oesophageal regurgitation .


The aim of the study was to assess whether regular treatment with metoclopramide , a D2-receptor antagonist with antiemetic and gastric prokinetic actions , could reduce the rate of aspiration and pneumonia .


Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of a nasogastric tube were recruited into a double-blind randomized placebo-controlled trial .


Participants received metoclopramide 10 mg or placebo 3 daily via the nasogastric tube for 21 days or until nasogastric feeds were discontinued .


Clinical signs of pneumonia were recorded daily .


Pneumonia was diagnosed if the patient had relevant clinical signs , high inflammatory markers , and new infiltrates on the chest radiograph .


Sixty patients ( mean age , 78 years ; 38 women ; mean National Institutes for Health Stroke Scale score , 19.25 ) were randomized in a 1:1 ratio .


There were significantly more episodes of pneumonia in the placebo group than in the metoclopramide group ( rate ratio , 5.24 ; P < 0.001 ) .


There were also significant differences in favor of metoclopramide in the rate of aspiration , oxygen saturation , highest inflammatory markers , and National Institutes for Health Stroke Scale .


There was no significant difference in mortality between the groups .


This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube .


These findings need to be confirmed in larger randomized and blinded trials .


https://www.clinicaltrialsregister.eu .


EudraCT no : 2006-002570-22 , URL : http://www.controlled-trials.com/ISRCTN18034911/18034911 .


To analyze the correlation of the tympanic injection of triamcinolone acetonide , middle ear pressure ( MEP ) and radioactive secretory otitis media ( RSOM ) with nasopharyngeal carcinoma ( NPC ) after radiotherapy .


Fifty-two patients suffering NPC without otitis media before radiotherapy were randomly divided into three groups .


17 cases with 34 ears were distributed into treatment group I , and radiotherapy 1 hour before the start of each side of the tympanic cavity injection of triamcinolone acetonide injection , 1-7 weeks 1 times a week .


Treatment group I had 17 cases with 34 ears , and radiotherapy 1 hour before the start of each side of the tympanic cavity injection of triamcinolone acetonide injection , 1-12 weeks 1 times a week .


And control group consisted of 18 cases with 36 ears who did n't accept such treatment .


In all 104 ears , MEP was tested at the begin of radiotherapy and the end of 1st , 2nd , 3rd month after radiotherapy .


From the beginning of radiotherapy to the end of th 1st , 2nd , 3rd month after radiotherapy , the morbidity of RSOM gradually increased and MEP decreased in the treatment group I , II and the control group , in which treatment group II showed the lowest morbidity of RSOM and MEP was maximum ( P < 0.01 ) , and the treatment group I showed the lower morbidity of RSOM and MEP was greater ( P < 0.05 ) , while the control group showed the highest morbidity of RSOM and MEP was minimum ( P > 0.05 ) .


Tympanic injection of triamcinolone acetonide could reduce radiation injury , and medication time was positively correlated with the MEP , and a negative correlation with RSOM morbidity , and the longer treatment , the more significant the effect is .


The difference is most obvious at the end of 3rd month after radiotherapy .


It may be due to the more active repairation after radiation damage in middle ears , but long-term efficacy must continue to observe .


The development of osteoarthritis ( OA ) involves inflammation , but the evidence for participation of genes propagating or inhibiting inflammation in the OA process is inconsistent .


We investigated the associations of common variants in the TNF gene , and their interactions with other cytokine genes , with hand OA among Finnish women .


This cross-sectional study was based on bilateral hand radiographs of 542 female dentists and teachers which were classified according to the presence of OA ( radiographic K-L score 2 in 3 joints ) using reference images .


The genotypes were determined by PCR-based methods .


The degree of pairwise linkage disequilibrium ( LD ) and haplotypes were constructed and analyzed by the SNPStats software .


The associations between four TNF SNPs and hand OA were tested using logistic regression adjusting for age , occupation , and BMI , and fitting a log-additive model of inheritance .


Gene-gene interactions of TNF SNPs with IL4R and IL10 SNPs were examined by stratified logistic regression analyses .


Possible interactions of the TNF SNPs with variants in the previously reported IL1 and IL6 genes in influencing hand OA were also explored .


Two TNF polymorphisms ( '' -1031 '' and '' -863 '' ) were associated with hand OA ( OR = 1.45 , 95 % CI 1.01-2 .07 and 1.55 , 1.06-2 .25 , respectively ) .


These associations retained when adjusting further for IL1 `` 3954 '' and IL6 `` 174 '' .


The TNF G-A-G haplotype was associated with an increased risk of hand OA ( 1.61 , 1.10-2 .37 , p = 0.01 ) .


Interactions were observed between TNF '' -1031 '' and IL4R Ser503Pro , TNF '' -1031 '' and IL10 '' -1082 '' , and TNF '' -863 '' and IL10 '' -1082 '' SNPs with regard to hand OA ( p = 0.012 , p = 0.0068 , and p = 0.02 , respectively ) .


The carriage of the TNF '' -1031 '' minor allele doubled the risk ( 2.01 , 1.26 - 3.22 ) only in women with the IL4R Ser/Ser genotype .


Similarly , the TNF '' -1031 '' and '' -863 '' minor alleles were associated with an increased risk of hand OA only in IL10 G/G or A/A homozygotes ( 2.54 , 1.45-4 .47 and 2.60 , 1.46-4 .62 , respectively ) but not in heterozygotes ( G/A ) .


Our results suggest that the TNF gene variants play a role in the etiology of hand OA .


In addition , the findings are suggestive of a gene-gene interaction of the TNF with IL4R and IL10 genes .


The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus ( T2DM ) .


A phase IIIb , open-label , 1:1 randomized , active-controlled , 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted .


Patients were administered lixisenatide before breakfast or the main meal .


The primary endpoint was change from baseline at week 24 in glycated haemoglobin ( HbA1c ) .


Other endpoints : changes in body weight , fasting plasma glucose ( FPG ) , 7-point self-monitored plasma glucose ( SMPG ) and Diabetes Treatment Satisfaction Questionnaire status ( DTSQs ) score .


Adverse events ( AEs ) were monitored .


Mean change in HbA1c from baseline at week 24 was -0.65 % ( -7.1 mmol/mol ; main meal ) and -0.74 % ( -8.1 mmol/mol ; breakfast ) .


Mean changes in FPG , body weight and DTSQs score were comparable between groups .


The mean change in body weight ( kg ) was -2.60 ( main meal ) and -2.80 ( breakfast group ) .


The 7-point SMPG profiles showed greatest reductions in postprandial glucose after the meal at which lixisenatide was administered , with a residual effect seen on the subsequent meal .


AE rates were similar between groups , including gastrointestinal AEs .


Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin .


Lixisenatide treatment allows flexibility in administration timing .


Weight lost by obese patients is almost always regained over time .


Extended treatment may improve maintenance , but solid evidence is lacking .


We determined effectiveness of maintenance therapy after a weight loss program .


Together 201 patients ( mean age 47 years and BMI 42kg/m ( 2 ) , 71 % women ) were randomly assigned to either a 17-week weight loss program followed by a one-year maintenance program or to a weight loss program without subsequent maintenance intervention .


The weight loss program included behavior modification and a very-low-calorie diet , and maintenance program behavior modification .


The primary outcome measure was percentage of patients with 5 % or more weight loss at the end of maintenance ( week 69 ) and one year later ( week 121 ) .


Secondary outcomes were weight related changes in lifestyle and quality of life .


At week 69 , 52 % of the patients with and 44 % of those without maintenance program had lost weight 5 % , P = 0.40 , and , at week 121 , 33 % and 34 % , P = 0.77 , respectively .


At week 121 secondary outcomes did not differ between the groups among those successfully followed up .


This one-year maintenance program was not effective in preventing weight regain in severely obese patients .


Trial Registration .


This trial is registered under clinicaltrials.gov Identifier : NCT00590655 .


This study aims to investigate the effects of low-level laser therapy ( LLLT ) on biceps brachi muscular fatigue in 20 young females .


Exhausting physical activity leads to muscular fatigue , which could decrease muscular strength , and may cause impairment in motor control and muscle pain .


Several biochemical and biophysical resources have been studied in an attempt to accelerate the recovery of muscle fatigue .


Among these , LLLT is emphasized .


Twenty subjects were randomized in one laser group and one placebo group in two sessions of a crossover design experimental procedure ; the second session taking place within 7 days of the first .


In the first session , subjects underwent a collection of surface electromyographic ( SEMG ) data of the biceps brachii muscle , followed by active or placebo LLLT at the same muscle , followed then by another EMG sample of biceps brachii .


Blood samples were collected five times during the experimental procedure .


Second session procedures were identical to the first , with exception of LLLT , which was the opposite of the first session .


The fatigue protocol consisted of 60 sec of elbow flexion-extension movement performed with 75 % of one maximum repetition .


Blood lactate , EMG fatigue , and the number of elbow flexion-extension repetitions during the fatigue protocol were used to evaluate the effects of laser therapy ( 808 nm wavelength , 100 mW output power , power density of 35.7 W/cm ( 2 ) , 70 sec each point and 7 J/point on eight points ) .


No statistical differences were found for eletromyographic fatigue and blood lactate values between groups .


Mean numbers of elbow flexion-extension repetitions were 22.6 7.58 after placebo , and 25.1 9.89 after active LLLT group , but these differences were not statistically significant ( p = 0.342 ) .


LLLT had limited effects on delaying muscle fatigue in a young female sample , although a tendency was observed in the active laser group toward showing lower electromyography fatigue of biceps brachii muscle .


No intergroup differences were found in the number of muscle contractions and lactate concentration .


To determine the optimal single-dose radiotherapy schedule for pain from bone metastases in a multi-centre , international , randomised trial .


651 patients were randomised to either 8Gy ( n = 325 ) or 4Gy ( n = 326 ) radiotherapy .


Pain at 4 , 8 , 12 , 24 and 52weeks was assessed using a Categorical Scale ( CS ) and a Visual Analogue Scale ( VAS ) .


The primary endpoint was response at 4weeks .


There was no significant difference in patient demographics and other co-variates .


The complete response ( CR ) rate and ORR ( complete or partial response ) for all follow-up times were higher after 8Gy ( p = 0.02 ) .


The Kaplan-Meier actuarial rate ( categorical scale ) at 4weeks for ORR was 80 % after 8Gy compared to 68 % after 4Gy ( p = 0.0015 ) .


117 re-treatments were given of which 72 were in the 4Gy group and 45 in 8Gy arm ( p = 0.01 ) .


There was a marked consistent difference in pain relief at all time points in favour of 8Gy .


These data reinforce the case for single dose 8Gy radiotherapy to be recommended for metastatic bone pain in all healthcare settings .


Chronic hepatitis C virus ( HCV ) infection in patients with stage 4-5 chronic kidney disease increases the risk of death and renal graft failure , yet patients with hepatitis C and chronic kidney disease have few treatment options .


This study assesses an all-oral , ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease .


In this phase 3 randomised study of safety and observational study of efficacy , patients with HCV genotype 1 infection and chronic kidney disease ( stage 4-5 with or without haemodialysis dependence ) were randomly assigned to receive grazoprevir ( 100 mg , NS3/4A protease inhibitor ) and elbasvir ( 50 mg , NS5A inhibitor ; immediate treatment group ) or placebo ( deferred treatment group ) once daily for 12 weeks .


Randomisation was done centrally with an interactive voice response system .


An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling .


The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks ( SVR12 ) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control .


The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group .


After 4 weeks of follow-up ( study week 16 ) , unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir .


The primary efficacy hypothesis was tested at a two-sided significance level ( type I error ) of 005 using an exact test for a binomial proportion .


Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata .


The study is registered at ClinicalTrials.gov , number NCT02092350 .


224 patients were randomly assigned to the immediate treatment group with grazoprevir and elbasvir ( n = 111 ) or the deferred treatment group ( n = 113 ) , and 11 were assigned to the intensive pharmacokinetic population .


Overall , 179 ( 76 % ) were haemodialysis-dependent , 122 ( 52 % ) had HCV genotype 1a infection , 189 ( 80 % ) were HCV treatment-naive , 14 ( 6 % ) were cirrhotic , and 108 ( 46 % ) were African American .


Of the 122 patients receiving grazoprevir and elbasvir , six were excluded from the primary efficacy analysis for non-virological reasons ( death , lost-to-follow-up [ n = 2 ] , non-compliance , patient withdrawal , and withdrawal by physician for violent behaviour ) .


No patients in the combined immediate treatment group and intensive pharmacokinetic population and five ( 4 % ) in the deferred treatment group discontinued because of an adverse event .


Most common adverse events were headache , nausea , and fatigue , occurring at similar frequencies in patients receiving active and placebo drugs .


SVR12 in the combined immediate treatment group and intensive pharmacokinetic population was 99 % ( 95 % CI 953-1000 ; 115/116 ) , with one relapse 12 weeks after end of treatment when compared with a historical control of 45 % , based on meta-analyses of interferon-based regimens used in clinical trials of patients infected with HCV who are on haemodialysis .


Once-daily grazoprevir and elbasvir for 12 weeks had a low rate of adverse events and was effective in patients infected with HCV genotype 1 and stage 4-5 chronic kidney disease .


Merck Sharp & Dohme Corp. .


To evaluate the efficacy and safety of the novel oral anticoagulants under conservative hemostasis with tranexamic acid in hip arthroplasty .


All patients received 40 mg of enoxaparin 12 hours prior to surgery and on the operating day , and then they received either 10 mg of rivaroxaban ( 40 patients ) , 220 mg of dabigatran ( 42 patients ) or 40 mng of enoxaparin ( 39 patients ) .


Tranexamic acid with doses of 10 - 20 mg/kg was administered to all patients : within 30 minutes prior to surgery and 6 hours after the first infision .


The hemorrhagic and thrombotic complications in a hospital outpatient therapy and outcomes in 35 days after surgery were evaluated .


Minor bleeding was observed only in the rivaroxaban group , the complications rate in hospital was 2.5 % , among outpatients 3.1 % .


At hospital discharge the DVT was 12.5 % in rivaroxaban group , 7 % in dabigatran and 8 % in enoxaparin group ( p > 0.05 ) .


Asymptomatic distal DVT was found in 82 % of patients by ultrasound screening .


The new oral anticoagulants are effective and safe for venous thromboembolism preventing after hip re placement .


Routine use of tranexamic acid was not accompanied by increased risk of DVT


This article is based on our previously reported results of irregular bowel movement and disturbances of the intestinal microbiota/environment in gastrectomized patients .


A placebo-controlled , double-blind comparative study was carried out to evaluate the effects of a fermented milk beverage containing Lactobacillus casei strain Shirota ( LcS ) in such patients .


The major evaluated factors of this article were `` bowel movement '' and `` quality of life . ''


The secondary evaluated factors were `` fecal microbiota '' and `` enteric environment . ''


Of the 190 gastrectomized subjects who participated in our previously reported defecation survey , 134 subjects judged as having abnormal defecation gave consent to participate in this study .


These subjects continuously ingested the test beverage containing 40 billion LcS or placebo ( one bottle per day , 4 weeks ) .


In the LcS-ingested group , among the 118 subjects who completed the tests , the assessments of the subjects were based on their division into groups based on their symptoms with our scoring system for constipation/diarrhea ; although there was no significant ingestion effect in total , in the constipation group , LcS reduced the degree of constipation compared with that in the placebo group .


In the diarrhea group , LcS ingestion improved diarrhea compared with that in the preingestion state .


Fecal Staphylococcus level was decreased .


The results suggest the possibility that the continuous consumption of LcS-fermented milk relieves irregular bowel movement in gastrectomized patients .


We have assessed the utility of autologous mesenchymal stem cell ( MSC ) peripheral vein infusion as a possible therapeutic modality for patients with end-stage liver diseases .


Forty patients with post-hepatitis C virus ( HCV ) end-stage liver disease were randomized into two groups : Group 1 ( GI ) : 20 patients who received granulocyte colony-stimulating factor ( G-CSF ) for 5days followed by autologous MSCs peripheral-vein infusion and group 2 ( GII ) : 20 patients who received regular liver-supportive treatment only ( control group ) .


In MSC-infused patients ( GI ) , 54 % showed near normalization of liver enzymes and improvement in liver synthetic function .


Significant changes were reported in albumin ( P = 0.000 ) , bilirubin ( P = 0.002 ) , increased international normalized ratio ( INR ) ( P = 0.017 ) , prothrombin concentration ( P = 0.029 ) and alanine transaminase ( ALT ) levels ( P = 0.029 ) , with stabilization of clinical and biochemical status in 13 % of cases .


None of the patients in GII showed any significant improvement .


Hepatic fibrosis was assessed in GI by detection of procollagen IIIC peptide level ( PIIICP ) and procollagen III N peptide level ( PIIINP ) .


The pretreatment values of s-PIIICP and s-PIIINP were 9.44.2 and 440189 , respectively , with a decrease to 8.12.6 and 388102 , respectively , 3months after MSC therapy .


However , the difference was statistically nonsignificant ( P = 0.7 ) .


A significant correlation coefficient was reported after 3months between the s-PIIINP and prothrombin concentration ( P = -0.5 ) and between s-PIIICP and ascites ( P = 0.550 ) .


First , autologous MSC infusion into a peripheral vein is as effective as the previously reported intrahepatic infusion .


Second , MSCs have a supportive role in the treatment of end-stage liver disease , with satisfactory tolerability and beneficial effects on liver synthetic functions and hepatic fibrosis .


Third , IV infusion of MSCs after G-CSF mobilization improves s-albumin within the first 2weeks and prothrombin concentration and alanine Taransaminase after 1month .


According to the data from this current study and those previously reported by our group , we recommend further studies on patients ' infusion with pure CD133 and CD34 followed by IV infusion of in vitro-differentiated MSCs within 1week and another infusion after 3months .


ClinicalTrials.gov NCT01729221 .


Registered 17 November 2012 .


Local application of mitomycin-c ( MMC ) seems to be effective in reducing adhesions and stenosis after FESS .


However this is not clearly seen in frontal sinusotomy .


This study assesses the effectiveness of local MMC in the frontal ostium using a foamy material ( otowick ) and compared with cottonoids .


Forty-seven patients with chronic rhinosinusitis without polyps enrolled in this study .


Two subgroups were studied : one with MMC application in one nostril using cottonoids and a second with MMC injected in an otowick .


In all patients MMC was applied twice , intraoperatively and 4 weeks later .


In both groups normal saline was applied to the other nostril on the same material with the MMC side .


Six months postoperatively all patients were assessed endoscopically by a clinician blinded to the MMC side .


Overall , MMC application was more effective than normal saline in both groups .


Otowick use presented favorable initial results especially in primary cases regarding ostium patency , and need for revision surgery .


The use of MMC cottonoids did not show any benefit in primary cases .


The described technique seems to be effective in maintaining frontal ostium patency as it provides a more precise and deeper drug delivery to this area .


This pilot study aimed to test the possibility of therapeutic benefit imparted by early intervention based on sequential tumour marker ( TM ) measurements during follow-up of primary breast cancer ( PBC ) patients .


Patients with oestrogen receptor positive PBC with no clinical and/or radiological evidence of metastases were recruited and followed-up 3-monthly with clinical assessment and TM ( CA15 .3 and CEA ) measurements .


The clinical team was blinded to the TM results .


Asymptomatic patients who developed raised TMs ( based on pre-defined cut-offs ) were randomised to either ` treatment change ' ( either start or change of adjuvant endocrine agent to another agent ) or ` no change ' ( control ) .


Patients who developed symptomatic metastases came off the study .


The primary and secondary endpoints were intervals from randomisation to symptomatic metastases and to last follow-up/death respectively .


Eighty-five patients ( median age = 54 years ( 30-72 ) ) were recruited with a median follow-up of 81 months ( 1-124 ) .


Sixteen patients were randomised as described .


There was no significant difference ( treatment change versus no change ) with regards to interval from randomisation to symptomatic metastases - 23 ( 2-62 ) and 22 ( 1-63 ) months respectively ( p = 0.9 ) , as well as interval from randomisation to last follow-up/death - 36 ( 7-63 ) and 37 ( 10-63 ) months respectively ( p = 0.9 ) .


Despite long follow-up ( up to 10 + years ) , this small study has thus far shown no significant difference in outcome .


However , we have confirmed the feasibility of this study design but a larger study will be required to show if there is a benefit to this approach .


Progressive - cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes , but comparative data on - cell-protective therapies are lacking in the early stage of type 2 diabetes .


Here we evaluated the comparative glycaemic efficacy and impact on - cell function of three antihyperglycaemic agents that have a - cell-protective effect , exenatide , insulin and pioglitazone , in newly diagnosed patients with type 2 diabetes .


In this 48-week , multicentre , parallel-group study , 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1 : 1 : 1 to receive exenatide , insulin or pioglitazone .


The primary end-point was the change in glycosylated haemoglobin ( HbA1c ) from baseline .


Secondary end-points included effects on weight , blood pressure , lipid profiles and - cell function assessed by homeostasis model assessment , fasting proinsulin : insulin ( PI/I ) , disposition index ( DI ) and acute insulin response ( AIR ) .


At week 48 , mean [ 95 % confidence interval ( CI ) ] HbA1c changes from baseline were -1.8 % ( -1.55 % to -2.05 % ) with exenatide , -1.7 % ( -1.52 % to -1.96 % ) with insulin and -1.5 % ( -1.23 % to -1.71 % ) with pioglitazone .


Treatment differences were -0.20 % ( 95 % CI -0.46 % to 0.06 % ) for exenatide versus insulin ( P = 0.185 ) , and -0.37 % ( 95 % CI -0.63 % to -0.12 % ) for exenatide versus pioglitazone ( P = 0.002 ) .


Significant improvements from baseline in AIR , PI/I and DI were observed with all treatments , with the greatest improvements in DI , as well as weight , blood pressure and lipid profile , observed with exenatide .


All three agents showed efficacy regarding glycaemic control and metabolic benefits ; however , exenatide showed the greatest efficacy .


- cell function improved in all treatment groups ; hence , early initiation of - cell-protective therapy may halt the decline in - cell function in type 2 diabetes .


Evidence suggests that brief physiotherapy programmes are as effective for acute whiplash-associated disorders as more comprehensive programmes ; however , whether this also holds true for chronic whiplash-associated disorders is unknown .


We aimed to estimate the effectiveness of a comprehensive exercise programme delivered by physiotherapists compared with advice in people with a chronic whiplash-associated disorder .


PROMISE is a two group , pragmatic randomised controlled trial in patients with chronic ( > 3 months and < 5 years ) grade 1 or 2 whiplash-associated disorder .


Participants were randomly assigned by a computer-generated randomisation schedule to receive either the comprehensive exercise programme ( 20 sessions ) or advice ( one session and telephone support ) .


Sealed opaque envelopes were used to conceal allocation .


The primary outcome was pain intensity measured on a 0-10 scale .


Outcomes were measured at baseline , 14 weeks , 6 months , and 12 months by a masked assessor .


Analysis was by intention to treat , and treatment effects were calculated with linear mixed models .


The trial is registered with the Australian New Zealand Clinical Trials Registry , number ACTRN12609000825257 .


172 participants were allocated to either the comprehensive exercise programme ( n = 86 ) or advice group ( n = 86 ) ; 157 ( 91 % ) were followed up at 14 weeks , 145 ( 84 % ) at 6 months , and 150 ( 87 % ) at 12 months .


A comprehensive exercise programme was not more effective than advice alone for pain reduction in the participants .


At 14 weeks the treatment effect on a 0-10 pain scale was 00 ( 95 % CI -07 to 07 ) , at 6 months 02 ( -05 to 10 ) , and at 12 months -01 ( -08 to 06 ) .


CNS hyperexcitability and symptoms of post-traumatic stress did not modify the effect of treatment .


We recorded no serious adverse events .


We have shown that simple advice is equally as effective as a more intense and comprehensive physiotherapy exercise programme .


The need to identify effective and affordable strategies to prevent and treat acute through to chronic whiplash associated disorders is an important health priority .


Future avenues of research might include improving understanding of the mechanisms responsible for persistent pain and disability , investigating the effectiveness and timing of drugs , and study of content and delivery of education and advice .


The National Health and Medical Research Council of Australia , Motor Accidents Authority of New South Wales , and Motor Accident Insurance Commission of Queensland .


To observe the changes in cardiac function , peripheral blood B and T lymphocyte attenuator ( BTLA ) and oxidative stress related indicators in rheumatoid arthritis ( RA ) patients , thus to explore the mechanism underlying the improving effect of Xinfeng Capsule ( XFC ) on cardiac function .


The study enrolled 100 RA patients and divided them randomly into 2 groups , XFC treatment group and leflunomide ( LEF ) control group ( n = 50 per group ) .


The treatment lasted 30 days for one course .


Other 40 healthy people from Medical Examination Center were included as a normal control ( NC ) group .


Flow cytometry was used to detect the expression and activation level of BTLA , Westergren method was used to determine erythrocyte sedimentation rate ( ESR ) , and automatic biochemical analyzer to examine high sensitivity C-reactive protein ( hs-CRP ) and rheumatoid factor ( RF ) .


ELISA method was performed to observe related cytokines ( IL-1 , IL-17 , IL-35 , IFN - ) and markers of oxidative stress such as total antioxidant capacity ( TAOC ) , malondialdehyde ( MDA ) , reactive oxygen species ( ROS ) , superoxide dismutase ( SOD ) , glutathione ( GSH ) .


Echocardiography was utilized to survey cardiac function parameters including heart ejection fraction ( EF % ) , stroke volume ( SV % ) , fractional shortening ( FS % ) , E peak velocities ( E ) and A peak velocities ( A ) of mitral valve flow , and the ratio of filling fraction of E and A ( E/A ) .


Compared with the NC group , EF % , E peak velocity , E/A were significantly reduced while A peak velocity increased in RA patients , and FS % was not found obviously different .


In addition , IL-1 , IL-17 and inflammatory indexes like ESR , CRP increased while BTLA , IL-35 , IFN - decreased significantly ; Serum ROS , MDA rose and SOD , GSH dropped significantly in RA patients .


Correlation analysis showed that the cardiac function parameters EF , FS were negatively correlated with CD24 cells and CD19CD24 cells , that E/A was positively correlated with BTLA , that A peak velocity was positively related to CD19 cells , that EF was positively related to ROS , that SV was positively related with MDA , SOD , that E peak velocity was negatively correlated with TAOC .


After drug intervention , XFC treatment group got 86 % total effective rate .


XFC obviously improved cardiac function regarding EF % , FS % , E peak , E/A and other parameters , increased serum SOD , GSH capacity , eliminated ROS , MDA , increased BTLA , IL-35 , IFN - , and reduced IL-1 , IL-17 .


Compared with LEF group , XFC had a better improving effect on DAS28 and cardiac function parameters .


XFC can increase BTLA expression of CD19 and CD24 B cells and reduce B cell-mediated abnormal humoral immunity and oxidative stress damage , thus improving cardiac function and quality of life .


Ibuprofen ( IBU ) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus ( HsPDA ) , with an efficacy inversely related to gestational age ( 57-89 % ) .


This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation .


A prospective , randomized , double-dummy study was conducted on 112 very low birth weight infants ( mean gestational age 27.2 weeks , SD 2 ; birth weight 1,019 g , SD 330 ) with HsPDA , 56 of whom were given IBU in conventional 15-min intermittent boluses , while the other 56 were administered IBU as a 24-hour continuous infusion , both at standard doses ( 10/5/5 mg/kg ) .


Extensive echocardiography was performed before and after treatment , and adverse effects were monitored .


Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants ( 64.3 % ) after bolus administration and in 46 of 55 ( 83.6 % ) after continuous infusion ( p = 0.020 ) , and in 9 of 26 ( 34.6 % ) and 24 of 30 ( 80.0 % ) , respectively , in the infants with a gestational age of 23-27 weeks ( p = 0.006 ) .


Sustained pharmacological closure was observed in 38 of 56 infants ( 67.9 % ) after bolus IBU and in 47 of 55 ( 85.5 % ) after continuous infusion ( p = 0.029 ) .


Surgical ligation was used less after continuous infusion than after bolus IBU ( 5.5 vs. 19.6 % ; p = 0.024 ) .


The continuous infusion group had fewer symptoms of necrotizing enterocolitis ( NEC ) , especially in the more preterm infants , while other neonatal morbidity and mortality rates were similar .


Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA , with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants .


This study aimed at analyzing the prevalence of hepatitis B virus ( HBV ) DNA among hepatitisB surface antigen ( HBsAg ) - negative donations by cobas TaqScreen MPX test ( Roche Molecular Systems ) and discussing the meaning of a reactive minipool ( MP ) that does not resolve to an individual donation ( ID ) - reactive result .


Nucleic acid amplification testing ( NAT ) was performed in 12 Chinese blood centers on 826,044 serologic negative donations in MPs of six .


MP-reactive pools that were resolved to ID-reactive donations were confirmed by Roche TaqMan viral load assays .


Antibody to hepatitisB surface antigen and antibody to hepatitisB core antigen ( anti-HBc ) results were also analyzed .


Cycle threshold ( Ct ) values of reactive MPs were analyzed in relation to the probability of pool resolution .


A total of 1267 of 137,674 pools were reactive , of which 839 donations were reactive by ID-NAT .


The MP6 HBV NAT-yield rate lay between 1 in 1600 and 1 in 1000 .


At MP Ct values equal or below 37 , the probability of pool resolution was approximately 80 % .


The prevalence of anti-HBc in ID-reactive donations was 81 % .


The proportion of reactive pools that could not be resolved was 36 % .


The prevalence of anti-HBc in donations implicated in nonresolved MPs was significantly higher than those in nonreactive MPs ( 48 % vs. 37 % , p = 0.016 ) .


The anti-HBc data suggest that approximately 10 % of nonresolved MPs contain HBV DNA from a low-viral-load occult carrier .


We consider ID-NAT resolution testing in duplicate to minimize HBV transmission risk associated with transfusing nonreactive donations implicated in reactive MPs .


To compare 1-year clinical efficacy of ( 1 ) initial triple disease-modifying antirheumatic drug therapy ( iTDT ) with initial methotrexate ( MTX ) monotherapy ( iMM ) and ( 2 ) different glucocorticoid ( GC ) bridging therapies : oral versus a single intramuscular injection in early rheumatoid arthritis .


In a single-blinded randomised clinical trial patients were randomised into three arms : ( A ) iTDT ( methotrexate + sulfasalazine + hydroxychloroquine ) with GCs intramuscularly ; ( B ) iTDT with an oral GC tapering scheme and ( C ) MTX with oral GCs similar to B. Primary outcomes were ( 1 ) area under the curve ( AUC ) of Health Assessment Questionnaire ( HAQ ) and Disease Activity Score ( DAS ) and ( 2 ) the proportion of patients with radiographic progression .


281 patients were randomly assigned to arms A ( n = 91 ) , B ( n = 93 ) or C ( n = 97 ) .


The AUC DAS and HAQ were respectively -2.39 ( 95 % CI -4.77 to -0.00 ) and -1.67 ( 95 % CI -3.35 to 0.02 ) lower in patients receiving iTDT than in those receiving iMM .


After 3 months , treatment failure occurred less often in the iTDT group , resulting in 40 % fewer treatment intensifications .


The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time .


No differences were seen between the two GC bridging therapies .


Respectively 21 % , 24 % and 23 % of patients in arms A , B and C had radiographic progression after 1 year .


Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM .


Treatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM .


However , no difference in radiographic progression is seen .


Both GC bridging therapies are equally effective and , therefore , both can be used .


ISRCTN26791028 .


Cysteine proteinases ( CPs ) from papaya ( Carica papaya ) possess anthelmintic properties against human soil-transmitted helminths ( STH , Ascaris lumbricoides , Trichuris trichiura and hookworm ) , but there is a lack of supportive and up-to-date efficacy data .


We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis .


First , we assessed efficacy by means of egg ( ERR ) and adult worm reduction rate ( WRR ) of a single-oral dose of 450 mol active CPs ( CP450 ) against low ( inoculum of 300 eggs ) and high ( inoculum of 3,000 eggs ) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole ( ALB ) .


In the second trial , we determined and compared the efficacy of a series of CP doses ( 45 [ CP45 ] , 115 [ CP115 ] , 225 [ CP225 ] , and 450 [ CP450 ] mol ) against high intensity infections .


CP450 was highly efficacious against both levels of infection intensity , resulting in ERR and WRR of more than 97 % .


For both levels of infection intensity , CP450 was significantly more efficacious compared to ALB by means of WRR ( low infection intensity : 99.0 % vs. 39.0 % ; high infection intensity ; 97.4 % vs. 23.2 % ) .


When the efficacy was assessed by ERR , a significant difference was only observed for high intensity infections , CP450 being more efficacious than ALB ( 98.9 % vs. 59.0 % ) .


For low infection intensities , there was no significant difference in ERR between CP450 ( 98.3 % ) and ALB ( 64.4 % ) .


The efficacy of CPs increased as a function of increasing dose .


When determined by ERR , the efficacy ranged from 2.1 % for CP45 to 99.2 % for CP450 .


For WRR the results varied from -14.0 % to 99.0 % , respectively .


Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450 , the latter being more efficacious .


A single dose of 450 mol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB .


Although these results highlight the possibility of papaya CPs for controlling human STH , further development is needed in order to obtain and validate an oral formulation for human application .


School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects .


However , there is a striking paucity on long-term follow-ups .


The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-randomized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat , aerobic fitness and physical activity .


Initially , 28 classes from 15 elementary schools in Switzerland were grouped into an intervention ( 16 classes from 9 schools , n = 297 children ) and a control arm ( 12 classes from 6 schools , n = 205 children ) after stratification for grade ( 1st and 5th graders ) .


Three years after the end of the multi-component physical activity program of nine months including daily physical education ( i.e. two additional lessons per week on top of three regular lessons ) , short physical activity breaks during academic lessons , and daily physical activity homework , 289 ( 58 % ) participated in the follow-up .


Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( questionnaires ) .


After adjustment for grade , gender , baseline value and clustering within classes , children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up ( 0.373 z-score units [ 95 % - CI : 0.157 to 0.59 , p = 0.001 ] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up ) , while the immediate beneficial effects on the other primary outcomes were not sustained .


Apart from aerobic fitness , beneficial effects seen after one year were not maintained when the intervention was stopped .


A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention .


ControlledTrials.com ISRCTN15360785 .


The objective of this study was to investigate functional results , the amount of time that patients missed from regular working activities , and the incidence of residual mechanical ankle instability following conservative treatment of a first episode of severe lateral ankle ligament sprain ( with articular instability ) .


This prospective and randomized study included 186 patients with severe lateral ankle ligament injuries , who were randomly assigned into 2 conservative treatment groups .


In group A , participants were treated with a walking boot with weight-bearing allowed , pain management , ice , and elevation with restricted joint mobilization for 3 weeks .


In group B , patients were treated with a functional brace for 3 weeks .


After this period , patients from both groups were placed in a short , functional brace for an additional 3 weeks , during which they also started a rehabilitation program .


No statistically significant difference was found in pain intensity score between the 2 groups ; however , functional evaluations based on the AOFAS ankle and hindfoot score system showed a statistically significant improvement in the group treated with the functional brace .


In addition , the average recovery period necessary for patients of group B to resume their duties was shorter than that for patients in group A. No significant difference was detected in residual mechanical ankle instability between the 2 groups .


Patients with severe lateral ankle ligament lesions treated with a functional brace were shown to exhibit somewhat better results than those treated with a walking boot , and both methods presented a very low incidence of residual chronic instability .


We found adequate conservative treatment was sufficient to reestablish ankle stability and that functional treatment had a marginally better clinical short-term outcome with a shorter average recovery period .


Level I , prospective randomized study .


Efforts to reduce risk of tuberculosis disease in children include development of effective vaccines .


Our aim was to test safety and immunogenicity of the new adenovirus 35-vectored tuberculosis vaccine candidate AERAS-402 in infants , administered as a boost following a prime with the Bacille Calmette-Guerin vaccine .


In a phase 1 randomised , double-blind , placebo-controlled , dose-escalation trial , BCG-vaccinated infants aged 6-9 months were sequentially assigned to four study groups , then randomized to receive an increasing dose-strength of AERAS-402 , or placebo .


The highest dose group received a second dose of vaccine or placebo 56 days after the first .


The primary study outcome was safety .


Whole blood intracellular cytokine staining assessed immunogenicity .


Forty-two infants received AERAS-402 and 15 infants received placebo .


During follow-up of 182 days , an acceptable safety profile was shown with no serious adverse events or discontinuations related to the vaccine .


AERAS-402 induced a specific T cell response .


A single dose of AERAS-402 induced CD4T cells predominantly expressing single IFN - whereas two doses induced CD4T cells predominantly expressing IFN - , TNF - and IL-2 together .


CD8T cells were induced and were more likely to be present after 2 doses of AERAS-402 .


AERAS-402 was safe and immunogenic in healthy infants previously vaccinated with BCG at birth .


Administration of the highest dose twice may be the most optimal vaccination strategy , based on the induced immunity .


Multiple differences in T cell responses when infants are compared with adults vaccinated with AERAS-402 , in the same setting and using the same whole blood intracellular cytokine assay , suggest specific strategies may be important for vaccination for each population .


Endoscopic ultrasound fine needle aspiration has a central role in the diagnostic algorithm of solid pancreatic masses .


Data comparing the fine needle aspiration performed with different aspiration volume and without aspiration are lacking .


We compared endoscopic ultrasound fine needle aspiration performed with the 22 gauge needle with different aspiration volumes ( 10 , 20 and 0 ml ) , for adequacy , diagnostic accuracy and complications .


Prospective clinical study at four referral centres .


Endoscopic ultrasound fine needle aspiration was performed with a 22G needle with both volume aspiration ( 10 and 20 cc ) and without syringe , in randomly assigned sequence .


The cyto-pathologist was blinded as to which aspiration was used for each specimen .


100 patients met the inclusion criteria , 88 completed the study .


The masses had a mean size of 32.2111.24 mm .


Sample adequacy evaluated on site was 87.5 % with 20 ml aspiration vs. 76.1 % with 10 ml ( p = 0.051 ) , and 45.4 % without aspiration ( 20 ml vs. 0 ml p < 0.001 ; 10 ml vs. 0 ml p < 0.001 ) .


The diagnostic accuracy was significantly better with 20 ml than with 10 ml and 0 ml ( 86.2 % vs. 69.0 % vs. 49.4 % p < 0.001 ) .


A significantly higher adequacy and accuracy were observed with the 20 ml aspiration puncture , therefore performing all passes with this volume aspiration may improve the diagnostic power of fine needle aspiration .


Mutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC .


This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab ( mitomycin C ) in the randomised phase III MAX study .


DNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue .


Mutation status was determined using pyrosequencing , confirmed with Sanger sequencing ( for equivocal RAS ) and correlated with efficacy outcomes .


Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM .


Of the available 280 of the 471 ( 59.4 % ) patients , mutations in KRAS exons 2 , 3 and 4 and NRAS 2 , 3 and 4 were as follows : 32 % , 2.9 % , 2.2 % , 1.4 % , 0.7 % and 0 % ( total RAS MT 39 % ) .


The PIK3CA MT rate was 7.5 % exon 9 and 3.6 % exon 20 .


Extended RAS gene mutation status ( WT vs MT ) had no prognostic impact for PFS ( HR 0.91 ( 0.71-1 .17 ) ) or OS ( HR 0.95 ( 0.71-1 .25 ) ) .


The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS ( HR 0.56 ( 0.37-0 .85 ) for RAS MT and HR 0.69 ( 0.5-0 .97 ) for RAS WT ; P for interaction 0.50 ) .


The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic .


Of KRAS exon 2 WT patients , 10 % had additional RAS mutations .


Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS , or predictive of bevacizumab outcome in patients with advanced CRC .


In the present study , we calculated the success rate of the modified Epley maneuver and determined the effectiveness of post-maneuver positional restriction in terms of the prevention of early and late recurrence .


The present study was conducted on 78 patients who had unilateral benign paroxysmal positional vertigo ( BPPV ) of the posterior semicircular canal ( SCC ) and who were treated in the Otorhinolaryngology Department of Susehri State Hospital .


The Dix-Hallpike test was performed on all patients .


After the involved canal was identified using this test , we guided patients through the modified Epley repositioning maneuver .


A maximum of two maneuvers were performed in the same session .


The patients were randomly divided into two groups .


One group was not advised any positional restriction , while the second group was advised positional restriction for 10 days after the procedure .


Recurrences during 1-90 days after the treatment were noted as early recurrences , while those that occurred after 90 days were noted as late recurrences .


In the restriction group ( n = 39 ) , repositioning was successful after a single maneuver in 32 ( 82.05 % ) patients and after two maneuvers in 5 ( 12.8 % ) patients .


Repositioning failed in two ( 5.1 % ) patients .


In the non-restriction group ( n = 39 ) , repositioning was successful after a single maneuver in 31 ( 79.4 % ) patients and after two maneuvers in 6 ( 15.3 % ) patients .


Thus , the success rate was 94.8 % in each group .


Early recurrence occurred in 3 ( 8.1 % ) of 37 patients in the restriction group and 2 ( 5.4 % ) of 37 patients in the non-restriction group ( p > 0.05 ) .


Late recurrence occurred in 5 ( 13.5 % ) of 37 patients in both the restriction and non-restriction groups ( p > 0.05 ) .


Postural restriction after a canalith repositioning procedure does not improve procedural success or decrease early and late recurrence rates .


However , the number of patients was too small to detect a difference between both treatment groups .


Ethanol rapidly eradicated experimental biofilm .


Clinical studies of ethanol lock to prevent catheter-related infections ( CRIs ) suggest preventive efficacy .


No such studies have been done in intensive care units ( ICU ) .


To determine whether ethanol lock decreases the risk of major CRI in patients with short-term dialysis catheters ( DCs ) .


A randomized , double-blind , placebo-controlled trial was performed in 16 ICUs in seven university hospitals and one general hospital in France between June 2009 and December 2011 .


Adults with insertion of a nontunneled , nonantimicrobial-impregnated double-lumen DC for an expected duration greater than 48 hours , to perform renal-replacement therapy or plasma exchange , were randomly allocated ( 1:1 ) to receive a 2-minute catheter lock with either 60 % wt/wt ethanol solution ( ethanol group ) or 0.9 % saline solution ( control group ) at the end of DC insertion and after each renal-replacement therapy or plasma exchange session .


The main outcome was major CRI defined as either catheter-related clinical sepsis without bloodstream infection or catheter-related bloodstream infection during the ICU stay .


The intent-to-treat analysis included 1,460 patients ( 2,172 catheters , 12,944 catheter-days , and 8,442 study locks ) .


Median DC duration was 4 days ( interquartile range , 2-8 ) and was similar in both groups .


Major CRI incidence did not differ between the ethanol and control groups ( 3.83 vs. 2.64 per 1,000 catheter-days , respectively ; hazard ratio , 1.55 ; 95 % confidence interval , 0.83-2 .87 ; P = 0.17 ) .


No significant differences occurred for catheter colonization ( P = 0.57 ) or catheter-related bloodstream infection ( P = 0.99 ) .


A 2-minute ethanol lock does not decrease the frequency of infection of DCs in ICU patients .


Clinical trial registered with www.clinicaltrials.gov ( NCT 00875069 ) .


Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose , and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets .


Children with nutritional rickets ( age : 0.5-5 years , n = 61 ) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection .


Serum calcium , phosphate , alkaline phosphatase , urinary calcium/creatinine ratio , serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up .


No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters .


Serum 25 hydroxy vitamin D > 100 ng/ml was found in two children in the oral group and one child in the intramuscular group .


No child developed hypercalcemia or hypercalciuria after starting treatment .


Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets .


Psychiatric disorders are common among patients with irritable bowel syndrome ( IBS ) which may make a psychiatric evaluation appropriate .


The Hospital Anxiety and Depression Scale ( HADS ) has been recommended internationally for screening .


The Common Mental Disorder Questionnaire ( CMDQ ) is a novel Danish instrument recommended for use in general practice , but it lacks validation .


The objective of this study was to test the reliability and the convergent validity of the anxiety and depression subscales of the CMDQ and the HADS in patients with IBS .


A total of 149 patients with IBS completed the CMDQ and the HADS twice in a year .


Data were analysed with respect to internal consistency ( Cronbach 's alpha ) , agreement on case identification ( ) and correlation between scores ( Spearman 's rank correlation coefficient ) .


All subscales showed satisfactory internal consistency .


Cases identified by the CMDQ 's anxiety and depressions subscales differed considerably from those identified with the HADS with only fair-moderate agreement , while the correlation between the scores on the CMDQ and the HADS was only moderate for both anxiety and depressions .


The subscales for anxiety disorder and depression on the CMDQ showed internal consistency , but only fair to moderate agreement and correlation , which yielded an unsatisfying convergent validity compared to the HADS .


More studies in different populations and research on the cut-off values for possible cases could make the CMDQ more useful .


Danish Council for Independent Research ; Region Zealand 's Health Sciences Research Foundation ; Councils for Quality Assurance in Primary Care in Region Zealand .


NCT00659763 .


Delayed ischemic neurological deficits ( DINDs ) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage .


In this trial , we investigated the therapeutic potential of prostacyclin , an endogen substance with known effect on vascular tone and blood flow regulation , on factors related to DIND .


This trial is a single-center , randomized , blinded , clinical , pilot trial with 3 arms .


Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute , prostacyclin 2 ng/kg per minute , or placebo .


The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10 .


Primary outcome was the difference in change from baseline in global cerebral blood flow .


Secondary outcome measures were occurrence of DIND , angiographic vasospasm , and clinical outcome at 3 months .


No statistically significant difference in change of global cerebral blood flow was found between the intervention groups .


The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group , although this difference was not statistically significant .


No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups .


Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible .


Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range .


It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes .


http://www.clinicaltrials.gov .


Unique identifier : NCT01447095 .


Although the use of drug-eluting stents ( DESs ) in patients with coronary artery disease has contributed to a significant reduction in in-stent restenosis and repeat revascularization , treating diffuse long lesions using DESs remains challenging due to the high rates of in-stent restenosis and stent thrombosis .