Delayed hemolysis has been described in hyperparasitemic nonimmune travelers , but it is unknown if African children are equally at risk .


Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambarn , Gabon , and Kumasi , Ghana .


The primary outcome was incidence of delayed hemolysis on day 14 .


In total , 72 children contributed complete data sets necessary for primary outcome assessment .


Delayed hemolysis was detected in 5 children ( 7 % ) , with 1 child reaching a nadir in hemoglobin of 2.8 g/dL .


Patients with delayed hemolysis had higher parasite counts on admission ( geometric mean parasite densities ( GMPD ) 306 968/L vs 92 642/L , P = .028 ) and were younger ( median age : 24 months vs 43 months , P = .046 ) than the rest of the cohort .


No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed .


Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria .


Physicians should be aware of this complication and consider prolonged follow-up .


Pan-African Clinical Trials Registry : PACTR201102000277177 ( www.pactr.org ) .


Increased arterial stiffness as measured by aortic pulse wave velocity ( aPWV ) predicts cardiovascular events and mortality and is elevated in patients with COPD .


Prior investigation suggests that a long-acting - agonist ( LABA ) / inhaled corticosteroid ( ICS ) lowers aPWV in patients with baseline aPWV 11 m/s .


This study compared the effect of the ICS/LABA fluticasone furoate/vilanterol ( FF/VI ) , 100/25 g , delivered via the ELLIPTA dry powder inhaler , with tiotropium bromide ( TIO ) , 18 g , on aPWV .


This multicenter , randomized , blinded , double-dummy , parallel-group , 12-week study compared FF/VI and TIO , both administered once daily .


The primary end point was aPWV change from baseline at 12 weeks .


Safety end points included adverse events ( AEs ) , vital signs , and clinical laboratory tests .


Two hundred fifty-seven patients with COPD and aPWV 11 m/s were randomized ; 87 % had prior cardiovascular events and/or risk .


The mean difference in aPWV between FF/VI and TIO at week 12 was not significant ( P = .484 ) .


Because the study did not contain a placebo arm , a post hoc analysis was performed to show that both treatments lowered aPWV by an approximate difference of 1 m/s compared with baseline .


The proportion of patients reporting AEs was similar with FF/VI ( 24 % ) and TIO ( 18 % ) .


There were no changes in clinical concern for vital signs or clinical laboratory tests .


No differences on aPWV were observed between FF/VI and TIO .


However , further studies with a placebo arm are required to establish definitively whether long-acting bronchodilators lower aPWV .


Both treatments demonstrated an acceptable tolerability profile .


ClinicalTrials.gov ; No. : NCT01395888 ; URL : www.clinicaltrials.gov .


Vandetanib is a selective inhibitor of vascular endothelial growth factor receptor ( VEGFR ) , epidermal growth factor receptor ( EGFR ) and rearranged during transfection ( RET ) signalling , indicated for the treatment of medullary thyroid cancer .


We investigated potential drug-drug interactions between vandetanib and metformin [ organic cation transporter 2 ( OCT2 ) substrate ; NCT01551615 ] ; digoxin [ P-glycoprotein ( P-gp ) substrate ; NCT01561781 ] ; midazolam [ cytochrome P450 ( CYP ) 3A4 substrate ; NCT01544140 ] ; omeprazole ( proton pump inhibitor ) or ranitidine ( histamine H2-receptor antagonist ; both NCT01539655 ) .


Four open-label , phase I studies were conducted in healthy volunteers : n = 14 ( metformin ) , n = 14 ( digoxin ) , n = 17 ( midazolam ) , n = 16 ( omeprazole ) , n = 18 ( ranitidine ) .


Three of these comprised the following regimens : metformin 1000mgvandetanib 800mg , midazolam 7.5 mgvandetanib 800mg , or digoxin 0.25 mgvandetanib 300mg .


The randomized study comprised vandetanib 300mg alone and then either ( i ) omeprazole 40mg ( days 1-4 ) , and omeprazole + vandetanib ( day 5 ) ; or ( ii ) ranitidine 150mg ( day 1 ) , and ranitidine + vandetanib ( day 2 ) .


The primary objective assessed metformin , digoxin , midazolam and vandetanib pharmacokinetics .


Vandetanib + metformin increased metformin area under the plasma concentration-time curve from zero to infinity ( AUC0 - ) and maximum observed plasma concentration ( Cmax ) by 74 and 50 % , respectively , and decreased the geometric mean metformin renal clearance ( CLR ) by 52 % versus metformin alone .


Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration ( AUC0-last ) and Cmax by 23 and 29 % , respectively , versus digoxin alone , with only a 9 % decrease in CLR .


Vandetanib had no effect on midazolam exposure .


Vandetanib exposure was unchanged during co-administration with omeprazole/ranitidine .


Treatment combinations were generally well tolerated .


Patients receiving vandetanib with metformin/digoxin may require additional monitoring of metformin/digoxin , with dose adjustments where necessary .


Vandetanib with CYP3A4 substrates or omeprazole/ranitidine is unlikely to result in clinically relevant drug-drug interactions .


To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus ( T2DM ) .


This double-blind study randomized 267 uncontrolled type 2 diabetes patients ( HbA1c 7.5 % and 11.5 % ) , post 3 months ' treatment with glimepiride/gliclazide and metformin , to additionally receive hydroxychloroquine 400mg/day ( n = 135 ) or pioglitazone 15mg/day ( n = 132 ) for 24 weeks .


Efficacy was assessed by changes in HbA1c , fasting ( FBG ) and post-prandial ( PPG ) blood glucose at Week 12 and Week 24 .


At Week 12 and Week 24 , HbA1c , FBG and PPG significantly reduced from baseline in both groups .


Mean reduction in glycemic parameters at Week 12 ( HbA1c : -0.56 % vs -0.72 % , p = 0.394 ; FBG : -0.99 mmol/L vs -1.05 mmol/L , p = 0.878 ; PPG : -1.93 mmol/L vs -1.52 mmol/L , p = 0.423 ) and Week 24 ( HbA1c : -0.87 % vs -0.90 % , p = 0.909 ; FBG : -0.79 mmol/L vs -1.02 mmol/L , p = 0.648 ; PPG : -1.77 mmol/L vs -1.36 mmol/L , p = 0.415 ) was not significantly different between the hydroxychloroquine and pioglitazone groups .


Change in total cholesterol ( TC ) and LDL-C was significant in favor of hydroxychloroquine ( TC : -0.37 mmol/L vs 0.03 mmol/L , p = 0.002 ; LDL-C : -0.23 mmol/L vs 0.09 mmol/L , p = 0.003 ) .


Triglycerides significantly reduced in both groups at Week 24 .


Mean HDL-C remained unchanged .


Study treatments were well tolerated .


With favorable effects on glycemic parameters and lipids , hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM .


The sample size for this study was small .


However , based on the encouraging results of this proof-of-concept study , longer duration studies in larger population can be conducted to further confirm these findings .


TRIAL REGISTRATION DETAILS : Clinical Trial Registry-India URL : http://ctri.nic.in , Registration Number : CTRI/2009/091 / 001036 .


Swirling flow , organized in vortices , contributes to adequate left ventricular function .


In this study , we apply a novel echocardiographic flow-mapping technique , vector flow mapping ( VFM ) , to evaluate the main characteristics of left ventricular vortices and its relation to filling parameters .


Forty-eight subjects underwent conventional transthoracic echocardiographic examination with additional intracardiac flow assessment with VFM using a Aloka Alpha-10 system and experimental VFM analysis software .


To analyze vortex behavior , its rotation direction , duration , location inside the left ventricle , size , and intensity were assessed in apical long-axis view .


Its relation to conventional left ventricular filling parameters was then analyzed .


Two vortex components were consistently identified following each transmitral filling wave .


The anterior component of these visualized vortices was analyzed , due to its higher significance in the cardiac cycle , following early filling ( V1 ) and atrial contraction ( V2 ) .


Differences were observed in several aspects of vortex behavior between V1 and V2 , particularly in patients with normal left ventricular filling parameters .


These differences may be related to varying roles of vortices in different periods of the cardiac cycle .


Vector flow mapping allowed visualization and measurement of several parameters defining vortex behavior inside the cardiac cycle .


The differences observed in these parameters between vortices in different phases of the cardiac cycle may be related to their role in optimizing cardiac function .


Assess golimumab efficacy/safety through 5years in patients with active ankylosing spondylitis ( AS ) .


356 patients with AS were randomly assigned to placebo , golimumab 50mg or 100mg every 4weeks .


At week 16 , patients with inadequate response early escaped with blinded dose adjustments ( placebo to 50mg , 50mg to 100mg ) .


At week 24 , all patients receiving placebo crossed over to 50mg .


Blinded active therapy continued through week 104 ; from week 104 to week 252 , the golimumab dose could be adjusted .


Intent-to-treat and observed efficacy data were assessed by randomised treatment groups .


At week 256 , and with > 4.5 years of golimumab , overall intent-to-treat Assessment in SpondyloArthritis international Society criteria for 20 % improvement ( ASAS20 ) and ASAS40 response rates were 66.0 % ( 235/356 ) and 57.0 % ( 203/356 ) , respectively ; Bath AS Disease Activity Index 50 % improvement response was 55.9 % ( 199/356 ) .


Observed response rates among the 255 ( 72 % ) patients who continued golimumab through week 252 were consistent , albeit somewhat higher .


Among patients who increased golimumab from 50 to 100mg , 60.6 % ( 20/33 ) and 44.7 % ( 17/38 ) achieved ASAS20/ASAS40 responses , respectively , following 2 consecutive doses of golimumab 100mg .


Golimumab safety through week 268 was similar to that through week 24 regardless of dose .


Clinical improvements observed in patients treated with golimumab through week 24 were sustained through week 256 ( 5years ) .


Long-term golimumab safety is consistent with that of other established tumour-necrosis-factor-antagonists .


ClinicalTrials.gov : NCT00265083 .


Attention-Deficit/Hyperactivity Disorder ( ADHD ) in adults is one of the predictive and treatable risk factors for delinquency , including intimate partner violence ( IPV ) .


Effective treatment of IPV needs to address personal dynamic risk factors , offender typology , and dynamics of the domestic violence .


It is unknown whether treatment of ADHD symptoms contributes to a decrease in IPV .


The ITAP study aims to investigate the relationship between treatment of ADHD symptoms and IPV in patients in forensic mental health care .


Moreover , this study examines the role of comorbid psychopathology , subtype of the offender , and dynamics of the domestic violence .


The ITAP study is a longitudinal observational study .


Participants are followed one year through various assessments : one before starting treatment ( t0 ) , and four during treatment ( 8 , 16 , 24 and 52 weeks after start of the treatment ) .


All participants receive treatment for IPV , ADHD , and comorbid psychopathology , if present .


The primary outcome measure is the change in severity of IPV ; the primary predictive variable is the change in severity of ADHD symptoms .


The secondary outcome measure is the observation of the therapist about change in the offender 's general violent behaviour , within and outside the partner relationship .


Data are analysed in a multiple regression model with change in severity of IPV as the dependent variable and change in severity of ADHD symptoms as the primary predictor .


Other predictive variables taken into account in the analyses are presence of comorbid psychopathology and personality disorder , subtype of the offender , and dynamics of the domestic violence .


In addition , compliance with treatment and content of the treatment are documented .


Research on the treatment process of IPV offenders and victims is complicated by many factors .


This observational design will not allow inferences about causality but may reveal clinically important factors that contribute to more effective treatment of IPV .


The Netherlands National Trial Register ( NTR ) , trial ID NTR3887 .


Nitrogen dioxide ( NO2 ) , a ubiquitous atmospheric pollutant , may enhance the asthmatic response to allergens through eosinophilic activation in the airways .


However , the effect of NO2 on inflammation without allergen exposure is poorly studied .


We investigated whether repeated peaks of NO2 , at various realistic concentrations , induce changes in airway inflammation in asthmatics .


Nineteen nonsmokers with asthma were exposed at rest in a double-blind , crossover study , in randomized order , to 200 ppb NO2 , 600 ppb NO2 , or clean air once for 30 min on day 1 and twice for 30 min on day 2 .


The three series of exposures were separated by 2 weeks .


The inflammatory response in sputum was measured 6 hr ( day 1 ) , 32 hr ( day 2 ) , and 48 hr ( day 3 ) after the first exposure , and compared with baseline values measured twice 10-30 days before the first exposure .


Compared with baseline measurements , the percentage of eosinophils in sputum increased by 57 % after exposure to 600 ppb NO2 ( p = 0.003 ) but did not change significantly after exposure to 200 ppb .


The slope of the association between the percentage of eosinophils and NO2 exposure level was significant ( p = 0.04 ) .


Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 ( p = 0.001 ) .


Lung function , which was assessed daily , was not affected by NO2 exposure .


We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner .


Musculoskeletal pain is a major contributor to short and long term work absence .


Patients seek care from their general practitioner ( GP ) and yet GPs often feel ill-equipped to deal with work issues .


Providing a vocational case management service in primary care , to support patients with musculoskeletal problems to remain at or return to work , is one potential solution but requires robust evaluation to test clinical and cost-effectiveness .


This protocol describes a cluster randomised controlled trial , with linked qualitative interviews , to investigate the effect of introducing a vocational advice service into general practice , to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work .


General practices ( n = 6 ) will be randomised to offer best current care or best current care plus a vocational advice service .


Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited .


Data collection will be through patient completed questionnaires at baseline , 4 and 12 months .


The primary outcome is self-reported work absence at 4 months .


Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits .


A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs , nurse practitioners ( NPs ) , patients and vocational advisors .


This paper presents the rationale , design , and methods of the Study of Work And Pain ( SWAP ) trial .


The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues .


Current Controlled Trials ISRCTN52269669 .


To investigate whether prophylactic postoperative NIV prevents respiratory complications following lung resection surgery in COPD patients .


In seven thoracic surgery departments , 360 COPD patients undergoing lung resection surgery were randomly assigned to two groups : conventional postoperative treatment without ( n = 179 ) or with ( n = 181 ) prophylactic NIV , applied intermittently during 6 h per day for 48 h following surgery .


The primary endpoint was the rate of acute respiratory events ( ARE ) at 30 days postoperatively ( ITT analysis ) .


Secondary endpoints were acute respiratory failure ( ARF ) , intubation rate , mortality rate , infectious and non-infectious complications , and duration of ICU and hospital stay .


ARE rates did not differ between the prophylactic NIV and control groups ( 57/181 , 31.5 vs. 55/179 , 30.7 % , p = 0.93 ) .


ARF rate was 18.8 % in the prophylactic NIV group and 24.5 % in controls ( p = 0.20 ) .


Re-intubation rates were similar in the prophylactic NIV and control group [ 10/181 ( 5.5 % ) and 13/179 ( 7.2 % ) , respectively , p = 0.53 ] .


Mortality rates were 5 and 2.2 % in the control and prophylactic NIV groups , respectively ( p = 0.16 ) .


Infectious and non-infectious complication rates , and duration of ICU and hospital stays were similar between groups .


Prophylactic postoperative NIV did not reduce the rate of ARE in COPD patients undergoing lung resection surgery and did not influence other postoperative complications rates , mortality rates , and duration of ICU and hospital stay .


Aspirin exacerbated respiratory disease ( AERD ) is comprised of aspirin/acetylsalicylic acid ( ASA ) sensitivity , bronchial asthma , and nasal polyposis .


Treatment of this condition is challenging and may include topical/systemic steroids , endoscopic sinus surgery , and/or aspirin desensitization .


A prospective crossover pilot study ( n = 10 ) was conducted in which patients were randomized into either of 2 groups with 6 weeks of regular diet ( R ) or 6 weeks of a low salicylate diet ( LS ) .


The study was conducted in a tertiary otolaryngology clinic .


Patients with AERD were enrolled in the study .


Subjective ( Sino-nasal Outcome Test-22 [ SNOT-22 ] , Nasal Sinus Symptom Scale [ NSSS ] , and the Asthma Control Questionnaire-7 [ ACQ-7 ] ) and objective outcome instruments ( Peri-Operative Sinus Evaluation [ POSE ] and Lund-Kennedy Endoscopic Score [ LKES ] ) were used to evaluate patients at baseline , 6 weeks ( at crossover ) , and 12 weeks .


Wilcoxon rank sum tests demonstrated that patients on the low salicylate diet had improved scores compared to their regular diet when evaluated by 4 of the 5 outcome measures ( SNOT-22 pLS = 0.0059 , NSSS pLS = 0.0195 , LKES pLS = 0.0039 , POSE pLS = 0.005 ) .


Results of the pilot study indicate that implementation of a low salicylate diet improves the nasal symptoms and nasal endoscopy findings of individuals with AERD .


Further research is required to support these findings .


Although the standard treatment for venous ulcers is compression , drugs may be used as adjunctive therapy .


Simvastatin has shown potential wound-healing properties ; however , no studies have investigated its use in venous ulcers .


To assess the efficacy and safety of simvastatin in venous ulcer healing when combined with standard treatment for ulcers .


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


Outcome measures were the proportion of healed ulcers , healing time , total surface area healed and Dermatology Life Quality Index ( DLQI ) scores .


Sixty-six patients were randomized into two groups : a simvastatin ( n = 32 ) and a control ( n = 34 ) group .


Among ulcers 5cm , 100 % were healed in the simvastatin group , and 50 % were healed in the control group [ relative risk ( RR ) 010 , 95 % confidence interval ( CI ) 00141-0707 ] .


The average healing times for ulcers 5cm were 689078weeks and 840113weeks for the simvastatin and control groups , respectively ( P < 0001 ) .


Among ulcers > 5cm , 67 % closed in the simvastatin group , with a mean healing time of 917107weeks .


No ulcers of this size closed in the control group ( RR 033 , 95 % CI 0132-0840 ) .


The simvastatin group had lower DLQI scores ( P < 0001 ) post-treatment .


No adverse effects were documented .


Simvastatin 40mg daily , in addition to standard wound care and compression , is associated with a significant improvement in healing rate and time , as well as an improved patient quality of life when compared with placebo in the management of venous ulcers .


How platelet ( PLT ) product characteristics such as dose , source ( whole blood derived [ WBD ] vs. apheresis ) , storage duration , and ABO matching status affect the risks of transfusion-related adverse events ( TRAEs ) is unclear .


Similarly , more information is needed to define how recipient characteristics affect the frequency of TRAEs after PLT transfusion .


In the multicenter Platelet Dose ( `` PLADO '' ) study , pediatric and adult hematology-oncology patients with hypoproliferative thrombocytopenia were randomized to receive low-dose ( LD ) , medium-dose ( MD ) , or high-dose ( HD ) PLT prophylaxis for a pretransfusion PLT count of not more than 1010 ( 9 ) / L. All PLT units ( apheresis or WBD ) were leukoreduced .


Post hoc analyses of PLADO data were performed using multipredictor models .


A total of 5034 PLT transfusions to 1102 patients were analyzed .


A TRAE occurred with 501 PLT transfusions ( 10.0 % ) .


The most common TRAEs were fever ( 6.6 % of transfusions ) , allergic or hypersensitivity reactions ( 1.9 % ) , and sinus tachycardia ( 1.8 % ) .


Patients assigned HD PLTs were more likely than LD or MD patients to experience any TRAE ( odds ratio for HD vs. MD , 1.50 ; 95 % confidence interval , 1.10-2 .05 ; three-group comparison p = 0.02 ) .


PLT source and ABO matching status were not significantly related to overall TRAE risk .


Compared to a patient 's first PLT transfusion , subsequent PLT transfusions were less likely to have a TRAE reported , primarily due to a lower risk of allergic or hypersensitivity reactions .


The most important PLT unit characteristic associated with TRAEs was PLT dose per transfusion .


HD PLTs may increase the risk of TRAEs , and LD PLTs may reduce the risk .


Epilepsy is a complex chronic disorder which affects health-related quality of life ( HRQOL ) , especially in women .


This study is a pragmatic randomised controlled trial involving women with epilepsy ( WWE ) over 18 years of age .


One hundred eighty-two WWE entered the study and 144 ( 79.1 % ) completed it .


The t-test for comparing the final QOLIE-31 scores between groups yielded a t = -2.166 and confidence interval ( CI ) ( 95 % ) : -10.125 ; -0.4625 , p-value = 0.0319 .


The change ( ) in the QOLIE-31 score for the IG was 12.45 points ( p-value < 0.001 ) and for the control group it was 2.61 ( p-value = 0.072 ) .


With 10.7 as the minimally important change we found a relative risk of 2.17 ( CI : 1.37 ; 3.43 ) and a number needed to treat ( NNT ) of 3.5 .


The study demonstrated that the application of a pharmaceutical care programme significantly improves HRQOL in WWE .


The NNT we found allows a recommendation to implement the PC programme for the additional benefit that would be obtained in patients ' HRQOL .


Current Controlled Trials ISRCTN46864306 IPHIWWE study .


To determine the effect of moderate-intensity aerobic exercise on the quality of life ( QOL ) and physical functioning in breast cancer survivors .


We randomly assigned 62 breast cancer survivors to an exercise ( N = 30 ) or control group ( N = 32 ) .


The exercise group trained at a moderate intensity progressing from 25 to 40 min over a 10-week period .


The control group did not train .


Outcomes were assessed at baseline and postintervention .


The primary outcomes were overall QOL -- as assessed by the functional assessment of cancer therapy-breast ( FACT-B ) scale .


Secondary outcomes were changes in various subscales of overall QOL , and changes in body composition outcomes : body weight , body mass index , and changes in performance in a 12 min walk test ( 12MWT ) .


Sixty-two of 73 women randomized ( 84.9 % ) completed the study .


There were no significant differences amongst the two groups at baseline for any variable .


In the exercise group significant improvements were demonstrated for the FACT-B ( 13.4 points , P < 0.003 ) , functional assessment of cancer therapy-general ( FACT-G ) ( 9.16 points , P < 0.008 ) , the functional well-being subscale ( P < 0.010 ) , and the emotional well-being subscale ( P < 0.035 ) compared to the control group .


No significant changes in body weight or BMI were observed .


Exercise group showed a significant increase in 12MWT ( P < 0.009 ) .


We conclude that 10 week of moderate-intensity aerobic exercise program significantly improves QOL and physical functioning in breast cancer survivors .


Future studies are needed to evaluate the effectiveness of similar exercise programs over longer periods of time and involving a greater number of breast cancer survivors .


The most common technique for posterior cruciate ligament ( PCL ) reconstruction is transtibial or tibial inlay .


However , few studies have reported long-term outcome comparisons between the 2 techniques .


Tibial inlay PCL reconstruction with patellar tendon autograft will exhibit better clinical and radiographic outcomes than transtibial PCL reconstruction with hamstring autograft .


Cohort study ; Level of evidence , 3 .


A total of 66 patients ( 66 knees ) treated with PCL reconstruction for chronic injuries constituted the study cohort .


Patients were divided into 2 groups : transtibial with hamstring ( 36 patients ) and tibial inlay with patellar tendon ( 30 patients ) .


The mean time from injury to reconstruction was 12.2 months ( range , 2-60 months ) , and the mean follow-up was 148 months ( range , 98-196 months ) .


Outcomes were measured by use of Lysholm knee scores , Tegner activity scores , return to preinjury sports activity , posterior drawer test , laxity test with a Telos device , and development of osteoarthritis .


The preoperative mean Lysholm knee score was 59.9 ( range , 37-70 ) in the transtibial group and 54.5 ( range , 22-76 ) in the tibial inlay group , improving postoperatively to 89.9 ( range , 74-100 ) and 92.1 ( range , 80-100 ) , respectively .


The mean Tegner activity scores increased from 2.5 ( range , 2-5 ) to 5.9 ( range , 4-7 ) in the transtibial group and 2.3 ( range , 2-4 ) to 6.0 ( range , 3-8 ) in the tibial inlay group .


Twenty-one patients ( 58.3 % ) in the transtibial group and 19 patients ( 63.3 % ) in the tibial inlay group were able to return to preinjury sports activity .


In the posterior drawer test , 6 patients in the transtibial group and 4 patients in the tibial inlay group showed grade II laxity .


The mean side-to-side difference was 10.1 mm ( range , 7-12 mm ) in the transtibial group and 10.4 mm ( range , 9-13 mm ) in the tibial inlay group , improving postoperatively to 4.1 mm ( range , 0-8 mm ) and 4.2 mm ( range , 1-8 mm ) , respectively .


There was significant improvement between preoperative and final follow-up values .


However , there were no significant differences between the 2 groups in final follow-up outcomes .


Final follow-up radiographs showed that 6 patients ( 16.7 % ) in the transtibial group and 3 patients ( 10.0 % ) in the tibial inlay group were rated grade C according to International Knee Documentation Committee guidelines .


Clinical and radiographic outcomes between the 2 PCL reconstruction techniques were comparable .


Osteoarthritis was observed in patients , with a significant proportion presenting loss of joint space .


Examined factors , excluding meniscectomy , were not correlated with the development of osteoarthritis .


Vitamin D supplementation during pregnancy is a well-accepted recommendation worldwide ; however , the debate about the correct dose is ongoing .


We aimed to compare daily doses of 600 , 1,200 , and 2,000 IU in this randomized , controlled study .


The study group consisted of 91 pregnant women aged 16-42 years admitted to Kocaeli Maternity and Children Hospital between April 2011 and April 2012 .


The participants were randomly divided into 3 groups .


600 , 1,200 , and 2,000 IU/day of vitamin D was supplemented to group 1 ( control group , n = 31 ) , group 2 ( n = 31 ) , and group 3 ( n = 32 ) , respectively .


Serum calcium , 25-hydroxyvitamin D ( 25OHD ) , and the calcium/creatinine ratio in spot urine samples were measured in the follow-up period .


The serum calcium and 25OHD levels of the mothers ' infants were measured as well .


The frequency of vitamin D sufficiency after supplementation was 80 % in group 3 and it was significantly higher than in groups 1 ( 42 % ) and 2 ( 39 % ) ( p = 0.03 ) .


The frequency of vitamin D sufficiency in the infants of the participants was 91 % in group 3 and it was significantly higher than in groups 1 ( 36 % ) and 2 ( 52 % ) ( p = 0.006 ) .


At least 2,000 IU/day of vitamin D is needed to ensure adequate vitamin D status in pregnancy and early infancy .


Microvascular obstruction ( MVO ) secondary to ischaemic-reperfusion injury is an important but underappreciated determinant of short - and longer-term outcome following percutaneous coronary intervention ( PCI ) treatment of ST-elevation myocardial infarction ( STEMI ) .


Several small studies have demonstrated a reduction in the degree of MVO utilising a variety of vasoactive agents , with adenosine and sodium nitroprusside ( SNP ) being most evaluated .


However , the evidence base remains weak as the trials have had variable endpoints , differing drug doses and delivery .


As such , the results regarding benefit are conflicting .


The REperfusion Facilitated by LOcal adjunctive therapy in STEMI ( REFLO-STEMI ) trial is a multicentre , prospective , randomised , controlled , open label , study with blinded endpoint analysis : Patients presenting within 6 h of onset of STEMI and undergoing planned primary PCI ( P-PCI ) with TIMI 0/1 flow in the infarct-related artery ( IRA ) and no significant bystander coronary artery disease on angiography , are randomised into one of three groups : PCI with adjunctive pharmacotherapy ( intracoronary adenosine or SNP ) or control ( standard PCI ) .


All receive Bivalirudin anticoagulation and thrombus aspiration .


The primary outcome is infarct size ( IS ) ( determined as a percentage of total left ventricular mass ) measured by cardiac magnetic resonance imaging ( CMRI ) undertaken at 48 to 72 h post P-PCI .


Secondary outcome measures include MVO ( hypoenhancement within infarct core ) on CMRI , angiographic markers of microvascular perfusion and MACE during 1-month follow-up .


The study aims to recruit 240 patients ( powered at 80 % to detect a 5 % absolute reduction in IS ) .


The REFLO-STEMI study has been designed to address the weaknesses of previous trials , which have collectively failed to demonstrate whether adjunctive pharmacotherapy with adenosine and/or SNP can reduce measures of myocardial injury ( infarct size and MVO ) and improve clinical outcome , despite good basic evidence that they have the potential to attenuate this process .


The REFLO-STEMI study will be the most scientifically robust trial to date evaluating whether adjunctive therapy ( intracoronary adenosine or SNP following thrombus aspiration ) reduces CMRI measured IS and MVO in patients undergoing P-PCI within 6 h of onset of STEMI .


Trial registered 20th November 2012 : ClinicalTrials.gov Identifier NCT01747174 .


To compare the difference in the clinical efficacy on mild and moderate female stress urinary incontinence ( FSUI ) between transcutaneous acupoint electrical stimulation and oral administration of midodrine hydrochloride tablets .


Ninety cases of mild and moderate FSUI were randomized into an observation group and a control group , 45 cases in each one .


In the observation group , the transcutaneous acupoint electrical stimulation was applied to Ciliao ( BL 32 ) , Shenshu ( BL 23 ) , Zigong ( EX-CA 1 ) , Guanyuan ( CV 4 ) and Qihai ( CV 6 ) , once a day .


In the control group , midodrine hydrochloride tablets were prescribed for oral administration , 2.5 mg per treatment , three times each day .


The duration of treatment was 4 weeks .


The score of international consultation on incontinence questionnaire-urinary incontinence short form ( ICI-Q-SF ) and leakage of urine in 1 h urinal pad test were observed before and after treatment in the patients of the two groups , and the efficacy was compared between the two groups .


The score of ICI-Q-SF and leakage of urine in urinal pad test after treatment were all improved apparently as compared with those before treatment in the two groups ( all P < 0.01 ) , and the results in the observation group were better than those in the control group ( both P < 0.01 ) .


The total effective rate was 86.7 % ( 39/45 ) in the observation group , which was better than 68.9 % ( 31/45 , P < 0.05 ) in the control group .


The transcutaneous acupoint electrical stimulation achieves the better efficacy on FSUI as compared with the oral administration of midodrine hydrochloride tablets .


This therapy effectively improves the patient 's urine control ability and reduces leakage of urine .


The aim of this study was to examine the level of compliance and persistence in patients with postmenopausal osteoporosis ( OP ) receiving daily risedronate ( 5 mg ) with either fixed dosing of three different timing regimens ( A : before breakfast ; B : in-between meals ; C : before bedtime ) or with flexible dosing and the effect on urinary N-terminal telopeptide of Type 1 collagen ( NTX-1 ) .


The study included 448 patients with postmenopausal OP .


Patients were randomly assigned into six treatment groups each with a permutation of the treatment sequence ( ABC , BCA , etc. ) in the crossover phase ( 3 x 1 week ) and randomized to 23 weeks of either the daily flexible ( either regimen A , B or C ) or fixed timing ( only regimen A , B , or C ) in the patient 's preference phase .


Urinary NTX-1 was tested .


A total of 433 patients participated in the patient 's preference phase ( 49.7 % preferred flexible and 50.3 % fixed timing ) .


There was no significant difference between the proportion of responders who were both compliant and persistent in the flexible ( 54.4 % ) and fixed regimens ( 53.7 % ) ( p = 0.8803 ) .


A significant difference between the flexible and fixed regimens was seen in persistence in favor of the flexible regimen ( p = 0.0306 ) .


There was no significant difference between the flexible and fixed regimens in terms of compliance ( p = 0.4611 ) .


Change in urinary NTX-1 did not show any difference between the two regimens .


At the final visit , 51 % of patients in the flexible and 55 % in the fixed regimen group considered the used risedronate regimen as excellent or very good ( p = 0.1440 ) .


A flexible dosing with daily risedronate appears be a valuable option in terms of compliance and persistence for patients with postmenopausal OP .


Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance .


We assessed the efficacy and safety of ceftolozane-tazobactam , a novel antibacterial with Gram-negative activity , in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis .


ASPECT-cUTI was a randomised , double-blind , double-dummy , non-inferiority trial done in 209 centres in 25 countries .


Between July , 2011 , and September , 2013 , hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 15 g ceftolozane-tazobactam every 8 h or intravenous high-dose ( 750 mg ) levofloxacin once daily for 7 days .


The randomisation schedule was computer generated in blocks of four and stratified by study site .


The next allocation was obtained by the study site pharmacist via an interactive voice-response system .


The primary endpoint was a composite of microbiological eradication and clinical cure 5-9 days after treatment in the microbiological modified intention-to-treat ( MITT ) population , with a non-inferiority margin of 10 % .


This study is registered with ClinicalTrials.gov , numbers NCT01345929 and NCT01345955 .


Of 1083 patients enrolled , 800 ( 739 % ) , of whom 656 ( 820 % ) had pyelonephritis , were included in the microbiological MITT population .


Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure ( 306 [ 769 % ] of 398 vs 275 [ 684 % ] of 402 , 95 % CI 23-146 ) and , as the lower bound of the two-sided 95 % CI around the treatment difference was positive and greater than zero , superiority was indicated .


Adverse event profiles were similar in the two treatment groups and were mainly non-serious .


Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis .


Cubist Pharmaceuticals .


The validity of the Talk Test ( TT ) is well documented , but the reliability of the test is not clear .


The aim of this study was to assess the absolute and relative intertester reliability of the TT in cardiac patients .


Cardiac patients ( n = 64 ) who had completed an exercise rehabilitation program were consecutively included in the study .


Patients performed a submaximal ramp cycle ergometer test with the TT as intensity indicator .


Every patient was tested twice on the same day by 2 different physiotherapists with a break of maximum 45 minutes between tests .


Physiotherapists were randomized to tests .


Workload in watts at the first negative stage of the TT was registered as the test result .


Patients and physiotherapists were blinded to test results of the first test .


Absolute reliability of the TT was assessed with Bland-Altman plot , standard error of measurement , and minimal detectable change .


Relative reliability was assessed using the intraclass correlation coefficient ( ICC ) .


Mean difference in peak workload between test and retest was 0.8 W ( 95 % CI : -4.8 to 3.3 ) .


Limit of agreement was estimated to be +31 / -32 W. Standard error of measurement was 11 W ( 95 % CI : 10-14 ) , and minimal detectable change was 32 W.


The ICC was 0.85 ( 95 % CI : 0.78 to 0.91 ) .


Although the ICC was acceptable , we found a weak absolute intertester reliability of the TT and that the test is an insufficient measure to monitor exercise intensity and safety of cardiac patients when 2 or more physiotherapists may be administering the TT .


Advances in information technology ( IT ) now permit population-based preventive screening , but the best methods remain uncertain .


We evaluated whether involving primary care providers ( PCPs ) in a visit-independent population management IT application led to more effective cancer screening .


We conducted a cluster-randomized trial involving 18 primary care practice sites and 169 PCPs from June 15 , 2011 , to June 14 , 2012 .


Participants included adults eligible for breast , cervical , and/or colorectal cancer screening .


In practices randomized to the intervention group , PCPs reviewed real-time rosters of their patients overdue for screening and provided individualized contact ( via a letter , practice delegate , or patient navigator ) or deferred screening ( temporarily or permanently ) .


In practices randomized to the comparison group , overdue patients were automatically sent reminder letters and transferred to practice delegate lists for follow-up .


Intervention patients without PCP action within 8 weeks defaulted to the automated control version .


The primary outcome was adjusted average cancer screening completion rates over 1-year follow-up , accounting for clustering by physician or practice .


Baseline cancer screening rates ( 80.8 % vs 80.3 % ) were similar among patients in the intervention ( n = 51,071 ) and comparison group ( n = 52,799 ) .


Most intervention providers used the IT application ( 88 of 101 , 87 % ) and users reviewed 7984 patients overdue for at least 1 cancer screening ( 73 % sent reminder letter , 6 % referred directly to a practice delegate or patient navigator , and 21 % deferred screening ) .


In addition , 6128 letters were automatically sent to patients in the intervention group ( total of 12,002 letters vs 16,378 letters in comparison practices ; P < .001 ) .


Adjusted average cancer screening rates did not differ among intervention and comparison practices for all cancers combined ( 81.6 % vs 81.4 % ; P = .84 ) nor breast ( 82.7 % vs 82.7 % ; P = .96 ) , cervical ( 84.1 % vs 84.7 % ; P = .60 ) , or colorectal cancer ( 77.8 % vs 76.2 % ; P = .33 ) .


Involving PCPs in a visit-independent population management IT application resulted in similar cancer screening rates compared with an automated reminder system , but fewer patients were sent reminder letters .


This suggests that PCPs were able to identify and exclude from contact patients who would have received automated reminder letters but not undergone screening .


Providing long-term follow-up of the natural history of age-related macular degeneration ( AMD ) and associated risk factors will facilitate future epidemiologic studies and clinical trials .


To describe 10-year progression rates to intermediate or advanced AMD .


We observed the Age-Related Eye Disease Study ( AREDS ) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed .


Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers .


Participants aged 55 to 80 years with no AMD or AMD of varying severity ( n = 4757 ) were followed up in the AREDS trial for a median duration of 6.5 years .


When the trial ended , 3549 of the 4203 surviving participants were followed for 5 additional years .


Treatment with antioxidant vitamins and minerals .


Development of varying stages of AMD and changes in visual acuity .


The rates of progression to large drusen and advanced AMD ( neovascular AMD or central geographic atrophy ) were evaluated using annual fundus photographs assessed centrally .


Best-corrected visual acuity was measured at annual study visits .


The risk of progression to advanced AMD increased with increasing age ( P = .01 ) and severity of drusen .


Women ( P = .005 ) and current smokers ( P < .001 ) were at increased risk of neovascular AMD .


In the oldest participants with the most severe AMD status at baseline , the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1 % and 26.0 % , respectively .


Similarly , rates of progression to large drusen increased with increasing severity of drusen at baseline , with 70.9 % of participants with bilateral medium drusen progressing to large drusen and 13.8 % to advanced AMD in 10 years .


Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25 ; eyes that developed advanced AMD had a median visual acuity of 20/200 .


The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD .


These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations .


Non-alcoholic fatty liver disease ( NAFLD ) represents a range of liver conditions from simple fatty liver to progressive end stage liver disease requiring liver transplantation .


NAFLD is common in the population and in certain sub groups ( e.g. type 2 diabetes ) up to 70 % of patients may be affected .


NAFLD is not only a cause of end stage liver disease and hepatocellular carcinoma , but is also an independent risk factor for type 2 diabetes and cardiovascular disease .


Consequently , effective treatments for NAFLD are urgently needed .


The WELCOME study is testing the hypothesis that treatment with high dose purified long chain omega-3 fatty acids will have a beneficial effect on a ) liver fat percentage and b ) two histologically validated algorithmically-derived biomarker scores for liver fibrosis .


In a randomised double blind placebo controlled trial , 103 participants with NAFLD were randomised to 15-18months treatment with either 4g/day purified long chain omega-3 fatty acids ( Omacor ) or 4g/day olive oil as placebo .


Erythrocyte percentage DHA and EPA enrichment ( a validated proxy for hepatic enrichment ) was determined by gas chromatography .


Liver fat percentage was measured in three discrete liver zones by magnetic resonance spectroscopy ( MRS ) .


We also measured body fat distribution , physical activity and a range of cardiometabolic risk factors .


Recruitment started in January 2010 and ended in June 2011 .


We identified 178 potential participants , and randomised 103 participants who met the inclusion criteria .


The WELCOME study was approved by the local ethics committee ( REC : 08/H0502/165 ; www.clinicalTrials.gov registration number NCT00760513 ) .


Nasya/Prevalin is a natural , drug-free nasal spray for treatment and prevention of allergic rhinitis .


Because of its thixotropic property , it forms a barrier on the nasal mucosa , preventing allergen contact .


This study assesses the clinical efficacy and safety of Nasya/Prevalin in a nasal provocation test with house dust mite allergens .


In this randomised , double-blind , placebo-controlled trial , 20 subjects suffering from allergic rhinitis because of house dust mite allergens received a single dose of Nasya/Prevalin or saline spray before allergen challenge .


Total nasal symptom score and total ocular symptom score were assessed 15 , 30 , 60 , 75 , 90 , 120 and 240min after challenge .


Further , the appearance of the mucosa was examined by rhinoscopy .


A single treatment with Nasya/Prevalin led to a significant reduction of TNSS at 60 , 75 and 90min after dust mite allergen challenge as compared with placebo ( pVCAS = 0.021 , pVCAS = 0.035 , pVCAS = 0.036 , respectively ) .


Mucosa changes assessed by the rhinoscopic score ( on swelling , secretion and colour ) were significantly worse in the placebo group compared with the Nasya/Prevalin group ( P = 0.033 ) .


Nasya/Prevalin was well tolerated , and the safety was comparable with placebo .


Treatment with Nasya/Prevalin was effective in preventing allergic reactions induced by dust mite allergen challenge .


To assess the efficacy of Yishen Jiejing Decoction ( YJD ) in treating poststroke shoulder-hand syndrome ( SHS ) patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome .


Totally 60 SHS patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome were randomly assigned to two groups , the treatment group and the control group , 30 cases in each group .


Conventional rehabilitation training and therapeutics were applied in all patients .


Besides , patients in the treatment group took 50 mL YJD , twice a day .


One month without interruption consisted of one course of treatment .


The curative effects of each group were evaluated respectively before treatment and at one month after treatment .


The neurologic impairment , TCM syndrome , and the improvement of upper limbs movement were assessed by the neurologic impairment integral , scoring for TCM syndrome diagnostics , Fugl-Meyer Assessment ( U-FMA ) .


Adverse reactions were observed at the same time .


The effective rate of stroke was 86.67 % and the effective rate of SHS was 90.00 % in the treatment group , higher than those of the control group ( P < 0.05 ) .


Both groups got improvement in neurologic impairment , stroke induced blood stasis syndrome , yin deficiency yang hyperactivity syndrome , and the improvement of upper limbs movement after treatment ( all P < 0.05 ) .


Besides , all the improvement was obviously superior in the treatment group ( P < 0.05 ) .


No adverse reaction occurred during the course of treatment .


The curative effect of YJD combined with conventional rehabilitation training was confirmative and superior to the control group .


Polyphonic music ( music consisting of several instruments playing in parallel ) is an intuitive way of embedding multiple information streams .


The different instruments in a musical piece form concurrent information streams that seamlessly integrate into a coherent and hedonistically appealing entity .


Here , we explore polyphonic music as a novel stimulation approach for use in a brain-computer interface .


In a multi-streamed oddball experiment , we had participants shift selective attention to one out of three different instruments in music audio clips .


Each instrument formed an oddball stream with its own specific standard stimuli ( a repetitive musical pattern ) and oddballs ( deviating musical pattern ) .


Contrasting attended versus unattended instruments , ERP analysis shows subject - and instrument-specific responses including P300 and early auditory components .


The attended instrument can be classified offline with a mean accuracy of 91 % across 11 participants .


This is a proof of concept that attention paid to a particular instrument in polyphonic music can be inferred from ongoing EEG , a finding that is potentially relevant for both brain-computer interface and music research .


Laparoscopic surgery requires certain specific skills .


There have been several attempts to minimize the learning curve with training outside the operation room .


Although simulators have been well validated as tools to teach technical skills , their integration into comprehensive curricula is lacking .


Several randomized controlled trials and systematic reviews have demonstrated that the technical skills learned on these simulators transfer to the operating room .


Currently , however , the integration of these simulated models into formal residency training curricula is lacking .


In our institute , we have adopted the Tuebingen Trainer devised by Professor GF Buess from Germany .


The purpose of this study was to evaluate the training of surgical residents on an ex vivo phantom model for basic laparoscopic skill acquisition and its transferability to the OR performance .


Seventeen general surgery residents were randomized into 2 groups : Laparoscopic Training Group ( n = 9 , Group A ) and Standard Training Group ( n = 8 , Group B ) .


Group A underwent training in the Minimally Invasive Surgery Training Centre on the porcine phantom model and did 10 laparoscopic cholecystectomies , whereas Group B did not undergo training in the Minimally Invasive Surgery Training Centre .


All the participants performed a laparoscopic cholecystectomy in the operation theater in the presence of a consultant who was blinded to the training status of the participants .


The performance of the residents in both groups in the operation theater was assessed using GOALS criteria , surgical performance assessment parameters , task-specific checklists , and visual analog scale for gallbladder perforation difficulty and overall competence .


The Laparoscopic Training Group had better performance than the Standard Training Group regarding operation time , GOALS criteria , and Task-specific checklists .


Although the surgical performance assessments , i.e. cystic duct and artery identification scores , gallbladder perforation scores , and liver injury scores , were better in the Laparoscopic Training Groups , they were not statistically significant .


The overall difficulty of the surgery was comparable in both the groups .


The Laparoscopic Training Group exhibited significant overall competence on visual analog scale scores .


Our study has clearly shown that training on the Tuebingen Trainer with integrated porcine organs results in a statistically significant improvement in the operating room performance of surgical residents as compared with the nontrained residents , thereby indicating a transfer of skills from training to the operating room .


Physical activity during childhood and adolescence is associated with substantial health benefits and tracks into adulthood .


Nevertheless , only 22.7 % of German adolescents are sufficiently physically active .


Thus , the promotion of an active lifestyle in youth is an essential issue of public health.This study will evaluate the implementation and efficacy of the `` luft . ''


program to enhance physical activity in adolescence .


`` luft . ''


is a multicomponent school-based program developed on the basis of effective strategies for health interventions and behavioral change .


The `` luft . ''


physical activity program targets four different levels .


( a ) Each student receives a pedometer and documents his/her steps over 12 weeks using an interactive user account on the `` luft . ''


homepage .


( b ) For classes there will be different competitions , with achieving the most steps in selected weeks , the highest increases of steps and developing the most inventive ideas to promote physical activity in school .


Besides , the intervention includes four educational lessons .


( c ) The headmasters and teaching staff of the participating schools will get information material with suggestions and encouragement to enhance physical activity in school .


Participating teachers will be invited to an introductory seminar .


( d ) Parents will be provided with informational material about the program and will be invited to a parent-teacher conference about the benefits of being physically active and how they can support their children in engaging in a physically active lifestyle.To evaluate the efficacy of the `` luft . ''


physical activity program , a two-arm cluster randomized controlled trial will be conducted in three waves : ( 1 ) baseline assessment , January/February 2014 , ( 2 ) post assessment , June/July 2014 and ( 3 ) 12-month follow-up assessment , June/July 2015 .


Data collection will include physical and medical testing , self-administered questionnaires , group discussions and document analyses .


aims at fostering a physically active lifestyle in adolescence while a considerable decline of physical activity is present .


Physical activity programs based in the school setting and following a multicomponent approach have been proven to be most successful .


Furthermore , the use of pedometers is promising to enhance physical activity during the entire day and targets a wide range of adolescents regarding fitness and weight .


Current Controlled Trials ISRCTN49482118 .


Glycopyrronium is a once-daily ( od ) long-acting muscarinic antagonist for the maintenance treatment of chronic obstructive pulmonary disease ( COPD ) .


The GLOW7 study evaluated the efficacy and safety of od glycopyrronium 50 g in predominantly Chinese patients with moderate-to-severe COPD .


In this 26-week , multi-center , double-blind , placebo-controlled , parallel-group study , men and women 40 years with moderate-to-severe COPD were randomized to glycopyrronium 50 g od or placebo ( 2:1 ) .


The primary objective was to confirm the significant improvement of trough forced expiratory volume in 1 second ( FEV1 ) following 12 weeks of treatment with glycopyrronium compared with placebo .


Secondary objectives included the effect of glycopyrronium on health status ( St George 's Respiratory Questionnaire ) , breathlessness ( Transition Dyspnea Index ) , other lung function parameters , rescue medication use , and COPD exacerbations .


Safety and tolerability were also evaluated .


Of the 460 patients randomized , 459 were included in the full analysis set ( glycopyrronium , n = 306 ; placebo , n = 154 ; mean age 64.7 years ; mean post-bronchodilator FEV1 : 50.8 % predicted ) ; 425 ( 92.4 % ) completed the study .


At Week 12 , glycopyrronium signifcantly improved trough FEV1 with a least square means treatment difference of 141 mL ( 95 % confidence interval 111 mL , 171 mL ; P < 0.001 ) compared with placebo .


The mean treatment effect of glycopyrronium was greater than the minimum clinically important difference versus placebo in both St George 's Respiratory Questionnaire total score ( -4.92 ; P < 0.001 ) and Transition Dyspnea Index focal score ( 1.0 ; P < 0.001 ) at week 26 .


Glycopyrronium reduced the risk of exacerbations in terms of time to first moderate or severe exacerbation by 28 % ( P = 0.153 ) and rate of moderate or severe COPD exacerbation by 29 % ( P = 0.119 ) compared with placebo .


Incidence of death was 1.3 % with glycopyrronium and 0 % in placebo during the treatment period .


Overall incidence of adverse events ( glycopyrronium 43.6 % ; placebo 47.4 % ) and serious adverse events ( glycopyrronium 5.6 % ; placebo 9.1 % ) were similar .


In predominantly Chinese patients with moderate-to-severe COPD , od glycopyrronium 50 g significantly improved lung function , dyspnea , and health status compared with placebo .


The safety and tolerability profile of glycopyrronium was comparable to placebo .


Blood pressure normally declines during the night ( ` dipping ' ) ; a blunted nocturnal decline is an important cardiovascular risk factor .


Marriage may be associated with lower ambulatory blood pressure , although this may be confounded by socio-economic and dietary factors .


We examined the association of marital status with nocturnal dipping and night-time SBP amongst individuals on a controlled diet .


We analysed 325 individuals enrolled in the Dietary Approaches to Stop Hypertension trial who had available 24-h SBP data and who ingested a control diet .


Logistic and linear regression models were fit to estimate the association of marital status with nocturnal dipping and mean night-time SBP .


Of the 325 individuals , 52.9 % were men , the average age was 45.1 years and 48.9 % reported being married .


Compared with nonmarried individuals , those who were married had greater adjusted odds of dipping [ odds ratio ( OR ) 2.26 ; 95 % confidence interval ( CI ) 1.26-4 .03 ; P = 0.01 ] .


In adjusted models , being married was associated with lower night-time SBP ( -2.4 mmHg ; 95 % CI -3.8 to -0.9 mmHg ; P = 0.002 ) , with the suggestion of a greater association in married men compared with married women ( -3.1 vs. -1.7 mmHg ) ; there was less difference for married nonblacks compared with married blacks ( -2.7 and -2.4 mmHg , respectively ) .


Being married is independently associated with a greater likelihood of nocturnal dipping and with lower night-time SBP among individuals participating in a controlled dietary intervention ; the association was particularly strong in married men .


Marital status is a variable that may be considered in future analyses of ambulatory blood pressure .


This study aimed to determine if preoperative oral administration of metoclopramide , chlorpromazine , gabapentin , or dexamethasone would effectively reduce postoperative nausea and vomiting ( PONV ) in the first 24 hours after surgery in patients undergoing maxillofacial trauma surgery .


One hundred fifty patients with maxillofacial skeletal trauma that need open reduction and internal fixation were randomly assigned to receive one of the following drugs orally , 1 hour preoperative : 10 mg metoclopramide ( group A ) , 300 mg gabapentin ( group B ) , 100 mg chlorpromazine ( group C ) , 5 mg dexamethasone ( group D ) , and placebo ( group E ) .


All patients were observed in the first 24 hours for PONV .


Data analysis was done with the SPSS software ( version 19 ) , using chi-square test , Fisher exact test , and multiple logistic regression methods .


The incidence of vomiting was significantly lower in groups A ( 2/30 ) , B ( 3/30 ) , and C ( 2/30 ) compared with the placebo group ( 9/30 ) ( P < 0.05 ) .


Also , the incidence of postoperative nausea was significantly high in the placebo group ( 11/30 ) as compared to treatment groups A ( 2/30 ) , B ( 3/30 ) , and C ( 3/30 ) ( P < 0.05 ) .


No significant differences in the incidence of PONV were found between groups D ( 7/30 ) and E ( P > 0.05 ) .


Of all demographic variables , anesthesia time ( P = 0.034 ) and surgery time ( P = 0.047 ) were predictors of PONV .


Our results demonstrated that premedication with oral metoclopramide , gabapentin , or chlorpromazine can significantly decrease the incidence of PONV in patients undergoing maxillofacial trauma surgery .


To understand whether combination antiretroviral therapy ( cART ) has been optimized , we asked whether 3-drug protease inhibitor ( PI ) - based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared with similarly applied 3-drug PI-based cART .


Forty newly HIV-1-infected patients were randomized 1:2 to receive 3-drug ( N = 14 ) or 5-drug ( N = 26 ) therapy .


The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase-polymerase chain reaction and the single copy assay after 48 weeks .


Secondary end points included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4 T cells at week 96 and quantitative and qualitative immunologic responses .


At 48 weeks , 34 subjects remained on study and are included in the as-treated analysis .


Three of 11 ( 27.3 % ) in the 3-drug arm and 9 of 21 ( 42.9 % ) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard reverse transcriptase-polymerase chain reaction and single copy assay ( P = 0.46 , Fisher exact test ) .


No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96 weeks of therapy .


Mean levels of infectious HIV-1 in resting CD4 T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 infectious units per million , respectively ( P = 0.81 ) .


No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation .


Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART .


To investigate the effects of different target plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane ( MAC ) for blocking adrenergic response ( BAR ) during laparoscopic gynaecological surgery with carbon dioxide insufflation .


Seventy-five gynaecological patients with ASA I-II undergoing laparoscopic surgery were randomly assigned to three groups .


Anaesthesia was induced by sevoflurane , and 0.1 mg kg ( -1 ) of vecuronium i.v. was injected to facilitate tracheal intubation .


After intubation the target plasma concentrations of remifentanil in Groups 1 , 2 , and 3 were adjusted to 0 , 1 , and 2 ng ml ( -1 ) , respectively .


The changes in haemodynamics were observed before and after the creation of carbon dioxide pneumoperitoneum .


The MAC BAR of sevoflurane in each group was determined by using an up-and-down sequential-allocation technique , and blood samples were collected at corresponding time points to determine the concentrations of remifentanil , norepinephrine , and epinephrine .


In Groups 1 , 2 and 3 , the MAC BAR of sevoflurane was 4.6 % ( CI 95 % : 4.3-4 .9 % ) , 2.4 % ( CI 95 % : 2.2-2 .6 % ) , and 1.7 % ( CI 95 % : 1.4-2 .1 % ) , respectively .


No significant differences were found in the increase of norepinephrine , epinephrine , and mean arterial pressure after compared with before insufflation of pneumoperitoneum among the three groups .


Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus .


At similar MAC BAR the haemodynamic and adrenergic response is not affected by the infused remifentanil concentration .


The number of this clinical trial registry is ChiCTR-TRC-13004005 , and the Universal Trial Number is U1111-1151-5630 .


Anesthesiologists use various medications to provide surgical patients with pain relief in the postoperative period .


Other modalities , such as music , could be used in conjunction with opioids and nonsteroidal anti-inflammatory drugs ( NSAIDs ) to decrease pain and lower heart rate and blood pressure .


Our hypothesis was that patients listening to jazz in a postanesthesia care unit ( PACU ) would have lower heart rates and blood pressures and reduced pain and anxiety .


The study objective was to determine if listening to jazz music in the PACU , when compared to wearing noise-canceling headphones with no music playing , would decrease heart rate , blood pressure , pain , or anxiety in patients undergoing a hysterectomy .


The research design was a prospective , randomized study .


The study was conducted in the PACU at the Penn State Hershey Medical Center in Hershey , PA , USA .


A total of 56 patients , aged 18-75 y , who were categorized as status 1 or 2 according to the American Society of Anesthesiologists ( ASA ) Physical Status Classification System , and who were undergoing elective laparoscopic or abdominal hysterectomies , were enrolled in the study .


Patients were randomly assigned either to listen to jazz music where the beats per min ( BPM ) was < 100 ( experimental group , n = 28 ) or to wear noise-canceling headphones ( control group , n = 28 ) for 30 min while in the PACU after their surgery .


Heart rate was the primary outcome , and secondary outcomes included systolic and diastolic blood pressure , an anxiety score , and a pain score .


All outcome measures were initially recorded at baseline upon the patient 's arrival in the PACU .


Heart rate and blood pressure were recorded postoperatively every 5 min for the initial 30 min that a patient was in the PACU .


Pain was checked every 10 min during the 30-min period ; anxiety was checked at 30 min .


Heart rates of patients in the noise-cancellation group were significantly lower when compared with baseline ( P < .05 ) , at all time points .


For patients in the jazz group , heart rates were significantly lower at 15 , 20 , 25 , and 30 min when compared with baseline .


The pain scores were significantly lower ( P < .05 ) in the noise-cancellation group compared with the jazz group at 10 min into the recovery period .


Overall , the results showed that patients responded not only to music but also to silence in the PACU .


Using music and/or noise reduction could decrease opioid administration , promote relaxation , and improve patient satisfaction .


Cold Water Immersion ( CWI ) is commonly used to manage delayed onset muscle soreness ( DOMS ) resulting from exercise .


Scientific evidence for an optimal dose of CWI is lacking and athletes continue to use a range of a treatment protocols and water temperatures .


To compare the effectiveness of four different water immersion protocols and a passive control intervention in the management of DOMS .


Randomised controlled trial with blinded outcome assessment .


University Research Laboratory .


50 healthy participants with laboratory induced DOMS randomised to one of five groups : Short contrast immersion ( 1min 38C/1min 10C3 ) , Short intermittent CWI ( 1min3 at 10C ) ; 10min CWI in 10C ; 10min CWI in 6C ; or control ( seated rest ) .


muscle soreness , active range of motion , pain on stretch , muscle strength and serum creatine kinase .


10min of CWI in 6C was associated with the lowest levels of muscle soreness and pain on stretch however values were not statistically different to any of the other groups .


There were no statistically significant differences between groups for any other outcomes .


Altering the treatment duration , water temperature or dosage of post exercise water immersion had minimal effect on outcomes relating to DOMS .


The aim of this study was to investigate the efficacy of rikkunshito ( RKT ) , a traditional Japanese medicine , combined with proton pump inhibitor ( PPI ) in patients with PPI-refractory non-erosive reflux disease ( NERD ) .


Patients with PPI-refractory NERD ( n = 242 ) were randomly assigned to the RKT group [ rabeprazole ( 10 mg/day ) + RKT ( 7.5 g/t .


i.d. ) for 8 weeks ] or the placebo group ( rabeprazole + placebo ) .


After the 4 - and 8-week treatments , we assessed symptoms and quality of life ( QOL ) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease ( FSSG ) , Gastrointestinal Symptom Rating Scale ( GSRS ) , and Short-Form Health Survey-8 ( SF-8 ) .


There were no significant differences in FSSG and GSRS score improvement between these groups after the 4 - and 8-week treatments .


The mental component summary ( MCS ) scores of the SF-8 improved more in the RKT group ( from 45.8 8.1 to 48.5 7.4 ) than in the placebo group ( from 47.7 7.1 to 48.4 7.5 ) after the 4-week treatment ( P < 0.05 ) .


The 8-week treatment with RKT was more effective for improvement of the degree of MCS score in patients with a low body mass index ( < 22 ) ( P < 0.05 ) and significantly improved the acid-related dysmotility symptoms of FSSG in female and elderly patients ( 65 years ) .


There were no significant differences in improvement of GERD symptoms in patients with PPI-refractory NERD between these groups .


However , RKT may be useful for improving mental QOL in non-obese patients and acid-related dyspeptic symptoms , especially in women and the elderly .


Beta-adrenergic blockade has been shown to improve left ventricular function , reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction ( HFrEF ) , with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related .


The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents .


We conducted a prospective pilot randomized controlled trial .


Twenty eight patients with CHF were randomized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration ( NLT ) clinic , led by a nurse specialist with the support of a cardiologist in a CHF clinic , or by their primary care physician ( usual care ( UC ) ) .


The primary endpoint was time to maximal beta-adrenergic receptor blocker dose .


The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months .


The patients were predominantly men ( 72 % ) , age 67 16 years ; New York Heart Association ( NYHA ) functional class I ( 32 % ) , II ( 44 % ) and III ( 20 % ) ; baseline left ventricular ejection fraction 33 10 % , and a low mean Charlson co-morbidity score of 2.5 1.4 .


The time to maximum dose was shorter in the NLT group compared to the UC group ( 90 14 vs 166 8 days , p < 0.0005 ) .


At six months , in the NLT group there were nine patients ( 82 % ) on high dose and one patient ( 9 % ) on low dose beta-adrenergic receptor blocker compared to the UC group with five ( 42 % ) patients reaching maximum dose and five ( 42 % ) patients on low dose ( p = 0.04 ) .


The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months ( p = 0.006 ) .


A NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF .


Australian Clinical Trials Registry ( ACTRN012606000383561 ) .


Recombinant leptin ( metreleptin ) treatment restores bone mineral density in women with hypothalamic amenorrhea ( HA ) , a condition characterized by hypoleptinemia , which has adverse impact on bone health .


The objective of the study was to investigate how metreleptin exerts its positive effect on bone metabolism in humans .


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


The study was conducted at Beth Israel Deaconess Medical Center ( Boston , Massachusetts ) .


Women ( n = 18 ) with HA and hypoleptinemia for at least 6 months were randomized to receive either metreleptin or placebo for 36 weeks .


Serum samples were obtained at baseline and 12 , 24 , and 36 weeks of treatment .


Circulating levels of leptin , intact PTH ( iPTH ) , receptor activator of nuclear factor-B ligand ( RANKL ) , osteoprotegerin ( OPG ) , sclerostin , dickkopf-1 , and fibroblast growth factor-23 .


Metreleptin administration significantly increased leptin levels throughout the treatment period ( P = .001 ) .


iPTH decreased over the 36 weeks of treatment ( P = .01 ) .


There was a trend toward a decrease in serum RANKL and increase in serum OPG in the metreleptin-treated group .


The RANKL to OPG ratio was significantly decreased within the metreleptin ( P = .04 ) but not the placebo group .


Metreleptin had no effect on serum sclerostin , dickkopf-1 , and fibroblast growth factor-23 .


Metreleptin treatment over 36 weeks decreases iPTH and RANKL to OPG ratio levels in hypoleptinemic women with HA .


We have previously found that sarcosine , a glycine transporter I inhibitor , can improve the psychiatric symptoms of schizophrenia .


In this study , we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson 's disease ( PD ) patients with dementia .


An 8-week , double-blind , placebo-controlled trial was conducted in patients who had PD with dementia ( PD-D ) .


Neuropsychiatric manifestations were measured before and at week 2 ( V1 ) , week 4 ( V2 ) and week 8 ( V3 ) after treatment .


Linear regression with the generalized estimating equations was applied for data analysis .


Fifteen patients were randomized into a sarcosine group ; the other 15 into a placebo group .


The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score ( P = 0.049 ) at V1 and Neuropsychiatry Inventory ( P = 0.039 ) at V2 between the treatment and placebo groups .


By excluding the advanced patients from analysis , there were significant differences in Unified Parkinson 's Disease Rating Scale V2 ( P = 0.004 ) and V3 ( P = 0.040 ) , Hamilton Depression Rating Scale V1 ( P = 0.014 ) and V2 ( P = 0.047 ) , Neuropsychiatry Inventory V1 ( P = 0.002 ) and V2 ( P < 0.001 ) and Behavior Pathology in Alzheimer 's Disease Rating Scale V2 ( P = 0.025 ) in favor of sarcosine .


Sarcosine temporally improved depression and neuropsychiatric symptoms in PD-D patients without exacerbating the motor or cognitive features ; the beneficial effects were more prominent in patients with mild-moderate severity .


Enhancement of N-methyl-D-aspartate receptor-glycine cascade may lead to a novel path for the management of PD-D .


To compare the astigmatic outcomes of LASIK with a single excimer laser platform using either wavefront-guided ( WFG ) or wavefront-optimized ( WFO ) modes .


Sixty-eight eyes of 34 patients underwent LASIK for myopia with the Wavelight Allegretto Eye-Q 400-Hz laser platform ( Alcon Laboratories , Inc. , Henberg , Switzerland ) .


One eye underwent WFG-LASIK and the contralateral eye underwent WFO-LASIK .


Alpins vector analysis of astigmatism was performed using manifest refraction measured preoperatively and 12 months postoperatively and vertexed to the corneal plane .


Eyes were stratified for subgroup analysis based on preoperative manifest astigmatism .


WFG-LASIK and WFO-LASIK were similar with regard to surgically induced astigmatism , difference vector , magnitude of error , correction index , flattening index , and index of success .


The angle of error was 80 % less in the WFG group compared to the WFO group ( 1.92 0.67 vs 9.66 3.7 , P = .04 ) .


WFG-LASIK and WFO-LASIK using the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser platform produce similar astigmatic results in myopic patients ; however , the WFG mode may produce slightly more predictable astigmatic corrections .


Painful oral mucositis ( OM ) is a significant toxicity during radiotherapy for head and neck cancers .


The aim of this randomized , double-blind , placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain .


In all , 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain .


Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day .


Pain questionnaires were administered at baseline and at 5 , 15 , 30 , 60 , 120 , and 240 minutes .


Patients were then given the option to continue doxepin .


The primary end point was pain reduction as measured by the area under the curve ( AUC ) of the pain scale using data from day 1 .


Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin ( -9.1 ) than for placebo ( -4.7 ; P < .001 ) .


Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin ( intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm ; P < .001 ) .


Doxepin was associated with more stinging or burning , unpleasant taste , and greater drowsiness than the placebo rinse .


More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study .


A doxepin rinse diminishes OM pain .


Further studies are warranted to determine its role in the management of OM .


Biomarkers may contribute to risk stratification in coronary heart disease ( CHD ) .


We examined whether plasma midregional proadrenomedullin ( MR-proADM ) concentration at baseline and its change over one year predicts long-term outcomes in stable CHD patients .


The LIPID study randomised patients 3-36 months after an acute coronary syndrome with total cholesterol 4.0-7 .0 mmol/L ( 155-271 mg/dL ) , to placebo or pravastatin 40 mg .


Follow-up was 6.0 years .


MR-proADM plasma concentrations at baseline and one year later were determined in 7863 and 6658 patients , respectively .


These were categorised into quartiles to perform Cox regression analysis , adjusting for baseline parameters .


Baseline MR-proADM concentrations predicted major CHD events ( non-fatal myocardial infarction or CHD death ; hazard ratio ( HR ) 1.52 , 1.26-1 .84 for Q4-Q1 ) , CHD death ( HR 2.21 , 1.67-2 .92 ) , heart failure ( HR 2.30 , 1.78-2 .97 ) and all-cause mortality ( HR 1.82 , 1.49-2 .23 ) .


Associations were still significant after adjustment for baseline B-type natriuretic peptide ( BNP ) concentration .


Increase in MR-proADM after one year was associated with increased risk of subsequent CHD events ( HR 1.34 , 1.08-1 .66 ) , non-fatal myocardial infarction ( HR 1.50 , 1.12-2 .03 ) , heart failure ( HR 1.78 , 1.37-2 .30 ) and all-cause mortality ( HR 1.31 , 1.04-1 .64 ) .


Associations with heart failure and all-cause mortality remained significant after adjusting for baseline and change in BNP concentration .


Change in MR-proADM moderately improved risk reclassification for major CHD events ( net reclassification improvement ( NRI ) 3.48 % ) but strongly improved risk reclassification for heart failure ( NRI 5.60 % ) .


Baseline and change in MR-proADM concentrations over one year are associated with risk of major clinical events , even after adjustment for BNP concentrations .


Developing efficacious medications to treat methamphetamine dependence is a global challenge in public health .


Topiramate ( TPM ) is undergoing evaluation for this indication .


The molecular mechanisms underlying its effects are largely unknown .


Examining the effects of TPM on genome-wide gene expression in methamphetamine addicts is a clinically and scientifically important component of understanding its therapeutic profile .


In this double-blind , placebo-controlled clinical trial , 140 individuals who met the DSM-IV criteria for methamphetamine dependence were randomized to receive either TPM or placebo , of whom 99 consented to participate in our genome-wide expression study .


The RNA samples were collected from whole blood for 50 TPM - and 49 placebo-treated participants at three time points : baseline and the ends of weeks 8 and 12 .


Genome-wide expression profiles and pathways of the two groups were compared for the responders and non-responders at Weeks 8 and 12 .


To minimize individual variations , expression of all examined genes at Weeks 8 and 12 were normalized to the values at baseline prior to identification of differentially expressed genes and pathways .


At the single-gene level , we identified 1054 , 502 , 204 , and 404 genes at nominal P values < 0.01 in the responders vs. non-responders at Weeks 8 and 12 for the TPM and placebo groups , respectively .


Among them , expression of 159 , 38 , 2 , and 21 genes was still significantly different after Bonferroni corrections for multiple testing .


Many of these genes , such as GRINA , PRKACA , PRKCI , SNAP23 , and TRAK2 , which are involved in glutamate receptor and GABA receptor signaling , are direct targets for TPM .


In contrast , no TPM drug targets were identified in the 38 significant genes for the Week 8 placebo group .


Pathway analyses based on nominally significant genes revealed 27 enriched pathways shared by the Weeks 8 and 12 TPM groups .


These pathways are involved in relevant physiological functions such as neuronal function/synaptic plasticity , signal transduction , cardiovascular function , and inflammation/immune function .


Topiramate treatment of methamphetamine addicts significantly modulates the expression of genes involved in multiple biological processes underlying addiction behavior and other physiological functions .


We explored psychometric properties of the Osteoporosis Assessment Questionnaire 2.0 in terms of reliability , validity , and responsiveness with generic , clinical , demographic , and preference-based data collected from a population of postmenopausal women with osteoporosis .


The Multiple Outcomes of Raloxifene Evaluation study was a randomized , placebo-controlled , multinational clinical trial evaluating efficacy and safety of raloxifene .


The Osteoporosis Assessment Questionnaire 2.0 , a generic quality of life measure ( Nottingham Health Profile ) , and a preference-based measure ( Health Utilities Index ) were administered at baseline and annually .


Psychometric properties of the 14 Osteoporosis Assessment Questionnaire 2.0 domains were evaluated by standard statistical techniques .


This study included a subset of 1477 women from the Multiple Outcomes of Raloxifene Evaluation study population completing the questionnaires .


Mean ( standard deviation ) age was 68.4 ( 6.8 ) years .


Prevalent vertebral fractures were found in 70 % ( n = 1038 ) of women .


Internal consistency was > 0.7 in 9 Osteoporosis Assessment Questionnaire 2.0 domains .


Correlations were moderate and significant for similar Osteoporosis Assessment Questionnaire 2.0 domain scores , Nottingham Health Profile domains , and Health Utilities Index scores .


All but 2 Osteoporosis Assessment Questionnaire 2.0 domains distinguished between patients with or without prevalent vertebral fractures and detected worsening with increased number of vertebral fractures .


Women with 1 incident vertebral fracture generally had a greater worsening in Osteoporosis Assessment Questionnaire 2.0 scores ( excluding social activity and support of family and friends ) from baseline to study endpoint compared with women without incident vertebral fractures .


Most domains in the Osteoporosis Assessment Questionnaire 2.0 demonstrated robust psychometric properties ; however , several domains not showing these criteria may need to be reassessed and removed for a potentially shorter and validated version of the Osteoporosis Assessment Questionnaire .


There is growing evidence suggesting that prolonged sitting has negative effects on people 's weight , chronic diseases and mortality .


Interventions to reduce sedentary time can be an effective strategy to increase daily energy expenditure .


The purpose of this study is to evaluate the effectiveness of a six-month primary care intervention to reduce daily of sitting time in overweight and mild obese sedentary patients .


The study is a randomized controlled trial ( RCT ) .


Professionals from thirteen primary health care centers ( PHC ) will randomly invite to participate mild obese or overweight patients of both gender , aged between 25 and 65 years old , who spend 6 hours at least daily sitting .


A total of 232 subjects will be randomly allocated to an intervention ( IG ) and control group ( CG ) ( 116 individuals each group ) .


In addition , 50 subjects with fibromyalgia will be included.Primary outcome is : ( 1 ) sitting time using the activPAL device and the Marshall questionnaire .


The following parameters will be also assessed : ( 2 ) sitting time in work place ( Occupational Sitting and Physical Activity Questionnaire ) , ( 3 ) health-related quality of life ( EQ-5D ) , ( 4 ) evolution of stage of change ( Prochaska and DiClemente 's Stages of Change Model ) , ( 5 ) physical inactivity ( catalan version of Brief Physical Activity Assessment Tool ) , ( 6 ) number of steps walked ( pedometer and activPAL ) , ( 7 ) control based on analysis ( triglycerides , total cholesterol , HDL , LDL , glycemia and , glycated haemoglobin in diabetic patients ) and ( 8 ) blood pressure and anthropometric variables .


All parameters will be assessed pre and post intervention and there will be a follow up three , six and twelve months after the intervention .


A descriptive analysis of all variables and a multivariate analysis to assess differences among groups will be undertaken .


Multivariate analysis will be carried out to assess time changes of dependent variables .


All the analysis will be done under the intention to treat principle .


If the SEDESTACTIV intervention shows its effectiveness in reducing sitting time , health professionals would have a low-cost intervention tool for sedentary overweight and obese patients management .


A service of the U.S. National Institutes of Health .


Developed by the National Library of Medicine .


ClinicalTrials.gov NCT01729936 .


This study investigated the effects of low-dose tranexamic acid on post-coronary artery bypass surgery bleeding .


Diffuse microvascular bleeding is still a common problem after cardiac procedures .


This study was designed to evaluate the hemostatic effects of low-dose tranexamic acid in on-pump coronary artery bypass graft surgery .


In this prospective randomized placebo-controlled study , 150 patients who were candidates for coronary artery bypass were enrolled and randomly assigned to 1 of 2 groups ( tranexamic acid or placebo ) .


Total drainage volume and the need for transfusion as well as surgical complications were recorded and compared in the 2 groups .


There was significantly less mediastinal chest tube drainage up to 48h in the tranexamic acid group ( 432210mL ) compared to the placebo group ( 649235mL , p = 0.006 ) .


In the placebo group , 43 ( 58 % ) patients were given allogeneic blood during hospital stay compared to 22 ( 25 % ) in the tranexamic acid group ( p < 0.001 ) .


No significant difference in postoperative complications was seen .


The use of low-dose tranexamic acid can significantly reduce blood loss and need for transfusion , with no increase in complications .


The aim of this study was to investigate the relationship between intraoperative vasopressin infusion and postoperative cardiac enzymes .


A prospective , double-blind , randomized , controlled study .


A single tertiary cardiac center .


One hundred consecutive patients undergoing cardiac surgery with or without cardiopulmonary bypass .


The study was approved by the Institutional Review Board , and patients provided informed consent to participate .


Patients were randomized by computer into 2 equal groups : Vasopressin or control .


The blinded study included vasopressin administered at a dose of 1.8 U/h or 1.8 mL/h of normal saline , along with catecholamines .


The drug was administered continually during surgery while patients needed catecholamines .


The intervention was discontinued upon admission to the intensive care unit when information regarding the true character of the drug was reported to the doctor in charge of patients in the intensive care unit by one of the investigators .


Primary outcomes were CK-MB and troponin T levels measured at 0 , 6 , and 12 hours postoperatively .


Of the 100 patients , 8 were excluded ; the remaining 92 were randomized to either the vasopressin ( n = 47 ) or control ( n = 45 ) group .


There were no significant differences in demographic data between the groups .


Postoperatively at 0 , 6 , and 12 hours , there were no differences in CK-MB ( U/l ) ( 37.5 57.9 v 32.0 21.5 , 29.4 41.1 v 24.4 23.1 , and 21.4 21.3 v. 21.8 32.4 , respectively ) and troponin T ( 752.4 638.2 v 762.7 557.1 , 753.8 507.3 v 777.6 515.0 , and 774.6 572.6 v 698.7 540.2 , respectively ) values .


Vasopressin infusion has been used to treat catecholamine-unresponsive shock .


In this study , intraoperative vasopressin was used safely as a possible first-line drug for treating hypotension ; however , it did not increase the levels of cardiac enzymes after cardiac surgery .


Functional Strength Training ( FST ) could enhance recovery late after stroke .


The aim of this study was to evaluate the feasibility of a subsequent fully powered , randomized controlled trial .


The study was designed as a randomized , observer-blind trial .


Both interventions were provided for up to one hour a day , four days a week , for six weeks .


Evaluation points were before randomization ( baseline ) , after six weeks intervention ( outcome ) , and six weeks thereafter ( follow-up ) .


The study took place in participants ' own homes .


Participants ( n = 52 ) were a mean of 24.4 months after stroke with a mean age of 68.3 years with 67.3 % male .


All had difficulty using their paretic upper ( UL ) and lower limb ( LL ) .


Participants were allocated to FST-UL or FST-LL by an independent randomization service .


The outcome measures were recruitment rate , attrition rate , practicality of recruitment strategies , occurrence of adverse reactions , acceptability of FST , and estimation of sample size for a subsequent trial .


Primary clinical efficacy outcomes were the Action Research Arm Test ( ARAT ) and the Functional Ambulation Categories ( FAC ) .


Analysis was conducted using descriptive statistics and thematic analysis of participants ' views of FST .


A power calculation used estimates of clinical efficacy variance to estimate sample size for a subsequent trial .


The screening process identified 1,127 stroke survivors of whom 52 ( 4.6 % ) were recruited .


The recruitment rate was higher for referral from community therapists than for systematic identification of people discharged from an acute stroke unit .


The attrition rate was 15.5 % at the outcome and follow-up time-points .


None of the participants experienced an adverse reaction .


The participants who remained in the study at outcome had received 68 % of the total possible amount of therapy .


Participants reported that their experience of FST provided a sense of purpose and involvement and increased their confidence in performing activities .


The power calculation provides estimation that 150 participants in each group will be required for a subsequent clinical trial .


This study found that a subsequent clinical trial was feasible with modifications to the recruitment strategy to be used .


Controlled-trials .


com ISCTN71632550 , 30 January 2009 .


To evaluate the usefulness of antibiotic + steroid irrigation of the middle ear in patients with otitis media with small perforation and pulsatile discharge .


A prospective , randomised , evaluator-blinded study was carried at a single tertiary care centre over eight years , looking at 100 patients with chronic suppurative otitis media involving small tympanic membrane perforations and pulsatile mucopurulent discharge .


The patients were randomised and divided into two groups .


In group A , the examination under microscope , with suction cleaning of the external canal , was followed by irrigation of the middle ear with antibiotic + steroid solution for up to one week , while group B was prescribed self-administration of the same drops with systemic antibiotics .


The patients were followed up daily for 10 days to monitor otorrhoea relief and on a weekly basis subsequently to monitor the healing of the tympanic membrane .


Forty-nine patients in group A had a dry ear after 3-7 days of daily suction and the irrigation of middle ear with the antibiotic + steroid solution and 44 had a healed tympanic membrane after an average three months of follow-up .


Five patients with dry ear but persistent perforation underwent tympanoplasty , while only one patient with a persistent ear discharge underwent mastoid exploration .


In group B , eight patients on oral antibiotics and self-administration of the same drops had dry ear while 34 had dry ear after receiving intravenous antibiotics .


Thirty perforations healed spontaneously and 12 required tympanoplasty .


In 8 patients , the tympano-mastoid was explored and these patients had dry , hearing ears only after surgery .


Patients with chronic suppurative otitis media involving small perforations and pulsatile discharge can be managed conservatively with simple suction cleaning + middle ear irrigation with antibiotics + steroid drops .


Nutrients such as -3 fatty acids including fish oil components eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) suppress the growth and promote apoptosis of tumor cells , improve immune function and reduce the effects of systemic inflammatory response syndrome .


We sought to investigate the effect of -3 fish oil fat emulsion-based parenteral nutrition ( PN ) on nutritional state , immune function , inflammatory reaction , expression of tumor factors and complication incidence in patients after surgical resection of gastric cancer .


Forty-eight patients after surgical operation of gastric tumor in hospital were randomly divided into the control group and intervention group .


Patients in both groups were treated with iso-nitrogen and iso-caloric parenteral nutrition support .


In addition , the intervention group received -3 fish oil fat emulsion and the control group received soybean oil .


The indicators of nutrition , immune function and inflammation in the two groups were detected on the day before the operation and postoperative day 6 .


The rate of complication was compared between the two groups .


There was no significant difference in nutritional state , liver function and renal function between the two groups ( P > 0.05 ) .


However , the levels of inflammatory markers were significantly decreased ( P < 0.01 ) , and the rate of complication was also decreased in the intervention group as compared with the control group .


-3 fish oil fat emulsion-based parenteral nutrition alleviates the inflammatory reaction and reduces the rate of inflammatory complications .


Cryolipolysis is a noninvasive and well-tolerated treatment for reduction of localized subcutaneous fat .


Although several studies demonstrate the safety and efficacy of this procedure , volumetric fat reduction from this treatment has not been quantified .


This prospective study investigated the change in volume of fat after cryolipolysis treatment using three-dimensional ( 3D ) photography .


A prospective study of subjects treated with cryolipolysis on the flank ( love handle ) was performed at Massachusetts General Hospital .


Volume measurements were performed with a Canfield Scientific Vectra three-dimensional camera and software to evaluate the amount of post procedure volume change .


Clinical outcomes were assessed with caliper measurements , subject surveys , and blinded physician assessment of photographs .


Eleven subjects were enrolled in this study .


Each subject underwent a single cycle of cryolipolysis to one flank .


The untreated flank served as an internal control .


The follow-up time after treatment was 2 months .


The mean amount of calculated absolute fat volume loss using 3D photography from baseline to 2 months follow-up visit was 56.225.6 from the treatment site and 16.617.6 cc from the control ( P < 0.0001 ) .


A mean absolute difference of 39.6 cc between the treated and untreated sides was calculated at 2 months post-treatment .


Comparison of caliper measurements from baseline to 2 months post-treatment demonstrated significant reduction of the treated flank from 45.65.8 mm at baseline to 38.64.6 mm at 2 months post-treatment ( P < 0.001 ) .


The untreated flank did not show significant reduction with caliper measurements demonstrating 45.35.0 mm at baseline and 44.65.1 mm at 2 months post-treatment ( P = 0.360 ) .


No unexpected side effects or adverse events were reported .


Post-treatment satisfaction surveys demonstrated 82 % of subjects were satisfied with the results .


Cryolipolysis is a safe , well-tolerated , and effective noninvasive fat removal methodology that on average leads to 39.6 cc of fat loss of the treated flank at 2 months after a single treatment cycle .


Samatasvir is a pan-genotypic inhibitor of the hepatitis C ( HCV ) non-structural protein 5A ( NS5A ) .


This study evaluated the antiviral activity , pharmacokinetics and safety of samatasvir monotherapy in treatment-nave subjects infected with HCV genotype 1-4 .


Thirty-four genotype 1 and thirty genotype 2 , 3 or 4 subjects were randomized to receive for 3days placebo or samatasvir 25-100mg per day .


Plasma samples for HCV RNA , pharmacokinetics and sequencing were collected up to day 10 .


Samatasvir achieved potent antiviral activity across genotypes : mean maximum reductions from baseline were 3.2-3 .6 ( genotype 1a ) , 3.0-4 .3 ( genotype 1b ) , 3.2-3 .4 ( genotype 3 ) , and 3.6-3 .9 ( genotype 4 ) log10/ml respectively ; no viral rebound was observed during the 3-day treatment period .