In the yin-yang needling group , the acupoints of yin meridians such as Zuwuli ( LR 10 ) , Xuehai ( SP 10 ) , Yinlingquan ( SP 9 ) and Sanyinjiao ( SP 6 ) , etc. and the acupoints of yang meridians such as Biguan ( ST 31 ) , Liangqiu ( ST 34 ) and Yanglingquan ( GB 34 ) , etc. were selected .


The reducing manipulation of respiratory reinforcing and reducing technique was applied to the acupoints of yin meridians and the reinforcing manipulation was applied to the acupoints of yang meridians .


The kinematics time parameters were determined and compared before and 4 weeks after treatment .


After treatment , the differences in the gait cycle , the phase time of standing ( % ) , the phase time of single support ( % ) , the phase time of unilateral sway ( % ) on the affected ( healthy ) foot and phase time of double support ( % ) were significant as compared with those before treatment in the patients of the two groups ( all P < 0.05 ) , in which , the gait cycle ( 1.75 + / - 0.21 vs 2.02 + / - 0.37 ) , the phase time of standing ( % ) on the affected ( healthy ) foot [ ( 65.41 + / - 5.20 ) % vs ( 68.37 + / - 6.24 ) % , ( 70.99 + / - 6.47 ) % vs ( 74.51 + / - 5.19 ) % ] , the phase time of unilateral sway ( % ) on the affected ( healthy ) foot [ ( 36.08 + / - 4.86 ) % vs ( 33.65 + / - 2.94 ) % , ( 31.04 + / - 3.41 ) % vs ( 26.77 + / - 2.67 ) % ] and the phase time of double support ( % ) [ ( 36.91 + / - 5.10 ) % vs ( 41.22 + / - 5.39 ) % ] in the yin-yang needling group were improved much obviously after treatment as compared with those in the conventional acupuncture group .


The differences in support phase time ( % ) , single support phase time ( % ) and sway phase time ( % ) were significant between the affected limb and healthy limb of the two groups after treatment ( all P < 0.05 ) .


Yin-yang respiratory reinforcing and reducing needling technique effectively improves hemiplegic gait movement cycle and walking function in patients of ischemic stroke , which is superior to the conventional acupuncture treatment .


Biofeedback is a self-regulation therapy by which the patient learns how to optimize the functioning of his autonomic nervous system .


It has been applied to patients with various cardiovascular disorders .


The purpose of this study was to investigate the practical feasibility and the psychophysiological effects of biofeedback applied to heart rate variability ( HRV biofeedback ) in order to increase cardiac coherence in coronary artery disease ( CAD ) patients participating in a cardiac rehabilitation programme .


In this randomised and controlled study , 31 CAD patients were randomly assigned to an experimental or to a control group .


The experimental group participated in a programme of 10 sessions of cardiac coherence biofeedback training , in addition to the rehabilitation programme .


The control group participated in the usual cardiac rehabilitation programme only .


Physiological variables ( systolic and diastolic blood pressure , SDNN ) and psychosocial variables ( anxiety , depression , type D personality ) were measured at the start and at the end of the programme in both groups .


Statistical comparisons assessed the inter and intra group differences .


The small sample size precludes any firm conclusions concerning the effect of cardiac coherence biofeedback on physiological or psychological variables .


However , we observed a significant increase of the percentage of cardiac coherence , in relation with an increased SDNN index .


Our study demonstrated the practical feasibility of cardiac coherence biofeedback training in CAD patients .


Further research is desirable to investigate the potential benefit of cardiac coherence biofeedback as an adjunct to stress management in cardiac rehabilitation .


Each year approximately 3000 patients in the United Kingdom undergo surgery for esophagogastric cancer .


Jejunostomy feeding tubes , placed at the time of surgery for early postoperative nutrition , have been shown to have a positive impact on clinical outcomes in the short term .


Whether feeding out of hospital is of benefit is unknown .


Local experience has identified that between 15 and 20 % of patients required ` rescue ' jejunostomy feeding for nutritional problems and weight loss while at home .


This weight loss and poor nutrition may contribute to the detrimental effect on the overall quality of life ( QoL ) reported in these patients .


This randomized pilot and feasibility study will provide preliminary information on the routine use of jejunostomy feeding after hospital discharge in terms of clinical benefits and QoL .


Sixty participants undergoing esophagectomy or total gastrectomy will be randomized to receive either a planned program of six weeks of home jejunostomy feeding after discharge from hospital ( intervention ) or treatment-as-usual ( control ) .


The intention of this study is to inform a multi-centre randomized controlled trial .


The primary outcome measures will be recruitment and retention rates at six weeks and six months .


Secondary outcome measures will include disease specific and general QoL measures , nutritional parameters , total and oral nutritional intake , hospital readmission rates , and estimates of healthcare costs .


Up to 20 participants will also be enrolled in a qualitative sub-study that will explore participants ' and carers ' experiences of home tube feeding.The results will be disseminated by presentation at surgical , gastroenterological and dietetic meetings and publication in appropriate peer review journals .


A patient-friendly lay summary will be made available on the University of Leicester and the University Hospitals of Leicester NHS Trust websites .


The study has full ethical and institutional approval and started recruitment in July 2012 .


UKClinical Research Network ID # 12447 ( Main study ) ; UKCRN ID # 13361 ( Qualitative sub study ) ; ClinicalTrials.gov #NCT 01870817 ( First registered 28 May 2013 ) .


To investigate whether the neural representations underlying alternating two acupoint combinations ( ACs ) are the same or not .


In this functional magnetic resonance imaging study , two sets of analgesia ACs were utilized , including Waiguan ( TE5 ) and Qiuxu ( GB40 ) for Group A , and Neiguan ( PC6 ) and Taichong ( LR3 ) for Group B , which are the most commonly adopted in clinical treatment .


Each group had 20 healthy subjects .


An experimental design was proposed , which consisted of a pre-needling resting phase , a needling phase and a post-needling resting phase .


This paradigm optimally mimics the clinical protocol as well as focuses on both the stimulation and the resting periods .


The results were subjected to general linear model analysis , conjunction analysis and the functional connectivity analysis .


The rostral anterior cingulated cortex was engaged in the initiative period of the acupuncture effect in both groups , and it was chosen as the seed region for the functional connectivity analysis for the following resting period .


The results showed that several shared brain regions were involved in both groups , in particular the insula , amygdala and hypothalamus .


Moreover , significant differences were located at the posterior cingulated cortex as revealed by a two sample - test ( P < 0.05 , corrected ) .


Other regions showed no significant differences .


This finding was further supported by the spatial correlation analysis that the two groups were significantly correlated ( r = 0.51 , P < 0.01 ) .


This preliminary research helps us understand the neurophysiological mechanisms of acupuncture when following clinical guidelines on ACs , as well as provides an important opportunity to develop better treatment strategies for reducing , or even preventing pain .


To assess whether a dementia care coordination intervention delays time to transition from home and reduces unmet needs in elders with memory disorders .


18-month randomized controlled trial of 303 community-living elders .


28 postal code areas of Baltimore , MD. .


Age 70 + years , with a cognitive disorder , community-living , English-speaking , and having a study partner available .


18-month care coordination intervention to systematically identify and address dementia-related care needs through individualized care planning ; referral and linkage to services ; provision of dementia education and skill-building strategies ; and care monitoring by an interdisciplinary team .


Primary outcomes were time to transfer from home and total percent of unmet care needs at 18months .


Intervention participants had a significant delay in time to all-cause transition from home and the adjusted hazard of leaving the home was decreased by 37 % ( Hazard ratio : 0.63 , 95 % Confidence Interval : 0.42-0 .94 ) compared with control participants .


Although there was no significant group difference in reduction of total percent of unmet needs from baseline to 18 months , the intervention group had significant reductions in the proportion of unmet needs in safety and legal/advance care domains relative to controls .


Intervention participants had a significant improvement in self-reported quality of life ( QOL ) relative to control participants .


No group differences were found in proxy-rated QOL , neuropsychiatric symptoms , or depression .


A home-based dementia care coordination intervention delivered by non-clinical community workers trained and overseen by geriatric clinicians led to delays in transition from home , reduced unmet needs , and improved self-reported QOL .


This study investigated long-term effects and implementation processes of workplace strength training for musculoskeletal disorders .


333 and 140 laboratory technicians from private and public sector companies , respectively , replied to a 3-year follow-up questionnaire subsequent to a 1-year randomized controlled trial ( RCT ) with high-intensity strength training for prevention and treatment of neck , shoulder , and arm pain .


Being a natural experiment , the two participating companies implemented and modified the initial training program in different ways during the subsequent 2 years after the RCT .


At 3-year follow-up the pain reduction in neck , shoulder , elbow , and wrist achieved during the first year was largely maintained at both companies .


However , the private sector company was rated significantly better than the public sector company in ( 1 ) training adherence , ( 2 ) training culture , that is , relatively more employees trained at the workplace and with colleagues , ( 3 ) self-reported health changes , and ( 4 ) prevention of neck and wrist pain development among initially pain-free employees .


This natural experiment shows that strength training can be implemented successfully at different companies during working hours on a long-term basis with lasting effects on pain in neck , shoulder , and arm .


This double-blind , randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure .


There were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide ( 200 g , twice a day [ bid ] ) , oral dexamethasone ( 4 mg , bid ) , or placebo ( 46 in each group ) .


They traveled to 3900 m altitude from 400 m by car .


Medication started 1 day before high-altitude exposure and continued until the third day of exposure .


Primary outcome measure was the incidence of acute mountain sickness after exposure .


One hundred twenty-four subjects completed the study ( 42 , 39 , and 43 in the budesonide , dexamethasone , and placebo groups , respectively ) .


Demographic characteristics were comparable among the 3 groups .


After high-altitude exposure , significantly fewer participants in the budesonide ( 23.81 % ) and dexamethasone ( 30.77 % ) groups developed acute mountain sickness compared with participants receiving placebo ( 60.46 % ) ( P = .0006 and P = .0071 , respectively ) .


Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation ( SpO2 ) than the placebo group at altitude .


Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group .


Four subjects in the dexamethasone group reported adverse reactions .


Both inhaled budesonide ( 200 g , bid ) and oral dexamethasone ( 4 mg , bid ) were effective for the prevention of acute mountain sickness , especially its severe form , compared with placebo .


Budesonide caused fewer adverse reactions than dexamethasone .


To evaluate heart rate variability ( HRV ) , hemodynamics , mechanics , dyspnea and blood gases following different mechanical ventilation ( MV ) settings .


No study has evaluated physiological changes during T-piece trials following different MV settings .


In 8 COPD patients on prolonged MV we applied in random order two MV settings : i ) pressure support ( PS ) 20 cm H2O + positive end-expiratory pressure ( PEEP ) 0 cm H2O ( setting-1 ) and ii ) PS 15 cm H2O + PEEP 5 cm H2O ( setting-2 ) , each followed by a 30 min T-piece trial .


Setting-1 induced greater minute ventilation , tidal volume/inspiratory time and lower pulmonary artery occlusion pressure ; setting-2 reduced intrinsic PEEP .


Mechanics and hemodynamics data did not differ , but all HRV time domain indices were reduced only after setting-1 , suggesting a decreased parasympathetic and increased sympathetic cardiac modulation .


The T-piece trial following setting-2 seems less stressful on neural control of HRV .


Future studies on T-piece trials should consider the residual effect of the MV setting .


There is a gap in the literature regarding learning outcomes linked to the use of high-fidelity simulators compared to that of traditional teaching methods .


To examine the effect of using high-fidelity simulators on knowledge and skills acquisition and retention with university students .


A randomized two-arm trial using two different educational approaches on 90 nursing students assigned randomly to two groups was used at two points of time .


The results showed significant differences in favor of the participants in the high-fidelity simulator group on both the acquisition and retention of knowledge and skills over time .


However , a significant loss of cardiopulmonary resuscitation knowledge and skills occurred at 3 months after training in both groups .


The findings of this study may assist educators in integrating high-fidelity simulators in education and training .


In addition , the findings may help nursing educators to arrange additional cardiopulmonary resuscitation training sessions in order to improve cardiac arrested patients ' outcomes .


High-fidelity simulation ( HFS ) provides students with interactive learning experiences in a safe controlled environment .


HFS enables teachers to implement critical clinical scenarios , such as cardiac arrest , without risk to patients .


Integrating the simulation training into nursing curricula will help to overcome the challenges that face many courses , specifically the shortage of clinical areas for training and the increase in numbers of nursing students .


To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications .


In this phase III , randomized , double-blind , multicenter , 52-week study , the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment , as assessed with estimated glomerular filtration rate and categorized as mild , moderate , or severe ( 60 to 89 , 30 to 59 , and 15 to 29 mL/min/1 .73 m ( 2 ) , respectively ) .


Secondary end points included fasting plasma glucose ( FPG ) , weight , achievement of treatment targets , hyperglycemic rescue , and safety .


Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years , BMI of 30.4 kg/m ( 2 ) , HbA1c of 8.2 % ( 66 mmol/mol ) , and diabetes disease duration of 11.2 years .


HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin ( -0.83 % vs. -0.52 % , P = 0.0003 ) .


Decreases in HbA1c , FPG , and weight were seen through week 52 .


Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin ( P = 0.0017 ) .


Results of safety assessments were similar between groups , and most adverse events ( AEs ) were mild or moderate .


The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows : overall , 31.7 % , 25.2 % ; diarrhea , 10.0 % , 6.5 % ; nausea , 4.8 % , 3.3 % ; and vomiting , 1.6 % , 1.2 % , respectively .


Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy .


Antihypertensive drugs are used to control blood pressure ( BP ) and reduce macro - and microvascular complications in hypertensive patients with diabetes .


The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan .


Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine ( 5 mg/day ) or losartan ( 100 mg/day ) .


Patient evaluation included BP measurement , ambulatory BP monitoring , and assessment of vascular parameters using applanation tonometry , pulse wave velocity ( PWV ) , and flow-mediated dilation ( FMD ) of the brachial artery .


A total of 42 patients were evaluated ( 21 in each group ) , with a predominance of women ( 71 % ) in both groups .


The mean age of the patients in both groups was similar ( amlodipine group : 54.9 4.5 years ; losartan group : 54.0 6.9 years ) , with no significant difference in the mean BP [ amlodipine group : 145 14 mmHg ( systolic ) and 84 8 mmHg ( diastolic ) ; losartan group : 153 19 mmHg ( systolic ) and 90 9 mmHg ( diastolic ) ] .


The augmentation index ( 30 % 9 % and 36 % 8 % , p = 0.025 ) and augmentation pressure ( 16 6 mmHg and 20 8 mmHg , p = 0.045 ) were lower in the amlodipine group when compared with the losartan group .


PWV and FMD were similar in both groups .


Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan .


However , the use of losartan may be associated with independent vascular reactivity to the pressor effect .


The objective of the current study was to evaluate the efficacy of aminaphtone to control gum bleeding .


Fifteen male and 15 female children , aged between 10 and 18 years with a mean age of 13.4 years and with gingival bleeding , were enrolled in this randomized , double-blind , placebo-controlled , Phase IV clinical trial .


The inclusion criterion was gingivitis with gingival bleeding .


Participants were prescribed either aminaphtone or placebo .


Thirty identical boxes containing blister packs of identical pills of either aminaphtone or placebo were produced and coded with unique numbers by the manufacturer ( Baldacci Laboratory , Brazil ) and donated for this trial .


A research assistant administered aminaphtone ( Capilarema 75 mg ) to fifteen patients or placebo to fifteen patients twice daily for 5 days .


Intraoral clinical evaluations of bleeding were made before starting medication/placebo and then at 3 and 5 days after administration .


On comparing the number of bleeding points before and after treatment between the aminaphtone and placebo groups , we found significantly higher reductions with the medication ( P < 0.0001 ) .


Aminaphtone reduces gum bleeding in gingivitis , and may have a supportive role in the control of bleeding .


Magnetic resonance perfusion ( MRP ) and computed tomographic perfusion ( CTP ) are being increasingly applied in acute stroke trials and clinical practice , yet the comparability of their perfusion values is not well validated .


The aim of this study was to validate the comparability of CTP and MRP measures .


A 3-step approach was used .


Step 1 was a derivation step , where we analyzed 45 patients with acute ischemic stroke who had both CTP and MRP performed within 2 hours of each other and within 9 hours of stroke onset .


In this step , we derived the optimal perfusion map with the least difference between MRP and CTP .


In step 2 , the optimal map was validated on whole-brain perfusion data of 15 patients .


Step 3 was to apply the optimal perfusion map to define cross-modality reperfusion from acute CTP to 24-hour MRP in 45 patients and , in turn , to assess how accurately this predicted 3-month clinical outcome .


Among 8 different perfusion maps included in this study , time to peak of the residual function ( T ( max ) ) was the only one with a nonsignificant difference between CTP and MRP in delineating perfusion defects .


This was validated on whole-brain perfusion data , showing high concordance of T ( max ) between the 2 modalities ( concordance correlation coefficient of Lin , > 0.91 ) ; the best concordance was at 6 s.


At T ( max ) > 6 s threshold , MRP and CTP reached substantial agreement in mismatch classification ( > 0.61 ) .


Cross-modality reperfusion calculated by T ( max ) > 6 s strongly predicted good functional outcome at 3 months ( area under the curve , 0.979 ; P < 0.05 ) .


MRP and CTP can be used interchangeably if one uses T ( max ) measurement .


Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery .


The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study .


Twenty-three living donor liver transplantation ( LDLT ) donors were randomly assigned to either an experimental ( AO ) group , received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake , or a control ( CT ) group , administered no supplement .


Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system .


The antioxidative capacity of 90.9 % patients in the AO group increased after immunonutrition .


Compared to the CT group , the AO group was found to have higher antioxidant capacity and transferrin levels ; lower WBC , lymphocyte , and neutrophil counts ; and briefer duration of postoperative fever during the postsurgical period .


No significant differences were found between the 2 groups regarding the nutritional parameters ; liver functioning parameters ; immunological parameters ; intraoperative factors ; postoperative outcomes .


Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome .


The RITA-3 ( Third Randomised Intervention Treatment of Angina ) trial compared outcomes of a routine early invasive strategy ( coronary arteriography and myocardial revascularization , as clinically indicated ) to those of a selective invasive strategy ( coronary arteriography for recurrent ischemia only ) in patients with non-ST-segment elevation acute coronary syndrome ( NSTEACS ) .


At a median of 5 years ' follow-up , the routine invasive strategy was associated with a 24 % reduction in the odds of all-cause mortality .


This study reports 10-year follow-up outcomes of the randomized cohort to determine the impact of a routine invasive strategy on longer-term mortality .


We randomized 1,810 patients with NSTEACS to receive routine invasive or selective invasive strategies .


All randomized patients had annual follow-up visits up to 5 years , and mortality was documented thereafter using data from the Office of National Statistics .


Over 10 years , there were no differences in mortality between the 2 groups ( all-cause deaths in 225 [ 25.1 % ] vs. 232 patients [ 25.4 % ] : p = 0.94 ; and cardiovascular deaths in 135 [ 15.1 % ] vs. 147 patients [ 16.1 % ] : p = 0.65 in the routine invasive and selective invasive groups , respectively ) .


Multivariate analysis identified several independent predictors of 10-year mortality : age , previous myocardial infarction , heart failure , smoking status , diabetes , heart rate , and ST-segment depression .


A modified post-discharge Global Registry of Acute Coronary Events ( GRACE ) score was used to calculate an individual risk score for each patient and to form low-risk , medium-risk , and high-risk groups .


Risk of death within 10 years varied markedly from 14.4 % in the low-risk group to 56.2 % in the high-risk group .


This mortality trend did not depend on the assigned treatment strategy .


The advantage of reduced mortality of routine early invasive strategy seen at 5 years was attenuated during later follow-up , with no evidence of a difference in outcome at 10 years .


Further trials of contemporary intervention strategies in patients with NSTEACS are warranted .


( Third Randomised Intervention Treatment of Angina trial [ RITA-3 ] ; ISRCTN07752711 ) .


Communication about end-of-life care is a core clinical skill .


Simulation-based training improves skill acquisition , but effects on patient-reported outcomes are unknown .


To assess the effects of a communication skills intervention for internal medicine and nurse practitioner trainees on patient - and family-reported outcomes .


Randomized trial conducted with 391 internal medicine and 81 nurse practitioner trainees between 2007 and 2013 at the University of Washington and Medical University of South Carolina .


Participants were randomized to an 8-session , simulation-based , communication skills intervention ( N = 232 ) or usual education ( N = 240 ) .


Primary outcome was patient-reported quality of communication ( QOC ; mean rating of 17 items rated from 0-10 , with 0 = poor and 10 = perfect ) .


Secondary outcomes were patient-reported quality of end-of-life care ( QEOLC ; mean rating of 26 items rated from 0-10 ) and depressive symptoms ( assessed using the 8-item Personal Health Questionnaire [ PHQ-8 ] ; range , 0-24 , higher scores worse ) and family-reported QOC and QEOLC .


Analyses were clustered by trainee .


There were 1866 patient ratings ( 44 % response ) and 936 family ratings ( 68 % response ) .


The intervention was not associated with significant changes in QOC or QEOLC .


Mean values for postintervention patient QOC and QEOLC were 6.5 ( 95 % CI , 6.2 to 6.8 ) and 8.3 ( 95 % CI , 8.1 to 8.5 ) respectively , compared with 6.3 ( 95 % CI , 6.2 to 6.5 ) and 8.3 ( 95 % CI , 8.1 to 8.4 ) for control conditions .


After adjustment , comparing intervention with control , there was no significant difference in the QOC score for patients ( difference , 0.4 points [ 95 % CI , -0.1 to 0.9 ] ; P = .15 ) or families ( difference , 0.1 [ 95 % CI , -0.8 to 1.0 ] ; P = .81 ) .


There was no significant difference in QEOLC score for patients ( difference , 0.3 points [ 95 % CI , -0.3 to 0.8 ] ; P = .34 ) or families ( difference , 0.1 [ 95 % CI , -0.7 to 0.8 ] ; P = .88 ) .


The intervention was associated with significantly increased depression scores among patients of postintervention trainees ( mean score , 10.0 [ 95 % CI , 9.1 to 10.8 ] , compared with 8.8 [ 95 % CI , 8.4 to 9.2 ] ) for control conditions ; adjusted model showed an intervention effect of 2.2 ( 95 % CI , 0.6 to 3.8 ; P = .006 ) .


Among internal medicine and nurse practitioner trainees , simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care but was associated with a small increase in patients ' depressive symptoms .


These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment .


clinicaltrials.gov Identifier : NCT00687349 .


NSAIDs , such as diclofenac , are the most commonly used medications to treat osteoarthritis ( OA ) , but they are associated with dose-related adverse events ( AEs ) .


Low-dose submicron diclofenac was developed using a new , proprietary dry milling process that creates submicron drug particles ( SoluMatrix Fine Particle Technology * ) , enabling effective treatment at lower doses than other commercially available diclofenac drug products .


This phase 3 study evaluated the efficacy and safety of low-dose submicron diclofenac 35mg three times daily ( tid ) and twice daily ( bid ) in patients with OA pain .


This double-blind study enrolled patients 40 years of age with clinically and radiographically confirmed ( Kellgren-Lawrence grade II-III ) hip or knee OA .


Eligible patients were chronic NSAID and/or acetaminophen ( APAP ) users with baseline Western Ontario and McMasters Universities Osteoarthritis Index ( WOMAC ) pain subscale scores 40mm by visual analog scale and an OA flare ( 15mm increase in WOMAC pain subscale score following discontinuation of NSAIDs/APAP at screening ) .


Patients were randomized to submicron diclofenac 35mg tid , submicron diclofenac 35mg bid , or placebo for 12 weeks .


ClinicalTrials.gov identifier : NCT01461369 .


Efficacy parameters included mean change from baseline in WOMAC pain subscale score at week 12 ( primary efficacy parameter ) and in average total WOMAC score over 12 weeks .


Submicron diclofenac 35mg tid significantly improved WOMAC pain subscale scores from baseline at 12 weeks ( -44.1 ; p = 0.0024 ) compared with placebo ( -32.5 ) .


Submicron diclofenac 35mg bid provided numerical improvement in pain at week 12 that did not reach statistical significance ( -39.0 ; p = 0.0795 ) compared with placebo .


Submicron diclofenac 35mg tid ( -35.9 ; p = 0.0002 ) and 35mg bid ( -30.3 ; p = 0.0363 ) improved the average total WOMAC score in treated patients over 12 weeks compared with placebo ( -23.2 ) .


The most frequent AEs in the submicron diclofenac-treated groups were diarrhea , headache , nausea , and constipation .


The inclusion of patients with a documented requirement for analgesic therapy ( OA ` flare ' ) at baseline and the high rates of rescue medication usage in the placebo group may have impacted the study outcome for the submicron diclofenac treatment groups .


Low-dose submicron diclofenac is an effective therapeutic option for the treatment of OA pain .


The phase 3 TRANSFORMS and FREEDOMS studies established the efficacy of fingolimod in reducing multiple sclerosis ( MS ) relapses and magnetic resonance imaging lesions compared with intramuscular ( IM ) interferon ( IFN ) -1 a and placebo over 12 and 24 months , respectively .


To investigate the efficacy of fingolimod at the approved 0.5 mg dose in patients early in the MS disease course , post hoc subgroup analyses of TRANSFORMS ( n = 272 ) and FREEDOMS ( n = 217 ) data were conducted in patients who experienced their first MS symptom < 3 years before randomization .


Fingolimod 0.5 mg reduced annualized relapse rate by 73.4 % ( P = 0.0002 ) versus IFN-1a IM and by 67.4 % ( P < 0.0001 ) versus placebo in patients with < 3 years since first symptom ; respective reductions were 45.4 % and 51.4 % in subgroups of patients with 3 years since first symptom .


For patients with < 3 years since their first symptom , significantly fewer new/newly enlarged T2 lesions were observed with fingolimod versus IFN-1a IM ( mean number , 1.94 vs. 2.95 ; P = 0.036 ) or placebo ( 4.1 vs. 10.7 ; P < 0.001 ) ; the mean number of gadolinium-enhancing T1 lesions was significantly reduced versus placebo ( 0.3 vs. 1.1 ; P < 0.001 ) .


Fingolimod 0.5 mg is highly effective in reducing relapses and MRI activity in patients early in the MS disease course .


Scarring from bacterial keratitis remains a leading cause of visual loss .


To determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection .


The Steroids for Corneal Ulcers Trial ( SCUT ) was a randomized , double-masked , placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis .


Here , we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT .


We define earlier administration of corticosteroids ( vs placebo ) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics .


We assess the effect of topical corticosteroids ( vs placebo ) on 3-month best spectacle-corrected visual acuity in patients who received corticosteroids or placebo earlier vs later .


Further analyses were performed for subgroups of patients with non-Nocardia keratitis and those with no topical antibiotic use before enrollment .


Patients treated with topical corticosteroids as adjunctive therapy within 2 to 3 days of antibiotic therapy had approximately 1-line better visual acuity at 3 months than did those given placebo ( -0.11 logMAR ; 95 % CI , -0.20 to -0.02 logMAR ; P = .01 ) .


In patients who had 4 or more days of antibiotic therapy before corticosteroid treatment , the effect was not significant ; patients given corticosteroids had 1-line worse visual acuity at 3 months compared with those in the placebo group ( 0.10 logMAR ; 95 % CI , -0.02 to 0.23 logMAR ; P = .14 ) .


Patients with non-Nocardia keratitis and those having no topical antibiotic use before the SCUT enrollment showed significant improvement in best spectacle-corrected visual acuity at 3 months if corticosteroids were administered earlier rather than later .


There may be a benefit with adjunctive topical corticosteroids if application occurs earlier in the course of bacterial corneal ulcers .


We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome ( IRIS ) occurring within 12 weeks of starting antiretroviral therapy , and to evaluate its association with patient outcome at 48 weeks .


HIV-tuberculosis co-infected and antiretroviral therapy-nave adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment , and were then followed for 48 weeks .


Tuberculosis cases were diagnosed using WHO guidelines , and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS .


The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm ( 3 ) and HIV-1 RNA of 5.6 log10 copies/mL .


Mortality at week 48 was 6.1 % ( 35/573 ) .


Fifty-three ( 9.2 % ) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy .


Being female and having a low CD4 count , high HIV-1 RNA load , low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS .


After adjustment for baseline body mass index , CD4 count and hemoglobin , occurrence of tuberculosis-IRIS was independently associated with 48-week mortality ( aOR 2.72 95 % CI 1.14-6 .54 ) .


Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS .


In this large prospective cohort , tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation .


Rifaximin , a nonabsorbable antibiotic that decreases lipopolysaccharide ( LPS ) in cirrhotics , may decrease the elevated levels of microbial translocation , T-cell activation and inflammation in human immunodeficiency virus ( HIV ) - positive immune nonresponders to antiretroviral therapy ( ART ) .


HIV-positive adults receiving ART for 96 weeks with undetectable viremia for 48 weeks and CD4 ( + ) T-cell counts < 350 cells/mm ( 3 ) were randomized 2:1 to rifaximin versus no study treatment for 4 weeks .


T-cell activation , LPS , and soluble CD14 were measured at baseline and at weeks 2 , 4 , and 8 .


Wilcoxon rank sum tests compared changes between arms .


Compared with no study treatment ( n = 22 ) , rifaximin ( n = 43 ) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8 ( + ) T-cell activation ( median change , 0.0 % with rifaximin vs +0.6 % with no treatment ; P = .03 ) .


This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm .


Similarly , although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14 , there were no significant changes within the rifaximin arm .


In immune nonresponders to ART , rifaximin minimally affected microbial translocation and CD8 ( + ) T-cell activation .


Trial registration number.NCT01466595 .


Canagliflozin , a sodium glucose co-transporter 2 inhibitor , lowers plasma glucose in individuals with hyperglycemia by inhibiting renal glucose reabsorption and increasing glucosuria .


Urinary tract infections ( UTIs ) were characterized in patients with type 2 diabetes mellitus enrolled in Phase III studies of canagliflozin .


Analyses were performed in 2 pooled datasets : Population 1 ( N = 2313 ; mean exposure [ weeks ] : canagliflozin , 24.3 ; placebo , 23.8 ) including patients from 4 placebo-controlled studies ; Population 2 ( N = 9439 ; mean exposure [ weeks ] : canagliflozin , 68.1 ; control , 64.4 ) including patients from 8 placebo - and active-controlled studies ( including patients with renal impairment or high risk of cardiovascular disease , and older patients ) .


Individual studies in special patient populations and 2 active-controlled studies were analyzed separately .


Patients with a prior history of UTIs were not excluded from these studies .


Urinary tract infection frequency and characteristics were systematically collected , with additional information for each event collected using supplemental electronic case report forms .


In Populations 1 and 2 , canagliflozin 100 and 300 mg were associated with small increases in the incidence of UTIs compared with control , with no dose-dependence .


Urinary tract infections with canagliflozin were similar to those with control in severity , and upper UTIs were infrequent across groups .


No increase in serious events or those leading to discontinuation were seen with canagliflozin versus control .


Time to the first occurrence of symptomatic UTIs tended to be earlier with canagliflozin than placebo in Population 1 , and similar with canagliflozin and control in Population 2 ; median duration of events was similar across groups in both populations .


The proportion of patients with recurrent events was low across groups .


Canagliflozin was associated with a small increase in incidence of UTIs in patients with type 2 diabetes mellitus , with no increase in serious or upper UTIs .


To compare the erosion protection efficacy of a stabilised , stannous fluoride ( SnF2 ) dentifrice versus a sodium fluoride ( NaF ) dentifrice using a modified in situ clinical model .


This study , a randomised parallel group in situ design with in vivo product use and ex vivo acid challenge , compared : A , a dentifrice containing 1,450 ppm F as NaF ; B , a dentifrice containing 1,450 ppm F ( 1,100 ppm F as SnF2 + 350 ppm F as NaF ) ; and T , tap water .


Sample size was n = 4 per group ( total of 12 subjects ) and within each subject appliances were placed on each side of the mouth ( left and right ) .


Enamel specimens were placed in different positions of the mouth ( front , mid-front , mid-rear , rear ) in each appliance ( total = 8 specimens per subject ) .


Product treatment was twice per day ( lingual brushing for 30 seconds followed by swishing for 90 seconds with the resultant product/saliva slurry ) in vivo for 15 days , and ex vivo acid treatment ( 0.02 m citric acid 5 minutes four times per day ; total exposure time = 300 minutes ) .


Data were analysed using a general linear repeated measures model with treatment , side and position as fixed effects .


Within subjects , correlations were modelled assuming a different correlation and variance for treatment B relative to the other groups .


Pairwise treatment differences were performed using a 5 % two-sided significance level .


Enamel loss ( in m ) was significantly lower ( P < 0.005 ) for treatment B versus treatments A and T. Treatment B reduced enamel surface loss by 86.9 % relative to treatment A.


There was no statistical difference in mean enamel loss ( P = 0.51 ) between treatments A and T. Enamel loss was not statistically different for side ( left vs. right ; P = 0.44 ) or position ( front , mid-front , mid-rear , rear ; P = 0.36 ) .


This modified in situ erosion model confirmed the enhanced erosion protection benefits of a stabilised SnF2 dentifrice versus a conventional NaF dentifrice , validating the ability of the model to safely and effectively demonstrate differences in the erosion protection potential of oral care products .


Renin-angiotensin system ( RAS ) inhibition has proven to be helpful in reducing cardiovascular and kidney disease progression in the general population ; whether kidney transplant patients would derive similar benefits is unknown .


RAS inhibition also reduces posttransplantation erythrocytosis in kidney transplant recipients , but its effect on hemoglobin ( Hb ) levels in patients without posttransplantation erythrocytosis is unclear .


The Specific Management of Anemia and Hypertension in Renal Transplant ( SMAhRT ) recipients study was designed to examine the cardiovascular benefits of RAS blockade with telmisartan 80 mg versus placebo , and Hb management with darbepoetin in a randomized , double-blind , single-center controlled trial in 2,000 patients over 3 years .


The primary efficacy variable was a composite of all-cause mortality , myocardial infarction or stroke .


The SMAhRT study was stopped prematurely due to a lower than expected event rate .


At that point , 136 patients were enrolled and were followed for a mean duration of 15 months .


The use of RAS blockade was not associated with an increased risk of adverse events such as worsening anemia or hyperkalemia .


Likewise , the correction of Hb with darbepoetin was not associated with any increase in thrombotic events .


This study provides insight into the safety of RAS inhibition and Hb correction with an erythrocyte-stimulating agent in kidney transplant recipients .


Although many initiatives exist to improve the availability of healthy foods in corner stores , few randomized trials have assessed their effects .


This study evaluated , in a randomized controlled trial , the effects of a first-generation healthy corner store intervention on students ' food and beverage purchases over a 2-year period .


Participants ( n = 767 ) were fourth - , fifth - , and sixth-grade students .


Ten schools and their nearby corner stores ( n = 24 ) were randomly assigned to the healthy corner store intervention or an assessment-only control .


Intercept surveys directly assessed the nutritional characteristics of students ' corner store purchases at baseline , 1 and 2 years .


Students ' weight and heights were measured at baseline , 1 and 2 years .


There were no differences in energy content per intercept purchased from control or intervention schools at year 1 ( P = 0.12 ) or 2 ( P = 0.58 ) .


There were no differences between control and intervention students in BMI z score ( year 1 , P = 0.83 ; year 2 , P = 0.98 ) or obesity prevalence ( year 1 , P = 0.96 ; year 2 , P = 0.58 ) .


A healthy corner store initiative did not result in significant changes in the energy content of corner store purchases or in continuous or categorical measures of obesity .


These data will help to inform future interventions .


We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease ( NAFLD ) .


This was a 6-month intervention study including 93 males with NAFLD , matched for age and body mass index ( BMI ) .


Subjects were randomized into three groups to receive olive oil ( n = 30 ) , canola oil ( n = 33 ) , and commonly used soyabean/safflower oil ( control ; n = 30 ) as cooking medium ( not exceeding 20 g/day ) along with counseling for therapeutic lifestyle changes .


The BMI , fasting blood glucose ( FBG ) and insulin levels , lipids , homeostasis model of assessment for insulin resistance ( HOMA-IR ) , HOMA denoting - cell function ( HOMA-CF ) , and disposition index ( DI ) were measured at pre - and post-intervention .


Data were analyzed with one-way analysis of variance ( ANOVA ) and Tukey 's Honestly Significant Difference multiple comparison test procedures .


Olive oil intervention led to a significant decrease in weight and BMI ( ANOVA , P = 0.01 ) compared with the control oil group .


In a comparison of olive and canola oil , a significant decrease in fasting insulin level , HOMA-IR , HOMA-CF , and DI ( P < 0.001 ) was observed in the olive oil group .


Pre - and post-intervention analysis revealed a significant increase in high-density lipoprotein level ( P = 0.004 ) in the olive oil group and a significant decrease in FBG ( P = 0.03 ) and triglyceride ( P = 0.02 ) levels in the canola oil group .


The pre - and post-intervention difference in liver span was significant only in the olive ( 1.14 2 cm ; P < 0.05 ) and canola ( 0.66 0.33 cm ; P < 0.05 ) oil groups .


In the olive and canola oil groups , post-intervention grading of fatty liver was reduced significantly ( grade I , from 73.3 % to 23.3 % and from 60.5 % to 20 % , respectively [ P < 0.01 ] ; grade II , from 20 % to 10 % and from 33.4 % to 3.3 % , respectively [ P < 0.01 ] ; and grade III , from 6.7 % to none and from 6.1 % to none , respectively ) .


In contrast , in the control oil group no significant change was observed .


Results suggest significant improvements in grading of fatty liver , liver span , measures of insulin resistance , and lipids with use of canola and olive oil compared with control oils in Asian Indians with NAFLD .


An association of clinical and subclinical hypothyroidism with mild cognitive impairment ( MCI ) has not been established .


To evaluate the association of clinical and subclinical hypothyroidism with MCI in a large population-based cohort .


A cross-sectional , population-based study was conducted in Olmsted County , Minnesota .


Randomly selected participants were aged 70 to 89 years on October 1 , 2004 , and were without documented prevalent dementia [ CORRECTED ] .


A total of 2050 participants were evaluated and underwent in-person interview , neurologic evaluation , and neuropsychological testing to assess performance in memory , attention/executive function , and visuospatial and language domains .


Participants were categorized by consensus as being cognitively normal , having MCI , or having dementia according to published criteria .


Clinical and subclinical hypothyroidism were ascertained from a medical records linkage system .


Association of clinical and subclinical hypothyroidism with MCI .


Among 1904 eligible participants , the frequency of MCI was 16 % in 1450 individuals with normal thyroid function , 17 % in 313 persons with clinical hypothyroidism , and 18 % in 141 individuals with subclinical hypothyroidism .


After adjusting for covariates ( age , educational level , sex , apolipoprotein E 4 , depression , diabetes mellitus , hypertension , stroke , body mass index , and coronary artery disease ) we found no significant association between clinical or subclinical hypothyroidism and MCI ( odds ratio [ OR ] , 0.99 [ 95 % CI , 0.66-1 .48 ] and 0.88 [ 0.38-2 .03 ] , respectively ) .


No effect of sex interaction was seen on these effects .


In stratified analysis , the odds of MCI with clinical and subclinical hypothyroidism among men was 1.02 ( 95 % CI , 0.57-1 .82 ) and 1.29 ( 0.68-2 .44 ) and , among women , was 1.04 ( 0.66-1 .66 ) and 0.86 ( 0.37-2 .02 ) , respectively .


In this population-based cohort of elderly people , neither clinical nor subclinical hypothyroidism was associated with MCI .


Our findings need to be validated in a separate setting using the published criteria for MCI and confirmed in a longitudinal study .


To evaluate the clinical performance of adhesive restorations of resin composite and resin-modified glass-ionomer cements in primary molars .


This randomized clinical trial included subjects ( 5-9 year-old children ) selected at two university centers ( UFRGS and UNIFRA ) .


The sample consisted of 132 primary molars presenting active cavitated carious lesions ( with radiographic involvement of the inner half of the dentin ) , located on the occlusal and occlusal-proximal surface .


The sample was randomly divided into three groups , according to the restorative material : ( G1 ) universal restorative system ( Adper Single Bond 2 system and Filtek Z350 ) ; ( G2 ) : Resin-modified glass-ionomer cement ( Vitremer ) ; and ( G3 ) : Low shrink restorative system ( Filtek P90 ) .


The restorations were clinically and radiographically followed every 6 months for up to 18 months using the USPHS modified criteria for clinical evaluation .


Survival estimates for restoration longevity were evaluated using the Kaplan-Meier method .


Log-rank test ( P < 0.05 ) was used to compare the differences in the success rate according to the type of the restorative material .


The type of restorative material used did not influence the longevity of the restorations .


After clinical follow-up , there was no statistical difference in the rates of success for the three materials used to restore active cavitated carious lesions in primary molars .


The survival rates for the follow-up were similar regarding the number of restored surfaces and the caries removal technique ( partial or complete ) .


Mean estimated time of survival was 17.2 months ( 95 % CI : 16.7-17 .7 ) .


Estimated survival rates of the restorations were 100 % , 98 % , 88 % and 65 % at 1 , 6 , 12 and 18 months of clinical evaluations , respectively .


This study aimed to evaluate whether a high relative ADP induced aggregation ( r-ADP-agg ) is associated with an increased mortality in patients after coronary stent implantation .


Several trials were not able to improve clinical outcome by adapting platelet inhibition in patients after coronary stent implantation and high platelet reactivity ( HPR ) .


Platelet monitoring is complex and conventional definition of adenosindiphosphate ( ADP ) induced aggregation alone might not transfer the whole picture of adequate platelet inhibition in vivo .


In a prospective single-centre observational trial multiple electrode aggregometry was performed in whole blood of patients after stent implantation .


r-ADP-agg was defined as the ADP-thrombin receptor activating peptide ratio to reflect an individual degree of P2Y12 dependent platelet inhibition with a cut-off value for HPR of 50 % .


The primary end point was mortality .


Follow-up was completed in 176 of 184 patients ( 96 % ) with a mean follow-up time of 3.7 years .


35 ( 20 % ) patients revealed an r-ADP-agg 50 % .


An r-ADP-agg 50 % was associated with an increased mortality [ unadjusted hazard ratio ( HR ) 7.006 ( 2.561-19 .17 ) ; p = 0.0001 ] .


In a multivariable Cox regression analysis mortality was independently associated with an r-ADP-agg 50 % [ HR 3.324 ( 1.542-7 .165 ) ; p = 0.0022 ] , ACS-setting [ HR 3.249 ( 1.322-7 .989 ) ; p = 0.0102 ] and severely reduced LV function [ HR 5.463 ( 2.098-14 .26 ) ; p = 0.0005 ] .


An r-ADP-agg 50 % is associated with an increased mortality in patients after coronary stent implantation .


Furthermore , r-ADP-agg might represent a better tool to predict clinical outcome than the conventional ADP induced platelet aggregation alone .


The familial Mediterranean fever 50 score ( FMF50 ) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF .


To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine .


We re-analyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome .


The FMF50 score required improvement by 50 in five of six criteria ( attack frequency , attack duration , global patient assessment , global physician assessment , frequency of attacks with arthritis , and levels of acute-phase reactants ) without worsening of the sixth criterion .


In the original trial rilonacept was considered effective according to the primary outcome measure ( differences in the attack frequency ) with eight analyzable patients considered responders and four as non-responders .


According to the FMF50 score , only two participants would have been considered respondersto rilonacept , and one to placebo .


Only two participants had 50 % differences between rilonacept and placebo in five criteria .


The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by 50 % in only 2 participants and 5 participants had no attacks of arthritis either during screening ( before randomization ) or during treatment with rilonacept .


The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study .


To test the effectiveness of messages designed to reduce vaccine misperceptions and increase vaccination rates for measles-mumps-rubella ( MMR ) .


A Web-based nationally representative 2-wave survey experiment was conducted with 1759 parents age 18 years and older residing in the United States who have children in their household age 17 years or younger ( conducted June-July 2011 ) .


Parents were randomly assigned to receive 1 of 4 interventions : ( 1 ) information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention ; ( 2 ) textual information about the dangers of the diseases prevented by MMR from the Vaccine Information Statement ; ( 3 ) images of children who have diseases prevented by the MMR vaccine ; ( 4 ) a dramatic narrative about an infant who almost died of measles from a Centers for Disease Control and Prevention fact sheet ; or to a control group .


None of the interventions increased parental intent to vaccinate a future child .


Refuting claims of an MMR/autism link successfully reduced misperceptions that vaccines cause autism but nonetheless decreased intent to vaccinate among parents who had the least favorable vaccine attitudes .


In addition , images of sick children increased expressed belief in a vaccine/autism link and a dramatic narrative about an infant in danger increased self-reported belief in serious vaccine side effects .


Current public health communications about vaccines may not be effective .


For some parents , they may actually increase misperceptions or reduce vaccination intention .


Attempts to increase concerns about communicable diseases or correct false claims about vaccines may be especially likely to be counterproductive .


More study of pro-vaccine messaging is needed .


In Asian countries , paclitaxel once per week is used as second-line treatment in advanced gastric cancer , including human epidermal growth factor receptor 2 ( HER2 ) - positive tumors .


The role of anti-HER2 agents , including lapatinib , in this setting and population is unclear .


TyTAN was a two-part , parallel-group , phase III study in Asian patients .


An open-label , dose-optimization phase ( n = 12 ) was followed by a randomized phase ( n = 261 ) , in which patients who were HER2 positive by fluorescence in situ hybridization ( FISH ) received lapatinib 1,500 mg once per day plus once-per-week paclitaxel 80 mg/m ( 2 ) or paclitaxel alone .


The primary end point was overall survival ( OS ) .


Secondary end points included progression-free survival ( PFS ) , time to progression ( TTP ) , overall response rate ( ORR ) , time to response , response duration , and safety .


Analyses were based on immunohistochemistry ( IHC ) and gastrectomy status , prior trastuzumab therapy , and regional subpopulations .


Median OS was 11.0 months with lapatinib plus paclitaxel versus 8.9 months with paclitaxel alone ( P = .1044 ) , with no significant difference in median PFS ( 5.4 v 4.4 months ) or TTP ( 5.5 v 4.4 months ) .


ORR was higher with lapatinib plus paclitaxel versus paclitaxel alone ( odds ratio , 3.85 ; P < .001 ) .


Better efficacy with lapatinib plus paclitaxel was demonstrated in IHC3 + compared with IHC0/1 + and 2 + patients and in Chinese compared with Japanese patients .


A similar proportion of patients experienced adverse events with each treatment ( lapatinib plus paclitaxel , 100 % v paclitaxel alone , 98 % ) .


Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3 + advanced gastric cancer but did not significantly improve OS in the intent-to-treat population .


To evaluate the efficacy of a brief 4-w group-administered treatment program of cognitive behavior therapy for insomnia ( CBT-I ) for older adults with sleep maintenance insomnia .


Randomized controlled trial of CBT-I compared to waitlist control with comparisons at pretreatment , posttreatment , and 3-mo follow-up .


Flinders University Sleep and Circadian Rhythm Research Laboratory , Adelaide , South Australia .


One-hundred eighteen adults with sleep maintenance insomnia ( mean age = 63.76 y , standard deviation = 6.45 y , male = 55 ) .


A 4-w , group-based treatment program of CBT-I including bedtime restriction therapy , sleep education , and cognitive restructuring .


Seven-day sleep diaries , actigraphy , and several self-report measures to assess perceived insomnia severity , daytime functioning , and confidence in and beliefs about sleep .


The brief group-administered CBT-I program produced improvements in the timing and quality of sleep including later bedtimes , earlier out-of-bed times , reduced wake after sleep onset , and improved sleep efficiency .


Participants also reported a reduction of the Insomnia Severity Index , Flinders Fatigue Scale , Epworth Sleepiness Scale , Daytime Feeling and Functioning Scale , Sleep Anticipatory Anxiety Questionnaire , the Dysfunctional Beliefs and Attitudes Scale , and increased Sleep Self-Efficacy Scale .


The treatment program used in the current study has demonstrated potential for a brief , inexpensive , and effective treatment of sleep maintenance insomnia in the older adult population .


Eating carbohydrate foods with a high glycemic index ( GI ) has been postulated to result in fetoplacental overgrowth and higher infant body fat .


A diet with a low glycemic index ( LGI ) has been shown to reduce birth percentiles and the ponderal index ( PI ) .


We investigated whether offering LGI dietary advice at the first antenatal visit would result in a lower fetal birth weight , birth percentile , and PI than providing healthy eating ( HE ) advice .


This advice had to be presented within the resources of routine antenatal care .


The Pregnancy and Glycemic Index Outcomes study was a 2-arm , parallel-design , randomized , controlled trial that compared the effects of LGI dietary advice with HE advice on pregnancy outcomes .


Eligible volunteers who attended for routine antenatal care at < 20 wk of gestation were randomly assigned to either group .


A total of 691 women were enrolled , and 576 women had final data considered .


In the LGI group , the GI was reduced from a mean ( SEM ) of 56 0.3 at enrollment to 52 0.3 ( P < 0.001 ) at the final assessment .


There were no significant differences in primary outcomes of fetal birth weight , birth percentile , or PI .


In a multivariate regression analysis , the glycemic load was the only significant dietary predictor ( P = 0.046 ) of primary outcomes but explained < 1 % of all variation .


A low-intensity dietary intervention with an LGI diet compared with an HE diet in pregnancy did not result in any significant differences in birth weight , fetal percentile , or PI .


A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension .


This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure , but data from prospective , randomized trials are limited .


A double-blind , randomized , controlled trial was conducted at 4 sites in the United States .


We enrolled 534 individuals 18 to 50 years of age with low vitamin D status ( 25-hydroxyvitamin D levels 25 ng/mL ) and systolic blood pressure of 120 to 159 mm Hg .


Participants were randomized to high-dose ( 4000 IU/d ) versus low-dose ( 400 IU/d ) oral vitamin D3 for 6 months .


The primary end point was change in mean 24-hour systolic blood pressure .


Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures .


The median age was 38 years , and 62 % of participants were men .


Forty-six percent of participants were white , and 48 % were black .


The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL .


Four-hundred fifty-five participants ( 85 % ) had at least 1 follow-up blood pressure measurement ; 383 participants ( 72 % ) completed the full 6-month study .


At the end of the study , there was no significant difference in the primary end point ( change in mean 24-hour systolic blood pressure , -0.8 versus -1.6 mm Hg in the high-dose and low-dose arms ; P = 0.71 ) or in any of the secondary end points .


Furthermore , there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months ( Spearman correlation coefficient , -0.05 , P = 0.34 ) .


Results were consistent across prespecified subgroups .


Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency .


Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal .


http://www.clinicaltrials.gov .


Unique identifier : NCT01240512 .


Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling .


Moreover , the utility of biological markers in predicting threshold levels is uncertain .


We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose ( ED ) and severity of clinical reaction in children with peanut allergy with B-cell , T-cell , and effector cell markers .


A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy .


All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred .


Severity of symptoms was graded from I to V. Biological markers were measured before challenge .


Forty-five of 63 patients showed objective symptoms after greater than 30 minutes , with a median latency of clinical reaction of 55 minutes .


By using a log-normal dose-distribution model , the ED5 was calculated to be 1.95 mg of peanut protein .


The ED was significantly and inversely correlated with peanut - and Ara h 2-specific IgE levels , skin prick test responses , basophil activation , and TH2 cytokine production by PBMCs .


Symptom severity did not correlate with any of the markers or the ED .


This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes .


By using this model , threshold levels , but not severity , could be correlated with biological markers .


Bleeding esophageal varices has been studied extensively , but bleeding gastric varices ( BGV ) has received much less investigation .


However , BGV has been reported in 30 % of patients with acute variceal bleeding .


In our studies of 1,836 bleeding cirrhotics , 12.7 % were bleeding from gastric varices .


BGV mortality rate of 45-55 % has been reported .


The BGV literature has mainly involved retrospective case reports , often with short-term follow-up .


We sought to describe the results of a prospective , randomized , controlled trial ( RCT ) in unselected , consecutive patients with BGV comparing endoscopic therapy ( ET ) with portacaval shunt ( PCS ; n = 518 ) , and later comparing emergency transjugular intrahepatic portosystemic shunt ( TIPS ) with emergency portacaval shunt ( EPCS ; n = 70 ) .


Initially , our RCT involved 518 patients with BGV comparing ET with direct PCS regarding control of bleeding , mortality rate , and disability .


When entry of patients ended , the RCT was expanded to compare emergency TIPS with EPCS ( n = 70 ) .


This RCT of BGV was separate from our other RCTs of bleeding esophageal varices .


Initially , ET was compared with PCS .


In the second part of our RCT , emergency TIPS was compared with emergency PCS ( EPCS ) .


Outcomes were survival , control of bleeding , portal-systemic encephalopathy ( PSE ) , quality of life , and direct costs of care .


In the RCT of ET versus PCS , 28 and 30 % , respectively , were in Child class C.


In the expanded RCT of TIPS versus EPCS , 40 and 41 % , respectively , were in Child class C. Permanent control of BGV was achieved in 97-100 % of patients treated by emergency or elective PCS , compared with 27-29 % by ET .


TIPS was even less effective , achieving long-term control of BGV in only 6 % .


Survival rates after PCS were greater at all time intervals and in all Child classes ( P < .001 ) .


Repeated episodes of PSE occurred in 50 % of TIPS patients , 16-17 % treated by ET , and 8-11 % treated by PCS .


Shunt stenosis or occlusion occurred in 67 % of TIPS patients , in contrast with 0-2 % of PCS patients .


These results support the conclusion that PCS is uniformly effective , whereas ET and TIPS are not very effective .


To measure the extent , determinants and results of bypassing local primary care clinics for childbirth among women in rural parts of the United Republic of Tanzania .


Women were selected in 2012 to complete a structured interview from a full census of all 30076 households in clinic catchment areas in Pwani region .


Eligibility was limited to those who had delivered between 6 weeks and 1 year before the interview , were at least 15 years old and lived within the catchment areas .


Demographic and delivery care information and opinions on the quality of obstetric care were collected through interviews .


Clinic characteristics were collected from staff via questionnaires .


Determinants of bypassing ( i.e. delivery of the youngest child at a health centre or hospital without provider referral ) were analysed using multivariate logistic regression .


Bypasser and non-bypasser birth experiences were compared in bivariate analyses .


Of 3019 eligible women interviewed ( 93 % response rate ) , 71.0 % ( 2144 ) delivered in a health facility ; 41.8 % ( 794 ) were bypassers .


Bypassing likelihood increased with primiparity ( odds ratio , OR : 2.5 ; 95 % confidence interval , CI : 1.9-3 .3 ) and perceived poor quality at clinics ( OR : 1.3 ; 95 % CI : 1.0-1 .7 ) and decreased if clinics recently underwent renovations ( OR : 0.39 ; 95 % CI : 0.18-0 .84 ) and/or performed 4 obstetric signal functions ( OR : 0.19 ; 95 % CI : 0.08-0 .41 ) .


Bypassers reported better quality of care on six of seven quality of care measures .


Many pregnant women , especially first-time mothers , choose to bypass local primary care clinics for childbirth .


Perceived poor quality of care at clinics was an important reason for bypassing .


Primary care is failing to meet the obstetric needs of many women in this rural , low-income setting .


Long-term effects of behavioural weight loss interventions on diabetes complications are unknown .


In a secondary analysis of the Look AHEAD ( Action for Health in Diabetes ) multicentre randomised clinical trial , we assessed whether an intensive lifestyle intervention ( ILI ) affects the development of nephropathy in people with type 2 diabetes .


Overweight or obese people aged 45-76 years with type 2 diabetes were randomly assigned ( 1:1 ) to ILI or to a diabetes support and education ( DSE ) group by a central web-based data management system , stratified by clinical centre and blocked with random block sizes .


The ILI was designed to achieve and maintain weight loss through reduced caloric consumption and increased physical activity .


The interventions were terminated early because of absence of effect on the primary outcome of cardiovascular disease events in the main Look AHEAD trial .


Albuminuria and estimated glomerular filtration rate were prespecified as two of many other outcomes and were assessed from baseline until the interventions ended .


They were combined post hoc to define the main outcome for this report , very-high-risk chronic kidney disease ( CKD ) , based on the 2013 Kidney Disease Improving Global Outcomes ( KDIGO ) classification .


Outcomes assessors and laboratory staff were masked to treatment , but participants and interventionists were not masked .


Time-to-event data were analysed by intention to treat by the Kaplan-Meier method and proportional hazards models .


The Look AHEAD trial is registered with ClinicalTrials.gov , NCT00017953 .


Of the 5145 participants randomly assigned in the Look AHEAD trial ( 2570 to ILI and 2575 to DSE ) , analyses for very-high-risk CKD were done in 2423 ( 94 % ) of patients in the ILI group and 2408 ( 94 % ) of those in the DSE group .


After a median of 80 years ( IQR 79-99 ) of follow-up , the incidence of very-high-risk CKD was lower in the ILI group than in the DSE group , with incidence rates of 091 cases per 100 person-years in the DSE group and 063 per 100 person-years in the ILI group ( difference 027 cases per 100 person-years , hazard ratio 069 , 95 % CI 055-087 ; p = 00016 ) .


This effect was partly attributable to reductions in bodyweight , HbA1c , and systolic blood pressure .


There were no safety concerns regarding kidney-related adverse events .


Weight loss should be considered as an adjunct to medical treatments to prevent or delay progression of CKD in overweight or obese people with type 2 diabetes .


National Institute of Diabetes and Digestive and Kidney Diseases .


To identify factors associated with variability in rifampin plasma pharmacokinetics and explore the relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration .


In this randomized , cross-over study , 12 healthy volunteers received either efavirenz 600mg/day or efavirenz 600mg with rifampin 600mg/day for 8days .


After a washout period of at least 2weeks , subjects crossed over to the alternate 8-day regimen .


Samples were obtained for pharmacokinetic assessment on day 8 of each study cycle .


Drugs concentrations were determined by a validated high-performance liquid chromatography .


Pharmacokinetic parameters were calculated using noncompartmental analysis .


Multivariate analysis was used to examine factors associated with rifampin pharmacokinetics .


Spearman correlation analysis was used to investigate relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration .


Of 11 evaluable subjects , the median interquartile range , rifampin peak concentration ( Cmax ) , area under the concentration-time curve ( AUC0-24hour ) , and weight-normalized clearance were 8.9 ( 7.3-13 .8 ) g/ml , 48.8 ( 29.6-67 .4 ) gh/ml , and 0.19 ( 0.11-0 .29 ) L/h/kg , respectively .


Solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) c. 388AG and SLCO1B1 c. 463CA polymorphisms jointly had significant effect on rifampin Cmax ( R ( 2 ) = 0.75 ) .


Male sex and SLCO1B1 c. 463CA polymorphism together influenced rifampin AUC0-24hour ( R ( 2 ) = 0.52 ) and weight-normalized clearance ( R ( 2 ) = 0.65 ) .


All four volunteers with rifampin Cmax less than8g/ml ( lower end of the normal range ) had c. 463CA genotype .


Rifampin Cmax and AUC0-24hour had no significant relationship with the efavirenz AUC0-24hour ratio or weight-normalized clearance ratio in the presence versus absence of rifampin ( p > 0.05 ) .


Men with the SLCO1B1c .463 CA genotype are at increased risk of lower rifampin plasma exposure .


However , plasma rifampin concentrations did not correlate with the extent of induction of efavirenz clearance by rifampin during coadministration .


The aim of this study is to assess the prevalence of non-opioid drug use among opioid-addicted , buprenorphine injecting individuals in Georgia , during and after a 12-week course of buprenorphine-naloxone ( Suboxone ) or methadone .


Randomized controlled trial with daily observed Suboxone or methadone and weekly counseling , urine tests and timeline followback ( TLFB ) in weeks 0-12 and 20 , and the Addiction Severity Index ( ASI ) at weeks 0 , 4 , 8 , 12 , 20 .


Of the 80 patients ( 40/group , 4 women ) , 68 ( 85 % ) completed the 12-weeks of study treatment and 66 ( 82.5 % ) completed the 20-week follow-up .


At baseline , injecting more than one drug in the last 30 days was reported by 68.4 % of patients in the methadone and 72.5 % in the Suboxone groups .


Drug use was markedly reduced in both treatment conditions but there were significant differences in the prevalence of specific drugs with more opioid ( 1.5 vs. 0.2 % ; p = 0.03 ) , less amphetamine ( 0.2 vs. 2.8 % ; p < 0.001 ) and less marijuana ( 1.7 vs. 10.2 % ; p < 0.001 ) positive urine tests in the methadone vs. Suboxone groups .


At the 20-week follow-up , TLFB results on the 34 that continued methadone or the 3 on Suboxone showed less opioid ( 5.6 vs. 27.6 % ; p < 0.001 ) , illicit buprenorphine ( 2.7 vs. 13.8 % ; p = 0.005 ) , benzodiazepine ( 13.5 vs. 34.5 % ; p < 0.001 ) , and marijuana ( 2.8 vs. 20.7 % ; p < 0.001 ) use than the 29 who did not continue opioid substitution therapy .


Despite small but significant differences in opioid and other drug use , both treatments were highly effective in reducing opioid and non-opioid drug use .


To determine the effectiveness of an interactive educational intervention on a physiotherapy guideline for hip and knee osteoarthritis .


Physiotherapists were randomly allocated to a 3-h interactive educational course with the collaboration of three patient partners or no intervention .


Assessments comprised questionnaires on adherence ( score range 0-24 ) , knowledge ( score range 0-76 ) , and barriers to use the guideline ( score range 0-80 ) .


Assessments were conducted 1 week before the interactive course ( T0 ) immediately after ( T1 ) , and 3 months thereafter ( T2 ) .


Change scores were compared between the groups by means of Mann-Whitney U tests and linear mixed models .


284 of 4328 eligible PTs ( 7 % ) were included .


The intervention ( n = 133 ) was significantly more effective than no intervention ( n = 151 ) concerning self-reported adherence and knowledge with mean differences in change scores ( 95 % CI ) at T1 and T2 being 1.4 ( 0.7-2 .0 ) and 0.9 ( 0.2-1 .7 ) for adherence and 6.8 ( 4.5-9 .1 ) and 3.9 ( 1.7-6 .2 ) for knowledge , ( all p values < 0.005 ) .


In both groups the barrier score increased at T1 and decreased at T2 , with a significantly larger increase at T1 and decrease at T2 in the intervention group ( mean differences 3.1 ( 1.8-4 .4 ) and 3.3 ( 0.5-6 .1 ) , respectively .


A short interactive educational course with patient participation on a PT guideline on hip and knee osteoarthritis showed a small to moderate positive effect on self-reported guideline adherence and knowledge , whereas for perceived barriers an advantage was only seen on the longer term .


Moderate , regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce .


We evaluated the relations between wine consumption , health status , circulating biomarkers , and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial .


A brief questionnaire on dietary habits was administered at baseline to 6973 patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell ` Insufficienza Cardiaca-Heart Failure ( GISSI-HF ) trial .


The relations between wine consumption , fatal and nonfatal clinical end points , quality of life , symptoms of depression , and circulating biomarkers of cardiac function and inflammation ( in subsets of patients ) were evaluated with simple and multivariable-adjusted statistical models .


Almost 56 % of the patients reported drinking at least 1 glass of wine per day .


After adjustment , clinical outcomes were not significantly different in the predefined 4 groups of wine consumption .


However , patients with more frequent wine consumption had a significantly better perception of health status ( Kansas City Cardiomyopathy Questionnaire score , adjusted P < 0.0001 ) , less frequent symptoms of depression ( Geriatric Depression Scale , adjusted P = 0.01 ) , and lower plasma levels of biomarkers of vascular inflammation ( osteoprotegerin and C-terminal proendothelin-1 , adjusted P < 0.0001 , and pentraxin-3 , P = 0.01 ) after adjusting for possible confounders .


We show for the first time in a large cohort of patients with chronic heart failure that moderate wine consumption is associated with a better perceived and objective health status , lower prevalence of depression , and less vascular inflammation , but does not translate into more favorable clinical 4-year outcomes .


URL : http://www.clinicaltrials.gov .


Unique identifier : NCT0033633 .


Recent randomised controlled trials have compared the effects of albumin and hydroxyethyl starch ( HES ) v crystalloids on patient-centred outcomes in critically ill patients .


The Saline v Albumin Fluid Evaluation ( SAFE ) trial reported patient-centred outcomes at 28 days in 6933 patients assigned to fluid resuscitation with either 4 % albumin or 0.9 % saline ; the Crystalloid v Hydroxyethyl Starch Trial ( CHEST ) reported patient-centred outcomes at 28 days in 6644 patients assigned to fluid resuscitation with either 6 % HES ( 130/0 .4 ) or 0.9 % saline .


As the two trials used a common reference fluid ( 0.9 % saline ) and had most trial methods and data collection points harmonised , a comparison of 4 % albumin and 6 % HES ( 130/0 .4 ) on patient-centred outcomes at 28 days in critically ill patients using the individual patient data from the two trials is feasible .


To prepublish the statistical analysis plan ( SAP ) of an individual patient data comparative analysis of the SAFE and CHEST studies .


The statistical analyses are described in detail with the appropriate statistical analysis specified .


The planned statistical analyses are described in detail for the SAFE and CHEST individual patient data comparative analysis .


We outline the proposed statistical analysis for the baseline characteristics , processes of care and the outcomes .


Subgroups are defined with statistical comparisons between the fluid groups and in each subgroup explained .


We have developed a SAP for the SAFE / CHEST individual patient data comparative analysis to increase the internal validity of the study and minimise bias .


Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD .


Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood .


In this study , we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD .


Twenty subjects with severe COPD were randomized into two groups : no treatment ( Control , n = 10 , 63.64.6 years , FEV1 29.613.3 % pred ) or inhaled tiotropium 18g once daily for 1 month ( n = 10 , 66.55.4 years , FEV1 33.011.1 % pred ) .


All subjects were allowed to continue their daily medications other than anti-cholinergics during the study .


Constant cycle exercise with 75 % of maximal workload and spirometry were performed before and 1 month after treatment .


Diaphragmatic EMG ( EMGdi ) and respiratory pressures were recorded with multifunctional esophageal catheter .


Efficiency of neural respiratory drive , defined as the ratio of minute ventilation ( VE ) and diaphragmatic EMG ( VE/EMGdi % max ) , was calculated .


Modified British Medical Research Council Dyspnea Scale ( mMRC ) was used for the evaluation of dyspnea before and after treatment .


There was no significant difference in spirometry before and after treatment in both groups .


Diaphragmatic EMG decreased significantly at rest ( 28.110.9 % vs. 22.610.7 % , P < 0.05 ) and mean efficiency of neural respiratory drive at the later stage of exercise increased ( 39.82.9 vs. 45.23.9 , P < 0.01 ) after 1-month treatment with tiotropium .


There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group .


The score of mMRC decreased significantly ( 2.50.5 vs. 1.90.7 , P < 0.05 ) after 1-month treatment with tiotropium , but without significantly difference in control group .


Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise , which might account for the improvement in exercise tolerance in COPD .


Combined treatment with a bisphosphonate and vitamin D has been proposed for postmenopausal osteoporosis .


A new , fixed-dose combination tablet of ibandronate plus vitamin D3 has been developed for monthly administration to treat postmenopausal osteoporosis .


The main objective of the present study was to compare the pharmacokinetics of vitamin D3 administered in 2 forms : a newly developed ibandronate 150-mg/vitamin D3 24,000-IU tablet ( DP-R206 , test drug ) and a stand-alone vitamin D3 24,000-IU tablet ( reference drug ) .


A secondary objective was to evaluate the safety and tolerability of DP-R206 in healthy adult male Korean volunteers .


This study was a single-dose , open-label , randomized-sequence , 2-treatment , 2-way crossover trial .


Blood samples were collected from 24 hours ' predose to 120 hours ' postdose .


The plasma concentrations of vitamin D3 were analyzed by using a validated HPLC-MS/MS method .


Pharmacokinetic parameters were calculated , and the 90 % CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using ANOVA .


Thirty-sex healthy adult male Korean volunteers with a mean ( SD ) age of 25.8 ( 2.7 ) years , a mean height of 174.0 ( 5.9 ) cm , and a mean weight of 69.1 ( 6.2 ) kg were enrolled ; 29 participants completed the study .


The 90 % CIs of the ratios of the geometric means ( test drug/reference drug ) of the baseline-corrected Cmax , AUC0-last , and AUC0 - values were 0.93 to 1.24 , 0.89 to 1.19 , and 0.87 to 1.18 , respectively .


The 90 % CIs of the ratios of the geometric means ( test drug/reference drug ) of the baseline-uncorrected Cmax , AUC0-last , and AUC0 - values were 0.93 to 1.24 , 0.88 to 1.19 , and 0.87 to 1.18 , respectively .


Eighty-four adverse events ( AEs ) were reported in 24 of 32 subjects receiving DP-R206 , and 14 AEs were reported in 8 of 29 subjects receiving the vitamin D3 24,000-IU tablet .


All of the subjects who experienced AEs recovered without sequelae , and no serious AEs were observed .


The vitamin D3 pharmacokinetics were similar for DP-R206 and the 24,000-IU vitamin D3 tablet .


DP-R206 was well tolerated .


Care management interventions in the German health-care system have been evaluated with promising results , but further research is necessary to explore their full potential in the context of multi-morbidity .


Our aim in this trial is to assess the efficacy of a primary care practice network-based care management intervention in improving self-care behaviour among patients with type 2 diabetes mellitus and multiple co-occurring chronic conditions .


The study is designed as a prospective , 18-month , multicentre , investigator-blinded , two-arm , open-label , individual-level , randomized parallel-group superiority trial .


We will enrol 582 patients with type 2 diabetes mellitus and at least two severe chronic conditions and one informal caregiver per patient .


Data will be collected at baseline ( T0 ) , at the primary endpoint after 9months ( T1 ) and at follow-up after 18months ( T2 ) .


The primary outcome will be the differences between the intervention and control groups in changes of diabetes-related self-care behaviours from baseline to T1 using a German version of the revised Summary of Diabetes Self-Care Activities ( SDSCA-G ) .


The secondary outcomes will be the differences between the intervention and control groups in : changes in scores on the SDSCA-G subscales , glycosylated haemoglobin A level , health-related quality of life , self-efficacy , differences in ( severe ) symptomatic hypoglycaemia , cost-effectiveness and financial family burden .


The intervention will be delivered by trained health-care assistants as an add-on to usual care and will consist of three main elements : ( 1 ) three home visits , including structured assessment of medical and social needs ; ( 2 ) 24 structured telephone monitoring contacts ; and ( 3 ) self-monitoring of blood glucose levels after T1 in 3-month intervals .


The control group will receive usual care .


The confirmatory primary analysis will be performed following the intention-to-treat ( ITT ) principle .


The efficacy of the intervention will be quantified using two-level linear regression stratified by type of medical treatment adjusted for baseline values on the SDSCA-G .


Secondary analyses will be performed according to the ITT principle .


In health economic evaluations , we will estimate the incremental cost-effectiveness ratios .


We hope that the results of this study will provide insights into the efficacy of practice network-based care management among patients with complex health-care needs .


Current Controlled Trials ISRCTN 83908315 ( ISRCTN assigned 25 February 2014 ) .


To determine if cats anaesthetised with alfaxalone have different recoveries to cats anaesthetised with a combination of ketamine and diazepam .


Anaesthesia for ovariohysterectomy was induced in cats with either alfaxalone ( n = 23 ) or a combination of ketamine and diazepam ( n = 22 ) .


All cats were premedicated with combinations of acepromazine and morphine .


Recoveries were scored using a categorical grading scheme applied to 18 parameters over 60 minutes following extubation .


The parameters scored covered movement , sensitivity to touch , sound and light , body position , sneezing and vocalisation .


One person scored all recoveries and they were blinded to the induction drug used .


Scores were compared between drugs at different times using the Kruskal-Wallis rank sum test .


Recovery scores were not normally distributed .


Analysis of the data using the Kruskal-Wallis rank sum test revealed that cats induced with alfaxalone showed an increase in recovery scores at 5 minutes for pawing at the head ( p = 0.001 ) .


No parameters differed significantly at 10 and 20 minutes .


For cats anaesthetised with ketamine and diazepam there was an increase at 30 minutes in pacing , jerky sudden movements , unsettledness and increased sensitivity to touch at the surgical site and on the head ( p0 .01 ) .


At 60 minutes cats anaesthetised with ketamine and diazepam still showed an increase in unsettledness compared to those cats anaesthetised with alfaxalone ( p = 0.005 ) .


The results suggest that recoveries of cats following alfaxalone induction are significantly different to recoveries after induction with ketamine and diazepam .


Overall , cats induced with ketamine and diazepam had more active and unsettled recoveries than alfaxalone over the 60-minute period observed .


Cats recovering from alfaxalone anaesthesia have more settled recoveries than cats recovering from ketamine and diazepam anaesthesia .


If a quiet settled recovery is desired following a surgical procedure , alfaxalone is likely to be a better choice than ketamine and diazepam .


Psychosocial stress is accompanied by an increase in the activity of the hypothalamic-pituitary-adrenocortical ( HPA ) - axis and by an increase in food intake .


At present , no studies have been conducted to examine the impact of a potent laboratory stress test on the chewing frequency .


Thirty-one healthy participants ( 14 females , mean age 27.13 ) were compared after they had fulfilled the protocol of a standardized psychosocial stress test , the Trier Social Stress Test ( TSST ) , and after a resting condition of silent reading in reference to their chewing frequency , chewing efficacy , food intake , and eating preferences .


As part of the design free salivary cortisol levels and heart rate variability were measured repeatedly before and after the TSST and the resting condition .


After the TSST , the participants exhibited a significantly higher mean chewing frequency than after the resting condition ( F ( 2,60 ) = 3.600 , p = .035 , ( 2 ) = .107 ) .


The testing condition had no influence on the amount of food intake .


Following the psychosocial stress , however , the participants reported a significantly less general appetite ( Z = -3.921 , p < .001 ) and less of an appetite for eggs ( Z = -2.023 , p = .043 ) than after their resting condition .


No correlation was found between the salivary cortisol response and the chewing frequency .


The results indicated that psychosocial stress is associated with an increase in chewing frequency , as measured with a sound-based apparatus , and with a decrease in appetite .


Health knowledge and literacy are among the main determinants of health .


Assessment of these issues via Web-based surveys is growing continuously .


Research has suggested that approximately one-fifth of respondents submit cribbed answers , or cheat , on factual knowledge items , which may lead to measurement error .


However , little is known about methods of discouraging cheating in Web-based surveys on health knowledge .


This study aimed at exploring the usefulness of imposing a survey time limit to prevent help-seeking and cheating .


On the basis of sample size estimation , 94 undergraduate students were randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition knowledge , with or without a time limit of 15 minutes ( 30 seconds per item ) ; the topic of nutrition was chosen because of its particular relevance to public health .


The questionnaire consisted of two parts .


The first was the validated consumer-oriented nutrition knowledge scale ( CoNKS ) consisting of 20 true/false items ; the second was an ad hoc questionnaire ( AHQ ) containing 10 questions that would be very difficult for people without health care qualifications to answer correctly .


It therefore aimed at measuring cribbing and not nutrition knowledge .


AHQ items were somewhat encyclopedic and amenable to Web searching , while CoNKS items had more complex wording , so that simple copying/pasting of a question in a search string would not produce an immediate correct answer .


A total of 72 of the 94 subjects started the survey .


Dropout rates were similar in both groups ( 11 % , 4/35 and 14 % , 5/37 in the untimed and timed groups , respectively ) .


Most participants completed the survey from portable devices , such as mobile phones and tablets .


To complete the survey , participants in the untimed group took a median 2.3 minutes longer than those in the timed group ; the effect size was small ( Cohen 's r = .29 ) .


Subjects in the untimed group scored significantly higher on CoNKS ( mean difference of 1.2 points , P = .008 ) and the effect size was medium ( Cohen 's d = 0.67 ) .


By contrast , no significant between-group difference in AHQ scores was documented .


Unexpectedly high AHQ scores were recorded in 23 % ( 7/31 ) and 19 % ( 6/32 ) untimed and timed respondents , respectively , very probably owing to `` e-cheating '' .


Cribbing answers to health knowledge items in researcher-uncontrolled conditions is likely to lead to overestimation of people 's knowledge ; this should be considered during the design and implementation of Web-based surveys .


Setting a time limit alone may not completely prevent cheating , as some cheats may be very fast in Web searching .


More complex and contextualized wording of items and checking for the `` findability '' properties of items before implementing a Web-based health knowledge survey may discourage help-seeking , thus reducing measurement error .


Studies with larger sample sizes and diverse populations are needed to confirm our results .


Trametinib , an oral mitogen/extracellular signal-related kinase ( MEK ) 1/2 inhibitor , holds promise for malignancies with rat sarcoma ( RAS ) mutations , like pancreas cancer .


This phase II study was designed to determine overall survival ( OS ) in patients with pancreas cancer treated with trametinib and gemcitabine .


Secondary end-points included progression-free survival ( PFS ) , overall response rate ( ORR ) and duration of response ( DOR ) ; safety end-points were also assessed .


Adults with untreated metastatic adenocarcinoma of the pancreas were randomised ( 1:1 ) to receive intravenous gemcitabine 1000 mg/m ( 2 ) ( weekly 7 for 8 weeks , then days 1 , 8 and 15 of 28-day cycles ) plus trametinib or placebo 2mg daily .


RAS mutations were determined in circulating free DNA ( cfDNA ) and archival tumour tissue .


OS was evaluated in kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutant and wild-type subgroups .


Baseline characteristics for 160 patients were similar in both treatment arms .


There was no significant difference in OS ( hazard ratio ( HR ) 0.98 ; 95 % confidence interval ( CI ) , 0.67-1 .44 ; P = .453 ) ; median OS was 8.4 months with gemcitabine plus trametinib and 6.7 months with gemcitabine plus placebo .


Median PFS ( 16 versus 15 weeks ) , ORR ( 22 % versus 18 % ) and median DOR ( 23.9 versus 16.1 weeks ) were also similar for trametinib and placebo arms , respectively .


KRAS mutation-positive patients ( n = 103 ) showed no difference in OS between arms .


Thrombocytopenia , diarrhoea , rash and stomatitis were more frequent with trametinib , as was grade 3 anaemia .


The addition of trametinib to gemcitabine did not improve OS , PFS , ORR or DOR in patients with previously untreated metastatic pancreas cancer .


Outcomes were independent of KRAS mutations determined by cfDNA .


Transurethral resection of prostate ( TURP ) is considered the gold standard for the surgical treatment of BPH .


Irrigant fluid absorption by the patient is a potentially serious complication of TURP and can lead to dilutional hyponatremia and TURP syndrome .


Other common complications of TURP include urinary tract infection and secondary haemorrhage .


The objective of this study was to compare the frequency of postoperative complications ( Urinary Tract infection and dilutional hyponatremia ) between 1.5 % glycine and sterile distilled water used as irrigant in BPH patients after TURP .


This randomized controlled trial was conducted in department of Urology , PIMS Islamabad , from August 2013 to February 2014 .


A total of 170 adult male patients between 50-80 years of age undergoing TURP with prostate volume more than 30cc on ultrasound .


85 patients each were randomly allocated to two groups .


In group-A , glycine was used as irrigan , t solution during TURP while in group-B distilled water was used .


Serum sodium levels were measured at 6th postoperative hour to look for dilutional hyponatremia .


On the 15th postoperative day they were inquired about any clinical features of urinary tract infection .


Also urine routine examination was performed to look for the presence of WBCs in the urine .


Post-operative dilutional hyponatremia was observed in 13 ( 15.3 % ) patients in Group A and in 10 ( 11.8 % ) patients in group-B .


The difference between both the groups being nonsignificant ( p-value = 0.501 ) .


Frequency of postoperative urinary tract infection on 15th postoperative day in group-A was 23 ( 27.1 % ) while in group-B it was 16 ( 18.8 % ) , the difference among both the groups being insignificant ( p-value = 0.202 ) .


Although the frequency of postoperative complications like UTI and dilutional hyponatremia was less with sterile distilled water , yet , the difference was statistically not significant .


To compare efficacy and safety of two , once-daily basal insulin formulations [ insulin lispro protamine suspension ( ILPS ) vs. insulin glargine ( glargine ) ] added to oral antihyperglycaemic medications ( OAMs ) and exenatide BID in suboptimally controlled type 2 diabetes ( T2D ) patients .


This 24-week , open-label , multicentre trial randomized patients to bedtime ILPS ( n = 171 ) or glargine ( n = 168 ) .


Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95 % confidence intervals ( CIs ) for change in haemoglobin A1c ( HbA1c ) from baseline to week 24 ( adjusted for baseline HbA1c ) with non-inferiority margin 0.4 % .