It has been developed to classify patients , but also to provide visual insight into the burden of COPD and to provide treatment advice .


Netherlands Trial Register , NTR3788 .


The aim of this study was to assess the effects of darapladib , a selective oral investigational lipoprotein-associated phospholipase A2 inhibitor , on both plasma and plaque lipoprotein-associated phospholipase A2 activity .


Patients undergoing elective carotid endarterectomy were randomized to darapladib 40 mg ( n = 34 ) , 80 mg ( n = 34 ) , or placebo ( n = 34 ) for 14 days , followed by carotid endarterectomy 24 hours after the last dose of study medication .


Darapladib 40 mg and 80 mg reduced plasma lipoprotein-associated phospholipase A2 activity by 52 % and 81 % , respectively , versus placebo ( both P < 0.001 ) .


Significant reductions in plaque lipoprotein-associated phospholipase A2 activity were also observed compared with placebo ( P < 0.0001 ) , which equated to a 52 % and 80 % decrease compared with placebo .


No significant differences were observed between groups in plaque lysophosphatidylcholine content or other biomarkers , although a dose-dependent decrease in plaque matrix metalloproteinase-9 mRNA expression was observed with darapladib 80 mg ( P = 0.053 vs placebo ) .


In a post-hoc analysis , plaque caspase-3 ( P < 0.001 ) and caspase-8 ( P < 0.05 ) activity were found to be significantly lower in the darapladib 80-mg group versus placebo .


No major safety concerns were identified in the study .


Short-term treatment ( 14 4 days ) with darapladib produced a robust , dose-dependent reduction in plasma lipoprotein-associated phospholipase A2 activity .


More importantly , darapladib demonstrated placebo-corrected reductions in carotid plaque lipoprotein-associated phospholipase A2 activity of similar magnitude .


Darapladib was generally well tolerated and no safety concerns were identified .


Additional studies of longer duration are needed to explore whether these pharmacodynamic effects are associated with improved clinical outcomes , as might be hypothesized .


The CpG island methylator phenotype ( CIMP ) , defined by a high frequency of aberrantly methylated genes , is a characteristic of a subclass of colon tumors with distinct clinical and molecular features .


Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy .


We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan ( IFL ) .


We analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery , from April 1999 through April 2001 .


The primary end point of the trial was overall survival and the secondary end point was disease-free survival .


DNA isolated from available tumor samples ( n = 615 ) was used to determine CIMP status based on methylation patterns at the CACNA1G , IGF2 , NEUROG1 , RUNX3 , and SOCS1 loci .


The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards ; interactions with treatment and BRAF , KRAS , and mismatch repair ( MMR ) status were also investigated .


Of the tumor samples characterized for CIMP status , 145 were CIMP positive ( 23 % ) .


Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors ( hazard ratio = 1.36 ; 95 % confidence interval : 1.01-1 .84 ) .


Treatment with IFLshowed a trend toward increased overall survival for patients with CIMP-positive tumors , compared with treatment with fluorouracil and leucovorin ( hazard ratio = 0.62 ; 95 % CI : 0.37-1 .05 ; P = .07 ) , but not for patients with CIMP-negative tumors ( hazard ratio = 1.38 ; 95 % CI : 1.00-1 .89 ; P = .049 ) .


In a 3-way interaction analysis , patients with CIMP-positive , MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy ( for the interaction , P = .01 ) .


CIMP was more strongly associated withresponse to IFL than MMR status .


Results for disease-free survival times were comparable among all analyses .


Patients with stage III , CIMP-positive , MMR-intact colon tumors have longer survival times when irinotecan is added to combination therapy with fluorouracil and leucovorin .


We assessed the effectiveness of Circle of Life ( COL ) , an HIV-preventive intervention developed specifically for American Indian and Alaska Native ( AI/AN ) middle school youths .


By partnering with a tribal community , we conducted a longitudinal wait-listed group randomized trial with 635 seventh and eighth graders in 13 schools of a Northern Plains tribe .


We surveyed participants at baseline , 3 months , and 12 months from 2006 to 2007 .


COL was found to increase HIV knowledge in the short term , but had no effect on sexual activity compared with those who did not receive it .


However , COL was found to be effective for delaying the onset of sexual activity , with the greatest reduction in risk occurring for those receiving COL at early ages .


Community partnership was key to successful project design , implementation , and analysis .


The project confirmed the importance of the timing of interventions in early adolescence .


COL may be a key resource for reducing sexual risk among AI/AN youths .


Patients with radioactive iodine ( ( 131 ) I ) - refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options .


In this study , we assessed the efficacy and safety of orally administered sorafenib in the treatment of patients with this type of cancer .


In this multicentre , randomised , double-blind , placebo-controlled , phase 3 trial ( DECISION ) , we investigated sorafenib ( 400 mg orally twice daily ) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid cancer that had progressed within the past 14 months .


Adult patients ( 18 years of age ) with this type of cancer were enrolled from 77 centres in 18 countries .


To be eligible for inclusion , participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria In Solid Tumors ( RECIST ) ; Eastern Cooperative Oncology Group performance status 0-2 ; adequate bone marrow , liver , and renal function ; and serum thyroid-stimulating hormone concentration lower than 05 mIU/L .


An interactive voice response system was used to randomly allocate participants in a 1:1 ratio to either sorafenib or matching placebo .


Patients , investigators , and the study sponsor were masked to treatment assignment .


The primary endpoint was progression-free survival , assessed every 8 weeks by central independent review .


Analysis was by intention to treat .


Patients in the placebo group could cross over to open-label sorafenib upon disease progression .


Archival tumour tissue was examined for BRAF and RAS mutations , and serum thyroglobulin was measured at baseline and at each visit .


This study is registered with ClinicalTrials.gov , number NCT00984282 , and with the EU Clinical Trials Register , number EudraCT 2009-012007-25 .


Patients were randomly allocated on a 1:1 basis to sorafenib or placebo .


The intention-to-treat population comprised 417 patients ( 207 in the sorafenib group and 210 in the placebo group ) and the safety population was 416 patients ( 207 in the sorafenib group and 209 in the placebo group ) .


Median progression-free survival was significantly longer in the sorafenib group ( 108 months ) than in the placebo group ( 58 months ; hazard ratio [ HR ] 059 , 95 % CI 045-076 ; p < 00001 ) .


Progression-free survival improved in all prespecified clinical and genetic biomarker subgroups , irrespective of mutation status .


Adverse events occurred in 204 of 207 ( 986 % ) patients receiving sorafenib during the double-blind period and in 183 of 209 ( 876 % ) patients receiving placebo .


Most adverse events were grade 1 or 2 .


The most frequent treatment-emergent adverse events in the sorafenib group were hand-foot skin reaction ( 763 % ) , diarrhoea ( 686 % ) , alopecia ( 671 % ) , and rash or desquamation ( 502 % ) .


Sorafenib significantly improved progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory differentiated thyroid cancer .


Adverse events were consistent with the known safety profile of sorafenib .


These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer .


Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals ( an Amgen subsidiary ) .


Cardiometabolic risk is the risk of cardiovascular disease ( CVD ) , diabetes , or stroke , which are leading causes of mortality and morbidity worldwide .


The objective of this study was to determine the potential of low-calorie cranberry juice ( LCCJ ) to lower cardiometabolic risk .


A double-blind , placebo-controlled , parallel-arm study was conducted with controlled diets .


Thirty women and 26 men ( mean baseline characteristics : 50 y ; weight , 79 kg ; body mass index , 28 kg/m ( 2 ) ) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage .


Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage , containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving , respectively .


Fasting serum triglycerides ( TGs ) were lower after consuming LCCJ and demonstrated a treatment baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect ( 1.15 0.04 mmol/L vs. 1.25 0.04 mmol/L , respectively ; P = 0.027 ) .


Serum C-reactive protein ( CRP ) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ ln transformed values of 0.522 0.115 ln ( mg/L ) vs. 0.997 0.120 ln ( mg/L ) , P = 0.0054 , respectively , and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed ] .


LCCJ lowered diastolic blood pressure ( BP ) compared with the placebo beverage ( 69.2 0.8 mm Hg for LCCJ vs. 71.6 0.8 mm Hg for placebo ; P = 0.048 ) .


Fasting plasma glucose was lower ( P = 0.03 ) in the LCCJ group ( 5.32 0.03 mmol/L ) than in the placebo group ( 5.42 0.03 mmol/L ) , and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values ( P = 0.035 ) .


LCCJ can improve several risk factors of CVD in adults , including circulating TGs , CRP , and glucose , insulin resistance , and diastolic BP .


This trial was registered at clinicaltrials.gov as NCT01295684 .


To assess the impact of sugammadex on activated partial thromboplastin time ( APTT ) and international normalized ratio for prothrombin time ( PT ( INR ) ) in healthy subjects and characterize the concentration-dependency of sugammadex effects on APTT and prothrombin time ( PT ) in normal human plasma in vitro .


Eight healthy subjects ( 18 - 45 years of age ) were administered intravenous doses of 4 mg/kg sugammadex , 16 mg/kg sugammadex , or placebo in a randomized , placebo-controlled , three period cross-over trial .


The primary endpoint was area under the curve from 2 to 60 minutes post-dose ( AUC2-60min ) for APTT and PT ( INR ) .


In vitro , the effects of sugammadex on APTT and PT were assessed in pooled normal human citrate plasma .


In subjects dosed with 4 and 16 mg/kg sugammadex , geometric mean ratios ( treated vs. placebo ) for AUC2-60min were 1.085 ( 95 % confidence interval , 0.888 - 1.325 ) and 1.019 ( 0.868 - 1.195 ) , respectively , for APTT , and 1.047 ( 0.904 - 1.213 ) and 1.096 ( 0.953 - 1.261 ) , respectively , for PT ( INR ) .


At individual timepoints , mean APTT and PT ( INR ) increased by up to 22 % after 16 mg/kg sugammadex compared with placebo .


All such increases occurred within 30 minutes post-dose .


Sugammadex was generally well tolerated .


In the in vitro experiments , addition of sugammadex to plasma resulted in limited , concentration dependent increases in both APTT and PT .


At 200 g/mL ( the mean maximum concentration reached therapeutically ) , the relative increases were 29 % and 19 % , respectively .


Administration of sugammadex is associated with a dose-related , limited and transient prolongation of APTT and PT ( INR ) that is unlikely to be of clinical relevance .


Besides diabetic patients , glycated hemoglobin ( HbA1c ) levels have been reported to predict mortality in non-diabetics patients .


However , the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown .


Thus , we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients .


HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients .


Overall and cardiovascular mortality were evaluated over a 3 year follow-up .


Mean HbA1c level was 4.88 0.46 % ( 3.5 - 6.9 % ) .


During the 28.3 10.6 months follow-up period , 67 patients ( 13.7 % ) died ; 31 from cardiovascular causes .


In Kaplan-Meier analysis , patients in the lowest ( < 4.69 % ) and highest HbA1c ( > 5.04 % ) tertiles had poorer overall survival compared to the middle HbA1c tertile ( p < 0.001 ) .


Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall ( HR = 3.60 , 95 % CI 1.57 - 8.27 , p = 0.002 ) and cardiovascular ( HR = 6.66 , 95 % CI 1.51 - 29.4 ; p = 0.01 ) mortality .


Also , low HbA1c levels tended to be associated with overall mortality ( HR = 2.26 , 95 % CI 0.96 - 5.29 , p = 0.06 ) .


Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients , whereas lower HbA1c levels are not .


Indoxyl sulfate ( IS ) suppresses erythropoietin ( EPO ) activity and exerts renal damage .


The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties ; however , its roles in the treatment of anemia remain unclear in chronic kidney disease ( CKD ) patients .


Fifty-one Stage 5 predialysis CKD patients with hemoglobin < 10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator ( CERA , A ) and CERA alone ( B ) , with a 4-week washout period in between .


Mean changes of serum creatinine , estimated glomerular filtration rate ( eGFR ) and hemoglobin levels from the baseline were compared between two treatments .


The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A , and 5.14 mg/dL and 5.61 g/dL in the Treatment B group , respectively ( treatment effect P = 0.025 , period effect P = 0.467 , carryover effect P = 0.384 ) .


The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A , and 9.63 g/dL and 9.54 g/dL in the Treatment B group , respectively ( treatment effect P = 0.039 , period effect P = 0.001 , carryover effect P = 0.060 ) .


Use of AST-120 significantly reduced IS and p-cresyl sulfate ( PCS ) levels .


Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels ( B = 0.049 , P = 0.005 ) .


Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients .


The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels .


The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients .


Two studies examined the hypothesis that the presence vs. absence of holiday food cues leads dieters to bolster self-regulatory resources and reduce consumption of a snack food .


Study 1 evaluated snack-food consumption on a holiday vs. a non-holiday and in Study 2 , the proposed underlying mechanism -- the bolstering of self-regulatory resources when facing holiday-related cues -- was explored .


Study 1 followed a quasi-experimental design in which participants ( N = 152 ) consumed candies either on a holiday or a non-holiday .


Dieting behaviour was measured and the main outcome measure was consumption quantity .


In Study 2 , a true experiment , participants ( N = 110 ) read primes associated with holiday eating , holiday history or a neutral topic .


Self-regulatory bolstering was assessed as the main outcome measure .


Study 1 showed that dieters consume more of a food item on an ordinary day relative to a holiday ; the consumption patterns of non-dieters did not vary based on holiday cues .


Study 2 demonstrated that dieters , but not non-dieters , bolster self-regulatory resources to a greater extent in the presence vs. absence of a holiday food cue .


Dieters are better equipped to defend their diet-related goals when facing strong holiday-related temptations than weaker , everyday temptations .


To investigate the pathogenesis of globozoospermia , fertilization ability of round-headed sperm , and the application value of assisted oocyte activation in intracytoplasmic sperm injection ( ICSI ) for the wives of glohozoospermia men .


We collected oocytes from the wives of 2 globozoospermia patients and randomly divided them into two groups after ICSI to receive calcium ionophore A23187-activation and conventional treatment , respectively .


We reviewed the relevant literature published at home and abroad , and discussed the etiology of globozoospermia , fertilization ability of round-headed sperm , and treatment options for this disease .


Quality embryos were obtained in the A23187-activation group while no fertilized oocytes , oocyte cleavage , quality embryos , or blastular formation were found in the conventional treatment group .


Both women achieved pregnancy and gave birth to healthy neonates after transfer of the quality embryos from the A23187-activation group .


Calcium ionophore A23187 can be applied to ICSI for the wives of globozoospermia men and bring about desirable clinical outcomes .


Meanwhile , attention should be paid to its safety .


A fixed-dose combination of clindamycin phosphate 1.2 % and tretinoin 0.025 % gel ( VELTIN ( clindamycin phosphate and tretinoin ) 1.2 % / 0.025 % Gel [ VELTIN ] ) ( clindamycin/tretinoin gel ) is currently available for the once-daily topical treatment of acne .


Two-phase I studies were conducted to evaluate the phototoxic and photoallergic potential of clindamycin/tretinoin gel .


Study 1 ( phototoxic ) ( n = 37 ) and Study 2 ( photoallergic ) ( n = 58 ) were single-center , evaluator-blinded , randomized , vehicle-controlled , phase 1 studies conducted in healthy volunteers .


In Study 1 , clindamycin/tretinoin gel patches , vehicle gel patches and blank patches ( no gel ) were applied concurrently for 24 hours to nave sites .


After patch removal , sites were irradiated with 16 joules/cm2 of ultraviolet A light ( UVA ) then 0.75 minimal erythema dose ( MED ) of UVA/ultraviolet B light ( UVB ) , the same irradiation protocol followed by 15 joules/cm2 of visible light ( VIS ) , or served as non-irradiated controls .


Study 2 examined the effect of repeated drug exposure and involved an induction period ( 6 repeat phases at the same body sites during which clindamycin/tretinoin gel and vehicle gel patches were applied for 24 hours , removed and sites irradiated with UVB + / - VIS ) , followed by a rest period ( 10 to 17 days ) , then a challenge period that used the protocol described for Study 1 .


In both studies , inflammatory responses and other cutaneous effects were evaluated at 1 , 24 , 48 , and 72 hours after patch removal .


No subject experienced any adverse events in Study 1 ( phototoxic ) .


One subject in Study 2 ( photoallergic ) experienced AEs ( diffuse erythema ; mild application site irritation at one each of UV/VIS-irradiated clindamycin/tretinoin gel and vehicle gel patch sites ) considered definitely related to study product that resulted in discontinuation from the study .


Data from Study 1 and the challenge phase from Study 2 showed most subjects had no visible inflammatory reaction to clindamycin/tretinoin gel after irradiation .


Clindamycin/tretinoin gel has a favorable safety profile following UV/visible irradiation and a low potential for phototoxicity and photoallergenicity .


To assess changes in health related quality of life after a cognitive behavioural program for patients diagnosed with abridged somatization disorder in primary care .


A multicentre , randomized , parallel group , controlled trial was designed .


168 patients were recruited from 29 primary health care centres in Spain and were randomly assigned to one of the three study arms : treatment as usual improved with Smith 's norms , individual cognitive behavioural treatment , and group cognitive behavioural treatment .


Health-related quality of life was assessed using SF-36 Health Survey .


Individual cognitive behavioural treatment achieves greater changes in health related quality of life than group cognitive behavioural therapy and treatment as usual .


Improvement in health related quality of life was fully observed at 12 month , and partially at 6 months .


The modality of intervention interacts with time in all dimensions except for Physical functioning and Vitality .


Patients who received individual cognitive behavioural therapy treatment had better scores in Physical and Mental health summary measures at 12 month follow-up .


Individual cognitive behavioural treatment is the most effective way to improve health related quality of life in abridged somatization disorder patients , and its effects are sustained over time .


Also , regardless of the type of intervention , physical functioning improves compared with treatment as usual .


Ventricular fibrillation is common after aortic declamping in patients undergoing open heart surgery .


This situation has a negative impact on morbidity and mortality .


The aim of this prospective study was to compare the effect of administering lidocaine versus amiodarone before aortic declamping during elective coronary bypass grafting , paying close attention to when the initial effect of amiodarone sets in .


In this double blind , prospective , randomized , controlled study , 86 patients who were candidates for elective coronary artery bypass grafting were recruited into three groups : group lidocaine ( group L , n = 29 ) ; group amiodarone ( group A , n = 27 ) ; and group placebo ( group P , n = 30 ) .


Group L patients received 1.5 mg/kg of lidocaine 2 minutes before aortic declamping and group A patients received 300 mg of amiodarone intravenously 15 minutes before release of the aortic cross clamp .


The primary endpoints were the incidence of ventricular fibrillation and the number of shocks required to terminate ventricular fibrillation .


The frequency of ventricular fibrillation occurrence was significantly higher in group P ( 70 % ) when compared with group A ( 37 % ) and group L ( 38 % ) ( P = .017 ) .


There was no statistically significant difference between the amiodarone and the lidocaine groups regarding ventricular fibrillation .


However , when ventricular fibrillation occurred , the percentage of patients requiring electrical defibrillation was significantly higher in both group L and group P when compared with group A ( P = .023 ) .


We suggest that during coronary arterial bypass surgery , administration of an amiodarone regime before release of the aortic cross clamp , paying particular attention to the start of the initial effect of amiodarone , is no more effective than lidocaine for prevention from arrhythmia ; however , amiodarone reduces the need for electrical defibrillation .


We evaluated angiogenesis-targeted sunitinib therapy in a randomized , double-blind trial of metastatic castration-resistant prostate cancer ( mCRPC ) .


Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo .


Patients also received oral prednisone 5 mg twice daily .


The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival ( PFS ) .


Two interim analyses were planned .


Overall , 873 patients were randomly assigned to receive sunitinib ( n = 584 ) or placebo ( n = 289 ) .


The independent data monitoring committee stopped the study for futility after the second interim analysis .


After a median overall follow-up of 8.7 months , median OS was 13.1 months and 11.8 months for sunitinib and placebo , respectively ( hazard ratio [ HR ] , 0.914 ; 95 % CI , 0.762 to 1.097 ; stratified log-rank test , P = .168 ) .


PFS was significantly improved in the sunitinib arm ( median 5.6 v 4.1 months ; HR , 0.725 ; 95 % CI , 0.591 to 0.890 ; stratified log-rank test , P < .001 ) .


Toxicity and rates of discontinuations because of adverse events ( AEs ; 27 % v 7 % ) were greater with sunitinib than placebo .


The most common treatment-related grade 3/4 AEs were fatigue ( 9 % v 1 % ) , asthenia ( 8 % v 2 % ) , and hand-foot syndrome ( 7 % v 0 % ) .


Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia ( 20 % v 11 % ) , anemia ( 9 % v 8 % ) , and neutropenia ( 6 % v < 1 % ) .


The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC .


The role of antiangiogenic therapy in mCRPC remains investigational .


Prior unblinded studies have suggested that catheter-based renal-artery denervation reduces blood pressure in patients with resistant hypertension .


We designed a prospective , single-blind , randomized , sham-controlled trial .


Patients with severe resistant hypertension were randomly assigned in a 2:1 ratio to undergo renal denervation or a sham procedure .


Before randomization , patients were receiving a stable antihypertensive regimen involving maximally tolerated doses of at least three drugs , including a diuretic .


The primary efficacy end point was the change in office systolic blood pressure at 6 months ; a secondary efficacy end point was the change in mean 24-hour ambulatory systolic blood pressure .


The primary safety end point was a composite of death , end-stage renal disease , embolic events resulting in end-organ damage , renovascular complications , or hypertensive crisis at 1 month or new renal-artery stenosis of more than 70 % at 6 months .


A total of 535 patients underwent randomization .


The mean ( SD ) change in systolic blood pressure at 6 months was -14.1323.93 mm Hg in the denervation group as compared with -11.7425.94 mm Hg in the sham-procedure group ( P < 0.001 for both comparisons of the change from baseline ) , for a difference of -2.39 mm Hg ( 95 % confidence interval [ CI ] , -6.89 to 2.12 ; P = 0.26 for superiority with a margin of 5 mm Hg ) .


The change in 24-hour ambulatory systolic blood pressure was -6.7515.11 mm Hg in the denervation group and -4.7917.25 mm Hg in the sham-procedure group , for a difference of -1.96 mm Hg ( 95 % CI , -4.97 to 1.06 ; P = 0.98 for superiority with a margin of 2 mm Hg ) .


There were no significant differences in safety between the two groups .


This blinded trial did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control .


( Funded by Medtronic ; SYMPLICITY HTN-3 ClinicalTrials.gov number , NCT01418261 . )


There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery , both among patients who are already on an aspirin regimen and among those who are not .


Using a 2-by-2 factorial trial design , we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo .


The results of the aspirin trial are reported here .


The patients were stratified according to whether they had not been taking aspirin before the study ( initiation stratum , with 5628 patients ) or they were already on an aspirin regimen ( continuation stratum , with 4382 patients ) .


Patients started taking aspirin ( at a dose of 200 mg ) or placebo just before surgery and continued it daily ( at a dose of 100 mg ) for 30 days in the initiation stratum and for 7 days in the continuation stratum , after which patients resumed their regular aspirin regimen .


The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days .


The primary outcome occurred in 351 of 4998 patients ( 7.0 % ) in the aspirin group and in 355 of 5012 patients ( 7.1 % ) in the placebo group ( hazard ratio in the aspirin group , 0.99 ; 95 % confidence interval [ CI ] , 0.86 to 1.15 ; P = 0.92 ) .


Major bleeding was more common in the aspirin group than in the placebo group ( 230 patients [ 4.6 % ] vs. 188 patients [ 3.8 % ] ; hazard ratio , 1.23 ; 95 % CI , 1.01 , to 1.49 ; P = 0.04 ) .


The primary and secondary outcome results were similar in the two aspirin strata .


Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding .


( Funded by the Canadian Institutes of Health Research and others ; POISE-2 ClinicalTrials.gov number , NCT01082874 . )


There is a lack of appetite studies in free-living subjects supplying the habitual diet with either sucrose or artificially sweetened beverages and foods .


Furthermore , the focus of artificial sweeteners has only been on the energy intake ( EI ) side of the energy-balance equation .


The data are from a subgroup from a 10-wk study , which was previously published .


The objective was to investigate changes in EI and energy expenditure ( EE ) as possible reasons for the changes in body weight during 10 wk of supplementation of either sucrose or artificial sweeteners in overweight subjects .


Supplements of sucrose-sweetened beverages and foods ( 2 g/kg body weight ; n = 12 ) or similar amounts containing artificial sweeteners ( n = 10 ) were given single-blind in a 10-wk parallel design .


Beverages accounted for 80 % and solid foods for 20 % by weight of the supplements .


The rest of the diet was free choice .


Indirect 24-h whole-body calorimetry was performed at weeks 0 and 10 .


At week 0 the diet was a weight-maintaining standardized diet .


At week 10 the diet consisted of the supplements and ad libitum choice of foods .


Visual analog scales were used to record appetite .


Body weight increased in the sucrose group and decreased in the sweetener group during the intervention .


The sucrose group had a 3.3-MJ higher EI but felt less full and had higher ratings of prospective food consumption than did the sweetener group at week 10 .


Basal metabolic rate was increased in the sucrose group , whereas 24-h EE was increased in both groups at week 10 .


Energy balance in the sucrose group was more positive than in the sweetener group at the stay at week 10 .


The changes in body weight in the 2 groups during the 10-wk intervention seem to be attributable to changes in EI rather than to changes in EE .


Cluster randomised crossover trial with seven wards randomly allocated to intervention or control arm .


Medical and surgical wards of a university hospital with active MRSA control programme .


All patients hospitalized > 48 h in study wards and screened for MRSA on admission and discharge Intervention : Rapid PCR-based screening test for MRSA compared with control screening test by enrichment culture using chromogenic agar .


We determined the benefit of PCR-detection versus culture-based detection of MRSA colonisation upon patient admission on early implementation of isolation precautions and reduction of hospital transmission of MRSA .


Cumulative rate of MRSA hospital acquisition of in patients screened negative on admission .


The sequential order of inclusion of study wards in each arm was randomised by assigning a number to each ward and using a computer generated list of random numbers .


Of 3704 eligible patients , 67.8 % were evaluable for the study .


Compared with culture , PCR-screening reduced the median test reporting time from admission from 88 to 11 hours ( p < 0.001 ) and the median time from admission to isolation from 96 to 25 hours ( p < 0.001 ) .


MRSA acquisition was detected in 36 patients ( 3.2 % ) in the control arm and 34 ( 3.2 % ) in the intervention arm .


The incidence density rate of hospital acquired MRSA was 2.82 and 2.57 / 1,000 exposed patient-days in the control and intervention arm , respectively ( risk ratio 0.91 ( 95 % confidence interval , 0.60-1 .39 ) .


Poisson regression model adjusted for colonisation pressure , compliance with hand hygiene and antibiotic use indicated a RR 0.99 ( 95 % CI , 0.69 to 1.44 ) .


Universal PCR screening for MRSA on admission to medical and surgical wards in an endemic setting shortened the time to implement isolation precautions but did not reduce nosocomial acquisition of MRSA .


clinicaltrials.gov NCT00846105 .


To compare postoperative sensitivity following composite restoration placed in supra gingival class-V cavities using self etch adhesive and total etch adhesive .


A randomized clinical trial .


Operative Dentistry Department of Armed Forces Institute of Dentistry , Rawalpindi , from July to December 2009 .


A total of 70 patients having class-V supra gingival carious lesions were divided into two groups .


Classes-V cavities not exceeding 3 mm were prepared .


One treatment group was treated with self etch adhesive ( adhe SE one Ivoclar ) and the control group was treated with total-etch adhesive ( Eco-Etch Ivoclar ) after acid etching with 37 % phosphoric acid .


Light cured composite ( Te-Econom Ivoclar ) restoration was placed for both groups and evaluated for postoperative sensitivity immediately after restoration , after 24 hours and after one week .


Data was recorded on visual analogue scale .


Comparison of sensitivity between the two treatment groups on application cold stimulus after 24 hours of restoration showed significant difference ; however , no statistically significant difference was observed at baseline , immediately after restoration and at 1 week follow-up with cold stimulus or compressed air application .


Less postoperative sensitivity was observed at postoperative 24 hours assessment in restoration placed using SE adhesives compared to TE adhesives .


Thus , the use of SE adhesives may be helpful in reducing postoperative sensitivity during 24 hours after restoration placement .


To evaluate masticatory efficiency ( ME ) and oral health-related quality of life ( OHRQoL ) in patients rehabilitated with implant-retained mandibular overdentures .


In this randomized controlled clinical trial , 50 edentulous patients visiting the Implant Center and Department of Prosthodontics , West China College of Stomatology , Sichuan University , Chengdu , China between June 2010 and June 2012 were selected and received 2 implant-retained mandibular overdenture treatments .


All patients were rehabilitated with maxillary complete dentures .


The ME and OHRQoL were determined both one month before the mandibular complete denture was anchored to the osseointegrated implants , and 6 months after anchoring .


Paired t-tests were used to compare means of ME , and oral health impact profile-49 ( OHIP-49 ) domains scores between pre - and post-implant .


Linear regression models were utilized to seek correlations between ME and OHIP domains scores .


The ME increased from pre - to post-implant retained mandibular overdentures significantly ( p < 0.001 ) .


The total OHIP score and 4 subscales scores were changed significantly from pre - to post-implant ; namely , functional limitation , psychological discomfort , physical disability , and physical pain .


The total OHIP score , functional limitation , physical disability , and physical pain subscale scores were related to ME .


Implant-retained mandibular over dentures can significantly improve patients ' ME and OHRQoL .


The improvement in OHRQoL is mainly because of the improved ME .


An improved chewing experience , and pain relief also contributes to improvement of OHRQoL .


To observe the clinical efficacy on chronic stable angina pectoris treated with acupuncture at Neiguan ( PC 6 ) and explore the impacts of acupuncture on peripheral blood neutrophil to lymphocyte ratio ( NLR ) in the patients of stable angina pectoris .


Thirty patients of chronic stable angina pectoris met the inclusive criteria were randomized into an acupuncture group ( 15 cases ) and a medication group ( 15 cases ) , and a healthy control group ( 15 cases of the same ages ) was set up separately .


In the acupuncture group , at the same time of the basic medication , acupuncture was applied to bilateral Neiguan ( PC 6 ) , once every two days , 3 days a week , totally for 4 weeks .


In the medication group , the basic medication was applied , without acupuncture intervention .


In the healthy control group , no any intervention was applied .


The attack frequency of angina pectoris , dose of nitrogly-cerin , the evaluation of visual analogue scale ( VAS ) , Seattle angina questionnaire ( SAQ ) , the six-minute walking test ( 6MWT ) , the self-rating anxiety scale ( SAS ) and the self-rating depression scale ( SDS ) were observed before and after treatment in the subjects .


Additionally , the peripheral blood cells were detected to analyze specifically the changes in NLR before and after treatment and observe the relationship between NLR and clinical efficacy .


Compared with the medication group , the attack frequency of angina pectoris was reduced within 30 days ( P < 0.01 ) ; the dose of nitroglycerin was reduced ( P < 0.01 ) ; VAS was reduced ( P < 0.01 ) and SAQ was increased ( P < 0.05 ) in the acupuncture group .


The differences in 6 MWT , SAS and SDS were not significant between the two groups after treatment ( all P > 0.05 ) .


Additionally , compared with the medication group , in 30 days of acupuncture , NLR was reduced apparently in the acupuncture group ( P < 0.05 ) .


Acupuncture relieves the clinical symptoms of chronic stable angina pectoris , but has not apparent effects on motor ability and psychological health .


Corresponding to that before treatment , the decreased NRL in the patients of acupuncture group suggests the potential good prognosis on coronary heart disease after acupuncture .


Guidelines recommending head of bed ( HOB ) elevation greater than 30 to prevent ventilator-associated pneumonia conflict with guidelines to prevent pressure ulcers , which recommend HOB elevation less than 30 .


To examine the feasibility of 45 HOB elevation and describe and compare the occurrence of reflux , aspiration , and pressure ulcer development at 30 and 45 HOB elevation .


A randomized 2-day crossover trial was conducted .


HOB angle was measured every 30 seconds .


Oral and tracheal secretions were analyzed for pepsin presence .


Skin was assessed for pressure ulcers .


Wilcoxon signed rank tests and Kendall correlations were conducted .


Fifteen patients were enrolled ; 11 completed both days .


Patients were maintained at 30 ( mean , 30 ) for 96 % of minutes and at 45 ( mean , 39 ) for 77 % of minutes .


No patients showed signs of pressure ulcers .


A total of 188 oral secretions were obtained , 82 ( 44 % ) were pepsin-positive ; 174 tracheal secretions were obtained , 108 ( 62 % ) were pepsin-positive .


The median percentage of pepsin-positive oral secretions was not significantly higher ( P = .11 ) at 30 elevation ( 54 % ) than at 45 elevation ( 20 % ) .


The median percentage of pepsin-positive tracheal secretions was not significantly higher ( P = .37 ) at 30 elevation ( 71 % ) than 45 elevation ( 67 % ) .


Deeper sedation correlated with increased reflux ( P = .03 ) .


HOB elevation greater than 30 is feasible and preferred to 30 for reducing oral secretion volume , reflux , and aspiration without pressure ulcer development in gastric-fed patients receiving mechanical ventilation .


More deeply sedated patients may benefit from higher HOB elevations .


Force feedback might improve surgical performance during minimally invasive surgery .


This study sought to determine whether training with force feedback shortened the tissue-handling learning curve , and examined the influence of real-time visual feedback compared with postprocessing feedback .


Medical students without experience of minimally invasive surgery were randomized into three groups : real-time force feedback , postprocessing force feedback and no force feedback ( control ) .


All performed eight suturing tasks consecutively , of which the first and eighth were the premeasurement and postmeasurement tasks respectively ( no feedback ) .


Depending on randomization , either form of feedback was given during the second to seventh task .


Time , mean force non-zero and maximum force were measured with a force sensor .


Results of the groups were compared with one-way ANOVA , and intragroup improvement using a paired-samples t test .


A total of 72 students took part .


Both intervention groups used significantly lower interaction forces than the control group during the knot-tying phase of the postmeasurement task and improved their interaction forces significantly during the knot-tying phase .


The form of feedback did not influence its effectiveness .


The tissue-handling skills of medical students improved significantly when they were given force feedback of their performance .


This effect was seen mainly during the knot-tying phase of the suturing task .


Despite the efficacy of TNF inhibitors , most patients with psoriatic arthritis maintain a residual synovial inflammation .


The main aim of the study was to evaluate the effects of mud-bath therapy on clinical picture of PsA patients treated with TNF inhibitors .


The secondary outcome was to assess synovial inflammation in hand joints detected by contrast-enhanced ultrasound .


Other aims were to verify the risk of arthritis flare and to evaluate the effects of spa treatment on functional ability and on quality of life .


Thirty-six patients with psoriatic arthritis , treated in the last 6 months with TNF inhibitors , were enrolled .


After 1:1 randomisation , 18 patients ( group A ) underwent mud-bath therapy ( 12 mudpacks and 12 thermal baths ) , maintaining treatment with TNF inhibitors ; 18 patients ( group B ) continued pharmacological therapy alone .


CRP , PASI , DAS28 , swollen and tender joint count , VAS pain , HAQ and SF-36 were evaluated at baseline ( T0 ) and after 45 days ( T1 ) .


Synovial inflammation detected by contrast-enhanced ultrasound , analysed by a software system , was also assessed .


A significant improvement in PASI ( P < 0.005 ) , DAS28 ( P < 0.05 ) , swollen joint count and tender joint count ( P < 0.001 ) , and HAQ ( P < 0.001 ) between T0 and T1 was observed in group A. No patient underwent a flare-up of arthritis .


Ultrasound videos demonstrated a significant appearance delay ( P < 0.05 ) and faster washout ( P < 0.02 ) of contrast dye in group A patients with respect to group B.


These data suggest a decrease of residual synovial inflammation and a beneficial clinical effect of spa therapy in psoriatic arthritis patients treated with TNF inhibitors .


This longitudinal study examined the association between trajectories of cigarette smoking and unemployment across a 29-year time period from mean age 14 to mean age 43 .


Participants came from a community-based random sample of residents in 2 upstate New York counties .


Data were collected at 7 timepoints .


Using growth mixture modeling , 5 trajectory groups of cigarette smokers were identified .


The trajectory groups were as follows : heavy/continuous smokers , occasional smokers , late-starting smokers , quitters/decreasers , and nonsmokers .


Multivariate logistic regression analysis was used to study the relationship between the participant 's trajectory group membership and unemployment in the fifth decade of life .


The association was determined with controls for age , gender , current cigarette use , current alcohol use , current marijuana use , physical diseases , occupation , educational level , past unemployment experience , socioeconomic status measures of family of origin , depressive mood , and self-control from adolescence through the early 40s .


The findings indicate that patterns of adolescent and young adult cigarette smoking have implications for later unemployment .


Overall , the results showed that people who fell into the categories of heavy/continuous smokers ( adjusted odds ratio [ AOR ] = 3.84 ) and occasional smokers ( AOR = 4.03 ) were more likely to be unemployed at mean age 43 when compared with nonsmokers .


There was no significant difference between the quitters/decreasers and the nonsmokers with respect to unemployment .


Intervention programs designed to deal with unemployment should consider focusing on heavy/continuous and occasional cigarette smokers as risk factors for unemployment .


Rotavirus infections , prevalent in human populations worldwide are mostly caused by Group A viruses .


Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis .


However , the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality .


A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines .


This study was conducted in two cohorts .


In the first cohort , 20 healthy adults were administered a single dose of the rotavirus vaccine ( highest antigen concentration planned for infants ) or placebo and were followed up for 10 days for safety .


Following demonstration of safety in adult volunteers , 100 healthy infants were recruited ( cohort 2 ) and randomly divided into five equal study groups .


They were administered three doses of either the investigational rotavirus vaccine ( BRV-TV ) at one of the three antigen concentrations or Rotateq or Placebo at 6-8 , 10-12 and 14-16 weeks of age .


All infants were followed up for safety till 28 days after the third dose .


Immune response to the vaccine , in terms of seroresponse and geometric mean concentrations , was compared across the five study groups .


Increase in anti-rotavirus serum IgA antibodies from baseline , demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo .


Sero-response rates for placebo , BRV-TV dose-levels 10 ( 5.0 ) FFU , 10 ( 5.8 ) FFU , 10 ( 6.4 ) FFU , and Rotateq at 28 days post third dose were 11.1 % , 27.8 % , 41.2 % , 83.3 % , and 63.2 % respectively using the four-fold or more criteria .


The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10 ( 6.4 ) FFU had a higher sero-response rate compared to the active comparator arm ( RotaTeq ) , 28 days post each vaccine dose .


The safety profile was comparable across the treatment groups .


Overall , the results showed that all three doses of BRV-TV vaccine were safe , well tolerated and displayed good immunogenicity ( dose-response ) in healthy Indian infants .


Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 ( CDK4 and CDK6 ) , which promote progression from the G1 phase to the S phase of the cell cycle .


We assessed the efficacy of palbociclib ( an inhibitor of CDK4 and CDK6 ) and fulvestrant in advanced breast cancer .


This phase 3 study involved 521 patients with advanced hormone-receptor-positive , human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy .


We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant .


Premenopausal or perimenopausal women also received goserelin .


The primary end point was investigator-assessed progression-free survival .


Secondary end points included overall survival , objective response , rate of clinical benefit , patient-reported outcomes , and safety .


A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred .


The median progression-free survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.5 to not estimable ) with palbociclib-fulvestrant and 3.8 months ( 95 % CI , 3.5 to 5.5 ) with placebo-fulvestrant ( hazard ratio for disease progression or death , 0.42 ; 95 % CI , 0.32 to 0.56 ; P < 0.001 ) .


The most common grade 3 or 4 adverse events in the palbociclib-fulvestrant group were neutropenia ( 62.0 % , vs. 0.6 % in the placebo-fulvestrant group ) , leukopenia ( 25.2 % vs. 0.6 % ) , anemia ( 2.6 % vs. 1.7 % ) , thrombocytopenia ( 2.3 % vs. 0 % ) , and fatigue ( 2.0 % vs. 1.2 % ) .


Febrile neutropenia was reported in 0.6 % of palbociclib-treated patients and 0.6 % of placebo-treated patients .


The rate of discontinuation due to adverse events was 2.6 % with palbociclib and 1.7 % with placebo .


Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy , palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone .


( Funded by Pfizer ; PALOMA3 ClinicalTrials.gov number , NCT01942135 . )


To investigate the effectiveness of self-weighing twice a day with a supportive program installed on a body composition monitor in overweight adults .


Sixty adults with BMI > 24 kg/m ( 2 ) were randomly assigned to either a group that weighed themselves once per day ( group 1 , n = 30 ) or a group that weighed themselves twice per day ( group 2 , n = 30 ) .


Group 1 was instructed to self-weigh at the same time once per day and group 2 was instructed to self-weigh immediately after waking up in the morning and immediately before going to bed every day for twelve weeks .


In addition , participants in group 2 was received the daily target setting during morning weighing and the difference between the measured weight and the target weight during bedtime weighing .


Average weight reduction in group 1 was significantly lower than that in group 2 ( 1.0 1.4 kg vs. 2.7 2.1 kg , p < 0.05 ) .


The proportion of participants who lost 5 % of their pre-program weight in group 2 was significantly higher than that in group 1 ( 28.6 % vs. 3.6 % , p < 0.05 ) .


A self-weighing twice per day plus daily target setting and feedback is more effective in promoting weight loss than once-daily self-measurement .


The DiaMind trial showed beneficial immediate effects of mindfulness-based cognitive therapy ( MBCT ) on emotional distress , but not on diabetes distress and HbA1c .


The aim of the present report was to examine if the effects would be sustained after six month follow-up .


In the DiaMind trial , 139 outpatients with diabetes ( type-I or type-II ) and a lowered level of emotional well-being were randomized into MBCT ( n = 70 ) or a waiting list with treatment as usual ( TAU : n = 69 ) .


Primary outcomes were perceived stress , anxiety and depressive symptoms , and diabetes distress .


Secondary outcomes were , among others , health status , and glycemic control ( HbA1c ) .


Compared to TAU , MBCT showed sustained reductions at follow-up in perceived stress ( p < .001 , d = .76 ) , anxiety ( p < .001 , assessed by HADS d = .83 ; assessed by POMS d = .92 ) , and HADS depressive symptoms ( p = .004 , d = .51 ) , but not POMS depressive symptoms when using Bonferroni correction for multiple testing ( p = .016 , d = .48 ) .


No significant between-group effect was found on diabetes distress and HbA1c .


This study showed sustained benefits of MBCT six months after the intervention on emotional distress in people with diabetes and a lowered level of emotional well-being .


Dutch Trial Register NTR2145 , http://www.trialregister.nl .


Cost-effectiveness of treatment for posttraumatic stress disorder ( PTSD ) may depend on type of treatment ( eg , pharmacotherapy vs psychotherapy ) and patient choice of treatment .


We examined the cost-effectiveness of treatment with prolonged exposure therapy versus pharmacotherapy with sertraline , overall treatment preference , preference for choosing prolonged exposure therapy , and preference for choosing pharmacotherapy with sertraline from the US societal perspective .


Two hundred patients aged 18 to 65 years with PTSD diagnosis based on DSM-IV criteria enrolled in a doubly randomized preference trial .


Patients were randomized to receive their treatment of choice ( n = 97 ) or to be randomly assigned treatment ( n = 103 ) .


In the choice arm , patients chose either prolonged exposure therapy ( n = 61 ) or pharmacotherapy with sertraline ( n = 36 ) .


In the no-choice arm , patients were randomized to either prolonged exposure therapy ( n = 48 ) or pharmacotherapy with sertraline ( n = 55 ) .


The total costs , including direct medical costs , direct nonmedical costs , and indirect costs , were estimated in 2012 US dollars ; and total quality-adjusted life-year ( QALY ) was assessed using the EuroQoL Questionnaire-5 dimensions ( EQ-5D ) instrument in a 12-month period .


This study was conducted from July 2004 to January 2009 .


Relative to pharmacotherapy with sertraline , prolonged exposure therapy was less costly ( - $ 262 ; 95 % CI , - $ 5,068 to $ 4,946 ) and produced more QALYs ( 0.056 ; 95 % CI , 0.014 to 0.100 ) when treatment was assigned , with 93.2 % probability of being cost-effective at $ 100,000 / QALY .


Independently , giving a choice of treatment also yielded lower cost ( - $ 1,826 ; 95 % CI , - $ 4,634 to $ 749 ) and more QALYs ( 0.010 ; 95 % CI , -0.019 to 0.044 ) over no choice of treatment , with 87.0 % probability of cost-effectiveness at $ 100,000 / QALY .


Giving PTSD patients a choice of treatment appears to be cost-effective .


When choice is not possible , prolonged exposure therapy may provide a cost-effective option over pharmacotherapy with sertraline .


ClinicalTrials.gov identifier : NCT00127673 .


To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression ( eNOS ) , nitric oxide ( NO ) production and oxygen metabolism in human placenta .


The study included 20 nulliparous in gestational week 16-20 , attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups : The exercise group ( n = 10 ) took part in an exercise session three times a week for 12 weeks which consisted of : aerobic exercise at an intensity of 55-75 % of their maximum heart rate for 60 min and 25 mins .


Resistance exercise included 5 exercise groups circuit training ( 50 repetitions of each ) using barbells ( 1-3 kg/exercise ) and low-to-medium resistance bands .


The control group ( n = 10 ) undertook their usual physical activity .


Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation .


A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression .


Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism .


Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol ( p = 0.05 ) .


Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8 % and 37 % respectively in the placental mitochondria of exercising women ( p = 0.05 ) .


Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta .


Collectively , these data demonstrate that chronic exercise increases eNOS/NO production , presumably by increasing endothelial shear stress .


This adaptation may contribute to the beneficial effects of exercise on the vascular and antioxidant system and in turn reduce the risk of preeclampsia , diabetes or hypertension during pregnancy .


To compare differences of clinical therapeutic effect of heat-sensitive moxibustion with different doses for irritable bowel syndrome ( IBS ) .


Sixty cases of IBS were randomly divided into a saturated-dose group ( 30 cases ) and a traditional-dose group ( 30 cases ) .


Heat-sensitive moxibustion was applied in both groups .


The acupoints that had the strongest heat-sensitive feeling were selected and treated by warm and suspended moxibustion with moxa stick .


Disappearance of heat-sensitive feeling was taken as the sign of treatment time in the saturated-dose group , while the traditional-dose group was treated for 15 min each time .


The treatment in both groups was given twice a day for first 5 days , and from the sixth day it was given once a day for continuous 25 times , totally 30 days .


Clinical symptom scores and therapeutic effect before and after treatment in two groups were observed .


After the treatment , the cured and markedly effective rate was 75.0 % ( 21/28 ) in the saturated-dose group , which was inferior to 44.4 % ( 12/27 ) in the traditional-dose group ( P < 0.05 ) .


The clinical symptom scores , including diarrhea , abdominal distension and pain , were obviously reduced in two groups compared with those before the treatment ( all P < 0.05 ) .


Compared with the traditional-dose group , the symptom scores of diarrhea and abdominal distension in the saturated-dose group were obviously decreased ( 0.87 + / - 0.13 vs 1.27 + / - 0.21 , P < 0.01 ; 1.12 + / - 0.41 vs 1.32 + / - 0.26 , P < 0.05 ) .


The moxibustion featured with disappearance of heat-sensitive feeling and saturated dose has better therapeutic effect than that with traditional-dose for treatment of IBS .


As individual dynamic amount of moxibustion , disappearance of heat-sensitive and quantitation varies from person to person , which is one of the key factors to obtain the best curative effect .


Interventions requiring abstinence from alcohol are neither preferred by nor shown to be highly effective with many homeless individuals with alcohol dependence .


It is therefore important to develop lower-threshold , patient-centered interventions for this multimorbid and high-utilizing population .


Harm-reduction counseling requires neither abstinence nor use reduction and pairs a compassionate style with patient-driven goal-setting .


Extended-release naltrexone ( XR-NTX ) , a monthly injectable formulation of an opioid receptor antagonist , reduces craving and may support achievement of harm-reduction goals .


Together , harm-reduction counseling and XR-NTX may support alcohol harm reduction and quality-of-life improvement .


Study aims include testing : a ) the relative efficacy of XR-NTX and harm-reduction counseling compared to a community-based , supportive-services-as-usual control , b ) theory-based mediators of treatment effects , and c ) treatment effects on publicly funded service costs .


This RCT involves four arms : a ) XR-NTX + harm-reduction counseling , b ) placebo + harm-reduction counseling , c ) harm-reduction counseling only , and d ) community-based , supportive-services-as-usual control conditions .


Participants are currently/formerly homeless , alcohol dependent individuals ( N = 300 ) .


Outcomes include alcohol variables ( i.e. , craving , quantity/frequency , problems and biomarkers ) , health-related quality of life , and publicly funded service utilization and associated costs .


Mediators include 10-point motivation rulers and the Penn Alcohol Craving Scale .


XR-NTX and harm-reduction counseling are administered every 4weeks over the 12-week treatment course .


Follow-up assessments are conducted at weeks 24 and 36 .


If found efficacious , XR-NTX and harm-reduction counseling will be well-positioned to support reductions in alcohol-related harm , decreases in costs associated with publicly funded service utilization , and increases in quality of life among homeless , alcohol-dependent individuals .


The Protocolised Management in Sepsis ( ProMISe ) trial is an open , multicentre , randomised controlled trial ( RCT ) of the clinical effectiveness and cost-effectiveness of early , goal directed , protocolised resuscitation compared with usual resuscitation for patients presenting to emergency departments ( EDs ) in the United Kingdom with early signs of severe sepsis or septic shock .


The rationale for the ProMISe trial derives from a single-centre United States RCT that reported a reduction in hospital mortality from 46.5 % to 30.5 % .


To describe the proposed statistical analyses for the evaluation of clinical effectiveness for the ProMISe trial .


It is important to complete this plan before inspecting the data , and before completion of two related international studies , so that post-hoc , data-derived decisions are avoided .


The primary and secondary outcomes were defined precisely , and the approach to safety monitoring and data collection summarised , with a description of the planned statistical analyses including prespecified subgroup and secondary analyses .


The primary outcome is all-cause mortality at 90 days .


The primary analysis will be reported as a relative risk and absolute risk reduction and tested with the Fisher exact test .


Prespecified subgroup analyses will be based on age , baseline Medical Emergency Department Sepsis score , baseline Sequential Organ Failure Assessment score , and time from ED presentation to randomisation .


Secondary analyses include adjustment for baseline covariates , estimation of learning curve effects and adjustment for noncompliance .


In keeping with best practice , we have developed a statistical analysis plan for the ProMISe trial and place it in the public domain before inspecting data from the trial .


Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke .


In an exploratory analysis , we examined whether long-term survival varied by baseline characteristics after alteplase .


In this open-treatment , international , randomized , controlled trial , ischemic stroke patients were randomly allocated < 6 hours of onset to intravenous alteplase ( 0.9 mg/kg ) plus standard care ( n = 1515 ) or standard care alone ( n = 1520 ) .


We followed patients to death , censoring when last known to be alive .


We grouped patients by delay to randomization , and good or poor predicted prognosis ( calculated from baseline National Institutes of Health Stroke Scale [ NIHSS ] score and age ) .


We present absolute mortality differences between treated and control groups at 7 days , 6 months , and 18 months poststroke .


Alteplase was not associated with a significant increase in mortality within 18 months ( 0.6 % [ 95 % confidence interval ( CI ) , -2.9 % to +4.2 ] P = 0.72 ] in all patients with complete vital status ( 99.9 % , 3034/3035 ) .


In patients randomized < 3 hours of stroke , 18-month mortality was lower in the alteplase-treated group than the control group ( 40.6 % [ 95 % CI , 42.6-52 .7 ] versus 47.8 % [ 95 % CI , 35.5-45 .3 ] ; P = 0.0434 ] .


The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early ( < 3 hours ) compared with late ( 3-6 hours ; +9 % [ 95 % CI , 1-17 ] ; P = 0.0317 ) .


Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis ( +8 % [ 95 % CI , 2-14 ] ; P = 0.0091 ) .


These exploratory analyses of the third International Stroke Trial ( IST-3 ) trial support improving acute stroke patients ' access to earlier alteplase treatment , treatment of patients with poor prognosis , and further randomized controlled trials in minor stroke to replicate these findings .


http://www.controlled-trials.com .


Unique identifier : ISRCTN25765518 .


Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications ( severe pre-eclampsia , small-for-gestational-age infants , and placental abruption ) .


We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia .


In this open-label randomised trial undertaken in 36 tertiary care centres in five countries , we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications .


Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin ( 5000 international units once daily up to 20 weeks ' gestation , and twice daily thereafter until at least 37 weeks ' gestation ) or to no antepartum dalteparin ( control group ) .


Randomisation was done by a web-based randomisation system , and was stratified by country and gestational age at randomisation day with a permuted block design ( block sizes 4 and 8 ) .


At randomisation , site pharmacists ( or delegates ) received a randomisation number and treatment allocation ( by fax and/or e-mail ) from the central web randomisation system and then dispensed study drug to the local coordinator .


Patients and study personnel were not masked to treatment assignment , but the outcome adjudicators were masked .


The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia , small-for-gestational-age infant ( birthweight < 10th percentile ) , pregnancy loss , or venous thromboembolism .


We did intention-to-treat and on-treatment analyses .


This trial is registered with ClinicalTrials.gov , number NCT00967382 , and with Current Controlled Trials , number ISRCTN87441504 .


Between Feb 28 , 2000 , and Sept 14 , 2012 , 292 women consented to participate and were randomly assigned to the two groups .


Three women were excluded after randomisation because of ineligibility ( two in the antepartum dalteparin group and one in the control group ) , leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin .


Some patients crossed over to the other group during treatment , and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group .


Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis ( dalteparin 25/146 [ 171 % ; 95 % CI 114-242 % ] vs no dalteparin 27/143 [ 189 % ; 95 % CI 128-263 % ] ; risk difference -18 % [ 95 % CI -106 % to 71 % ) ) and on-treatment analysis ( dalteparin 28/143 [ 196 % ] vs no dalteparin 24/141 [ 170 % ] ; risk difference +26 % [ 95 % CI -64 to 116 % ] ) .


In safety analysis , the occurrence of major bleeding did not differ between the two groups .


However , minor bleeding was more common in the dalteparin group ( 28/143 [ 196 % ] ) than in the no dalteparin group ( 13/141 [ 92 % ] ; risk difference 104 % , 95 % CI 23-184 ; p = 001 ) .


Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism , pregnancy loss , or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding .


Canadian Institutes of Health Research , Heart and Stroke Foundation of Canada , and Pharmacia and UpJohn .


To compare a walking reeducation program with robotic locomotor training plus overground therapy ( LKOGT ) to conventional overground training ( OGT ) in individuals with incomplete upper motor neuron ( UMN ) or lower motor neuron ( LMN ) injuries having either traumatic or nontraumatic nonprogressive etiology .


Randomized open controlled trial with blind evaluation by an independent observer .


An inpatient spinal cord injury rehabilitation center .


A total of 88 adults within 6 months of spinal cord injury onset ( group A , 44 with UMN injury , and group B , 44 with LMN injury ) were graded on the American Spinal Injury Association Impairment Scale as C or D. Each of these groups was then randomly allocated to conditions 1 or 2 .


Condition 1 : Subgroups A1 and B1 were treated with LKOGT for 60 minutes .


Condition 2 : Subgroups A2 and B2 received 60 minutes of conventional OGT 5 days per week for 8 weeks .


Subjects with UMN and LMN were randomized into 2 training groups .


Ten-meter walk test and 6-minute walk test ( 6MWT ) .


Walking Index for Spinal Cord Injury II , lower extremity motor score ( LEMS ) , and the FIM-Locomotor were secondary outcome measures .


By using the LKOGT program compared with OGT , we found significant differences in the 6MWT for groups A1 and B1 .


LKOGT also provided higher scores than did OGT in secondary outcomes such as the LEMS and the FIM-Locomotor .


Robotic-assisted step training yielded better results in the 6MWT and the LEMS in patients with UMN and LMN .


This planned secondary analysis of the Outcomes Following Vaginal Prolapse Repairs and Midurethral Sling trial assessed whether treatment knowledge differed between randomized groups at 12 months and whether treatment success was affected by treatment perception .


Sham suprapubic tension-free vaginal tape ( TVT ) incisions were made in the Outcomes Following Vaginal Prolapse Repairs and Midurethral Sling trial participants randomized to no-TVT .


Primary surgical outcomes and maintenance of blinding was assessed at 12 months .


Knowledge of treatment assignment was compared between groups , and the relationship with treatment success rates was assessed .


Prior to the 12 month postoperative visit , only 4 % of treated participants ( 13 of 336 ) formally reported unmasking .


At 12 months , 94 % of the randomized participants ( 315 of 336 ) provided treatment knowledge data .


Sixteen TVT participants ( 10 % ) reported treatment knowledge ; most ( n = 15 , 94 % ) were correct ; 17 of the sham participants ( 11 % ) reported treatment knowledge ; half ( n = 8 , 47 % ) were correct .


Similar proportions of unmasked participants who reported no treatment knowledge correctly guessed/perceived treatment assignment ( sham , 46 [ 33 % ] vs TVT , 44 [ 33 % ] ) .


We did not detect significant differences in treatment success rates based on perception within and across received treatment groups ( perceived sham vs TVT overall [ P = .76 ] ) .


Of those receiving TVT , more participants perceiving TVT had treatment success compared with those who perceived sham ( 84 % vs 74 % ; P = .29 ) .


Among sham participants , more participants perceiving sham had success compared with those who perceived receiving TVT ( 65 % vs 56 % ; P = .42 ) .


Sham surgical incisions effectively mask TVT randomization .


These findings may help to inform future surgical trial designs .


Tubeless mini-percutaneous nephrolithotomy ( MPCNL ) for treating renal calculi was introduced in response to concerns over the use of adult nephrolithotomy apparatus in small children .


However , it is unclear whether tubeless mini-PCNL ( MPCNL ) is of any benefit in the treatment of children .


This study therefore aimed to assess the possible benefits of MPCNL , as compared to standard PCNL , in preschool children .


Seventy-eight preschool children under 3 years with renal calculi were randomized into two groups ( PCNL and MPCNL ) .


Operative time , hemoglobin decrease , blood transfusion rate , postoperative complications and length of hospital stay in the two groups were statistically compared .


Recovery time was significantly shorter for patients receiving MPCNL than those treated with standard PCNL ( 4.6 versus 7.7 days , P < 0.05 ) .


Treating preschool children with tubeless percutaneous nephrolithotomy has advantages over standard PCNL , including faster recovery and shorter hospital stay .


Insulin degludec/liraglutide ( IDegLira ) is a novel combination of insulin degludec ( IDeg ) and liraglutide .


This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes .


In a 26-week , double-blind trial , patients with type 2 diabetes ( A1C 7.5-10 .0 % [ 58-86 mmol/mol ] ) on basal insulin ( 20-40 units ) and metformin with or without sulfonylurea/glinides were randomized ( 1:1 ) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L .


Maximum allowed doses were 50 dose steps ( equal to 50 units IDeg plus 1.8 mg liraglutide ) and 50 units for IDeg .


The primary end point was change in A1C from baseline .


A total of 413 patients were randomized ( mean A1C 8.8 % [ 73 mmol/mol ] ; BMI 33.7 kg/m2 ) .


IDeg dose , alone or as part of IDegLira , was equivalent ( 45 units ) .


A1C decreased by 1.9 % ( 21 mmol/mol ) with IDegLira and by 0.9 % ( 10 mmol/mol ) with IDeg ( estimated treatment difference -1.1 % [ 95 % CI -1.3 , -0.8 ] , -12 mmol/mol [ 95 % CI -14 , -9 ; P < 0.0001 ) .


Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg , P < 0.0001 .


Hypoglycemia incidence was comparable ( 24 % for IDegLira vs. 25 % for IDeg ) .


Overall adverse events were similar , and incidence of nausea was low in both groups ( IDegLira 6.5 % vs. IDeg 3.5 % ) .


IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss .


These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component .


To assess the feasibility , safety , and effectiveness of early rapid icy normal saline infusion to attain mild hypothermia in cardiac arrest patients .


A single-center prospective randomized controlled trial was conducted .


From March 2011 to October 2013 , patients who had recovery of spontaneous circulation ( ROSC ) after cardiopulmonary resuscitation ( CPR ) in Beijing Daxing District People 's Hospital were randomly divided into two groups .


In icy normal saline group , patients received a rapid infusion of 1 000 mL of 4 centigrade normal saline intravenously to attain a mild hypothermia .


In the control group , the patients were treated with ice bag on head , and axillary temperature was monitored .


For all patients , rectal temperature was measured and recorded immediately and 1 hour later .


The occurrence of pulmonary edema on initial chest X-ray at 6 hours , occurrence of tremor within 48 hours , ventricular fibrillation recurring within 48 hours , and consciousness or death within 14 days were recorded .


A total of 45 patients were enrolled , including 23 patients in icy normal saline group and 22 in control group .


The patients in icy normal saline group had a rectal temperature descended from ( 36.7 0.9 ) centigrade to ( 34.9 0.7 ) centigrade 1 hour later , while the patients in control group had a rectal temperature risen from ( 36.5 1.0 ) centigrade to ( 37.9 0.9 ) centigrade 1 hour later .


There was significant difference in rectal temperature between two groups ( t = 2.228 , P = 0.031 ) .


The number of patients who successfully awaken within 14 days in ice normal saline group was significantly larger than that in control group ( 13 cases vs. 7 cases , = 65.710 , P = 0.021 ) .


There was no statistical difference in the occurrence of acute pulmonary edema ( 4 cases vs. 6 cases ) , tremor ( 2 cases vs. 0 case ) , ventricular fibrillation recurrence ( 4 cases vs. 5 cases ) and death within 14 days ( 11 cases vs. 12 cases , all P > 0.05 ) .


The study shows that early rapid i.v. infusion of 4 centigrade normal saline is feasible , safe and effective for cerebral resuscitation .


To compare in a randomised trial the safety and efficacy of the FemoSeal vascular closure device ( VCD ) versus manual compression ( MC ) after femoral access coronary angiography ( CAG ) .


In 13 months , 1,014 patients were included and 1,001 patients entered analysis .


Median [ interquartile range ] closure time was 8.0 [ 6-10 ] minutes after MC versus 1.0 [ 1-1 ] minute ( p < 0.0001 ) for the FemoSeal VCD .


Bed rest for one hour after the closure procedure was recommended in both groups .


The primary endpoint of incidence of large groin haematoma was 6.7 % in the MC group vs. 2.2 % ( p = 0.002 ) in the FemoSeal group .


The combined endpoint of 14-day adverse vascular events occurred in 1.0 % in the MC group vs. 0.6 % in the FemoSeal VCD group ( p = 0.7 ) .


Manual compression ( OR 3.3 , 95 % CI : 1.5-7 .2 , p = 0.002 ) , female gender ( OR 2.1 , 95 % CI : 1.1-3 .9 , p = 0.018 ) , and multiple punctures ( OR 10.5 , 95 % CI : 3.2-34 .3 , p = 0.001 ) were identified as independent predictors of adverse events and large haematomas .


Closure of femoral access after coronary angiography by the FemoSeal vascular closure device was safe , faster , and associated with significantly fewer in-hospital large haematomas as compared to closure by manual compression .


Type 2 diabetes is a common metabolic disease with the potential for prevention of complications .


The prevention requires a high level of lasting actions from the patients , which may be burdensome .


The aim of this trial was to evaluate the effectiveness of a training course for general practice nurses in motivation support at 18 months follow-up in the affiliated type 2 diabetes population .


Forty general practices with nurse-led diabetes consultations from the area of Aarhus , Denmark were randomised 11 to either intervention or usual practice .


Intervention practices were offered a 16-hour Self-determination theory-based course including communication training for general practice nurses delivered over 10 months .


The affiliated diabetes populations ( aged 40-74 years ) were identified from registers ( intervention n = 2,005 ; usual n = 2,029 ) .


Primary outcomes were register-based glycated haemoglobin ( HbA1c ) - , total cholesterol levels , and well-being measured by the Problem Areas In Diabetes scale ( PAID ) and the mental component summary score , SF12 ( SF12 , mcs ) .


Intention-to-treat analyses were performed .


Predefined subgroups analyses were performed .


The differences between the intervention - and the control practices ' mean HbA1c and total cholesterol at follow-up adjusted for baseline values and clustering were respectively : -0.02 % - points ( 95 % CI : -0.11 to 0.07 ; p : 0.67 ) ; 0.08 mmol/l ( 95 % CI : 0.01 to 0.15 ; p : 0.02 ) .


Differences in median scores adjusted for clustering were for PAID : 1.25 ; p = 0.31 and SF12 , mcs : 0.99 ; p = 0.15 .


Women in intervention practices differed from women in usual practices on mean HbA1c : -0.12 % - points ( -0.23 to -0.02 ; p = 0.02 ) and SF12 , mcs : 2.6 ; p = 0.01 .


Offering a training course for general practice nurses in applying the Self-determination theory in current type 2 diabetes care had no effect compared with usual practice measured by HbA1c and total cholesterol levels and the well-being at 18 months of follow-up in a comprehensive register-based diabetes population .


Subgroup analyses suggested a possible effect in women , which deserves further attention .


ClinicalTrials.gov ( Identifier NCT01187069 ) .


To investigate the efficacy of the intraoperative posterior pericardial window technique in preventing pericardial tamponade following open heart surgery .


Adult patients undergoing coronary and/or valve surgery were randomly divided into a control ( traditional ) or a pericardial window ( PW ) technique group .


Pre - , intra - , peri - and postoperative clinical data were collected prospectively , including incidence of pericardial tamponade , cardiac arrest , drainage volume , ventilation assistance time and moderate-to-large pericardial effusion .


In total , 458 patients were included : 230 controls and 228 in the PW group .


The incidence of pericardial tamponade in the PW group was significantly lower than in controls .


Cardiac arrest occurred in one patient ( 0.4 % ) in the PW group and five ( 2.2 % ) controls ; this difference was not statistically significant .


Moderate-to-large pericardial effusion after drainage extubation and new-onset atrial fibrillation were significantly more common in controls than in the PW group .


After stratification by age ( 70 versus > 70 years ) , there was no between-group difference in duration of endotracheal intubation , although in the PW group , after removal of the tracheal cannula , duration of noninvasive positive pressure ventilation was significantly longer in older patients .


The pericardial window procedure did not increase the rate or severity of procedure-related complications .


This simple technique significantly decreased the incidence of postoperative pericardial tamponade and new-onset atrial fibrillation .


To evaluate the efficacy of comprehensive interventions based on the three TCM patterns on symptoms and quality of life of COPD patients .


An open-label , randomized , controlled trial .


Four hospitals in China .


352 patients were randomly divided into two groups .


Patients in the trial group were given conventional Western medicine and Bu-Fei Jian-Pi granules , Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules respectively ; patients in the control group were given conventional Western medicine .


Data collection was performed at baseline , in the 3rd and 6th month during the treatment period , and the 12th month during the follow-up period .


Symptoms , including cough , sputum , pant , chest tightness , short of breath , lassitude , cyanosis and symptom total score ; quality of life , measured by the WHOQOL-BREF questionnaire and adult COPD quality of life questionnaire ( COPD-QOL ) .


Of the 352 patients , 306 fully completed the study .


After treatment and follow-up , there were significant differences between two groups in the following : cough , sputum , pant , chest tightness , shortness of breath , lassitude score and symptom total score ( P < .05 ) ; physical , psychological , social and environment domain ( P < .05 ) of the WHOQOL-BREF ; daily living ability , social activity , depression symptoms and anxiety symptoms domain ( P < .05 ) of the COPD-QOL .


There were no differences between two groups in cyanosis and adverse events .


Based on the TCM patterns , Bu-Fei Jian-Pi granules , Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on symptoms and quality of life of COPD patients .


Nelarabine has shown impressive single agent clinical activity in T-cell acute lymphoblastic leukemia ( T-ALL ) , but has been associated with significant neurotoxicities in heavily pre-treated patients .


We showed previously that it was safe to add nelarabine to a BFM-86 chemotherapy backbone ( AALL00P2 ) .


Children 's Oncology Group ( COG ) AALL0434 is a Phase III study designed to test the safety and efficacy of nelarabine when incorporated into a COG augmented BFM-based regimen , which increases exposure to agents with potential neurotoxicity compared to the historical AALL00P2 regimen .


AALL0434 included a safety phase to assess nelarabine toxicity .


Patients with high-risk ( HR ) T-ALL were randomized to receive Capizzi-style escalating methotrexate ( MTX ) plus pegaspargase or high dose ( HD ) MTX with/without six five-days courses of nelarabine .


We report results from 94 patients who participated in the initial safety phase of the study .


There were no differences in the incidence of peripheral motor neuropathies , sensory neuropathies or central neurotoxicities among those randomized to the nelarabine ( n = 47 ) and non-nelarabine arms ( n = 47 ) .


The addition of nelarabine to COG-augmented BFM chemotherapy regimen is safe and feasible .


The ongoing AALL0434 Efficacy Phase will determine whether the addition of nelarabine treatment improves outcome for patients with T-ALL .


In a previous single-center , open-label randomized 3-month study of triple oral antidiabetes drug ( OAD ) therapy , we investigated factors affecting the glycemic control afforded by sitagliptin , high-dose metformin , and low-dose glimepiride .


Patients were prospectively assigned to either Group 1 ( 50 % reduction in metformin ) or Group 2 ( discontinuation of glimepiride ) and compared .


The results showed that the glycated hemoglobin ( HbA1c ) levels of patients in Group 2 deteriorated more than those in Group 1 , whereas HbA1c levels were maintained in some patients in both groups .


To determine the factors associated with maintenance of HbA1c under this triple OAD regimen , data from the prospective study were further analyzed .


In both Groups 1 and 2 , the baseline HbA1c level was higher in patients with HbA1c 7.0 % after 3 months of treatment than those with an HbA1c level of < 7.0 % .


A generalized linear model revealed that high-dose metformin was associated with a deterioration of HbA1c levels in Group 2 .


Together , the findings indicate that glimepiride and high-dose metformin are important for sustained glycemic control in triple OAD therapy with sitagliptin , metformin , and sulfonylurea .


Conduct of emergency research under waiver of consent produces special challenges .


Moreover , the act of performing research may have unintended effects , potentially beneficial or detrimental .


The Dispatcher-Assisted Randomized Trial ( DART ) was designed to compare 2 types of dispatcher cardiopulmonary ( CPR ) instruction , but not intended to affect the proportion of arrest victims that received bystander CPR .


We sought to determine whether odds of receiving bystander CPR were higher during DART than during the periods before and after .


We conducted an observational cohort study of 8626 adults who suffered non-traumatic out-of-hospital cardiac arrest prior to emergency medical services ( EMS ) arrival in greater King County , Washington , between January 1 , 1999 , and December 31 , 2011 .


Bystander CPR status was assessed through review of dispatch recordings and EMS reports to classify any bystander CPR ( any B-CPR ) , and further categorized as bystander CPR with or without dispatcher assistance ( DA-CPR and B-CPR , no DA ) .


We used multivariable logistic regression to evaluate odds of B-CPR before , during , and after DART .


The proportions receiving any B-CPR were 52 % before DART ( 1817/3468 ) , 59 % during DART ( 2093/3527 ) , and 54 % after DART ( 885/1631 ) .


Compared to the period before DART , odds of receiving any B-CPR were higher during DART ( OR = 1.35 , 95 % CI = 1.23-1 .49 ) , but no different after ( OR = 1.10 , 0.98-1 .24 ) .


Compared to the before period , odds of DA-CPR were higher during DART ( OR = 1.79 , 1.59-2 .02 ) but no different after ( OR = 0.94 , 0.80-1 .10 ) .


Odds of bystander CPR were higher during the trial , an increase related to higher likelihood of DA-CPR .


The finding suggests a possible indirect community-wide benefit due to the interventional trial .


Opioid-induced constipation ( OIC ) is a common adverse effect of opioid therapy .


To evaluate the long-term safety and tolerability of naloxegol , an oral , peripherally acting - opioid receptor antagonist ( PAMORA ) , in patients with noncancer pain and OIC .


A 52-week , multicenter , open-label , randomised , parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for 4 weeks .


Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care ( UC ; investigator-chosen laxative regimen ) treatment for OIC .


The safety set comprised 804 patients ( naloxegol , n = 534 ; UC , n = 270 ) .


Mean exposure duration was 268 days with naloxegol and 297 days with UC .


Frequency of adverse events ( AEs ) was 81.8 % with naloxegol and 72.2 % with UC .


Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain ( 17.8 % vs. 3.3 % ) , diarrhoea ( 12.9 % vs. 5.9 % ) , nausea ( 9.4 % vs. 4.1 % ) , headache ( 9.0 % vs. 4.8 % ) , flatulence ( 6.9 % vs. 1.1 % ) and upper abdominal pain ( 5.1 % vs. 1.1 % ) .


Most naloxegol-emergent gastrointestinal AEs occurred early , resolving during or after naloxegol discontinuation and were mild or moderate in severity ; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain .


Pain scores and mean daily opioid doses remained stable throughout the study ; no attributable opioid withdrawal AEs were observed .


Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug ; no AEs were reported nor adjudicated as bowel perforations .


In patients with noncancer pain and opioid-induced constipation , naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated .


Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment .


We describe the rationale , design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer ( CAP ) trial , a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen ( PSA ) testing .


Seven hundred and eighty-five general practitioner ( GP ) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate .


In the intervention arm , men aged 50-69 years were invited to undergo PSA testing , and those diagnosed with localised prostate cancer were invited into a treatment trial .


Control arm practices undertook standard UK management .


All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations .


The primary outcome is prostate cancer mortality at a median 10-year-follow-up .


Among randomised practices , 271 ( 68 % ) in the intervention arm ( 198,114 men ) and 302 ( 78 % ) in the control arm ( 221,929 men ) consented to participate , meeting pre-specified power requirements .


There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices ( or men within those practices ) .


The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening .


To verify the clinical efficacy of acupuncture combined with auricle cutting method for treatment of blood stasis-type psoriasis .


Fifty-six cases of blood stasis-type psoriasis were randomly divided into a combined therapy group , a auricle cutting group , an acupuncture group and a control group , 14 cases in each one .


Based on regular treatment of TCM decoction in four groups , the combined therapy group was treated with acupuncture and auricle cutting method , and the auricle cutting group was treated with sham-acupuncture and auricle cutting , and the acupuncture group was treated with acupuncture and sham auricle cutting , and the control group was treated with sham-acupuncture and sham auricle cutting .


The acupuncture was applied at Dazhui ( GV 14 ) , Feishu ( BL 13 ) , Ganshu ( BL 18 ) and Geshu ( BL 17 ) , etc. , and manipulated with routine technique ; in the sham acupuncture , the needle was inserted into dermis layer so that the needles could be swung without being dropped out .


In the auricle cutting , erbeixin ( P1 ) of unilateral auricle was selected and cut by Chan needle to perform bloodletting ; in the sham auricle cutting , the neighborhood approximately 0.5 cm next to erbeixin ( P ) of auricle was selected as cutting area .


The treatment was given once a day , seven days as a treatment session for totally two sessions .


Psoriasis area and severity index ( PASI ) before and after treatment was observed and efficacy of each group was compared .


The effective rate was 57.1 % ( 8/14 ) in the combined therapy group , which was superior to 14.3 % ( 2/14 ) in the auricle cutting group , 7.1 % ( 1/14 ) in the acupuncture group and 0.0 % ( 0/14 ) in the control group ( all P < 0.05 ) .


The scores of PASI were all decreased in each group after the treatment ( all P < 0.05 ) , which was the most significant in the combined therapy group ( all P < 0.05 ) .


After factorial analysis , the main effect was P < 0.05 in the auricle cutting , P < 0.05 in the acupuncture and P < 0.05 in interaction effect of combined therapy .


The scores of PASI of blood stasis-type psoriasis could be effectively reduced by acupuncture , auricle cutting method and TCM decoction , among which the interaction effect of auricle cutting and acupuncture combined with TCM decoction is the most significant .


The deep-fried Mars bar has been cited as ` all that is wrong with the high-fat , high-sugar Scottish diet ' .


We investigated the effect of ingestion of a deep-fried Mars bar or porridge on cerebrovascular reactivity .


We hypothesised that deep-fried Mars bar ingestion would impair cerebrovascular reactivity , which is associated with increased risk of ischaemic stroke .


Twenty-four fasted volunteers were randomised to receive a deep-fried Mars bar and then porridge ( control ) , or vice-versa .


We used transcranial Doppler ultrasound to calculate Breath Holding Index as a surrogate measure of cerebrovascular reactivity .


Change in Breath Holding Index post-ingestion was the primary outcome measure .


Twenty-four healthy adults ( mean ( SD ) age 21.5 ( 1.7 ) years , 14 males ) completed the protocol .


Deep-fried Mars bar ingestion caused a non-significant reduction in cerebrovascular reactivity relative to control ( mean difference in absolute Breath Holding Index after deep-fried Mars bar versus porridge -0.11 , p = 0.40 ) .


Comparison of the difference between the absolute change in Breath Holding Index between genders demonstrated a significant impairment of cerebrovascular reactivity in males ( mean difference women minus men of 0.65 , 95 % CI 0.30 to 1.00 , p = 0.0003 ) .


Ingestion of a bolus of sugar and fat caused no overall difference in cerebrovascular reactivity , but there was a modest decrease in males .


Impaired cerebrovascular reactivity is associated with increased stroke risk , and therefore deep-fried Mars bar ingestion may acutely contribute to cerebral hypoperfusion in men .


To evaluate changes in salivary gland echostructure and vascularization after rituximab treatment in patients with primary Sjgren 's syndrome ( SS ) .


Twenty-eight patients with primary SS included in the multicenter , randomized , double-blind , placebo-controlled Tolerance and Efficacy of Rituximab in Primary Sjgren 's Syndrome ( TEARS ) trial underwent salivary gland ultrasonography before the first placebo or rituximab infusion and then 6 months later .


Trial inclusion criteria were scores of 50 mm on at least 2 of 4 visual analog scales ( VAS ) evaluating dryness , pain , fatigue , and global disease ; and recent-onset ( < 10 years ) biologically active primary SS and/or systemic primary SS .


Patients were randomly assigned ( 1:1 ) to rituximab ( 1 gm at weeks 0 and 2 ) or placebo .


Ultrasonography of both parotid and submandibular glands was performed to assess echostructure ( using a semiquantitative score of 0-4 , with improvement defined as a 1-point decrease ) , size of each gland , and vascularization based on the resistive index of the transverse facial artery of the parotid gland before and after lemon juice stimulation .


Of the 28 patients , 5 ( 18 % ; 3 in the placebo group and 2 in the rituximab group ) had clinically detectable bilateral parotid gland enlargement at baseline .


Parotid parenchyma echostructure improved in 50 % of the rituximab-treated patients versus 7 % of the placebo-treated patients ( P = 0.03 ) .


In the submandibular glands , echostructure also improved in a larger proportion of rituximab-treated patients , although the difference was not significant ( 36 % versus 7 % of placebo-treated patients ; P = 0.16 ) .


Gland sizes and resistive index remained unchanged .


Ultrasonography showed improved salivary gland echostructure in patients with primary SS receiving rituximab , with no changes in salivary gland size or vascularization , 6 months after the first infusion .


The aim of this study was to describe the aims , methods , donor and recipient cohort characteristics , and potential impact of the Cornea Preservation Time Study ( CPTS ) .


The CPTS is a randomized clinical trial conducted at 40 clinical sites ( 70 surgeons ) designed to assess the effect of donor cornea preservation time ( PT ) on graft survival 3 years after Descemet stripping automated endothelial keratoplasty ( DSAEK ) .


Eyes undergoing surgery for Fuchs endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were randomized to receive donor corneas stored 7 days or 8 to 14 days .


Donor and patient characteristics , tissue preparation and surgical parameters , recipient and donor corneal stroma clarity , central corneal thickness , intraocular pressure , complications , and a reading center-determined central endothelial cell density were collected .


Surveys were conducted to evaluate pre-CPTS PT practices .


The 1330 CPTS donors were : 49 % > 60 years old , 27 % diabetic , had a median eye bank-determined screening endothelial cell density of 2688 cells/mm , and 74 % eye bank prepared for DSAEK .


A total of 1090 recipients ( 1330 eyes including 240 bilateral cases ) had : median age of 70 years , were 60 % female , 90 % white , 18 % diabetic , 52 % phakic , and 94 % had Fuchs endothelial corneal dystrophy .


Before the CPTS , 19 eye banks provided PT data on 20,852 corneas domestically placed for DSAEK in 2010 to 2011 ; 96 % were preserved 7 days .


Of 305 American Academy of Ophthalmology members responding to a pre-CPTS survey , 233 ( 76 % ) set their maximum PT preference at 8 days or less .


The CPTS will increase understanding of factors related to DSAEK success and , if noninferiority of longer PT is shown , will have great potential to extend the available pool of endothelial keratoplasty donors.Clinical Trial Registration-URL : http://www.clinicaltrials.gov .