Compared with the control group , Treatment groups 1 and 2 showed decreases in 2 or more times of PS use , maximum OI , duration of continuous positive airway pressure treatment , and incidence of air leak syndrome and pulmonary hypertension .


Early use of sufficient PS in late preterm and full-term infants with RDS can reduce complications , secondary use of PS , duration of mechanical ventilation and length of hospital stay , and hospitalization expense .


To determine the association of arterial partial pressure of carbon dioxide PaCO2 with severe intraventricular haemorrhage ( sIVH ) , bronchopulmonary dysplasia ( BPD ) , and neurodevelopmental impairment ( NDI ) at 18-22months in premature infants .


Secondary exploratory data analysis of Surfactant , Positive Pressure , and Oxygenation Randomised Trial ( SUPPORT ) .


Multiple referral neonatal intensive care units .


1316 infants 24 0/7 to 27 6/7 weeks gestation randomised to different oxygenation ( SpO2 target 85-89 % vs 91-95 % ) and ventilation strategies .


Blood gases from postnatal day 0 to day14 were analysed .


Five PaCO2 variables were defined : minimum ( Min ) , maximum ( Max ) , SD , average ( time-weighted ) , and a four level categorical variable ( hypercapnic ( highest quartile of Max PaCO2 ) , hypocapnic ( lowest quartile of Min PaCO2 ) , fluctuators ( hypercapnia and hypocapnia ) , and normocapnic ( middle two quartiles of Max and Min PaCO2 ) ) .


PaCO2 variables were compared for infants with and without sIVH , BPD and NDI ( death ) .


Multivariable logistic regression models were developed for adjusted results .


sIVH , BPD and NDI ( death ) were associated with hypercapnic infants and fluctuators .


Association of Max PaCO2 and outcomes persisted after adjustment ( per 10mmHg increase : sIVH/death : OR 1.27 ( 1.13 to 1.41 ) ; BPD/death : OR 1.27 ( 1.12 to 1.44 ) ; NDI/death : OR 1.23 ( 1.10 to 1.38 ) , death : OR 1.27 ( 1.12 to 1.44 ) , all p < 0.001 ) .


No interaction was found between PaCO2 category and SpO2 treatment group for sIVH/death , NDI/death or death .


Max PaCO2 was positively correlated with maximum FiO2 ( rs0 .55 , p < 0.0001 ) and ventilator days ( rs0 .61 , p < 0.0001 ) .


Higher PaCO2 was an independent predictor of sIVH/death , BPD/death and NDI/death .


Further trials are needed to evaluate optimal PaCO2 targets for high-risk infants .


Peyronie 's disease described as penile curvature , fibromathosis and pain that occur most often in men aged 40 to 60 years .


The main complaint that caused the patient to visit the clinic is nodules on the upper surface of the penis , causing curvature and distortion particularly during erection , but they do n't have any urinary problem .


In this study , we evaluated the effect of verapamil compared to pentoxifylline in Peyronie 's disease .


In this study , 90 patients with signs and symptoms of Peyronie 's disease which were diagnosed and were in the age range 40 to 70 years enrolled .


The patients were randomly divided into 3 groups .


First group received pentoxifylline orally at a dose of 400 mg three times a day , in the second group verapamil ( 10 mg every other week for up to 12 sessions ) was injected into the lesion and the third group received both treatments in combination .


In patients , who received pentoxifylline , curvature reduction was 26.7 % , plaque size reduction was 30 % , the recovery rate of erectile dysfunction was 46.7 % and pain reduced was 73.3 % .


Each of these cases in patients , who used beta-blockers , was 36.7 % , 33.3 % , 66.7 % and 76.6 % .


In combination therapy , curvature reduction was 36.7 % , plaque size reduction was 33.3 % , the recovery rate of erectile dysfunction was 86.7 % and pain reduced was 80 % .


In our study there was no significant difference between two groups using verapamil or pentoxifylline , but there was a significant improvement in combination therapy group .


Due to our results we propose that combination therapy can improve results and should be considered as a choice in treatment of Peyronie 's disease .


Magnesium deficiency is associated with poor physical performance , but no trials are available on how magnesium supplementation affects elderly people 's physical performance .


The aim of our study was to investigate whether 12 wk of oral magnesium supplementation can improve physical performance in healthy elderly women .


In a parallel-group , randomized controlled trial , 139 healthy women ( mean SD age : 71.5 5.2 y ) attending a mild fitness program were randomly allocated to a treatment group ( 300 mg Mg/d ; n = 62 ) or a control group ( no placebo or intervention ; n = 77 ) by using a computer-generated randomization sequence , and researchers were blinded to their grouping .


After assessment at baseline and again after 12 wk , the primary outcome was a change in the Short Physical Performance Battery ( SPPB ) ; secondary outcomes were changes in peak torque isometric and isokinetic strength of the lower limbs and handgrip strength .


A total of 124 participants allocated to the treatment ( n = 53 ) or control ( n = 71 ) group were considered in the final analysis .


At baseline , the SPPB scores did not differ between the 2 groups .


After 12 wk , the treated group had a significantly better total SPPB score ( = 0.41 0.24 points ; P = 0.03 ) , chair stand times ( = -1.31 0.33 s ; P < 0.0001 ) , and 4-m walking speeds ( = 0.14 0.03 m/s ; P = 0.006 ) than did the control group .


These findings were more evident in participants with a magnesium dietary intake lower than the Recommended Dietary Allowance .


No significant differences emerged for the secondary outcomes investigated , and no serious adverse effects were reported .


Daily magnesium oxide supplementation for 12 wk seems to improve physical performance in healthy elderly women .


These findings suggest a role for magnesium supplementation in preventing or delaying the age-related decline in physical performance .


To evaluate whether perioperative indomethacin and antibiotic administration at the time of examination-indicated cerclage placement prolongs gestation .


This is a randomized controlled trial performed at a single tertiary care hospital between March 2010 and November 2012 .


Women older than 18 years of age with a singleton pregnancy between 16 0/7 and 23 6/7 weeks of gestation undergoing an examination-indicated cerclage were eligible .


Women were randomly assigned to receive either perioperative indomethacin and antibiotics or no perioperative prophylactic medications .


The primary outcome was gestational latency after cerclage placement .


Fifty women were required to be randomized to show , with 80 % power , a 28-day improvement in latency assuming a latency without intervention of 5035 days .


Fifty-three patients were enrolled with three lost to follow-up .


A greater proportion of pregnancies were prolonged by at least 28 days among women who received indomethacin and perioperative antibiotics ( 24 [ 92.3 % ] compared with 15 [ 62.5 % ] , P = .01 ) .


However , gestational age at delivery and neonatal outcomes were statistically similar between groups .


Among women receiving an examination-indicated cerclage in the second trimester , gestation was significantly more likely to be prolonged by 28 days among women who received perioperative indomethacin and antibiotics .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT01114516 .


I.


The aim of this prospective randomized study was to evaluate a red clover based isoflavones supplementation in the treatment of climacteric syndrome and its effects on cardiovascular risk serum profile .


The study included 150 healthy postmenopausal women that were randomly assigned to receive phytoestrogens tablets , amounting in a total daily intake of 60.8 mg red clover isoflavones plus 19.2 mg soy isoflavones ( n = 75 ) , or placebo ( n = 75 ) .


The authors evaluated teh following : daily number of hot flushes and Kupperman Index at baseline and after one and three months ; serum total , high-density lipoprotein ( HDL ) and low-density lipoprotein ( LDL ) cholesterol , triglycerides , prothrombin time ( PT ) , partial thromboplastin time ( PTT ) , fibrinogen , and antithrombin III ( ATIII ) at baseline and after three and six months .


One hundred twenty-eight patients completed the study : 67 in the active group and 61 in the placebo group .


The treatment led to a progressive significant reduction ( p < 0.05 ) of the number of hot flushes in the active group compared to placebo already after one month , while Kupperman Index was statistically reduced after three months .


No significant variation in total cholesterol , LDL-cholesterol , HDL-cholesterol , triglycerides , PT , PTT , fibrinogen , and ATIII were found .


The present findings suggest that a red clover based isoflavones supplementation in healthy postmenopausal women is promptly effective on climacteric syndrome , improves neurovegetative symptoms , safe on cardiovascular risk serum profile , and does not modify lipids and coagulation .


Myofascial pain syndrome is a regional condition of muscle pain and stiffness and is classically characterized by the presence of trigger points in affected musculature .


Botulinum toxin type A ( BoNT-A ) has been shown to have antinociceptive properties and elicit sustained muscle relaxation , thereby possibly affording even greater relief than traditional strategies .


Our goal was to determine whether direct injection of BoNT-A into painful muscle groups is effective for cervical and shoulder girdle myofascial pain .


An enriched protocol design was used , wherein 114 patients with cervical and shoulder girdle myofascial pain underwent injection of BoNT-A to determine their response to the drug .


Fifty-four responders were then enrolled in a 12-week , randomized , double-blind , placebo-controlled trial .


Pain scales and quality of life measures were assessed at baseline and at routine follow-up visits until completion of the study after 26 weeks .


Injection of BoNT-A into painful muscle groups improved average visual numerical pain scores in subjects who received a second dose of BoNT-A compared to placebo ( P = 0.019 [ 0.26 , 2.78 ] ) .


Subjects who received a second dose of BoNT-A had a reduced number of headaches per week ( P = 0.04 [ 0.07 , 4.55 ] ) .


Brief Pain Inventory interference scores for general activity and sleep were improved ( P = 0.046 [ 0.038 , 3.700 ] and 0.02 [ 0.37 , 4.33 ] , respectively ) in those who received a second dose of BoNT-A .


BoNT-A injected directly into painful muscle groups improves average pain scores and certain aspects of quality of life in patients experiencing severe cervical and shoulder girdle myofascial pain .


A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy ( complete cytoreductive surgery ( CRS ) , hyperthermic intraperitoneal chemotherapy ( HIPEC ) , and systemic chemotherapy ) on overall survival ( OS ) in patients with gastric carcinomatosis .


Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum , and resectable to `` no evidence of disease '' were randomized to gastrectomy , metastasectomy , HIPEC , and systemic FOLFOXIRI ( GYMS arm ) or FOLFOXIRI alone ( SA arm ) .


Seventeen patients were enrolled ( 16 evaluable ) ; 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction ( CCR0 ) .


Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm .


Four patients in the GYMS arm survived > 12 months , 2 patients close to 2 years at last follow-up , and 1 patient more than 4 years , with 2 of these patients still alive .


No patient in the SA arm lived beyond 11 months .


All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index ( PCI ) of 15 .


Maximal cytoreductive surgery combined with regional ( HIPEC ) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival .


To report additional ocular outcomes of intensive treatment of hyperglycemia , blood pressure , and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) study .


Double 22 factorial , multicenter , randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors .


In the glycemia trial , targets of intensive and standard treatment were : hemoglobin A1c < 6.0 % and 7.0 % to 7.9 % , respectively , and in the blood pressure trial : systolic blood pressures of < 120 and < 140 mmHg , respectively .


The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin .


Of the 3472 ACCORD Eye Study participants enrolled , 2856 had 4-year data ( 85 % of survivors ) .


Eye examinations and fundus photographs were taken at baseline and year 4 .


Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study ( ETDRS ) methods .


Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy .


As previously reported , there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials , but no significant effect in the blood pressure trial .


Results were similar for retinopathy progression by 1 , 2 , and 4 or more steps on the person scale and for 2 steps on the eye scale .


In the subgroup of patients with mild retinopathy at baseline , effect estimates were large ( odds ratios , 0.30 ; P < 0.001 ) , but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline .


Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants , whose average age and diabetes duration were 62 and 10 years , respectively , and who had cardiovascular disease or cardiovascular risk factors .


The effect seemed stronger in patients with mild retinopathy .


Similar slowing of progression was observed in patients treated with fenofibrate , with no effect observed with intensive blood pressure treatment .


This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression , and fenofibrate should be considered for treatment of diabetic retinopathy .


Cooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health , environmental , and social problems .


The public health burden of household air pollution includes an estimated four million premature deaths each year .


To be effective and generate useful insight into potential solutions , cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture , and include interdisciplinary measurement strategies along a continuum of outcomes .


REACCTING ( Research on Emissions , Air quality , Climate , and Cooking Technologies in Northern Ghana ) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana .


The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different `` rungs '' in the cookstove technology ladder : a locally-made low-tech rocket stove and the imported , highly efficient Philips gasifier stove .


Intervention households were randomized into four different groups , three of which received different combinations of two improved stoves , while the fourth group serves as a control for the duration of the study .


Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest .


We assess stove use and cooking behavior , cooking emissions , household air pollution and personal exposure , health burden , and local to regional air quality .


Integrated analysis and modeling will tackle a range of interdisciplinary science questions , including examining ambient exposures among the regional population , assessing how those exposures might change with different technologies and behaviors , and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes .


REACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes .


By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives , this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs .


The mean follow-up in the clinical trials of antiplatelet drugs in the secondary prevention of ischemic atherothrombotic stroke ranges from 1 to 5.5 years .


Thus , the safety and efficacy of these drugs in the very long term is not totally documented .


We have assessed the safety and effectiveness of triflusal and aspirin for a very long-term period in the secondary prevention of patients with ischemic atherothrombotic stroke .


Patients with atherothrombotic ischemic stroke , including TIA , who participated in randomized clinical trials of triflusal versus aspirin were included in the study .


The period of recruitment was between 1983 and 1999 .


After finishing their participation in the clinical trials , patients were followed up in the Neurology Department of our hospital .


All patients were treated with aspirin or triflusal during a mean period of 17.2 years .


Groups were comparable with respect to sex , age , risk factor and etiology of the stroke .


Adverse events and vascular events ( including stroke recurrence , ischemic heart disease and vascular death ) that appeared throughout the study were registered .


Statistical analysis was performed using the statistical package SPSS 15.0 for Windows .


Kaplan-Meier curves and the log-rank test were used to compare treatments .


A total of 441 patients ( 305 men ) with a mean age ( SD ) of 51.112.4 years were included in the study ; 288 patients ( 65.3 % ) were treated with triflusal and 153 with aspirin .


There were no statistically significant differences between aspirin and triflusal concerning new vascular events ( 72.5 vs. 60.4 % ; p = 0.28 ) , stroke recurrence ( 49.7 vs. 46.5 % ; p = 0.53 ) , ischemic heart events ( 54.9 vs. 55.6 % ; p = 0.90 ) , vascular death ( 25.5 vs. 24 % ; p = 0.73 ) and global mortality ( 42.5 vs. 42 % ; p = 0.92 ) .


The incidence of serious bleeding ( upper digestive tract hemorrhage and cerebral hemorrhage ) was 18.3 % in aspirin-treated patients and 5.5 % in triflusal-treated patients ( p < 0.001 ) .


In reference to other adverse events , no significant differences were found between aspirin and triflusal .


In the secondary prevention of ischemic stroke , very long-term treatment with triflusal or aspirin seems to have a similar efficacy , but triflusal is safer with a lower hemorrhagic risk .


Triflusal may be an alternative therapy , particularly in patients who present aspirin resistance .


Low caste adolescent girls living in rural northern Karnataka are at increased risk of school drop-out , child marriage , and entry into sex-work , which enhances their vulnerability to HIV , early pregnancy and adverse maternal and child health outcomes .


This protocol describes the evaluation of Samata , a comprehensive , multi-level intervention designed to address these structural drivers of HIV risk and vulnerability .


The Samata study is a cluster randomised controlled trial that will be conducted in eighty village clusters ( 40 intervention ; 40 control ) in Bijapur and Bagalkot districts in northern Karnataka .


The intervention seeks to reach low caste girls and their families ; adolescent boys ; village communities ; high school teachers and school governing committees ; and local government officials .


All low caste ( scheduled caste/tribe ) adolescent girls attending 7th standard ( final year of primary school ) will be recruited into the study in two consecutive waves , one year apart .


Girls ( n = 2100 ) , their families ( n = 2100 ) and school teachers ( n = 650 ) will be interviewed at baseline and at endline .


The study is designed to assess the impact of the intervention on four primary outcomes : the proportion of low caste girls who ( i ) enter into secondary school ; ( ii ) complete secondary school ; ( iii ) marry before age 15 ; and ( iv ) engage in sex before age 15 .


Observers assessing the outcomes will be blinded to group assignment .


The primary outcome will be an adjusted , cluster-level intention to treat analysis , comparing outcomes in intervention and control villages at follow-up .


We will also conduct survival analyses for the following secondary outcomes : marriage , sexual debut , pregnancy and entry into sex work .


Complementary monitoring and evaluation , qualitative and economic research will be used to explore and describe intervention implementation , the pathways through which change occurs , and the cost-effectiveness of the intervention .


This is an innovative trial of a comprehensive intervention to improve the quality of life and reduce HIV vulnerability among marginalised girls in northern Karnataka .


The findings will be of interest to programme implementers , policy makers and evaluation researchers working in the development , education , and sexual and reproductive health fields .


ClinicalTrials.Gov NCT01996241 .


16th November 2013 .


Individuals with serious mental illness have high rates of obesity and a need for specialized weight loss intervention programs .


This study examines the efficacy of the RENEW weight loss intervention and examines the impact of the intervention setting on outcomes .


136 individuals with serious mental illness from 4 different settings were randomly assigned to receive the RENEW weight loss intervention or a control condition of treatment as usual .


The RENEW intervention is a one year program that includes an intensive , maintenance and intermittent supports phase .


The intervention group experienced a modest weight loss of 4.8 lbs at 3 months , 4.1 lbs at 6 months and a slight weight gain of 1.5 lbs at 12 months .


The control group gained a total of 6.2 lbs at 12 months .


However when settings were examined separately the responder sites had a weight loss of 9.4 lbs at 3 months , 10.9 lbs at 6 months and 7 lbs at 12 months .


These results suggest that the settings in which individuals receive services may act as a support or hindrance toward response to weight loss interventions .


The concept of the obesogenic environment deserves further examination as a factor in the success of weight loss programs .


To observe the impacts of different frequencies of electroacupuncture ( EA ) on post-operative cognitive function and the change in serum S-100beta protein under the compound anesthesia of acupuncture and drugs .


One hundred and twenty-four patients of abdominal operation at selective time were randomized into a routine drug anesthesia group ( group A , 24 cases ) , a meridian point 2 Hz group ( group B , 26 cases ) , a me ridian point 2 Hz/100 Hz group ( group C , 25 cases ) , a meridian point 100 Hz group ( group D , 24 cases ) and a transcutaneous acupoint electric stimulation 2 Hz/100 Hz group ( group E , 25 cases ) .


In group A , the endotrachea-lgeneral anesthesia was applied .


In the rest groups , the acupuncture anesthesia was induced for 30 min before the endotracheal general anesthesia , at Baihui ( GV 20 ) , Yintang ( GV 29 ) and Neiguan ( PC 6 ) , with G6805-2 electric acupuncture apparatus used .


In group B , the continuous wave and 2Hz in frequency were selected .


In group C , the disperse-dense wave and 2 Hz/100 Hz in frequency were selected .


In group D , the continuous wave and 100 Hz in frequency were selected .


In group E , the disperse-dense wave and 2 Hz/100 Hz in frequency were selected , and the electrode pads were stick on the acupoints and connected with the electric stimulation till the end of operation .


Mini-mental state examination ( MMSE ) was adopted to evaluate and record the changes in cognitive function 1 day before operation and on the 3rd day after operation .


The conditions of post-operative cognitive dysfunction ( POCD ) in the patients and the changes in serum S-100beta protein were monitored before and at the end of operation .


The incidence rate of POCD on the 3rd day after operation was 41.7 % ( 10/24 ) in group A.


The incidence rates of POCD were 26.9 % ( 7/26 ) , 16.0 % ( 4/25 ) , 33.3 % ( 8/24 ) and 16.0 % ( 4/25 ) in group B , C , D and E separately .


Compared with group A , the incidence rate of PCOD in group B , C , D and E were reduced ( all P < 0.05 ) , the incidence rate in group C and E were lower than that in groups B and D ( all P < 0.05 ) .


At the end of operation , the level of serumS-100beta protein was ( 0.186 + / - 0.027 ) microg/L in group A , the levels were ( 0.165 + / - 0.028 ) microg/L , ( 0.166 + / - 0.027 ) microg/L , ( 0.163 + / - 0.025 ) microg/L and ( 0.164 + / - 0.025 ) microg/L in group B , C , D and E separately .


The levels of serum S-100beta protein in group B , C , D and E were lower than that in group A separately ( all P < 0.05 ) .


The general anesthesia assisted with EA at different frequencies reduces the incidence of cognitive dysfunctionand , decreases the level of serum S-100beta protein after intestinal cancer resection .


The effects of the meridian point electric stimulation at 2 Hz/100 Hz and the transcutaneous electric stimulation at 2 Hz/100 Hz are the best .


Hence , these two approaches of anesthesia deserve to be recommended practically .


Many features can influence the choice of a supraglottic airway device ( SAD ) , including ease of insertion , adequate ventilation pressures and lack of adverse effects .


The goal of this randomized prospective trial was to compare the performance of the i-gel with that of the LMA-Supreme .


One hundred adult patients ( American Society of Anesthesiologists I-III ) scheduled to undergo elective surgery under general anesthesia were randomized to either an i-gel ( n = 50 ) or an LMA-Supreme ( n = 50 ) .


The primary objective was to compare ventilation pressures .


Secondary objectives included time and number of attempts needed to introduce the device , adverse effects , and repositioning .


The endoscopic view of the glottic aperture and the position of the drain tubes in relation to the esophagus were also evaluated .


The devices were inserted successfully in 46 ( 92 % ) patients in both groups .


There was no significant difference in the [ mean ( SD ) ] leak pressure [ i-gel : 23 ( 7 ) cm H2O vs LMA-Supreme : 21 ( 8 ) cm H2O ; P = 0.14 ] or peak inspiratory pressure between both devices .


Insertion time was shorter with the i-gel than with the LMA-Supreme [ 19 ( 7 ) sec vs 27 ( 17 ) sec , respectively ; P = 0.003 ] .


The vocal cords were completely visualized more often through the i-gel ( 70 % ) than through the LMA-Supreme ( 50 % ) ( P = 0.007 ) .


Esophageal mucosa was easily visualized through the drain port in all but four patients , two patients in each group .


There was no difference between groups regarding preoperative or postoperative complications .


Postoperative patient discomfort was generally mild and comparable between both devices .


Both the LMA-Supreme and the i-gel offer similar performance for positive pressure ventilation in paralyzed patients during general anesthesia .


The i-gel was associated with a slightly faster insertion time and better fibrescopic visualization of the glottis .


This trial was registered at Clinicaltrials.gov : NCT01001078 .


To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants .


A prospective , randomized , controlled trial was conducted at 5 neonatal intensive care units in Turkey .


VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death .


The primary outcome was NEC ( Bell stage 2 ) .


The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) .


The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls .


The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3-0 .9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2-0 .8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1-3 .6 ) .


In VLBW infants , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC .


To examine whether behavioural strategies designed to improve children 's sleep problems could also improve the symptoms , behaviour , daily functioning , and working memory of children with attention deficit hyperactivity disorder ( ADHD ) and the mental health of their parents .


Randomised controlled trial .


21 general paediatric practices in Victoria , Australia .


244 children aged 5-12 years with ADHD attending the practices between 2010 and 2012 .


Sleep hygiene practices and standardised behavioural strategies delivered by trained psychologists or trainee paediatricians during two fortnightly consultations and a follow-up telephone call .


Children in the control group received usual clinical care .


At three and six months after randomisation : severity of ADHD symptoms ( parent and teacher ADHD rating scale IV-primary outcome ) , sleep problems ( parent reported severity , children 's sleep habits questionnaire , actigraphy ) , behaviour ( strengths and difficulties questionnaire ) , quality of life ( pediatric quality of life inventory 4.0 ) , daily functioning ( daily parent rating of evening and morning behavior ) , working memory ( working memory test battery for children , six months only ) , and parent mental health ( depression anxiety stress scales ) .


Intervention compared with control families reported a greater decrease in ADHD symptoms at three and six months ( adjusted mean difference for change in symptom severity -2.9 , 95 % confidence interval -5.5 to -0.3 , P = 0.03 , effect size -0.3 , and -3.7 , -6.1 to -1.2 , P = 0.004 , effect size -0.4 , respectively ) .


Compared with control children , intervention children had fewer moderate-severe sleep problems at three months ( 56 % v 30 % ; adjusted odds ratio 0.30 , 95 % confidence interval 0.16 to 0.59 ; P < 0.001 ) and six months ( 46 % v 34 % ; 0.58 , 0.32 to 1.0 ; P = 0.07 ) .


At three months this equated to a reduction in absolute risk of 25.7 % ( 95 % confidence interval 14.1 % to 37.3 % ) and an estimated number needed to treat of 3.9 .


At six months the number needed to treat was 7.8 .


Approximately a half to one third of the beneficial effect of the intervention on ADHD symptoms was mediated through improved sleep , at three and six months , respectively .


Intervention families reported greater improvements in all other child and family outcomes except parental mental health .


Teachers reported improved behaviour of the children at three and six months .


Working memory ( backwards digit recall ) was higher in the intervention children compared with control children at six months .


Daily sleep duration measured by actigraphy tended to be higher in the intervention children at three months ( mean difference 10.9 minutes , 95 % confidence interval -19.0 to 40.8 minutes , effect size 0.2 ) and six months ( 9.9 minutes , -16.3 to 36.1 minutes , effect size 0.3 ) ; however , this measure was only completed by a subset of children ( n = 54 at three months and n = 37 at six months ) .


A brief behavioural sleep intervention modestly improves the severity of ADHD symptoms in a community sample of children with ADHD , most of whom were taking stimulant medications .


The intervention also improved the children 's sleep , behaviour , quality of life , and functioning , with most benefits sustained to six months post-intervention .


The intervention may be suitable for use in primary and secondary care.Trial registration Current Controlled Trials ISRCTN68819261 .


The physical and mental health of college students tends to continuously decline around the world .


Since they are in a significant transition period which presents opportunities and challenges in health promotion , it is important to improve their health in this period .


As a traditional Chinese exercise form which combines movements with breath and mind , Baduanjin may be one of the selectable effective exercises .


However , evidence of Baduanjin exercise for college students has not been completely established .


The primary aim of this trial is to evaluate the effectiveness and safety of Baduanjin exercise for physical and mental health of college students through a rigorous randomization , parallel-controlled design .


We will conduct a randomized , single-blind , parallel-controlled trial .


A total of 222 college students from Fujian University of Traditional Chinese Medicine who meet the eligibility criteria will be recruited and randomly allocated into Baduanjin training or usual exercise control group .


Baduanjin training will last 12 weeks ( 1 h per day , 5 days per week ) .


The physical and psychological outcomes , including lumbar muscle strength , lumbar proprioception function , physical fitness , as well as self-reported symptom intensity , stress , self-esteem , mood , quality of life , quality of sleep , and adverse events , will be evaluated by blinded outcome assessors at baseline , 13 weeks ( at the end of intervention ) , and 25 weeks ( after the 12-week follow-up period ) .


This protocol presents an objective design of a randomized , single-blind trial that aims to evaluate the effectiveness and safety of Baduanjin exercise for physical and mental health of college students .


If the outcome is positive , the results will provide higher-quality evidence to better inform the college students regarding their selection about whether to receive such exercise .


Chinese Clinical Trial Registry : ChiCTR-TRC-13003329 .


Registration date : 18 July , 2013 .


Methamphetamine use has been previously associated with poor medication adherence , but , to date , there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence .


We pooled data from two previous , randomized controlled trials ( using bupropion and mirtazapine , respectively ) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system ( MEMS ) cap as a repeated measure .


We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings .


We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings ( AOR : 0.69 ; 95 % CI : 0.49-0 .98 ) .


In addition , age ( AOR : 1.07 ; 95 % CI : 1.02-1 .11 ) and depressive symptoms ( AOR : 0.78 ; 95 % CI : 0.64-0 .90 ) were significantly associated with adherence .


Finally , participants were more likely to open their study medication bottles on days when they presented for in-person urine testing .


Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials , which corroborates prior research .


These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles .


Chronic venous disease is a group of symptoms caused by functional and structural defects of the venous vessels .


One of the most common aspects of this disease is the occurrence of varicose veins .


There are many ways of prevention and treatment of varicose veins , but in Poland the leading one is still surgery .


As in every medical procedure there is the possibility of some complications .


One of them is deep vein thrombosis ( DVT ) .


The diagnosis of DVT can be difficult , especially when access to a specialist is limited , such as in case of rural patients .


The aim of the study .


The aim of the study was estimation of the influence of LMWH primary prophylaxis on the formation of postoperative DVT , as well as sensitivity and specificity of clinical examination and D-dimer value in diagnosis of postoperative DVT in women .


The study was conducted in a group of 93 women operated on in the Department of General , Vascular Surgery and Angiology at the Karol Marcinkowski University of Medical Sciences in Pozna , Poland .


The patients had undergone a varicose vein operation and were randomly divided into two groups : A - 48 women receiving LMWH during two days of the perioperative period , B - 45 women receiving LMWH during seven days of the perioperative period .


There was no significant difference in the postoperative DVT complications in both groups .


The value of D-dimer > 0.987 mcg/ml and swelling > 1.5 cm of shin ( in comparison to the preoperative period ) plays a significant role in diagnosis of DVT .


The extended primary prophylaxis with LMWH does not affect the amount or quality of thrombotic complications after varicose vein operation .


If the DVT occurs , the evaluation of the D - dimer and careful clinical examination can be a useful method for its diagnosis .


Preliminary studies have shown that rituximab ( RTX ) is effective in the treatment of active Graves ' orbitopathy ( GO ) .


We conducted a double-blind , randomized trial ( European Clinical Trials Database [ EudraCT ] 2007-003910-33 ) to compare RTX with iv methylprednisolone ( ivMP ) in patients with active moderate to severe GO .


Thirty-two patients were randomized to receive either ivMP ( 7.5 g ) or RTX ( 2000 or 500 mg ) .


The primary end point was the decrease of the clinical activity score of 2 points or to less than 3 at week 24 .


Changes of proptosis , lid fissure , diplopia and eye muscle motility , and quality of life score were secondary end points .


The number of therapeutic responses , disease reactivation , and surgical procedures required during follow-up and the patients ' quality of life were also assessed .


The clinical activity score decreased with both treatments but more after RTX at 16 , 20 , and 24 weeks ( P < .04 , P < .02 , P < .006 , respectively ) , whether 1000 mg RTX twice or 500 mg RTX once was used ( P = NS ) .


At 24 weeks 100 % of RTX patients improved compared with 69 % after ivMP ( P < .001 ) .


Disease reactivation was never observed in RTX patients but was observed in five after ivMP .


Patients treated with RTX scored better motility at 52 weeks in both the right ( P = .014 ) and the left eye ( P = .026 ) .


Overall rehabilitative surgical procedures carried out during follow-up ( at 76 wk ) were 12 in 16 ivMP patients and 5 in 15 RTX patients ( P = .049 ) .


The results of this trial confirm preliminary reports on a better therapeutic outcome of RTX in active moderate to severe GO , when compared with ivMP , even after a lower RTX dose .


The better eye motility outcome , visual functioning of the quality of life assessment , and the reduced number of surgical procedures in patients after RTX seem to suggest a disease-modifying effect of the drug .


Web-based brief alcohol interventions are effective in reducing alcohol use among students when measured at limited follow-up time points .


To date , no studies have tested Web-based brief alcohol intervention effectiveness over time by using a large number of measurements .


Testing whether the What Do You Drink ( WDYD ) Web-based brief alcohol intervention can sustain a reduction in alcohol use among heavy-drinking students aged 18-24 years at 1 - , 3 - , and 6-month follow-up intervals .


A purely Web-based , 2-arm , parallel-group randomized controlled trial applying an ecological momentary assessment approach with 30 weekly measurements was conducted in the Netherlands ( 2010-2011 ) .


Participants were recruited offline and online .


A total of 907 participants were randomized into the experimental condition ( n = 456 ) including the single-session and fully automated WDYD intervention , or into the control condition ( n = 451 ) including assessment only .


Weekly alcohol consumption and frequency of binge drinking were the self-assessed outcome measures .


Attrition rates of the 907 participants were 110 ( 12.1 % ) , 130 ( 14.3 % ) , and 162 ( 17.9 % ) at 1 - , 3 - , and 6-month follow-up intervals , respectively .


Latent growth curve analyses according to the intention-to-treat principle revealed that participants in the experimental condition had significantly lower weekly alcohol consumption compared to participants in the control condition that was sustained at 3-month follow-up ( intercept = -2.60 , P < .001 ; slope = 0.16 , P = .08 ) .


Additional linear regression analyses indicated that this intercept difference resulted from significantly higher levels of alcohol units per week for participants in the control condition compared to those in the experimental condition at 1-month ( beta = -2.56 , SE 0.74 , Cohen 's d = 0.20 , P = .001 ) , 3-month ( beta = -1.76 , SE 0.60 , Cohen 's d = 0.13 , P = .003 ) , and 6-month ( beta = -1.21 , SE 0.58 , Cohen 's d = 0.09 , P = .04 ) follow-up intervals .


Latent growth curve analyses further indicated that participants in the experimental condition had a significantly lower frequency of binge drinking compared to participants in the control condition that was sustained at 6-month follow-up ( intercept = -0.14 , P = .01 ; slope = 0.004 , P = .19 ) .


This intercept difference resulted from higher levels in this outcome for participants in the control condition relative to participants in the experimental condition at 1-month ( beta = -1.15 , SE 0.06 , Cohen 's d = 0.16 , P = .01 ) , 3-month ( beta = -0.12 , SE 0.05 , Cohen 's d = 0.09 , P = .01 ) , and 6-month ( beta = -0.09 , SE 0.05 , Cohen 's d = 0.03 , P = .045 ) follow-up intervals .


The WDYD intervention was shown to be effective in preventing an increase in weekly alcohol consumption and frequency of binge drinking directly after the intervention .


This effect was sustained 3 and 6 months after the intervention .


Netherlands Trial Register NTR2665 ; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2665 ( Archived by WebCite at http://webcitation.org/6LuQVn12M ) .


To determine whether increased elimination of gadobenate ion via the hepatobiliary pathway might compensate for reduced/absent elimination via the urinary pathway in the event of compromised renal function , as a possible protective mechanism against nephrogenic systemic fibrosis ( NSF ) .


15 male Crl : CD ( ) R ( SD ) Br rats ( Charles River Italia , Como , Italy ) randomized to three treatment groups : ( 1 ) animals with occluded bile ducts , ( 2 ) animals with occluded renal vessels and ( 3 ) control animals , each received 0.25 mmol kg ( -1 ) of bodyweight of gadobenate dimeglumine ( MultiHance ( ) ; Bracco Imaging SpA , Milan , Italy ) .


Urine and bile were collected from 0-30 , 30-60 , 60-120 , 120-240 and 240-480 min after gadobenate dimeglumine administration prior to exsanguination .


Determinations of gadobenate ion in blood , bile and urine were performed by high-performance liquid chromatography .


Gadolinium ( Gd ( 3 + ) ) levels in excised liver and kidneys were determined by X-ray fluorescence .


The recovery of gadobenate ion in the urine of rats with bile duct occlusion was significantly higher than that in the urine of normal rats ( 89.1 4.2 % vs 60.6 2.8 % ; p < 0.0001 ) .


Conversely , mean recovery in the bile of rats with renal vessel occlusion was significantly higher than that in the bile of normal rats ( 96.16 0.55 % vs 33.5 4.7 % ; p < 0.0001 ) .


Gadobenate ion was not quantifiable in any group 8 h post-injection .


Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination .


The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd ( 3 + ) elimination via the hepatobiliary route .


Oral propranolol has been used to treat complicated infantile hemangiomas , although data from randomized , controlled trials to inform its use are limited .


We performed a multicenter , randomized , double-blind , adaptive , phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy .


Infants were randomly assigned to receive placebo or one of four propranolol regimens ( 1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months ) .


A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis .


The primary end point was success ( complete or nearly complete resolution of the target hemangioma ) or failure of trial treatment at week 24 , as assessed by independent , centralized , blinded evaluations of standardized photographs .


Of 460 infants who underwent randomization , 456 received treatment .


On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment , the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis .


The frequency of successful treatment was higher with this regimen than with placebo ( 60 % vs. 4 % , P < 0.001 ) .


A total of 88 % of patients who received the selected propranolol regimen showed improvement by week 5 , versus 5 % of patients who received placebo .


A total of 10 % of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up .


Known adverse events associated with propranolol ( hypoglycemia , hypotension , bradycardia , and bronchospasm ) occurred infrequently , with no significant difference in frequency between the placebo group and the groups receiving propranolol .


This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma .


( Funded by Pierre Fabre Dermatologie ; ClinicalTrials.gov number , NCT01056341 . )


People with type 1 diabetes ( T1DM ) require insulin therapy to sustain life , and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications .


Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump ( continuous subcutaneous insulin infusion ) , a more costly option with benefits for some patients .


The UK National Institute for Health and Care Excellence ( NICE ) recommend the use of pumps for patients with the greatest need , citing insufficient evidence to approve extension to a wider population .


Far fewer UK adults use pumps than in comparable countries .


Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment .


This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections , where both groups are provided with high-quality structured education .


A multicentre , parallel group , cluster randomised controlled trial among 280 adults with T1DM .


All participants attended the week-long dose adjustment for normal eating ( DAFNE ) structured education course , and receive either multiple daily injections or pump therapy for 2years .


The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis .


The primary outcome will be the change in glycosylated haemoglobin ( HbA1c ) at 24months in those participants whose baseline HbA1c is at or above 7.5 % ( 58mmol/mol ) .


The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5 % ( 58mmol/mol ) or less at 24months .


The protocol was approved by the Research Ethics Committee North West , Liverpool East and received Medicines and Healthcare products Regulatory Agency ( MHRA ) clinical trials authorisation .


Each participating centre gave National Health Service R&D approval .


We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations , including lay user groups .


ISRCTN 61215213 .


To optimize palliation in incurable locally advanced non-small cell lung cancer ( NSCLC ) , the International Atomic Energy Agency conducted a prospective randomized study ( NCT00864331 ) comparing protracted palliative radiotherapy ( RT ) course with chemotherapy ( CHT ) followed by short-course palliative RT. .


Treatment-naive patients with histologically confirmed NSCLC , stage IIIA/IIIB , received either 39Gy in 13 fractions as RT alone ( arm A , n = 31 ) or 2-3 platinum-based CHT cycles followed by 10Gy in a single fraction or 16Gy in 2 fractions separated by one week ( arm B , n = 34 ) .


Primary outcome was overall survival .


Treatment groups were balanced with respect to various variables .


Median survival for all 65 patients was 8months , while median survival was 7.1 and 8.1 months for the two arms , respectively ( log-rank p = 0.4 by study arm , and p = 0.6 by Cox regression and stratified by country and sub-stage ) .


One and three year survival rates for the two arms were 29 % , and 9 % and 41 % , and 6 % , respectively .


There were no differences in any of the following endpoints : any failure , local failure , regional failure , contralateral thoracic failure , and distant failure between the two arms .


High-grade ( 3 ) toxicity was similar between the two arms .


Symptoms , adverse events of any kind , KPS and body-mass index , were not different during treatment and during follow-up .


There was no grade 5 toxicity .


This incomplete and underpowered trial only hinted similar outcome between the treatment arms .


Therefore , combined CHT-RT can perhaps be considered , in limited resource setting , where access to RT remains inadequate .


Medical expulsive therapy ( MET ) using alpha-blockers is effective for distal ureteral calculi ( UC ) .


We aimed to evaluate the efficacy of tamsulosin for proximal UC expulsion .


An open-label randomized controlled trial was conducted with 108 patients who agreed to conservative management for single , radiopaque , proximal UC 6 mm and were randomized into group A ( n = 54 , conservative managements only ) or B ( n = 54 , 0.2 mg tamsulosin once a day ) .


The primary end-point was stone passage rates ( SPR ) in the intention-to-treat population in 4 treatment weeks .


The secondary end-points were estimated in per-protocol population and were time to stone passage , post-trial Euro-quality-of-life ( EuroQOL ) score , oral analgesic requirements , and willingness to undergo conservative treatment again .


The two groups were well balanced in terms of baseline patient and stone characteristics .


Seventy nine patients ( 73.2 % ; 35 of group A and 44 of group B ) completed the study protocol .


The overall SPR was 60.2 % ( 65/108 ) .


Group B had a higher SPR ( 74.1 % ; 40/54 ) than group A ( 46.3 % ; 25/54 ; p = 0.003 ) and a significantly shorter time to stone passage ( mean days , A : 19.6 vs. B : 14.3 , p = 0.005 ) .


The groups did not differ in post-trial EuroQOL score or oral analgesic requirements , whereas 74.3 % ( 26/35 ) of group A and 90.9 % ( 40/44 ) of group B were willing to undergo conservative treatment again ( p = 0.048 ) .


Univariate logistic regression analysis showed that stone size ( OR = 1.447 , p = 0.045 ) and tamsulosin treatment ( OR = 3.314 , p = 0.004 ) significantly predicted stone expulsion .


On multivariate analysis , only tamsulosin was statistically significant ( OR = 3.198 , p = 0.021 ) .


Tamsulosin was associated with significantly higher stone expulsion rate and shorter expulsion time in proximal UC 6 mm compared with conservative managements only .


Our results indicate that similar to patients with distal UC , MET using tamsulosin is a reasonable treatment option for patients with proximal UC .


To address the public health crisis of overweight and obese preschool-age children , the Nutrition And Physical Activity Self Assessment for Child Care ( NAP SACC ) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge , center-level nutrition and physical activity policies and practices , and children 's body mass index ( BMI ) .


A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California , Connecticut , and North Carolina , including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old .


The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants .


Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents .


Blinded research assistants reviewed each center 's written health and safety policies , observed nutrition and physical activity practices , and measured randomly selected children 's nutritional intake , physical activity , and height and weight pre - and post-intervention .


Hierarchical linear models and multiple regression models assessed individual - and center-level changes in knowledge , policies , practices and age - and sex-specific standardized body mass index ( zBMI ) , controlling for state , parent education , and poverty level .


Results showed significant increases in providers ' and parents ' knowledge of nutrition and physical activity , center-level improvements in policies , and child-level changes in children 's zBMI based on 209 children in the intervention and control centers at both pre - and post-intervention time points .


The NAP SACC intervention , as delivered by trained child health professionals such as child care health consultants , increases provider knowledge , improves center policies , and lowers BMI for children in child care centers .


More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic .


National Clinical Trials Number NCT01921842 .


Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors .


The chronic care model was proven effective in improving chronic disease outcomes in developed countries , but there is little evidence of its effectiveness in developing countries .


The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention ( multifaceted chronic disease management strategies based on the chronic care model ) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting .


This paper presents the study protocol .


A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur , Malaysia .


Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care .


Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period .


The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team , training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing .


For type 2 diabetes mellitus , the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5 % .


For hypertension without type 2 diabetes mellitus , the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg .


Secondary outcomes include the proportion of patients achieving targets for serum lipid profile , body mass index and waist circumference .


Other outcome measures include medication adherence levels , process of care and prescribing patterns .


Patients ' assessment of their chronic disease care and providers ' perceptions , attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated .


Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings .


The evidence should instigate crucial primary care system change in Malaysia .


ClinicalTrials.gov NCT01545401 .


This study compared the therapeutic effect of monotherapy with a nonsteroidal anti-inflammatory drug ( NSAID ) patch vs an NSAID patch combined with transcutaneous electric nerve stimulation ( TENS ) , a heating pad , or topical capsaicin in the treatment of patients with myofascial pain syndrome ( MPS ) of the upper trapezius .


A randomized , single-blind , controlled study of combination therapy for patients with MPS was performed .


Ninety-nine patients were randomly assigned to one of four different self-management methods for treatment : NSAID patch ( N = 25 ) , NSAID patch + TENS ( N = 24 ) , NSAID patch + heating pad ( N = 25 ) , and NSAID patch + topical capsaicin ( N = 25 ) .


The NSAID patch used in this study was a ketoprofen patch .


All treatment groups were observed for 2 weeks , and the numeric rating scale ( NRS ) pain score , cervical active range of motion , pressure pain threshold , and Neck Disability Index were assessed .


There was no significant difference between the NSAID patch alone group and the three combination therapy groups with respect to decrease in NRS score from baseline ( day 0 ) to each period of observation .


In covariate analysis , although there was no difference among the groups in most of the periods , the data at day 14 indicated a trend ( P = 0.057 ) .


There were no significant differences in the other variables .


We did not observe a statistical difference in improvements to the clinical variables among the four different methods .


However , further studies regarding the effectiveness of a mixture of topical capsaicin and ketoprofen in patients with MPS should be considered .


In view of freezing of gait 's circumstances of occurrence in Parkinson 's disease , attentional resources appear to be involved in step initiation failure .


Anticipatory postural adjustments ( APAs ) are essential because they allow unloading of the stepping leg and so create the conditions required for progression .


Our main objective was to establish whether or not a change in attentional load during step initiation modulates APAs differently in patients with vs. without freezing of gait .


Three groups of 15 subjects were recruited : elderly people and parkinsonian patients with or without freezing of gait .


Attention was modulated before step execution by means of an auditory oddball discrimination task with event-related potential recording .


The primary endpoint was the occurrence of inappropriate APAs following the attentional task , i.e. APAs not followed by a step after an intercurrent auditory stimulus .


In parkinsonian patients with freezing of gait , inappropriate APAs were recorded in 63 % of the trials and were observed more frequently than in patients without freezing of gait ( 51 % ) and elderly controls ( 48 % ) .


Furthermore , inappropriate APAs in freezers were longer and more ample than in parkinsonian non-freezers and controls .


Lastly , postural preparation was impaired in the parkinsonian patients .


Our results indicate that allocation of attentional resources during step preparation influences the release of APAs differently in freezers and non-freezers .


Modulating attentional load is partly responsible for triggering an inappropriate motor program .


This difficulty in focusing attention or resisting interference may contribute ( at least in part ) to the gait initiation failure observed in parkinsonian freezers .


To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis .


Case-control neurophysiological and behavioral study of patients with chronic stroke .


Research institution .


Eighty-six referred patients were screened to enroll 9 participants ( N = 9 ) with a > 6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation .


Eight age - and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison .


Not applicable .


Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex ( M1 ) during nonparetic arm force .


We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis .


Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario ( 20 % 7 % vs -1 % 4 % , F1 ,12 = 6.61 , P = .025 ) .


Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function .


Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm .


Though our study is limited in generalizability by the small sample size , we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke .


For many patients , adhering to postmenopausal osteoporosis treatment is a challenge .


Higher treatment satisfaction is associated with greater persistence with these therapies , which is associated with better outcomes .


This study aimed to evaluate the change in treatment satisfaction in postmenopausal women who were suboptimally adherent to daily or weekly oral bisphosphonates and who transitioned to denosumab vs a monthly oral bisphosphonate .


Pooled data of outpatients from two international , multicenter , randomized , open-label studies were analyzed .


Postmenopausal women ( n = 1703 ) age 55 years or greater with low bone mineral density who were suboptimally adherent with prior oral bisphosphonate therapy , as assessed by the Osteoporosis-Specific Morisky Medication Adherence Scale , were included in the study .


Patients received denosumab , a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B ligand , 60 mg s.c. every 6 months vs the oral bisphosphonates ibandronate or risedronate , 150 mg once monthly for 12 months .


Change in treatment satisfaction scores from baseline to months 6 and 12 were measured using the Treatment Satisfaction Questionnaire for Medication ( TSQM ) .


The TSQM is a validated tool that measures perception of four domains of treatment satisfaction : effectiveness , side effects , convenience , and global satisfaction .


Patients in both treatment groups showed improvement from baseline for all four TSQM domains at 6 and 12 months .


However , the denosumab group had significantly ( all P < .001 ) greater improvements among all four TSQM domains at 6 and 12 months compared with the oral bisphosphonate group .


Women with low adherence to oral bisphosphonates reported greater treatment satisfaction when transitioned to denosumab vs switching to a monthly oral bisphosphonate .


Mild hypoxia is common in stroke patients and may have significant adverse effects on the ischemic brain after stroke .


The use of oxygen treatment is rapidly increasing in European stroke units but is not without side effects .


It impedes early mobilization , could pose an infection risk , and may encourage the formation of toxic free radicals , leading to further damage to the ischemic brain .


In the Stroke Oxygen Pilot Study ( 2 or 3L/min for 72hours ) neurological recovery at one week was better in the oxygen group than in controls , and after correction for difference in baseline stroke severity and prognostic factors , there was a trend to better outcome with oxygen at six months .


Oxygen was as effective in mild as in severe strokes.Oxygen saturation is lower at night than during the day , and episodes of oxygen desaturation are common during sleep .


Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia without interfering with daytime mobilization and rehabilitation.Before wider use of oxygen supplementation becomes established it is important to obtain better evidence on which patients benefit from such treatment .


Participants will be randomized to one of three groups : the first will receive continuous oxygen for 72hours ( at a rate of 2 or 3L/min depending on baseline oxygen saturation ) , the second group will receive nocturnal oxygen only ( at a rate of 2 or 3L/min depending on baseline oxygen saturation ) and the third group will not receive any oxygen ( control ) .


A baseline assessment is performed at randomization and a one-week follow-up completed .


Outcome data at three , six and twelve months will be obtained via a questionnaire sent to the patient by the trial center .


This study will provide evidence on the effectiveness of oxygen supplementation for the treatment of stroke and whether nocturnal oxygen is a potentially beneficial therapy regimen .


This trial is registered with the ISRCTN register ID number ISRCTN52416964 .


To investigate the blood pressure ( BP ) responses to cardiovascular stress test after a combined exercise circuit session at moderate intensity .


Twenty individuals ( 10 male/10 fem ; 33.4 6.9 years ; 70.2 15.8 kg ; 170.4 11.5 cm ; 22.3 6.8 % body fat ) were randomized in a different days to control session with no exercise or exercise session consisting of 3 laps of the following circuit : knee extension , bench press , knee flexion , rowing in the prone position , squats , shoulder press , and 5 min of aerobic exercise at 75-85 % of age-predicted maximum heart rate and/or 13 on the Borg Rating of Perceived Exertion [ scale of 6 to 20 ] .


The sets of resistance exercise consisted of 15 repetitions at ~ 50 % of the estimated 1 repetition maximum test .


Systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were measured at rest and during 1h of recovery in both experimental sessions .


After that , blood pressure reactivity ( BPR ) was evaluated using the Cold Pressor Test .


During 1h of exercise recovery , there was a reduction in SBP ( 3-6 mmHg ) and DBP ( 2-5 mmHg ) in relation to pre-session rest ( p < 0.01 ) , while this reduction was not observed in the control session .


A decline in BPR ( 4-7 mmHg ; p < 0.01 ) was observed 1h post-exercise session , but not in the control session .


Post-exercise reductions in SBP and DBP were significantly correlated with BPR reductions ( r = 0.50-0 .45 ; p < 0.05 ) .


A combined exercise circuit session at moderate intensity promoted subsequent post-exercise hypotension and acutely attenuated BPR in response to a cardiovascular stress test .


In addition , the post-exercise BP reduction was correlated with BPR attenuation in healthy adults of both genders .


Major depressive disorder ( MDD ) is the leading cause of disability in the developed world , yet broadly effective treatments remain elusive .


Up to 40 % of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have `` treatment-resistant depression '' ( TRD ) .


There is an urgent need for cost-effective , non-pharmacologic , evidence-based treatments for TRD .


Mindfulness-Based Cognitive Therapy ( MBCT ) is an effective treatment for relapse prevention and residual depression in major depression , but has not been previously studied in patients with TRD in a large randomized trial .


The purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy .


MBCT was compared to an active control condition , the Health-Enhancement Program ( HEP ) , which incorporates physical activity , functional movement , music therapy and nutritional advice .


HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects .


Originally investigated in a non-clinical sample to promote stress reduction , HEP was adapted for a depressed population for this study .


Individuals age 18 and older with moderate to severe TRD , who failed to respond to at least two trials of antidepressants in the current episode , were recruited to participate .


All participants were taking antidepressants ( Treatment as usual ; TAU ) at the time of enrollment .


After signing an informed consent , participants were randomly assigned to either MBCT or HEP condition .


Participants were followed for 1year and assessed at weeks 1-7 , 8 , 24 , 36 , and 52 .


Change in depression severity , rate of treatment response and remission after 8weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating ( HAM-D ) 17-item scale .


The participant-rated Quick Inventory of Depression Symptomology ( QIDS-SR ) 16-item scale was the secondary outcome measure of depression severity , response , and remission .


Treatment-resistant depression entails significant morbidity and has few effective treatments .


We studied the effect of augmenting antidepressant medication with MBCT , compared with a HEP control , for patients with TRD .


Analyses will focus on clinician and patient assessment of depression , participants ' clinical global impression change , employment and social functioning scores and quality of life and satisfaction ratings .


ClincalTrials.gov identifier : NCT01021254 .


To assess the long-term effect on symptoms and quality of life of esomeprazole 20mg once daily , a recommended dose for maintenance therapy of gastroesophageal reflux disease ( GERD ) .


This is a post hoc analysis of 5 year data from patients in the LOTUS trial ( ClinicalTrials.gov identifier : NCT00251927 ) who were randomized to esomeprazole 20mg once daily .


All participants had chronic , symptomatic GERD responsive to treatment .


Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments .


Investigations included gastrointestinal endoscopy ( with biopsy sampling ) , 24 hour esophageal pH monitoring and laboratory measurements .


In total , 157 of 256 patients randomized to esomeprazole 20mg once daily remained on this dose until the end of follow-up or study discontinuation , whereas 99 patients had their dose increased because of inadequate symptom control ( of these , 29 subsequently returned to the allocated dose ) .


On logistic regression , a long objectively defined GERD history , smoking , female sex , absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40mg daily ( all p < 0.05 ) .


Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20mg once daily , with no more than mild symptom severity , and mean ( standard deviation ) percentage time with intraesophageal pH < 4 was reduced from 10.7 ( 10.7 ) pre-randomization to 6.3 ( 10.2 ) at 6 months and 4.9 ( 7.3 ) at 5 years .


The number of serious adverse events was low ( 0.079 per patient per year ) .


Post hoc analysis with no control group .


Esomeprazole at a maintenance dose of 20mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication , with durable symptom control and sustained reductions in intraesophageal acid exposure .


In the Systolic Hypertension in Europe trial ( NCT02088450 ) , we investigated whether systolic blood pressure variability determines prognosis over and beyond level .


Using a computerised random function and a double-blind design , we randomly allocated 4695 patients ( 60 years ) with isolated systolic hypertension ( 160-219 / < 95 mm Hg ) to active treatment or matching placebo .


Active treatment consisted of nitrendipine ( 10-40 mg/day ) with possible addition of enalapril ( 5-20 mg/day ) and/or hydrochlorothiazide ( 12.5-25 .0 mg/day ) .


We assessed whether on-treatment systolic blood pressure level ( SBP ) , visit-to-visit variability independent of the mean ( VIM ) or within-visit variability ( WVV ) predicted total ( n = 286 ) or cardiovascular ( n = 150 ) mortality or cardiovascular ( n = 347 ) , cerebrovascular ( n = 133 ) or cardiac ( n = 217 ) endpoints .


At 2 years , mean between-group differences were 10.5 mm Hg ( p < 0.0001 ) for SBP , 0.29 units ( p = 0.20 ) for VIM , and 0.07 mm Hg ( p = 0.47 ) for WVV .


Active treatment reduced ( p0 .048 ) cardiovascular ( -28 % ) , cerebrovascular ( -40 % ) and cardiac ( -24 % ) endpoints .


In analyses dichotomised by the median , patients with low vs. high VIM had similar event rates ( p0 .14 ) .


Low vs. high WVV was not associated with event rates ( p0 .095 ) , except for total and cardiovascular mortality on active treatment , which were higher with low WVV ( p0 .0003 ) .


In multivariable-adjusted Cox models , SBP predicted all endpoints ( p0 .0043 ) , whereas VIM did not predict any ( p0 .058 ) .


Except for an inverse association with total mortality ( p = 0.042 ) , WVV was not predictive ( p0 .15 ) .


Sensitivity analyses , from which we excluded blood pressure readings within 6 months after randomisation , 6 months prior to an event or both were confirmatory .


The double-blind placebo-controlled Syst-Eur trial demonstrated that blood-pressure lowering treatment reduces cardiovascular complications by decreasing level but not variability of SBP .


Higher blood pressure level , but not higher variability , predicted risk .


ClinicalTrials.gov NCT02088450 .


The aim of the study was to compare the effect of six ( A6 regimen ) vs two meals a day , breakfast and lunch ( B2 regimen ) , on body weight , hepatic fat content ( HFC ) , insulin resistance and beta cell function .


In a randomised , open , crossover , single-centre study ( conducted in Prague , Czech Republic ) , we assigned 54 patients with type 2 diabetes treated with oral hypoglycaemic agents , both men and women , age 30-70 years , BMI 27-50kg / m ( 2 ) and HbA1c 6-11 .8 % ( 42-105mmol / mol ) , to follow two regimens of a hypoenergetic diet , A6 and B2 , each for 12weeks .


Randomisation and allocation to trial groups ( n = 27 and n = 27 ) were carried out by a central computer system .


Individual calculations of energy requirements for both regimens were based on the formula : ( resting energy expenditure1 .5 ) -2,092 kJ .


The diet in both regimens had the same macronutrient and energy content .


HFC was measured by proton magnetic resonance spectroscopy .


Insulin sensitivity was measured by isoglycaemic-hyperinsulinaemic clamp and calculated by mathematical modelling as oral glucose insulin sensitivity ( OGIS ) .


Beta cell function was assessed during standard meal tests by C-peptide deconvolution and was quantified with a mathematical model .


For statistical analysis , 22 crossover ANOVA was used .


The intention-to-treat analysis included all participants ( n = 54 ) .


Body weight decreased in both regimens ( p < 0.001 ) , more for B2 ( -2.3 kg ; 95 % CI -2.7 , -2.0 kg for A6 vs -3.7 kg ; 95 % CI -4.1 , -3.4 kg for B2 ; p < 0.001 ) .


HFC decreased in response to both regimens ( p < 0.001 ) , more for B2 ( -0.03 % ; 95 % CI -0.033 % , -0.027 % for A6 vs -0.04 % ; 95 % CI -0.041 % , -0.035 % for B2 ; p = 0.009 ) .


Fasting plasma glucose and C-peptide levels decreased in both regimens ( p < 0.001 ) , more for B2 ( p = 0.004 and p = 0.04 , respectively ) .


Fasting plasma glucagon decreased with the B2 regimen ( p < 0.001 ) , whereas it increased ( p = 0.04 ) for the A6 regimen ( p < 0.001 ) .


OGIS increased in both regimens ( p < 0.01 ) , more for B2 ( p = 0.01 ) .


No adverse events were observed for either regimen .


Eating only breakfast and lunch reduced body weight , HFC , fasting plasma glucose , C-peptide and glucagon , and increased OGIS , more than the same caloric restriction split into six meals .


These results suggest that , for type 2 diabetic patients on a hypoenergetic diet , eating larger breakfasts and lunches may be more beneficial than six smaller meals during the day .


Trial registration ClinicalTrials.gov number , NCT01277471 , completed .


Funding Grant NT/11238 -4 from Ministry of Health , Prague , Czech Republic and the Agency of Charles University - GAUK No 702312 .


Invasive treatment ( coronary angiography and intervention if feasible ) of patients with acute coronary syndrome ( ACS ) has been shown to lead to better outcomes than medical therapy alone , but the elderly have been under-represented in many of the studies .


In the elderly , medical therapy is common in ACS .


Fear of complications related to the procedure and unclear benefit in older patients are common reasons for invasive procedures being withheld .


Our hypothesis is that invasive treatment of elderly patients with ACS will lead to a better outcome in terms of survival and quality of life than medical therapy alone , with acceptable risk .


This multicenter , randomized controlled trial of patients 80 years of age and over has two parallel treatment arms , a medical group and an invasive group .


In Swedish hospitals , 200 patients with non-ST elevation myocardial infarction or unstable angina will be randomized to medical or invasive treatment strategy .


The primary outcome measure is the combined endpoint major adverse cardiac or cerebrovascular event ( MACCE ) within one year .


Secondary outcome measures include quality of life , angina , and adverse events such as bleeding .


Assessments will be conducted during hospitalization , at 1 month after allocation , and at 12 months .


This study seeks to determine the efficacy and safety of invasive and medical treatment strategies in the elderly with ACS .


The study is currently recruiting .


ClinicalTrials.gov trial identifier : NCT02126202 .


Registered on 7 January 2014 .


Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction , but less is known about the association in heart failure with preserved ejection fraction .


We examined the prevalence of elevated high-sensitivity troponin T ( hs-TnT ) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion ( PARAMOUNT ) trial , in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan .


We assessed the association between hs-TnT and cardiac structure and function , and the effect of LCZ696 , compared with valsartan , on hs-TnT over 36 weeks .


Elevated hs-TnT in the myocardial injury range ( > 0.014 g/L ) was found in 55 % of patients and was associated with older age , history of diabetes mellitus , higher N-terminal pro-brain natriuretic peptide , lower estimated glomerular filtration rate , and larger left atrial size , left ventricular volume , and mass .


LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks ( 12 % reduction ; P = 0.05 ) and at 36 weeks ( 14 % reduction ; P = 0.03 ) compared with valsartan .


Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure , function , and elevated baseline N-terminal pro-brain natriuretic peptide .


Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction .


http://www.clinicaltrials.gov .


Unique identifier : NCT00887588 .


Investigations meeting current standards are limited for the effect of house dust mite ( HDM ) allergy immunotherapy in asthmatic patients .


This trial investigated the efficacy and safety of a standardized quality ( SQ ; allergen standardization method proprietary to the trial sponsor ) HDM SLIT-tablet ( ALK , Hrsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease .


This publication reports the results of the endpoints related to asthma .


Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses ( 1 , 3 , or 6 SQ-HDM ) or placebo .


Their use of inhaled corticosteroid ( ICS ) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control .


The primary end point was a reduction in ICS dose from the individual subject 's baseline dose after 1 year of treatment .


The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 g ( P = .004 ) .


Relative mean and median reductions were 42 % and 50 % for 6 SQ-HDM and 15 % and 25 % for placebo , respectively .


No statistically significant differences were observed for the other assessed asthma parameters , reflecting the intended controlled status of the trial subjects .


The most common adverse events were local reactions in the mouth .


The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo .


Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control .


All active doses were well tolerated .


Pill-taking , expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder ( MDD ) .


Aims To examine the effects of medication , placebo and supportive care on treatment outcome , and the relationships of expectations and therapeutic alliance to improvement .


A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication .


Expectations of medication effectiveness , general treatment effectiveness and therapeutic alliance were measured ( trial registration at ClinicalTrials.gov : NCT00200902 ) .


Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone .


Therapeutic alliance predicted response to medication and placebo ; expectations of medication effectiveness at enrolment predicted only placebo response .


Pill treatment yielded better outcome than supportive care alone .


Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment , suggesting that they were shaped by prior experiences outside the clinical trial .


Adrenocortical carcinoma is a rare , aggressive cancer for which few treatment options are available .


Linsitinib ( OSI-906 ) is a potent , oral small molecule inhibitor of both IGF-1R and the insulin receptor , which has shown acceptable tolerability and preliminary evidence of anti-tumour activity .


We assessed linsitinib against placebo to investigate efficacy in patients with advanced adrenocortical carcinoma .


In this international , double-blind , placebo-controlled phase 3 study , adult patients with histologically confirmed locally advanced or metastatic adrenocortical carcinoma were recruited at clinical sites in nine countries .


Patients were randomly assigned ( 2:1 ) twice-daily 150 mg oral linsitinib or placebo via a web-based , centralised randomisation system and stratified according to previous systemic cytotoxic chemotherapy for adrenocortical carcinoma , Eastern Cooperative Oncology Group performance status , and use of one or more oral antihyperglycaemic therapy at randomisation .


Allocation was concealed by blinded block size and permuted block randomisation .


The primary endpoint was overall survival , calculated from date of randomisation until death from any cause .


The primary analysis was done in the intention-to-treat population .


This study is registered with ClinicalTrials.gov , number NCT00924989 .


Between Dec 2 , 2009 , and July 11 , 2011 , 139 patients were enrolled , of whom 90 were assigned to linsitinib and 49 to placebo .


The trial was unblinded on March 19 , 2012 , based on data monitoring committee recommendation due to the failure of linsitinib to increase either progression-free survival or overall survival .


At database lock and based on 92 deaths , no difference in overall survival was noted between linsitinib and placebo ( median 323 days [ 95 % CI 256-507 ] vs 356 days [ 249-556 ] ; hazard ratio 094 [ 95 % CI 061-144 ] ; p = 077 ) .


The most common treatment-related adverse events of grade 3 or worse in the linsitinib group were fatigue ( three [ 3 % ] patients vs no patients in the placebo group ) , nausea ( two [ 2 % ] vs none ) , and hyperglycaemia ( two [ 2 % ] vs none ) .


No adverse events in the linsitinib group were deemed to be treatment related ; one death ( due to sepsis and megacolon ) in the placebo group was deemed to be treatment related .


Linsitinib did not increase overall survival and so can not be recommended as treatment for this general patient population .


Further studies of IGF-1R and insulin receptor inhibitors , together with genetic profiling of responders , might pave the way toward individualised and improved therapeutic options in adrenocortical carcinoma .


Astellas .


Many patients experience moderate to severe postoperative pain .


Nitrous oxide ( NO ) exerts analgesia by inhibition of N-methyl-D-aspartate receptors .


Ketamine , another N-methyl-D-aspartate receptor antagonist , reduces postoperative opioid consumption and pain .


A similar effect of NO is plausible , yet understudied .


The goal of this study was to determine the effects of NO anesthesia on early postsurgical opioid consumption and pain .


This was a retrospective , secondary analysis of the Vitamins In Nitrous Oxide trial , where 500 patients undergoing general anesthesia for noncardiac surgery received 60 % NO and 125 received no NO ( otherwise , inclusion/exclusion criteria were identical ) .


Exclusion criteria for this study were regional anesthesia , not extubated after surgery , transfer to intensive care unit , no available postanesthesia care unit record , postsurgical sedation , or treated with naloxone .


Primary outcomes were cumulative opioid consumption measured in morphine equivalents and pain scores during the immediate recovery phase .


Four hundred forty-two patients met inclusion criteria .


No difference in intraoperative and postoperative opioid consumption was observed between patients who received NO ( n = 353 ) and patients who did not ( n = 89 ) .


The median [ interquartile range ] postoperative morphine equivalent dose was 6.7 mg [ 1.7-14 .1 mg ] for patients who received NO and 6.7 mg [ 2.1-15 .4 mg ] for patients who did not ( P = 0.73 ) .


The maximum pain score was 6 [ 4-8 ] for patients who received NO versus 6 [ 3-8 ] for patients who received NO-free anesthesia ( P = 0.52 ) .


The prevalence of moderate to severe pain was 69 % for patients who received NO and 68 % for patients who did not ( P = 0.90 ) .


Nitrous oxide anesthesia was not associated with decreased opioid administration , pain , or incidence of moderate to severe pain in the early postoperative phase .


To determine whether electroacupuncture ( EA ) intervention combined with general anesthesia ( GA ) strategy can reduce early post-operative morbidity and medical costs in patients undergoing heart valve replacement operation under cardiopulmonary bypass .


A total of 160 heart valve replacement surgery patients undergoing cardiopulmonary bypass were randomly divided into GA and EA + GA groups ( n = 80 in each group ) .


Patients of the GA group were given with intravenous injection of Fentanyl , Midazolam , Vecuronium Bromide , etc. and routine tracheal intubation .


EA ( 3-4 Hz , 2.0-2 .2 mA ) was applied to bilateral Zhongfu ( LU 1 ) , Chize ( LU 5 ) and Ximen ( PC 4 ) beginning about 20 mm before the surgery in the EA + GA group .


Endotracheal intubation was not employed but only prepared as a standby for patients of the EA + GA group .


The dosage of narcotic drugs , duration of surgery , duration of aertic blockage , rate of cardiac re-beating , volumes of post-operative blood transfusion , discharge volume , cases of post-operative pulmonary infection , vocal cord injury , and the time of first bed-off , first eating and duration in intensive care unit ( IOU ) residence .


etc. were recorded .


The successful rates of heart valve replacement surgery were similar in both GA and EA + GA groups .


Compared with the GA group , the dosages of Fentanyl , Midazolam and Vecuronium of the EA + GA group were significantly lower ( P < 0.05 , P < 0.01 ) , the numbers of patients needing blood-transfusion , antibiotics treatment , and suffering from pulmonary infection were fewer , the time of first bed-off and duration of hospitalizetion and IOU residence were considerably shorter ( P < 0.05 , P < 0.01 ) and the total medical cost was obviously lower ( P < 0.05 ) in the EA + GA group .


EA combined with general anesthesia strategy for heart valve replacement surgery without endotracheal intubation is safe and can reduce post-operative morbidity and medical costs in patients undergoing heart valve replacement surgery under cardiopulmonary bypass .


To assess the cost-effectiveness of a nurse facilitated , cognitive behavioural self-management programme for patients with heart failure compared with usual care including the un-facilitated access to the same manual , from the perspective of the NHS .


Data were obtained from a pragmatic , multi-centre , randomized controlled ` open ' trial conducted in seven centres in the UK between 2006 and 2008 .


Effectiveness was estimated as Quality-Adjusted Life Years .


Resource use was measured prospectively on all patients using information provided by patients in postal questionnaires , case-note review , electronic record review and interviews with patients .


Unit costs were obtained from the literature and applied to the relevant resource use to estimate total costs .


Multiple imputation was used to handle missing data .


There were no substantial differences in the utility scores between treatment groups in all follow-up assessments , in the use of medication or outpatient visits and both groups report a similar frequency of contact with health care professionals .


After controlling for baseline utility and using imputed dataset , treatment was associated with a reduction in QALY of 0.004 and a additional cost of 69.49 .


The probability that the intervention is cost-effective for thresholds between 20,000 and 30,000 is around 45 % .


There is little evidence that the addition of the intervention had any effect on costs or outcomes .


The uncertainty around both estimates of cost and effectiveness mean that it is not reasonable to make recommendations based on cost-effectiveness alone .


Major depressive disorder ( MDD ) is frequently associated with underactivity of the dorsolateral prefrontal cortex ( DLPFC ) which has led to this brain region being identified as an important target for the development of neurobiological treatments .


Transcranial direct current stimulation ( tDCS ) administered to the DLPFC has antidepressant efficacy , however the magnitude of antidepressant outcomes are limited .


Concurrent cognitive activity has been shown to enhance tDCS induced stimulation effects .


Cognitive control training ( CCT ) is a new cognitive therapy for MDD that aims to enhance DLPFC activity via behavioral methods .


We tested the hypothesis that co-administration of DLPFC tDCS and CCT would result in a greater reduction in depressive symptomology than administration of tDCS or CCT alone .


27 adult participants with MDD were randomized into a three-arm sham-controlled between-groups pilot study comparing the efficacy of 2 mA tDCS + CCT , sham tDCS + CCT and sham CCT + 2 mA tDCS ( 5 sessions administered on consecutive working days ) .


Blinded assessments of depression severity and cognitive control were conducted at baseline , end of treatment and a three week follow up review .


All three treatment conditions were associated with a reduction in depression severity at the end of five treatment sessions .


However , only administration of tDCS + CCT resulted in sustained antidepressant response at follow up , the magnitude of which was greater than that observed immediately following conclusion of the treatment course .


The results provide preliminary evidence that concurrent CCT enhances antidepressant outcomes from tDCS .


In the current sample , participants receiving concurrent tDCS and CCT continued to improve following cessation of treatment .


The clinical superiority of a combined therapeutic approach was apparent even in a small sample and following a relatively short treatment course .


Isolated systolic hypertension is a highly prevalent disease among the elderly .


The little available evidence on the efficacy of nitrates for treating the disease is based on small experimental studies .


We performed a multicenter , randomized , double-blind , phase III , placebo-controlled trial in 154 patients aged over 65 years with refractory isolated systolic hypertension .


Patients were randomized to placebo or 40 mg/day of extended-release isosorbide mononitrate added to standard therapy and titrated to 60 mg/day at week 6 if blood pressure exceeded 140/90 mmHg.The primary objective was to assess the effect on clinical pulse pressure of extended-release isosorbide mononitrate added to standard therapy in patients aged over 65 years with refractory isolated systolic hypertension after 3 months of treatment.The secondary objectives were as follows : to quantify the effect of adding the study drug on central blood pressure and vascular compliance using the augmentation index and pulse wave velocity ; to evaluate the safety profile by recording adverse effects ( frequency , type , severity ) and the percentage of patients who had to withdraw from the trial because of adverse events ; to quantify the percentage of patients who reach a clinical systolic blood pressure < 140 mmHg or < 130 mmHg measured by ambulatory blood pressure monitoring ; and to quantify the change in pulse pressure measured by ambulatory blood pressure monitoring .


Few clinical trials have been carried out to test the effect of oral nitrates on isolated systolic hypertension , even though these agents seem to be effective .


Treatment with extended-release isosorbide mononitrate could improve control of systolic blood pressure without severe side effects , thus helping to reduce the morbidity and mortality of the disease .


EUDRACT Number : 2012-002988-10 .


Acne scarring remains a stubborn clinical problem .


Few treatments have been shown to bedefinitely effective for this problem .


Polymethylmethacrylate ( PMMA ) microspheres in collagen ( ArteFill , Suneva Medical Inc , Santa Barbara , CA ) have shown long-term benefit for nasolabial fold treatment .


A pilot study has shown benefit for PMMA-collagen in atrophic acne scarring .


We sought to demonstrate the safety and effectiveness of PMMA-collagen for acne scarring in a controlled , blinded trial .


Subjects with at least 4 moderate to severe rolling , atrophic scars randomly received PMMA-collagen or saline injections .


Subjects underwent up to 2 injection sessions and were followed up for 6 months .


Efficacy was assessed using a validated rating scale for each scar .


In all , 147 subjects underwent injections .


Success was achieved by 64 % of those treated with PMMA-collagen compared with 33 % of control subjects ( P = .0005 ) .


The treatment showed excellent safety with generally mild , reversible adverse events .


No significant differences in efficacy or safety were noted between genders , for darker skin types , or in older age groups .


Subjects were followed up for only 6 months .


PMMA-collagen demonstrates substantial effectiveness in the treatment of atrophic acne scars of the face while maintaining an excellent safety profile .


Further follow-up should be undertaken to demonstrate longer-term benefit and safety .


Parenteral artesunate is recommended as first-line therapy for severe malaria .


While its efficacy is firmly established , data on safety are still incomplete .