The embedded qualitative study will include focus groups with clinicians to investigate attitudes to recruiting to the study , identify the challenges of progressing to a full randomized controlled trial , and also semi-structured interviews with patients and relatives/carers to explore their attitudes towards participating in the study and potential barriers and concerns to participation .


Finally , a UK wide survey exercise will be undertaken to develop a classification and enumeration system for the cancer associated thrombosis models and pathways of care .


There is a lack of evidence determining the length of anticoagulation for patients with cancer associated thrombosis and subsequently treatment length varies .


The ALICAT study will consider the feasibility of recruiting patients to a phase three trial .


Current Controlled Trials ISRCTN37913976 .


For women with hormone receptor-positive , operable breast cancer , surgical oophorectomy plus tamoxifen is an effective adjuvant therapy .


We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes .


Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days ( n = 509 ) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles , or in the next one to six days .


Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days ( n = 231 ) were excluded from random assignment and received immediate surgical treatments .


All patients began tamoxifen within 6 days of surgery and continued this for 5 years .


Kaplan-Meier methods , the log-rank test , and multivariable Cox regression models were used to assess differences in five-year disease-free survival ( DFS ) between the groups .


All statistical tests were two-sided .


The randomized midluteal phase surgery group had a five-year DFS of 64 % , compared with 71 % for the immediate surgery random assignment group ( hazard ratio [ HR ] = 1.24 , 95 % confidence interval [ CI ] = 0.91 to 1.68 , P = .18 ) .


Multivariable Cox regression models , which included important prognostic variables , gave similar results ( aHR = 1.28 , 95 % CI = 0.94 to 1.76 , P = .12 ) .


For overall survival , the univariate hazard ratio was 1.33 ( 95 % CI = 0.94 to 1.89 , P = .11 ) and the multivariable aHR was 1.43 ( 95 % CI = 1.00 to 2.06 , P = .05 ) .


Better DFS for follicular phase surgery , which was unanticipated , proved consistent across multiple exploratory analyses .


The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial .


The goal of this study was to investigate the differential efficacy of clopidogrel or aspirin monotherapy according to smoking status in patients with atherosclerotic vascular disease .


Smoking enhances clopidogrel-induced platelet inhibition , which may explain the higher relative benefit among smokers observed in trials evaluating dual antiplatelet therapy .


Whether smoking has an impact on clinical outcomes in patients requiring a single antiplatelet agent remains unknown .


This was a post-hoc analysis of the CAPRIE ( Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events ) trial that compared clopidogrel and aspirin monotherapy in patients ( N = 19,184 ) with atherosclerotic vascular disease .


Current smokers ( n = 5,688 ) had an increased risk of ischemic events compared with never smokers ( n = 4,135 ; hazard ratio [ HR ] : 1.24 [ 95 % confidence interval ( CI ) : 1.08 to 1.42 ] ) and ex-smokers ( n = 9,381 ; HR : 1.32 [ 95 % CI : 1.18 to 1.47 ] ) ( p < 0.001 ) .


Clopidogrel was associated with a reduction in ischemic events among current smokers ( 8.3 % vs. 10.8 % ; HR : 0.76 [ 95 % CI : 0.64 to 0.90 ] ) , whereas no benefit over aspirin was seen in the combined group of ex-smokers/never-smoked patients ( 10.4 % vs. 10.6 % ; HR : 0.99 [ 95 % CI : 0.89 to 1.10 ] ; p = 0.01 for interaction ) .


Among current smokers , clopidogrel also reduced myocardial infarction , vascular death , and death from any cause compared with aspirin .


No interaction between smoking status and study treatment was observed for bleeding events .


In a post-hoc analysis of the CAPRIE population , current smokers appeared to have enhanced benefit with clopidogrel therapy for secondary prevention compared with aspirin .


These results should be considered hypothesis generating for future prospective studies assessing the impact of specific platelet-inhibiting strategies according to smoking status .


To evaluate the efficacy of faculty-led problem-based learning ( PBL ) vs online simulated-patient case in fourth-year ( P4 ) pharmacy students .


Fourth-year pharmacy students were randomly assigned to participate in either online branched-case learning using a virtual simulation platform or a small-group discussion .


Preexperience and postexperience student assessments and a survey instrument were completed .


While there were no significant differences in the preexperience test scores between the groups , there was a significant increase in scores in both the virtual-patient group and the PBL group between the preexperience and postexperience tests .


The PBL group had higher postexperience test scores ( 74.811.7 ) than did the virtual-patient group ( 66.513.6 ) ( p = 0.001 ) .


The PBL method demonstrated significantly greater improvement in postexperience test scores than did the virtual-patient method .


Both were successful learning methods , suggesting that a diverse approach to simulated patient cases may reach more student learning styles .


Hamilton depression rating scale ( HAMD ) subscales provide an economic alternative for the full scale ; however , their ability to detect onset of improvement in the early course of treatment ( EI ) has not yet been researched .


The present study investigated in patients with major depression ( MD ) whether the subscales are a comparable option to predict treatment remission in the early course of treatment .


Based on data from 210 MD patients of a 6-week randomised , placebo-controlled trial comparing mirtazapine ( MIR ) and paroxetine ( PAR ) , the discriminative and predictive validity of EI for ( stable ) remission at treatment end was evaluated for seven subscales and the HAMD17 in the total and in treatment subgroups ( MIR vs. PAR ) .


Receiver operating characteristics ( ROC ) curves ( at week 2 ) and the Clinical Global Impression scales ( CGI ) ( at study endpoint ) were used to validate the 20 % EI criterion for the subscales .


Only the Evans6 and Toronto7 subscale had almost the same predictive value as the HAMD17 ( e.g. , sensitivities stable remission Evans6/Toronto7 : 96/95 % vs. 96 % HAMD17 ) .


The optimal cut-off for EI to predict remission was just below 20 % for most subscales and slightly over 20 % for stable remission .


Study sample representativeness , non-independence of subscales , missing external validation criterion , lack of control group .


The Evans6 and Toronto7 subscales are valuable alternatives in situations , where economic aspects play a larger role .


A sum score reduction of 20 % as definition for EI seems also appropriate for the HAMD subscales , in the total as well as in the antidepressant subgroups .


To evaluate the effectiveness and safety of a T-piece resuscitator compared with a self-inflating bag for providing mask ventilation to newborns at birth .


Newborns at 26 weeks gestational age receiving positive-pressure ventilation at birth were included in this multicenter cluster-randomized 2-period crossover trial .


Positive-pressure ventilation was provided with either a self-inflating bag ( self-inflating bag group ) with or without a positive end-expiratory pressure valve or a T-piece with a positive end-expiratory pressure valve ( T-piece group ) .


Delivery room management followed American Academy of Pediatrics and International Liaison Committee on Resuscitation guidelines .


The primary outcome was the proportion of newborns with heart rate ( HR ) 100 bpm at 2 minutes after birth .


A total of 1027 newborns were included .


There was no statistically significant difference in the incidence of HR100 bpm at 2 minutes after birth between the T-piece and self-inflating bag groups : 94 % ( 479 of 511 ) and 90 % ( 466 of 516 ) , respectively ( OR , 0.65 ; 95 % CI , 0.41-1 .05 ; P = .08 ) .


A total of 86 newborns ( 17 % ) in the T-piece group and 134 newborns ( 26 % ) in the self-inflating bag group were intubated in the delivery room ( OR , 0.58 ; 95 % CI , 0.4-0 .8 ; P = .002 ) .


The meanSD maximum positive inspiratory pressure was 262 cm H2O in the T-piece group vs 285 cm H2O in the self-inflating bag group ( P < .001 ) .


Air leaks , use of drugs/chest compressions , mortality , and days on mechanical ventilation did not differ significantly between groups .


There was no difference between the T-piece resuscitator and a self-inflating bag in achieving an HR of 100 bpm at 2 minutes in newborns26 weeks gestational age resuscitated at birth .


However , use of the T-piece decreased the intubation rate and the maximum pressures applied .


To compare operative time with use of THUNDERBEAT ( TB ) vs standard electrosurgery ( SES ) during laparoscopic radical hysterectomy and pelvic lymphadenectomy to treat gynecologic tumors .


Evidence obtained from a properly designed , randomized , controlled trial ( Canadian Task Force classification I ) .


Gynecologic Oncology Unit of the Catholic University of the Sacred Heart in Rome , Italy .


Fifty patients with early cervical cancer ( FIGO stages IA2 , IB1 , IIA < 2 cm ) or locally advanced cervical cancer ( FIGO stages IB2 , IIA > 2cm , IIB ) who received neoadjuvant treatment ( chemotherapy or radiochemotherapy ) and demonstrated a complete or partial clinical response and early stage endometrioid endometrial cancer ( FIGO stages IB , II ) were randomly assigned to undergo TB ( arm A ) or SES ( arm B ) .


Laparoscopic radical hysterectomy with bilateral pelvic lymphadenectomy , using an easily reproducible technique was performed .


Fifty patients were available for analysis , with 25 women randomly assigned to TB ( arm A ) and 25 to SES ( arm B ) .


The median operative time was 85 minutes for TB vs 115 minutes for SES ( p = .001 ) .


At multivariate analysis , endometrial cancer ( p = .001 ) and TB ( p = .001 ) were independently associated with shorter operating time .


No differences in perioperative outcomes and postoperative complications were observed between the 2 arms .


Patients who underwent TB reported less postoperative pain , both at rest ( p = .005 ) and after the Valsalva maneuver ( p = .008 ) , with less additional analgesic therapy other than standard therapy required in patients who underwent SES ( p = .02 ) .


TB is associated with shorter operative time and less postoperative pain than is the standard technique ( SES ) in patients with uterine cancer .


To evaluate the long-term efficacy of pain reduction by two dose-fractionation schedules for radiotherapy of painful shoulder syndrome .


Between February 2006 and February 2010 , 312evaluable patients were recruited for this prospective trial .


All patients received low-dose orthovoltage radiotherapy .


One course consisted of 6fractions in 3weeks .


In the case of insufficient pain remission after 6weeks , a second course was administered .


Patients were randomly assigned to one of two groups to receive single doses of either 0.5 or 1.0 Gy .


Endpoint was pain reduction .


Pain was measured before radiotherapy , as well as immediately after ( early response ) , 6weeks after ( delayed response ) and approximately 3years after ( long-term response ) completion of radiotherapy using a questionnaire-based visual analogue scale ( VAS ) and a comprehensive pain score ( CPS ) .


Median follow-up was 35months ( range11-57 ) .


The overall early , delayed and long-term response rates for all patients were 83 , 85 and 82 % , respectively .


The mean VAS scores before treatment and those for early , delayed and long-term response in the 0.5 - and 1.0-Gy groups were 56.823.7 and 53.221.8 ( p = 0.16 ) ; 38.236.1 and 34.024.5 ( p = 0.19 ) ; 33.027.2 and 23.722.7 ( p = 0.04 ) and 27.925.8 and 32.126.9 ( p = 0.25 ) , respectively .


The mean CPS values before treatment and those for early , delayed and long-term response were 9.73.0 and 9.52.7 ( p = 0.31 ) ; 6.13.6 and 5.43.6 ( p = 0.10 ) ; 5.33.7 and 4.13.7 ( p = 0.05 ) and 4.03.9 and 5.34.4 ( p = 0.05 ) , respectively .


No significant differences in the quality of the long-term response were found between the 0.5 - and 1.0-Gy arms ( p = 0.28 ) .


Radiotherapy is an effective treatment for the management of benign painful shoulder syndrome .


For radiation protection reasons , the dose for a radiotherapy series should not exceed 3.0 Gy .


Management of recent-onset schizophrenia ( SZ ) and schizoaffective disorder ( SA ) is challenging owing to frequent insufficient response to antipsychotic agents .


This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA .


Sixty out - and inpatients who met DSM-IV criteria for SZ/SA , with suboptimal response to antipsychotics were recruited for an 8-week , double-blind , randomized , placebo-controlled , two-center add-on trial , that was conducted between 2008 and 2011 .


Participants were randomized to receive either pregnenolone ( 50mg/day ) or placebo added on to antipsychotic medications .


The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores .


Secondary outcomes included assessments of functioning , and side-effects .


Analysis was by linear mixed model .


Fifty-two participants ( 86.7 % ) completed the trial .


Compared to placebo , adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes ( d = 0.79 ) .


Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers ( armsvisitmood stabilizers ; P = 0.010 ) .


Likewise , pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo ( d = 0.57 ) , especially on blunted affect , avolition and anhedonia domain scores .


Other symptoms , functioning , and side-effects were not significantly affected by adjunctive pregnenolone .


Antipsychotic agents , benzodiazepines and sex did not associate with pregnenolone augmentation .


Pregnenolone was well tolerated .


Thus , add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder , especially among patients who are not treated with concomitant mood stabilizers .


Further studies are warranted .


Loneliness in older people is associated with poor health-related quality of life ( HRQoL ) .


We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people .


An internal pilot tested the feasibility of the trial and intervention .


Participants aged > 74years , with good cognitive function , living independently in one UK city were recruited through general practices and other sources , then randomised to : ( 1 ) 6weeks of short one-to-one telephone calls , followed by 12weeks of group telephone calls with up to six participants , led by a trained volunteer facilitator ; or ( 2 ) a control group .


The main trial required the recruitment of 248 participants in a 1-year accrual window , of whom 124 were to receive telephone befriending .


The pilot specified three success criteria which had to be met in order to progress the main trial to completion : recruitment of 68 participants in 95days ; retention of 80 % participants at 6months ; successful delivery of telephone befriending by local franchise of national charity .


The primary clinical outcome was the Short Form ( 36 ) Health Instrument ( SF-36 ) Mental Health ( MH ) dimension score collected by telephone 6months following randomisation .


We informed 9,579 older people about the study .


Seventy consenting participants were randomised to the pilot in 95days , with 56 ( 80 % ) providing valid primary outcome data ( 26 intervention , 30 control ) .


Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators .


The trial was closed early as a result .


The mean 6-month SF-36 MH scores were 78 ( SD 18 ) and 71 ( SD 21 ) for the intervention and control groups , respectively ( mean difference , 7 ; 95 % CI , -3 to 16 ) .


Recruitment and retention of participants to a definitive trial with a recruitment window of 1year is feasible .


For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre , and/or involve dedicated management of volunteers .


ISRCTN28645428 .


To evaluate the effectiveness of an educational intervention to decrease pediatric emergency department ( PED ) visits and adverse care practices for upper respiratory infections ( URI ) among predominantly Latino Early Head Start ( EHS ) families .


Four EHS sites in New York City were randomized .


Families at intervention sites received 3 1.5-hour education modules in their EHS parent-child group focusing on URIs , over-the-counter medications , and medication management .


Standard curriculum families received the standard EHS curriculum , which did not include URI education .


During weekly telephone calls for 5 months , families reported URI in family members , care sought , and medications given .


Pre - and post-intervention knowledge-attitude surveys were also conducted .


Outcomes were compared between groups .


There were 154 families who participated ( 76 intervention , 78 standard curriculum ) including 197 children < 4 years old .


Families were primarily Latino and Spanish-speaking .


Intervention families were significantly less likely to visit the PED when their young child ( age 6 to < 48 months ) was ill ( 8.2 % vs 15.7 % ; P = .025 ) .


The difference remained significant on the family level ( P = .03 ) .


These families were also less likely to use an inappropriate over-the-counter medication for their < 2-year-old child ( odds ratio , 0.29 ; 95 % confidence interval , 0.09-0 .95 ; 12.2 % vs 32.4 % , P = .034 ) and/or incorrect dosing tool for their < 4-year-old child ( odds ratio , 0.24 ; 95 % confidence interval , 0.08-0 .74 ; 9.8 % vs 31.1 % ; P < .01 ) .


The mean difference in Knowledge-Attitude scores for intervention families was higher .


A URI health literacy-related educational intervention embedded into EHS decreased PED visits and adverse care practices .


The promising results of Schroth scoliosis-specific exercises for adolescent idiopathic scoliosis found in low-quality studies will be strengthened by confirmation in a randomised controlled trial .


1 .


Are Schroth exercises combined with standard care for 6 months more effective than standard care alone in improving radiographic and clinical outcomes for adolescents with idiopathic scoliosis ?


2 .


Will the outcomes of the control group ( who will be offered Schroth therapy delayed by 6 months ) improve after 6 months of Schroth therapy ?


3 .


Are the effects maintained 6 months after discontinuing the supervised intervention ?


This is an assessor-blinded and statistician-blinded randomised controlled trial with transfer of the controls to the exercise group after 6 months .


Two hundred and fifty-eight consecutive adolescents with idiopathic scoliosis , aged 10 to 16 years , treated with or without a brace , with curves between 10 and 45 deg Cobb and Risser sign 3 will be recruited from three scoliosis clinics .


Combined with standard care , the Schroth group will receive five individual training sessions , followed by weekly group classes and daily home exercises for 6 months .


Controls will only receive standard care consisting of observation or bracing , and will be offered Schroth therapy 6 months later .


Curve severity ( Cobb angle ) and vertebral rotation will be assessed from radiographs at baseline , 6 and 12 months .


Secondary clinical outcomes ( back muscle endurance , surface topography measures of posture , and self-reported perceived spinal appearance and quality of life ) will be assessed at baseline , and every 3 months until 1-year follow-up .


Data will be analysed using intention-to-treat linear mixed models .


The results will demonstrate whether Schroth exercises combined with standard of care can improve outcomes in adolescents with idiopathic scoliosis .


This study has potential to influence clinical practice worldwide , where exercises are not routinely prescribed for adolescents with idiopathic scoliosis .


Endogenous insulin secretion , measured by C-peptide area under the curve ( AUC ) , can be tested using both the glucagon stimulation test ( GST ) and the mixed-meal tolerance test ( MMTT ) .


This study compares these two stimulation methods using long-term data from patients newly diagnosed with type 1 diabetes or with latent autoimmune diabetes .


A recently completed phase 3 intervention study with DiaPep277 demonstrated improved glycemic control and a significant treatment effect of glucagon-stimulated C-peptide secretion .


Unexpectedly , MMTT failed to detect differences between the treated and control groups .


Data from 343 patients in two balanced-randomized , double-blind , placebo-controlled , parallel-group trials of DiaPep277 were used to compare and correlate between GST - and MMTT-derived C-peptide AUC .


Pearson 's correlations were calculated for absolute C-peptide AUC at baseline and 12 and 24 months and for long-term changes in AUC ( AUC ) .


The absolute AUC values obtained at any single time point by the two tests were well correlated in both data sets ( r = 0.74-0 .9 ) .


However , the correlations between the AUC were much weaker ( r = 0.39-0 .58 ) .


GST-stimulated C-peptide secretion was stable over the fasting glucose range permitted for the test ( 4-11 .1 mmol/L ) , but MMTT-stimulated C-peptide secretion decreased over the same range , implying differences in sensitivity to glucose .


Measurement of long-term changes in stimulated C-peptide , reflecting endogenous insulin secretion , during the course of intervention trials may be affected by the method of stimulation , possibly reflecting different sensitivities to the physiological status of the tested subject .


The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over .


An analysis by the pre-specified subgroups [ age , sex , history of cardiovascular disease ( CVD ) and initial SBP ] was performed .


The Hypertension in the Very Elderly Trial was a randomized , double-blind , placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe , China , Australasia and Tunisia .


Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg .


For total mortality , benefits were consistent : men [ hazard ratio 0.82 , 95 % confidence interval ( CI ) 0.62-1 .11 ] , women ( hazard ratio 0.77 , 95 % CI 0.66-0 .99 ) , those aged 80-84 .9 ( hazard ratio 0.76 , 95 % CI 0.60-0 .96 ) , those aged 85 and over ( hazard ratio 0.87 , 95 % CI 0.64-1 .20 ) , those with a history of CVD ( hazard ratio 0.76 , 95 % CI 0.48-1 .20 ) and those without ( hazard ratio 0.81 , 95 % CI 0.65-0 .99 ) , and similarly across a range of baseline SBPs .


The point estimates for cardiovascular mortality , strokes , heart failure and cardiovascular events were all in favour of benefit .


In the per-protocol analysis , strokes were reduced by 34 % ( P = 0.026 ) , total mortality by 28 % ( P = 0.001 ) , cardiovascular event by 37 % ( P < 0.001 ) and heart failure by 72 % ( P < 0.001 ) .


In hypertensive patients aged 80 or more , treatment based on indapamide ( sustained-release ) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD ( the majority ) , supporting the need for treatment even at this advanced age .


There were too few aged 90 or over to determine benefit from treatment at extreme age .


Several studies suggest that most school-age children are poorly informed about cancer risk factors .


This study examines the effectiveness of the ` Be smart against cancer ' ( BSAC ) program in promoting cancer awareness and intentions to engage in health-promoting behavior .


235 seventh-grade students were randomized to either the intervention ( N = 152 ) or the wait-control group ( N = 83 ) .


The intervention included the modules : `` What is cancer ?


, '' `` Sun protection , '' `` Non smoking , '' and `` Physical activity , Healthy nutrition , and Limited alcohol consumption . ''


Outcomes measured at baseline and at the end of the one week BSAC program included knowledge of cancer and its behavioral risk factors , health-promoting intentions , and reported risk behavior .


BSAC was effective in increasing knowledge about cancer and risk factors for cancer ( p < .001 ) , as well as in increasing intentions to engage in health-promoting behavior ( p < .001 ) , independent of a student 's risk profile .


Knowledge did not serve as a mediator for intention building .


The BSAC is an effective school-based program for raising awareness of cancer , associated risk factors and intentions to engage in cancer-preventive behavior .


The results indicate that the effectiveness of BSAC is independent of a student 's risk profile .


Therefore , it holds considerable promise as a broadly applicable program to raise cancer awareness and promote healthy behavior intentions .


Tuberous sclerosis complex ( TSC ) is characterized by benign tumours in multiple organs , including the brain , kidneys , skin , lungs and heart .


Our objective was to evaluate everolimus , an mTOR inhibitor , in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma ( SEGA ) associated with TSC .


EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 ( NCT00789828 ) , a prospective , double-blind , randomized , placebo-controlled , Phase 3 study , examined everolimus in treating SEGA associated with TSC .


Patients with serial SEGA growth from pre-baseline to baseline scans were randomly assigned ( 2:1 ) to receive 4.5 mg/m ( 2 ) / day everolimus ( target blood trough : 5-15 ng/mL ; n = 78 ) or placebo ( n = 39 ) .


Angiomyolipoma response rates were analysed in patients ( n = 44 ) with target baseline angiomyolipoma lesions ( 1 angiomyolipoma ; longest diameter 1.0 cm ) .


An angiomyolipoma response rate , defined as the proportion of patients with confirmed angiomyolipoma response , was assessed by kidney CT or MRI screening at baseline , at 12 , 24 and 48 weeks and annually .


Angiomyolipoma response rates were 53.3 % ( 16/30 ) and 0 % ( 0/14 ) for everolimus - and placebo-treated patients , respectively .


Angiomyolipoma reductions 50 % in the sum of volumes of all target lesions were seen only in everolimus-treated patients ( 56.5 , 78.3 and 80.0 % ) compared with placebo-treated patients ( 0 % at each time point ) at Weeks 12 , 24 and 48 , respectively .


Greater percentages of everolimus-treated patients had angiomyolipoma reductions 30 % at these same time points ( 82.6 , 100 and 100 % versus 8.3 , 18.2 and 16.7 % for everolimus versus placebo , respectively ) .


Everolimus showed efficacy in reducing angiomyolipoma lesion volume in patients with SEGA associated with TSC.The trial is registered with ClinicalTrials.gov , number NCT00789828 ; http://clinicaltrials.gov/ct2/show/NCT00789828?term=EXIST-1&rank=1 .


To evaluate the relationship between spectral-domain optical coherence tomography ( OCT ) and standard automated perimetry ( SAP ) in healthy and glaucoma individuals .


The sample comprised 338 individuals divided into 2 groups according to intraocular pressure and visual field outcomes .


All participants underwent a reliable SAP and imaging of the optic nerve head with the Cirrus OCT. .


Pearson correlations were calculated between threshold sensitivity values of SAP ( converted to linear scale ) and OCT parameters .


Mean age did not differ between the control and glaucoma groups ( 59.55 9.7 years and 61.05 9.4 years , resp. ; P = 0.15 ) .


Significant differences were found for the threshold sensitivities at each of the 52 points evaluated with SAP ( P < 0.001 ) and the peripapillary retinal nerve fiber layer ( RNFL ) thicknesses , except at 3 and 9 clock-hour positions between both groups .


Mild to moderate correlations ( ranging between 0.286 and 0.593 ; P < 0.001 ) were observed between SAP and most OCT parameters in the glaucoma group .


The strongest correlations were found between the inferior RNFL thickness and the superior hemifield points .


The healthy group showed lower and weaker correlations than the glaucoma group .


Peripapillary RNFL thickness measured with Cirrus OCT showed mild to moderate correlations with SAP in glaucoma patients .


Post-menopausal women are at higher risk of cardiovascular disease and bone demineralization .


Phytosterols ( PS ) may be used for hypercholesterolemia in some groups and - cryptoxanthin ( - Cx ) displays a unique anabolic effect on bone .


Our aim was to assess the changes in cardiovascular and bone turnover markers from the oral intake of - Cx and PS in post-menopausal women .


A randomized , double-blind , crossover study with - Cx ( 0.75 mg/day ) and PS ( 1.5 g/day ) , single and combined , was performed in 38 postmenopausal women .


Diet was supplemented with 1 250 mL milk-based fruit drink/day for 4 weeks with a wash-out period of 4-weeks in between .


Serum - Cx and PS were determined by UPLC and CG-FID respectively .


Outcome variables included markers of bone turnover and cardiovascular risk .


Biological effect was assessed by paired t test and generalized estimating equations analysis that included the previous treatment , the order of intervention and the interactions .


The intake of beverages containing - Cx and PS brought about a significant increase in serum levels of - Cx , - sitosterol and campesterol .


Intervention caused changes in almost all the markers while the order , previous treatment and the interaction did not reach statistical significance .


Only the intake of the beverage containing - Cx plus PS brought about significant decreases in total cholesterol , c-HDL , c-LDL and bone turnover markers .


- Cx improves the cholesterol-lowering effect of PS when supplied simultaneously and this combination may also be beneficial in reducing risk of osteoporosis .


ClinicalTrials.gov number NCT01074723 .


Nonadherence to treatment leads to suboptimal treatment outcomes and enormous costs to the economy .


This is especially important in Parkinson 's disease ( PD ) .


The progressive nature of the degenerative process , the complex treatment regimens and the high rates of comorbid conditions make treatment adherence in PD a challenge .


Clinicians have limited face-to-face consultation time with PD patients , making it difficult to comprehensively address non-adherence .


The rapid growth of digital technologies provides an opportunity to improve adherence and the quality of decision-making during consultation .


The aim of this randomised controlled trial ( RCT ) is to evaluate the impact of using a smartphone and web applications to promote patient self-management as a tool to increase treatment adherence and working with the data collected to enhance the quality of clinical consultation .


A 4-month multicentre RCT with 222 patients will be conducted to compare use of a smartphone - and internet-enabled Parkinson 's tracker smartphone app with treatment as usual for patients with PD and/or their carers .


The study investigators will compare the two groups immediately after intervention .


Seven centres across England ( 6 ) and Scotland ( 1 ) will be involved .


The primary objective of this trial is to assess whether patients with PD who use the app show improved medication adherence compared to those receiving treatment as usual alone .


The secondary objectives are to investigate whether patients who receive the app and those who receive treatment as usual differ in terms of quality of life , quality of clinical consultation , overall disease state and activities of daily living .


We also aim to investigate the experience of those receiving the intervention by conducting qualitative interviews with a sample of participants and clinicians , which will be administered by independent researchers .


ISRCTN45824264 ( registered 5 November 2013 ) .


The role of adjuvant bisphosphonates in early breast cancer is uncertain .


We therefore did a large randomised trial to investigate the effect of the adjuvant use of zoledronic acid on disease-free survival ( DFS ) in high-risk patients with early breast cancer .


In the AZURE trial , an open-label , international , multicentre , randomised , controlled , parallel-group phase 3 trial , women ( age 18 years ) with stage II or III breast cancer were randomly assigned ( 1:1 ) by a central automated 24-h computer-generated telephone minimisation system ( balanced for number of involved axillary lymph nodes , tumour stage , oestrogen receptor status , type and timing of systemic therapy , menopausal status , statin use , and treatment centre ) to receive standard adjuvant systemic treatment alone ( control group ) or with 4 mg intravenous zoledronic acid every 3-4 weeks for six doses , then every 3 months for eight doses , followed by every 6 months for five doses , for a total of 5 years of treatment .


The primary endpoint was disease-free survival ( DFS ) .


Secondary endpoints were invasive DFS ( IDFS ) , overall survival , time to bone metastases , time to distant recurrence , and subgroup analyses of variables included in the randomisation .


All patients have completed study treatment .


Results from the intention-to-treat final analysis of this fully recruited study are presented after a median follow-up of 84 months ( IQR 66-93 ) .


This final efficacy analysis was planned to take place after 940 DFS events .


This trial is registered with ClinicalTrials.gov , NCT00072020 .


3360 women were recruited from 174 centres in seven countries between Sept 4 , 2003 , and Feb 16 , 2006 .


The number of DFS events did not differ between groups : 493 in the control group and 473 in the zoledronic acid group ( adjusted hazard ratio [ HR ] 094 , 95 % CI 082-106 ; p = 030 ) .


IDFS ( HR 093 , 95 % CI 082-105 ; p = 022 ) , overall survival ( 093 , 081-108 ; p = 037 ) , and distant recurrences ( 093 , 081-107 ; p = 029 ) were much the same in both groups .


Zoledronic acid reduced the development of bone metastases , both as a first event ( HR 078 , 95 % CI 063-096 ; p = 0020 ) and at any time during follow-up ( 081 , 068-097 ; p = 0022 ) .


The effects of zoledronic acid on DFS were not affected by oestrogen-receptor status .


However , zoledronic acid improved IDFS in those who were over 5 years since menopause at trial entry ( n = 1041 ; HR 077 , 95 % CI 063-096 ) but not in all other ( premenopause , perimenopause , and unknown status ) menopausal groups ( n = 2318 ; HR 103 , 95 % CI 089-120 ) .


33 cases of suspected osteonecrosis of the jaw have been reported , with 26 confirmed on central review , all in the zoledronic acid group ( 17 % , 95 % CI 10-24 ) .


These results suggest no overall benefit from the addition of zoledronic acid to standard adjuvant treatments for early breast cancer .


However , zoledronic acid does reduce the development of bone metastases and , for women with established menopause , improved disease outcomes .


Novartis Global and NIHR Cancer Research Network .


This study was designed to test the hypothesis of whether amlodipine reduces the risk for death in patients with heart failure due to a nonischemic cardiomyopathy .


A pre-specified subgroup analysis in an earlier , large-scale , placebo-controlled study suggested that amlodipine might reduce the risk for death in patients with heart failure due to a nonischemic cardiomyopathy .


To evaluate this hypothesis , 1654 patients with severe heart failure due to a nonischemic cardiomyopathy ( ejection fraction < 30 % ) were randomly assigned to amlodipine ( target dose : 10 mg/d ) or placebo added to conventional therapy for heart failure for a median of 33 months .


There were 278 deaths in the amlodipine group and 262 deaths in the placebo group ( hazard ratio : 1.09 ; 95 % confidence interval [ CI ] : 0.92 to 1.29 ; p = 0.33 ) .


The differences between the 2 groups in the risks for cardiovascular death and hospitalization were also not significant .


When the results from patients with a nonischemic cardiomyopathy in both the earlier trial and in the current study were combined , there was no evidence of a favorable or unfavorable effect of amlodipine on mortality ( hazard ratio : 0.97 ; 95 % CI : 0.83 to 1.13 ; p = 0.66 ) .


Both trials , however , observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of uncontrolled hypertension and chest pain in patients treated with amlodipine .


These results of the current trial , viewed together with the results from the earlier study , indicate that amlodipine does not exert favorable effects on the clinical course of patients with heart failure , regardless of the presence or absence of underlying coronary artery disease .


These findings indicate the need for great caution when striking benefits are observed in subgroups of patients or in trials not primarily designed to assess such effects .


The aim of our study was to investigate the relationship between nasal irrigation techniques ( NIT ) and the survival rate and the quality of life ( QOL ) in patients with nasal sinusitis ( NS ) .


We studied data from 1134 patients with nasopharyngeal carcinoma ( NPC ) who received radical radiotherapy , which were randomly divided into three groups ( A , B and C ) .


Group A used nasal irrigator ; Group B used homemade nasal irrigation ( NI ) connector combined with enemator ; and Group C used nasal sprayer .


The clinical effects , 5-year overall survival ( OS ) and progression-free survival ( PFS ) were observed .


Furthermore , the QOL in patients with NS was evaluated using the Sino-Nasal Outcome Test 20 .


The median follow-up time was 69 months .


The 5-year OS and PFS were 80.5 % and 73.2 % , respectively , for all patients .


There was no significant difference in OS , PFS , xerostomia and neck skin toxicity grade 3 and greater among groups .


There was no difference among groups .


The incidence of NS was the highest in group C.


The symptoms of NS seriously affected the QOL period of 1 year .


Group C showed no improvement during the follow-up period , which for A and B , by contrast , had after 1 year .


Although the exact mechanism remains to be explored in NIT , our findings suggest that patients with NPC should nasal irrigate for 2 years after radiotherapy .


Our study shows that a nasal irrigator is necessary for patients with NPC for a high QOL in terms of NS .


To evaluate the safety and efficacy of high-intensity focused ultrasound ( HIFU ) cyclocoagulation in reducing intraocular pressure ( IOP ) in patients with refractory glaucoma by using a novel miniaturized delivery device ( EyeOP1 ) .


We conducted a 12-month open-label multicenter prospective study ( EyeMUST1 Study ) .


Patients with primary ( primary open-angle glaucoma [ POAG ] ) or secondary refractory glaucoma were treated in two groups depending on the duration of each ultrasound shot ( group 1 : 4 seconds ; group 2 : 6 seconds ) .


The primary efficacy outcome was based on IOP reduction at 6 and 12 months .


Fifty-two patients were enrolled : 36 ( 69 % ) had POAG and 16 ( 31 % ) had secondary glaucoma .


Group 1 ( n = 24 ) and group 2 ( n = 28 ) had similar demographics and baseline characteristics .


In group 1 , IOP was reduced from a mean preoperative value of 29.7 7.7 mm Hg ( n = 3.5 glaucoma medications ) to a mean postoperative value of 21.3 6.7 mm Hg ( n = 3.5 glaucoma medications ) and 20.1 6.7 mm Hg ( n = 3.2 glaucoma medications ) at 6 and 12 months , respectively .


In group 2 , IOP was reduced from a mean preoperative value of 29.0 7.4 mm Hg ( n = 3.3 glaucoma medications ) to a mean postoperative value of 20.2 7.4 mm Hg ( n = 3.4 glaucoma medications ) and 18.5 6.6 mm Hg ( n = 3.5 glaucoma medications ) at 6 and 12 months , respectively .


At 12 months , the IOP reduction was sustained in both groups ( 32 % IOP reduction in group 1 and 36 % IOP reduction in group 2 ) .


The overall tolerance of the technique was good , with no serious adverse events .


The new miniaturized HIFU EyeOP1 delivery device seems to be effective in decreasing IOP in patients with refractory glaucoma .


The technology offers a good safety profile .


( ClinicalTrials.gov number , NCT01338467 . )


To compare the efficacy and safety of new insulin glargine 300 units/mL ( Gla-300 ) with glargine 100 units/mL ( Gla-100 ) in people with type 2 diabetes on basal insulin ( 42 units/day ) plus mealtime insulin .


EDITION 1 ( NCT01499082 ) was a 6-month , multinational , open-label , parallel-group study .


Adults with glycated hemoglobin A1c ( HbA1c ) 7.0-10 .0 % ( 53-86 mmol/mol ) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5 .6 mmol/L .


Primary end point was HbA1c change from baseline ; main secondary end point was percentage of participants with one or more confirmed ( 3.9 mmol/L ) or severe nocturnal hypoglycemia from week 9 to month 6 .


Participants ( n = 807 ) had mean age 60 years , diabetes duration 16 years , BMI 36.6 kg/m ( 2 ) , and HbA1c 8.15 % ( 65.6 mmol/mol ) .


HbA1c reduction was equivalent between regimens ; least squares mean difference -0.00 % ( 95 % CI -0.11 to 0.11 ) ( -0.00 mmol/mol [ -1.2 to 1.2 ] ) .


Fewer participants reported one or more confirmed ( 3.9 mmol/L ) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 ( 36 vs. 46 % with Gla-100 ; relative risk 0.79 [ 95 % CI 0.67-0 .93 ] ; P < 0.005 ) ; nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment .


No between-treatment differences in tolerability or safety were identified .


Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia .


To evaluate pazopanib 10 mg/mL eye drops ( pazopanib ) in healthy subjects and in subjects with previously untreated subfoveal choroidal neovascularization secondary to age-related macular degeneration .


Study 1 ( single center , randomized , placebo-controlled , double-masked ) included 3 cohorts of 12 to 13 healthy subjects each who instilled pazopanib or placebo 4 times daily for 2 weeks .


Study 2 ( multicenter open-label ) included 19 subjects with neovascular age-related macular degeneration who instilled pazopanib 4 times daily for 12 weeks .


Both studies evaluated pharmacokinetics and safety .


Study 2 also evaluated efficacy .


Steady-state concentrations of pazopanib in plasma seemed to be reached by Week 2 .


At Week 4 ( Study 2 ) , there were no meaningful changes from baseline in the mean central retinal thickness ( 37.9 m ) or best-corrected visual acuity ( 0.1 letters ) ( primary endpoint ) , retinal morphology , choroidal neovascularization size , or total lesion size .


Complement Factor H genotype had no effect on changes from baseline in the best-corrected visual acuity or central retinal thickness .


The most common pazopanib-related ocular adverse events included eye irritation ( Study 1 , n = 7 ) and instillation site pain ( Study 2 , n = 3 ) .


No serious adverse events were reported .


Pazopanib was well tolerated .


In subjects with previously untreated neovascular age-related macular degeneration , pazopanib instilled 4 times daily as monothereapy did not seem to improve the best-corrected visual acuity or decrease the central retinal thickness .


Characterized as a sudden and temporary loss of consciousness and postural tone , with quick and spontaneous recovery , syncope is caused by an acute reduction of systemic arterial pressure and , therefore , of cerebral blood flow .


Unsatisfactory results with the use of drugs allowed the nonpharmacological treatment of neurocardiogenic syncope was contemplated as the first therapeutic option .


To compare , in patients with neurocardiogenic syncope , the impact of a moderate intensity aerobic physical training ( AFT ) and a control intervention on the positivity of head-up tilting test ( HUT ) and orthostatic tolerance time .


Were studied 21 patients with a history of recurrent neurocardiogenic syncope and HUT .


The patients were randomized into : trained group ( TG ) , n = 11 , and control group ( CG ) , n = 10 .


The TG was submitted to 12 weeks of AFT supervised , in cycle ergometer , and the CG to a control procedure that consisted in 15 minutes of stretching and 15 minutes of light walk .


The TG had a positive effect to physical training , with a significant increase in peak oxygen consumption .


The CG did not show any statistically significant change before and after the intervention .


After the intervention period , 72.7 % of the TG sample had negative results to the HUT , not having syncope in the revaluation .


The program of supervised aerobic physical training for 12 weeks was able to reduce the number of positive HUT , as it was able to increase tolerance time in orthostatic position during the HUT after the intervention period .


Lumboperitoneal shunt surgery has the potential to alleviate symptoms of normal pressure hydrocephalus but the benefits of such surgery have not been tested in a randomised trial .


The aim of this trial was to determine the safety and efficacy of the lumboperitoneal shunt surgery for this disorder .


For the open-label randomised SINPHONI-2 trial , eligible participants ( 60-85 years of age ) with idiopathic normal pressure hydrocephalus , with ventriculomegaly , and tightness of the high-convexity and medial subarachnoid spaces on MRI , were recruited from 20 neurological and neurosurgical centres in Japan .


Enrolled participants were randomly assigned in a 1:1 ratio according to a random code generated by the trial statistician , with a permuted block design ( using a block size of 4 or 6 ) within each centre , to receive lumboperitoneal shunt surgery within 1 month after randomisation , or to surgery postponed for 3 months .


Patients and assessors were not masked to treatment assignment .


The primary endpoint was favourable outcome , defined as an improvement of one point or more on the modified Rankin scale ( mRS ) at 3 months after randomisation , analysed by intention to treat , and the main secondary endpoint was the same outcome 12 months after surgery , analysed per protocol .


This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry ( UMIN-CTR ) , number UMIN000002730 .


Between March 1 , 2010 , and Oct 19 , 2011 , 93 patients with idiopathic normal pressure hydrocephalus were enrolled and randomly assigned to the immediate treatment group ( n = 49 ) or the postponed treatment group ( n = 44 ) .


More patients in the immediate treatment group than in the postponed treatment group had an improvement of one point or more on the mRS at 3 months : 32 ( 65 % ) of 49 in the immediate group vs 2 ( 5 % ) of 44 in the postponed group ( difference 61 % [ 95 % CI 42-68 ] ; p < 00001 ) .


The number of patients who had an improvement of one point or more on the mRS at 12 months after surgery was similar between the two groups : 30 ( 67 % ) of 45 patients in the immediate group vs 22 ( 58 % ) of 38 in the postponed group ( difference 9 % [ 95 % CI -14 to 31 ] ; p = 0496 ) .


The proportions of patients with serious adverse events did not differ significantly between the groups during the 3 months post-randomisation ( 7 [ 15 % ] of 46 in the immediate group vs 1 [ 2 % ] of 42 in the postponed group ; p = 0060 ) .


During the 12 months after surgery , 19 ( 22 % ) of 87 patients had serious adverse events , the most common of which was cerebral infarction ( six patients [ 7 % ] ) .


Our results suggest that lumboperitoneal shunt surgery might be beneficial for patients with idiopathic normal pressure hydrocephalus and , if these findings are confirmed in larger studies , could be a first-line treatment option for this disease .


Johnson & Johnson and Nihon Medi-Physics .


Breast magnetic resonance imaging ( MRI ) has shown high sensitivity in determining tumor extent , multifocality , and occult contralateral breast cancer .


Low specificity , unnecessary mastectomies , and costs are arguments against MRI .


The purpose of this study was to determine whether preoperative breast MRI would affect primary surgical management , reduce reexcision/reoperation procedures , and influence the choice of neoadjuvant treatment in patients with newly diagnosed breast cancer .


This prospective , randomized , multicenter study included 440 breast cancer patients younger than aged 56 years from three , Swedish , large-volume breast units .


Patients were randomly allocated on a 1:1 basis to either preoperative staging with breast MRI ( n = 220 ) or no breast MRI ( n = 220 ) ( control group ) .


Treatment planning of all patients was discussed at multidisciplinary team conferences .


In patients randomized to the MRI group , who had an observed higher percentage of planned breast-conserving surgery ( BCS ) compared with the control group , a change from suggested breast conservation to mastectomy occurred in 23 of 153 ( 15 % ) patients .


Breast MRI provided additional information in 83 of 220 ( 38 % ) patients , which caused a change in treatment plan in 40 ( 18 % ) .


The breast reoperation rate was significantly lower in the MRI group : 11 of 220 ( 5 % ) versus 33 of 220 ( 15 % ) in the control group ( p < 0.001 ) .


The number of mastectomies , axillary reoperations , and the number of patients receiving neoadjuvant chemotherapy after definitive treatment did not differ significantly between the groups .


Preoperative staging with breast MRI in women younger than age 56 years altered the treatment plan in 18 % of the patients .


Although a higher MRI-related conversion rate from breast conservation to mastectomy was found , the final numbers of mastectomies did not differ between the two groups .


The breast reoperation rate in the MRI group was significantly reduced .


Pain at the surgery site is a common complaint in patients who experience percutaneous nephrolithotomy ( PCNL ) .


The aim of this double-blind , randomized clinical trial is evaluation of the effect of scheduled infusion of bupivacaine on postsurgical pain and narcotic consumption after tubeless PCNL under spinal anesthesia .


Forty patients were randomly divided into two groups .


A small caliber fenestrated feeding tube was placed into the nephrostomy tract under direct vision in a manner in which its tip lied close to the renal capsule .


The study group received infusion of diluted bupivacaine while physiologic saline was injected in the control group .


Each patient was given the same dose every 6 hours until 24 hours after the surgical procedure .


Mean pethidine injection was significantly lower in the group who underwent bupivacaine instillation ( 20.514.5 vs 3.972.4 mg : P = 0.009 ) .


There was no significant difference between mean visual analogue scale ( VAS ) score in these two groups after 6 and 12 hours while it was significantly lower after 18 and 24 hours in the patients who had received bupivacaine .


Mean time to the first analgesic request was significantly longer in the study group ( 11.35 vs 6.44 hours : P = 0.001 ) .


Intermittent perirenal instillation of bupivacaine via the nephrostomy tract after PCNL decreases the need for more systemic narcotics and provides acceptable analgesia in the postoperative period .


Inflammation plays a major role in diabetes-associated cardiovascular disease ( CVD ) .


There is uncertainty whether diet and physical activity interventions can be successfully integrated into healthcare settings and reduce markers of inflammation and risk of CVD in patients with type 2 diabetes ( T2D ) .


Systemic markers of inflammation were determined in a 12-month , real-world , multicenter , randomized , controlled trial that investigated the effect of diet , diet plus physical activity , and usual care in 593 individuals with newly diagnosed T2D .


During the first 6 months , serum C-reactive protein ( CRP ) improved by -21 ( -36 to -1.4 ) % and -22 ( -38 to -3.1 ) % in diet and diet plus physical activity arms versus usual care .


There were also improvements in adiponectin and soluble intercellular adhesion molecule-1 ( sICAM-1 ) .


Though medication-adjusted CRP was improved between 6 and 12 months for usual care , both interventions were more successful in reducing the relative risk of a high-risk CRP level of > 3 mg/L ( risk ratios of 0.72 [ 0.55 to 0.95 ] for diet versus usual care and 0.67 [ 0.50 to 0.90 ] for diet plus activity versus usual care ) .


Furthermore , sICAM-1 ( a marker of vascular risk ) , remained substantially lower than usual care in both intervention arms at 12 months .


Motivational , unsupervised diet and/or diet plus physical activity interventions given soon after diagnosis in real-world healthcare settings improve markers of inflammation and cardiovascular risk in patients with T2D , even after accounting for the effect of adjustments to medication to try and control blood pressure , glycated hemoglobin , and lipids .


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


Unique identifier : ISRCTN92162869 .


This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder ( MDD ) outpatients with and without melancholic features .


Reflecting the emphasis in DSM-5 , we also include impairment and distress .


Participants were assessed pre-treatment on clinical features ( severity , risk factors , comorbid conditions , illness course ) , psychological profile ( personality , emotion regulation ) , functional capacity ( social and occupational function , quality of life ) and distress/coping ( negativity bias , emotional resilience , social skills , satisfaction with life ) .


Participants were randomized to sertraline , escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission , response , and change in impairment and distress .


Patients with melancholic features ( n = 339 ; 33.7 % ) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood .


Psychologically , melancholic patients were defined by introversion , and a greater use of suppression to regulate negative emotion .


Melancholics also had poorer capacity for social and occupational function , and physical and psychological quality of life , along with poorer coping , reflected in less emotional resilience and capacity for social skills .


Post-treatment , melancholic patients had lower remission and response , but some of this effect was due to the more severe symptoms pre-treatment .


The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants .


Due to the cross-sectional nature of this study , causal pathways can not be concluded .


Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with ones emotions .


This distinctly poorer capacity for social skills remained post-treatment .


The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment .


The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations , such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate ( HC-ac ) ophthalmic ointments of 2.5 % and 1 % are more effective than a 0.5 % eye ointment .


In this randomized , double-blind , placebo-controlled , parallel-group clinical study , the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects .


Median time to clinically relevant response as estimated by 50 % reduction in clinical signs and symptoms ( CSS ) total score over the entire trial was similar for subjects treated with HC-ac 2.5 % ( 73.5 h ) and for subjects treated with HC-ac 1.0 % ( 67.7 h ) and was considerably and significantly longer for subjects treated with HC-ac 0.5 % ( 111.8 h ) [ p < 0.001 for both dosages ] .


All trial medications were safe and well tolerated .


Hydrocortisone acetate 2.5 % and Hydrocortisone acetate 1 % eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa , and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5 % therapy .


Current Controlled Trials ISRCTN15464650 .


Patients with multiple sclerosis ( MS ) lose brain volume ( BV ) faster than healthy individuals .


Our purpose , within the 12-month phase 3 TRANSFORMS study , was to examine the effect of treatment on BV loss in patient subgroups , establish correlations between baseline normalized BV ( NBV ) and baseline disease parameters , to identify variables predictive of baseline NBV and on-study percentage BV change ( PBVC ) , and to establish correlations between on-study PBVC and on-study efficacy outcomes .


Patients received fingolimod 0.5 mg or 1.25 mg , or intramuscular ( IM ) interferon -1 a ( IFN-1a ) for 12 months .


The effect of treatment on PBVC was examined in patient demographic , disease and magnetic resonance imaging ( MRI ) characteristic subgroups .


Pearson 's correlation analyses and a stepwise linear regression model were used to identify variables predictive of NBV and PBVC .


Fingolimod reduced BV loss over 12 months versus IFN-1a IM in all patient subgroups assessed , including individuals with or without gadolinium ( Gd ) - enhancing lesions at baseline .


Baseline T1 hypointense lesion volume had the strongest correlation with baseline NBV .


Baseline Gd-enhancing T1 lesion count was most predictive of change in PBVC over 12 months .


Our results improve understanding of the contributions of different baseline demographic , clinical and MRI characteristics to NBV , including factors that may be predictive of future BV loss .


In a Spanish Lung Cancer Group ( SLCG ) phase II trial , the combination of BRCA1 and receptor-associated protein 80 ( RAP80 ) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer ( NSCLC ) .


The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression .


An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients .


Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis .


Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial .


In both trials , patients in the control arm received docetaxel/cisplatin ; in the experimental arm , patients with low RAP80 expression received gemcitabine/cisplatin , those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin , and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone .


The primary end point was progression-free survival ( PFS ) .


Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS .


PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months , respectively [ log rank P = 0.07 ; hazard ratio ( HR ) 1.28 ; P = 0.03 ] .


In the Chinese trial , PFS was 4.74 and 3.78 months , respectively ( log rank P = 0.82 ; HR 0.95 ; P = 0.82 ) .


Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm .


However , the BREC studies provide proof of concept that an international , nonindustry , biomarker-directed trial is feasible .


Thanks to the groundwork laid by these studies , we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches .


NCT00617656/GECP-BREC and ChiCTR-TRC-12001860 / BREC-CHINA .


To determine pharmacokinetics of marbofloxacin in water buffalo calves ( Bubalus bubalis ) after multiple SC administrations and to assess differences in regimen efficacy .


18 healthy buffalo calves .


Calves ( n = 6 calves/group ) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages ( 2 mg/kg , q 24 h for 6 days [ regimen 1 ] ; 4 mg/kg , q 48 h for 6 days [ regimen 2 ] ; and 4 mg/kg , q 24 h for 3 days [ regimen 3 ] ) .


Serum marbofloxacin concentrations were analyzed .


Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica .


Mean SD area under the concentration-time curve was 5.92 0.40 gh/mL for regimen 1 , which differed significantly from that for regimens 2 ( 14.26 0.92 gh/mL ) and 3 ( 14.17 0.51 gh/mL ) .


Mean residence time and mean elimination half-life for regimen 2 ( 9.93 0.20 hours and 8.77 0.71 hours ) both differed significantly from those for regimens 1 ( 721 0.11 hours and 5.71 0.38 hours ) and 3 ( 759 0.13 hours and 737 1.19 hours ) .


Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility ( low , medium , and high ) of the strains .


Regimen 3 had the most favorable indices , and it would be conducive for owner compliance and require less handling of animals .


Cixutumumab , formerly IMC-A12 , is a recombinant human monoclonal immunoglobulin G1 antibody that targets insulin-like growth factor I receptor ( IGF-IR ) .


Cixutumumab was synergistic with castration in a hormone-sensitive prostate cancer xenograft model .


Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation ( AD ) to cixutumumab added to a luteinizing hormone-releasing hormone agonist with bicalutamide versus AD alone .


With 180 patients and one-sided alpha of 0.10 , there would be 90 % power to detect an absolute 20 % difference in undetectable prostate-specific antigen ( PSA ; 0.2 ng/mL ) rate at 28 weeks ( relative risk , 1.44 ) ; this end point was previously strongly correlated with survival .


Secondary end points included the proportion of patients with PSA > 4.0 ng/mL , safety and tolerability , circulating tumor cell ( CTC ) levels , and seven plasma IGF-IR biomarkers .


Fisher 's exact test was used for the primary end point , and extended Mantel-Haenszel ( 2 ) test was used for three PSA response categories .


The trial accrued 210 eligible patients ( 105 randomly assigned to each arm ) .


Patient characteristics were similar in both arms .


Undetectable PSA rate was 42 ( 40.0 % ) of 105 for cixutumumab plus AD and 34 ( 32.3 % ) of 105 for AD alone ( relative risk , 1.24 ; one-sided P = .16 ) .


Lower baseline CTCs ( 0 v 1 to 4 v 5/7 .5 mL whole blood ) were associated with higher rate of PSA response ( three categories ; P = .036 ) in 39 evaluable patients .


IGF-IR biomarkers were not correlated with PSA outcome , and cixutumumab did not significantly change these biomarker levels .


Cixutumumab plus AD did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer .


CTCs at baseline may carry prognostic value .


The risk for malignant melanoma is higher than expected in Parkinson 's disease ( PD ) .


The National Institutes of Health ( NIH ) Exploratory Trials in PD ( NET-PD ) Long-term Study 1 ( LS-1 ) trial is a contemporary phase 3 study of subjects with early , treated PD .


The objective of this work was to assess the incidence of malignant melanoma in a PD cohort .


Incident melanoma cases were identified from the adverse events log .


The expected number of cases was calculated , using the expected incidence rates and the number of person-years .


A total of 618 females and 1119 males were followed for 6452 person-years ; 19 new melanoma cases were observed .


The expected number was 5.29 .


The standardized event ratio compared to the general population was 3.6 ( 95 % confidence interval , 2.2-5 .6 ) .


The risk for developing melanoma was higher than expected in the NET-PD LS-1 cohort and was similar to the risk reported in earlier comparable clinical trial cohorts .


Dermatologic screening may be useful in Parkinson 's disease to identify melanoma at an early stage .


Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention .


Traditionally , primary open necrosectomy has been the treatment of choice .


In recent years , the surgical step-up approach , consisting of percutaneous catheter drainage followed , if necessary , by ( minimally invasive ) surgical necrosectomy has become the standard of care .


A promising minimally invasive alternative is the endoscopic transluminal step-up approach .


This approach consists of endoscopic transluminal drainage followed , if necessary , by endoscopic transluminal necrosectomy .


We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes .


The TENSION trial is a randomised controlled , parallel-group superiority multicenter trial .


Patients with ( suspected ) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible , will be randomised to either an endoscopic transluminal or a surgical step-up approach .


During a 4year study period , 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group .


The primary endpoint is a composite of death and major complications within 6months following randomisation .


Secondary endpoints include complications such as pancreaticocutaneous fistula , exocrine or endocrine pancreatic insufficiency , need for additional radiological , endoscopic or surgical intervention , the need for necrosectomy after drainage , the number of ( re - ) interventions , quality of life , and total direct and indirect costs .


The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications , as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis .


In this double-blind , randomized study , the authors compared the effects of a patient-controlled remifentanil and morphine combination with morphine alone on post-thoracotomy pain , analgesic consumption , and side effects .


A prospective , randomized , double-blind clinical study .


University hospital .


Volunteer patients at a university hospital undergoing elective thoracotomy surgery .


Patients were allocated randomly into 2 groups to receive patient-controlled analgesia : the morphine ( M ) group or the morphine plus remifentanil ( MR ) group .


Pain , discomfort , sedation scores , cumulative patient-controlled morphine consumption , rescue analgesic ( meperidine ) requirement and side effects were recorded for 24 hours .


Sixty patients were allocated randomly to receive intravenous patient-controlled analgesia with morphine alone ( M ) or morphine plus remifentanil ( MR ) in a double-blind manner .


Patients were allowed to use bolus doses of morphine ( 0.02 mg/kg ) or the same dose of a morphine plus remifentanil ( 0.2 g/kg ) mixture every 10 minutes without a background infusion .


VAS scores were lower in the MR group than in the M group at 30 minutes ( p = 0.04 ) , 1 hour ( p = 0.03 ) , and 2 hours ( p = 0.04 ) .


Mean cumulative doses of morphine were not significantly different at 27.815 mg for the M group and 21.910.5 mg for the MR group .


Significantly more patients needed meperidine in the M group ( p = 0.039 ) ; these also experienced more nausea ( p = 0.01 ) .


Coadministration of PCA remifentanil with morphine for the treatment of post-thoracotomy pain did not reduce morphine consumption but provided superior analgesia , less use of rescue analgesics , and fewer side effects compared to morphine alone .


To evaluate the effect of different maintenance recall intervals in patients with chronic periodontitis treated by full-mouth ultrasonic debridement .


Twenty-eight patients participated in the study and were divided into two groups : group 1 ( n = 14 ) underwent full-mouth ultrasonic debridement followed by monthly supportive periodontal therapy ; group 2 ( n = 14 ) underwent full-mouth ultrasonic debridement followed by supportive periodontal therapy delivered at 3-month intervals .


Plaque index ( PI ) , bleeding on probing ( BOP ) , pocket probing depth ( PD ) , gingival recession ( GR ) and clinical attachment level ( CAL ) were evaluated at baseline and after 3 and 6 months .


Subjects in group 1 had statistically significantly lower PI scores than did subjects in group 2 at six months .


However , no differences in BOP , PPD , GR and CAL were observed between groups at any of the time points evaluated .


Nonetheless , while full-mouth BOP and PPD scores progressively decreased over time in group 1 , the same parameters were significantly reduced at 3 months in group 2 , but remained stable thereafter .


The proportion of moderate and deep pockets decreased progressively over time in the group of monthly recalls , while the proportion of moderate to deep sites decreased significantly in group 2 only at 3 months ; no additional reductions were seen at 6 months .


Supportive periodontal therapy both at one - and three-month intervals promotes short-term stability of clinical improvements obtained after full-mouth ultrasonic debridement in patients with chronic periodontitis .


It is well documented that heightened levels of parenting stress have a negative influence on children 's socio-emotional and behavioral development .


Parenting stress may therefore be regarded as an outcome variable in its own right .


This study investigated whether a sensitizing intervention influences stress reported by parents of prematurely born children until the children were age nine .


Preterm infants ( N = 146 , birth weight < 2,000 g ) were randomized to intervention ( N = 72 ) with the Mother-Infant Transaction Program ( MITP ) or a preterm control group ( N = 74 ) that received standard hospital care .


A term reference group comprised 75 healthy , full-term neonates .


Parents reported on the Parenting Stress Index ( PSI ) when the children were 6 months , 1 , 2 , 3 , 5 , 7 years old and on the PSI-Short Form ( PSI-SF ) at age 9 .


Main outcomes were the mother 's and father 's reports of total , child and parent-related stress .


Cross-sectional and longitudinal analyses were performed using linear mixed models ( LMM ) , taking dependency in the data caused by twin pairs and repeated measures into account .


Response rates were high across all follow-ups , and still reached 85 % from mothers and 72 % from fathers at 9 years .


Mothers in the intervention group reported better longitudinal development of child-related stress than mothers of preterm controls , as they perceived their children as being more adaptable and less moody throughout childhood until the age of seven .


Less stress in the intervention group was revealed by cross-sectional analysis of maternal reports at all ages , while fathers reported similar differences at ages three and five .


Parents in the intervention group reported stronger agreement on several stress scores on several occasions .


Fathers with high interventional participation ( mean 54 % ) reported significantly less stress at age nine than those who participated less .


Both parents in the intervention group reported levels of stress similar to those experienced by the term reference group at all follow-ups , while differences between the preterm control and term reference groups increased .


This early intervention reduces stress among parents of prematurely born children to a level reported by parents of term-born children and enhances agreement between parents .


Clinical Trials Gov identifier NCT00222456 , 05.09.2005 .


Present combination antiretroviral therapy ( cART ) alone does not cure HIV infection and requires lifelong drug treatment .


The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration .


Our aim was to assess the efficacy , safety , and immunogenicity of Vacc-4x , a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24 ( Gag ) , in adults infected with HIV-1 .


Between July , 2008 , and June , 2010 , we did a multinational double-blind , randomised , phase 2 study comparing Vacc-4x with placebo .


Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART ( viral load < 50 copies per mL ) with CD4 cell counts of 400 10 ( 6 ) cells per L or greater .


The trial was done at 18 sites in Germany , Italy , Spain , the UK , and the USA .


Participants were randomly assigned ( 2:1 ) to Vacc-4x or placebo .


Group allocation was masked from participants and investigators .


Four primary immunisations , weekly for 4 weeks , containing Vacc-4x ( or placebo ) were given intradermally after administration of adjuvant .


Booster immunisations were given at weeks 16 and 18 .


At week 28 , cART was interrupted for up to 24 weeks .


The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption .


Analyses were by modified intention to treat : all participants who received one intervention .


Furthermore , safety , viral load , and immunogenicity ( as measured by ELISPOT and proliferation assays ) were assessed .


The 52 week follow-up period was completed in June , 2011 .


For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate .


This study is registered with ClinicalTrials.gov , number NCT00659789 .


174 individuals were screened ; because of slow recruitment , enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo .


There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28 .


Of the participants who resumed cART , 30 ( 34 % ) were in the Vacc-4x group and 11 ( 29 % ) in the placebo group , and percentage changes in CD4 counts were not significant ( mean treatment difference -571 , 95 % CI -1301 to 159 ) .


However , a significant difference in viral load was noted for the Vacc-4x group both at week 48 ( median 23,100 copies per mL Vacc-4x vs 71,800 copies per mL placebo ; p = 0025 ) and week 52 ( median 19,550 copies per mL vs 51,000 copies per mL ; p = 0041 ) .


One serious adverse event , exacerbation of multiple sclerosis , was reported as possibly related to study treatment .


Vacc-4x was immunogenic , inducing proliferative responses in both CD4 and CD8 T-cell populations .


The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination .


Vacc-4x was safe , well tolerated , immunogenic , seemed to contribute to a viral-load setpoint reduction after cART interruption , and might be worth consideration in future HIV-cure investigative strategies .


Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA .


The goal of this study was to analyze the differences in ultrasound characteristics of papillary thyroid carcinoma ( PTC ) originating in the thyroid isthmus versus that originating from the lobes .


From a retrospective review of our institution 's database of records dated between January 2007 and December 2008 , we identified 48 patients with classic PTCs located in the isthmus .


All the patients had undergone preoperative ultrasound imaging , total thyroidectomy with bilateral central lymph node dissection , and postoperative follow-up for at least 2 years .


As a control group , 96 patients with classic PTCs located in the lobe who had undergone total thyroidectomy with bilateral central lymph node dissection during the same period were randomly matched to the study patients for age , sex , and tumor size .


According to the clinicopathologic analyses , the incidence of extrathyroidal extension was higher in the patients with a tumor originating in the isthmus than in the control group ( p = 0.026 ) .


According to the imaging analyses , the tumors originating in the isthmus more frequently had a circumscribed margin ( p = 0.030 ) , a wider-than-tall shape ( p < 0.001 ) , and the suspicion of extrathyroidal extension ( p < 0.001 ) than those originating from the lobes .


The results of this study showed that PTCs originating in the isthmus were more likely to have extrathyroidal extension than those originating from the lobes .


Therefore , careful ultrasound evaluation should be performed on masses in the thyroid isthmus even if ultrasound shows a circumscribed mass with a wider-than-tall shape .


The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma .


We examined patterns of first relapse in the study .


From September 2002 to July 2010 , 1712 patients < 22 years old with stage I-IIA with bulk , I-IIAE , I-IIB , and IIIA-IVA with or without doxorubicin , bleomycin , vincristine , etoposide , prednisone , and cyclophosphamide were enrolled .


Patients were categorized as rapid ( RER ) or slow early responders ( SER ) after 2 cycles of doxorubicin , bleomycin , vincristine , etoposide , prednisone , and cyclophosphamide ( ABVE-PC ) .


The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiation therapy ( IFRT ) .


RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response ( CR ) was achieved .


RER without CR patients were non-randomly assigned to 21 Gy IFRT .


Relapses were characterized without respect to site ( initial , new , or both ; and initial bulk or initial nonbulk ) , and involved field radiation therapy field ( in-field , out-of-field , or both ) .


Patients were grouped by treatment assignment ( SER ; RER/no CR ; RER/CR/IFRT ; and RER/CR/no IFRT ) .


Summary statistics were reported .


At 4-year median follow-up , 244 patients had experienced relapse , 198 of whom were fully evaluable for review .


Those who progressed during treatment ( n = 30 ) or lacked relapse imaging ( n = 16 ) were excluded .


The median time to relapse was 12.8 months .


Of the 198 evaluable patients , 30 % were RER/no CR , 26 % were SER , 26 % were RER/CR/no IFRT , 16 % were RER/CR/IFRT , and 2 % remained uncategorized .


The 74 % and 75 % relapses involved initially bulky and nonbulky sites , respectively .


First relapses rarely occurred at exclusively new or out-of-field sites .


By contrast , relapses usually occurred at nodal sites of initial bulky and nonbulky disease .


Although response-based therapy has helped define treatment for selected RER patients , it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses .


To explore the impact of intracoronary bolus administration of tirofiban combined with nitroprusside through thrombus aspiration catheter or thrombus aspiration alone on myocardial reperfusion and major adverse cardiovascular events rate in acute anterior myocardial infarction patients with heavy thrombosis burden .


Ninety consecutive acute anterior myocardial infarction patients with heavy thrombosis burden [ ( 59.8 11.5 ) years old ] were randomly assigned to thrombus aspiration group ( Group A , n = 30 ) , thrombus aspiration and intracoronary tirofiban bolus ( 25 g/kg prior to the first balloon inflation , Group B , n = 30 ) , thrombus aspiration and intracoronary tirofiban combined with nitroprusside bolus ( 200 g prior to the first balloon inflation , Group C , n = 30 ) with random number table .


Baseline clinical data , angiographic features before and after percutaneous coronary intervention ( PCI ) and major adverse cardiovascular events after PCI between 3 groups were compared .


The baseline clinical data and angiographic features among 3 groups were similar ( all P > 0.05 ) .


The time of pain to balloon was ( 5.5 3.8 ) hours .


After primary PCI , myocardial tissue perfusion was significantly better in Group C than in Group A and Group B : TMP grade < 3 [ 10.0 % ( 3/30 ) vs. 40.0 % ( 12/30 ) and 33.3 % ( 10/30 ) , P < 0.01 and P < 0.05 ] .


Left ventricular ejection fraction at 5 to 7 days after PCI also tended higher in Group C than in the other 2 groups ( P = 0.05 ) .


One patient died of heart failure at 7th day after PCI in Group A , and no patient died in Group B and C. Thirty days after PCI , there was no re-myocardial infarction and target vessel revascularization event among 3 groups .


The bleeding complication rate during 30 days follow-up was similar among 3 groups ( P > 0.05 ) .


Intracoronary bolus application of tirofiban combined with nitroprusside through thrombus aspiration catheter after thrombus aspiration is associated with an improvement of myocardial reperfusion without increasing bleeding complication and other adverse cardiovascular events rate compared with thrombus aspiration alone in patients with acute anterior myocardial infarction and heavy thrombosis burden undergoing primary PCI .


Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders .


Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment .


The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial .


The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode ( MDE , unipolar and bipolar disorder according to DSM IV criteria ) .


The specific aim is to test the hypothesis that lithium plus treatment as usual ( TAU ) , compared to placebo plus TAU , results in a significantly greater decrease in suicidal ideation and/or behavior over 5weeks in inpatients with MDE .


We initiated a randomized , placebo-controlled multicenter trial .


Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale ( S-STS ) will be randomly allocated to add lithium or placebo to their treatment as usual .


Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome .


There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior .


The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5weeks of treatment .


ClinicalTrials.gov identifier : NCT02039479 .


To study the impact of impaired cerebral autoregulation on cortical neurophysiology , long term potentiation ( LTP ) - like plasticity , motor learning and brain structure .


12 patients with unilateral occlusion or severe stenosis of the internal carotid artery were included .


Impairment of cerebral autoregulation was determined by vasomotor reactivity in transcranial Doppler sonography .


Corticomotor excitability , cortical silent period and LTP-like plasticity were assessed with transcranial magnetic stimulation , motor learning with a force production task , and brain structure with high-resolution MRI of the brain .


In the affected hemisphere , corticomotor excitability was significantly higher , cortical silent period and LTP-like plasticity significantly lower , compared to the contralateral side .


No significant difference emerged for motor learning , cortical thickness and white matter integrity between the hemispheres .


Despite decreased LTP-like plasticity in the affected hemisphere , motor learning was comparable between hemispheres , possibly due to gamma-aminobutyric-acid ( GABA ) B-mediated corticomotor excitability changes within the affected hemisphere .


Our results may help to develop interventions to beneficially modulate cortical physiology in the presence of cerebral hypoperfusion .


Pain after total knee arthroplasty ( TKA ) is severe , thus adequate pain control can be a challenge .


Intrathecal morphine ( ITM ) provides excellent postoperative analgesia for TKA , but may have side effects .


Femoral nerve block ( FNB ) also has been used for postoperative analgesia in TKA .


We examined postoperative analgesia efficacy and side effects of ITM combined with single shot femoral nerve block ( SSFNB ) after TKA , over the dosage range of 0.0 to 0.3 mg .


Sixty patients undergoing elective TKA received SSFNB ( 0.5 % bupivacaine 20 ml ) and spinal anesthesia with 15 mg of hyperbaric bupivacaine ( 0.5 % Heavy Marcaine ) were included in this study .


They were randomized to receive ITM ( 0 , 0.1 , 0.2 , and 0.3 mg ) .


A patient-controlled analgesia ( PCA ) device provided additional intravenous morphine .


Morphine consumption , pain score , and side effects were recorded at 0 , 1 , 4 , 8 , 12 , and 24 hour postoperative .


Patient satisfaction was rated at the 24-hour postoperative visit .


Morphine consumption was significant higher in 0 mg ITM group ( control ) than other groups , but there was no difference between ITM groups .


Pain score was significant lower in 0.3 mg ITM group compared to 0 mg at 1 hour ( 0.5 vs. 3.5 , respectively ; p-value = 0.013 ) and 4 hour ( 1.5 vs. 4.5 , respectively ; p-value = 0.037 ) postoperative period Side effects were not different in all groups .


The present study concluded that , low-dose ITM combination with SSFNB provided good pain relief with low side effects and reduced morphine consumption during the first 24 hours post TKA .


To evaluate the effects of transcranial direct current stimulation ( tDCS ) on esophageal peristalsis in patients with gastroesophageal reflux disease ( GERD ) .


Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study .


Esophageal manometry was performed before and during transcranial direct current stimulation ( tDCS ) of the right precentral cortex .


Half of patients were randomly assigned to anodal , half to sham stimulation .


Distal waves amplitude and pathological waves percentage were measured , after swallowing water boli , for ten subsequent times .


Last , a 24h pH-bilimetry was done to diagnose non-erosive reflux disease ( NERD ) or functional heartburn ( FH ) .


The values obtained before and during anodal or sham tDCS were compared .


Sixty-eight patients were enrolled in the study .


Distal waves mean amplitude increased significantly only during anodal tDCS in NERD ( p = 0.00002 ) and FH subgroups ( p = 0.008 ) while percentage of pathological waves strongly decreased only in NERDs ( p = 0.002 ) .


Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease ( ERD ) patients .


Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well .


In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology .


The wide heterogeneity in the early growth and metabolism of children born small for gestational age ( SGA ) , both before and during GH therapy , may reflect common genetic variations related to insulin secretion or sensitivity .


Combined multiallele single nucleotide polymorphism scores with known associations with insulin sensitivity or insulin secretion were analyzed for their relationships with spontaneous postnatal growth and first-year responses to GH therapy in 96 short SGA children .


The insulin sensitivity allele score ( GS-InSens ) was positively associated with spontaneous postnatal weight gain ( regression coefficient [ B ] : 0.12 SD scores per allele ; 95 % confidence interval [ CI ] , 0.01-0 .23 ; P = .03 ) and also in response to GH therapy with first-year height velocity ( B : 0.18 cm/y per allele ; 95 % CI , 0.02-0 .35 ; P = .03 ) and change in IGF-1 ( B : 0.17 SD scores per allele ; 95 % CI , 0.00-0 .32 ; P = .03 ) .


The association with first-year height velocity was independent of reported predictors of response to GH therapy ( adjusted P = .04 ) .


The insulin secretion allele score ( GS-InSec ) was positively associated with spontaneous postnatal height gain ( B : 0.15 ; 95 % CI , 0.01-0 .30 ; P = .03 ) and disposition index both before ( B : 0.02 ; 95 % CI , 0.00-0 .04 ; P = .04 ) and after 1 year of GH therapy ( B : 0.03 ; 95 % CI , 0.01-0 .05 ; P = .002 ) , but not with growth and IGF-1 responses to GH therapy .


Neither of the allele scores was associated with size at birth .


Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children .


Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response .


Many new brands of hyaluronic acid ( HA ) fillers are being produced , but comparative research on the characteristics of similar products is limited .


To test the efficacy , tolerability , and safety of a new HA filler , PP-501-B ( Cleviel Contour ; Pacific Pharma , Seoul , Korea ) , which is used for correcting nasolabial folds ( NLFs ) , and to compare the performance of PP-501-B with that of Restylane Perlane ( Q-Med ) .


A total of 103 subjects with visible NLFs were enrolled in this randomized , multicenter , patient/evaluator-blind , active-controlled , matched-pair clinical study .


Each subject was injected with PP-501-B in 1 NLF and Restylane Perlane in the other .


All participants were reassessed for cosmetic changes at 8 , 16 , and 24 weeks .


Wrinkle severity was rated using the 5-point Wrinkle Severity Rating Scale ( WSRS ) .


At Week 24 , the mean improvement in the WSRS compared with baseline was 1.87 0.73 for the PP-501-B side and 1.92 0.71 for the Restylane Perlane side .


Both fillers were well tolerated , and adverse reactions were mild .


The new HA filler , PP-501-B , to the market , with suitable characteristics and ample safety profiles , will widen the selection of agents for physicians and patients because the purpose , area , and depth of filler injections vary .


The effect of weight loss by diet or diet and exercise on salivary cortisol levels , a measure of hypothalamic pituitary adrenal activity , in overweight individuals is not known .


The objective was to test the hypothesis that 24 weeks of moderate caloric restriction ( CR ) ( 25 % ) by diet or diet and aerobic exercise would alter morning and diurnal salivary cortisol levels .


Randomized control trial in an institutional research center .


Thirty-five overweight ( BMI : 27.80.7 kg/m ( 2 ) ) but otherwise healthy participants ( 16 M/19 F ) .


Participants were randomized to either calorie restriction ( CR : 25 % reduction in energy intake , n = 12 ) , calorie restriction + exercise ( CR+EX : 12.5 % reduction in energy intake +12.5 % increase in exercise energy expenditure , n = 12 ) or control ( healthy weight-maintenance diet , n = 11 ) for 6 months .


Salivary cortisol measured at 8:00 , 8:30 , 11:00 , 11:30 , 12:30 , 13:00 , 16:00 and 16:30 .


Morning cortisol was defined as the mean cortisol concentration at 08:00 and 08:30 .


Diurnal cortisol was calculated as the mean of the 8 cortisol measures across the day .


In the whole cohort , higher morning and diurnal cortisol levels were associated with impaired insulin sensitivity ( morning : P = 0.004 , r ( 2 ) = 0.24 ; diurnal : P = 0.02 , r ( 2 ) = 0.15 ) .


Using mixed model analysis , there was no significant effect of group , time or sex on morning or diurnal cortisol levels .


A 10 % weight loss with a 25 % CR diet alone or with exercise did not impact morning or diurnal salivary cortisol levels .


Triple therapy with telaprevir ( TVR ) , pegylated interferon and ribavirin has improved antiviral efficacy in patients with chronic hepatitis C ( CH-C ) .


However , the severe adverse effects caused by TVR are important to resolve .


In this prospective , randomized , multicenter , open-label study , the antiviral efficacy and safety in the reduced administration of TVR were examined .


A total of 81 CH-C Japanese patients with HCV genotype 1 were randomized into two regimens of TVR 2250 mg ( TVR-2250 ) or 1500 mg ( TVR-1500 ) and treated with triple therapy for 24 weeks .


The mean HCV RNA at start , 2 and 4 weeks of treatment were 6.69 0.70 , 1.05 0.74 , 0.22 0.48 log10 IU/ml in the TVR-2250 group and 6.70 0.62 , 1.02 0.62 , 0.13 0.41 log10 IU/ml in the TVR-1500 group .


The SVR rates were 85 % in both groups ( 35/41 and 34/40 , respectively ) .


There were no patients with viral breakthrough in either group .


As for adverse effects , rash more than moderate and severe anemia with < 8.5 g/dl of hemoglobin were higher in the TVR-2250 group than in the TVR-1500 group ( p = 0.046 , p < 0.001 , respectively ) .


The increase in serum creatinine levels and decrease in estimated glomerular filtration rates were higher in the TVR-2250 group than in the TVR-1500 group .


The lower dose of TVR ( 1500 mg/day ) can result in similar SVR rates and lower treatment-related adverse effects compared to the higher dose of TVR ( 2250 mg/day ) in triple therapy ( UMIN : 000007313 , 000007330 ) .


This study investigates utilisation patterns for prescription opioid analgesics in the Australian community and how these are associated with a framework of individual-level factors related to healthcare use .


Self-reported demographic and health information from participants in the 45 and Up Study cohort were linked to pharmaceutical claims from 2006-2009 .


Participants comprised 19,816 people with 1 opioid analgesic dispensing in the 12-months after recruitment to the cohort and 79,882 people not dispensed opioid analgesics .


All participants were aged 45 years , were social security pharmaceutical beneficiaries , with no history of cancer .


People dispensed opioid analgesics were classified as having acute ( dispensing period < 90 days ) , episodic ( 90 days and < 3 ` authority ' prescriptions for increased quantity supply ) or long-term treatment ( 90 days and 3 authority prescriptions ) .


Of participants dispensed opioid analgesic 52 % received acute treatment , 25 % episodic treatment and 23 % long-term treatment .


People dispensed opioid analgesics long-term had an average of 14.9 opioid analgesic prescriptions/year from 2.0 doctors compared with 1.5 prescriptions from 1.1 doctors for people receiving acute treatment .


People dispensed opioid analgesics reported more need-related factors such as poorer physical functioning and higher psychological distress .


Long-term users were more likely to have access-related factors such as low-income and living outside major cities .


After simultaneous adjustment , association with predisposing health factors and access diminished , but indicators of need such as osteoarthritis treatment , paracetamol use , and poor physical function were the strongest predictors for all opioid analgesic users .


People dispensed opioid analgesics were in poorer health , reported higher levels of distress and poorer functioning than people not receiving opioid analgesics .


Varying dispensing profiles were evident among people dispensed opioid analgesics for persistent pain , with those receiving episodic and long-term treatment dispensed the strongest opioid analgesics .


The findings highlight the broad range of factors associated with longer term opioid analgesics use .


Primary percutaneous coronary intervention ( P-PCI ) is the preferred reperfusion option in ST-elevation myocardial infarction , but its benefits become attenuated as time to its potential delivery becomes prolonged .


Based on the STrategic Reperfusion Early After Myocardial Infarction trial , we assessed the impact of increasing time delay on outcomes in patients randomised to a pharmacoinvasive strategy ( PI ) or P-PCI .


Thirty-day clinical outcomes were examined according to PCI-related delay ( P-RD ) .


Data from hospitals that enrolled > 10 randomised patients were used and P-RD categorised as 55min , > 55-97min and > 97min .


Composite of death/congestive heart failure/cardiogenic shock/myocardial infarction in PI and P-PCI arms occurred in 10.6 % versus 10.3 % ( 55min , p = 0.910 ) ; 13.9 % versus 17.9 % ( > 55-97min , p = 0.148 ) and 13.5 % versus 16.2 % ( > 97min , p = 0.470 ) , respectively .