Ischemic events occurred more frequently among patients with PAD ( 25.3 % ) versus no PAD ( 12.2 % , P < .001 ) , and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD ( 9.1 % ) versus no PAD ( 5.0 % , P = .004 ) .


Similar rates of the composite end point ( cardiovascular death , myocardial infarction , or stroke ) occurred in patients with PAD treated with vorapaxar and placebo ( 21.7 % vs 24.8 % , P interaction = .787 ) .


Patients with PAD treated with vorapaxar , when compared with placebo , also had a numerical reduction in peripheral revascularization procedures ( 8.1 % vs 9.0 % , P = .158 ) and a lower extremity amputation rate ( 0.9 % vs 1.5 % , P = .107 ) .


Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD ( hazard ratio 1.47 , 95 % CI 0.89-2 .45 ) and without ( hazard ratio 1.48 , 95 % CI 1.22-1 .79 ; P interaction = .921 ) .


Patients with NSTE ACS and PAD were at increased risk for ischemic events .


Lower rates of ischemic end points , peripheral revascularization , and amputation with vorapaxar did not reach statistical significance but warrant further investigation .


Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk .


This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography ( TEG ) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction ( STEMI ) .


467 consecutive patients with STEMI undergoing percutaneous coronary intervention ( PCI ) were enrolled .


Twenty tag single nucleotide polymorphisms ( SNPs ) selected from ABCB1 gene and CYP2C19 * 2 , * 3 , * 17 were detected by the ligase detection reaction .


Platelet reactivity was assessed by TEG .


The follow-up period was 12months .


By receiver operating characteristic curve analysis , the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition ( BARC ) 3b bleedings , yielding an area under the curve ( AUC ) of 0.707 ( 95 % CI 0.662-0 .749 , p = 0.009 ; cut-off value > 93.4 % ) .


ADP inhibition can also predict BARC 3 bleedings with an AUC of 0.594 ( 95 % CI 0.546-0 .640 , p = 0.05 ; cut-off value > 92.5 % ) .


After adjustment for established risk factors of bleeding including the gain of function CYP2C19 * 17 allele , age , female gender , renal function , the multivariable logistic regression model demonstrated that ADP inhibition > 92.5 % ( OR 2.247 , 95 % CI 1.082-4 .665 , P = 0.03 ) , carriage of rs1045642 ( OR 2.943 , 95 % CI 1.195-7 .247 , P = 0.019 ) and rs7779562 ( OR 0.453 , 95 % CI 0.219-0 .936 , P = 0.032 ) were independent predictors of BARC 3 bleedings .


These associations were validated in a second cohort of 504 STEMI patients .


In STEMI patients treated with clopidogrel after PCI , the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk , and ADP inhibition in TEG has a predictive value of bleedings .


The growing demand for cancer genetic services underscores the need to consider approaches that enhance access and efficiency of genetic counseling .


Telephone delivery of cancer genetic services may improve access to these services for individuals experiencing geographic ( rural areas ) and structural ( travel time , transportation , childcare ) barriers to access .


This cluster-randomized clinical trial used population-based sampling of women at risk for BRCA1/2 mutations to compare telephone and in-person counseling for : 1 ) equivalency of testing uptake and 2 ) noninferiority of changes in psychosocial measures .


Women 25 to 74 years of age with personal or family histories of breast or ovarian cancer and who were able to travel to one of 14 outreach clinics were invited to participate .


Randomization was by family .


Assessments were conducted at baseline one week after pretest and post-test counseling and at six months .


Of the 988 women randomly assigned , 901 completed a follow-up assessment .


Cluster bootstrap methods were used to estimate the 95 % confidence interval ( CI ) for the difference between test uptake proportions , using a 10 % equivalency margin .


Differences in psychosocial outcomes for determining noninferiority were estimated using linear models together with one-sided 97.5 % bootstrap CIs .


Uptake of BRCA1/2 testing was lower following telephone ( 21.8 % ) than in-person counseling ( 31.8 % , difference = 10.2 % , 95 % CI = 3.9 % to 16.3 % ; after imputation of missing data : difference = 9.2 % , 95 % CI = -0.1 % to 24.6 % ) .


Telephone counseling fulfilled the criteria for noninferiority to in-person counseling for all measures .


BRCA1/2 telephone counseling , although leading to lower testing uptake , appears to be safe and as effective as in-person counseling with regard to minimizing adverse psychological reactions , promoting informed decision making , and delivering patient-centered communication for both rural and urban women .


To investigate the relation of residual worst lead ST segment elevation ( WL-STE ) after ST segment myocardial infarction ( STEMI ) with infarct size and microvascular injury assessed by cardiovascular magnetic resonance ( CMR ) imaging .


WL-STE in patients with acute reperfused STEMI has been shown to identify high risk patients for major adverse cardiovascular events ( MACE ) .


However , the relation of WL-STE with myocardial damage is unknown .


In this multicentre study we analysed ECG data 90min after primary percutaneous coronary intervention ( PCI ) in 763 STEMI patients .


WL-STE was defined as the absolute magnitude of STE in the most affected lead on the post-PCI ECG .


Patients were categorised into three groups ( < 1mm , 1-2mm , and 2mm ) .


CMR was performed within 1week after infarction for comprehensive assessment of myocardial damage using a standardised protocol .


The primary clinical endpoint was MACE defined as death , reinfarction , and new congestive heart failure within 12months after infarction .


WL-STE < 1mm , 1-2mm , and 2mm was present in 155 ( 20 % ) , 328 ( 43 % ) , and 280 ( 37 % ) patients , respectively .


Myocardial damage determined by CMR demonstrated a graded relationship of infarct size ( median ( IQR ) 13.3 ( 6.2-20 .3 ) % LV vs 13.7 ( 7.6-21 .3 ) % LV vs 22.5 ( 15.6-31 .2 ) % LV , p < 0.001 ) , the myocardial salvage index ( 60.8 ( 37.0-84 .5 ) vs 55.0 ( 36.6-73 .9 ) vs 42.7 ( 26.2-58 .2 ) , p < 0.001 ) , and microvascular obstruction ( 0.0 ( 0.0-0 .9 ) % LV vs 0.0 ( 0-1 .0 ) % LV vs 1.2 ( 0.0-3 .6 ) % LV , p < 0.001 ) across the three groups .


WL-STE 2mm was strongly associated with MACE 12month after infarction ( HR 1.93 , 95 % CI 1.11 to 3.37 ; p = 0.02 ) .


This largest CMR study to date correlating post-PCI WL-STE with markers of myocardial damage demonstrates that WL-STE is significantly associated with infarct size , myocardial salvage , microvascular obstruction , and MACE in a high risk STEMI population .


NCT00712101 .


The role of planning in binge eating episodes is unknown .


We investigated the characteristics of planning associated with food cues in binging patients .


We studied planning based on backward reasoning , reasoning that determines a sequence of actions back to front from the final outcome .


A cross-sectional study was conducted with 20 healthy participants , 20 bulimia nervosa ( BN ) , 22 restrictive ( ANR ) and 23 binging anorexia nervosa ( ANB ) , without any concomitant impulsive disorder .


In neutral/relaxing , binge food and stressful conditions , backward reasoning was assessed with the Race game , promotion of delayed large rewards with an intertemporal discounting task , attention with the Simon task , and repeating a dominant behavior with the Go/No-go task .


BN and to a lower extent ANB patients succeeded more at the Race game in food than in neutral condition .


This difference discriminated binging from non-binging participants .


Backward reasoning in the food condition was associated with lower approach behavior toward food in BN patients , and higher food avoidance in ANB patients .


Enhanced backward reasoning in the food condition related to preferences for delayed large rewards in BN patients .


In BN and ANB patients the enhanced success rate at the Race game in the food condition was associated with higher attention paid to binge food .


These findings introduce a novel process underlying binges : planning based on backward reasoning is associated with binges .


It likely aims to reduce craving for binge foods and extend binge refractory period in BN patients , and avoid binging in ANB patients .


Shifts between these goals might explain shifts between eating disorder subtypes .


The reported incidence of injuries due to cardiopulmonary resuscitation using manual chest compressions ( manual CPR ) varies greatly .


Our aim was to elucidate the incidence of CPR-related injuries by manual chest compressions compared to mechanical chest compressions with the LUCAS device ( mechanical CPR ) in non-survivors after out-of-hospital cardiac arrest .


In this prospective multicentre trial , including 222 patients ( 83 manual CPR/139 mechanical CPR ) , autopsies were conducted after unsuccessful CPR and the results were evaluated according to a specified protocol .


Among the patients included , 75.9 % in the manual CPR group and 91.4 % in the mechanical CPR group ( p = 0.002 ) displayed CPR-related injuries .


Sternal fractures were present in 54.2 % of the patients in the manual CPR group and in 58.3 % in the mechanical CPR group ( p = 0.56 ) .


Of the patients in the manual CPR group , there were 64.6 % with at least one rib fracture versus 78.8 % in the mechanical CPR group ( p = 0.02 ) .


The median number of rib fractures among patients with rib fractures was 7 in the manual CPR group and 6 in the mechanical CPR group .


No CPR-related injury was considered to be the cause of death .


In patients with unsuccessful CPR after out-of-hospital cardiac arrest , rib fractures were more frequent after mechanical CPR but there was no difference in the incidence of sternal fractures .


No injury was deemed fatal by the pathologist .


Anecdotal reports suggest that clopidogrel may prevent migraine attacks .


We undertook a pilot randomised trial .


We randomised consecutive migraineurs with four to 15 headache days per 28-day month to receive clopidogrel 75mg or placebo daily for three months .


Headache was primarily assessed with a headache diary .


There were no statistically significant treatment effects .


The number of headache days fell by 1.9 on clopidogrel and 1.6 on placebo ( adjusted difference 0.02 , CI -2.07 to 2.12 ) .


Headache severity rose by 0.14 points ( out of 10 ) on clopidogrel , and fell by 0.63 on placebo ; treatment effect 0.7 points ( CI -0.11 to 1.57 ) .


The main treatment effect did not depend on the presence or absence of migraine with aura at baseline , a patent foramen ovale ( PFO ) or atrial septal aneurysm .


The evidence is inconclusive , but a multicentre trial would be feasible recruiting from primary care .


Pre-hospital emergency care is a particularly vulnerable setting for workplace violence .


However , there is no literature available to date on the psychological consequences of violence in pre-hospital emergency care .


To evaluate the psychological consequences of exposure to workplace violence from patients and those accompanying them in pre-hospital emergency care .


A retrospective cross-sectional study .


70 pre-hospital emergency care services located in Madrid region .


A randomized sample of 441 health care workers ( 135 physicians , 127 nurses and 179 emergency care assistants ) .


Data were collected from February to May 2012 .


The survey was divided into four sections : demographic/professional information , level of burnout determined by Maslach Burnout Inventory ( MBI ) , mental health status using General Health Questionnaire ( GHQ-28 ) and frequency and type of violent behaviour experienced by staff members .


The health care professionals who had been exposed to physical and verbal violence presented a significantly higher percentage of anxiety , emotional exhaustion , depersonalization and burnout syndrome compared with those who had not been subjected to any aggression .


Frequency of verbal violence ( more than five times ) was related to emotional exhaustion and depersonalization .


Type of violence ( i.e. physical aggression ) is especially related to high anxiety levels and frequency of verbal aggression is associated with burnout ( emotional exhaustion and depersonalization ) .


Psychological counselling should be made available to professional staff who have been subjected to physical aggression or frequent verbal violence .


Lorcaserin , a novel selective 5-HT2C receptor agonist , is approved by the US Food and Drug Administration ( FDA ) for weight management in combination with lifestyle modification for adults with obesity and adults with overweight and 1 weight-related comorbid condition .


The safety and effectiveness of lorcaserin in adult patients without type 2 diabetes mellitus was established based on 2 phase III clinical trials of similar design : Behavioral Modification and Lorcaserin for Overweight and Obesity Management ( BLOOM ) and Behavioral Modification and Lorcaserin Second Study for Obesity Management ( BLOSSOM ) .


This report presents a prespecified analysis of pooled data from these trials .


Co-primary end points in this analysis include the proportion of patients with a reduction in baseline body weight of 5 % and 10 % , and a change in weight from baseline .


Key secondary end points include changes from baseline values in lipid parameters , quality-of-life measures , glycemic indicators , and vital signs .


At week 52 , more than twice as many lorcaserin-treated patients achieved a weight loss of 5 % compared with placebo ( lorcaserin , 47.1 % ; placebo , 22.6 % ) , and lorcaserin-treated patients lost significantly more body weight ( lorcaserin , -5.8 % ; placebo , -2.5 % ) .


A significantly greater proportion of lorcaserin-treated patients achieved a weight loss of 10 % ( lorcaserin , 22.4 % ; placebo , 8.7 % ) .


There were statistically significant improvements in lipid parameters , glycemic indicators , quality-of-life measures , and vital signs in the lorcaserin group compared with placebo .


The most common adverse events associated with lorcaserin treatment were headache , upper respiratory tract infection , and nasopharyngitis .


Lorcaserin-treated patients had a rate of FDA-defined valvulopathy similar to placebo .


This pooled analysis of the phase III BLOOM and BLOSSOM trials shows that lorcaserin 10 mg twice daily , in combination with diet and exercise , is safe and tolerable , and is associated with statistically significant weight loss and clinically relevant improvements in cardiometabolic parameters .


A novel multidimensional index of nociception , the nociception level ( NoL ) index , derived from the nonlinear composite of heart rate ( HR ) , HR variability , amplitude of the photoplethysmogram , skin conductance , fluctuations in skin conductance , and their time derivatives , was used to assess nociception during anesthesia .


Seventy-two American Society of Anesthesiologists I to III patients received propofol ( target bispectral index , 45 ) and one of six remifentanil target concentrations in the range of 0 to 5 ng/ml .


The NoL , mean arterial pressure ( MAP ; derived from a beat-to-beat finger cuff measurement ) , and HR were measured during nonnoxious , moderate noxious ( skin incision ) , and intense noxious ( intubation ) stimulation .


Values are represented as average ( 95 % CI ) .


NoL , HR , and MAP did not change during nonnoxious events .


Incision increased HR by 1.3 / min ( -0.46 to 3.1 / min ; not significant ) , MAP by 7.9 mmHg ( -1.9 to 13.0 mmHg ; not significant ) , and NoL by 8.0 ( 0.4 to 16.0 ; P < 0.001 ) .


Intubation increased HR by 7.0 / min ( 1.4 to 12.0 / min ; P < 0.001 ) , MAP by 13.0 mmHg ( 3.1 to 20 mmHg ; P < 0.001 ) , and NoL by 18.0 ( 7.8 to 29.0 ; P < 0.001 ) .


The NoL area under the curve ( 0.95 ) of the receiver operating characteristic curve was greater compared with HR ( 0.84 , P < 0.001 ) and MAP ( 0.78 , P < 0.001 ) .


Under nonnociceptive conditions , remifentanil had no effect on NoL , in contrast to HR and MAP that showed a dose-dependent decrease .


The NoL is a reliable measure of moderate and intense noxious stimulation and outperforms HR and MAP in differentiating noxious from nonnoxious stimuli .


In contrast to HR and MAP , the NoL was not affected by hemodynamic effects of remifentanil .


The objective of this study was to assess the evolution of T1 contrast ( T1c ) between cardiovascular tissues , contrast agents , and magnetic field strengths .


This Health Insurance Portability and Accountability Act-compliant study was approved by the institutional review board , and written informed consent was obtained from all participants .


Eight healthy volunteers were recruited to undergo 4 consecutive magnetic resonance ( MR ) scans with the same imaging parameters .


Scans 1 and 2 were performed using a 3-T MR scanner , and scans 3 and 4 were performed using a 1.5-T MR scanner .


Gadofosveset trisodium ( 0.03 mmol/kg ) was injected for scans 1 and 3 , and gadopentetate dimeglumine ( Gd-DTPA ) ( 0.1 mmol/kg ) was used for scans 2 and 4 .


Modified Look-Locker inversion recovery T1 maps with a midventricular short-axis view were acquired before contrast and repeated every 5 minutes until 45 minutes after contrast agent administration .


T1 contrast tissue ( T1 ( myocardium ) - T1 ( blood ) ) , T1c agent ( T1Gd-DTPA - T1 ( Gadofosveset ) ) , and T1c field ( T1 ( 3T ) - T1 ( 1.5 T ) ) were calculated and compared using t tests .


The T1c tissue of the 3-T scanner was larger than that of the 1.5-T scanner for both contrast agents .


In both the myocardium and the blood pool , the T1c agent of the 1.5-T scanner was larger than that of the 3-T scanner .


Gadofosveset trisodium exhibited a larger T1c field and T1c tissue than did Gd-DTPA .


The T1c tissue induced by Gd-DTPA diminished faster than that induced by gadofosveset trisodium at both 1.5 and 3 T.


Our study demonstrates the independent effects of timing , contrast agent type , and magnetic field strength on postcontrast T1c under general physiological conditions .


The behaviors of T1c can be used to tailor quantitative MR imaging protocols for various clinical purposes .


The purpose of this study was to evaluate the diagnostic accuracy of real-time shear-wave elastography for assessment of liver fibrosis in an unselected patient population , comparing shear-wave elastography measurements obtained at and remote from the site of random liver biopsy .


In a prospective study of 50 patients ( 21 with and 29 without hepatitis C ) referred for clinically indicated random liver biopsy for diffuse liver disease , shear-wave elastography measurements were taken from four locations before biopsy : one at the left lobe , two at the right lobe , and one at the biopsy location .


The mean , minimum , maximum , and SD of shear-wave elastography were compared with pathologic grading .


Steatosis and serum markers were analyzed using multiple logistic regression .


Optimized shear-wave elastography thresholds were calculated using AUC analysis .


The AUC ( 95 % CI ) at the biopsy site , ipsilateral lobe , and contralateral lobe were 0.82 ( 0.63-1 .0 ) , 0.84 ( 0.67-1 .0 ) , and 0.59 ( 0.19-0 .99 ) in hepatitis C patients ; 0.89 ( 0.75-1 .0 ) , 0.88 ( 0.73-1 .0 ) , and 0.93 ( 0.80-1 .0 ) in nonhepatitis C patients ; and 0.85 ( 0.74-0 .96 ) , 0.89 ( 0.79-0 .99 ) , and 0.80 ( 0.67-0 .93 ) in all patients , respectively .


Optimized biopsy site shear-wave elastography values for detecting Metavir score F2 or greater were 1.87 m/s ( 75 % sensitivity and specificity ) , 2.00 m/s ( 80 % sensitivity and specificity ) , and 1.89 m/s ( 76 % sensitivity and specificity ) in hepatitis C , nonhepatitis C , and all patients , respectively .


Steatosis and serum markers were not significant .


Real-time shear-wave elastography accurately predicted significant fibrosis ( stage 2 ) in an unselected patient population with diffuse disease , including patients with and without hepatitis C. Shear-wave elastography best predicts pathologic grading when taken at the biopsy site or ipsilateral lobe in hepatitis C patients .


Percentage steatosis was not predictive of shear-wave elastography results .


We evaluate patients with shock and traumatic brain injury who were previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome .


This was a secondary analysis of patients with shock and traumatic brain injury who were aged 15 years or older and enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 emergency medical services agencies transporting to 46 Level I and II trauma centers in 11 sites ( May 2006 through May 2009 ) .


Inclusion criteria were systolic blood pressure less than or equal to 70 mm Hg or systolic blood pressure 71 to 90 mm Hg with pulse rate greater than or equal to 108 beats/min ( shock cohort ) and Glasgow Coma Scale score less than or equal to 8 ( traumatic brain injury cohort ) ; patients meeting both criteria were placed in the shock cohort .


Primary outcomes were 28-day mortality ( shock cohort ) and 6-month Glasgow Outcome Scale-Extended score less than or equal to 4 ( traumatic brain injury cohort ) .


There were 778 patients in the shock cohort ( 26 % 28-day mortality ) and 1,239 patients in the traumatic brain injury cohort ( 53 % 6-month Glasgow Outcome Scale-Extended score 4 ) .


Out-of-hospital time greater than 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort ( adjusted odds ratio [ aOR ] 1.42 ; 95 % confidence interval [ CI ] 0.77 to 2.62 ) or traumatic brain injury cohort ( aOR 0.77 ; 95 % CI 0.51 to 1.15 ) .


However , shock patients requiring early critical hospital resources and arriving after 60 minutes had higher 28-day mortality ( aOR 2.37 ; 95 % CI 1.05 to 5.37 ) ; this finding was not observed among a similar traumatic brain injury subgroup .


Among out-of-hospital trauma patients meeting physiologic criteria for shock and traumatic brain injury , there was no association between time and outcome .


However , the subgroup of shock patients requiring early critical resources and arriving after 60 minutes had higher mortality .


Noncompliance with scheduled ambulatory saliva sampling is common and has been associated with biased cortisol estimates in nonpregnant subjects .


This study is the first to investigate in pregnant women strategies to improve ambulatory saliva-sampling compliance , and the association between sampling noncompliance and saliva cortisol estimates .


We instructed 64 pregnant women to collect eight scheduled saliva samples on two consecutive days each .


Objective compliance with scheduled sampling times was assessed with a Medication Event Monitoring System and self-reported compliance with a paper-and-pencil diary .


In a randomized controlled study , we estimated whether a disclosure intervention ( informing women about objective compliance monitoring ) and a reminder intervention ( use of acoustical reminders ) improved compliance .


A mixed model analysis was used to estimate associations between women 's objective compliance and their diurnal cortisol profiles , and between deviation from scheduled sampling and the cortisol concentration measured in the related sample .


Self-reported compliance with a saliva-sampling protocol was 91 % , and objective compliance was 70 % .


The disclosure intervention was associated with improved objective compliance ( informed : 81 % , noninformed : 60 % ) , F ( 1,60 ) = 17.64 , p < 0.001 , but not the reminder intervention ( reminders : 68 % , without reminders : 72 % ) , F ( 1,60 ) = 0.78 , p = 0.379 .


Furthermore , a woman 's increased objective compliance was associated with a higher diurnal cortisol profile , F ( 2,64 ) = 8.22 , p < 0.001 .


Altered cortisol levels were observed in less objective compliant samples , F ( 1,705 ) = 7.38 , p = 0.007 , with delayed sampling associated with lower cortisol levels .


The results suggest that in pregnant women , objective noncompliance with scheduled ambulatory saliva sampling is common and is associated with biased cortisol estimates .


To improve sampling compliance , results suggest informing women about objective compliance monitoring but discourage use of acoustical reminders .


There is currently little evidence defining the clinical importance of detecting and treating isolated distal DVT ( IDDVT ) .


International guidelines vary regarding diagnostic and therapeutic advice .


The potential benefits of anticoagulation are unquantified .


We sought to evaluate the feasibility of a randomized controlled study within a modern framework and provide a primary outcome point estimate .


In this open-label , external pilot randomized controlled trial , consecutive , symptomatic , ambulatory patients with IDDVT were approached for inclusion .


Participants were allocated to receive either therapeutic anticoagulation or conservative management .


Patients underwent blinded color-duplex imaging at 7 and 21 days and follow-up at 3 months .


Principal feasibility outcomes included recruitment rate and attrition .


The principal clinical outcome was a composite including proximal propagation , pulmonary embolism , death attributable to VTE disease , or major bleeding .


Analysis was by intention to treat .


In total , 93 patients with IDDVT were screened , and 70 of those eligible ( 88.6 % ) were recruited .


All patients but one were followed-up by direct contact after 90 days .


Allocation crossover occurred in 15 patients ( 21.4 % ) .


The principal clinical outcome occurred in four of 35 of those conservatively treated ( 11.4 % ) and zero of 35 in the anticoagulated group ( absolute risk reduction , 11.4 % ; 95 % CI , -1.5 to 26.7 , P = .11 , number needed to treat of nine ) .


There were no major bleeding episodes .


We have established the feasibility of definitive study regarding the value of therapeutic anticoagulation in IDDVT and provide an approximate point estimate for serious complications with a contemporary conservative strategy .


Current Controlled Trials ; No. : ISRCTN75175695 ; URL : www.controlled-trials.com .


Considering both the burden determined by major depressive disorder ( MDD ) itself and the high refractoriness and recurrence index , alternative strategies , such as trigeminal nerve stimulation ( TNS ) , are the cutting edge instruments to optimize clinical response and to avoid treatment discontinuation and relapse of symptoms .


Trigeminal nerve stimulation is an incipient simple , low-cost interventional strategy based on the application of an electric current over a branch of the trigeminal nerve with further propagation of the stimuli towards brain areas related to mood symptoms .


The study was a phase II , randomized , sham-controlled trial with 40 patients with MDD .


Patients with moderate or severe depressive symptoms as assessed by adequate clinical scales underwent a 10-day intervention protocol .


Regarding main clinical outcome , analysis of variance ( ANOVA ) was performed to evaluate mean change scores in depressive symptoms as assessed by the HDRS-17 between baseline ( t1 ) , after intervention protocol ( t2 ) , and during one-month follow-up ( t3 ) .


There was a significant interaction between the mean percentage changes in depressive symptoms according to the HDRS in the two groups across the three assessments ( F = 6.38 , df = 2 , p = 0.0033 ) .


Post hoc analyses ( Bonferroni method ) demonstrated a statistically significant difference between depressive symptoms at baseline and t1 ( p = 0.01 ) and between depressive symptoms at baseline and t2 ( p = 0.009 ) .


No severe adverse effects were reported .


Our results in the present controlled trial highlight the possibility of more practical treatment protocols for clinical research , which are similar to those for different neuromodulation strategies such as transcranial direct current stimulation ( tDCS ) .


The in-office administration of TNS in our protocol is similar to the schedule for repetitive transcranial magnetic stimulation ( rTMS ) , though over fewer treatment sessions .


Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD .


Moderate wound pain and opiate analgesia requirement is reported following thyroid and parathyroid surgery .


A randomized clinical trial was performed to investigate whether intraoperative superficial cervical plexus block ( SCPB ) would decrease postoperative pain and analgesia use .


Patients were randomized to incisional local anaesthesia ( control ) or incisional local anaesthesia plus intraoperative SCPB .


The primary outcome measure was pain , assessed by a visual analogue scale ( VAS ) .


Secondary outcome measures were analgesia use ( strong opiates defined as having potency at least as strong as that of oral morphine ) , respiratory rate and sedation score .


Primary outcome measures were analysed with non-parametric tests , as well as with receiver operating characteristic ( ROC ) curves calculated as area under the curve ( AUC ) to discriminate between trial limbs .


Twenty-nine patients were randomized to each group .


Pain ( VAS ) scores were lower in patients who received intraoperative SCPB than in controls 30min after surgery and subsequently ( P < 0020 at all time points ) , with a median pain score of zero on the day of operation in the SCPB group .


Corresponding analysis of ROC curves showed differences between groups at 30min ( AUC = 0722 , P = 0012 ) , 90min ( AUC = 0747 , P = 0005 ) , 150min ( AUC = 0803 , P < 0001 ) and 210min ( AUC = 0849 , P < 0001 ) after surgery , and at 07.00 hours on postoperative day 1 ( AUC = 0710 , P = 0017 ) .


Fewer patients in the SCPB group required strong opiates ( 5 of 29 versus 16 of 29 in the control group ; P = 0003 ) and rescue opiates ( 6 of 29 versus 20 of 29 ; P < 0001 ) .


Intraoperative SCPB reduces pain scores following thyroid and parathyroid surgery , and reduces the requirement for strong and rescue opiates .


2009-012671-98 ( https://www.clinicaltrialsregister.eu ) .


Elevated blood viscosity is a risk factor for atherosclerosis , thrombosis and other cardiovascular events .


Our previous studies have suggested that consumption of Yerba mate tea ( Ilex paraguariensis ) has strong antioxidant and lipid-lowering properties in animals .


The in vivo effects of Yerba mate on blood viscosity in humans , however , have not been studied .


This study aims to investigate the effect of Yerba mate tea on the reduction of blood viscosity and the improvement of microcirculatory parameters commonly regarded as risk factors for serious cardio and cerebrovascular disorders .


142 subjects with high blood viscosity were recruited in this randomized , double-blind , placebo-controlled study .


Yerba mate tea or placebo ( 5 g/day ) was administered to different groups for 6 weeks .


After treatment , results of hemorheological indexes , nailfold microcirculation , 6-keto-PGF1 and TXB2 and lipid profiles of subjects in the Yerba mate tea group were compared with those in the placebo-receiving group .


Parameters of blood viscosity and microcirculation were improved in the subjects from the Yerba mate tea group but not in placebo-receiving patients .


After treatment , whole blood viscosity , plasma viscosity and the Equation K value of erythrocyte sedimentation rate ( ESRK ) decreased significantly in the Yerba mate group .


Meanwhile , shape , flow state and nailfold microcirculation appeared positively changed .


Specifically , blood flow speeds accelerated gradually and nailfold weighted integral values decreased significantly .


Moreover , the vasodilator 6-keto PGF1 increased while the thromboxane TXB2 decreased in serum samples of subjects in the Yerba mate-receiving group .


Overall , Yerba mate tea-receiving subjects saw nearly all measured values improve to levels comparable to those characteristic of patients with normal microcirculation .


These results indicate the therapeutic capacity of Yerba mate tea in the treatment of high blood viscosity .


Here , Yerba mate tea played a role in the regulation of various indexes of hemorheology , nailfold microcirculation , and the platelet aggregating factors 6-keto-PGF1a and TXB2 .


The regulation of these might be correlated with reduced blood viscosity and accelerating blood flow .


Thus , Yerba mate tea may reduce some key risk-factors of cardiovascular disease .


Daily consumption of Yerba mate tea may be a better-tolerated option for individuals with high blood viscosity and microcirculatory disturbance and as such , a novel preventative strategy for patients at-risk for vascular disease .


For the management of retinal disease , the use of intravitreous injections of anti-vascular endothelial growth factor has increased .


Recent reports have suggested that this therapy may cause sustained elevation of intraocular pressure ( IOP ) and may potentially increase the risk of glaucoma for patients with retinal disease .


To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments for eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab .


An exploratory analysis was conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial .


Study enrollment dates were from March 20 , 2007 , to December 17 , 2008 .


Of 582 eyes ( of 486 participants ) with center-involved diabetic macular edema and no preexisting open-angle glaucoma , 260 were randomly assigned to receive a sham injection plus focal/grid laser treatment , and 322 were randomly assigned to receive ranibizumab plus deferred or prompt focal/grid laser treatment .


The cumulative probability of sustained IOP elevation , defined as IOP of at least 22 mm Hg and an increase of at least 6 mm Hg from baseline at 2 consecutive visits , or the initiation or augmentation of ocular hypotensive therapy , through 3 years of follow-up .


The mean ( SD ) baseline IOP in both treatment groups was 16 ( 3 ) mm Hg ( range , 5-24 mm Hg ) .


The cumulative probability of sustained IOP elevation or of initiation or augmentation of ocular hypotensive therapy by 3 years , after repeated ranibizumab injections , was 9.5 % for the participants who received ranibizumab plus prompt or deferred focal/grid laser treatment vs 3.4 % for the participants who received a sham injection plus focal/grid laser treatment ( difference , 6.1 % [ 99 % CI , -0.2 % to 12.3 % ] ; hazard ratio , 2.9 [ 99 % CI , 1.0-7 .9 ] ; P = .01 ) .


The distribution of IOP and the change in IOP from baseline at each visit through 3 years were similar in each group .


In eyes with center-involved diabetic macular edema and no prior open-angle glaucoma , repeated intravitreous injections of ranibizumab may increase the risk of sustained IOP elevation or the need for ocular hypotensive treatment .


Clinicians should be aware of this risk and should consider this information when following up with patients who have received intravitreous injections of anti-vascular endothelial growth factor for the treatment of diabetic macular edema .


To compare outcomes of intravitreal therapy from an observational study cohort with those of participants receiving treatment in the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab ( MARINA ) for the treatment of neovascular age-related macular degeneration ( wet AMD ) .


Database observational study .


Participants in the observational cohort were chosen to match demographic features and entry criteria of the treatment group from MARINA .


Outcomes over 12 months were compared .


Eight hundred twenty-one anti-vascular endothelial growth factor ( anti-VEGF ) - nave eyes treated with ranibizumab with 12 months or more of follow-up were included in the total Fight Retinal Blindness !


( FRB-All ) cohort , whereas a subset of this cohort of 401 eyes who were matched to the MARINA treatment group were included as the FRB-MARINA cohort .


Intravitreal ranibizumab therapy of 0.5 mg for wet AMD .


Visual acuity ( VA ) in logarithm of the minimum angle of resolution ( logMAR ) letters and treatments given were recorded continuously and anonymously in an electronic database for 12 months .


Locally weighted scatterplot smoothing ( LOESS ) regression was used to plot change in visual acuity data over the course of 12 months for both the FRB-All cohort and the FRB-MARINA cohort , whereas results from the MARINA trial were taken from the published study report .


Change in VA in logMAR letters over 12 months , treatment , and visit intensity .


Mean visual acuity improvement after 12 months in FRB-MARINA ( +5.5 letters ) was similar to that of the 0.5-mg group from MARINA ( +7.2 letters ) .


Improvement in FRB-ALL was slightly less ( +4.9 letters ) .


Mean treatment effect compared with the MARINA control group was similar for the MARINA treated group ( +17.6 letters ) and the FRB-MARINA cohort ( +15.9 letters ) .


A mean of 7.3 injections in 12 months was received by the observational cohorts .


Similarity of mean VA improvement in the matched observational cohort with that of the phase 3 clinical trial suggests that these results can be achieved in real-world clinical practice with a modified treatment regimen .


Interventions to support people with hypertension in attending clinics and taking their medication have potential to improve outcomes , but delivery on a wide scale and at low cost is challenging .


Some trials evaluating clinical interventions using short message service ( SMS ) text-messaging systems have shown important outcomes , although evidence is limited .


We have developed a novel SMS system integrated with clinical care for use by people with hypertension in a low-resource setting .


We aim to test the efficacy of the system in improving blood pressure control and treatment adherence compared to usual care .


The SMS Text-message Adherence suppoRt trial ( StAR ) is a pragmatic individually randomised three-arm parallel group trial in adults treated for hypertension at a single primary care centre in Cape Town , South Africa .


The intervention is a structured programme of clinic appointment , medication pick-up reminders , medication adherence support and hypertension-related education delivered remotely using an automated system with either informational or interactive SMS text-messages .


Usual care is supplemented by infrequent non-hypertension related SMS text-messages .


Participants are 1:1:1 individually randomised , to usual care or to one of the two active interventions using minimisation to dynamically adjust for gender , age , baseline systolic blood pressure , years with hypertension , and previous clinic attendance .


The primary outcome is the change in mean systolic blood pressure at 12-month follow-up from baseline measured with research staff blinded to trial allocation .


Secondary outcomes include the proportion of patients with 80 % or more of days medication available , proportion of participants achieving a systolic blood pressure less than 140mmHg and a diastolic blood pressure less than 90mmHg , hospital admissions , health status , retention in clinical care , satisfaction with treatment and care , and patient related quality of life .


Anonymised demographic data are collected on non-participants .


The StAR trial uses a novel , low cost system based on widely available mobile phone technology to deliver the SMS-based intervention , manage communication with patients , and measure clinically relevant outcomes .


The results will inform implementation and wider use of mobile phone based interventions for health care delivery in a low-resource setting .


NCT02019823 .


FlexTouch ( FT ) is a new prefilled insulin pen with no push-button extension and a low injection force used to deliver several basal insulins , including insulin degludec across a wide dose range ( 1 - 80 units with FT 100 IU/ml [ FT100 ] and 2 - 160 units with 200 IU/ml [ FT200 ] ) .


This study was carried out to evaluate whether the novel features of FT affect the preferences of the device among patients with diabetes and healthcare professionals compared with the widely used SoloSTAR pen .


A multicenter , randomized , open-label , crossover study compared FT100 and FT200 with SoloSTAR .


The study included patients with either type 1 ( n = 22 ) or type 2 diabetes ( n = 42 ) , nurses ( n = 32 ) and physicians ( n = 32 ) .


Subjects were randomized to test each of the FT100 , FT200 and SoloSTAR pens in a crossover set up .


Subjects performed injections into a foam cushion at 4 - 6 different doses per device ( 2 , 20 , 40 , 80 , 120 and 160 IU ) .


Overall , a significantly higher proportion of subjects , including dexterity-impaired and pen-naive patients , preferred to use FT100 ( 93.0 % ; 119/128 ) and FT200 ( 91.4 % ; 117/128 ) compared with 2.3 % ( 3/128 ) and 3.9 % ( 5/128 ) who preferred SoloSTAR ( p < 0.001 ) , respectively .


FT100 and FT200 were preferred over SoloSTAR by nurses , physicians and patients with diabetes .


This may be due to the novel design of FT , which improves ease of use , preference and confidence in delivering a complete , accurate dose of insulin , even at high doses .


Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity .


We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 ( vitD3 ) versus placebo to sustain increased serum 25-hydroxyvitamin D ( 25 ( OH ) D ) and improve immune status in HIV-infected subjects .


This was a double-blind trial of perinatally acquired HIV ( PHIV ) - infected subjects or behaviorally acquired HIV ( BHIV ) - infected subjects ( 5.0-24 .9 years ) .


Safety , 25 ( OH ) D-related parameters and immune status were assessed at baseline , 3 , 6 and 12 months .


Fifty-eight subjects enrolled ( 67 % male , 85 % African American and 64 % BHIV ) and 50 completed with no safety concerns .


In unadjusted analyses , there were no differences between randomization groups at baseline ; at 3 , 6 and 12 months , 25 ( OH ) D was higher with supplementation than baseline and higher than with placebo ( P < 0.05 ) .


In adjusted mixed models , in the supplementation group , the fixed effect of 25 ( OH ) D was higher ( P < 0.001 ) .


Percentage of naive T-helper cells ( Th naive % ) were significantly ( P < 0.01 ) and T-helper cells ( CD4 % ) marginally ( P < 0.10 ) increased with supplementation in those taking highly active antiretroviral therapy ( HAART ) , and RNA viral load was reduced ( P 0.05 ) .


In exploratory linear models , change in 25 ( OH ) D predicted RNA viral load at 3 and 12 months and CD4 % at 3 months ( P < 0.05 ) .


Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25 ( OH ) D. Supplementation improved some clinically important HIV immune markers in subjects on HAART .


Adjunct therapy with high-dose , daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation .


To evaluate the immediate effect of repetitive wrist extension on grip strength in patients with distal radial fracture .


Interventional study .


Patients who were admitted to a hospital department of occupational therapy .


Consecutive patients with a unilateral distal radial fracture ( N = 28 ) .


Each patient was randomly allocated to either the experimental group ( n = 14 ) or the control group ( n = 14 ) .


The experimental group performed 30 repetitive wrist extensions with maximal isometric contraction of the extensors of their affected hands during a 6-minute intervention period , whereas the control group did not perform the exercise .


Grip strength was measured just before and after the intervention period .


Pain during grip strength measurements was also quantified using the visual analog scale .


Wrist extension strength was measured 10 minutes after the grip strength measurement .


Grip strength increased immediately after repetitive wrist extension in the experimental group , but it remained the same in the control group .


Visual analog scale scores indicated that pain was relieved only in the experimental group .


However , pain was unrelated to strength production .


The intervention used in this study might be useful during physical examination to reveal the potential grip strength of patients .


The intervention may also be an effective warm-up training procedure in preparation for conventional grip-strengthening exercises .


Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia .


Pregnenolone is neuroprotective and enhances learning and memory , myelination , and microtubule polymerization .


Treatment with pregnenolone elevates allopregnanolone ( a neurosteroid that enhances GABAA receptor responses ) and pregnenolone sulfate ( a positive NMDA receptor modulator ) .


Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids .


The objective of this study is to conduct a randomized controlled trial of adjunctive pregnenolone in schizophrenia .


Following a placebo lead-in , 120 participants were randomized to pregnenolone or placebo for 8 weeks ( Institute for Mental Health , Singapore ) .


Primary endpoints were changes in MATRICS Consensus Cognitive Battery ( MCCB ) composite scores ( cognitive symptoms ) , UCSD Performance-based Skills Assessment-Brief ( UPSA-B ) composite scores ( functional capacity ) , and Scale for Assessment of Negative Symptoms ( SANS ) total scores ( negative symptoms ) .


A modified intent-to-treat analysis approach was utilized .


No significant changes compared to placebo were demonstrated in composite MCCB scores .


In contrast , participants randomized to pregnenolone ( n = 56 ) demonstrated greater improvements in functional capacity ( UPSA-B composite changes ) compared to placebo ( n = 55 ) , p = 0.03 .


Pregnenolone was also superior to placebo in the communication subscale of the UPSA-B ( p < 0.001 ) .


Serum pregnenolone changes post-treatment were correlated with UPSA-B composite score changes in females ( r s = 0.497 , p < 0.042 , n = 17 ) but not in males .


Mean total SANS scores were very low at baseline and did not improve further post-treatment .


Pregnenolone was well-tolerated .


Pregnenolone improved functional capacity in participants with schizophrenia , but did not improve cognitive symptoms over an 8-week treatment period .


Neurosteroid changes correlated with functional improvements in female participants .


Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia .


Polyphenol-rich foods such as pomegranate , green tea , broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis , apoptosis and proliferation .


Although some have been investigated in small , phase II studies , this combination has never been evaluated within an adequately powered randomised controlled trial .


In total , 199 men , average age 74 years , with localised prostate cancer , 60 % managed with primary active surveillance ( AS ) or 40 % with watchful waiting ( WW ) following previous interventions , were randomised ( 2:1 ) to receive an oral capsule containing a blend of pomegranate , green tea , broccoli and turmeric , or an identical placebo for 6 months .


The median rise in PSA in the food supplement group ( FSG ) was 14.7 % ( 95 % confidence intervals ( CIs ) 3.4-36 .7 % ) , as opposed to 78.5 % in the placebo group ( PG ) ( 95 % CI 48.1-115 .5 % ) , difference 63.8 % ( P = 0.0008 ) .


In all , 8.2 % of men in the FSG and 27.7 % in the PG opted to leave surveillance at the end of the intervention ( 2 P = 0.014 ) .


There were no significant differences within the predetermined subgroups of age , Gleason grade , treatment category or body mass index .


There were no differences in cholesterol , blood pressure , blood sugar , C-reactive protein or adverse events .


This study found a significant short-term , favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated , specific blend of concentrated foods .


Its influence on decision-making suggests that this intervention is clinically meaningful , but further trials will evaluate longer term clinical effects , and other makers of disease progression .


To evaluate the efficacy and safety of PMC therapy ( Prednisone , Methotrexate , Chloroquine ) combined Langchuang Fuzheng Jiedu Capsule ( LFJC ) , thus choosing a better therapy of integrative medicine for SLE in the period of glucocorticoid use .


Sixty active SLE patients were randomly assigned to two groups , the control group and the treatment group .


Those in the control group received PMC therapy ( As for Prednisone , it was given at the daily dose of 1 mg/kg till 2 weeks after the condition being stable or after 8 weeks of treatment .


Then the dose was reduced by 10 % every two weeks .


When the dose was reduced to 0.5 mg/kg daily , it was reduced by 2.5 mg per two weeks .


When the dose was reduced to 15 mg daily , the dose was reduced to 2.5 mg per four weeks .


As for Methotrexate , 10 mg each time , once a week .


As for Chloroquine , 100 mg each time , twice daily ) , while those in the treatment group received PMC therapy ( the same way as that for the control group ) combined with LFJC ( consisting of Astragalus membranaceus 50 g , Angelica sinensis 20 g , Ligusticum Chuanxiong 20 g , prepared Rehmannia Rhizome 30 g , Herba Serissae 30 g , Centella 30 g , centipede 4 g , scorpions 10 g , nidus versace 12 g , et al. , 0.5 g per pill , containing 5.7 g crude drug .


When the hormone was given at a large dose , LFJC was administered at 12 pills each time , three times daily ) .


When the hormone was given at a middle dose , LFJC was administered at 8 pills each time , three times daily .


When the hormone was given at a small dose , LFJC was administered at 6 pills each time , three times daily .


The treatment course was six months .


The improvement of symptoms and signs between before and after treatment , SLE disease activity index ( SLEDAI ) , efficacy of Chinese medical syndrome , UPro quantitation , erythrocyte sedimentation rate ( ESR ) , complement 3 ( C3 ) , C-reactive protein ( CRP ) , the reduction and withdrawal of hormones , and infection of the respiratory tract were observed .


The difference in post-SLEDAI was obviously larger in the treatment group than in the control group ( P < 0.05 ) .


The fatigue severity scale ( FSS ) was less after treatment than before treatment in the treatment group , showing statistical difference when compared with that of the control group ( P < 0.05 ) .


The total effective rate was 93.33 % in the treatment group , showing statistical difference when compared with that of the control group ( 86.66 % ; chi2 = 6.736 , P < 0.05 ) .


The ESR decreased after treatment in the treatment group , showing statistical difference when compared with that of the control group ( P < 0.01 ) .


C3 increased after treatment in the treatment group , showing statistical difference when compared with that of the control group ( P < 0.05 ) .


The hormone was reduced to ( 13.70 + / - 5.42 ) mg/d by the end of the therapeutic course in the treatment group , obviously less than that of the control group [ ( 17.63 + / - 7.80 ) mg/d , P < 0.05 ) .


Seven patients suffered from secondary infection of the respiratory tract infection in the treatment group ( 5 from upper respiratory tract infection and 2 from lower respiratory tract infection ) , obviously less than those of the control group ( 25 from upper respiratory tract infection and 10 from lower respiratory tract infection ) ( P < 0.05 ) .


PMC combined LFJC was a better treatment program for severe active SLE ( SLEDAI > or = 15 ) .


It was more safe and effective when compared with using Western medicine alone .


It could enhance the efficacy of hormones and help reduction/withdrawal of hormones .


Infections occur in 30 % of stroke patients and are associated with unfavorable outcomes .


Preventive antibiotic therapy lowers the infection rate after stroke , but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown .


The PASS is a multicenter , prospective , phase three , randomized , open-label , blinded end-point ( PROBE ) trial of preventive antibiotic therapy in acute stroke .


Patients are randomly assigned to either ceftriaxone at a dose of 2 g , given every 24 h intravenously for 4 days , in addition to standard stroke-unit care , or standard stroke-unit care without preventive antibiotic therapy .


The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections .


This paper presents in detail the statistical analysis plan ( SAP ) of the Preventive Antibiotics in Stroke Study ( PASS ) and was submitted while the investigators were still blinded for all outcomes .


The primary outcome is the score on the modified Rankin Scale ( mRS ) , assessed by ordinal logistic regression analysis according to a proportional odds model .


Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome ( mRS 0 to 2 ) versus unfavorable outcome ( mRS 3 to 6 ) .


Secondary outcome measures are death rate at discharge and 3 months , infection rate during hospital admission , length of hospital admission , volume of post-stroke care , use of antibiotics during hospital stay , quality-adjusted life years and costs .


Complications of treatment , serious adverse events ( SAEs ) and suspected unexpected serious adverse reactions ( SUSARs ) are reported as safety outcomes .


The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP .


Current controlled trials ; ISRCTN66140176 .


Date of registration : 6 April 2010 .


Chronic uncomplicated musculoskeletal pain in the spine ( cervical , thoracic or lumbar ) is highly prevalent and may severely limit the daily activities of those affected by it .


To evaluate the efficacy and safety of treatment with auriculopressure applied to patients with non-specific spinal pain .


A multicentre randomised controlled trial with two parallel arms ( true auriculopressure ( TAP ) and placebo auriculopressure ( PAP ) ) was performed .


The intervention phase lasted 8weeks and outcomes were measured 1week after the last intervention ( T1 ) and 6months after baseline ( T2 ) .


The primary outcome measure was change in pain intensity according to a 100mm visual analogue scale ( pain VAS ) at T1 .


Secondary outcome measures were the Lattinen index , the McGill Pain Questionnaire and the SF-12 health-related quality of life scale ( Spanish version in every case ) .


There were 265 participants ( TAP group , n = 130 ; PAP group , n = 135 ) .


Pain was most frequently located in the upper back ( 55.1 % , n = 146 ) , followed by the lower back ( 25.3 % , n = 67 ) and the dorsal area ( 12.5 % , n = 33 ) .


Nineteen patients ( 7.2 % ) reported pain affecting the entire spine .


There were statistically significant differences between TAP and PAP in the change in the pain VAS at T1 of 10mm ( 95 % CI 2.8 to 17.3 , p = 0.007 ) and in the change in the pain VAS at T2 of 7.2 mm ( 95 % CI 0.02 to 14.3 , p = 0.049 ) in favour of TAP .


We also observed a statistically significant difference of 3.4 points in the physical component of the SF-12 in favour of TAP at T2 ( 95 % CI 0.45 to 6.3 , p = 0.024 ) .


No severe adverse effects were detected or reported during treatment .


The application of auriculopressure in patients with non-specific spinal pain in primary healthcare is effective and safe , and therefore should be considered for inclusion in the portfolio of primary healthcare services .


ISRCTN01897462 .


To compare changes in intraocular pressure ( IOP ) immediately after clear corneal incision ( CCI ) cataract surgery between eyes in which IOP was adjusted to a high or normal range at the conclusion of surgery .


Hayashi Eye Hospital , Fukuoka , Japan .


Comparative case series .


Either eye of patients scheduled for phacoemulsification was randomized to 1 of 2 groups as follows : eyes that were to be adjusted to ( 1 ) high IOP ( 22 to 40 mm Hg ) or ( 2 ) normal IOP ( 10 to 21 mm Hg ) .


The IOP was measured using a rebound tonometer preoperatively ; at the conclusion of surgery ; and 15 , 30 , 60 , 120 , and 180 minutes and 24 hours postoperatively .


The Seidel test and anterior segment optical coherence tomography ( AS-OCT ) were performed .


The mean IOP at the conclusion of surgery was 31.3 mm Hg in the high IOP group and 17.1 mm Hg in the normal IOP group .


The IOP decreased to approximately 15 mm Hg by 15 minutes and did not change until 60 minutes in either group .


The mean IOP did not differ significantly between groups throughout the observation period ( P .0634 ) .


Hypotony of 5 mm Hg or less was not detected in any eye .


The Seidel test was negative and based on AS-OCT , the wound was closed at 60 minutes in all eyes .


After adjusting IOP to a high or normal range , the IOP normalized within 15 minutes postoperatively and was stable for 24 hours .


The wound was closed within 60 minutes postoperatively .


Bacillus Calmette-Gurin ( BCG ) is considered the most effective treatment to reduce recurrence and progression of non-muscle invasive bladder cancer ( NMIBC ) but can induce local side effects leading to treatment discontinuation or interruption .


Aim of this exploratory study is to investigate if the sequential administration of Hyaluronic acid ( HA ) may reduce local side effects of BCG .


30 consecutive subjects undergoing BCG intravesical administration for high risk NMIBC were randomized to receive BCG only ( Group A ) or BCG and HA ( Group B ) .


A 1 to 10 Visual Analog Scale ( VAS ) for bladder pain , International Prostate Symptom Score ( IPSS ) and number of micturitions per day were evaluated in the two groups before and after six weekly BCG instillations .


Patients were also evaluated at 3 and 6 months by means of cystostopy and urine cytology .


One out of 30 ( 3,3 % ) patients in group A dropped out from the protocol , for local side effects .


Mean VAS for pain was significantly lower in group B after BCG treatment ( 4.2 vs. 5.8 , p = 0.04 ) .


Post vs. pre treatment differences in VAS for pain , IPSS and number of daily micturitions were all significantly lower in group B. Three patients in group A and 4 in group B presented with recurrent pathology at 6 month follow up .


These preliminary data suggest a possible role of HA in reducing BCG local side effects and could be used to design larger randomized controlled trials , assessing safety and efficacy of sequential BCG and HA administration .


NCT02207608 ( ClinicalTrials.gov ) 01/08/2014 .


Policlinico Tor Vergata Ethics Committee , resolution n 69-2011 .


Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 ( HER2 ) - positive breast cancer were first reported in 2005 .


One of these reports , the joint analysis of North Central Cancer Treatment Group NCCTG N9831 ( Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer ) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 ( Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2 ) , was updated in 2011 .


We now report the planned definitive overall survival ( OS ) results from this joint analysis along with updates on the disease-free survival ( DFS ) end point .


In all , 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in both trials .


The required number of events for the definitive statistical analysis for OS ( 710 events ) was reached in September 2012 .


Updated analyses of overall DFS and related subgroups were also performed .


Median time on study was 8.4 years .


Adding trastuzumab to chemotherapy led to a 37 % relative improvement in OS ( hazard ratio [ HR ] , 0.63 ; 95 % CI , 0.54 to 0.73 ; P < .001 ) and an increase in 10-year OS rate from 75.2 % to 84 % .


These results were accompanied by an improvement in DFS of 40 % ( HR , 0.60 ; 95 % CI , 0.53 to 0.68 ; P < .001 ) and increase in 10-year DFS rate from 62.2 % to 73.7 % .


All patient subgroups benefited from addition of this targeted anti-HER2 agent .


The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence .


Optimal therapy for children and adolescents with advanced stage anaplastic large cell lymphoma ( ALCL ) is unknown .


ANHL0131 examined whether a maintenance regimen including vinblastine compared to the standard APO ( doxorubicin , prednisone , vincristine , methotrexate , 6-mercaptopurine ) regimen would result in superior event-free survival .


One hundred and twenty five eligible patients were enrolled .


Induction was identical for both arms .


Post induction patients were randomized to receive APO with vincristine every 3 weeks or a regimen that substituted vincristine with weekly vinblastine ( APV ) .


There was no difference between the patients randomized to the APO versus APV arms in either event free survival ( EFS ) or overall survival ( OS ) ( three year EFS 74 % vs. 79 % , P = 0.68 and three years OS of 84 % vs. 86 % , P = 0.87 , respectively ) .


Patients in the APV arm required dose reduction secondary to myelosuppression and had a higher incidence of neutropenia as well as infection with neutropenia compared to those in the APO arm ( P < 0.001 , P = 0.019 , respectively ) .


Treatment with weekly vinblastine instead of every three week vincristine as part of multi-agent maintenance therapy did not result in improvement in EFS or OS .


Weekly vinblastine was associated with increased toxicity .


( ClinicalTrials.gov Identifier NCT00059839 ) .


Multiple sclerosis ( MS ) treatment options are primarily limited to immunomodulatory therapies in MS non-progressive forms .


Nutrition intervention studies suggest that diet may be considered as a complementary treatment to control disease progression .


Therefore , dietary intervention may help to improve wellness and ameliorate symptoms of MS patients .


To assess the effect of a low-fat diet with antioxidant supplementation on biochemical markers of institutionalized patients with progressive forms of multiple sclerosis .


A randomized prospective placebo-controlled study involving 9 participants , 5 of them assigned to the intervention group ( low-fat diet and antioxidant supplementation ) and the other 4 to the placebo group ( low-fat diet ) .


The effect of the dietary intervention , involving diet modification and antioxidant supplementation , was examined for 42 days by measuring anthropometric , biochemical parameters and oxidative stress markers in blood at baseline ( day 0 ) , intermediate ( day 15 ) and end ( day 42 ) stages of the treatment .


The intervention group obtained C reactive protein levels significantly lower than those observed in the corresponding placebo group at the end of the study .


Oxidative stress and inflammatory markers isoprostane 8-iso-PGF2 and interleukine IL-6 values also diminished after dietary intervention in the intervention group .


Catalase activity increased significantly in the intervention group prior antioxidant supplementation .


No significant differences were observed in other oxidative stress markers .


The results suggest that diet and dietary supplements are involved in cell metabolism modulation and MS-related inflammatory processes .


Consequently , low fat diets and antioxidant supplements may be used as complementary therapies for treatment of multiple sclerosis .


To compare the effects between dezocine and flurbiprofen axetil on postoperative sore throat ( POST ) after maxillofacial procedures .


In the study , 90 adult patients with maxillofacial diseases were divided randomly into control group ( group C ) , flurbiprofen group ( group F ) and dezocine group ( group D ) .


Physiological saline , flurbiprofen axetil ( 1 mg/kg ) and dezocine ( 0.1 mg/kg ) were administered intravenously for each group 30 minutes before the end of the operation .


We recorded visual analogue scale ( VAS ) and Bruggrmann comfort scale ( BCS ) at the time points of 0.5 h , 1 h , 2 h , and 6 h after extubation .


The incidence of POST in group D decreased significantly ( P < 0.05 ) .


There was no difference between the incidences of groups F and C.


The VAS of group F was lower than that of group C ( P < 0.01 ) just at the time points of 0.5 h and 1 h after extubation , from then on , there was no difference between the 2 groups .


The VAS of group D was lower than that of group F , and the BCS was higher than that of group F significantly .


Dezocine has notable analgesia effect for postoperative sore throat , so it is a better choice to carry out postoperative analgesia after maxillofacial procedures .


Only a few studies have provided information on awareness , use , and harm perceptions of e-cigarettes in Europe .


We fill the knowledge gap in Italy .


We used data from a face-to-face survey conducted in 2013 of a sample of 3,000 individuals , representative of the Italian population aged 15 years ( 51.1 million inhabitants ) .


Awareness of e-cigarettes was 91.1 % ; it was lowest among women ( 87.8 % ) , the elderly ( 78.4 % ) , those with less education ( 84.1 % ) , and never-smokers ( 89.0 % ) .


Ever e-cigarette use was 6.8 % overall and was inversely related to age , whereas no significant difference was observed according to sex .


With regard to smoking status , 2.6 % of never-smokers , 7.0 % of ex-smokers , and 20.4 % of current smokers tried the e-cigarette at least once .


Regular e-cigarette use was 1.2 % overall , 1.5 % among men , and 0.9 % among women , and it was highest among young ( 2.4 % ) and current smokers ( 3.7 % ) .


Among 36 e-cigarette regular users , 22.0 % did not change their smoking habit , 67.7 % reduced traditional cigarette consumption , and 10.4 % quit smoking .


After fewer than 3 years from the opening of the first Italian e-cigarette shop , more than 45 million Italians have heard about e-cigarettes , 3.5 million have tried e-cigaretts , and more than 600,000 Italians regularly use e-cigarettes .


Three out of 4 e-cigarette users reported to have favorably modified their smoking habit ; however , 90 % of users did not quit smoking as a consequence of starting vaping e-cigarettes .


Almost 900,000 Italian never-smokers , particularly young never-smokers , have tried this new and potentially addictive product at least once .


It has been suggested that perturbations in branched-chain amino acid ( BCAA ) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs .


Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism , but there is limited evidence in humans .


We hypothesize that a diet rich in BCAAs will increase BCAA catabolism , which will manifest in a reduction of fasting plasma BCAA concentrations .


The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry .


Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey ( whey group , n = 16 ) or gelatin ( gelatin group , n = 11 ) protein supplement .


When matched for total protein by weight , whey protein has 3 times the amount of BCAAs compared with gelatin protein .


Postintervention plasma abundances of Ile ( gelatin group : 637 18 , quantifier ion peak height 100 ; whey group : 744 65 ) , Leu ( gelatin group : 1210 33 ; whey group : 1380 79 ) , and Val ( gelatin group : 2080 59 ; whey group : 2510 230 ) did not differ between treatment groups .


BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline ( r = 0.52 , 0.43 , and 0.49 for Leu , Ile , and Val , respectively ; all , P < 0.05 ) , but correlations were no longer significant at postintervention .


Pro- and Cys-related pathways were found discriminant of whey protein vs. gelatin protein supplementation in multivariate statistical analyses .


These findings suggest that BCAA metabolism is , at best , only modestly affected at a whey protein supplementation dose of 20 g/d .


Furthermore , the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity .


This trial was registered at clinicaltrials.gov as NCT00739479 .


The aim was to study a client-centred activities of daily living ( ADL ) intervention ( CADL ) compared with the usual ADL intervention ( UADL ) in people with stroke regarding : independence in ADL , perceived participation , life satisfaction , use of home-help service , and satisfaction with training and , in their significant others , regarding : caregiver burden , life satisfaction , and informal care .


In this multicentre study , 16 rehabilitation units were randomly assigned to deliver CADL or UADL .


The occupational therapists who provided the CADL were specifically trained .


Eligible for inclusion were people with stroke treated in a stroke unit 3 months after stroke , dependent in two ADL , not diagnosed with dementia , and able to understand instructions .


Data were collected at inclusion and three months thereafter .


To detect a significant difference between the groups in the Stroke Impact Scale ( SIS ) domain `` participation '' , 280 participants were required .


Intention-to-treat analysis was applied .


At three months , there was no difference in the outcomes between the CADL group ( n = 129 ) and the UADL group ( n = 151 ) , or their significant others ( n = 87/n = 93 ) except in the SIS domain `` emotion '' in favour of CADL ( p = 0.04 ) .


The CADL does not appear to bring about short-term differences in outcomes and longer follow-ups are required .


Early nutrition is recognized as a target for the effective prevention of childhood obesity .


Protein intake was associated with more rapid weight gain during infancy-a known risk factor for later obesity .


We tested whether the reduction of protein in infant formula reduces body mass index ( BMI ; in kg/m ( 2 ) ) and the prevalence of obesity at 6 y of age .


The Childhood Obesity Project was conducted as a European multicenter , double-blind , randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004 .


Formula-fed infants ( n = 1090 ) were randomly assigned to receive higher protein ( HP ) - or lower protein ( LP ) - content formula ( within recommended amounts ) in the first year of life ; breastfed infants ( n = 588 ) were enrolled as an observational reference group .


We measured the weight and height of 448 ( 41 % ) formula-fed children at 6 y of age .


BMI was the primary outcome .


HP children had a significantly higher BMI ( by 0.51 ; 95 % CI : 0.13 , 0.90 ; P = 0.009 ) at 6 y of age .


The risk of becoming obese in the HP group was 2.43 ( 95 % CI : 1.12 , 5.27 ; P = 0.024 ) times that in the LP group .


There was a tendency for a higher weight in HP children ( 0.67 kg ; 95 % CI : -0.04 , 1.39 kg ; P = 0.064 ) but no difference in height between the intervention groups .


Anthropometric measurements were similar in the LP and breastfed groups .


Infant formula with a lower protein content reduces BMI and obesity risk at school age .


Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity .


This trial was registered at clinicaltrials.gov as NCT00338689 .


Effective treatment algorithms are needed to guide diabetes care at hospital discharge in general medicine and surgery patients with type 2 diabetes .


This was a prospective , multicenter open-label study aimed to determine the safety and efficacy of a hospital discharge algorithm based on admission HbA1c .


Patients with HbA1c < 7 % ( 53.0 mmol/mol ) were discharged on their preadmission diabetes therapy , HbA1c between 7 and 9 % ( 53.0-74 .9 mmol/mol ) were discharged on a preadmission regimen plus glargine at 50 % of hospital daily dose , and HbA1c > 9 % were discharged on oral antidiabetes agents ( OADs ) plus glargine or basal bolus regimen at 80 % of inpatient dose .


The primary outcome was HbA1c concentration at 12 weeks after hospital discharge .


A total of 224 patients were discharged on OAD ( 36 % ) , combination of OAD and glargine ( 27 % ) , basal bolus ( 24 % ) , glargine alone ( 9 % ) , and diet ( 4 % ) .


The admission HbA1c was 8.7 2.5 % ( 71.6 mmol/mol ) and decreased to 7.3 1.5 % ( 56 mmol/mol ) at 12 weeks of follow-up ( P < 0.001 ) .


The change of HbA1c from baseline at 12 weeks after discharge was -0.1 0.6 , -0.8 1.0 , and -3.2 2.4 in patients with HbA1c < 7 % , 7-9 % , and > 9 % , respectively ( P < 0.001 ) .


Hypoglycemia ( < 70 mg/dL ) was reported in 22 % of patients discharged on OAD only , 30 % on OAD plus glargine , 44 % on basal bolus , and 25 % on glargine alone and was similar in patients with admission HbA1c 7 % ( 26 % ) compared with those with HbA1c > 7 % ( 31 % , P = 0.54 ) .


Measurement of HbA1c on admission is beneficial in tailoring treatment regimens at discharge in general medicine and surgery patients with type 2 diabetes .


The primary target cells for the human immunodeficiency virus ( HIV ) infection in the genital tract are CD4 T cells that express CCR5 on the surface .


Alterations in genital tract T cells that express CCR5 could impact HIV acquisition risk .


We hypothesized that , when compared with baseline , the use of a hormonal intrauterine device ( IUD ) would alter HIV target cells ( primarily CCR5 + CD4 cells ) in the female genital tract more than a nonhormonal IUD .


Thirty-four healthy HIV-negative women aged 18-40 years who were seeking an IUD for contraception were assigned randomly to receive a levonorgestrel IUD or a copper T380A IUD .


A parallel group of 8 control women who did not need contraception was also enrolled .


Genital tract mucosal immune cell populations that were collected by cervical cytobrush and endometrial biopsy before and 2 months after IUD placement were analyzed by flow cytometry .


Mean differences in cell number and percent that expressed receptors from baseline to follow-up examination were evaluated with the use of paired Student t tests .


Neither IUD altered the number of T cells within the upper and lower genital tracts .


Levonorgestrel IUD users had a decrease in T cells that expressed the HIV coreceptor CCR5 in the endometrium and cervix after 2 months of use compared with baseline .


There was a decrease in activated endometrial T cells in levonorgestrel IUD users and a decrease in activated cervical T cells in copper IUD users after 2 months of IUD use , compared with baseline .


Women who use IUDs have reduced expression of the CCR5 HIV coreceptor on T cells in the endometrium and cervix compared with expression before IUD placement .


These findings suggest that susceptibility to HIV infection would not be increased by IUD use .


To investigate the hospital cost and short-term clinical outcome of traditional minimally invasive hysterectomy vs robot-assisted hysterectomy in women primarily not considered candidates for vaginal surgery .


Randomized controlled trial ( Canadian Task Force classification I ) .


University Hospital in Sweden .


One hundred twenty-two women with uterine size 16 gestational weeks scheduled to undergo minimally invasive hysterectomy because of benign disease .


Robot-assisted hysterectomy or traditional vaginal or laparoscopic minimally invasive hysterectomy .


All women underwent surgery as randomized .


There were no demographic differences between the 2 groups .


Vaginal hysterectomy was possible in 41 % in the traditional minimally invasive group , at a mean hospital cost of $ 4579 compared with $ 7059 for traditional laparoscopic hysterectomy .


This was reflected in a mean hospital cost of $ 993 more per robotic-assisted hysterectomy than for traditional minimally invasive hysterectomy when the robot was a preexisting investment .


This hospital cost increased by $ 1607 when including investments and cost of maintenance .


A per-protocol subanalysis comparing laparoscopy and robotics demonstrated similar hospital cost when the robot was a preexisting investment ( $ 7059 vs $ 7016 ) .


Robotic-assisted hysterectomy was associated with less blood loss and fewer postoperative complications .


A similar hospital cost can be attained for laparoscopy and robotics when the robot is a preexisting investment .


From the perspective of hospital costs , robotic-assisted hysterectomy is not advantageous for treating benign conditions when a vaginal approach is feasible in a high proportion of patients .


National Institutes of Health Stroke Scale ( NIHSS ) item profiles that were recently proposed may prove useful both clinically and for research studies .


We aimed to validate the NIHSS item profiles in an acute cohort .


We conducted a retrospective analysis on pooled data from randomized clinical trials .


We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping , a-NIHSS item profiles .


We implemented an independent latent class analysis to derive secondary symptom grouping , b-NIHSS item profiles .


Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles ' discrimination and calibration to the data .


The outcomes evaluated included modified Rankin Scale ( mRS ; using the full distribution and dichotomized , mRS , 0-1 ) at day 90 and mortality by 90 days .


We identified 10 271 patients .


Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner , adjusted for age and thrombolysis treatment , for each set of NIHSS item profiles .


Similar patterns were observed for mRS 0 to 1 , and inverse patterns were seen for mortality .


The c-statistics of a-NIHSS and b-NIHSS item profiles for mRS 0 to 1 were similar at 0.71 ( 95 % confidence interval , 0.70-0 .72 ) and for mortality , 0.74 ( 0.73-0 .75 ) and 0.75 ( 0.73-0 .76 ) , respectively .


Calibration was good .


These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke .


This approach has the potential to enhance the clinical value of the overall NIHSS score .


The current study was undertaken to investigate the efficacy and safety of erlotinib versus pemetrexed as second-line therapy for patients with advanced epidermal growth factor receptor ( EGFR ) wild-type and EGFR fluorescence in situ hybridization ( FISH ) - positive lung adenocarcinoma .


In this open-label , randomized , phase 2 study , patients with EGFR wild-type and EGFR FISH-positive adenocarcinoma who had developed disease progression after 1 prior platinum-based chemotherapy were randomly assigned ( 1:1 ) to receive erlotinib or pemetrexed until the time of disease progression or death , unacceptable toxicity , or a request for discontinuation by the patient .


The primary endpoint was progression-free survival ( PFS ) .


A total of 123 patients were enrolled ( 61 in the erlotinib arm and 62 in the pemetrexed arm ) .


The median PFS was 4.1 months ( 95 % confidence interval [ 95 % CI ] , 1.6 months-6 .6 months ) in the erlotinib group versus 3.9 months ( 95 % CI , 2.7 months-5 .1 months ) in the pemetrexed group .


The difference in PFS between the 2 treatment groups was not significant ( hazard ratio , 0.92 ; 95 % CI , 0.62-1 .37 [ P = .683 ] ) .


The objective response rate appeared to be higher among patients receiving erlotinib compared with those receiving pemetrexed ( 19.7 % vs 8.1 % ; P = .062 ) .


The 3 most commonly recorded adverse events were rash ( 54.1 % ) , fatigue ( 19.7 % ) , and diarrhea ( 16.4 % ) in the erlotinib group and fatigue ( 25.8 % ) , nausea ( 24.2 % ) , and anorexia ( 14.5 % ) in the pemetrexed group .


There were no significant differences noted with regard to efficacy between erlotinib and pemetrexed in the second-line setting for patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma .


Both regimens appear to be effective treatment options for these patients .


To examine the impact of a weight loss intervention upon follicle stimulating hormone ( FSH ) levels in postmenopause .


Participants were postmenopausal , overweight , glucose-intolerant women not using exogenous estrogen ( n = 382 ) in the Diabetes Prevention Program .


Women were randomized to intensive lifestyle change ( ILS ) with the goals of weight reduction of at least 7 % of initial weight and 150 min per week of moderate-intensity exercise , metformin 850 mg twice a day , or placebo administered twice a day .


Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo ( 2.3 IU/l vs. -0.81 IU/l , P < 0.01 ) .


Increases in FSH were correlated with decreases in weight ( r = -0.165 , P < 0.01 ) and estradiol ( E2 ) ( r = -0.464 , P < 0.0001 ) after adjustment for age , race/ethnicity , and randomization arm .


Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels .


Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo .


Weight loss leads to small increases in FSH among overweight , postmenopausal women , potentially through pathways mediated by endogenous estrogen as well as other pathways .


Low levels of physical activity ( PA ) are associated with poor outcomes in people with COPD .


Interventions to increase PA could improve outcomes .


We tested the efficacy of a novel Internet-mediated , pedometer-based exercise intervention .


Veterans with COPD ( N = 239 ) were randomized in a 2:1 ratio to the ( 1 ) intervention group ( Omron HJ-720 ITC pedometer and Internet-mediated program ) or ( 2 ) wait-list control group ( pedometer ) .


The primary outcome was health-related quality of life ( HRQL ) , assessed by the St. George 's Respiratory Questionnaire ( SGRQ ) , at 4 months .


We examined the SGRQ total score ( SGRQ-TS ) and three domain scores : Symptoms , Activities , and Impact .


The secondary outcome was daily step counts .


Linear regression models assessed the effect of intervention on outcomes .


Participants had a mean age of 67 9 years , and 94 % were men .


There was no significant between-group difference in mean 4-month SGRQ-TS ( 2.3 units , P = .14 ) .


Nevertheless , a significantly greater proportion of intervention participants than control subjects had at least a 4-unit improvement in SGRQ-TS , the minimum clinically important difference ( 53 % vs 39 % , respectively , P = .05 ) .


For domain scores , the intervention group had a lower ( reflecting better HRQL ) mean than the control group by 4.6 units for Symptoms ( P = .046 ) and by 3.3 units for Impact ( P = .049 ) .


There was no significant difference in Activities score between the two groups .


Compared with the control subjects , intervention participants walked 779 more steps per day at 4 months ( P = .005 ) .


An Internet-mediated , pedometer-based walking program can improve domains of HRQL and daily step counts at 4 months in people with COPD .


Clinical Trials.gov ; No. : NCT01102777 ; URL : www.clinicaltrials.gov .


To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years .


Ten-year follow-up of a randomized , controlled single-blind trial ( Advanced Cognitive Training for Independent and Vital Elderly ( ACTIVE ) ) with three intervention groups and a no-contact control group .


Six U.S. cities .


A volunteer sample of 2,832 persons ( mean baseline age 73.6 ; 26 % African American ) living independently .


Ten training sessions for memory , reasoning , or speed of processing ; four sessions of booster training 11 and 35 months after initial training .


Objectively measured cognitive abilities and self-reported and performance-based measures of everyday function .


Participants in each intervention group reported less difficulty with instrumental activities of daily living ( IADLs ) ( memory : effect size = 0.48 , 99 % confidence interval ( CI ) = 0.12-0 .84 ; reasoning : effect size = 0.38 , 99 % CI = 0.02-0 .74 ; speed of processing : effect size = 0.36 , 99 % CI = 0.01-0 .72 ) .


At a mean age of 82 , approximately 60 % of trained participants , versus 50 % of controls ( P < .05 ) , were at or above their baseline level of self-reported IADL function at 10 years .


The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years ( reasoning : effect size = 0.23 , 99 % CI = 0.09-0 .38 ; speed of processing : effect size = 0.66 , 99 % CI = 0.43-0 .88 ) .


Memory training effects were no longer maintained for memory performance .


Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance ( effect size = 0.21 , 99 % CI = 0.01-0 .41 ) and the speed-of-processing intervention for speed-of-processing performance ( effect size = 0.62 , 99 % CI = 0.31-0 .93 ) .


Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self-reported IADL compared with the control group .


Reasoning and speed , but not memory , training resulted in improved targeted cognitive abilities for 10 years .


Attention deficits are often among the most persistent and debilitating impairments resulting from traumatic brain injury ( TBI ) .


This study examined the effects of lisdexamfetamine dimesylate ( Vyvanse ) in treating attention deficits due to moderate-to-severe TBI .


It was the first study of lisdexamfetamine dimesylate with this population and , in fact , was the first controlled trial in this area examining a stimulant medication option other than methylphenidate .


This was a 12-week , randomized , double-blind , placebo-controlled , cross-over trial .


A total of 22 rigorously selected cases were enrolled , 13 of whom completed the trial .


They were 16-42 years of age and had newly acquired attention deficits persisting for 6-34 months post-injury .


They were assessed on a broad range of neuropsychological and behavioural measures at baseline , 6-weeks and at 12-weeks .


Positive treatment effects were found involving selective measures of sustained attention , working memory , response speed stability and endurance and in aspects of executive functioning .


No major problems with safety or tolerability were observed .


Some moderating treatment effects were found from a broad range of pre-treatment subject characteristics and injury variables examined .


Avenues for further research and treatment applications in this area are discussed .


Extended sitting time at work is viewed as a crucial public health issue .


Encouraging workers to stand during their office hours via the installation of standing desks maybe one effective option to combat this .


Here , we investigate whether the installation of high desks in the workplace can induce positive changes in the amount of physical activity ( PA ) and thereby lead to subsequent improvements in anthropometric parameters .


Thirty-two white-collar workers ( 22 men and 10 women , mean age 44.2 ) were randomly divided into two groups .


A randomised crossover trial was performed for 13 weeks .


During the experimental period , subjects completed their office work in a standing position using stationary high desks ( standing work , SW ) for 10 hours per week or more ( SW period ) .


The subjects were asked to maintain their normal sitting working habits during the control period ( CONT period ) .


The primary outcome was PA , which was assessed objectively using a triaxial accelerometer during weekdays and weekends .


The secondary outcomes were anthropometric measurements .


For each group and each parameter , the mean values during each period were recorded and were compared by paired t test .


The daily total PA ( 10.2 2.4 vs. 9.7 2.3 METs h/day , P = 0.043 ) , MVPA ( 4.2 2.2 vs. 3.7 1.8 METs h/day , P = 0.025 ) , time spent in moderate PA ( 58.2 20.7 vs. 53.4 17.0 min/day , P = 0.019 ) and time spent in MVPA ( 62.8 25.1 vs. 57.0 20.3 min/day , P = 0.019 ) were significantly higher during the SW period compared to the CONT period .


A weekdays verses weekends subanalysis revealed that these parameters were significantly higher during the SW period compared to the CONT period during weekdays only .


No significant differences were noted before and after SW periods for most of the anthropometric measures , except waist circumference ( 83.7 7.9 vs. 83.0 7.9 cm , respectively , P = 0.007 ) .


Standing work , via the installation of high desks , significantly increases moderate to vigorous physical activity , especially on weekdays .


UMIN-CRT , UMIN000016731 , 7th March 2015 .


The aims of this study were to investigate the short-term benefit of etanercept ( ETN ) + MTX vs conventional synthetic DMARDs ( csDMARDs ; HCQ , LEF or SSZ ) + MTX in subjects with established RA .


The effect of disease duration ( 2 years vs > 2 years ) and severity ( moderate vs severe ) on treatment outcomes was also assessed .


Methods .


Data from Asian and Latin American subjects with inadequate response to MTX were pooled from the APPEAL ( ETN 25 mg biweekly + MTX or csDMARD + MTX ; NCT00422227 ) and Latin RA ( ETN 50 mg/week + MTX or csDMARD + MTX ; NCT00848354 ) studies .


Endpoints included the 28-joint DAS with ESR ( DAS28-ESR ) low disease activity ( LDA ; 3.2 ) , DAS28 remission ( < 2.6 ) and HAQ score 0.5 .


Four hundred seventy-eight subjects received ETN + MTX , 245 subjects received csDMARD + MTX [ HCQ + MTX ( n = 81 ) , LEF + MTX ( n = 69 ) , SSZ + MTX ( n = 95 ) ] .


At week 16 , significantly more subjects receiving ETN + MTX vs subjects on csDMARDs + MTX achieved DAS28-ESR LDA ( 39 % vs 18 % , P < 0.001 ) , remission ( 18 % vs 7 % , P < 0.001 ) and HAQ 0.5 ( 48 % vs 34 % , P < 0.001 ) .


For both treatment arms , these endpoints were achieved by a greater proportion of subjects with 2 years vs > 2 years disease duration and with moderate vs severe disease activity .


Overall , ETN + MTX was more effective in treating subjects with established RA than csDMARDs + MTX at 16 weeks .


More subjects with shorter disease duration and moderate disease activity achieved optimal response regardless of treatment regimen .


clinicaltrials.gov , NCT00422227 and NCT00848354 .


The National Emphysema Treatment Trial ( NETT ) was a randomized clinical trial designed to compare lung volume reduction surgery ( LVRS ) with maximal medical care for patients with severe emphysema .


The trial was halted early for a subgroup of patients with severe lung disease .


We report longer term follow-up for this high-risk subgroup .


In a randomized clinical trial , patients with moderate to severe emphysema were assigned to LVRS plus maximal medical care or to maximal medical care alone and followed prospectively for vital status over 15 years .


We focus on 140 high-risk patients .


Quality of life data were available through 6 years of follow-up and were assessed using the University of California , San Diego Shortness of Breath Questionnaire and the Self-Administered Quality of Well-Being Scale .


Through the first 3 years of follow-up , surgical patients in the high-risk subgroup had a significantly higher probability of death .


However , the mortality curves crossed and there was a trend favoring surgical treatment through the remainder of the follow-up .


The log-rank test suggested that the 2 groups were not significantly different ( p = 0.95 ) in survival .


Quality of life data suggested an advantage of LVRS through the first 5 years of follow-up ( p < 0.01 ) .


The combined quality-adjusted survival model favored the medical group for the first few years of follow-up and favored the LVRS group after 4 years .


The NETT was stopped early for high-risk patients with severe lung disease .


Longer term follow-up suggests that surgical patients in this high-risk subgroup ultimately achieved comparable outcomes .


The high risk of death within 30 days of the surgery may discourage use of the procedure for high-risk patients despite the potential for better long-term outcomes .


Docosahexaenoic acid ( DHA ) accumulates in the hippocampus and frontal lobes of the fetal brain during the last trimester of pregnancy .


These areas of the brain contribute to attention and working memory and inhibitory control ( WMIC ) .


We evaluated the effect of maternal omega-3 ( n-3 ) long-chain polyunsaturated fatty acid supplementation in pregnancy on child attention and WMIC .


A total of 185 term-born children of mothers who were randomly allocated to consume 800 mg DHA/d ( treatment ) or a placebo ( control ) from 20 wk of gestation until birth were assessed with multiple measures of attention and WMIC at a mean ( SD ) of 27 2 mo. .


Primary outcomes were the average time it took to be distracted when playing with a toy ( distractibility ) and the accuracy of remembering a new hiding location while inhibiting a learned response to search in the previous location ( WMIC ) .


Assessments were completed by 81 children in the treatment group ( mean SD age : 835 50.4 d ) and 77 children in the control group ( 839 65.6 d ) .


There was no effect of supplementation on primary outcomes [ distractibility mean difference : -0.2 s ( 95 % CI : -0.7 , 0.4 s ) ; WMIC mean difference : 8.9 mm ( 95 % CI : -10.6 , 28.3 mm ) ] .


There was no difference between DHA-supplemented and control groups except that treatment-group children looked away from the toys fewer times than controls when presented with multiple toys competing for attention but less accurately remembered a repeated hiding location .


These secondary effects were not consistent with any other outcomes and may have been a result of chance .


Cord plasma DHA was not consistently associated with attention and WMIC .


Maternal DHA supplementation during pregnancy does not enhance attention or WMIC in term-born preschoolers .


The DHA for Maternal and Infant Outcomes trial was registered at www.anzctr.org.au as ACTRN1260500056906 .


Oral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial .


To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica .


Randomized , double-blind , placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California .


Adults ( n = 269 ) with radicular pain for 3 months or less , an Oswestry Disability Index ( ODI ) score of 30 or higher ( range , 0-100 ; higher scores indicate greater dysfunction ) , and a herniated disk confirmed by magnetic resonance imaging were eligible .


Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone ( 5 days each of 60 mg , 40 mg , and 20 mg ; total cumulative dose = 600 mg ; n = 181 ) or matching placebo ( n = 88 ) .


The primary outcome was ODI change at 3 weeks ; secondary outcomes were ODI change at 1 year , change in lower extremity pain ( measured on a 0-10 scale ; higher scores indicate more pain ) , spine surgery , and Short Form 36 Health Survey ( SF-36 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores ( 0-100 scale ; higher scores better ) .


Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group , respectively .


The prednisone-treated group showed an adjusted mean 6.4-point ( 95 % CI , 1.9-10 .9 ; P = .006 ) greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point ( 95 % CI , 2.2-12 .5 ; P = .005 ) greater improvement at 52 weeks .


Compared with the placebo group , the prednisone group showed an adjusted mean 0.3-point ( 95 % CI , -0.4 to 1.0 ; P = .34 ) greater reduction in pain at 3 weeks and a mean 0.6-point ( 95 % CI , -0.2 to 1.3 ; P = .15 ) greater reduction at 52 weeks .


The prednisone group showed an adjusted mean 3.3-point ( 95 % CI , 1.3-5 .2 ; P = .001 ) greater improvement in the SF-36 PCS score at 3 weeks , no difference in the SF-36 PCS score at 52 weeks ( mean , 2.5 ; 95 % CI , -0.3 to 5.4 ; P = .08 ) , no change in the SF-36 MCS score at 3 weeks ( mean , 2.2 ; 95 % CI , -0.4 to 4.8 ; P = .10 ) , and an adjusted 3.6-point ( 95 % CI , 0.6-6 .7 ; P = .02 ) greater improvement in the SF-36 MCS score at 52 weeks .


There were no differences in surgery rates at 52-week follow-up .


Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group ( 49.2 % vs 23.9 % ; P < .001 ) .


Among patients with acute radiculopathy due to a herniated lumbar disk , a short course of oral steroids , compared with placebo , resulted in modestly improved function and no improvement in pain .


clinicaltrials.gov Identifier : NCT00668434 .