We report a clinical trial of attentional retraining in treatment-seeking smokers .


This was a double-blind randomised controlled trial that took place in UK smoking cessation clinics .


Smokers interested in quitting were randomised to five weekly sessions of attentional retraining ( N = 60 ) or placebo training ( N = 58 ) using a modified visual probe task from one week prior to quit day .


Both groups received 21 mg nicotine patches ( from quit day onwards ) and behavioural support .


Primary outcomes included change in attentional bias reaction times four weeks after quit day on the visual probe task and craving measured weekly using the Mood and Physical Symptoms Scale .


Secondary outcomes were changes in withdrawal symptoms , time to first lapse and prolonged abstinence .


No attentional bias towards smoking cues was found in the sample at baseline ( mean difference = 3 ms , 95 % CI = -2 , 9 ) .


Post-training bias was not significantly lower in the retraining group compared with the placebo group ( mean difference = -9 ms , 95 % CI = -20 , 2 ) .


There was no difference between groups in change in craving ( p = 0.89 ) and prolonged abstinence at four weeks ( risk ratio = 1.00 , 95 % CI = 0.70 , 1.43 ) .


Taken with one other trial , there appears to be no effect from clinic-based attentional retraining using the visual probe task .


Attentional retraining conducted out of clinic may prove more effective .


UK Clinical Trials ISRCTN 54375405 .


During team athletic events , athletic trainers commonly provide fluids with water bottles .


When a limited number of water bottles exist , various techniques are used to deliver fluids .


To determine whether fluid delivered via water-bottle administration influenced fluid consumption and hydration status .


Crossover study .


Outdoor field ( 22.2 C 3.5 C ) .


Nineteen participants ( 14 men , 5 women , age = 30 10 years , height = 176 8 cm , mass = 72.5 10 kg ) were recruited from the university and local running clubs .


The independent variable was fluid delivery with 3 levels : self-administration with mouth-to-bottle direct contact ( SA-DC ) , self-administration with no contact between mouth and bottle ( SA-NC ) , and external administration with no contact between the mouth and the bottle ( EA-NC ) .


Participants warmed up for 10 minutes before completing 5 exercise stations , after which an ad libitum fluid break was given , for a total of 6 breaks .


We measured the fluid variables of total volume consumed , total number of squirts , and average volume per squirt .


Hydration status via urine osmolality and body-mass loss , and perceptual variables for thirst and fullness were recorded .


We calculated repeated-measures analyses of variance to assess hydration status , fluid variables , and perceptual measures to analyze conditions across time .


The total volume consumed for EA-NC was lower than for SA-DC ( P = .001 ) and SA-NC ( P = .001 ) .


The total number of squirts for SA-DC was lower than for SA-NC ( P = .009 ) .


The average volume per squirt for EA-NC was lower than for SA-DC ( P = .020 ) and SA-NC ( P = .009 ) .


Participants arrived ( 601.0 21.3 mOsm/L ) and remained ( 622.3 38.3 mOsm/L ) hydrated , with no difference between conditions ( P = .544 ) ; however , the EA-NC condition lost more body mass than did the SA-DC condition ( P = .001 ) .


There was no main effect for condition on thirst ( P = .147 ) or fullness ( P = .475 ) .


External administration of fluid decreased total volume consumed via a decreased average volume per squirt .


The SA-DC method requires fewer squirts within a specific time frame .


Fluid breaks every 15 minutes resulted in maintenance of euhydration ; however , loss of body mass was influenced by fluid administration .


Athletic trainers should avoid external administration to promote positive hydration behaviors .


When fluid is self-administered , individual bottles may be the best clinical practice because more volume can be consumed per squirt .


To compare the effects of alfaxalone and propofol on intraocular ( IOP ) pressure in the canine eye .


Twenty-three healthy adult dogs .


Dogs were randomized to receive intravenous propofol ( n = 11 ) or alfaxalone ( n = 12 ) until loss of jaw tone , 20 min after intravenous premedication ( acepromazine 0.02-0 .03 mg/kg and hydromorphone 0.05-0 .1 mg/kg ) .


IOP was measured at baseline ( BL ) , 20 min postpremedication ( postpremed ) , loss of jaw tone ( postinduct ) , and immediately following orotracheal intubation ( postintub ) .


Between - and within-treatment effects were analyzed with two-way and one-way repeated measures ANOVA with Bonferroni 's post hoc test , respectively .


P < 0.05 was considered significant .


No significant IOP differences were detected between alfaxalone or propofol groups at any time point ( P > 0.05 ) .


Propofol : IOP did not change between BL ( 15.5 2.7 mmHg ) and postpremed ( 16.2 3.6 mmHg , P > 0.05 ) , or postinduct ( 19.1 5.2 mmHg ) and postintub ( 21.0 4.6 mmHg , P > 0.05 ) , but differed significantly between BL and postinduct ( P < 0.0001 ) , and postintub ( P < 0.0001 ) .


Alfaxalone : IOP did not change between BL ( 15.7 2.8 mmHg ) and postpremed ( 15.3 4.1 mmHg , P > 0.05 ) , or postinduct ( 19.2 4.9 mmHg ) and postintub ( 20.5 4.5 mmHg , P > 0.05 ) , but differed significantly between BL and postinduct ( P < 0.01 ) , and postintub ( P < 0.0001 ) .


These data show a potentially clinically significant increase in IOP following induction with propofol or alfaxalone , but no difference between agents .


Infantile colic is a painful condition in the first months of infancy .


Acupuncture is used in Scandinavia as a treatment for infantile colic .


A randomized controlled trial was carried out with the aim of testing the hypothesis that acupuncture treatment has a clinically relevant effect for this condition .


A prospective , blinding-validated , randomized controlled multicentre trial in general practice .


Research assistants and parents were blinded .


13 GPs ' offices in Southern Norway .


Three days of bilateral needling of the acupuncture point ST36 , with no treatment as control .


113 patients were recruited ; 23 patients were excluded , and 90 randomized ; 79 diaries and 84 interviews were analysed .


Difference in changes in crying time during the trial period between the intervention and control group .


The blinding validation questions showed a random distribution with p = 0.41 and 0.60 , indicating true blinding .


We found no statistically significant difference in crying time reduction between acupuncture and control group at any of the measured intervals , nor in the main analysis of differences in changes over time ( p = 0.26 ) .


There was a tendency in favour of the acupuncture group , with a non-significant total baseline-corrected mean of 13 minutes ( 95 % CI -24 to + 51 ) difference in crying time between the groups .


This was not considered clinically relevant , according to protocol .


This trial of acupuncture treatment for infantile colic showed no statistically significant or clinically relevant effect .


With the current evidence , the authors suggest that acupuncture for infantile colic should be restricted to clinical trials .


Endometrial biopsy is a common procedure for the investigation of many gynecological disorders including abnormal uterine bleeding , postmenopausal bleeding , abnormal cytology and infertility .


Most women experience some degree of discomfort and pain during the procedure .


Pain may occur during dilation of the cervix for insertion of the catheter and during endometrial biopsy , which further aggravates pain by inducing uterine contraction .


To determine pain levels during endometrial biopsy by comparing intrauterine instillation of levobupivacaine or lidocaine with placebo in a randomized , double-blinded trial in pre - and postmenopausal women .


Ninety patients were allocated to either control or experimental groups before endometrial biopsy .


The trial medication was intrauterine anesthesia , either 5 mL 0.9 % saline ( control group ) , or 5 mL 0.5 % levobupivacaine or 2 % lidocaine ( experimental groups ) .


Resident doctors used the same endometrial biopsy technique to minimize the risk of technical variation .


All tissue specimens were sent for cytopathological examination .


The pathologists , who were blinded to the study solution , analyzed all tissue specimens .


The primary outcome measure was pain experienced during the procedure .


Pain was assessed using a 10 cm visual analogue pain scale .


All observed adverse effects were recorded until the patients were discharged .


Pain scores of the intrauterine lidocaine and levobupivacaine groups were found to be significantly lower than the control group .


There was no difference between the levobupivacaine and lidocaine groups with regard to pain scores .


There was a moderately positive correlation between pain scores and endometrial thickness .


No complications were observed due to the procedure .


Most of the biopsy results were proliferative and secretory endometrium .


Insufficient material causing inconclusive results was observed mostly in the control group .


Transcervical intrauterine topical instillation of levobupivacaine or lidocaine causes pain relief during endometrial biopsy .


However , further studies are needed to evaluate the effectiveness of intrauterine anesthesia , to determine optimal concentration , volume and waiting time according to the type of local anesthetic agent , and to assess the applicability of the method to other intrauterine procedures .


The present study aimed to compare the effectiveness of the treatment programs of home-based exercise with and without self-manual therapy in individuals with knee osteoarthritis ( knee OA ) in community .


Forty-three participants with knee OA were randomly assigned in groups .


All participants received the same home-based exercise program with or without self-manual therapy over 12 weeks .


Outcome measures were pain intensity , range of motions , six-minute walk test distance , the knee injury and osteoarthritis outcome score ( KOOS ) , short-form 36 ( SF-36 ) and satisfaction .


The results showed that the self-manual therapy program significantly decreased pain at 4 weeks , increased flexion and extension at 4 and 12 weeks , and improved the KOOS in pain item and SF-36 in physical function and mental health items .


The home-based exercise group showed significant increase of the six-minute walk distance at 4 and 12 weeks , improvements in the KOOS in pain and symptom items and SF-36 in the physical function and role-emotional items .


Overall , the results favored a combination of self-manual therapy and home-based exercise for patients with knee OA , which apparently showed superior benefits in decreasing pain and improving active knee range of motions .


Central venous access devices in fluoropyrimidine therapy are associated with complications ; however , reliable data are lacking regarding their natural history , associated complications and infusion pump performance in patients with metastatic colorectal cancer .


We assessed device placement , use during treatment , associated clinical outcomes and infusion pump performance in the NO16966 trial .


Device replacement was more common with FOLFOX-4 ( 5-fluorouracil ( 5-FU ) + oxaliplatin ) than XELOX ( capecitabine + oxaliplatin ) ( 14.1 % vs 5.1 % ) .


Baseline device-associated events and post-baseline removal - / placement-related events occurred more frequently with FOLFOX-4 than XELOX ( 11.5 % vs 2.4 % and 8.5 % vs 2.1 % ) .


Pump malfunctions , primarily infusion accelerations in 16 % of patients , occurred within 1.6-4 .3 % of cycles .


Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not ( 97 out of 155 vs 452 out of 825 patients ) , predominantly with increased grade 3/4 neutropenia ( 53.5 % vs 39.8 % ) .


Febrile neutropenia rates were comparable between patient cohortsmalfunction .


Efficacy outcomes were similar in patient cohortsmalfunction .


Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4 .


Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events .


Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings .


Primary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system .


However , there remains a gap between recommended preventive services and actual practice .


This trial ( the BETTER Trial ) aimed to improve preventive care of heart disease , diabetes , colorectal , breast and cervical cancers , and relevant lifestyle factors through a practice facilitation intervention set in primary care .


Pragmatic two-way factorial cluster RCT with Primary Care Physicians ' practices as the unit of allocation and individual patients as the unit of analysis .


The setting was urban Primary Care Team practices in two Canadian provinces .


Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control ; 4 physicians in each team ( 32 physicians ) were randomly assigned to receive the patient-level intervention or wait-list control .


Patients randomly selected from physicians ' rosters were stratified into two groups : 1 ) general and 2 ) moderate mental illness .


The interventions involved a multifaceted , evidence-based , tailored practice-level intervention with a Practice Facilitator , and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored ` prevention prescription ' .


The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets , expressed as the ratio of eligible actions at baseline that were met at follow-up .


A cost-effectiveness analysis was conducted .


789 of 1,260 ( 63 % ) eligible patients participated .


On average , patients were eligible for 8.96 ( SD 3.2 ) actions at baseline .


In the adjusted analysis , control patients met 23.1 % ( 95 % CI : 19.2 % to 27.1 % ) of target actions , compared to 28.5 % ( 95 % CI : 20.9 % to 36.0 % ) receiving the practice-level intervention , 55.6 % ( 95 % CI : 49.0 % to 62.1 % ) receiving the patient-level intervention , and 58.9 % ( 95 % CI : 54.7 % to 63.1 % ) receiving both practice - and patient-level interventions ( patient-level intervention versus control , P < 0.001 ) .


The benefit of the patient-level intervention was seen in both strata .


The extra cost of the intervention was $ 26.43 CAN ( 95 % CI : $ 16 to $ 44 ) per additional action met .


A Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner .


The aim of this study was to assess the impact of digital versus traditional drainage devices on chest tube removal and patient satisfaction .


A randomized trial of digital versus traditional devices after lobectomy/segmentectomy was conducted at 4 international centers ( United Kingdom , Europe , Asia , United States ) .


Patients were managed with overnight suction followed by gravity drainage .


Chest tubes were removed when an air leak was not evident anymore and the drained fluid was less than 400 mL/d .


The groups ( digital , 191 patients ; traditional , 190 patients ) were well matched for baseline and surgical characteristics .


There were 325 lobectomies/bilobectomies and 56 segmentectomies , 308 of which were performed by video-assisted thoracic surgery ( VATS ) .


Patients randomized to digital systems had a significantly shorter air leak duration ( 1.0 versus 2.2 days ; p = 0.001 ) , duration of chest tube placement ( 3.6 versus 4.7 days ; p = 0.0001 ) , and postoperative length of stay ( 4.6 versus 5.6 days ; p < 0.0001 ) .


Subjective end points revealed a perceived improved ability to arise from bed ( p = 0.008 ) , system convenience for patients and personnel ( p = 0.02 ) , and the potential for being comfortable when discharged home with the device ( p = 0.06 ) .


A mean difference of 2.6 days from air leak cessation to tube removal was observed , which was similar in the 2 groups ( p = 0.7 ) .


Multivariable regression analysis showed that duration of chest tube placement after air leak cessation was directly associated with the amount of fluid drained during the first 48 hours ( p = 0.01 ) and the duration of air leak ( p = 0.008 ) , independent of hospital location .


Patients managed with digital drainage systems experienced a shorter duration of chest tube placement , shorter hospital stays , and higher satisfaction scores compared with those managed with traditional devices .


NCT01747889 . )


Pain after cesarean delivery is a leading cause of chronic pain and there are many attempts to reduce it without total success .


Gabapentin is effective in reducing acute and chronic pain with little experience in parturient .


The purpose of this study is to compare the effect of pre-emptive gabapentin with intrathecal fentanyl on reducing postoperative pain and morphine consumption in cesarean surgery .


Seventy-eight primiparous women who scheduled for non-emergency cesarean delivery were enrolled in the study and separated into two groups .


The control group received 12.5 mg of heavy bupivacaine 0.5 % plus 10 g of fentanyl intrathecally and the case group received 300 mg of gabapentin orally 2 h before surgery and 12.5 mg of heavy bupivacaine 0.5 % intrathecally .


Data collection including blood pressure , heart rate , neonate sedation , Apgar score , visual analogous scale at several hours , at first , need to analgesic postoperatively .


In the fentanyl group , the need for analgesic drug was earlier , total dose of morphine in 24 h and patient satisfaction was higher than the gabapentin group .


The mean visual analogous scale at several hours postoperatively in the fentanyl groups was significantly higher than the gabapentin groups ( P = 0.001 ) .


Preemptive use of gabapentin is a safe and effective way to reduce postoperative pain and morphine consumption in parturients after cesarean surgery .


To evaluate the effect of dexmedetomidine on emergence agitation after oral and maxillofacial surgery .


Fifty five patients who went into recovery room after oral and maxillofacial surgery were randomly divided into 2 groups : dexmedetomidine group ( n = 28 ) and control group ( n = 27 ) .


Patients in dexmedetomidine group were assigned to receive intravenous dexmedetomidine at a dose of 0.3 g/kg when they came into recovery room .


Patients in control group were assigned to receive intravenous normal saline .


Emergence agitation was assessed and extubation time after operation was recorded .


Mean arterial pressure , heart rate , arterial oxygen saturation , Ramsay scale were recorded at the time point of entering the recovery room instantly ( T0 ) and 5 minutes ( T1 ) , 15 minutes ( T2 ) , 30 minutes ( T3 ) , 60 minutes ( T4 ) , 120 minutes ( T5 ) after the patient came into recovery room .


Statistical analysis was performed using SAS 9.1 software package .


The incidence of emergence agitation was significantly lower in the dexmedetomidine group ( 18 % ) than in the control group ( 70 % ) ( P < 0.05 ) .


The Ramsay scale was significantly higher in dexmedetomidine group than in the control group at the time point of T1 , T2 , T3 , T4 ( P < 0.05 ) .


The heart rate was significantly lower in dexmedetomidine group than in the control group at the time point of T1 , T2 , T3 , T4 , T5 ( P < 0.05 ) .


Mean arterial pressure was significantly lower in dexmedetomidine group than in the control group at the time point of T2 , T3 ( P < 0.05 ) .


There was no significant difference on extubation time between 2 groups .


There was no postoperative respiratory depression in 2 groups .


Intravenous dexmedetomidine at a dose of 0.3 g/kg can reduce emergence agitation after oral and maxillofacial surgery with safety and efficacy .


The objective was to describe parent-reported child eating behavior and maternal parenting impact outcomes of an infant feeding intervention to reduce child obesity risk .


An assessor masked Randomized Controlled Trial ( RCT ) with concealed allocation of individual mother-infant dyads .


The NOURISH RCT enrolled 698 first-time mothers ( mean age 30.1 years , SD = 5.3 ) with healthy term infants ( 51 % female ) aged 4.3 months ( SD = 1.0 ) at baseline .


Outcomes were assessed 6 months post-intervention when the children were 2 years old .


Mothers reported on child eating behaviors using the Children 's Eating Behavior Questionnaire ( CEBQ ) , food preferences , and dietary intake using a 24-hour telephone recall .


Parenting was assessed using five scales validated for use in Australia .


Intervention effects were evident on the CEBQ overall ( MANOVA P = 0.002 ) and 4/8 subscales : child satiety responsiveness ( P = 0.03 ) , fussiness ( P = 0.01 ) , emotional overeating ( P < 0.01 ) , and food responsiveness ( P = 0.06 ) .


Intervention children `` liked '' more fruits ( P < 0.01 ) and fewer non-core foods and beverages ( P = 0.06 , 0.03 ) .


The intervention mothers reported greater `` autonomy encouragement '' ( P = 0.002 ) .


Anticipatory guidance on protective feeding practices appears to have modest positive impacts on child eating behaviors that are postulated to reduce future obesity risk .


Metacognitive dysfunction has been widely recognized as a feature of schizophrenia .


As it is linked with deficits in several aspects of daily life functioning , improvement of metacognition may lead to improvement in functioning .


Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia ; multiple case reports and a pilot study show promising results .


The present study aims to measure the effectiveness of an individual , manual-based therapy ( Metacognitive Reflection and Insight Therapy , MERIT ) in improving metacognition in patients with schizophrenia .


We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning , experience of symptoms , quality of life , depression , work readiness , insight and experience of stigma .


MERIT is currently evaluated in a multicenter randomized controlled trial .


Thirteen therapists in six mental health institutions in the Netherlands participate in this study .


Patients are randomly assigned to either MERIT or the control condition : treatment as usual ( TAU ) .


If proven effective , MERIT can be a useful addition to the care for schizophrenia patients .


The design brings along some methodological difficulties , these issues are addressed in the discussion of this paper .


Current Controlled Trials : ISRCTN16659871 .


Juvenile myoclonic epilepsy ( JME ) is a young-onset electroclinical syndrome , characterized by myoclonic , generalized tonic-clonic , and possibly typical absence seizures .


Interictal electroencephalography ( EEG ) displays 3-6 Hz spike/polyspike and wave pattern .


Photosensitivity is common .


Our aim was to explore the blood oxygen level-dependent ( BOLD ) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls , and to investigate the hemodynamic phenomena seen in patients with photosensitive JME .


We studied 13 JME patients and 18 healthy controls using EEG-functional magnetic resonance imaging ( fMRI ) performed during low luminance intermittent photic stimulation ( IPS ) .


The BOLD response to IPS was investigated both in JME and control groups .


In photosensitive JME subjects , we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response ( PPR ) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward .


The IPS evoked a positive BOLD response in striate and extrastriate visual areas , which was less in JME patients than in controls .


Moreover , people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex ( SM1 ) and in cortical regions belonging to the default mode network ( DMN ) .


In JME , the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1 , followed by BOLD signal decrements in the putamen , caudate nuclei , thalami , and SM1 .


Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks , with prominent involvement of basal ganglia circuitry .


The PPR could be a final expression of pathogenic phenomena occurring in the striato-thalamocortical system , possibly a core feature of system epilepsy JME .


To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community .


Pragmatic multicentre , two arm , parallel group , randomised controlled trial .


20 study sites in 16 medium to large cities throughout France .


706 women aged 75-85 , living in their own home , and with diminished balance and gait capacities , randomly allocated to the experimental intervention group ( exercise programme , n = 352 ) or the control group ( no intervention , n = 354 ) .


Weekly supervised group sessions of progressive balance training offered in community based premises for two years , supplemented by individually prescribed home exercises .


A geriatrician blinded to group assignment classified falls into one of three categories ( no consequence , moderate , severe ) based on physical damage and medical care .


The primary outcome was the rate of injurious falls ( moderate and severe ) .


The two groups were compared for rates of injurious falls with a `` shared frailty '' model .


Other outcomes included the rates of all falls , physical functional capacities ( balance and motor function test results ) , fear of falling ( FES-I ) , physical activity level , and perceived health related quality of life ( SF-36 ) .


Analysis was by intention to treat .


There were 305 injurious falls in the intervention group and 397 in the control group ( hazard ratio 0.81 , 95 % confidence interval 0.67 to 0.99 ) .


The difference in severe injuries ( 68 in intervention group v 87 in control group ) was of the same order of magnitude ( 0.83 , 0.60 to 1.16 ) .


At two years , women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group .


Among women who started the intervention ( n = 294 ) , the median number of group sessions attended was 53 ( interquartile range 16-71 ) .


Five injurious falls related to the intervention were recorded .


A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling.Trial registration ClinicalTrials.gov ( NCT00545350 ) .


We compared the efficacy of medical masks ( MM ) and N95 respirators ( N95 ) in preventing bacterial colonization/infection in healthcare workers ( HCWs ) .


A cluster randomized clinical trial ( RCT ) of 1441 hospital HCWs randomized to medical masks or N95 respirators , and compared to 481 control HCWs , was performed in Beijing , China , during the winter season of 2008-2009 .


Participants were followed for development of clinical respiratory illness ( CRI ) .


Symptomatic subjects were tested for Streptococcus pneumoniae , Bordetella pertussis , Chlamydia pneumoniae , Mycoplasma pneumoniae or Haemophilus influenza type B by multiplex polymerase chain reaction ( PCR ) .


The rate of bacterial colonization was 2.8 % in the N95 group ( p = 0.02 ) , 5.3 % among medical mask users ( p < 0.01 ) and 7.5 % among the controls ( p = 0.16 ) .


N95 respirators were significantly protective ( adjusted RR 0.34 , 95 % CI : 0.21-0 .56 ) against bacterial colonization .


Co-infections of two bacteria or a virus and bacteria occurred in up to 3.7 % of HCWs , and were significantly lower in the N95 arm .


N95 respirators were significantly protective against bacterial colonization , co-colonization and viral-bacterial co-infection .


We showed that dual respiratory virus or bacterial-viral co-infections can be reduced by the use of N95 respirators .


This study has occupational health and safety implications for health workers .


Fever and neutropenia ( FN ) often complicate anticancer treatment and can be caused by potentially fatal infections .


Knowledge of pathogen distribution is paramount for optimal patient management .


Microbiologically defined infections ( MDI ) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed .


Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN .


MDI were identified in a minority ( 22 % ) of pediatric cancer patients with FN .


In patients with , compared with patients without MDI , fever [ median , 5 ( interquartile range : 3-8 ) vs. 2 ( interquartile range : 1-3 ) days , P < 0.001 ] and hospitalization [ 10 ( 6-14 ) vs. 5 ( 3-8 ) days , P < 0.001 ] lasted longer , transfer to the intensive care unit was more likely [ 13 of 95 ( 14 % ) vs. 7 of 346 ( 2.0 % ) , P < 0.001 ] , and antibiotics were given longer [ 10 ( 7-14 ) vs. 5 ( 4-7 ) days , P < 0.001 ] .


Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [ 81 % ( 95 % confidence interval : 68-90 ) vs. 96.6 % ( 95 % confidence interval : 87-99 .4 ) , P = 0.004 ] .


MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients .


Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia .


The efficacy and safety of certolizumab pegol ( CZP ) in moderate-to-severe Crohn 's disease were demonstrated in two 26-week double-blind studies ( PRECiSE 1 & 2 ) .


To report the safety and efficacy outcomes of long-term , CZP therapy from PRECiSE 3 , in which patients received treatment up to 7years treatment .


Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400mg , open-label , every 4weeks ( without additional induction therapy ) for up to 7years , for up to 91 doses from study start .


Safety ( adverse events , including infections and malignancies ) and efficacy ( Harvey-Bradshaw Index , faecal calprotectin , C-reactive protein ) were prospectively monitored .


Remission was analysed using observed cases , last observation carried forward imputation and nonresponder imputation .


A total of 595 patients entered the study ; 117 ( 20 % ) completed 7years .


Discontinuation rates were 29.2 % , 13.6 % , 16.1 % , 7.9 % , 5.0 % , 4.5 % and 3.9 % ( years 1-7 respectively ) .


During 1920 patient-years of exposure to CZP , no new safety signals were observed .


Incidence rates ( new cases/100 patient-years ) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively .


No lymphoproliferative malignancies were reported .


Clinical remission rates were 68 % at each year ( observed cases ) ; rates by last observation carried forward and nonresponder imputation were 58 % and 45 % at year 1 , 56 % and 26 % at year 3 and 55 % and 13 % at year 7 respectively .


Certolizumab pegol was well tolerated in the long-term treatment of Crohn 's disease , with sustained remission in some patients continuing in the study for up to 7years .


ClinicalTrials.gov identifier NCT00552058 .


HIV-1 plasma viral load during treatment can be highly variable .


Thus , there is the need to find a measure of cumulative viremia that can be used to assess both the short - and long-term efficacy of highly active antiretroviral therapy ( HAART ) .


Here , we validate a measure of cumulative viremia to evaluate HAART efficacy .


We accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico .


We compared the proportion of individuals achieving a viral load < 50 and < 400 copies/mL at week 48 , against the cumulative plasma viral load , estimated as the area under the plasma viral load curve ( AUVLC ) .


High AUVLC indicates high cumulative viremia .


There was a strong and significant association between the proportion of individuals achieving a viral load < 50 and < 400 copies/mL at week 48 , with individuals suppressed having significant lower cumulative viremia .


The median area was 7513 ( 25th-75th percentile [ Q1-Q3 ] 6634-8180 ) if viral load < 50 copies/mL and 7679 ( Q1-Q3 6899-9373 ) if viral load 50 copies/mL ( p-value 0.0284 ) .


When the analysis was stratified by study arm , individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir .


Our findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART .


This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO , as a means to maximize the individual and public health benefit of HAART .


To determine whether differences could be detected in mobility outcomes during community mobility and home mobility tasks according to type of mobility assistive device .


Randomized , repeated measures .


Community mobility task : traversing 341.4 m between the rehabilitation clinic and hospital entrance ; home mobility task : traversing 39m into and out of a patient training bathroom and bedroom .


Community-dwelling , cognitively intact ambulatory veterans ( N = 59 ) who used a mobility device within the 14 days prior to the study .


Participants tested 3 types of mobility assistive devices with wheels : 4-wheeled walker ( WW ) , manual wheelchair ( MWC ) , and powered wheelchair ( PWC ) .


The first and last devices used by each participant were randomly assigned as either MWC or WW .


The PWC was always the second device .


Speed ( m/s ) , collisions ( total ) , fatigue ( 0-10 Likert scale ) , and pain ( 0-10 Likert scale , diagram ) .


The community mobility task was performed with all 3 devices by 52 ( 88 % ) veterans , and the home mobility task was performed with all 3 devices by 53 ( 90 % ) participants .


In each task , 28 participants used the WW and 28 participants used the MWC as the final device .


In the community mobility task , statistically significant differences ( P < .05 ) were seen with 1 device comparison for all studied outcomes ( eg , standardized mean difference for the MWC compared with the PWC showed -.67 fewer collisions for the MWC ) .


In the home mobility task , speed , collisions , and fatigue showed statistically significant ( P < .05 ) device-related differences ( eg , standardized mean difference for the WW compared with the MWC showed -.88 fewer collisions for the WW ) .


We found statistically significant and substantively different effects from 3 commonly used mobility assistive devices with wheels on diverse mobility outcomes when used in typical community mobility and home mobility tasks , providing proof of concept support for a research methodology applicable to comparative outcome studies of diverse mobility aids .


Ramadan fasting is a special model of hunger and particularly affects metabolic processes , including carbohydrate and lipid levels .


Endocrine changes induced by Ramadan fasting are not well known .


The aim of this article was to evaluate the changes in hormone levels in women before and after the special Muslim fasting period of Ramadan .


This study was performed in 30 healthy women in Obstetrics and Gynecology department during the Ramadan month of2011 .


Patients during and after the first menstrual period had menstrual cycles fasting blood samples taken on the same days .


Luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , estradiol ( E2 ) , testosterone , and prolactin ( PRL ) levels were determined .


Before and during fasting LH , FSH , E2 , testosterone and PRL levels were not statistically different .


Despite the limited available studies on these subjects in women , effect of Ramadan fasting on hormone levels were found to be within the normal limits .


This work intended to observe the effect of injecting botolinum toxin type A ( BTX-A ) for relieving spastic iliopsoas of cerebral palsy on children , and to investigate the improvement of this method for the motor function in these children .


From July 2006 to August 2012 , 37 children with spastic iliopsoas cerebral palsy were received rehabilitation therapy .


The age ranged from 3 to 15 years .


The control group were treated by conventional physical therapy ( PY ) .


The experimental group were treated not only by the conventional physical therapy , but also BTX-A injection .


The dose of BTX-A injection was according to the weight of the child and the Modified Ashworth Scale ( MAS ) .


The dose of the injection ranged from 15 IU to 45 IU with the average dose 31.213.9 IU .


There was no significant difference between two the groups on ages , weight and MAS , GMFM ( Gross Motor Function Measure ) and extension angle of hip joints before treatment .


In both groups , the Modified Ashworth Scale decreased , GMFM and extension angle of hip joints increased after eight weeks .


In the control group , the GMFM improved significantly .


In the experimental group , MAS , GMFM and extension angle of hip joints changed significantly after therapy .


There was significant difference between two groups in MAS , GMFM and extension angle of hip joints after two months .


The BTX-A injection can relieve iliopsoas spasticity of cerebral palsy on children efficiently .


This therapy can help children to correct abnormal gait and to improve their motor function .


This study sought to assess radiation exposure and operator discomfort when using left radial approach ( LRA ) versus right radial approach ( RRA ) for coronary diagnostic and percutaneous interventions .


The transradial approach is increasingly being adopted as the preferred vascular access for coronary interventions .


Currently , most are performed using an RRA .


This is in part due to the perceived increased operator physical discomforts as well increased radiation exposure with an LRA .


One hundred patients were randomized to an LRA or RRA .


Each operator ( n = 5 ) had an independent randomization process , and patients were stratified according to obesity status .


Operator radiation was measured using separate sets of radiation dosimeter badges placed externally on the head and thyroid and internally on the sternum .


Operator physical discomfort was surveyed at 2 time points : during vascular access and at the end of the procedure .


Moderate to severe physical discomfort was defined as a score of > 4 .


There were no significant differences in baseline and procedural variables between groups .


There was a significant increase in external radiation exposure using the RRA versus LRA ( head : median : 6.12 [ interquartile range ( IQR ) : 2.6 to 16.6 ] mRems vs. median : 12.0 [ IQR : 6.4 to 22.0 ] mRems , p = 0.02 ; thyroid : median : 10.10 [ IQR : 4.3 to 25 ] mRems vs. median : 18.70 [ IQR : 11.0 to 38 ] mRems , p = 0.001 ) .


More discomfort was reported with the LRA during access ( LRA : 22 % vs. RRA : 4 % ; p = 0.017 ) , but not during the procedure ( LRA : 10.0 % vs. RRA : 4.0 % , p = 0.43 ) .


This difference was almost entirely noted inobese patients ( LRA : 30.0 % vs. RRA : 3.7 % , p = 0.005 ) .


LRA is as effective as RRA , showing a safer profile with decreased radiation exposure to the operator , at the expense of more operator discomfort only during vascular access and limited to obese patients .


To determine dose-dependent effects of T administration on cardiovascular risk markers in women with low T levels .


Seventy-one hysterectomized women with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3 - , 6.25 - , 12.5 - , or 25-mg T enanthate for 24 weeks .


Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis , respectively .


Insulin resistance and inflammatory markers were measured at baseline and 24 weeks .


In a subset of women , magnetic resonance imaging of the abdomen was performed to quantify abdominal fat volume .


Fifty-nine women who completed the 24-week intervention were included in the final analysis .


The five groups were similar at baseline .


Mean on-treatment nadir total T concentrations were 14 , 79 , 105 , 130 , and 232 ng/dL in the placebo group and the 3 - , 6.25 - , 12.5 - , and 25-mg groups , respectively .


No significant changes in fasting glucose , fasting insulin , homeostatic model assessment of insulin resistance , high sensitivity C-reactive protein , adiponectin , blood pressure , and heart rate were observed at any T dose when compared to placebo .


Similarly , no dose - or concentration-dependent changes were observed in abdominal fat on magnetic resonance imaging .


Short-term T administration over a wide range of doses for 24 weeks in women with low T levels was not associated with worsening of cardiovascular risk markers .


The phe508del CFTR mutation causes cystic fibrosis by limiting the amount of CFTR protein that reaches the epithelial cell surface .


We tested combination treatment with lumacaftor , an investigational CFTR corrector that increases trafficking of phe508del CFTR to the cell surface , and ivacaftor , a CFTR potentiator that enhances chloride transport of CFTR on the cell surface .


In this phase 2 clinical trial , we assessed three successive cohorts , with the results of each cohort informing dose selection for the subsequent cohort .


We recruited patients from 24 cystic fibrosis centres in Australia , Belgium , Germany , New Zealand , and the USA .


Eligibility criteria were : confirmed diagnosis of cystic fibrosis , age at least 18 years , and a forced expiratory volume in 1 s ( FEV1 ) of 40 % or more than predicted .


Cohort 1 included phe508del CFTR homozygous patients randomly assigned to either lumacaftor 200 mg once per day for 14 days followed by addition of ivacaftor 150 mg or 250 mg every 12 h for 7 days , or 21 days of placebo .


Together , cohorts 2 and 3 included phe508del CFTR homozygous and heterozygous patients , randomly assigned to either 56 days of lumacaftor ( cohort 2 : 200 mg , 400 mg , or 600 mg once per day , cohort 3 : 400 mg every 12 h ) with ivacaftor 250 mg every 12 h added after 28 days , or 56 days of placebo .


The primary outcomes for all cohorts were change in sweat chloride concentration during the combination treatment period in the intention-to-treat population and safety ( laboratory measurements and adverse events ) .


The study is registered with ClinicalTrials.gov , number NCT01225211 , and EudraCT , number 2010-020413-90 .


Cohort 1 included 64 participants .


Cohort 2 and 3 combined contained 96 phe508del CFTR homozygous patients and 28 compound heterozygotes .


Treatment with lumacaftor 200 mg once daily and ivacaftor 250 mg every 12 h decreased mean sweat chloride concentration by 9.1 mmol/L ( p < 0.001 ) during the combination treatment period in cohort 1 .


In cohorts 2 and 3 , mean sweat chloride concentration did not decrease significantly during combination treatment in any group .


Frequency and nature of adverse events were much the same in the treatment and placebo groups during the combination treatment period ; the most commonly reported events were respiratory .


12 of 97 participants had chest tightness or dyspnoea during treatment with lumacaftor alone .


In pre-planned secondary analyses , a significant decrease in sweat chloride concentration occurred in the treatment groups between day 1 and day 56 ( lumacaftor 400 mg once per day group -9.1 mmol/L , p < 0.001 ; lumacaftor 600 mg once per day group -8.9 mmol/L , p < 0.001 ; lumacaftor 400 mg every 12 h group -10.3 mmol/L , p = 0.002 ) .


These changes were significantly greater than the change in the placebo group .


In cohort 2 , the lumacaftor 600 mg once per day significantly improved FEV1 from day 1 to 56 ( difference compared with placebo group : +5.6 percentage points , p = 0.013 ) , primarily during the combination period .


In cohort 3 , FEV1 did not change significantly across the entire study period compared with placebo ( difference +4.2 percentage points , p = 0.132 ) , but did during the combination period ( difference +7.7 percentage points , p = 0003 ) .


Phe508del CFTR heterozygous patients did not have a significant improvement in FEV1 .


We provide evidence that combination lumacaftor and ivacaftor improves FEV1 for patients with cystic fibrosis who are homozygous for phe508del CFTR , with a modest effect on sweat chloride concentration .


These results support the further exploration of combination lumacaftor and ivacaftor as a treatment in this setting .


Vertex Pharmaceuticals , Cystic Fibrosis Foundation Therapeutics Development Network .


The aim of this study was to assess the glucose-lowering and lipid-modifying effects , and safety profile of lobeglitazone , a novel peroxisome proliferator-activated receptor - agonist , compared to placebo as a monotherapy in patients with type 2 diabetes .


In this 24-week , multicenter , randomized , double-blind , parallel-group , placebo controlled study , 173 patients were randomly assigned ( a 21 ratio ) to lobeglitazone 0.5 mg ( n = 115 ) or matching placebo ( n = 58 ) orally once daily .


The primary endpoint was the change in glycated hemoglobin ( HbA1c ) from baseline to the end of treatment .


The secondary endpoints included various glycemic parameters , lipid parameters and safety profile ( ClinicalTrials.gov number NCT01001611 ) .


At 24 weeks , a significant reduction in HbA1c was observed with lobeglitazone versus placebo ( -0.44 % vs 0.16 % , mean difference -0.6 % , p < 0.0001 ) .


The goal of HbA1c < 7 % was achieved significantly more in the lobeglitazone group compared to the placebo group ( 44 % vs 12 % , p < 0.0001 ) .


Markers of insulin resistance were also improved in the lobeglitazone group .


In addition , lobeglitazone treatment significantly improved triglycerides , high density lipoprotein cholesterol , small dense low density lipoprotein cholesterol , free fatty acid , and apolipoprotein-B/CIII compared to placebo ( p < 0.01 , respectively ) .


More weight gain was observed in the lobeglitazone group than the placebo group ( 0.89 kg vs - 0.63 kg , mean difference 1.52 kg , p < 0.0001 ) .


The safety profile was comparable between the two groups and lobeglitazone was well tolerated .


Lobeglitazone 0.5 mg showed a favorable balance in the efficacy and safety profile .


The results support a potential role of lobeglitazone in treating type 2 diabetes .


Clinicaltrials.gov NCT01001611 .


Pulsed electromagnetic fields have been shown to reduce postoperative pain , inflammation , and narcotic requirements after breast reduction and augmentation surgical procedures .


This study examined whether pulsed electromagnetic field therapy could produce similar results in patients undergoing unilateral transverse rectus abdominis myocutaneous ( TRAM ) flap breast reconstruction , a significantly more complex and painful surgical procedure .


In this double-blind , placebo-controlled , randomized study , 32 patients undergoing unilateral TRAM flap breast reconstruction received active or sham pulsed electromagnetic field therapy .


Pain levels were measured by using a visual analogue scale ; narcotic use and wound exudate volume were recorded starting 1 hour postoperatively .


Wound exudates were analyzed for interleukin-1 .


Mean visual analogue scale pain scores were 2-fold higher in the sham cohort at 5 hours and 4-fold higher at 72 hours ( p < 0.01 ) , along with a concomitant 2-fold increase in narcotic use in sham patients ( p < 0.01 ) .


Wound exudate volume was 2-fold higher in the sham cohort at 24 hours ( p < 0.01 ) , and mean interleukin-1 concentration in wound exudates of sham patients was 5-fold higher at 24 hours ( p < 0.001 ) .


Pulsed electromagnetic field therapy significantly reduced postoperative pain , inflammation , and narcotic use following TRAM flap breast reconstruction , paralleling its effect in breast reduction patients .


Both studies also report a significant reduction of interleukin-1 in the wound exudate , supporting a mechanism involving a pulsed electromagnetic field effect on nitric oxide/cyclic guanosine monophosphate signaling , which modulates the body 's antiinflammatory pathways .


Adjunctive pulsed electromagnetic field therapy could impact the speed and quality of wound repair in many surgical procedures .


Therapeutic , I.


The objective of this study was to investigate the hypouricemic effects of green tea extract ( GTE ) in healthy individuals .


This study comprised 1-week control , 2-week interventional , and 1-week follow-up periods .


Participants were assigned randomly at the interventional period to consume GTE at 2 ( GTE2 ) , 4 ( GTE4 ) , or 6 ( GTE6 ) g/d .


Levels of serum uric acid ( SUA ) , uric acid clearance , and serum antioxidant power ( using trolox equivalent antioxidant capacity assay ) were measured at both ends of each study period .


Of 30 participants , 11 , 11 , and 8 received GTE2 , GTE4 , and GTE6 , respectively .


After 2 weeks of consumption , the mean SUA level tended to decrease in all groups , with no statistical significance .


Serum uric acid reduction was greatest in GTE2 ( from 4.81 0.81 mg/dL to 4.64 0.92 mg/dL , 3.53 % ) .


Uric acid clearance decreased significantly in GTE2 ( from 11.37 6.41 mL/min per 1.73 m to 7.44 2.74 mL/min per 1.73 m , 34.56 % , P < 0.05 ) and GTE4 ( from 8.36 3.41 mL/min per 1.73 m to 5.78 2.33 mL/min per 1.73 m , 30.86 % , P < 0.05 ) .


Serum antioxidant capacity ( TEAC ) increased significantly in GTE6 ( from 32.77 3.39 mg/mL to 35.41 3.17 mg/mL , 8.06 % , P < 0.05 ) .


There was no significant change in creatinine clearance .


Gastrointestinal adverse events were common , but usually mild , with no medical treatment required .


Green tea extract may modestly lower SUA level and decreases uric acid clearance .


Green tea extract also significantly elevated serum antioxidant capacity with a positive dosage effect .


The effect of GTE on SUA in healthy individuals was short term .


The effects of GTE on urate handling in patients with hyperuricemia or gout need to be determined .


An intradermal ( ID ) trivalent split-virion influenza vaccine ( IIV3-ID ) ( Fluzone ( ) Intradermal , Sanofi Pasteur , Swiftwater , PA ) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years .


This study examined whether adding a second B-lineage strain affects immunogenicity and safety .


This randomized , double-blind , multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine ( IIV4-ID ) in adults 18-64 years of age in the US during the 2012-2013 influenza season .


Participants were randomized 2:1:1 to receive a single injection of IIV4-ID , licensed IIV3-ID , or an investigational IIV3-ID containing the alternate B-lineage strain .


Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination .


1672 participants were vaccinated with IIV4-ID , 837 with licensed IIV3-ID , and 846 with an investigational IIV3-ID .


For all four vaccine strains , antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains .


For both B strains , post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain .


Adverse events were similar for IIV4-ID and IIV3-ID .


The most commonly reported solicited reactions were pain , pruritus , myalgia , headache , and malaise ; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination .


IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction .


Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains .


IIV4-ID was well tolerated without any safety concerns .


IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines .


Blood transfusions are frequently given to patients with septic shock .


However , the benefits and harms of different hemoglobin thresholds for transfusion have not been established .


In this multicenter , parallel-group trial , we randomly assigned patients in the intensive care unit ( ICU ) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less ( lower threshold ) or when the level was 9 g per deciliter or less ( higher threshold ) during the ICU stay .


The primary outcome measure was death by 90 days after randomization .


We analyzed data from 998 of 1005 patients ( 99.3 % ) who underwent randomization .


The two intervention groups had similar baseline characteristics .


In the ICU , the lower-threshold group received a median of 1 unit of blood ( interquartile range , 0 to 3 ) and the higher-threshold group received a median of 4 units ( interquartile range , 2 to 7 ) .


At 90 days after randomization , 216 of 502 patients ( 43.0 % ) assigned to the lower-threshold group , as compared with 223 of 496 ( 45.0 % ) assigned to the higher-threshold group , had died ( relative risk , 0.94 ; 95 % confidence interval , 0.78 to 1.09 ; P = 0.44 ) .


The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations .


The numbers of patients who had ischemic events , who had severe adverse reactions , and who required life support were similar in the two intervention groups .


Among patients with septic shock , mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold ; the latter group received fewer transfusions .


( Funded by the Danish Strategic Research Council and others ; TRISS ClinicalTrials.gov number , NCT01485315 . )


Most patients with acute coronary syndrome ( ACS ) are treated with statins , which reduce atherogenic triglyceride-rich lipoproteins .


It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment .


This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins .


Long-term and short-term relationships of triglycerides to risk after ACS were examined in the dal-OUTCOMES trial and atorvastatin arm of the MIRACL ( Myocardial Ischemia Reduction with Acute Cholesterol Lowering ) trial , respectively .


Analysis of dal-OUTCOMES included 15,817 patients ( 97 % statin-treated ) randomly assigned 4 to 12 weeks after ACS to treatment with dalcetrapib ( a cholesteryl ester transfer protein inhibitor ) or placebo and followed for a median 31 months .


Analysis of MIRACL included 1,501 patients treated with atorvastatin 80 mg daily beginning 1 to 4 days after ACS and followed for 16 weeks .


Fasting triglycerides at initial random assignment were related to risk of coronary heart disease death , nonfatal myocardial infarction , stroke , and unstable angina in models adjusted for age , sex , hypertension , smoking , diabetes , high-density lipoprotein cholesterol , and body mass index .


Fasting triglyceride levels were associated with both long-term and short-term risk after ACS .


In dal-OUTCOMES , long-term risk increased across quintiles of baseline triglycerides ( p < 0.001 ) .


The hazard ratio in the highest/lowest quintile ( > 175/80 mg/dl ) was 1.61 ( 95 % confidence interval : 1.34 to 1.94 ) .


There was no interaction of triglycerides and treatment assignment on the primary outcome .


In the atorvastatin group of MIRACL , short-term risk increased across tertiles of baseline triglycerides ( p = 0.03 ) , with a hazard ratio of 1.50 [ corrected ] ( 95 % confidence interval : 1.05 to 2.15 ) in highest/lowest tertiles ( > 195/135 mg/dl ) .


The relationship of triglycerides to risk was independent of low-density lipoprotein cholesterol in both studies .


Among patients with ACS treated effectively with statins , fasting triglycerides predict long-term and short-term cardiovascular risk .


Triglyceride-rich lipoproteins may be an important additional target for therapy .


( A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome ; NCT00658515 ) .


Both hepatitis C virus ( HCV ) mono-infected and HIV/HCV co-infected patients are in need of safe , effective , all-oral HCV regimens .


In a phase 2 study we aimed to assess the efficacy and safety of grazoprevir ( MK-5172 ; HCV NS3/4A protease inhibitor ) and two doses of elbasvir ( MK-8742 ; HCV NS5A inhibitor ) in patients with HCV mono-infection and HIV/HCV co-infection .


The C-WORTHY study is a phase 2 , multicentre , randomised controlled trial of grazoprevir plus elbasvir with or without ribavirin in patients with HCV ; here , we report findings for previously untreated ( genotype 1 ) patients without cirrhosis who were HCV mono-infected or HIV/HCV co-infected .


Eligible patients were previously untreated adults aged 18 years or older with chronic HCV genoype 1 infection and HCV RNA at least 10000 IU/mL in peripheral blood without evidence of cirrhosis , hepatocellular carcinoma , or decompensated liver disease .


In part A of the study we randomly assigned HCV-mono-infected patients to receive 12 weeks of grazoprevir ( 100 mg ) plus elbasvir ( 20 mg or 50 mg ) with or without ribavirin ( arms A1-3 ) ; in part B we assigned HCV-mono-infected patients to 8 or 12 weeks of grazoprevir ( 100 mg ) plus elbasvir ( 50 mg ) with or without ribavirin ( arms B1-3 ) and HIV/HCV co-infected patients to 12 weeks of therapy with or without ribavirin .


The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL 12 weeks after end of treatment ( SVR12 ) .


Randomisation was by presence or absence of ribavirin , 8 or 12 weeks of treatment , and dosage of elbasvir .


Patients were stratified by gentoype 1a versus 1b .


The patients , investigators , and study site personnel were masked to treatment group assignements but the funder was not .


Analysis was by intention to treat .


This trial is registered at ClinicalTrials.gov , number NCT01717326 .


218 patients with HCV mono-infection ( n = 159 ) and HIV/HCV co-infection ( n = 59 ) were enrolled .


SVR12 for patients treated for 12 weeks with or without ribavirin ranged from 93-98 % in mono-infected and 87-97 % in co-infected patients .


SVR12 rates in mono-infected and co-infected patients treated for 12 weeks without ribavirin were 98 % ( 95 % CI 88-100 ; 43/44 ) and 87 % ( 95 % CI 69-96 ; 26/30 ) , respectively , and with ribavirin were 93 % ( 95 % CI 85-97 ; 79/85 ) and 97 % ( 95 % CI 82-100 ; 28/29 ) , respectively .


Among mono-infected patients with genotype 1a infection treated for 8 weeks , SVR12 was 80 % ( 95 % CI 61-92 ; 24/30 ) .


Five of six patients who discontinued early for reasons other than virological failure had HCV RNA less than 25 IU/mL at their last study visit .


Virological failure among patients treated for 12 weeks occurred in seven patients ( 7/188 , 4 % ) and was associated with emergence of resistance-associated variants to one or both drugs .


The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients .


No patient discontinued due to an adverse event or laboratory abnormality .


The most common adverse events were fatigue ( 51 patients , 23 % ) , headache ( 44 , 20 % ) , nausea ( 32 , 15 % ) , and diarrhoea ( 21 , 10 % ) .


Once-daily grazoprevir plus elbasvir with or without ribavirin for 12 weeks in previously untreated HCV-mono-infected and HIV/HCV-co-infected patients without cirrhosis achieved SVR12 rates of 87-98 % .


These results support the ongoing phase 3 development of grazoprevir plus elbasvir .


Merck & Co , Inc. .


Treatment options for adults with attention deficit hyperactivity disorder ( ADHD ) are limited .


The study was conducted to confirm the clinically effective and safe dose of methylphenidate hydrochloride modified-release ( MPH-LA ) in adults with ADHD and evaluate the maintenance of effect of MPH-LA .


The study consisted of three treatment phases .


The double-blind dose-confirmation phase : 9-week double-blind period ( 3-week titration period , 6-week fixed dose ) with randomization to MPH-LA 40 , 60 , or 80mg/day or placebo .


The real-life dose-optimization phase : a 5-week re-titration period to optimal dose ; and the double-blind maintenance of effect phase , a 6-month double-blind randomized placebo-controlled maintenance of effect phase .


The three co-primary endpoints were change in Diagnostic and Statistical Manual of Mental Disorders-IV ADHD Rating Scale ( DSM-IV ADHD RS ) and Sheehan Disability Scale ( SDS ) total scores from baseline to end of 9-week confirmation phase and the percentage of treatment failures during the 6-month maintenance of effect phase .


725 of 863 screened patients were randomized to 40 ( N = 181 ) , 60 ( N = 182 ) , or 80mg ( N = 181 ) MPH-LA or placebo ( N = 181 ) , and 584 ( 80.6 % ) completed .


489 ( 83.7 % ) of completers were re-randomized to the double-blinded maintenance of effect phase and 235 ( 48.1 % ) of them completed .


Improvement from baseline in DSM-IV ADHD RS ( P < 0.0001 for all comparisons ) and SDS ( 40mg , P = 0.0003 ; 60mg , P = 0.0176 ; 80mg , P < 0.0001 ) total scores was significantly greater vs. placebo for all MPH-LA doses .


Treatment failure rate was significantly lower with MPH-LA ( 21.3 % ) versus placebo ( 49.6 % ) during the 6-month maintenance of effect phase .


Safety profile was consistent with the profile for MPH-LA in children ; percentage of serious adverse events was comparable between all MPH-LA arms ( 1.3 % ) and placebo ( 1.5 % ) , while percentage of adverse events was higher in MPH-LA arms .


MPH-LA provided and maintained significant symptomatic and functional improvement in adult ADHD patients .


To compare the effect of melatonin and gabapentin on anxiety , pain , sedation scores , and satisfaction of surgeon in patients of cataract surgery .


One hundred thirty patients aged between 35 and 85 years scheduled for cataract surgery were randomly allocated to three study groups to receive melatonin ( 6 mg ) , gabapentin ( 600 mg ) or placebo 90 min before arrival in the operating room .


Pain , anxiety , and sedation scores during block and surgery as well as the surgeon 's satisfaction with the surgery were assessed .


Anxiety scores decreased significantly in melatonin and gabapentin groups compared to the placebo group after premedication and extended to early postoperative period .


The level of anxiety showed no statistically significant difference between melatonin and gabapentin groups at any time of measurement .


There were significant differences between the pain scores during retrobulbar placement in gabapentin versus placebo ( 95 % CI 3 to 4 ; P = 0.001 ) and melatonin ( 95 % CI 3 to 4 ; P = 0.040 ) groups .


Also , there were significant differences between the sedation scores during retrobulbar placement in gabapentin and placebo groups ( 95 % CI 2 to 2.5 ; P = 0.046 ) .


The difference in sedation scores during retrobulbar placement in melatonin versus gabapentin and placebo groups was not significant .


Neither the intraoperative pain scores nor the postoperative pain scores were different between the three groups .


The surgeon reported similar quality of operation conditions during surgery for the three study groups .


The level of anxiety was significantly lower with both anxiolytic drugs compared to placebo .


Furthermore , gabapentin decreased the pain and improved the sedation scores only during retrobulbar placement compared to the placebo .


To investigate whether a 12-week physical and cognitive exercise program can improve cognitive function and brain activation efficiency in community-dwelling older adults .


Randomized controlled trial .


Kyoto , Japan .


Community-dwelling older adults ( N = 48 ) were randomized into an exercise group ( n = 24 ) and a control group ( n = 24 ) .


Exercise group participants received a weekly dual task-based multimodal exercise class in combination with pedometer-based daily walking exercise during the 12-week intervention phase .


Control group participants did not receive any intervention and were instructed to spend their time as usual during the intervention phase .


The outcome measures were global cognitive function , memory function , executive function , and brain activation ( measured using functional magnetic resonance imaging ) associated with visual short-term memory .


Exercise group participants had significantly greater postintervention improvement in memory and executive functions than the control group ( P < .05 ) .


In addition , after the intervention , less activation was found in several brain regions associated with visual short-term memory , including the prefrontal cortex , in the exercise group ( P < .001 , uncorrected ) .


A 12-week physical and cognitive exercise program can improve the efficiency of brain activation during cognitive tasks in older adults , which is associated with improvements in memory and executive function .


To explore potential predictors of self-reported paretic arm use at baseline and after task-specific training ( TST ) in survivors of stroke .


Data were obtained from a randomized controlled trial of somatosensory stimulation and upper limb TST in chronic stroke .


University laboratory .


Chronic ( 3mo ) survivors of stroke ( N = 33 ; mean age , 62y ; mean stroke duration , 38mo ) .


Participants received 12 sessions of TST preceded by either active ( n = 16 ) or sham ( n = 17 ) somatosensory stimulation to all 3 peripheral nerves .


Demographic and clinical characteristics were entered stepwise into multiple linear regression analyses to determine the factors that best predict baseline Motor Activity Log ( MAL ) amount of use rating and change 3 months after TST .


The Action Research Arm Test ( ARAT ) score predicted the amount of use at baseline ( R ( 2 ) = .47 , P < .001 ) ; in using this model , an ARAT score of 54 ( maximum of 57 ) is required to score 2.5 on the MAL ( use described as between rarely and sometimes ) .


After TST the change in the ARAT score predicted the change in the amount of use ( R ( 2 ) = .31 , P = .001 ) .


The predictive power of the model for change at 3 months increased if the Fugl-Meyer Assessment wrist component score was added ( R ( 2 ) = .41 , P = .001 ) .


Utilization of the paretic upper limb in activities of daily living requires high functional ability .


The increase in self-reported arm use after TST is dependent on the change in functional ability .


These results provide further guidance for rehabilitation decisions .


There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure ( HF ) .


We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload .


Fifty-six patients with congestive HF were randomized to receive standard medical therapy ( control group ; n = 29 ) or ultrafiltration ( ultrafiltration group ; n = 27 ) .


The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up .


Despite similar body weight reduction at hospital discharge in the 2 groups ( 7.5 5.5 and 7.9 9.0 kg , respectively ; P = .75 ) , a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year ( hazard ratio 0.14 , 95 % confidence interval 0.04-0 .48 ; P = .002 ) .


Ultrafiltration-induced benefit was associated with a more stable renal function , unchanged furosemide dose , and lower B-type natriuretic peptide levels .


At 1 year , 7 deaths ( 30 % ) occurred in the ultrafiltration group and 11 ( 44 % ) in the control group ( P = .33 ) .


In HF patients with severe fluid overload , first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF .


Pediatric inflammatory bowel disease ( IBD ) is associated with high rates of depression .


This study compared the efficacy of cognitive behavioral therapy ( CBT ) to supportive nondirective therapy ( SNDT ) in treating youth with comorbid IBD and depression .


Youth ( 51 % female and 49 % male ; age 9-17 years , mean age 14.3 years ) with depression and Crohn 's disease ( n = 161 ) or ulcerative colitis ( n = 56 ) were randomly assigned to a 3-month course of CBT or SNDT .


The primary outcome was comparative reduction in depressive symptom severity ; secondary outcomes were depression remission , increase in depression response , and improved health-related adjustment and IBD activity .


A total of 178 participants ( 82 % ) completed the 3-month intervention .


Both psychotherapies resulted in significant reductions in total Children 's Depression Rating Scale Revised score ( 37.3 % for CBT and 31.9 % for SNDT ) , but the difference between the 2 treatments was not significant ( p = .16 ) .


There were large pre-post effect sizes for each treatment ( d = 1.31 for CBT and d = 1.30 for SNDT ) .


More than 65 % of youth had a complete remission of depression at 3 months , with no difference between CBT and SNDT ( 67.8 % and 63.2 % , respectively ) .


Compared to SNDT , CBT was associated with a greater reduction in IBD activity ( p = .04 ) but no greater improvement on the Clinical Global Assessment Scale ( p = .06 ) and health-related quality of life ( IMPACT-III scale ) ( p = .07 ) .


This is the first randomized controlled study to suggest improvements in depression severity , global functioning , quality of life , and disease activity in a physically ill pediatric cohort treated with psychotherapy .


Clinical trial registration information-Reducing Depressive Symptoms in Physically Ill Youth ; http://clinical trials.gov ; NCT00534911 .


The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US , particularly those located in urban areas .


Despite the fact that HIV is often transmitted from one sexual partner to another , most HIV prevention interventions have focused only on individuals , rather than couples .


This five-year study investigates community-based implementation , effectiveness , and sustainability of ` Eban II , ' an evidence-based risk reduction intervention for African-American heterosexual , serodiscordant couples .


This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model ( PCM ) , a model of phased organizational change from exposure to adoption , implementation , and sustainability .


The primary implementation aims are to assist 10 community-based organizations ( CBOs ) to implement and sustain Eban II ; specifically , to partner with CBOs to expose providers to the intervention ; facilitate its adoption , implementation and sustainment ; and to evaluate processes and determinants of implementation , effectiveness , fidelity , and sustainment .


The primary effectiveness aim is to evaluate the effect of Eban II on participant ( n = 200 couples ) outcomes , specifically incidents of protected sex and proportion of condom use .


We will also determine the cost-effectiveness of implementation , as measured by implementation costs and potential cost savings .


A mixed methods evaluation will examine implementation at the agency level ; staff members from the CBOs will complete baseline measures of organizational context and climate , while key stakeholders will be interviewed periodically throughout implementation .


Effectiveness of Eban II will be assessed using a randomized delayed enrollment ( waitlist ) control design to evaluate the impact of treatment on outcomes at posttest and three-month follow-up .


Multi-level hierarchical modeling with a multi-level nested structure will be used to evaluate the effects of agency - and couples-level characteristics on couples-level outcomes ( e.g. , condom use ) .


This study will produce important information regarding the value of the Eban II program and a theory-guided implementation process and tools designed for use in implementing Eban II and other evidence-based programs in demographically diverse , resource-constrained treatment settings .


NCT00644163 .


The incidence of community-acquired methicillin-resistant Staphylococcus aureus infections is rising at an alarming pace .


Effective treatment has historically involved early dbridement and antibiotic administration .


This study was designed to prospectively determine the effectiveness of empiric therapy in treating hand infections .


A prospective randomized trial was conducted at a level I county hospital .


Patients with a hand infection received either empiric intravenous vancomycin at admission or intravenous cefazolin .


Outcomes were tracked using severity of infection , appropriate clinical response , and length of stay .


Cost-effectiveness was calculated using total cost for each patient in both groups .


Statistical analyses were performed .


Forty-six patients were enrolled in the study .


Twenty-four were randomized to cefazolin ( 52.2 percent ) and 22 ( 47.8 percent ) to vancomycin .


There was no statistical difference between cost of treatment ( p < 0.20 ) or mean length of stay ( p < 0.18 ) between the groups .


Patients randomized to cefazolin had higher mean costs of treatment compared with patients who were randomized to vancomycin ( p < 0.05 ) .


Patients with more severe infections had more expensive mean costs of treatment ( p < 0.0001 ) and longer mean length of stay ( p = 0.0002 ) .


Near the end of the study , the incidence of community-acquired methicillin-resistant S. aureus at the authors ' county hospital was discovered to be 72 percent , which caused the study to be terminated prematurely by the institutional review board because of the high incidence precluding further randomization .


Appropriate early treatment for methicillin-resistant S. aureus has not been definitively established .


No difference in outcome using cefazolin versus vancomycin as a first-line agent was identified .


Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction ( HFpEF ) and pulmonary hypertension ( PH ) .


The acute hemodynamic effects of riociguat , a novel soluble guanylate cyclase stimulator , were characterized in patients with PH and HFpEF .


Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50 % , mean pulmonary artery pressure ( mPAP ) 25 mm Hg , and pulmonary arterial wedge pressure ( PAWP ) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat ( 0.5 , 1 , or 2 mg ) .


The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters , safety , and pharmacokinetics .


There was no significant change in peak decrease in mPAP with riociguat 2 mg ( n = 10 ) vs placebo ( n = 11 , P = .6 ) .


However , riociguat 2 mg significantly increased stroke volume ( +9 mL [ 95 % CI , 0.4-17 ] ; P = .04 ) and decreased systolic BP ( -12 mm Hg [ 95 % CI , -22 to -1 ] ; P = .03 ) and right ventricular end-diastolic area ( -5.6 cm2 [ 95 % CI , -11 to -0.3 ] ; P = .04 ) , without significantly changing heart rate , PAWP , transpulmonary pressure gradient , or pulmonary vascular resistance .


Riociguat was well tolerated .


In patients with HFpEF and PH , riociguat was well tolerated , had no significant effect on mPAP , and improved exploratory hemodynamic and echocardiographic parameters .


ClinicalTrials.gov ; No. : NCT01172756 ; URL : www.clinicaltrials.gov .


Posttraumatic stress disorder ( PTSD ) is prevalent , persistent , and disabling .


Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials , geographic barriers impede rural veterans from engaging in these evidence-based treatments .


To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD .


The Telemedicine Outreach for PTSD ( TOP ) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses .


Outpatients were recruited from 11 Department of Veterans Affairs ( VA ) community-based outpatient clinics serving predominantly rural veterans .


Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale .


Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia , bipolar disorder , or substance dependence .


Two hundred sixty-five veterans were enrolled from November 23 , 2009 , through September 28 , 2011 , randomized to usual care ( UC ) or the TOP intervention , and followed up for 12 months .


Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers .


Off-site PTSD care teams included telephone nurse care managers , telephone pharmacists , telepsychologists , and telepsychiatrists .


Nurses conducted care management activities .


Pharmacists reviewed medication histories .


Psychologists delivered cognitive processing therapy via interactive video .


Psychiatrists supervised the team and conducted interactive video psychiatric consultations .


The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale .


Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy .


During the 12-month follow-up period , 73 of the 133 patients randomized to TOP ( 54.9 % ) received cognitive processing therapy compared with 16 of 132 randomized to UC ( 12.1 % ) ( odds ratio , 18.08 [ 95 % CI , 7.96-41 .06 ] ; P < .001 ) .


Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores ( from 35.0 to 29.1 ) compared with those in the UC arm ( from 33.5 to 32.1 ) at 6 months ( = -3.81 ; P = .002 ) .


Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores ( from 35.0 to 30.1 ) compared with those in the UC arm ( from 33.5 to 31.7 ) at 12 months ( = -2.49 ; P = .04 ) .


There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant .


Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores ( = -3.86 [ 95 % CI , -7.19 to -0.54 ] ; P = .02 ) and fully mediated the intervention effect at 12 months .


Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes .


clinicaltrials.gov Identifier : NCT00821678 .


Pregnancy is a recognised high risk period for excessive weight gain , contributing to postpartum weight retention and obesity development long-term .


We aimed to reduce postpartum weight retention following a low-intensity , self-management intervention integrated with routine antenatal care during pregnancy .


228 women at increased risk of gestational diabetes , < 15 weeks gestation were randomised to intervention ( 4 self-management sessions ) or control ( generic health information ) .


Outcomes , collected at baseline and 6 weeks postpartum , included anthropometrics ( weight and height ) , physical activity ( pedometer ) and questionnaires ( health behaviours ) .


Mean age ( 32.34.7 and 31.74.4 years ) and body mass index ( 30.45.6 and 30.35.9 kg/m2 ) were similar between intervention and control groups , respectively at baseline .


By 6 weeks postpartum , weight change in the control group was significantly higher than the intervention group with a between group difference of 1.455.1 kg ( 95 % CI : -2.86 , -0.02 ; p < 0.05 ) overall , with a greater difference in weight found in overweight , but not obese women .


Intervention group allocation , higher baseline BMI , GDM diagnosis , country of birth and higher age were all independent predictors of lower weight retention at 6 weeks postpartum on multivariable linear regression .


Other factors related to weight including physical activity , did not differ between groups .


A low intensity intervention , integrated with standard antenatal care is effective in limiting postpartum weight retention .


Implementation research is now required for scale-up to optimise antenatal health care .


Australian New Zealand Clinical Trial Registry Number : ACTRN12608000233325 .


Registered 7/5/2008 .


Categorization of colon cancers into distinct subtypes using a combination of pathway-based biomarkers could provide insight into stage-independent variability in outcomes .


We used a polymerase chain reaction-based assay to detect mutations in BRAF ( V600E ) and in KRAS in 2720 stage III cancer samples , collected prospectively from patients participating in an adjuvant chemotherapy trial ( NCCTG N0147 ) .


Tumors deficient or proficient in DNA mismatch repair ( MMR ) were identified based on detection of MLH1 , MSH2 , and MSH6 proteins and methylation of the MLH1 promoter .


Findings were validated using tumor samples from a separate set of patients with stage III cancer ( n = 783 ) .


Association with 5-year disease-free survival was evaluated using Cox proportional hazards models .


Tumors were categorized into 5 subtypes based on MMR status and detection of BRAF or KRAS mutations which were mutually exclusive .


Three subtypes were MMR proficient : those with mutations in BRAF ( 6.9 % of samples ) , mutations in KRAS ( 35 % ) , or tumors lacking either BRAF or KRAS mutations ( 49 % ) .


Two subtypes were MMR deficient : the sporadic type ( 6.8 % ) with BRAF mutation and/or or hypermethylation of MLH1 and the familial type ( 2.6 % ) , which lacked BRAF ( V600E ) or hypermethylation of MLH1 .


A higher percentage of MMR-proficient tumors with BRAF ( V600E ) were proximal ( 76 % ) , high-grade ( 44 % ) , N2 stage ( 59 % ) , and detected in women ( 59 % ) , compared with MMR-proficient tumors without BRAF ( V600E ) or KRAS mutations ( 33 % , 19 % , 41 % , and 42 % , respectively ; all P < .0001 ) .


A significantly lower proportion of patients with MMR-proficient tumors with mutant BRAF ( hazard ratio = 1.43 ; 95 % confidence interval : 1.11-1 .85 ; Padjusted = .0065 ) or mutant KRAS ( hazard ratio = 1.48 ; 95 % confidence interval : 1.27-1 .74 ; Padjusted < .0001 ) survived disease-free for 5 years compared with patients whose MMR-proficient tumors lacked mutations in either gene .


Disease-free survival rates of patients with MMR-deficient sporadic or familial subtypes was similar to those of patients with MMR-proficient tumors without BRAF or KRAS mutations .


The observed differences in survival rates of patients with different tumor subtypes were validated in an independent cohort .


We identified subtypes of stage III colon cancer , based on detection of mutations in BRAF ( V600E ) or KRAS , and MMR status that show differences in clinical and pathologic features and disease-free survival .


Patients with MMR-proficient tumors and BRAF or KRAS mutations had statistically shorter survival times than patients whose tumors lacked these mutations .


The tumor subtype found in nearly half of the study cohort ( MMR-proficient without BRAF ( V600E ) or KRAS mutations ) had similar outcomes to those of patients with MMR-deficient cancers .


This paper is embedded in a randomised controlled trial ( Alcohol and Employment ) that investigated whether welfare-to-work schemes combined with alcohol treatment were more effective than welfare-to-work schemes alone for helping unemployed welfare recipients with alcohol problems get back to employment and reduce their alcohol problems .


The implementation of Alcohol and Employment turned out to be challenging , and fewer welfare recipients than expected were enrolled .


The aim of this paper was to identify and investigate obstacles to the implementation of Alcohol and Employment .


Our main objective was to study the job consultants ' role in the implementation process as they were key personnel in conducting the trial .


The process evaluation was conducted in four Danish municipalities in 2011-2012 .


Data for identifying factors important for the implementation were collected through observations and focus group interviews with job consultants .


Data were analysed thematically and thoroughly discussed among members of the project team ; emerging themes were then grouped and read again repeatedly until the themes were consistent .


Three themes emerged as the main factors influencing the degree of implementation of Alcohol and Employment : ( 1 ) The job consultants ' personal attitudes toward alcohol were an important factor .


The job consultants generally did not consider a high alcohol intake to be an impediment to employment , or they thought that alcohol problems were only symptoms of more profound problems .


( 2 ) The job consultants ' perception of their own roles and responsibilities in relation to the welfare recipients was a barrier : they felt that addressing alcohol problems and at the same time sustaining trust with the welfare recipient was difficult .


Also , they did not consider alcohol problems to be their responsibility .


( 3 ) Shortage of time and resources among the job consultants was determined to be an influential factor .


We identified important factors at the individual level among the job consultants who threatened the implementation of Alcohol and Employment .


Future studies in similar settings can take advantage of these findings when preparing interventions that are implemented by job consultants or similar professionals .


ClinicalTrials.gov ID : NCT01416103 .


We designed a continuing medical education ( CME ) program to teach primary care physicians ( PCP ) how to engage in cancer risk communication and shared decision making with patients who have limited health literacy ( HL ) .


We evaluated whether training PCPs , in addition to audit-feedback , improves their communication behaviors and increases cancer screening among patients with limited HL to a greater extent than only providing clinical performance feedback .


Four-year cluster randomized controlled trial .


Eighteen PCPs and 168 patients with limited HL who were overdue for colorectal/breast/cervical cancer screening .


Communication intervention PCPs received skills training that included standardized patient ( SP ) feedback on counseling behaviors .


All PCPs underwent chart audits of patients ' screening status semiannually up to 24 months and received two annual performance feedback reports .


PCPs experienced three unannounced SP encounters during which SPs rated PCP communication behaviors .


We examined between-group differences in changes in SP ratings and patient knowledge of cancer screening guidelines over 12 months ; and changes in patient cancer screening rates over 24 months .


There were no group differences in SP ratings of physician communication at baseline .


At follow-up , communication intervention PCPs were rated higher in general communication about cancer risks and shared decision making related to colorectal cancer screening compared to PCPs who only received performance feedback .


Screening rates increased among patients of PCPs in both groups ; however , there were no between-group differences in screening rates except for mammography .


The communication intervention did not improve patient cancer screening knowledge .


Compared to audit and feedback alone , including PCP communication training increases PCP patient-centered counseling behaviors , but not cancer screening among patients with limited HL .


Larger studies must be conducted to determine whether lack of changes in cancer screening were due to clinic/patient sample size versus ineffectiveness of communication training to change outcomes .


To investigate the safety and short term outcome of high dose recombinant human erythropoietin ( rhEpo ) given shortly after birth and subsequently over the first 2 days for neuroprotection to very preterm infants .


Randomized , double masked phase II trial .


Preterm infants ( gestational age 26 0/7 -31 6/7 weeks ) were given rhEpo ( nt = 229 ; 3000 U/kg body weight ) or NaCl 0.9 % ( nc = 214 ) intravenously at 3 , 12-18 , and 36-42 hours after birth .


There were no relevant differences between the groups for short-term outcomes such as mortality , retinopathy of prematurity , intraventricular hemorrhage , sepsis , necrotizing enterocolitis , and bronchopulmonary dysplasia .


At day 7-10 , we found significantly higher hematocrit values , reticulocyte , and white blood cell counts , and a lower platelet count in the rhEpo group .


Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events .


ClinicalTrials.gov : NCT00413946 .


Delayed graft function , which is reported in up to 50 % of kidney-transplant recipients , is associated with increased costs and diminished long-term graft function .


The effect that targeted mild hypothermia in organ donors before organ recovery has on the rate of delayed graft function is unclear .


We enrolled organ donors ( after declaration of death according to neurologic criteria ) from two large donation service areas and randomly assigned them to one of two targeted temperature ranges : 34 to 35C ( hypothermia ) or 36.5 to 37.5 C ( normothermia ) .


Temperature protocols , which were initiated after authorization was obtained for the organ to be donated and for the donor 's participation in the study , ended when organ donors left the intensive care unit for organ recovery in the operating room .


The primary outcome was delayed graft function in the kidney recipients , which was defined as the requirement for dialysis during the first week after transplantation .


Secondary outcomes were the rates of individual organs transplanted in each treatment group and the total number of organs transplanted from each donor .


The study was terminated early , on the recommendation of an independent data and safety monitoring board , after the interim analysis showed efficacy of hypothermia .


At trial termination , 370 organ donors had been enrolled ( 180 in the hypothermia group and 190 in the normothermia group ) .


A total of 572 patients received a kidney transplant ( 285 kidneys from donors in the hypothermia group and 287 kidneys from donors in the normothermia group ) .


Delayed graft function developed in 79 recipients of kidneys from donors in the hypothermia group ( 28 % ) and in 112 recipients of kidneys from donors in the normothermia group ( 39 % ) ( odds ratio , 0.62 ; 95 % confidence interval , 0.43 to 0.92 ; P = 0.02 ) .


Mild hypothermia , as compared with normothermia , in organ donors after declaration of death according to neurologic criteria significantly reduced the rate of delayed graft function among recipients .


( Funded by the Health Resources and Services Administration ; ClinicalTrials.gov number , NCT01680744 . )


Antipsychotics are commonly used for management of behavioural symptoms in dementia , among people in residential care .


This continues to occur despite their modest effectiveness , potential harms including increased risk of death and stroke , and absence of detrimental effect when people with dementia were randomised to antipsychotic withdrawal .


This study aims to test the hypothesis that the multifaceted REducing Anti-Psychotic use in residential care-Huntington Disease ( REAP-HD ) programme is more effective than standard staff education ( SSE ) in reducing antipsychotic use for people with HD in residential care facilities ( RCF ) .


this is a cluster randomised controlled trial with blinded outcome assessment .


The study population is healthcare professionals looking after people with HD in individual RCF , in the state of New South Wales .


Each RCF will be centrally randomised to the REAP-HD programme or the comparator , SSE .


Blinded outcome assessment will be performed by examining drug charts and using the Neuropsychiatric Inventory-Q ( NPI-Q ) .


Primary outcome is the proportion of people with HD who have had a reduction in antipsychotic use 4 months after the intervention .


Secondary outcome measures are ( 1 ) change in severity of behavioural symptoms , as measured by the NPI-Q at 4 months ( to ensure antipsychotic reduction has not lead to worsening behavioural symptoms ) , and ( 2 ) proportion of people with HD who have had a reduction in antipsychotic dosage at 4 months for each strategy , compared to 4 months prior to enrolment ( to capture the possibility that both arms reduced antipsychotic use ) .


Analysis will be by Intention-To-Treat and take into account the clustering .


Recruitment is ongoing , as of July 2014 .


This protocol has been approved by the Western Sydney Local Health District Human Research Ethics Committee , trial registration ACTRN12614000083695 .


Study results will be disseminated through peer-reviewed publication in an anonymous manner .


ACTRN12614000083695 , the Australian New Zealand Clinical Trials Registry .


The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events .


In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed .


Fatal and non-fatal cardiovascular events were included .


Spirometry included forced expiratory volume measured in units of one-second percent predicted ( FEV1 % predicted ) and FEV1 divided by forced vital capacity ( FVC ; FEV1/FVC ) .


CT examinations were quantified for coronary artery calcium volume , pulmonary emphysema ( perc15 ) and bronchial wall thickness ( pi10 ) .


Data were analysed via a Cox proportional hazard analysis , net reclassification improvement ( NRI ) and C-indices .


184 participants experienced a cardiovascular event during a median follow-up of 2.9 years .


Age , pack-years and smoking status adjusted hazard ratios were 0.992 ( 95 % confidence interval ( CI ) 0.985-0 .999 ) for FEV1 % predicted , 1.000 ( 95 % CI 0.986-1 .015 ) for FEV1/FVC , 1.014 ( 95 % CI 1.005-1 .023 ) for perc15 per 10 HU , and 1.269 ( 95 % CI 1.024-1 .573 ) for pi10 per 1 mm .


The incremental C-index ( < 0.015 ) and NRI ( < 2.8 % ) were minimal .


Coronary artery calcium volume had a hazard ratio of 1.046 ( 95 % CI 1.034-1 .058 ) per 100 mm ( 3 ) , an increase in C-index of 0.076 and an NRI of 16.9 % ( P < 0.0001 ) .


Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events , but did not contain clinically relevant independent prognostic information for cardiovascular events .


Pulmonary CT biomarkers and spirometry are associated with cardiovascular events These pulmonary measurements do not contain clinically relevant independent prognostic information Only coronary calcium score improved cardiovascular risk prediction above age and smoking .


Effective and safe management of oral anticoagulant treatment ( OAT ) requires a high level of patient knowledge and adherence .


The aim of this study was to assess patient knowledge about OAT and factors associated with patient knowledge .


This is a baseline survey of a cluster-randomized controlled trial in 22 general practices with an educational intervention for patients or their caregivers .


We assessed knowledge about general information on OAT and key facts regarding nutrition , drug-interactions and other safety precautions of 345 patients at baseline .


Participants rated their knowledge about OAT as excellent to good ( 56 % ) , moderate ( 36 % ) or poor ( 8 % ) .


However , there was a discrepancy between self-rated knowledge and evaluated actual knowledge and we observed serious knowledge gaps .


Half of the participants ( 49 % ) were unaware of dietary recommendations .


The majority ( 80 % ) did not know which non-prescription analgesic is the safest and 73 % indicated they would not inform pharmacists about OAT .


Many participants ( 35-75 % ) would not recognize important emergency situations .


After adjustment in a multivariate analysis , older age and less than 10 years education remained significantly associated with lower overall score , but not with self-rated knowledge .


Patients have relevant knowledge gaps , potentially affecting safe and effective OAT .


There is a need to assess patient knowledge and for structured education programs .