Inflammatory bowel disease ( IBD ) is a chronic condition with an unpredictable disease course .


Rates of anxiety and depression among IBD patients in relapse ( active disease symptoms ) as well as in remission are higher than in the general population .


Previous studies suggest that the prolonged effect of pain , anxiety , distress and depression have a detrimental effect on patients ` quality of life ( QoL ) .


Poor QoL in itself is associated with further symptom relapse .


Mindfulness based cognitive therapy ( MBCT ) is a psychological group intervention that has the potential to improve QoL .


When used in other chronic conditions , it demonstrated reduced negative effect from pain and psychological factors at completion of an 8-week MBCT course .


The effect of MBCT has never been researched in IBD .


The aim of this study is to obtain the information required to design a full scale randomised controlled trial ( RCT ) that will examine the effectiveness of MBCT in improving quality of life for IBD patients .


This is an exploratory RCT with embedded process evaluation .


Forty IBD patients will be recruited from NHS outpatient gastroenterology clinics and will be randomised to either a MBCT ( intervention ) group or to a wait-list ( control ) group .


All participants will undergo 16 h of structured group training over an 8-week period , with the control group starting 6 months later than the intervention group .


Primary outcomes are recruitment , completion/retention rates and adherence and adaptation to the MBCT manual for IBD patients .


The secondary outcome is to assess the feasibility of collecting reliable and valid data on proposed outcome measures such as quality of life , anxiety , depression , disease activity and mindful awareness .


The process evaluation will use a survey and focus groups to assess the acceptability of the intervention and trial procedures for IBD patients .


The outcomes of this study will help define the barriers , uptake and perceived benefits of MBCT program for IBD patients .


This information will enable the design of a full-scale study assessing the effect of MBCT on quality of life for IBD patients .


Current Controlled Trials : ISRCTN27934462 .


General anesthesia usually requires mechanical ventilation , which is traditionally accomplished with constant tidal volumes in volume - or pressure-controlled modes .


Experimental studies suggest that the use of variable tidal volumes ( variable ventilation ) recruits lung tissue , improves pulmonary function and reduces systemic inflammatory response .


However , it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation .


The PROtective VARiable ventilation trial ( ` PROVAR ' ) is a single center , randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3hours .


PROVAR compares conventional ( non-variable ) lung protective ventilation ( CV ) with variable lung protective ventilation ( VV ) regarding pulmonary function and inflammatory response .


The primary endpoint of the study is the forced vital capacity on the first postoperative day .


Secondary endpoints include further lung function tests , plasma cytokine levels , spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications .


We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3hours .


PROVAR is the first randomized controlled trial aiming at intra - and postoperative effects of VV on lung function .


This study may help to define the role of VV during general anesthesia requiring mechanical ventilation .


Clinicaltrials.gov NCT01683578 ( registered on September 3 3012 ) .


To evaluate visual function in patients with symptomatic vitreomacular adhesion ( VMA ) / vitreomacular traction including when associated with macular hole after ocriplasmin treatment , and the association between resolution of the underlying condition and improvement in visual function .


Six hundred and fifty-two patients from 2 Phase 3 trials received a single intravitreal injection of ocriplasmin 125 g ( n = 464 ) or placebo ( n = 188 ) .


Mean and categorical changes from baseline in best-corrected visual acuity and 25-item Visual Function Questionnaire scores were used to evaluate visual function .


Subgroups with VMA resolution and full-thickness macular hole closure were compared .


Overall , 42 % of patients who achieved VMA resolution at Day 28 had a 2-line improvement in best-corrected visual acuity at Month 6 , and 20 % had a 3-line improvement .


Likewise , 69 % of patients with nonsurgical full-thickness macular hole closure at Day 28 had a 2-line improvement at Month 6 , and 48 % had a 3-line best-corrected visual acuity improvement .


Mean improvements in 25-item Visual Function Questionnaire scores were associated with achieving VMA resolution and nonsurgical full-thickness macular hole closure .


In patients with symptomatic VMA/vitreomacular traction , VMA resolution and nonsurgical full-thickness macular hole closure were each associated with improvements in visual function .


Resolving the underlying anatomical condition in symptomatic VMA/vitreomacular traction will increase the probability of achieving a clinically meaningful improvement in visual function .


It is well established in the literature that regular participation in physical activity is effective for chronic disease management and prevention .


Remote monitoring technologies ( ie , mHealth ) hold promise for engaging patients in self-management of many chronic diseases .


The purpose of this study was to test the effectiveness of an mHealth study with tailored physical activity prescription targeting changes in various intensities of physical activity ( eg , exercise , sedentary behavior , or both ) for improving physiological and behavioral markers of lifestyle-related disease risk .


Forty-five older adults ( aged 55-75 years ; mean age 63 5 years ) were randomly assigned to receive a personal activity program targeting changes to either daily exercise , sedentary behavior , or both .


All participants received an mHealth technology kit including smartphone , blood pressure monitor , glucometer , and pedometer .


Participants engaged in physical activity programming at home during the 12-week intervention period and submitted physical activity ( steps/day ) , blood pressure ( mm Hg ) , body weight ( kg ) , and blood glucose ( mmol/L ) measures remotely using study-provided devices .


There were no differences between groups at baseline ( P > 0.05 ) .


The intervention had a significant effect ( F ( 10 488 ) = 2.947 , P = 0.001 , P = 0.057 ) , with similar changes across all groups for physical activity , body weight , and blood pressure ( P > 0.05 ) .


Changes in blood glucose were significantly different between groups , with groups prescribed high-intensity activity ( ie , exercise ) demonstrating greater reductions in blood glucose than the group prescribed changes to sedentary behavior alone ( P < 0.05 ) .


Findings demonstrate the utility of pairing mHealth technologies with activity prescription for prevention of lifestyle-related chronic diseases among an at-risk group of older men and women .


RESULTS support the novel approach of prescribing changes to sedentary behaviors ( alone , and in conjunction with exercise ) to reduce risk of developing lifestyle-related chronic conditions .


To examine the feasibility of collecting data relating to irritable bowel syndrome ( IBS ) , symptoms by short message service ( SMS ) text and explore the data to assess its usefulness .


In a randomized parallel group design substudy , 59 consenting participants recruited from primary care to a trial of acupuncture for IBS ( ISRCTN 08827905 ) were randomized to receive a one-question SMS message at either 9:30 am or at 6:30 pm for 7days : `` On a scale of 0-9 , with 0 being no symptoms and 9 being the worst symptoms you could have , how would you score your IBS symptoms now ?


Please text back a single number . ''


Of the total messages , 59 % ( n = 203 ) were answered within 15minutes , 73.4 % ( n = 254 ) within 1hour , and 97 % ( n = 334 ) within 10hours .


Response rates to evening texts were higher ( 93.5 % vs. 87.6 % P = 0.05 ) and response times shorter though not significantly ( median : 0 vs. 5hours ; P = 0.12 ) .


There was no difference in mean scores , and morning symptoms varied more .


Mean scores correlated significantly with IBS trial primary outcome measure , the IBS symptom severity score , and secondary outcome measures .


Among IBS trial participants , data collection by SMS is feasible and acceptable , and there is potential for deriving meaningful data from the scores .


Keratosis pilaris ( KP ) is a common skin disorder of follicular prominence and erythema that typically affects the proximal extremities , can be disfiguring , and is often resistant to treatment .


Shorter-wavelength vascular lasers have been used to reduce the associated erythema but not the textural irregularity .


To determine whether the longer-wavelength 810-nm diode laser may be effective for treatment of KP , particularly the associated skin roughness/bumpiness and textural irregularity .


We performed a split-body , rater-blinded , parallel-group , balanced ( 1:1 ) , placebo-controlled randomized clinical trial at a dermatology outpatient practice of an urban academic medical center from March 1 to October 1 , 2011 .


We included all patients diagnosed as having KP on both arms and Fitzpatrick skin types I through III .


Of the 26 patients who underwent screening , 23 met our enrollment criteria .


Of these , 18 patients completed the study , 3 were lost to or unavailable for follow-up , and 2 withdrew owing to inflammatory hyperpigmentation after the laser treatment .


Patients were randomized to receive laser treatment on the right or left arm .


Each patient received treatment with the 810-nm pulsed diode laser to the arm randomized to be the treatment site .


Treatments were repeated twice , for a total of 3 treatment visits spaced 4 to 5 weeks apart .


The primary outcome measure was the difference in disease severity score , including redness and roughness/bumpiness , with each graded on a scale of 0 ( least severe ) to 3 ( most severe ) , between the treated and control sites .


Two blinded dermatologists rated the sites at 12 weeks after the initial visit .


At follow-up , the median redness score reported by the 2 blinded raters for the treatment and control sides was 2.0 ( interquartile range [ IQR ] , 1-2 ; P = .11 ) .


The median roughness/bumpiness score was 1.0 ( IQR , 1-2 ) for the treatment sides and 2.0 ( IQR , 1-2 ) for the control sides , a difference of 1 ( P = .004 ) .


The median overall score combining erythema and roughness/bumpiness was 3.0 ( IQR , 2-4 ) for the treatment sides and 4.0 ( IQR , 3-5 ) for the control sides , a difference of 1 ( P = .005 ) .


Three treatments with the 810-nm diode laser may induce significant improvements in skin texture and roughness/bumpiness in KP patients with Fitzpatrick skin types I through III , but baseline erythema is not improved .


Complete treatment of erythema and texture in KP may require diode laser treatment combined with other laser or medical modalities that address redness .


clinicaltrials.gov Identifier : NCT01281644 .


To determine the association between nonalcoholic fatty liver disease ( NAFLD ) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic ( CT ) angiography .


This study was approved by the local ethics committees ; informed consent was obtained .


Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography , or ROMICAT , II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included .


Readers assessed coronary CT angiography images for the presence of coronary plaque , significant stenosis ( 50 % ) , and high-risk plaque features ( positive remodeling , CT attenuation < 30 HU , napkin-ring sign , spotty calcium ) .


NAFLD was defined as hepatic steatosis at nonenhanced CT ( liver minus spleen CT attenuation < 1 HU ) without evidence of clinical liver disease , liver cirrhosis , or alcohol abuse .


To determine the association between high-risk plaque and NAFLD , univariable and multivariable logistic regression analyses were performed , with high-risk plaque as a dependent variable and NAFLD , traditional risk factors , and extent of coronary atherosclerosis as independent variables .


Overall , 182 ( 40.9 % ) of 445 patients had CT evidence of NAFLD .


High-risk plaque was more frequent in patients with NAFLD than in patients without NAFLD ( 59.3 % vs 19.0 % , respectively ; P < .001 ) .


The association between NAFLD and high-risk plaque ( odds ratio , 2.13 ; 95 % confidence interval : 1.18 , 3.85 ) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors .


NAFLD is associated with advanced high-risk coronary plaque , independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease .


Bioimpedance analysis ( BIA ) is well established to assess body composition .


Agreements between single - and multi-frequency bioimpedance ( SF-BIA , MF-BIS ) measurements in subjects undergoing 6 or 3 times/week hemodialysis ( HD ) were analyzed .


Total body water ( TBW ) and intra - and extracellular fluid ( ICF , ECF ) of subjects enrolled in the Frequent Hemodialysis Network ( FHN ) Daily Trial ( www.clinicaltrials.gov No .


NCT00264758 ) were measured with a Hydra 4200 at baseline ( BL ) and at 5 months ( M5 ) .


Volumes were computed using SF ( at 50 kHz ) and MF approaches .


Agreement was assessed by means of linear regression and Bland-Altman analysis and treatment effects by t test .


35 subjects ( 17 on the more frequent regimen , 26 males , 20 African-American , 48 9 years , pre-HD weight 84 19 kg ) were studied .


Assessments with SF-BIA and MF-BIS correlated significantly at BL and M5 in both arms .


No proportional errors , but systematic biases over the entire range of values were found at BL and M5 .


Agreement did not differ between subjects randomized to either HD treatment arm at both time points .


MF-BIS appears to have better precision than SF-BIA allowing the observation of a significant treatment effect by the intervention [ -1.5 ( 95 % CI -2.5 to -0.5 ) l ] on ECF , not found for ECF SF-BIA .


Precision also affected the statistical power of the SF-BIA data in the current analysis .


Both methods showed agreement without significant proportional errors regardless of HD frequency and can be used for longitudinal analyses .


SF-BIA has lower precision which needs thorough consideration in the design of future trials with similar outcomes .


To determine the efficacy of chest compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation , in comparison with that of aspiration alone , in removing secretions , normalizing hemodynamics , and improving respiratory mechanics in patients on mechanical ventilation .


This was a randomized crossover clinical trial involving patients on mechanical ventilation for more than 48 h in the ICU of the Porto Alegre Hospital de Clnicas , in the city of Porto Alegre , Brazil .


Patients were randomized to receive aspiration alone ( control group ) or compression accompanied by a 10-cmH2O increase in baseline inspiratory pressure on pressure support ventilation ( intervention group ) .


We measured hemodynamic parameters , respiratory mechanics parameters , and the amount of secretions collected .


We included 34 patients .


The mean age was 64.2 14.6 years .


In comparison with the control group , the intervention group showed a higher median amount of secretions collected ( 1.9 g vs. 2.3 g ; p = 0.004 ) , a greater increase in mean expiratory tidal volume ( 16 69 mL vs. 56 69 mL ; p = 0.018 ) , and a greater increase in mean dynamic compliance ( 0.1 4.9 cmH2O vs. 2.8 4.5 cmH2O ; p = 0.005 ) .


In this sample , chest compression accompanied by an increase in pressure support significantly increased the amount of secretions removed , the expiratory tidal volume , and dynamic compliance .


( ClinicalTrials.gov Identifier : NCT01155648 [ http://www.clinicaltrials.gov/] ) .


This study aimed to evaluate the effectiveness of multi-disciplinary treatment approaches in reducing neurological disabilities in premature infants .


A total of 117 infants who were born premature in our hospital between March 2008 and February 2010 but had no congenital malformations and no severe neonatal complications , were enrolled in this study .


They were randomly allocated to a multi-disciplinary treatment group ( n = 63 ) and a control group ( n = 54 ) .


While patients in the control group underwent an early conventional treatment , those in the multi-disciplinary treatment group were subjected to regular development monitoring , neurological examination and screening for brain injury , neuro-nutrition and neurodevelopment therapies , and rehabilitation training .


The incidence rates of abnormalities in posture , reflex , sleep , muscle tone and EEG were significantly lower in the multi-disciplinary treatment group than in the control froup ( P < 0.05 ) at corrected postnatal ages of 6-12 months .


At corrected postnatal ages of 6 , 12 , 18 and 24 months , both mental development index ( MDI ) and psychomotor development index ( PDI ) scores were significantly higher in the multi-disciplinary treatment group than in the control group ( P < 0.05 ) .


At corrected postnatal age of 3 years , incidence rates of cerebral palsy , language barrier , abnormal muscle tone and hearing impairment were significantly lower in the multi-disciplinary treatment group than in the control group ( P < 0.05 ) .


Early multi-disciplinary intervention approaches may significantly improve mental and motor developments and reduce the incidence of cerebral palsy-associated neurological disabilities in premature infants .


Enhanced muscle strength is seen when resistance exercise is combined with the consumption of nutritional supplements .


Although there is a limited number of studies available about the efficacy of gamma oryzanol supplementation with resistance exercise in humans , but its usage as a nutritional supplement for strength is common in athletes .


The aim of this study was to determine the effects of gamma oryzanol supplementation during 9-week resistance training on muscular strength and anthropometric measurements of young healthy males .


In this double-blind clinical trial , changes of anthropometric measurements and muscular strength were studied after chronic resistance exercise and gamma oryzanol supplementation in 30 healthy volunteers ( 16 in supplement and 14 in placebo ) .


Each day , gamma oryzanol supplement ( 600 mg ) and placebo ( the same amount of lactose ) were consumed after training .


The participants exercised with 80 per cent 1-Repetition Maximum ( 1-RM ) , for one hour and four days/week .


Anthropometric measurements and subjects ' 1-RM for muscular strength were determined at the commencement and end of the 9-week study .


There was no significant difference between the baseline characteristics and target variables at baseline between the two groups .


After gamma oryzanol supplementation , there was no significant difference in the means of anthropometric and skin fold measurements between the supplement and placebo groups .


However , there were significant differences between the supplement and placebo groups for 1-RM of bench press and leg curl , which showed that gamma oryzanol improved muscle strength following resistance training .


Our findings indicated that 600 mg/day gamma oryzanol supplementation during the 9-week resistance training did not change anthropometric and body measurements , but it increased muscular strength in young healthy males .


Further , studies need to be done in trained athletes , women , and in patients who suffer from muscular fatigue .


Bifurcation lesions are frequent among patients with symptomatic coronary disease treated by percutaneous coronary intervention .


Current evidence recommends a conservative ( provisional ) approach when treating the side branch ( SB ) .


The TRYTON ( Prospective , Single Blind , Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries ) bifurcation trial sought to compare treatment of de novo true bifurcation lesions using a dedicated bifurcation stent or SB balloon angioplasty .


We randomly assigned patients with true bifurcation lesions to a main vessel stent plus provisional stenting or the bifurcation stent .


The primary endpoint ( powered for noninferiority ) was target vessel failure ( TVF ) ( cardiac death , target vessel myocardial infarction , and target vessel revascularization ) .


The secondary angiographic endpoint ( powered for superiority ) was in-segment percent diameter stenosis of the SB at 9 months .


We randomized 704 patients with bifurcation coronary lesions at 58 centers ( 30 from Europe and 28 from the United States ) .


At 9 months , TVF was 17.4 % in the bifurcation stent group compared with 12.8 % in the provisional group ( p = 0.11 ) , mainly because of a higher periprocedural myocardial infarction rate ( 13.6 % vs. 10.1 % , p = 0.19 ) .


The TVF difference of +4.6 % ( 2-sided 95 % confidence interval : -1.0 to 10.3 ; upper limit of the 1-sided 95 % confidence interval : 10.3 ) was not within the pre-specified noninferiority margin of 5.5 % ( p = 0.42 for noninferiority ) .


The SB in-segment diameter stenosis among the angiographic cohort was lower in the bifurcation stent group compared with the provisional group ( 31.6 % vs. 38.6 % , p = 0.002 for superiority ) , with no difference in binary restenosis rates ( diameter stenosis50 % ) at 9 months follow-up ( 22.6 % vs. 26.8 % , p = 0.44 ) .


Provisional stenting should remain the preferred strategy for treatment of non-left main true coronary bifurcation lesions .


( Prospective , Single Blind , Randomized Controlled Study to Evaluate the Safety & Effectiveness of the Tryton Side Branch Stent Used With DES in Treatment of de Novo Bifurcation Lesions in the Main Branch & Side Branch in Native Coronaries [ TRYTON ] ; NCT01258972 ) .


Individuals with physical disabilities experience disparities in obesity ; yet few interventions have incorporated accommodations necessary for weight loss in this population .


This project compared the effectiveness of two weight loss interventions among individuals with physical disabilities .


Adults with physical disabilities who were overweight or obese were randomized across two diet approaches : a modified version of the MyPlate diet ( usual care ( UC ) ) and a modified Stoplight Diet ( SLDm ) supplemented with portion-controlled meals .


Project staff met monthly with each participant to measure weight , 24-recalls of diet intake , self-tracking of foods and beverages , and physical activity during the preceding month .


Of 126 enrollees , 70 % completed the initial 6-month diet phase and 60 % of these completed a 6-month follow-up phase .


Participants in the SLDm group reduced weight and BMI during the 6 month intervention , and maintained or lost more weight during the 6 month maintenance period .


Alternately , the UC diet resulted in a reduction in weight and BMI only at 6 months .


BMI from baseline was significantly more improved for SLDm than UC and , among those who lost weight , the SLDm group lost more weight at 6 and 12 months .


These results demonstrate that interventions with proper design and accommodations can overcome the barriers to weight loss unique to individuals with mobility impairments with low income .


Additionally , the results suggest that using portion control may be more effective than teaching portion sizes .


Previous studies have reported that obese people with trisomy 21 suffer from low-grade systemic inflammation .


A recent study has found that aerobic training reduced inflammation in obese women with Down syndrome .


To the best of our knowledge , the study reported in this paper is the first to determine for how long these effects were maintained after completion of the programme .


Twenty premenopausal obese women ( 18-30 years old ) with Down syndrome volunteered for this study .


Eleven were randomly assigned to the intervention group and performed a 10-week aerobic training programme , 3 sessions per week , consisting of warming-up followed by treadmill exercise ( 30-40 min ) at a work intensity of 55-65 % of peak heart rate and a cooling-down period .


The control group included 9 , age , sex and BMI matched women with Down syndrome that did not perform any training programme .


Fat mass percentage and distribution were measured .


Plasma level of IL-6 and high-sensitive C-reactive protein ( hs-CRP ) were monitored .


Time-course changes for these outcomes were assessed at pre - and post-intervention .


Further , they were re-evaluated at 1 , 3 and 6 months after completion of the programme .


Three months after completion of the programme , plasma levels of IL-6 and hs-CRP were significantly increased .


Up to 6 months later , both fat mass percentage and waist circumference ( WC ) were significantly increased .


Furthermore , physical fitness was also impaired in the intervention group .


No changes were observed in the control group .


A 3-month detraining period significantly impaired chronic inflammation in obese women with DS .


Physicians are a commonly targeted group in health research surveys , but their response rates are often relatively low .


The goal of this paper was to evaluate the effect of unconditional incentives in the form of a coffee card on physician postal survey response rates .


Following 13 key informant interviews and eight cognitive interviews a survey questionnaire was developed .


A random sample of 534 physicians , stratified by physician group ( geriatricians , family physicians , emergency physicians ) was selected from a national medical directory .


Using computer generated random numbers ; half of the physicians in each stratum were allocated to receive a coffee card to a popular national coffee chain together with the first survey mailout .


The intervention was a $ 10 Tim Hortons gift card given to half of the physicians who were randomly allocated to receive the incentive .


265 ( 57.0 % ) physicians completed the survey .


The response rate was significantly higher in the group allocated to receive the incentive ( 62.7 % vs 51.3 % in the control group ; p = 0.01 ) .


Our results indicate that an unconditional incentive in the form of a coffee gift card can substantially improve physician response rates .


Future research can look at the effect of varying amounts of cash on the gift cards on response rates .


In resource-poor settings , cold chain requirements present barriers for vaccine delivery .


We evaluated the immunogenicity and safety of tetanus toxoid ( TT ) vaccine in `` Controlled Temperature Chain '' ( CTC ; up to 40 C for < 30 days before administration ) , compared to standard cold chain ( SCC ; 2-8 C ) .


Prior to the study , stability parameters of TT-CTC were shown to meet international requirements .


A cluster randomized , non-inferiority trial was conducted in Mossala district , Chad , December 2012-March 2013 .


Thirty-four included clusters were randomized to CTC or SCC .


Women aged 14-49 years , eligible for TT vaccination and with a history of 1 TT dose , received two TT doses 4 weeks apart .


Participants were blinded to allocation strategy .


Tetanus antibody titers were measured using standard ELISA at inclusion and 4 weeks post-TT2 .


Primary outcome measures were post-vaccination seroconversion and fold-increase in geometric mean concentrations ( GMC ) .


Non-inferiority was by seroconversion difference ( TTSCC-TTCTC ) < 5 % and ratio of GMCs ( TTSCC/TTCTC ) < 1.5 .


Adverse events were monitored at health centers and at next contact with participants .


A total of 2128 women ( CTC = 1068 ; SCC = 1060 ) were recruited .


Primary intention to vaccinate analysis included 1830 participants ; 272 of these were included in the seroconversion analysis .


Seroconversion was reached by > 95 % of participants ; upper 95 % CI of the difference was 5.6 % .


Increases in GMC were over 4-fold ; upper 95 % CI of GMC ratio was 1.36 in the adjusted analysis .


Few adverse events were recorded .


This study demonstrates the immunogenicity and safety of TT in CTC at < 40 C for < 30 days .


The high proportion of participants protected at baseline results in a reduction of power to detect a 5 % non-inferiority margin .


However , results at a 10 % non-inferiority margin , the comparable GMC increases and vaccine 's stability demonstrated in the preliminary phase indicate that CTC can be an alternative strategy for TT delivery in situations where cold chain can not be maintained .


Although prevailing spinal nerve involvement has been recognized in a few detailed Guillain-Barr syndrome ( GBS ) autopsy reports , imaging studies addressing this question in cervical nerves are lacking .


We describe clinical , electrophysiological , ultrasonographic ( US ) and pathological findings in six consecutive early GBS patients , evaluated within 10 days of onset .


Patients ' ages ranged from 37 to 80 years .


Five patients required mechanical ventilation , two of them having died 9 and 28 days after onset .


Upper - and lower-limb nerve US showed abnormal findings in just 8.8 % of scanned peripheral nerves .


In comparison with 46 aged-matched control subjects , US of the fifth to seventh cervical nerves showed changes in four cases , which consisted of significant nerve enlargement , blurred boundaries of the corresponding ventral rami , or both .


Autopsy study in one case demonstrated that pathology , consisting of demyelination and endoneurial inflammatory oedema , mainly involved cervical and lumbar nerves .


In early GBS inflammatory oedema of spinal nerves is a pathogenically relevant feature to understanding the mechanism of ascending paralysis , particularly when conventional electrophysiological studies are normal or not diagnostic .


Findings advocate the use of cervical nerve US in early GBS .


AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer ( mCRC ) with cetuximab , capecitabine and irinotecan versus cetuximab , capecitabine and oxaliplatin .


This analysis investigated the impact of primary tumor location on outcome of patients .


Left-sided primary tumors were defined as tumors from rectum to left flexure , while tumors in the remaining colon were regarded right sided .


Overall survival ( OS ) , progression-free survival ( PFS ) and response rate were correlated with primary tumor location .


A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation .


Of 146 patients of the AIO KRK-0104 trial , 100 patients presented left-sided ( of those 68 KRAS codon 12/13 wild-type ) and 46 patients right-sided primary tumors ( of those 27 KRAS codon 12/13 wild-type ) .


Left-sided tumors were associated with significantly longer OS ( p = 0.016 , HR = 0.63 ) and PFS ( p = 0.02 , HR = 0.67 ) as compared to right-sided tumors .


These effects were present in the KRAS codon 12/13 wild-type population ( HR OS : 0.42 ; HR PFS : 0.54 ) , while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors ( HR OS : 1.3 ; HR PFS : 1.01 ) .


A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed .


Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy .


Left-sided primary tumor location might be a predictor of cetuximab efficacy .


The ideal preparation regimen for pediatric colonoscopy remains elusive , and available preparations continue to represent a challenge for children .


The aim of this study was to compare the efficacy , safety , tolerability , and acceptance of 4 methods of bowel cleansing before colonoscopy in children .


This randomized , investigator-blinded , noninferiority trial enrolled all children aged 2 to 18 years undergoing elective colonoscopy in a referral center for pediatric gastroenterology .


Patients were randomly assigned to receive polyethylene glycol ( PEG ) 4000 with simethicon ( PEG-ELS group ) or PEG-4000 with citrates and simethicone plus bisacodyl ( PEG-CS + Bisacodyl group ) , or PEG 3350 with ascorbic acid ( PEG-Asc group ) , or sodium picosulfate plus magnesium oxide and citric acid ( NaPico + MgCit group ) .


Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale .


The primary end point was overall colon cleansing .


Tolerability , acceptability , and compliance were also evaluated .


Two hundred ninety-nine patients were randomly allocated to the 4 groups .


In the per-protocol analysis , PEG-CS + Bisacodyl , PEG-Asc , and NaPico + MgCit were noninferior to PEG-ELS in bowel-cleansing efficacy of both the whole colon ( P = .910 ) and colonic segments .


No serious adverse events occurred in any group .


Rates of tolerability , acceptability , and compliance were significantly higher in the NaPico + MgCit group .


Low-volume PEG preparations ( PEG-CS + Bisacodyl , PEG-Asc ) and NaPico + MgCit are noninferior to PEG-ELS in children , representing an attractive alternative to high-volume regimens in clinical practice .


Because of the higher tolerability and acceptability profile , NaPico + MgCit would appear as the most suitable regimen for bowel preparation in children .


We estimated the prevalence and incidence of 14 human papillomavirus ( HPV ) types ( 6/11/16 / 18/31/33 / 35/39/45 / 51/52/56 / 58/59 ) in cervicovaginal swabs , and the attribution of these HPV types in cervical intraepithelial neoplasia ( CIN ) , and adenocarcinoma in situ ( AIS ) , using predefined algorithms that adjusted for multiple-type infected lesions .


A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine .


We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes , as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16 / 18/31/33 / 45/52/58 vaccine .


The cumulative incidence of persistent infection with 1 of the seven high-risk types included in the 9-valent vaccine was 29 % , 12 % , and 6 % for women ages 15 to 26 , 24 to 34 , and 35 to 45 years , respectively .


A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel .


After adjusting for multiple-type infected lesions , among women ages 15 to 45 years , these seven high-risk types were attributed to 43 % to 55 % of CIN1 , 70 % to 78 % of CIN2 , 85 % to 91 % of CIN3 , and 95 % to 100 % of AIS lesions , respectively .


The other tested types ( HPV35/39/51 / 56/59 ) were attributed to 23 % to 30 % of CIN1 , 7 % to 14 % of CIN2 , 3 % to 4 % of CIN3 , and 0 % of AIS lesions , respectively .


Approximately 85 % or more of CIN3/AIS , > 70 % CIN2 , and approximately 50 % of CIN1 lesions worldwide are attributed to HPV6/11/16 / 18/31/33 / 45/52/58 .


If 9-valent HPV vaccination programs are effectively implemented , the majority of CIN2 and CIN3 lesions worldwide could be prevented , in addition to approximately one-half of CIN1 .


Maintenance monotherapy with the PARP inhibitor olaparib significantly prolonged progression-free survival ( PFS ) versus placebo in patients with platinum-sensitive recurrent serous ovarian cancer .


We aimed to explore the hypothesis that olaparib is most likely to benefit patients with a BRCA mutation .


We present data from the second interim analysis of overall survival and a retrospective , preplanned analysis of data by BRCA mutation status from our randomised , double-blind , phase 2 study that assessed maintenance treatment with olaparib 400 mg twice daily ( capsules ) versus placebo in patients with platinum-sensitive recurrent serous ovarian cancer who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen .


Randomisation was by an interactive voice response system , stratified by time to progression on penultimate platinum-based regimen , response to the most recent platinum-based regimen before randomisation , and ethnic descent .


The primary endpoint was PFS , analysed for the overall population and by BRCA status .


This study is registered with ClinicalTrials.gov , number NCT00753545 .


Between Aug 28 , 2008 , and Feb 9 , 2010 , 136 patients were assigned to olaparib and 129 to placebo .


BRCA status was known for 131 ( 96 % ) patients in the olaparib group versus 123 ( 95 % ) in the placebo group , of whom 74 ( 56 % ) versus 62 ( 50 % ) had a deleterious or suspected deleterious germline or tumour BRCA mutation .


Of patients with a BRCA mutation , median PFS was significantly longer in the olaparib group than in the placebo group ( 112 months [ 95 % CI 83-not calculable ] vs 43 months [ 30-54 ] ; HR 018 [ 010-031 ] ; p < 00001 ) ; similar findings were noted for patients with wild-type BRCA , although the difference between groups was lower ( 74 months [ 55-103 ] vs 55 months [ 37-56 ] ; HR 054 [ 034-085 ] ; p = 00075 ) .


At the second interim analysis of overall survival ( 58 % maturity ) , overall survival did not significantly differ between the groups ( HR 088 [ 95 % CI 064-121 ] ; p = 044 ) ; similar findings were noted for patients with mutated BRCA ( HR 073 [ 045-117 ] ; p = 019 ) and wild-type BRCA ( HR 099 [ 063-155 ] ; p = 096 ) .


The most common grade 3 or worse adverse events in the olaparib group were fatigue ( in ten [ 7 % ] patients in the olaparib group vs four [ 3 % ] in the placebo group ) and anaemia ( seven [ 5 % ] vs one [ < 1 % ] ) .


Serious adverse events were reported in 25 ( 18 % ) patients who received olaparib and 11 ( 9 % ) who received placebo .


Tolerability was similar in patients with mutated BRCA and the overall population .


These results support the hypothesis that patients with platinum-sensitive recurrent serous ovarian cancer with a BRCA mutation have the greatest likelihood of benefiting from olaparib treatment .


AstraZeneca .


Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk .


We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness , diet and health .


This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation , provide preliminary evidence regarding efficacy , and explore feasibility and acceptability .


Primary outcomes were engagement in physical and cognitive activity .


Participants aged over 50 living independently in the community were recruited through a community Agewell Centre .


Following baseline assessment participants were randomly allocated to one of three conditions : control ( IC ) had an interview in which information about activities and health was discussed ; goal-setting ( GS n = 24 ) had an interview in which they set behaviour change goals relating to physical , cognitive and social activity , health and nutrition ; and goal-setting with mentoring ( GM , n = 24 ) had the goal-setting interview followed by bi-monthly telephone mentoring .


Participants and researchers were blinded to group assignment .


Participants were reassessed after 12months .


Seventy-five participants were randomised ( IC n = 27 , GS n = 24 , GM n = 24 ) .


At 12-month follow-up , the two goal-setting groups , taken together ( GS n = 21 , GM n = 22 ) , increased their level of physical ( effect size 0.37 ) and cognitive ( effect size 0.15 ) activity relative to controls ( IC n = 27 ) .


In secondary outcomes , the two goal-setting groups taken together achieved additional benefits compared to control ( effect sizes0 .2 ) in memory , executive function , cholesterol level , aerobic capacity , flexibility , balance , grip strength , and agility .


Adding follow-up mentoring produced further benefits compared to goal-setting alone ( effect sizes0 .2 ) in physical activity , body composition , global cognition and memory , but not in other domains .


Implementation of the recruitment procedure , assessment and intervention was found to be feasible and the approach taken was acceptable to participants , with no adverse effects .


A brief , low-cost goal-setting intervention is feasible and acceptable , and has the potential to achieve increased activity engagement .


Current Controlled Trials ISRCTN30080637 .


To investigate the effectiveness of surgical strategies for Shang Ring circumcision in the treatment of short frenulum praeputii in patients with redundant prepuce or phimosis .


Totally , 130 cases of short frenulum praeputii with redundant prepuce or phimosis were randomly assigned to an experimental group and a control group of equal number to receive Shang Ring circumcision , the former by transverse incision in the distal penis foreskin and pull-up of the interior board , and the latter by conventional transverse incision and longitudinal suture of the frenulum praeputii .


Comparisons were made between the two groups in the surgical duration , intraoperative blood loss , 24 h postoperative pain visual analog score ( VAS ) , postoperative complications , satisfaction with the penile appearance , and the quality of sexual life .


The surgical duration , intraoperative blood loss , 24 h postoperative VAS , postoperative sexual satisfaction , and satisfaction with penile appearance were ( 4.60 + / - 1.20 ) min , ( 2.61 + / - 1.81 ) ml , 1.73 + / - 0.76 , 98.5 % , and 98.5 % , respectively , in the experimental group , as compared with ( 21.60 + / - 6.30 ) min , ( 11.10 + / - 3.40 ) ml , 5.37 + / - 1.84 , 70.3 % and 69.8 % in the control , with statistically significant differences between the two groups ( P < 0.05 ) .


The incidence rates of such major complications as wound dehiscence , infection , and moderate to severe edema were 1.5 % ( 1/65 ) , 3.1 % ( 2/65 ) , and 4.6 % ( 3/65 ) , respectively , in the experimental group in comparison with 12.3 % ( 8/65 ) , 15.3 % ( 10/65 ) , and 30.7 % ( 20/65 ) in the control , with statistically significant differences between the two groups ( P < 0.05 ) .


None of patients had any serious complications .


Shang Ring circumcision by transverse incision in the distal penis foreskin and pull-up of the interior board , with its advantages of shorter operation time , less blood loss , mild pain , fewer complications , and higher satisfaction and acceptance of the patients , can be used as an safe and effective approach to the treatment of short frenulum praeputii .


Acotiamide is a first-in-class drug that is used to treat functional dyspepsia ( FD ) .


It is considered that acotiamide acts as an antagonist on muscarinic autoreceptors in the enteric nervous system and inhibits acetylcholinesterase activity .


We examined the effect of acotiamide on gastric emptying in healthy adult humans .


Twelve healthy adult males were enrolled in this double-blind crossover study .


Acotiamide or placebo was administered orally in the 12 subjects 30min before ingestion of a nutritional liquid meal ( 400Kcal/400mL ) .


Six of the 12 participants took 100mg of acotiamide or placebo , and six of the 12 participants took 300mg of acotiamide or placebo in a double-blind crossover fashion .


All subjects underwent measurement of gastric emptying by the ( 13 ) C breath test .


After the meal with placebo was ingested , the % dose/h curve ascended .


The % dose/h curve after a meal with 100 or 300mg of acotiamide ascended in an identical manner compared with the results with placebo .


No significant differences were observed at any studied time point , and there were no significant changes in gastric emptying parameters ( gastric emptying coefficient , t-1 / 2ex and t-lag ex ) .


A single administration of 100 or 300mg of acotiamide did not affect gastric emptying after a liquid meal in healthy adult humans .


Acotiamide has profound effects on restoring delayed gastric emptying and impaired accommodation in patients with FD but may have no effect on gastric emptying in healthy subjects .


Such pharmacological actions have not been observed in previous gastroprokinetic studies .


To observe the influence of Qingrehuatan decoction ( QRHT ) on serum metabolic profile in young essential hypertension ( YEH ) patients with abundant phlegm-heat syndrome and provide a basis for treatment with the decoction .


Twelve male YEH patients were randomly selected and serum samples were collected for examination before and after 4 weeks of the treatment with QRHT .


Twelve healthy males were randomly selected and their serum samples were collected as a control .


All serum samples were detected using metabolomic technology with 1H nuclear magnetic resonance .


Differences in metabolites were studied by principal component analysis and partial least squares-discriminate analysis , which produced scores and loadings plots .


After 4 weeks of treatment , serum substances could be distinguished between the YEH patients with abundant phlegm-heat syndrome and the control patients .


The specific serum endog - enous metabolites tended to improve after the treatment .


QRHT can appropriately increase the levels of glucose , lactic acid , citric acid , high-density lipoprotein , phosphatidylcholine , glycerophosphate choline , hydroxybutyrate , alanine , and glutamate .


QRHT could also decrease the levels of low-density lipoprotein/very low-density lipoprotein , lipids , N-acetyl glycoprotein , and O-acetyl glycoprotein .


QRHT can effectively ameliorate metabolic disorders in YEH Patients with abundant phlegm-heat syndrome .


1H NMR-based metabolomic technology can provide an objective basis for the treatment of YEH patients with abundant phlegm-heat syndrome using QRHT .


The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy ( CT ) in localized high-grade soft tissue sarcoma ( STS ) .


Both studies failed to demonstrate any benefit on overall survival ( OS ) .


The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. .


Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS ( large resection , R0/marginal resection , R1 ) were pooled .


Prognostic factors were assessed by univariate and multivariate analyses .


Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor .


A total of 819 patients had been enrolled with a median follow-up of 8.2 years .


Tumor size , high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival ( RFS ) and OS .


Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS .


A significant interaction between benefit of adjuvant CT and age , gender and R1 resection was observed for RFS and OS .


Males and patients > 40 years had a significantly better RFS in the treatment arms , while adjuvant CT was associated with a marginally worse OS in females and patients < 40 years .


Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms .


Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup .


Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS .


Based on these data , we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care .


To assess the association between minimum inhibitory concentration ( MIC ) and clinical outcomes in a fungal keratitis clinical trial .


Experimental study using data from a randomized comparative trial .


Of the 323 patients enrolled in the trial , we were able to obtain MIC values from 221 patients with monocular fungal keratitis .


The Mycotic Ulcer Treatment Trial I was a randomized , double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis .


Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines .


The relationship between MIC and clinical outcome was assessed .


The primary outcome was 3-month best spectacle-corrected visual acuity .


Secondary outcomes included 3-month infiltrate or scar size ; corneal perforation and/or therapeutic penetrating keratoplasty ; and time to re-epithelialization .


A 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size ( 0.21 mm ; 95 % confidence interval [ CI ] , 0.10-0 .31 ; P < 0.001 ) and increased odds of perforation ( odds ratio , 1.32 ; 95 % CI , 1.04-1 .69 ; P = 0.02 ) .


No correlation was found between MIC and 3-month visual acuity .


For natamycin-treated cases , an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size ( 0.29 mm ; 95 % CI , 0.15-0 .43 ; P < 0.001 ) and increased perforations ( odds ratio , 2.41 ; 95 % CI , 1.46-3 .97 ; P < 0.001 ) .


Among voriconazole-treated cases , the voriconazole MIC did not correlate with any of the measured outcomes in the study .


Decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation .


There was no association between susceptibility to voriconazole and outcome .


The aim of this study was to evaluate the effects of topical ropivacaine anesthesia on hemodynamic responses during intubation and extubation of hypertensive patients .


One hundred fifty patients with hypertension ASA II-III were scheduled for noncardiac operations .


Patients were divided into 3 groups : a control group receiving 5 ml saline , and 2 groups receiving topical anesthesia with 100 mg lidocaine or 37.5 mg ropivacaine .


Hemodynamic responses , including blood pressure and heart rate ( HR ) , were recorded at baseline ( T0 ) , before intubation ( T1 ) , during tracheal intubation ( T2 ) , 2 min after intubation ( T3 ) , upon eye opening on verbal commands ( T4 ) , during tracheal extubation ( T5 ) , and 2 min after extubation ( T6 ) .


Patients were injected with urapidil 5 mg during intubation and extubation if their systolic blood pressure ( SBP ) was 160 mmHg or diastolic blood pressure ( DBP ) was 90 mmHg , and esmolol 10 mg when HR was 90 bpm .


During extubation , the total dosages of urapidil and esmolol were significantly higher in the saline than in the lidocaine or ropivacaine groups , and were significantly lower in the ropivacaine than in the lidocaine group .


At T2 , SBP , SBP , MAP , and HR were lower in the lidocaine and ropivacaine groups than in the saline group , but the differences were not significant .


From T4 to T6 , SBP , DBP , MAP , and HR were significantly lower in the ropivacaine group than in the other 2 groups ( P < 0.05 each ) .


Topical lidocaine and ropivacaine anesthesia can effectively reduce hemodynamic responses during intubation , with ropivacaine better at inhibiting hemodynamic changes at emergence in hypertensive patients .


Adalimumab has been shown to be effective and well tolerated in patients with Crohn 's disease .


This analysis reports the results of a cohort of Japanese patients with moderate to severe Crohn 's disease who were evaluated for up to 3years to assess the long-term use of adalimumab .


The study consisted of a double-blind part and an open-label part .


Patients were included either in the 52-week double-blind , placebo-controlled part of the study followed by a 96-week open-label extension or in the open-label part from the beginning or in the event of a flare .


Patients were treated with adalimumab and evaluated for up to 148weeks as 3 data cohorts : the all-adalimumab cohort ( patients receiving 1 injection of adalimumab ) , the 148-week follow-up subcohort ( patients who completed 148weeks of follow-up after the first adalimumab dose ) , and the dose-escalation subcohort ( patients receiving adalimumab doses that increased to 80mg every other week ) .


In the all-adalimumab cohort ( n = 79 ) , clinical remission rates were approximately 30 % after 36weeks of exposure to adalimumab and for the remainder of the study ( 35 % , 33 % , and 28 % for weeks 48 , 108 , and 144 , respectively ) .


An improvement in quality of life was also maintained over the same period .


In the dose-escalation subcohort ( n = 40 ) , the clinical remission rate was 75 % ( 6/8 ) 48weeks after dose escalation .


Adalimumab was tolerated , and no deaths were reported .


Adalimumab is effective for maintaining long-term clinical remission in Japanese patients with moderate to severe Crohn 's disease ( NCT00445432 ) .


Melioidosis , an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei , is difficult to cure .


Antimicrobial treatment comprises intravenous drugs for at least 10 days , followed by oral drugs for at least 12 weeks .


The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole ( TMP-SMX ) plus doxycycline .


This regimen is used in Thailand but is associated with side-effects and poor adherence by patients , and TMP-SMX alone is recommended in Australia .


We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment .


For this multi-centre , double-blind , non-inferiority , randomised placebo-controlled trial , we enrolled patients ( aged 15 years ) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs .


Using a computer-generated sequence , we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks ( 1:1 ; block size of ten , stratified by study site ) .


We followed patients up every 4 months for 1 year and annually thereafter to the end of the study .


The primary endpoint was culture-confirmed recurrent melioidosis , and the non-inferiority margin was a hazard ratio ( HR ) of 1.7 .


This study is registered with www.controlled-trials.com , number ISRCTN86140460 .


We enrolled and randomly assigned 626 patients : 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline .


16 patients ( 5 % ) in the TMP-SMX plus placebo group and 21 patients ( 7 % ) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis ( HR 0.81 ; 95 % CI 0.42-1 .55 ) .


The criterion for non-inferiority was met ( p = 0.01 ) .


Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group ( 122 [ 39 % ] vs 167 [ 53 % ] ) .


Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment , and is preferable on the basis of safety and tolerance by patients .


Thailand Research Fund , the Melioidosis Research Center , the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster , and the Wellcome Trust .


Concomitant genetic alterations could account for transient clinical responses to tyrosine kinase inhibitors of the EGF receptor ( EGFR ) in patients harboring activating EGFR mutations .


We have evaluated the impact of pretreatment somatic EGFR T790M mutations , TP53 mutations , and Bcl-2 interacting mediator of cell death ( BCL2L11 , also known as BIM ) mRNA expression in 95 patients with EGFR-mutant non-small-cell lung cancer ( NSCLC ) included in the EURTAC trial ( trial registration : NCT00446225 ) .


T790M mutations were detected in 65.26 % of patients using our highly sensitive method based on laser microdissection and peptide-nucleic acid-clamping PCR , which can detect the mutation at an allelic dilution of 1 in 5,000 .


Progression-free survival ( PFS ) to erlotinib was 9.7 months for those with T790M mutations and 15.8 months for those without , whereas among patients receiving chemotherapy , it was 6 and 5.1 months , respectively ( P < 0.0001 ) .


PFS to erlotinib was 12.9 months for those with high and 7.2 months for those with low/intermediate BCL2L11 expression levels , whereas among chemotherapy-treated patients , it was 5.8 and 5.5 months , respectively ( P = 0.0003 ) .


Overall survival was 28.6 months for patients with high BCL2L11 expression and 22.1 months for those with low/intermediate BCL2L11 expression ( P = 0.0364 ) .


Multivariate analyses showed that erlotinib was a marker of longer PFS ( HR = 0.35 ; P = 0.0003 ) , whereas high BCL2L11 expression was a marker of longer PFS ( HR = 0.49 ; P = 0.0122 ) and overall survival ( HR = 0.53 ; P = 0.0323 ) .


Low-level pretreatment T790M mutations can frequently be detected and can be used for customizing treatment with T790M-specific inhibitors .


BCL2L11 mRNA expression is a biomarker of survival in EGFR-mutant NSCLC and can potentially be used for synthetic lethality therapies .


Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma , but the optimal duration and time to initiate chemotherapy is unknown .


Patients with pancreatic ductal adenocarcinoma treated within the international , phase III , European Study Group for Pancreatic Cancer-3 ( version 2 ) study were included if they had been randomly assigned to chemotherapy .


Overall survival analysis was performed on an intention-to-treat basis , retaining patients in their randomized groups , and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy .


There were 985 patients , of whom 486 ( 49 % ) received gemcitabine and 499 ( 51 % ) received fluorouracil ; 675 patients ( 68 % ) completed all six cycles of chemotherapy ( full course ) and 293 patients ( 30 % ) completed one to five cycles .


Lymph node involvement , resection margins status , tumor differentiation , and completion of therapy were all shown by multivariable Cox regression to be independent survival factors .


Overall survival favored patients who completed the full six courses of treatment versus those who did not ( hazard ratio [ HR ] , 0.516 ; 95 % CI , 0.443 to 0.601 ; P < .001 ) .


Time to starting chemotherapy did not influence overall survival rates for the full study population ( HR , 0.985 ; 95 % CI , 0.956 to 1.015 ) .


Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy , in favor of later treatment ( P < .001 ) .


Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma .


There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks , thus allowing adequate time for postoperative recovery .


In acute respiratory failure patients undergoing pressure support ventilation , a short cyclic recruitment maneuver ( Sigh ) might induce reaeration of collapsed lung regions , possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution .


We aimed to describe the regional effects of different Sigh rates on reaeration , strain , and ventilation heterogeneity , as measured by thoracic electrical impedance tomography .


Prospective , randomized , cross-over study .


General ICU of a single university-affiliated hospital .


We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300mm Hg and positive end-expiratory pressure at least 5cm H2O ( 15 with acute respiratory distress syndrome ) , undergoing pressure support ventilation as per clinical decision .


Sigh was added to pressure support ventilation as a 35cm H2O continuous positive airway pressure period lasting 3-4 seconds at different rates ( no-Sigh vs 0.5 , 1 , and 2 Sigh ( s ) / min ) .


All study phases were randomly performed and lasted 20 minutes .


In the last minutes of each phase , we measured arterial blood gases , changes in end-expiratory lung volume of nondependent and dependent regions , tidal volume reaching nondependent and dependent lung ( Vtnondep and Vtdep ) , dynamic intratidal ventilation heterogeneity , defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration ( VtHit ) .


With Sigh , oxygenation improved ( p < 0.001 vs no-Sigh ) , end-expiratory lung volume of nondependent and dependent regions increased ( p < 0.01 vs no-Sigh ) , Vtnondep showed a trend to reduction , and Vtdep significantly decreased ( p = 0.11 and p < 0.01 vs no-Sigh , respectively ) .


VtHit decreased only when Sigh was delivered at 0.5 / min ( p < 0.05 vs no-Sigh ) , while it did not vary during the other two phases .


Sigh decreases regional lung strain and intratidal ventilation heterogeneity .


Our study generates the hypothesis that in ventilated acute respiratory failure patients , Sigh may enhance regional lung protection .


To investigate the interactive effects between batroxobin and low molecular weight heparin ( LMWH ) in reducing peri-operative blood loss and coagulation function in patients who undergone the total hip replacement surgery .


240 ASA I - III patients received 4 000 IU LMWH 12 hours preoperatively before undergoing the total hip replacement operation , were randomly divided into two groups : testing group ( Group A , n = 120 ) and control group ( Group B , n = 120 ) receiving 2 U batroxobin or 50 mg mannitol 10 minutes before incision respectively .


Perioperative blood loss , postoperative 24 hours drainage and blood routine test , prothrombin time ( PT ) , activated partial thromboplastin time ( APTT ) and fibrinogen ( FIB ) were measured respectively .


Deep vein thrombosis ( DVT ) were measured through color Doppler B-ultrasound 3 days after the operation .


The perioperative blood loss in Group A ( 422.64 ml ) was less than that in Group B ( 667.67 ml ) ( P < 0.01 ) while red blood cell , hemoglobin , red blood cell volume and platelet were decreasing after operation in both groups but no significant difference was found between the two groups ( P > 0.05 ) .


There were no drug-related adverse effects found in the two groups , neither the difference in hospitalization between the two groups ( P > 0.05 ) .


Batroxobin ( 2 U ) could reduce the perioperative blood loss in patients with LMWH who had undergone the total hip replacement operation but did not show adverse effect on DVT .


With predicted increases in dementia incidence , interventions targeting neuroplasticity and neuroprotection are required .


Cognitive Training ( CT ) is an intervention which has been shown to improve aspects of cognition , but the pathophysiological mechanisms contributing to its efficacy are unknown .


We aimed to explore the neurobiological correlates of CT using Mismatch Negativity ( MMN ) , a neurophysiological marker of pre-attentive information processing , which in turn , is postulated to underpin higher-order cognitive processes .


As part of a larger randomized controlled trial , forty ` at risk ' ( i.e. , mild cognitive impairment or late-life depression ) participants aged 51-79 years underwent neurophysiological , neuropsychological , and psychiatric assessments before and after a multi-faceted seven-week CT program or a ` treatment-as-usual ' seven-week waitlist period .


The treatment group demonstrated significantly increased fronto-central MMN responses ( p < 0.05 ) , as well as improved phonemic verbal fluency ( p < 0.05 ) and decreased self-rated memory difficulties ( p < 0.05 ) following CT , in comparison to the waitlist control group .


However , there were no significant correlations between enhanced MMN and cognitive/psychosocial outcomes .


Results from this preliminary investigation indicate that CT is associated with enhanced neurophysiological mechanisms suggestive of improved pre-attentive processing , which may reflect alterations in underlying neurobiology .


Further research is warranted to confirm these findings , to explicate whether CT is associated with restorative or compensatory neuroplastic processes and to determine whether MMN is a useful biomarker for treatment response .


Children with gastroenteritis often develop dehydration with metabolic acidosis .


Serum ketones are frequently elevated in this population .


The goal was to determine the relationship between initial serum ketone concentration and both the degree of dehydration and the magnitude of acidosis .


This was a secondary analysis of a prospective trial of crystalloid administration for rapid rehydration .


Children 6 months to 6 years of age with gastroenteritis and dehydration were enrolled .


A point-of-care serum ketone ( beta-hydroxybutyrate ) concentration was obtained at the time of study enrollment .


The relationship between initial serum ketone concentration and a prospectively assigned and previously validated clinical dehydration score , and serum bicarbonate concentration , was analyzed .


A total of 188 patients were enrolled .


The median serum ketone concentration was elevated at 3.1 mmol/L ( interquartile range [ IQR ] = 1.2 to 4.6 mmol/L ) , and the median dehydration score was consistent with moderate dehydration .


A significant positive relationship was found between serum ketone concentration and the clinical dehydration score ( Spearman 's rho = 0.22 , p = 0.003 ) .


Patients with moderate dehydration had a higher median serum ketone concentration than those with mild dehydration ( 3.6 mmol/L vs. 1.4 mmol/L , p = 0.007 ) .


Additionally , the serum ketone concentration was inversely correlated with serum bicarbonate concentration ( = -0.26 , p < 0.001 ) .


Children with gastroenteritis and dehydration have elevated serum ketone concentrations that correlate with both degree of dehydration and magnitude of metabolic acidosis .


Point-of-care serum ketone measurement may be a useful tool to inform management decisions at the point of triage or in the initial evaluation of children with gastroenteritis and dehydration .


In this secondary analysis of results of the Clinical Outcomes in MEasurement-Based Treatment ( COMET ) trial , patient behaviors that might account for the differences observed in clinical outcomes were examined .


Patients ( N = 914 ) diagnosed as having major depressive disorder participated in telephone interviews either monthly for six months ( intervention ) or at three and six months ( usual care ) asking about antidepressant medication-taking , use of psychotherapy or counseling , and participation in depression support groups .


Physicians ( N = 83 ) in the intervention arm received monthly feedback regarding their patients ' depression severity .


A total of 664 ( 73 % ) patients completed the month 6 interview .


The adjusted odds of current antidepressant use at six months were 85 % greater ( p = .01 ) for patients in the intervention ( N = 380 ) versus usual care ( N = 284 ) arms , according to multivariate regression analyses .


More frequent measurement of depression symptoms was associated with greater medication persistence , which in turn may have mediated clinical improvements .


To explore whether psychosocial challenges impact effects of vocational rehabilitation in Veterans with Posttraumatic Stress Disorder ( PTSD ) .


A post hoc exploratory analysis of possible moderators of treatment was conducted on outcomes from a randomized , controlled trial of Individual Placement and Support in Veterans with PTSD .


When examining groups within each moderator , there was a greater IPS supportive employment benefit in gaining competitive employment for those with inadequate transportation ( number needed to treat [ NNT ] = 1.5 ) and inadequate housing ( NNT = 1.5 ) compared with the main finding of the pilot study ( NNT = 2.07 ) .


Compared with the main finding of the pilot study , there was no greater advantage of IPS for those with adequate transportation ( NNT = 2.4 ) or adequate housing ( NNT = 2.4 ) .


Compared with the main finding in the pilot study , those without a family care burden had a greater benefit from IPS ( NNT = 1.4 ) and those with family care burden had a reduced treatment effect ( NNT = 3.3 ) .


These results are exploratory and are not intended to guide clinical decision-making , but rather offer a potentially useful strategy in the design of larger trials of IPS .


To determine the effects of keratocyte loss on optical properties and vision after laser in situ keratomileusis ( LASIK ) with the flap created with a femtosecond laser or a mechanical microkeratome .


Randomized clinical paired-eye study .


Both eyes of 21 patients received LASIK for myopia or myopic astigmatism .


One eye of each patient was randomized by ocular dominance to flap creation with a femtosecond laser and the other eye to flap creation with a mechanical microkeratome .


Before LASIK and at 1 , 3 , and 6 months and 1 , 3 , and 5 years after LASIK , keratocyte density was measured using confocal microscopy , and high-contrast visual acuity and anterior corneal wavefront aberrations were measured by standard methods .


At each visit , all variables were compared between methods of creating the flap and to the same variable before treatment using paired tests with Bonferroni correction for multiple comparisons .


Keratocyte density in the flap decreased by 20 % during the first year after LASIK and remained low through 5 years ( P < .001 ) .


High-order wavefront aberrations increased and uncorrected visual acuity improved immediately after surgery , but these variables did not change further to 5 years .


There were no differences in any variables between treatments .


A sustained reduction in keratocyte density does not affect vision or optical properties of the cornea through 5 years after LASIK .


The method of creating a LASIK flap does not influence the changes in keratocyte density in the flap .


Many with alcohol and other drug dependence have concurrent marijuana use , yet it is not clear how to address it during addiction treatment .


This is partially due to the lack of clarity about whether marijuana use impacts one 's ability to achieve abstinence from the target of addiction treatment .


We examined the association between marijuana use and abstinence from other substances among individuals with substance dependence .


A secondary analysis of the Addiction Health Evaluation And Disease management study , a randomized trial testing the effectiveness of chronic disease management .


Individuals met criteria for drug or alcohol dependence and reported recent drug ( i.e. opioid or stimulant ) or heavy alcohol use .


Recruitment occurred largely at an inpatient detoxification unit , and all participants were referred to primary medical care .


The association between marijuana use and later abstinence from drug and heavy alcohol use was assessed using longitudinal multivariable models .


Of 563 study participants , 98 % completed at least one follow-up assessment and 535 ( 95 % ) had at least one pair of consecutive assessments and were included .


In adjusted analyses , marijuana use was associated with a 27 % reduction in the odds of abstinence from drug and heavy alcohol use ( adjusted odds ratio 0.73 [ 95 % CI , 0.56-0 .97 ] , P = 0.03 ) .


Marijuana use among individuals with alcohol or other drug dependence is associated with a lower odds of achieving abstinence from drug and heavy alcohol use .


These findings add evidence that suggests concomitant marijuana use among patients with addiction to other drugs merits attention from clinicians .


Delayed cord clamping ( DCC ) is recommended for premature infants to improve blood volume .


Most preterm infants are born by cesarean delivery ( CD ) , and placental transfusion may be less effective than in vaginal delivery ( VD ) .


We sought to determine whether infants < 32 weeks born by CD who undergo umbilical cord milking ( UCM ) have higher measures of systemic blood flow than infants who undergo DCC .


This was a 2-center trial .


Infants delivered by CD were randomly assigned to undergo UCM or DCC .


Infants delivered by VD were also randomly assigned separately .


UCM ( 4 strippings ) or DCC ( 45-60 seconds ) were performed .


Continuous hemodynamic measurements and echocardiography were done at site 1 .


A total of 197 infants were enrolled ( mean gestational age 28 2 weeks ) .


Of the 154 infants delivered by CD , 75 were assigned to UCM and 79 to DCC .


Of the infants delivered by CD , neonates randomly assigned to UCM had higher superior vena cava flow and right ventricular output in the first 12 hours of life .


Neonates undergoing UCM also had higher hemoglobin , delivery room temperature , blood pressure over the first 15 hours , and urine output in the first 24 hours of life .


There were no differences for the 43 infants delivered by VD .


This is the first randomized controlled trial demonstrating higher systemic blood flow with UCM in preterm neonates compared with DCC .


UCM may be a more efficient technique to improve blood volume in premature infants delivered by CD .


The objective of the study was to evaluate the effectiveness of a high-fidelity birth simulator ( Noelle ; Gaumard Scientific , Coral Gables , FL ) compared with a lower-cost , low-tech , birth simulator ( MamaNatalie ; Laerdal Medical , Stavanger , Norway ) in teaching medical students how to perform a spontaneous vaginal delivery ( SVD ) .


Prior to the obstetrics-gynecology clerkship , students were randomly assigned to 2 groups .


The MamaNatalie group ( MG ) completed 45 minutes of SVD simulation using an obstetrical abdominal-pelvic model worn by an obstetrics-gynecology faculty member .


The Noelle group ( NG ) completed 45 minutes of SVD simulation using a high-fidelity , computer-controlled mannequin facilitated by an obstetrics-gynecology faculty member .


The primary outcome was student performance during his or her first SVD as rated by supervising preceptors .


Surveys were also completed by students on confidence in performing steps of a SVD ( secondary outcome ) .


One hundred ten medical students ( 95 % of those eligible ) participated in this research study .


The final postclerkship survey was completed by 93 students ( 85 % follow-up rate ) .


There were no significant differences in performance of SVD steps between MG and NG students as rated by preceptors .


The SVD step with the least involvement by students was controlling the head ( 20.5 % in MG , 23.3 % in NG performed step with hands-off supervision ) .


Delivery of the placenta was the SVD step with the most involvement ( 65.9 % in MG , 52.3 % in NG performed step with hands-off supervision ) .


Baseline presimulation confidence levels were similar between MG and NG .


On the immediate postsimulation survey of confidence , MG students were significantly more confident in their ability to deliver the abdomen and legs and perform fundal massage with hands-off supervision ( P < .05 ) than NG students .


Following the clerkship , MG students were significantly more confident in their ability to control the head and deliver the abdomen and legs ( P < .05 ) than NG students .


MamaNatalie is as effective as Noelle in training medical students how to perform a SVD and may be a useful , lower-cost alternative in teaching labor and delivery skills to novice learners .


Because birth simulation interventions involve both a simulation model and facilitator , research is required to further determine the effect of human interaction on learning outcomes .


Worldwide prevalence of generalized anxiety disorder ( GAD ) is considered high ; in Europe lifetime prevalence has been estimated at 4.3 to 5.9 % .


High levels of anxiety disorders have been reported in university students , affecting 25 to 30 % of the population .


Young adults are some of the most vulnerable for the onset of mental health disorders and any stressors may act as a catalyst for their onset .


The absence of resources can often mean that many do not seek treatment .


Other factors that impede access to resources include such things as a lack of trained professionals , personal stigma , and waiting lists .


Anxiety disorders can be treated successfully ; indeed brief forms of cognitive-behavior therapy have been recommended .


One potential avenue for research and development is that of delivering low-intensity interventions online for students with GAD .


Therefore , the current study seeks to investigate the potential effectiveness for a low-intensity online CBT-based treatment for GAD in a service-based setting ; implemented as one step in a stepped-care model .


The research is a service-based effectiveness study utilizing a randomized waiting-list controlled design .


The active intervention consists of six weekly modules of online CBT .


Participants are assigned a supporter who provides weekly post-session feedback on progress and exercises .


Participants will complete the GAD-7 as the primary outcome measure .


Secondary outcomes include pathological worry , depression and measures of well-being .


At three-months follow-up data will be collected using the GAD-7 , BDI-II , PSWQ , ED-Q5 and WSAS .


Post-session data will be collected on significant in-session events in treatment ( HAT ) .


A satisfaction with treatment measure will be administered post-treatment ( SAT ) .


The study will be a contribution to the potential for a low-intensity internet-delivered program implemented in a service-based setting ; implemented as one step in a stepped-care model .


The study will be a contribution to the already established work in online treatments for anxiety worldwide .


The study will assess the utility of an innovative digital health solution ( SilverCloud ) to deliver such interventions .


Current Controlled Trials ISRCTN16303842 .


The aim of this study was to compare the effectiveness of single port/incision laparoscopic surgery ( SPILS ) with standard three-port laparoscopic surgery for appendicectomy in adults .


Feasibility data was collected to evaluate generalizability to other single-port techniques such as cholecystectomy .


This was a single-center , randomized controlled trial .


Participants were randomized to receive either SPILS or standard three-port laparoscopic appendicectomy .


The primary patient-reported outcomes were body image and cosmesis at 6 weeks .


The primary clinical outcome was pain at 1-7 days .


Secondary outcomes included duration of operation , conversion rates , complication rates , use of analgesia , hospital re-admission rates , re-operation rates , and time to return to normal activities .


Seventy-nine patients were randomized .


Sixty-seven completed the day 1-7 diary and 53 completed the 6-week follow-up .


SPILS patients answered significantly more favorably to the items in the body image scale [ mean ( SD ) 5.6 ( 1.0 ) vs. 7.0 ( 3.3 ) ; -1.4 ( 95 % CI -2.8 to 1.5 ; p = 0.03 ) ] and the cosmetic scale [ 18.9 ( 4.1 ) vs. 15.3 ( 5.8 ) ; 3.6 ( 95 % CI 0.7-6 .5 ; p = 0.016 ) ] compared with patients in the Standard group .


The duration of operation was shorter for SPILS , and patients required less morphine in recovery ; however , there were no statistically significant differences in other outcomes .


Patient-reported body image and cosmesis outcomes were better , and surgical outcomes were similar following SPILS .


However , the SPILS procedure is more technically demanding and may not be achievable or necessary in routine clinical care .


Further assessment of the findings is needed through larger multicenter studies .


To explore the protective effects of target blood glucose control on cardiac dysfunction in septic patients .


For this prospective and randomized interventional study , a total of 90 septic patients were divided into group A ( blood glucose levels of 4.4 to 6.1 mmol/L ) , group B ( 6.1 to 8.3 mmol/L ) and group C ( 8.3 to 10.0 mmol/L ) ( n = 30 each ) .


And 30 non-septic subjects were selected into control group .


Serial transthoracic echocardiogram ( TTEs ) was performed to measure left ventricle ejection fraction ( LVEF ) and ratio of blood flow velocity of mitral annulus during early diastole ( E ) and atrial contraction ( A ) before and 1 , 3 , 7 days after blood glucose control with insulin therapy .


The plasma level of brain natriuretic peptide ( BNP ) was detected by enzyme-linked immunosorbent assay ( ELISA ) .


The patient records were reviewed to obtain information about demographics , Acute Physiology and Chronic Health Evaluation II ( APACHE II ) scores , incidence of hypoglycemia and 28-days survival rates .


No significant inter-group improvement existed in mean values of LVEFs ( P = 0.184 ) .


And E/As differed among the groups and there was statistical difference between groups A and C ( P = 0.005 ) .


There was a increasing trend for the levels of BNP of groups A , B and C. And comparison of group A with group B/C had statistical variability ( PAB = 0.028 , P ( Ac ) = 0.000 ) .


LVEFs had no variation ( P = 0.310 , P = 0.174 ) while E/A and BNP were significantly higher or lower in group A than those in others at Day 1 and 3 ( P = 0.005 ) .


The LVEFs were similar at Day 7 and E/As and BNPs of groups A , B and C showed statistical differences .


The variation of E/As with time differed between groups A , B and C.


Maintaining a target blood glucose of 4.4 to 6.1 mmol/L may improve cardiac dysfunction .


Furthermore , it has more significant improvement of diastolic dysfunction than systolic counterpart .


Combined utilization of LVEF , E/A and BNP is better in evaluating critical ill patients with sepsis-induced cardiomyopathy under target blood glucose control .


It suggests that a glucose level of 4.4 to 6.1 mmol/L may benefit cardiac consistent dysfunction in septic patients during 7 days after treatment .


The aim of this study was to examine non-cavitated approximal caries using non-invasive treatment methods .


Molar and premolar teeth with approximal caries were used in this in vivo study .


Approximal caries lesions were evaluated with visual and radiographic inspection and with the DIAGNOdent device .


Five groups were formed to study non-invasive treatment , and each had at least 25 early approximal carious lesions .


Patients in the control group were not treated .


After the separation , either ozone application , acidulated phosphate fluoride gel , CPP-ACP-containing material ( Tooth Mousse ) , or an antibacterial bonding agent ( Clearfil Protect Bond ) was used .


For 18 months after the non-invasive treatment , radiological controls were used to observe the progress of the initial and approximal caries in the 1st , 3rd , 6th and 12th months of follow-up .


A Mann-Whitney U-test was used to perform the statistical analysis ; in-group comparisons were made with the Wilcoxon signed-rank test , and a quantitative assessment was performed using a chi-squared test .


At the end of 18 months , the caries lesions in the control group were observed to progress ( P < 0.01 ) .


The lesions that were scored as 1a during a visual inspection recovered by using non-invasive treatments .


Approximal caries lesions that were detected at the early stages remained stationary when using antibacterial agents and materials that promoted remineralisation .


Antibacterial agents and remineralisation materials can be used in treatment of early approximal caries lesions .


Co-administration of an investigational quadrivalent meningococcal serogroups A , C , W and Y tetanus toxoid conjugate vaccine ( MenACWY-TT ) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine ( DTaP ) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine ( HibMenCY-TT ) - primed toddlers .


Infants were randomized ( 5:1 ) and primed at 2 , 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus ( DTaP-HBV-IPV ) vaccine , or Hib-TT and DTaP-HBV-IPV ( Control ) .


HibMenCY-TT + DTaP-HBV-IPV vaccinees were re-randomized ( 2:2:1 ) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months ( MenACWY-TT group ) ; MenACWY-TT co-administered with DTaP at 15-18 months ( Coad group ) ; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months ( HibMenCY-TT group ) .


Controls received DTaP at 15-18 months .


Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study .


DTaP immunogenicity and reactogenicity were assessed one month post-vaccination .


Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria , tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin .


Following vaccination 99 % of children had anti-diphtheria/anti-tetanus concentrations 1.0 IU/ml .


Pertussis GMCs were lower in all investigational groups versus Control .


In post hoc analyses , pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated ( Schmitt , von Knig , et al. , 1996 ; Schmitt , Schuind , et al. , 1996 ) .


The reactogenicity profile of the Coad group was similar to DTaP administered alone .


Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers .


These data support the administration of a fourth DTaP dose following a 4-dose HibMenCY-TT vaccination series , or co-administered with MenACWY-TT in HibMenCY-TT-primed children .


Many patients with peripheral artery disease ( PAD ) have walking impairment despite therapy .


Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells ( PCs ) , but whether this is effective in patients with PAD is unknown .


To investigate whether therapy with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) improves exercise capacity in patients with intermittent claudication .


In a phase 2 double-blind , placebo-controlled study , 159 patients ( median [ SD ] age , 64 [ 8 ] years ; 87 % male , 37 % with diabetes ) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta , Georgia , between January 2010 and July 2012 .


Participants were randomized ( 1:1 ) to received 4 weeks of subcutaneous injections of GM-CSF ( leukine ) , 500 g/day 3 times a week , or placebo .


Both groups were encouraged to walk to claudication daily .


The primary outcome was peak treadmill walking time ( PWT ) at 3 months .


Secondary outcomes were PWT at 6 months and changes in circulating PC levels , ankle brachial index ( ABI ) , and walking impairment questionnaire ( WIQ ) and 36-item Short-Form Health Survey ( SF-36 ) scores .


Of the 159 patients randomized , 80 were assigned to the GM-CSF group .


The mean ( SD ) PWT at 3 months increased in the GM-CSF group from 296 ( 151 ) seconds to 405 ( 248 ) seconds ( mean change , 109 seconds [ 95 % CI , 67 to 151 ] ) and in the placebo group from 308 ( 161 ) seconds to 376 ( 182 ) seconds ( change of 56 seconds [ 95 % CI , 14 to 98 ] ) , but this difference was not significant ( mean difference in change in PWT , 53 seconds [ 95 % CI , -6 to 112 ] , P = .08 ) .


At 3 months , compared with placebo , GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 ( 95 % CI , 6.7 to 16.1 ) vs 4.8 ( 95 % CI , -0.1 to 9.6 ) , with a mean difference in change for GM-CSF vs placebo of 7.5 ( 95 % CI , 1.0 to 14.0 ; P = .03 ) .


Similarly , the distance score of the WIQ improved by 12.5 ( 95 % CI , 6.4 to 18.7 ) vs 4.8 ( 95 % CI , -0.2 to 9.8 ) with GM-CSF compared with placebo ( mean difference in change , 7.9 [ 95 % CI , 0.2 to 15.7 ] , P = .047 ) .


There were no significant differences in the ABI , WIQ distance and speed scores , claudication onset time , or mental or physical component scores of the SF-36 between the groups .


Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up .


The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication .


clinicaltrials.gov Identifier : NCT01041417 .


Previously , a study of ours showed that the combination of dabrafenib and trametinib improves progression-free survival compared with dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutation-positive metastatic melanoma .


The study was continued to assess the secondary endpoint of overall survival , which we report in this Article .


We did this double-blind phase 3 study at 113 sites in 14 countries .


We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma .


Participants were computer-randomised ( 1:1 ) to receive a combination of dabrafenib ( 150 mg orally twice daily ) and trametinib ( 2 mg orally once daily ) , or dabrafenib and placebo .


The primary endpoint was progression-free survival and overall survival was a secondary endpoint .


This study is registered with ClinicalTrials.gov , number NCT01584648 .


Between May 4 , 2012 , and Nov 30 , 2012 , we screened 947 patients for eligibility , of whom 423 were randomly assigned to receive dabrafenib and trametinib ( n = 211 ) or dabrafenib only ( n = 212 ) .


The final data cutoff was Jan 12 , 2015 , at which time 222 patients had died .


Median overall survival was 251 months ( 95 % CI 192-not reached ) in the dabrafenib and trametinib group versus 187 months ( 152-237 ) in the dabrafenib only group ( hazard ratio [ HR ] 071 , 95 % CI 055-092 ; p = 00107 ) .


Overall survival was 74 % at 1 year and 51 % at 2 years in the dabrafenib and trametinib group versus 68 % and 42 % , respectively , in the dabrafenib only group .


Based on 301 events , median progression-free survival was 110 months ( 95 % CI 80-139 ) in the dabrafenib and trametinib group and 88 months ( 59-93 ) in the dabrafenib only group ( HR 067 , 95 % CI 053-084 ; p = 00004 ; unadjusted for multiple testing ) .


Treatment-related adverse events occurred in 181 ( 87 % ) of 209 patients in the dabrafenib and trametinib group and 189 ( 90 % ) of 211 patients in the dabrafenib only group ; the most common was pyrexia ( 108 patients , 52 % ) in the dabrafenib and trametinib group , and hyperkeratosis ( 70 patients , 33 % ) in the dabrafenib only group .


Grade 3 or 4 adverse events occurred in 67 ( 32 % ) patients in the dabrafenib and trametinib group and 66 ( 31 % ) patients in the dabrafenib only group .


The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma .


Studies assessing dabrafenib and trametinib in combination with immunotherapies are ongoing .


GlaxoSmithKline .


Mild adverse events ( AEs ) are common with acupuncture , but the risk factors remain unclear .


A prospective study using a standardised AE assessment and acupuncture protocol was undertaken to address the question .


A 20-item AE report form investigated local and systemic AEs in 150 adults with insomnia randomised to receive traditional , minimal and non-invasive sham acupuncture .


Sociodemographic , clinical and psychological variables at baseline and past history and perceived credibility of acupuncture were assessed .


The incidence of any AEs per patient was 42.4 % with traditional acupuncture , 40.7 % with minimal acupuncture and 16.7 % with non-invasive sham acupuncture .


Traditional and minimal acupuncture were associated with a greater number of local AEs , while the presence of a chronic medical condition was predictive of fewer local and systemic AEs .


Greater severity of insomnia , anxiety , depression , somatic symptoms and pain catastrophising thoughts were associated with lower risk , but most of the significant correlations disappeared after logistic regression .


Divorce and widowhood were the only significant sociodemographic variables , while previous acupuncture treatment and perceived credibility of acupuncture were found to be unrelated .


The risk of any AEs was higher in participants receiving traditional acupuncture ( OR 4.26 ) and minimal acupuncture ( OR 4.27 ) and in those without medical comorbidity ( OR 3.39 ) .


The prevalence of AEs was higher than usual , probably due to the low threshold in our definition of AEs and the systematic collection from the patients ' perspective .


Baseline variables were largely unable to predict AEs associated with acupuncture .


Further studies should explore the roles of practitioners , patients ' anxiety during treatment and patient-practitioner interactions .


NCT01707706 .


Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography ( ERCP ) .


The aim of this prospective trial was to compare the effect of ulinastatin and nafamostat on the prophylaxis of post-ERCP complications .


A total of 159 patients who underwent ERCP were divided into ulinastatin ( n = 53 ) , nafamostat ( n = 53 ) and control ( n = 53 ) groups .


Each patient received ulinastatin ( 150,000 units ) , nafamostat ( 20 mg ) , or placebo from 2-4 h before ERCP to 6-8 h after ERCP .


The primary endpoint was the incidence of PEP , and the secondary endpoints were the incidence of post-ERCP hyperamylasemia , hyperlipasemia and abdominal pain .


The overall incidence of PEP was 6.3 % ( 10/159 ) and no significant differences were observed between ulinastatin and nafamostat groups in terms of the incidences of PEP ( 1.9 % and 3.8 % , P = 0.560 ) , hyperamylasemia , hyperlipasemia , and abdominal pain , although these were significantly lower than those of the control group ( P < 0.001 ) .


There was no significant difference for preventing PEP between ulinastatin and nafamostat and both drugs were efficacious for preventing post-ERCP complications .


Dysphagia is the most common complication of anterior cervical discectomy and fusion ( ACDF ) , and it is closely related to prevertebral soft-tissue swelling ( PSTS ) .


A few studies have found that local or systemic methylprednisolone is effective against laryngopharyngeal edema and airway obstruction .


To assess the effectiveness of short-term use of systemic methylprednisolone in relieving dysphagia and decreasing PSTS during the hospitalization period .


A prospective study .


Forty patients who underwent multilevel ( more than three levels ) ACDF with same plate fixation .


Radiologic and clinical measures .


Twenty of these patients were given 250 mg of methylprednisolone intravenously ( IV ) four times a day only for 24 hours after the operation ( at 6-hour intervals ) , whereas the remaining 20 did not receive methylprednisolone and served as controls .


We used the Bazaz scale to compare the degree of dysphagia between groups during the hospitalization period .


We used the C-spine lateral view to assess the degree of pre - and postoperative PSTS from C2 to C7 .


At the final follow-up , we assessed the relationship between the occurrence of complications and steroid use .


The degree of dysphagia according to the Bazaz scale was less severe in the group that received methylprednisolone ( p values ; postoperative Day [ POD ] 25 < .05 , POD 6 = .014 , POD 7 = .019 ) .


Prevertebral soft-tissue swelling was also significantly lower in the group that received methylprednisolone ( p values ; POD 2POD 5 < .005 , POD 1 = .061 , POD 6 = .007 , POD 7 = .091 ) .


The amount of PSTS and dysphagia did not differ according to sex , age , smoking history , or length of surgery .


The period of hospitalization in the experimental group was shorter than in the control group .


No complications related to steroid use were found at the final follow-up .


The short-term use of systemic methylprednisolone after ACDF appears to be effective in relieving dysphagia and decreasing the PSTS .


Furthermore , the short-term use of methylprednisolone was not associated with any adverse effects of short-term IV steroid usage , such as peptic ulcer disease or postoperative infection .


The clinical use of methylprednisolone in relieving dysphagia and decreasing PSTS deserves consideration during the early postoperative period .


Mass drug administration ( MDA ) with azithromycin , carried out for the control of blinding trachoma , has been linked to reduced mortality in children .


While the mechanism behind this reduction is unclear , it may be due , in part , to improved nutritional status via a potential reduction in the community burden of infectious disease .


To determine whether MDA with azithromycin improves anthropometric indices at the community level , we measured the heights and weights of children aged 1 to 4 years in communities where one ( single MDA arm ) or three annual rounds ( annual MDA arm ) of azithromycin had been distributed .


Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm .


Mean height-for-age , weight-for-age and weight-for-height z scores were compared between treatment arms .


No significant differences in mean height-for-age , weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms , nor was there a significant reduction in prevalence of stunting , wasting or underweight between arms .


Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia .