All patients with residual disease of @ cm after multiagent chemotherapy ( CTX ) were evaluated using additional positron emission tomography ( PET ) , and those with a PET-positive result were irradiated with @ Gy to the site of residual disease .


We re-evaluated all sites of disease before and after CTX , as well as the PET-positive residual tumor that was treated in all relapsed patients .


Documentation of radiation therapy ( RT ) , treatment planning procedures , and portal images were carefully analyzed and compared with the centrally recommended RT prescription .


The irradiated sites were compared with sites of relapse using follow-up computed tomography scans .


A total of @ patients were enrolled , and @ patients ( @ % ) received RT. .


Radiation therapy documents of @ irradiated patients ( @ % ) were analyzed , with @ irradiated patients ( @ % ) relapsing subsequently .


Eleven patients ( @ % ) had an in-field relapse , @ patients ( @ % ) relapsed outside the irradiated volume , and an additional @ patients ( @ % ) showed mixed in - and out-field relapses .


Of @ patients , @ ( @ % ) with adequately performed RT relapsed , compared with @ of @ patients ( @ % ) with inadequate RT. .


The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL .


Insufficient safety margins of local RT may contribute to in-field relapses .


The purpose of this study was to investigate the remineralization activation of the application of three fissure sealants ( FSs ) , alone or with gaseous ozone ( GO ) , on non-cavitated initial caries and evaluate the clinical success of FS .


Sixty children who had DIAGNOdent scores between @-@ on bilateral symmetric mandibular first permanent molars were included in study .


In a split-mouth design , teeth were assigned to experimental ( with GO ) and control ( without GO ) groups .


GO was applied to teeth on one side and then the same brand of randomly selected FSs was applied to the teeth on both sides .


Children were divided into @ groups based on type of FS ( Group @ : Aegis -LCB- Bosworth Co , North Hamlin Avenue Skokie , Illinois , USA -RCB- , Group @ : Fuji Triage -LCB- GC , Tokyo , Japan -RCB- , Group @ : Helioseal -LCB- Ivoclar Vivadent , Liechtenstein , Germany -RCB- ) .


All FSs were then examined for retention rates at @ , @ , @ , @ , and @ months ; at the end of @ months , all FSs were removed with an air-abrasion device and DIAGNOdent scores noted to compare with the initial values .


The application of GO with either Fuji Triage or Aegis FS was effective on remineralization ( p < @ ) ; however , the application of Helioseal FSs was not effective ( p > @ ) .


The @ ( st ) and @ ( th ) months ' full retention rates of Fuji Triage FSs was a significant difference ( p < @ ) from other FSs ( Aegis and Helioseal ) ( p > @ ) .


GO+A egis FS showed the highest remineralization ; and , at the end of @ months , its clinical success was higher than other FSs .


We wish to assess the clinical and cost-effectiveness of remote monitoring of heart failure patients with cardiac implanted electronic devices .


REM-HF is a multicentre , randomized , non-blinded , parallel trial designed to compare weekly remote monitoring-driven management with usual care for patients with cardiac implanted electronic devices ( ICD , CRT-D , or CRT-P ) .


The trial is event driven , and the final analysis will be performed when @ events have been observed or the study is terminated at the interim analysis .


We have randomized @ patients to be followed up for a minimum of @ years .


Patients will remain in the trial up to study termination .


The first patient was randomized in September @ and the study is expected to complete in early @ .


The primary combined endpoint is time to first event of all-cause death or unplanned hospitalization for cardiovascular reasons .


An economic evaluation will be performed , estimating the cost per quality-adjusted life year , with direct costs estimated from the National Health Service perspective and quality of life assessed by the EQ-@D , Short-Form @ , and Kansas City Cardiomyopathy Questionnaires .


The study design has been informed by a feasibility study .


REM-HF is a multicentre randomized study that will provide important data on the effect of remote monitoring-driven management of implanted cardiac devices on morbidity and mortality , as well as the cost-effectiveness of this approach .


We have previously shown that short sessions of whole body vibration ( WBV ) were not able to significantly improve fall risk among nursing home residents but some trends towards an improvement of motor capacity were observed .


The objective of the present study was to evaluate the impact of @-month training by WBV on functional and motor abilities among nursing home residents observed over a @-month period .


Patients were randomized into two groups : the WBV group which received three training sessions every week composed of five series of @ s of vibration at @ Hz intensity for a period of @ months and a control group with normal daily life .


The impact of this training on the risk of falls was assessed blindly after @ and @ months by the Tinetti Test , the `` Timed Up and Go '' test and a quantitative evaluation of a @-s walk performed with a tri-axial accelerometer .


The occurrence of falls was also observed .


@ elderly healthy volunteers , ( @ women and @ men , mean age @ @ years ) were included in this study .


There was no significant difference between the two groups regarding the Tinetti test ( p = @ ) , the `` Timed Up and Go '' test ( p = @ ) and the Locomtrix ( ) test , except for the step length , measured by dual task ( p < @ ) .


No significant inter-group difference in the frequency of falls was observed during the @ months of research .


A total of @ falls were recorded during the first @ months of experimentation : @ falls in the treated group and @ in the control group ( p = @ ) .


During the next @ months , @ falls occurred : @ falls in the treated group and @ in the control group ( p = @ ) .


This study failed to establish the effectiveness of low doses of WBV , under the conditions used in our study , on functional and motor abilities of institutionalized elderly patients .


However , given the positive results of other studies , further investigations , with modified therapeutic protocols , seem necessary to clarify the effects of WBV in the elderly .


To determine the efficacy and safety of @ doses of botulinum toxin type B ( rimabotulinumtoxinB , BoNT/B ) in spastic upper limb muscles .


Randomized , double-blind , placebo-controlled trial with a @-month follow-up .


Tertiary care center .


Referred sample of adult hemiparetic patients ( N = @ ) with disabling elbow flexor overactivity after stroke or traumatic brain injury .


Injection of @,@ U of rimabotulinumtoxinB ( fixed @U dose into elbow flexors ; n = @ ) , @,@ U ( @U into elbow flexors ; n = @ ) , or placebo ( n = @ ) into overactive upper limb muscles selected as per investigator 's discretion .


At @ month postinjection , active range of elbow extension ( goniometry ; primary outcome ) ; active upper limb function ( Modified Frenchay Scale -LSB- MFS -RSB- ) ; subjective global self-assessment ( GSA ) of arm pain , stiffness , and function ; rapid alternating elbow flexion-extension movement frequency over the maximal range ; elbow flexor spasticity grade and angle ( Tardieu ) , and tone ( Ashworth ) .


No adverse effects were associated with either BoNT/B dose .


Both doses improved active elbow extension versus placebo ( +@ ; @ % confidence interval , @-@ @ ; analysis of covariance , P = @ ) .


The high dose of BoNT/B also improved subject-perceived stiffness ( P = @ ) and the composite pain , stiffness , and function GSA ( P = @ ) , effects that persisted @ months from injection .


No MFS change was demonstrated , although subjects with a baseline MFS < @/@ seemed more likely to benefit from BoNT/B .


In this short-term study , BoNT/B up to @,@ U into spastic upper limb muscles , including the elbow flexors , was well tolerated and improved active elbow extension and subject-perceived stiffness .


Posttraumatic stress disorder ( PTSD ) symptoms in individuals who have experienced repeated trauma ( sexual and/or physical ) in early childhood can lead to problems associated with emotion regulation , interpersonal functioning and self-image .


This so-called complex PTSD is often accompanied by a comorbid personality disorder .


Although ptsd is associated with structural and functional abnormalities in emotion-regulation areas in the brain , it is not known whether complex PTSD shows similar abnormalities .


Experts take the view that before individuals with complex PTSD are given appropriate therapy they should receive a course of emotion-regulation therapy such as the one tested by Zlotnick e.a. ( @ ) in a randomised controlled trial ( RCT ) .


To replicate Zlotnick 's RCT in the Netherlands and to find out whether complex PTSD patients show specific structural and functional brain abnormalities and whether psychological recovery is linked to the ` normalisation ' of these abnormalities .


In a RCT with complex PTSD patients ( n = @ ) who had experienced trauma in early childhood , we compared normal individual treatment with treatment supported by ` Before and beyond ' , which consists of emotion-regulation therapy combined with cognitive group therapy .


In a subsample ( n = @ ) we also performed an mri ( repeated , n = @ ) in which individuals were required to execute an emotional memory and attention task .


In complex PTSD , structural abnormalities in the brain seemed to be more extensive than in PTSD and brain activity in complex PTSD seemed to be strikingly different from the brain activity seen in PTSD patients who had experienced only single trauma .


The results of the RCT indicate that ` Before and beyond ' is a clinically meaningful treatment ( with minimal drop-out ) for complex PTSD patients with a variety of personality disorders .


The psychological recovery of patients who received the emotion regulation and cognitive group treatment was associated with normalisation of brain function .


Treatment guidelines for ptsd patients can not be applied directly and automatically to complex PTSD because there is no scientific evidence to justify such a step .


The neurobiological profile of PTSD differs from that of complex PTSD .


Patients with complex PTSD seem to react favourably to emotion regulation therapy .


This treatment therefore could be a useful addition to the current PTSD guideline for this specific group .


There is a need for further research that focuses on complex PTSD patients .


Young children 's diets are currently suboptimal .


Given that mothers have a critical influence on children ' diets , they are typically a target of interventions to improve early childhood nutrition .


Understanding the maternal factors which mediate an intervention 's effect on young children 's diets is important , but has not been well investigated .


This research aimed to test whether maternal feeding knowledge , maternal feeding practices , maternal self-efficacy , and maternal dietary intakes acted as mediators of the effect of an intervention to improve child diet quality .


The Melbourne Infant Feeding Activity and Nutrition Trial ( InFANT ) Program was a cluster-randomized controlled trial , conducted from @-@ .


This novel , low-dose , health promotion intervention was delivered quarterly over @ months and involved educational activities , promotion of peer discussion , a DVD and written materials .


Post-intervention , when children were approximately @ months of age , child diets were assessed using multiple @-hour recalls and a purpose-developed index of diet quality , the Obesity Protective Dietary Index .


Maternal mediators were assessed using a combination of previously validated and purpose-deigned tools .


Mediation analysis was conducted using the test of joint significance and difference of coefficients methods .


Across @ parents ' groups in Melbourne , Australia , @ parents were recruited .


Post - intervention , higher maternal feeding knowledge and lower use of foods as rewards was found to mediate the direct intervention effect on child diet quality .


While other aspects of maternal feeding practices , self-efficacy and dietary intakes did not act as mediators , they were associated with child diet quality .


Mediation analysis of this novel health promotion intervention showed the importance of maternal feeding knowledge and use of foods as rewards in impacting child diet quality .


The other maternal factors assessed were appropriate targets but further research on how to impact these in an intervention is important .


This evidence of intervention efficacy and mediation provides important insights for planning future interventions .


To present our experience of a novel technique , bladder neck sling suspension technique , in patients undergoing robot-assisted radical prostatectomy ( RARP ) and evaluate its efficacy for improving early continence outcomes after RARP in comparison with that of the standard technique .


Fifty-seven consecutive patients underwent RARP between August @ and April @ .


We performed RARP with and without bladder neck sling suspension technique for @ ( sling group ) and @ ( nonsling group ) patients , respectively , and compared the urinary outcome between the groups .


Both subjective and objective assessments of urinary incontinence were performed before and after RARP .


The International Prostate Symptom Score ( P < @ ) and International Consultation on Incontinence Questionnaire-Short Form ( P < @ ) in the sling group were significantly lower , and Expanded Prostate Cancer Index Composite urinary incontinence score ( P < @ ) in the sling group was higher than those in nonsling group , @ weeks after RARP .


In addition , mean pad weight gain on @-hour pad test in the sling group was significantly smaller than that in the nonsling group , @ weeks after RARP ( P < @ ) .


Both patient perception and objective data of urinary incontinence @ weeks after RARP were better in the sling group than in the nonsling group .


Valsalva maneuver during cystography demonstrated that the mean posterior urethrovesical angle in the sling group was smaller than that in the nonsling group ( P < @ ) .


Bladder neck sling suspension technique is a simple and feasible procedure in RARP and can improve the early return of continence after RARP , although additional larger studies are required to confirm this finding .


High sensitivity C-reactive protein ( hs-CRP ) , an inflammatory biomarker , has been demonstrated to contribute to the process of atherosclerosis and artery stenosis .


The aim of this study was to evaluate whether hs-CRP level is associated with asymptomatic intracranial artery stenosis ( ICAS ) .


A random sample of @ participants aged @years or older ( @ % women ) were enrolled in the Asymptomatic Polyvascular Abnormalities Community study in @-@ .


Information on the potential risk factors for ICAS was collected and the presence of ICAS was assessed by transcranial Doppler in @ participants .


Participants were stratified into three groups according to hs-CRP levels .


A multivariate logistic regression was used to examine the association between hs-CRP levels and asymptomatic ICAS .


The prevalence of asymptomatic ICAS was @ % in this cohort .


The median of hs-CRP levels was positively associated with the increasing numbers of ICASs .


After adjusting for possible risk factors , hs-CRP @mg/l remained significantly associated with asymptomatic ICAS ( odds ratio @ , @ % confidence interval @-@ @ ) .


In this large community-based study , subjects with higher hs-CRP levels showed a mild increase in the prevalence of asymptomatic ICAS , independent of traditional vascular risk factors .


hs-CRP is an independent predictor of asymptomatic ICAS and intracranial atherosclerotic burden .


Diabetes and non-diabetic dysglycaemia are risk factors for accelerated cognitive decline .


In this planned substudy of the Outcome Reduction with Initial Glargine Intervention ( ORIGIN ) trial , we assessed whether normalising glucose with insulin glargine or administering omega-@ fatty acids in this population may slow this process or affect the development of cognitive impairment .


The ORIGIN trial recruited participants older than @ years with dysglycaemia who were taking either no or one oral glucose-lowering drug , who had additional risk factors for cardiovascular events , whose HbA@c was less than @ % , and who were not taking insulin .


Participants were recruited from @ sites in @ countries .


Participants were randomly assigned to either titrated basal insulin glargine targeting a fasting plasma glucose concentration of @ mmol/L or lower or standard care and to either omega-@ fatty acid ( @ g ) or placebo by a factorial design .


Outcome adjudicators and data analysts were masked to treatment allocation .


Cognitive function was assessed by the Mini-Mental State Examination ( MMS ) and Digit Symbol Substitution ( DSS ) .


The effect of insulin glargine or omega-@ fatty * acid on cognitive function over time , the annualised change in test scores , and the development of probable cognitive impairment were measured .


All analyses were restricted to those participants who had a cognitive measurement at both baseline and at least one follow-up visit .


The ORIGIN trial is registered with ClinicalTrials.gov , NCT@ .


Participants were randomly assigned between Sept @ , @ , and Dec @ , @ .


MMSE and DSS were assessed in @,@ and @ ORIGIN participants ( mean age @ years -LSB- SD @ -RSB- ) , who were followed up for a median of @ years ( IQR @-@ @ ) .


There was no difference in the rate of change of cognitive test scores between the insulin glargine and standard care groups ( for the MMSE @ , @ % CI -@ to @ , p = @ ; and for the DSS -@ , -@ to @ , p = @ ) or between the omega-@ fatty acid and placebo groups ( for the MMSE @ , @ % CI -@ to @ , p = @ ; and for the DSS -@ , -@ to @ , p = @ ) .


Similarly , the incidence of probable cognitive impairment did not differ between the insulin glargine and standard care groups ( p = @ ) or the omega-@ fatty acid and placebo groups ( p = @ ) .


In a subgroup analysis , allocation to insulin glargine versus standard care seemed to reduce the decline in the MMSE ( but not the DSS ) in participants with dysglycaemia but without evidence of diabetes ( pinteraction = @ ) .


In this relatively young cohort of people with dysglycaemia , insulin mediated normoglycaemia and omega-@ fatty acid for over @ years had a neutral effect on the rate of cognitive decline and on incident cognitive impairment .


Future studies should assess the effect of these interventions in an older cohort or the effect of other glucometabolic interventions on cognitive decline .


Nomegestrol acetate ( NOMAC ) / @-estradiol ( E@ ) is a monophasic oral contraceptive that contains a progesterone-derived progestogen ( NOMAC ) , and E@ , a bio-identical estrogen .


The primary objective of this thorough QT/QTc study was to investigate whether once-daily administration of therapeutic ( @ / @ mg ) and supratherapeutic ( @ / @ mg ) doses of NOMAC/E@ were associated with prolongation of the mean Fridericia-corrected QT ( QTcF ) interval in electrocardiograms at steady-state concentrations of NOMAC/E@ versus placebo .


The co-primary objective was to establish assay sensitivity after a single dose of moxifloxacin ( positive control ) .


This was a randomized , double-blind , parallel-group trial comparing @ / @ mg of NOMAC/E@ ( therapeutic dose ) , @ / @ mg of NOMAC/E@ ( supratherapeutic dose ) , placebo , and moxifloxacin @ mg .


Double-blind study medication was administered from day -@ to @ .


Healthy women aged @-@ years were randomized .


The largest time-matched mean QTcF difference compared with placebo for the therapeutic dose of NOMAC/E@ was @ ms , with an upper limit ( UL ) of a one-sided @ % confidence interval ( CI ) of @ ms , and @ ms with an UL @ % CI of @ ms for the supratherapeutic dose .


The UL for the time-matched QTcF differences compared with placebo were below the @ ms threshold defined in the ICH E@ guideline for all time points , both for the therapeutic and the supratherapeutic dose .


For moxifloxacin , assay sensitivity was demonstrated .


This thorough QT/QTc study showed that therapeutic and supratherapeutic doses of NOMAC/E@ were not associated with clinically relevant QTc interval prolongation in healthy women after a @-week period of dosing .


Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine ( NAC ) in chronic obstructive pulmonary disease ( COPD ) .


However , the required dose and responder phenotype remain unclear .


The current study investigated the effect of high-dose NAC on airway geometry , inflammation , and oxidative stress in COPD patients .


Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy .


Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC @ mg or placebo daily for @ months and were then crossed over to the alternative treatment for a further @ months .


Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC ( P = @ ) and glutathione peroxidase at baseline ( P = @ ) .


Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC ( P = @ ) , changes in glutathione peroxidase levels ( P = @ ) , and reduction in lobar functional residual capacity levels ( P = @ ) .


In the limited set of responders to NAC therapy , the changes in airway resistance were in the same order as changes induced by budesonide/formoterol .


A combination of glutathione , glutathione peroxidase , and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy .


The findings of this small pilot study need to be confirmed in a larger pivotal trial .


To describe and compare characteristics of older adults who drive after drinking and those who do not , whether an intervention addressing at-risk drinking reduces risk among those reporting driving after drinking , and reasons reported for driving after drinking .


Secondary data analysis of a randomized trial testing the efficacy of a multifaceted intervention to reduce at-risk drinking among adults with a mean age of @ years in primary care ( N = @ ) .


Almost a quarter of at-risk drinkers reported driving after drinking ( N = @ ) .


Compared to those who did not drive after drinking , those who did were more likely to be younger , male , and working .


They consumed a higher average number of drinks per week , had more reasons they were considered at-risk drinkers , and were more likely to meet at-risk drinking criteria due to amount of drinking and binge drinking .


Those driving after drinking at baseline reduced the frequency of this behavior at @ and @ months and there were no statistically significant differences in the proportions of persons still engaging in driving after drinking among those who were assigned to intervention or control groups .


Reasons for driving after drinking included not thinking that it was a problem and having to get home .


Driving after drinking is common in this population of older , at-risk drinkers recruited in primary care settings and , like younger adults , men and those reporting binge drinking are more likely to engage in this behavior .


Given that this behavior is dangerous and the population of older adults is fast growing , interventions addressing driving after drinking are needed .


Cost-effective guidance of therapeutic strategy in Crohn 's disease patients with secondary infliximab ( IFX ) treatment failure may be achieved by serum IFX and anti-IFX antibody ( Ab ) measurements by radioimmunoassay ( RIA ) .


This study investigated implications of using other techniques for this purpose .


This is a post hoc analysis of randomized clinical trial including @ Crohn 's disease patients with IFX failure in whom IFX and anti-IFX Ab measurements by RIA had been used for therapeutic guidance .


Samples were additionally assessed by enzyme-linked immunosorbent assay ( ELISA ) , homogeneous mobility shift assay ( HMSA ) , and functional cell-based reporter gene assay ( RGA ) .


IFX detection was comparable between assays ( @ % RIA , @ % ELISA , @ % HMSA , and @ % RGA ) , and it correlated significantly ( Pearson 's r = @-@ @ , P < @ ) .


However , IFX concentrations varied systematically between all pair of assays except RIA-RGA .


Anti-IFX Ab detection was variable ( @ % RIA , @ % ELISA , @ % HMSA , and @ % RGA ) , but correlated significantly ( Pearson 's r = @-@ @ ; P < @ ) .


Anti-IFX Abs detected by RIA and HMSA were often from sera without drug-neutralizing activity ( RGA ) .


Assays agreed on classification of underlying mechanism for treatment failure in most cases ( @-@ % ) .


The majority ( @-@ % ) failed IFX owing to pharmacodynamic problems , or had noninflammatory pathophysiology for symptoms resembling relapse .


Applied threshold for therapeutic vs. subtherapeutic IFX level influenced classifications .


The four different assays did not differ in terms of the ability to predict response to interventions defined by the algorithm .


Despite variable analytical properties , common assays result in similar classifications and interventions in patients with IFX treatment failure , and with comparable clinical outcomes .


Implications are , however , profound for the minority classified differently .


Randomized clinical trial .


To examine the effectiveness of cervical traction in addition to exercise for specific subgroups of patients with neck pain .


Cervical traction is frequently used , but its effectiveness has not been adequately examined .


Existing studies have failed to target patients most likely to respond .


Traction is typically recommended for patients with cervical radiculopathy .


A prediction rule has been described to identify a narrower subgroup of patients likely to respond to cervical traction .


Patients with neck pain and signs of radiculopathy were randomized to @ weeks of treatment with exercise , exercise with mechanical traction , or exercise with over-door traction .


Baseline assessment included subgrouping-rule status .


The primary outcome measure ( Neck Disability Index , scored @-@ ) and secondary outcome measure ( neck and arm pain intensity ) were assessed at @ weeks , @ months , and @ months after enrollment .


The primary analyses examined @-way treatment-by-time interactions .


Secondary analyses examined validity of the subgrouping rule by adding @-way interactions .


Eighty-six patients ( @ % female ; mean age , @ years ) were enrolled in the study .


Intention-to-treat analysis found lower Neck Disability Index scores at @ months in the mechanical traction group compared to the exercise group ( mean difference between groups , @ ; @ % confidence interval : @ , @ ) and over-door traction group ( mean difference between groups , @ ; @ % confidence interval : @ , @ ) , and at @ months in the mechanical traction group compared to the exercise group ( mean difference between groups , @ ; @ % confidence interval : @ , @ ) .


Secondary outcomes favored mechanical traction at several time points .


The validity of the subgrouping rule was supported on the Neck Disability Index at the @-month time point only .


Adding mechanical traction to exercise for patients with cervical radiculopathy resulted in lower disability and pain , particularly at long-term follow-ups .


The study protocol was registered at http://clinicaltrials.gov ( NCT@ ) .


Nicotinic acetylcholine receptors ( nAChRs ) were identified on eosinophils and shown to regulate inflammatory responses , but nAChR expression on basophils has not been explored yet .


We investigated surface receptor expression of nAChR @ , @ and @/@/@ subunits on basophils .


Furthermore , we examined the effects of ASM-@ , a synthetic nicotinic ligand , on in vitro anti-IgE and in vivo allergen-induced basophil activation .


Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined .


Purified basophils were stimulated with anti-IgE in the presence of ASM-@ with or without muscarinic or nicotinic antagonists for the measurement of CD@c expression and histamine release .


The effect of @ days of treatment with @ and @ mg ASM-@ on basophil CD@c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge .


nAChR @ , @ and @/@/@ receptor subunit expression was detected on basophils .


Stimulation of basophils with anti-IgE increased CD@c expression and histamine release , which was inhibited by ASM-@ ( @ ( -@ ) to @ ( - ) ( @ ) M , p < @ ) .


The effect of ASM-@ was reversed in the presence of muscarinic and nicotinic antagonists .


In subjects with mild asthma , ASM-@ inhalation significantly inhibited basophil CD@c expression measured @ h after allergen challenge ( p = @ ) .


This study shows that ASM-@ inhibits IgE - and allergen-induced basophil activation through both nicotinic and muscarinic receptors , and suggests that ASM-@ may be an efficacious agent for modulating allergic asthma responses .


Aprepitant is a neurokinin @ receptor antagonist approved for prevention of chemotherapy-induced and post-operative nausea and vomiting .


Early studies demonstrated promising antidepressant activity as monotherapy , although this was unsupported by subsequent phase @ trials .


This phase @ study evaluated whether aprepitant potentiated the antidepressant effects of paroxetine .


Outpatients with major depressive disorder were randomized to aprepitant @ mg + paroxetine @ mg , paroxetine + placebo , or aprepitant + placebo for @ weeks .


The primary endpoint was change in HAMD-@ total score .


Secondary/exploratory endpoints included changes in HAMA , CGI-S , CGI-I , and HAMD Item-@ scores at week @ .


A total of @ , @ , and @ patients received aprepitant + paroxetine , paroxetine + placebo , and aprepitant + placebo , respectively .


At week @ , mean changes in HAMD-@ were -@ ( @ % confidence interval -LSB- CI -RSB- : -@ , -@ ) , -@ ( @ % CI : -@ , -@ ) , and -@ ( @ % CI : -@ , -@ ) , respectively .


Pairwise comparisons of HAMD-@ change with combination therapy versus paroxetine alone demonstrated no significant difference ( p = @ ) .


Changes in CGI-S , CGI-I , and HAMD Item-@ scores were also comparable , although there was a greater reduction in anxiety ( HAMA ) with paroxetine alone than aprepitant + paroxetine ( p = @ ) .


Adverse events were generally more common with the combination than either monotherapy .


Concomitant use of aprepitant + paroxetine for @ weeks did not provide greater antidepressant benefit compared with paroxetine + placebo in patients with major depression .


A recent systematic review suggests that practice facilitation ( PF ) is a robust intervention for implementing evidence-based preventive care guidelines in primary care , but the ability of PF to improve chronic illness care remains unclear .


To examine the specific activities and Chronic Care model ( CCM ) components that primary care practices implemented and sustained in response to a @-month PF intervention .


The ABC trial tested the effectiveness of PF to improve care for diabetes in @ small community-based primary care practices that were randomized to `` initial '' or `` delayed '' intervention arms .


A trained facilitator met with each practice over @-months .


Facilitators used interactive consensus building to help practices implement one or more of quality improvement activities based on the CCM .


Facilitators prospectively recorded implementation activities reported by practice teams during monthly meetings and confirmed which of these were sustained at the end of the intervention .


@ practices implemented and sustained a total of @ unique activities -LSB- range @-@ , average @ ( SD = @ ) -RSB- .


The number ( % ) of practices that implemented @ or more key activities in each CCM component varied : Patient Self-Management Support : @ ( @ % ) ; Clinical Information Systems : @ ( @ % ) , Delivery System Design : @ ( @ % ) , Decision Support : @ ( @ % ) , Community Linkages : @ ( @ % ) ; Healthcare System Support : @ ( @ % ) .


The majority of practices ( @ % ) only implemented activities from @ or @ CCM components .


The number of sustained activities was associated with the number of PF visits , but not with practice characteristics .


In spite of the PF intervention , it was difficult for these small practices to implement comprehensive CCM changes .


Although practices implemented and sustained a remarkable number and variety of key activities , the majority of these focused on patient self-management support , as opposed to other components of the CCM , such as clinical information systems , decision support , delivery system redesign , and community linkages .


To demonstrate the superiority of estradiol valerate plus dienogest ( E ( @ ) V/DNG ) over ethinylestradiol plus levonorgestrel ( EE/LNG ) in reducing the number of days with dysmenorrheic pain among women with primary dysmenorrhea .


In a phase IIIb trial conducted at @ centers worldwide between April @ and November @ , otherwise healthy women aged @-@ years requesting contraception were randomized to daily oral administration of E ( @ ) V/DNG ( n = @ ) or EE/LNG ( n = @ ) for three @-daycycles .


The primary efficacy variable was number of days with dysmenorrheic pain , the category of which ( none , mild , moderate , severe ) was self-assessed on a daily basis ( irrespective of menstrual bleeding status ) and recorded on diary cards .


Notably , the women documented their pain as they experienced it before taking any ( permitted ) rescue medication .


Overall , @ and @ women receiving E ( @ ) V/DNG and EE/LNG , respectively , completed the study .


The mean SD change from baseline in number of days with dysmenorrheic pain was -@ @ days and -@ @ days for the E ( @ ) V/DNG and EE/LNG groups , respectively ( P = @ ) .


Both E ( @ ) V/DNG and EE/LNG led to considerable relief of dysmenorrheic complaints among women with primary dysmenorrhea , decreasing the number of days with dysmenorrheic pain from baseline to a similar extent .


ClinicalTrials.gov : NCT@ .


Treating anaemia with red blood cell ( RBC ) transfusion is frequent , but controversial , in patients with septic shock .


Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients .


We did a prospective cohort study at @ general intensive care units ( ICUs ) including all adult patients with septic shock in a @-month period .


Ninety-five of the @ included patients ( @ % ) received median @ ( interquartile range @-@ ) RBC units during shock .


The median pre-transfusion haemoglobin level was @ ( @-@ @ ) g/dl and independent of shock day and bleeding .


Patients with cardiovascular disease were transfused at higher haemoglobin levels .


Transfused patients had higher Simplified Acute Physiology Score ( SAPS ) II ( @ ( @-@ ) vs. @ ( @-@ ) , p = @ ) , more bleeding episodes , lower haemoglobin levels days @ to @ , higher Sepsis-related Organ Failure Assessment ( SOFA ) scores ( days @ and @ ) , more days in shock ( @ ( @-@ ) vs. @ ( @-@ ) , p = @ ) , more days in ICU ( @ ( @-@ ) vs. @ ( @-@ ) , p = @ ) and higher @-day mortality ( @ vs. @ % , p = @ ) .


The latter association was lost after adjustment for admission category and SAPS II and SOFA-score on day @ .


The decision to transfuse patients with septic shock was likely affected by disease severity and bleeding , but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients .


For patients with neuromuscular disorders , lung insufflation with positive pressure is an accepted technique to increase inspiratory volume over VC to improve peak cough flow ( PCF ) .


The aim of the study was to determine the pressure or volume required to achieve the highest individual PCF .


In @ patients dependent on noninvasive ventilation ( VC , @ % predicted ; age , @ yr ) and in @ healthy control subjects , insufflation capacity ( IC ) was measured during titration from @ to maximum @ mbar using intermittent positive pressure breathing ( IPPB ) or the lung insufflation assist maneuver ( LIAM ) of the VENTIlogic LS ventilator .


IPPB or LIAM titration resulted in a pressure-volume curve with an estimated total compliance of @ L/kPa in the patients and @ L/kPa in the controls and a plateau for IC at pressures between @ and @ mbar .


IPPB or LIAM improved VC from @ ml to a maximum IC ( ICmax ) of @,@ ml , and PCF improved from @ to @ L/min ( P < @ for all ) .


The highest individual PCF was achieved with @ mbar and an IC of @ ml , which was significantly below ICmax ( P < @ ) .


A submaximal insufflation is ideal for generating the best individual PCF even in patients with severely reduced compliance of the respiratory system .


Optimum insufflation capacity can be achieved using IPPB or LIAM with moderate pressures .


Both techniques are equally effective and considered safe .


To increase the safety and effectiveness of treatments for overactive bladder ( OAB ) with moderate symptoms in elderly patients .


Patients were examined at the Urodynamic Department of the Regional Diagnostic Center ( Vladivostok , Russian Federation ) from September @ , @ to December @ , @ .


The assignment of patients -LSB- n = @ , average age @ years , @ women ( @ % ) and @ men ( @ % ) -RSB- was random and blind in this placebo-controlled study .


Patients were distributed into subgroups according to the method of treatment as follows : group @ : n = @ , trospium @ mg/day + solifenacin @ mg/day ; group @ : n = @ , trospium @ mg/day + solifenacin @ mg/day ; group @ : n = @ , placebo .


All patients underwent a urodynamic examination in accordance with international standards before and @ months after treatment .


ICIQ-SF questionnaires recommended by the International Continence Society ( ICS ) and bladder diaries were used to evaluate the clinical results .


The clinical severity of the OAB symptoms and the effectiveness of the treatment were evaluated based on the frequency of episodes of incontinence ( EI ) per day .


Three or fewer EI per day were considered moderate dysfunction of the lower urinary tract .


Groups of elderly patients with moderate symptoms of OAB who were treated with standard - and low-dose trospium and solifenacin demonstrated a significant increase in the median values of reflex volume , bladder capacity , and detrusor compliance and a decrease in the frequency of urination and urinary urgencies .


The frequency of EI in both of the main groups decreased by almost @-fold in comparison to the initial data and reached the following values : group @ : @ ( -@ ) , p @ ; group A@ : @ ( -@ ) , p @ .


The correlation with the decrease in the frequency of EI in these groups was r = @ ( p @ ) .


The percentage of patients with a significant decrease ( EI @ ) among those treated with standard - and low-dose trospium and solifenacin increased synchronously , prompting us to suppose the absence of a direct correlation between medicine dose and therapeutic effect for moderate OAB symptoms .


The combination of low-dose trospium and solifenacin provides good clinical and urodynamic effects in elderly patients with moderate symptoms of OAB .


Combination of these drugs in standard doses for such patients is excessive .


Resistance to trastuzumab is a problem that remains to be solved in HER@-positive breast cancer .


We aimed to characterize profiles of genetic and epigenetic alterations in cancer-related pathways in HER@-positive breast cancers , using biopsy tissue samples obtained from patients enrolled in a prospective neoadjuvant clinical trial .


HER@-positive breast cancer tissue samples were collected and processed with the PAXgene Tissue System .


A total of @ breast cancers were analyzed .


Genetic alterations of @ cancer-related genes were analyzed by a bench-top next-generation sequencer .


DNA methylation statuses were analyzed by a bead array with @,@ probes .


The WNT pathway was potentially activated by aberrant methylation of its negative regulators , such as DKK@ and SFRP@ , in @ breast cancers .


The AKT/mTOR pathway was activated by mutations of PIK@CA in @ breast cancers .


The Notch pathway was potentially activated by mutations of NOTCH@ and NOTCH@ in @ breast cancers .


The p@ pathway was inactivated by mutations of TP@ in @ breast cancers and potentially by aberrant methylation of its downstream genes in @ breast cancers .


Cell adhesion was affected by mutations of CDH@ in @ breast cancer .


Genes involved in cancer-related pathways were frequently affected not only by genetic but also by epigenetic alterations in HER@-positive breast cancer .


Interventions are needed to reduce poor perinatal health .


We trained community health workers ( CHWs ) as home visitors to address maternal/infant risks .


In a cluster randomised controlled trial in Cape Town townships , neighbourhoods were randomised within matched pairs to @ ) the control , healthcare at clinics ( n = @ neighbourhoods ; n = @ women ) , or @ ) a home visiting intervention by CBW trained in cognitive-behavioural strategies to address health risks ( by the Philani Maternal , Child Health and Nutrition Programme ) , in addition to clinic care ( n = @ neighbourhoods ; n = @ women ) .


Participants were assessed during pregnancy ( @ % refusal ) and @ % were reassessed at two weeks post-birth , @ % at six months and @ % at @ months later .


We analysed @ measures of maternal/infant well-being over the @ month follow-up period using longitudinal random effects regressions .


A binomial test for correlated outcomes evaluated overall effectiveness over time .


The @ month post-birth assessment outcomes also were examined alone and as a function of the number of home visits received .


Benefits were found on @ of @ measures of outcomes , resulting in significant overall benefits for the intervention compared to the control when using the binomial test ( p = @ ) ; nevertheless , no effects were observed when only the @ month outcomes were analyzed .


Benefits on individual outcomes were related to the number of home visits received .


Among women living with HIV , intervention mothers were more likely to implement the PMTCT regimens , use condoms during all sexual episodes ( OR = @ ; p = @ ) , have infants with healthy weight-for-age measurements ( OR = @ ; p = @ ) , height-for-age measurements ( OR = @ , p < @ ) , breastfeed exclusively for six months ( OR = @ ; p < @ ) , and breastfeed longer ( OR = @ ; p < @ ) .


Number of visits was positively associated with infant birth weight @ grams ( OR = @ ; p = @ ) , healthy head-circumference-for-age measurements at @ months ( OR = @ , p = @ ) , and improved cognitive development at @ months ( OR = @ , p = @ ) .


Home visits to neighbourhood mothers by CHWs may be a feasible strategy for enhancing maternal/child outcomes .


However , visits likely must extend over several years for persistent benefits .


We have reported , in a randomized , controlled study , that tegafur-uracil ( UFT ) and protein-bound polysaccharide K ( PSK ) combination therapy significantly improves the @-year disease-free survival rate and reduces the risk of recurrence compared to UFT alone for Stage II or III colorectal cancer .


In this study , we examined the efficacy of PSK by stratifying patients according to the preoperative lymphocyte ratio ( Lym ) .


In a randomized , controlled study , @ patients were eligible ( @ in the UFT/PSK group and @ in the UFT group ) .


Of these , @ patients with available preoperative Lym data were analysed ( @ in the UFT/PSK group and @ in the UFT group ) .


Among patients with a preoperative Lym of < @ % , the relapse-free survival ( RFS ) rate was @ % in the UFT/PSK group and @ % in the UFT group ( p = @ ) .


However , in patients with a preoperative Lym of @ % , the RFS rate did not differ between the @ groups .


Similarly , overall survival was significantly higher in the UFT/PSK group than in the UFT group in patients with a preoperative Lym of < @ % , whereas no intergroup difference was found among patients with a preoperative Lym of @ % .


This study suggests that a low preoperative Lym is a good predictor for response to PSK in patients with Stage II or III colorectal cancer .


Persistent postsurgical pain ( PPP ) after thoracotomy effect @ % to @ % .


Nerve damage and central sensitization involving NDMDAr activation may play an important role .


This study evaluates the efficacy of adding intravenous ( IV ) or epidural ketamine to thoracic epidural analgesia ( TEA ) after thoracotomy .


Double-blind randomized study on patients undergoing thoracotomy allocated to one of the following : group Kiv ( IV racemic ketamine @ mg/kg preincisional +@ mg/kg/h for @ h ) , group Kep ( epidural racemic ketamine @ mg/kg preincisional +@ mg/kg/h for @ h ) , or group S ( saline ) .


Postoperative analgesia was ensured by TEA with ropivacaine and fentanyl .


Pain visual analog scales ( VAS ) , Neuropathic Pain Symptom Inventory , Catastrophizing Scale , and Quantitative Sensory Testing , measuring both the peri-incisional and distant hyperalgesia area , were conducted preoperatively and postoperatively until @ months .


Plasma ketamine levels and stability of the analgesic solutions were analyzed .


A total of @ patients were included .


PPP incidence was @ % at @ months .


Pain scores on coughing were significantly lower in Kiv and Kep than in S at @ and @ hours , but there were no differences afterwards .


There were no significant differences in pain at rest , Neuropathic Pain Symptom Inventory , and Catastrophizing Scale , or in the area of mechanical allodynia at any time .


Adverse effects were mild .


Plasma ketamine levels did not differ significantly between groups .


Analgesic solutions were stable .


Adding epidural or IV racemic ketamine to TEA after thoracotomy did not lead to any reduction in PPP or allodynia .


Epidural administration produced similar plasma ketamine levels to the IV route .


Whether current postoperative surveillance regimes result in improved overall survival ( OS ) of patients with extremity sarcomas is unknown .


We hypothesized that a less intensive followup protocol would not be inferior to the conventional followup protocol in terms of OS .


We ( @ ) assessed OS of patients to determine if less intensive followup regimens led to worsened survival and asked ( @ ) whether chest radiograph followup group was inferior to CT scan followup group in detecting pulmonary metastasis ; and ( @ ) whether less frequent ( @-monthly ) followup interval was inferior to more frequent ( @-monthly ) followup in detecting pulmonary metastasis and local recurrence .


A prospective randomized single-center noninferiority trial was conducted between January @ and June @ .


On the basis of @-year survival of @ % with intensive , more frequent followup , @ nonmetastatic patients were randomized to demonstrate noninferiority by a margin ( delta ) of @ % ( hazard ratio -LSB- HR -RSB- , @ ) .


The primary end point was OS at @years .


The secondary objective was to compare disease-free survival ( DFS ) ( time to recurrence ) at @years .


At minimum followup of @months ( median , @months ; range , @-@months ) , @ deaths were documented .


Three-year OS and DFS for all patients was @ % and @ % , respectively .


Three-year OS was @ % and @ % in chest radiography and CT groups , respectively ( HR , @ ; upper @ % confidence interval -LSB- CI -RSB- , @ ) .


DFS rate was @ % and @ % in chest radiography and CT groups , respectively ( HR , @ ; upper @ % CI , @ ) .


Three-year OS was @ % and @ % in @-monthly and @-monthly groups , respectively ( HR , @ ; upper @ % CI , @ ) .


DFS was @ % and @ % in @-monthly and @-monthly groups , respectively ( HR , @ ; upper @ % CI , @ ) .


Almost @ % of local recurrences were identified by patients themselves .


Inexpensive imaging detects the vast majority of recurrent disease in patients with sarcoma without deleterious effects on eventual outcomes .


Patient education regarding self-examination will detect most instances of local recurrence although this was not directly assessed in this study .


Although less frequent visits adequately detected metastasis and local recurrence , this trial could not conclusively demonstrate noninferiority in OS for a @-monthly interval of followup visits against @-monthly visits .


Level I , therapeutic study .


See Guidelines for Authors for a complete description of levels of evidence .


An elevated heart rate is an established marker of cardiovascular risk .


Previous analyses have suggested that ivabradine , a heart-rate-reducing agent , may improve outcomes in patients with stable coronary artery disease , left ventricular dysfunction , and a heart rate of @ beats per minute or more .


We conducted a randomized , double-blind , placebo-controlled trial of ivabradine , added to standard background therapy , in @,@ patients who had both stable coronary artery disease without clinical heart failure and a heart rate of @ beats per minute or more ( including @,@ patients with activity-limiting angina -LSB- class II on the Canadian Cardiovascular Society scale , which ranges from I to IV , with higher classes indicating greater limitations on physical activity owing to angina -RSB- ) .


We randomly assigned patients to placebo or ivabradine , at a dose of up to @ mg twice daily , with the dose adjusted to achieve a target heart rate of @ to @ beats per minute .


The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction .


At @ months , the mean ( SD ) heart rate of the patients was @ beats per minute in the ivabradine group versus @ beats per minute in the placebo group .


After a median follow-up of @ months , there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point ( @ % and @ % , respectively ; hazard ratio , @ ; @ % confidence interval , @ to @ ; P = @ ) , nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction .


Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina ( P = @ for interaction ) .


The incidence of bradycardia was higher with ivabradine than with placebo ( @ % vs. @ % , P < @ ) .


Among patients who had stable coronary artery disease without clinical heart failure , the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes .


( Funded by Servier ; SIGNIFY Current Controlled Trials number , ISRCTN@ . )


Providing care for adolescents with type @ diabetes is complex , demanding , and often unsuccessful .


Guided self-determination ( GSD ) is a life skills approach that has been proven effective in caring for adults with type @ diabetes .


To improve care , GSD was revised for adolescents , their parents , and interdisciplinary healthcare providers ( HCP ) to create GSD-Youth ( GSD-Y ) .


We evaluated the impact of GSD-Y after it was integrated into pediatric outpatient visits versus treatment-as-usual , focusing on glycemic control and the development of life skills in adolescents with type @ diabetes .


Seventy-one adolescents ( mean age : @ years , mean duration of diabetes : @ years , mean HbA@c : @ mmol/mol ( @ % ) , upon entering the study ) from two pediatric departments were randomized into a GSD-Y group ( n = @ , GSD-Y was provided during individual outpatient sessions ) versus a treatment-as-usual group ( n = @ ) .


The primary outcome was the HbA@c measurement .


The secondary outcomes were life skills development ( assessed by self-reported psychometric scales ) , self-monitored blood glucose levels , and hypo - and hyperglycemic episodes .


The analysis followed an intention-to-treat basis .


Fifty-seven adolescents ( @ % ) completed the trial , and @ ( @ % ) completed a six-month post-treatment follow-up .


No significant effect of GSD-Y on the HbA@c could be detected in a mixed-model analysis after adjusting for the baseline HbA@c levels and the identity of the HCP ( P = @ ) .


GSD-Y significantly reduced the amotivation for diabetes self-management after adjusting for the baseline value ( P = @ ) .


Compared with the control group , the trial completion was prolonged in the GSD-Y group ( P < @ ) , requiring more visits ( P = @ ) with a higher rate of non-attendance ( P = @ ) .


GSD-Y parents participated in fewer of the adolescents ' visits ( P = @ ) compared with control parents .


Compared with treatment-as-usual , GSD-Y did not improve HbA@c levels , but it did decrease adolescents ' amotivation for diabetes self-management .


Two common general anaesthetic methods are total i.v. anaesthesia ( TIVA ) and inhalation anaesthesia , but it is unclear whether this affects the patient 's perception of their quality of recovery .


The Quality of Recovery-@ questionnaire ( QoR-@ ) is a valid and reliable method to evaluate the extent of functional recovery after surgery with general anaesthesia .


This study therefore compared patient recovery using the QoR-@ in surgical patients who received TIVA with those who received desflurane anaesthesia .


Eighty females ( @-@ years old ) undergoing thyroid surgery were prospectively recruited and randomized to either the TIVA ( effect-site target controlled infusion using propofol and remifentanil ) or DES ( desflurane inhalation with manual infusion of remifentanil ) groups .


The QoR-@ was administered by an investigator blind to group allocation before surgery , and postoperative days @ and @ ( POD@ and POD@ ) .


Additional data including the incidence of nausea or vomiting , the consumption of antiemetic and analgesic agents in the post-anaesthesia care unit , and the duration of the hospital stay , were collected in all cases .


The QoR-@ score on POD@ was significantly higher in the TIVA group compared with the DES group ( @ vs @ , respectively ; P = @ ) , indicating a better quality of recovery in the TIVA group .


Among the five dimensions of the QoR-@ , physical comfort and physical independence were significantly better on POD@ and POD@ in the TIVA group .


This study demonstrates that the quality of recovery for female thyroid surgery patients is significantly better with TIVA compared with desflurane anaesthesia .


To determine the value of cardiac MRI for the monitoring and the prognosis of patients with acute myocarditis .


Cardiac MRI plays an increasingly important role in the diagnosis of acute myocarditis .


However , it is less established as a prognostic tool , which requires specific postprocessing of images .


In a prospective pilot study , we assessed the prognostic value of the evolution in a simplified visual quantitative score ( SQS ) of late gadolinium enhancement ( LGE ) between initial hospitalization and @ months later .


The prognostic value was assessed at @ year using a combination of death , heart transplant , and confirmed recurrence as main outcome .


Twenty-eight patients were included in this study .


A significant correlation was found between LGE measured by SQS and planimetry ( r = @ , P < @ ) .


Intraobserver and interobserver reproducibilities were good for SQS ( ICC = @ -LSB- @ % CI : @ to @ -RSB- , and @ -LSB- @ % CI : @ to @ -RSB- , respectively ) .


At initial hospitalization , patient characteristics between the two groups were similar .


Patients with stable or increased SQS suffered more frequently from clinical outcome events than patients with a decrease in SQS ( P = @ ) .


Monitoring of the evolution of LGE using a simple visual score is of interest to identify patients at risk of pejorative prognosis after acute myocarditis .


To evaluate maintenance of response while reducing intravenous abatacept dose from ~ @ mg/kg to ~ @ mg/kg in patients with early rheumatoid arthritis ( RA ) who achieved disease activity score ( DAS ) @ ( erythrocyte sedimentation rate , ESR ) < @ .


This @-year , multinational , randomised , double-blind substudy evaluated the efficacy and safety of ~ @ mg/kg and ~ @ mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS@ ( ESR ) < @ at year @ of the AGREE study .


The primary outcome was time to disease relapse ( defined as additional disease-modifying antirheumatic drugs , @ courses high-dose steroids , return to open-label abatacept ~ @ mg/kg , or DAS@ ( C reactive protein ) @ at two consecutive visits ) .


@ patients were randomised ( ~ @ mg/kg , n = @ ; ~ @ mg/kg , n = @ ) .


Three and five patients , respectively , discontinued , and four per group returned to open-label abatacept .


Relapse over time and the proportion of patients relapsing were similar in both groups ( @ % ( ~ @ mg/kg ) vs @ % ( ~ @ mg/kg ) ; HR : @ ( @ % CI @ to @ ) ) .


Mean steady-state trough serum concentration for the ~ @ mg/kg group was @-@ @ g/mL , compared with @-@ @ g/mL for the ~ @ mg/kg group .


This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS@ ( ESR ) < @ after @ year on abatacept ( ~ @ mg/kg ) .


This study aimed to determine if delayed sodium ( @ ) F-fluoride ( Na ( @ ) F ) PET/CT imaging improves quantification of vascular calcification metabolism .


Blood-pool activity can disturb the arterial Na ( @ ) F signal .


With time , blood-pool activity declines .


Therefore , delayed imaging can potentially improve quantification of vascular calcification metabolism .


Twenty healthy volunteers and @ patients with chest pain were prospectively assessed by triple time-point PET/CT imaging at approximately @ , @ , and @ minutes after Na ( @ ) F administration .


For each time point , global uptake of Na ( @ ) F was determined in the coronary arteries and thoracic aorta by calculating the blood-pool-corrected maximum standardized uptake value ( cSUV ( MAX ) ) .


A target-to-background ratio ( TBR ) was calculated to determine the contrast resolution at @ , @ , and @ minutes .


Furthermore , we assessed whether the acquisition time-point affected the relation between cSUV ( MAX ) and the estimated @-year risk for fatal cardiovascular disease ( SCORE % ) .


Coronary cSUV ( MAX ) ( P = @ ) and aortic cSUV ( MAX ) ( P = @ ) remained similar with time , whereas the coronary TBR ( P < @ ) and aortic TBR ( P < @ ) significantly increased with time .


Even though the contrast resolution improved with time , positive correlations between SCORE % and coronary cSUV ( MAX ) ( P < @ ) and aortic cSUV ( MAX ) ( P < @ ) were observed at all investigated time points .


Delayed Na ( @ ) F PET/CT imaging does not improve quantification of vascular calcification metabolism .


Although contrast resolution improves with time , arterial Na ( @ ) F avidity is invariant to the time between Na ( @ ) F administration and PET/CT acquisition .


Therefore , the optimal PET/CT acquisition time-point to quantify vascular calcification metabolism is achieved as early as @ minutes after Na ( @ ) F administration .


To investigate the injection frequency and visual acuity ( VA ) outcomes with combination therapy ( ranibizumab plus verteporfin photodynamic therapy , PDT ) versus monotherapy ( ranibizumab ) .


A total of @ patients with exudative age-related macular degeneration were randomized @:@ to ranibizumab @ mg plus single standard verteporfin PDT or ranibizumab @ mg plus sham PDT .


Ranibizumab was administered @ times monthly followed by ` as needed ' to month @ based on predetermined vision/anatomical criteria .


Retreatment rates , VA outcomes and safety were assessed .


During months @-@ , combination therapy patients required fewer ranibizumab injections ( mean @ ) compared with monotherapy patients ( @ ) .


Mean VA improved by @ letters with combination therapy versus @ letters in the monotherapy group at month @ .


Both treatment regimens were well tolerated .


The need for ranibizumab retreatment might be reduced by administering a single verteporfin PDT on the same day as the first ranibizumab injection , without compromising VA outcomes or safety .


Anthrax vaccine adsorbed ( AVA ) administered intramuscularly ( IM ) results in fewer adverse events ( AEs ) than subcutaneous ( SQ ) administration .


Women experience more AEs than men .


Antibody response , female hormones , race , and body mass index ( BMI ) may contribute to increased frequency of reported injection site AEs .


We analyzed data from the CDC AVA human clinical trial .


This double blind , randomized , placebo controlled trial enrolled @ participants and followed them through @ injections ( AVA or placebo ) over a period of @ months .


For the trial 's vaccinated cohort ( n = @ ) , we used multivariable logistic regression to model the effects of study group ( SQ or IM ) , sex , race , study site , BMI , age , and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade .


Also , in a women-only subset ( n = @ ) , we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs .


Participants who received SQ injections had significantly higher proportions of itching , redness , swelling , tenderness and warmth compared to the IM study group after adjusting for other risk factors .


The proportions of redness , swelling , tenderness and warmth were all significantly lower in blacks vs. non-black participants .


We found arm motion limitation , itching , pain , swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations .


In the SQ study group , redness and swelling were more common for obese participants compared to participants who were not overweight .


Females had significantly higher proportions of all AEs compared to males .


Menstrual phase was not associated with any AEs .


Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations .


Antibody responses to other vaccines may also vary by sex and race .


Further studies may provide better understanding for higher proportions of AEs in women and non-black participants .


To compare the efficacy and safety of a new low-dose oral contraceptive pill ( YAZ ) containing drospirenone @ mg and ethinylestradiol @ g with placebo in reducing symptoms of premenstrual dysphoric disorder ( PMDD ) .


This multicenter , double - blind , randomized clinical trial consisted of @ run - in and @ treatment cycles ( @ days ) with daily symptom charting ; @ women with symptoms of PMDD were randomized to either placebo group ( n = @ ) or YAZ group ( n = @ ) , and assessed with daily record of severity of problems scale ( DRSP ) and clinical global impressions scale ( CGI ) before , during and after the treatments .


Hormones were administered for @ days , followed by @ days of inactive pills .


Compared with baseline level of DRSP , both groups got improvement after treatment ; the YAZ group ( median -@ , range : -@ to @ ) had greater improvement than that in the placebo group ( median -@ , range : -@ to @ ) , while there was not significant difference ( P > @ ) .


The main adverse effects of YAZ included intermenstrual bleeding -LSB- @ % ( @/@ ) versus @ % ( @/@ ) -RSB- , menorrhagia -LSB- @ % ( @/@ ) versus @ % ( @/@ ) -RSB- , nausea -LSB- @ % ( @/@ ) versus @ % ( @/@ ) -RSB- and skin rash -LSB- @ % ( @/@ ) versus @ % ( @/@ ) -RSB- .


YAZ could improve symptoms of PMDD better than placebo , while without statistic significance in this study .


The most common adverse effects are intermenstrual bleeding , menorrhagia , nausea and rash .


Complementary feeding recommendations ( CFRs ) with the use of locally available foods can be developed by using linear programming ( LP ) .


Although its potential has been shown for planning phases of food-based interventions , the effectiveness in the community setting has not been tested to our knowledge .


We aimed to assess effectiveness of promoting optimized CFRs for improving maternal knowledge , feeding practices , and child intakes of key problem nutrients ( calcium , iron , niacin , and zinc ) .


A community-intervention trial with a quasi-experimental design was conducted in East Lombok , West Nusa Tenggara Province , Indonesia , on children aged @-@ mo at baseline .


A CFR group ( n = @ ) was compared with a non-CFR group ( n = @ ) .


The CFRs , which were developed using LP , were promoted in an intervention that included monthly cooking sessions and weekly home visits .


The mother 's nutrition knowledge and her child 's feeding practices and the child 's nutrient intakes were measured before and after the @-mo intervention by using a structured interview , @-h recall , and @-wk food-frequency questionnaire .


The CFR intervention improved mothers ' knowledge and children 's feeding practices and improved children 's intakes of calcium , iron , and zinc .


At the end line , median ( IQR ) nutrient densities were significantly higher in the CFR group than in the non-CFR group for iron -LSB- i.e. , @ mg/@ kcal ( @-@ @ mg/@ kcal ) compared with @ mg/@ kcal ( @-@ @ mg/@ kcal ) -RSB- and niacin -LSB- i.e. , @ mg/@ kcal ( @-@ @ mg/@ kcal ) compared with @ mg/@ kcal ( @-@ @ mg/@ kcal ) -RSB- .


However , median nutrient densities for calcium , iron , niacin , and zinc in the CFR group ( @ , @ , @ , and @ mg/@ kcal , respectively ) were still below desired densities ( @ , @ , @ , and @ mg/@ kcal , respectively ) .


The CFRs significantly increased intakes of calcium , iron , niacin , and zinc , but nutrient densities were still below desired nutrient densities .


When the adoption of optimized CFRs is constrained by economic access for or acceptability of nutrient-dense foods , other strategies need to be incorporated into interventions to ensure adequate intakes of these nutrients .


The @ year prevalence of depression in adolescents is about @ % .


Treatment with antidepressant medication is not recommended for initial treatment in young people due to concerns over high side effects , poor efficacy and addictive potential .


Evidence suggests that cognitive behaviour therapy ( CBT ) is an effective treatment for depression and is currently one of the main treatment options recommended in adolescents .


Given the affinity young people have with information technology they may be treated effectively , more widely and earlier in their illness evolution using computer-administered CBT ( CCBT ) .


Currently little is known about the clinical and resource implications of implementing CCBT within the National Health Service for adolescents with low mood/depression .


We aim to establish the feasibility of running a fully powered randomised controlled trial ( RCT ) .


Adolescents aged @-@ with low mood/depression , ( scoring @ on the Mood and Feelings Questionnaire ( MFQ ) ) , will be approached to participate .


Consenting participants will be randomised to either a CCBT programme ( Stressbusters ) or accessing selected websites providing information about low mood/depression .


The primary outcome measure will be the Beck Depression Inventory ( BDI ) .


Participants will also complete generic health measures ( EQ@D-Y , HUI@ ) and resource use questionnaires to examine the feasibility of cost-effectiveness analysis .


Questionnaires will be completed at baseline , @ and @-month follow-ups .


Progress and risk will be monitored via the MFQ administered at each treatment session .


The acceptability of a CCBT programme to adolescents ; and the willingness of clinicians to recruit participants and of participants to be randomised , recruitment rates , attrition rates and questionnaire completion rates will be collected for feasibility analysis .


We will estimate ` numbers needed ' to plan a fully powered RCT of clinical and cost-effectiveness .


Assess longterm tolerability , safety , and efficacy of subcutaneous ( SC ) abatacept ( ABA ) in methotrexate-refractory patients with rheumatoid arthritis ( RA ) .


The phase III , multinational Abatacept Comparison of Sub -LSB- QU -RSB- cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE ( ACQUIRE ) trial comprised a @-month , randomized , double-blind ( DB ) period , in which patients received intravenous ( IV ) or SC ABA , plus MTX , followed by an open-label , longterm extension ( LTE ) , in which patients received SC ABA , @ mg/week .


Safety and efficacy from the LTE ( @ yrs of exposure ) are reported .


Patients who completed the DB period ( @/@ , @ % ) entered the LTE ; @ patients ( @ % ) kept taking the treatment at time of reporting .


Mean ( SD ) was @ months ( @ ) ; median ( range ) exposure was @ ( @-@ ) months .


Patients entering the LTE had longstanding , moderate-to-severe disease -LSB- mean @ ( @ ) yrs and DAS@ ( C-reactive protein ) @ ( @ ) -RSB- .


Incidence rates ( events/@ patient-yrs ) were reported for serious adverse events ( @ , @ % CI @ , @ ) , infections ( @ , @ % CI @ , @ ) , serious infections ( @ , @ % CI @ , @ ) , malignancies ( @ , @ % CI @ , @ ) , and autoimmune events ( @ , @ % CI @ , @ ) .


Twenty-seven patients ( @ % ) experienced injection-site reactions ; all except @ were mild .


American College of Rheumatology @ , @ , and @ responses achieved during the DB period were maintained through the LTE , and on Day @ were @ % ( @ % CI @ , @ ) , @ % ( @ % CI @ , @ ) , and @ % ( @ % CI @ , @ ) for patients who kept taking SC ABA , and @ % ( @ % CI @ , @ ) , @ % ( @ % CI @ , @ ) , and @ % ( @ % CI @ , @ ) for those who switched from IV to SC ABA .


These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX ( ClinicalTrials.gov identifier NCT@ ) .


Alvimopan is indicated to accelerate the time to gastrointestinal recovery following partial bowel resection with primary anastomosis .


The approved dosing regimen includes an initial dose prior to surgery and @ mg twice daily after surgery for up to @ days ; however , there are no human studies evaluating the need for the preoperative dose .


We report our experience with gastrointestinal recovery when the preoperative dose is omitted .


To evaluate the efficacy of alvimopan therapy when the preoperative dose is not administered .


This retrospective study included elective surgery patients who underwent bowel resection with primary anastomosis without colostomy or ileostomy .


The study compared ( a ) patients who received alvimopan and received a dose preoperatively , ( b ) patients who received alvimopan but did not receive a dose preoperatively , and ( c ) matched control patients who did not receive alvimopan .


Length of stay following bowel resection , direct hospital costs , time to first bowel movement , and time to oral diet were evaluated .


Of @ patients who received alvimopan , @ received the preoperative dose and @ did not .


These @ patients were matched to similar control patients who received no alvimopan during their admission for resection .


Compared with controls , time to discharge was significantly shorter in patients who received alvimopan , regardless of whether the preoperative dose was administered ( P < @ ) or omitted ( P = @ ) .


Patients who did not receive the preoperative dose still experienced faster time to first bowel movement ( @ vs @ hours ; P = @ ) and faster time to first diet ( @ vs @ hours ; P < @ ) than non-alvimopan users .


Patients receiving the approved alvimopan dosing regimen experienced the most rapid recovery of gastrointestinal function .


However , administering alvimopan only postoperatively ( if the preoperative dose is omitted ) may still reduce the severity of postoperative ileus .


Retrospective studies have shown that a significant number of ovarian borderline tumors , ovarian metastases , and nonepithelial tumors were erroneously diagnosed as ovarian carcinomas .


This may lead to unnecessary morbidity , suboptimal therapeutic modalities , and unintended bias in clinical trials .


The aim of this study was to investigate the frequency and clinical significance of such diagnostic discrepancies .


Original histological slides from patients with ovarian carcinomas included in phase III chemotherapy trials of the Working Group on Gynecological Oncology ( AGO ) were reviewed by at least two specialized pathologists .


Diagnostic discrepancies were classified as being either clinically relevant ( major ) or clinically not relevant ( minor ) .


A total of @ out of @ patients from the AGO OVAR@ ( ICON@ ) trial gave consent to the second opinion on the pathology results .


All of the @ institutes of pathology responsible for the original diagnoses contributed to the study .


The first diagnosis and the second opinion pathology review were identical in @ out of @ ( @ % ) cases .


In @ cases ( @ % ) a minor discrepancy was found and @ cases ( @ % ) were shown to have a major discrepancy .


The assumption of a significant number or erroneous diagnoses in chemotherapy trials of ovarian carcinomas was confirmed .


A pathology review seems therefore desirable and may help to reduce unnecessary morbidity and optimize therapeutic strategies .


Moreover , improvement of quality in therapy trials may become possible .


In another study a new concept allowing a rapid pathology review before randomization of patients has now been successfully tested and it may well have potential to form the basis for modern networking consultation pathology .


To compare procedure times and complication rates of preincisional ultrasonographic ( US ) evaluation and perioperative US guidance in percutaneous dilatational tracheostomy ( PDT percutaneous dilatational tracheostomy ) with those of the current standard of care , PDT percutaneous dilatational tracheostomy performed without image guidance .


Between December @ and January @ , @ patients were included in this institutional review board-approved study after informed consent was obtained from the patients or their relatives .


The patients were divided randomly into two groups .


In group A ( n = @ ) , the possible causes of complications , such as aberrations of tracheal , thyroidal , and vascular structures , were determined with US , and tracheal measurements were performed by using US .


The clinician 's initial considerations at physical examination were compared with the US findings .


PDT percutaneous dilatational tracheostomy was subsequently performed with US guidance in suitable cases .


In group B ( n = @ ) , PDT percutaneous dilatational tracheostomy was performed solely on the basis of physical landmarks .


The procedure times and complication rates were compared across groups by using the Fisher exact test .


In group A , the puncture sites designated at the physical examination were reconsidered in @ ( @ % ) of @ cases .


The perioperative complication rates were slightly lower in group A ( @ % -LSB- @ of @ -RSB- ) than in group B ( @ % -LSB- @ of @ -RSB- ) ; however , the difference did not achieve statistical significance ( P = @ ) .


The mean procedure times for groups A and B were @ minutes @ ( standard deviation ) ( range , @-@ minutes ) and @ minutes @ ( range , @-@ minutes ) , respectively ( P = @ ) , and the numbers of patients in each group who required multiple puncture attempts were six ( @ % ) of @ and @ ( @ % ) of @ ( P = @ ) , respectively .


The use of US guidance before and during PDT percutaneous dilatational tracheostomy could render the procedure easier and safer , with fewer complications but a slightly longer procedure time .


To assess erectile function in middle-aged and older men with asexuality status and further analyze their specific reasons for this condition .


Men who had regular sexual intercourse attempts ( sex frequency @ time per month ) were classified into mild erectile dysfunction ( ED ) , moderate to severe ED and non-ED according to International Index of Erectile Function-@ , and men having no sexual intercourse attempts for at least @ months were defined as having an asexuality status .


The risk factors associated with ED were collected in a sample of @,@ Chinese men aged @ to @ years , and the self-report reasons for asexuality were recorded in asexual cohort individually .


Comparative analyses and multivariate regression models were conducted among these groups .


The prevalence rates of ED and asexuality status were @ % and @ % .


The asexuality status group had higher risk factors than the moderate to severe ED group in terms of old age ( age @ , adjusted odds ratio ( OR ) @ versus ( Vs. ) @ ) , diabetes ( crude OR : @ Vs. @ ) and hypertension ( crude OR : @ Vs. @ ) .


The specific reasons for the asexuality status were `` erectile difficulty '' ( @ % ) , `` do not care about sexuality '' ( @ % ) '' , `` no longer necessary to have sexuality at this age '' ( @ % ) , `` severe stress '' ( @ % ) , `` severe fatigue '' ( @ % ) and `` masturbation '' ( @ % ) .


Men with an asexual status suffer from higher risk factors for ED than men with moderate to severe ED .


The majority of this asexual status could be attributed to a full ED , although the reasons for this transient asexuality also involved sexual attitudes and interests , sexual partners and masturbation .


The aim of this study was to evaluate the Eye Retinopathy Trainer as a teaching tool for direct ophthalmoscopy examination by comparing it with the traditional method using volunteers .


Fourth year medical students received training in direct ophthalmoscopy using a simulation tool and human volunteers .


Ninety students were randomized into a Simulation Group or a Control Group by the inclusion or absence of the simulation model in classroom practice .


Differences between the groups were analyzed using unpaired Student 's t-test .


The Simulation Group was superior to the Control Group , with @ % successful in performing fundus examination in both the anatomical model simulation and the human model in comparison with @ % in the Control Group .


The Eye Retinopathy Trainer appears to be an effective teaching tool for practice and improvement of ophthalmologic examination among fourth year medical students .


PT@ is a sustained-release exenatide under clinical development for the treatment of type @ diabetes mellitus .


The aim of this study was to evaluate the pharmacokinetic properties , pharmacodynamic properties , and tolerability of PT@ after a single subcutaneous injection in healthy individuals .


A dose-block randomized , double-blind , placebo-controlled , dose-escalating study ( @ , @ , @ , and @ mg ) was performed in @ healthy individuals .


The plasma concentrations of exenatide in serial blood samples were quantified for @ days after dosing with an exendin-@ fluorescent immunoassay kit .


Noncompartmental analysis was performed to assess the pharmacokinetic characteristics of PT@ .


Oral glucose tolerance tests were repeated weekly until day @ ; the concentrations of serum glucose , serum C-peptide , plasma insulin , and plasma glucagon were measured for @ hours to evaluate the pharmacodynamic characteristics of PT@ .


Clinical laboratory tests , vital signs , physical examinations , @-lead ECGs , and adverse events were monitored to evaluate the safety profile and tolerability .


PT@ exhibits a biphasic pharmacokinetic profile , with the initial peak occurring @ hours after administration .


PT@ was quantifiable in the plasma until days @ , @ , @ , and @ ( median ) in the @-mg , @-mg , @-mg , and @-mg dosage groups of PT@ , respectively .


Systemic exposure increased proportionally to the dose during the entire dose range investigated .


The pharmacodynamic effect of PT@ on the postprandial response of insulin and C-peptide was significant on days @ to @ at the @-mg dose and was positively correlated with plasma exenatide concentrations , whereas the correlations with glucose and glucagon were not significant .


The fasting levels of these pharmacodynamic biomarkers were not altered by PT@ .


The most common adverse events were injection site induration and pruritus related to inflammatory foreign body reaction , which were mild and spontaneously resolved within several weeks .


The pharmacokinetic characteristics of PT@ were biphasic and dose proportional .


A single @-mg dose of PT@ significantly increased the insulin and C-peptide response to oral glucose loading and was well tolerated in healthy individuals .


To compare the effects of short-term and long-term thromboprophylaxis after total hip replacement on coagulation indicators in plasma sampled before and @ , @ and @ days post-operation .


A total of @ patients scheduled for elective total hip replacement were randomly assigned into the short-term ( n = @ ) or long-term ( n = @ ) thromboprophylaxis groups on oral rivaroxaban @ mg once daily for @ or @ days .


The primary efficacy hemostatic variables included thrombin-antithrombin complexes ( TAT ) , prothrombin fragment @ +@ ( F@t@ ) , D-dimer and fibrinogen ( Fib ) preoperatively and at Days @ , @ and @ postoperatively .


And ultrasonography was performed on all patients preoperatively and at days @ and @ postoperatively to exclude deep vein thrombosis of lower extremities .


None of them had deep vein thrombosis ( DVT ) of lower extremities .


Among them , TAT , F@ +@ , D-dimer and Fib post-operation were higher than those preoperative baseline values .


TAT and D-dimer peaked at day @ postoperatively while the peaks of F@ +@ and Fib appeared at day @ postoperatively .


At Day @ post-operation , the levels of TAT and F@ +@ in the long-term thromboprophylaxis group were significantly lower than those of the short-term thromboprophylaxis group ( P < @ ) .


The status of hypercoagulability may sustain at least @ days after total hip replacement .


Though not completely eliminated , it can still be reduced by prolonged thromboprophylaxis .


However , according to ultrasonography , the effects of short-term and long-term thromboprophylaxis on the incidence rate of DVT remain to be further explored .


Using a multidimensional approach , we assessed young women 's knowledge of oral contraceptives ( OC ) and its influence on OC continuation rates .


We used data from @ women aged @-@ years participating in a randomized controlled trial of an educational text message OC continuation intervention .


Women received @ months of daily text messages or routine care .


At baseline and @ months , we administered a comprehensive @-item questionnaire measuring knowledge of OC 's mechanism , effectiveness , use , side effects , risks , and benefits .


We ascertained OC continuation status and reasons for discontinuation at @ months .


We analyzed relationships between OC knowledge and continuation with multivariable logistic regression .


Young women scored , on average , @ out of @ points on the OC knowledge assessment at baseline and @ points at @ months .


The @-month OC continuation rate was @ % .


OC continuers had > @-points-higher OC knowledge scores at @ months than discontinuers ( p < @ ) .


Those who reported discontinuing their OCs for side effects and forgetfulness scored > @ points lower than women who discontinued for other reasons ( p-values < @ ) .


In multivariable regression models , each correct response on the baseline and @-month knowledge assessments was associated with a @ % and @ % increased odds of OC continuation , respectively .


Six-month OC knowledge scores were negatively associated with OC discontinuation due to side effects ( odds ratio -LSB- OR -RSB- @ ) and forgetfulness ( OR @ ) .


OC knowledge , which was low among young women in our study , was associated with OC continuation and common reasons for discontinuation .


Continued efforts to characterize relationships between OC knowledge and behavior and to test the effectiveness of different components of interventions aimed at increasing knowledge , addressing side effects , and improving use of OCs are warranted .


Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability .


Concentrations of globotriaosylceramide ( Gb@ ) , globotriaosylsphingosine ( lyso-Gb@ ) / related analogues were investigated in pediatric and adult Fabry cohorts .


The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform , using an HPLC column , for urine analysis of treated and untreated pediatric and adult Fabry patients , to establish correlations between the excretion of Fabry biomarkers with gender , treatment , types of mutations , and to evaluate the biomarker reliability for early detection of pediatric Fabry patients .


A UPLC-MS/MS was used for biomarker analysis .


Reference values are presented for all biomarkers .


Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort , with females having lower urinary levels of all biomarkers .


Urinary distribution of lyso-Gb@ / related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts .


Children with the late-onset p.N@S mutation had normal urinary levels of Gb@ , and lyso-Gb@ but abnormal levels of related analogues .


In this study , Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb@ / related analogue profile .


Binge drinking is responsible for over half of all alcohol-related deaths and results in significant health and economic costs to individuals and society .


Knowledge of genetic aspects of this behavior , particularly as it emerges in young adulthood , could lead to improved treatment and prevention programs .


We have focused on the association of variation in neuronal nicotinic receptor subunit genes ( CHRNs ) in a cohort of @ Hispanic and non-Hispanic White young adults who are part of the Social and Emotional Contexts of Adolescent Smoking Patterns ( SECASP ) study .


Fifty-five single nucleotide polymorphisms ( SNPs ) covering the variation in @ CHRNs ( CHRNA@ , CHRNB@ , CHRNA@ , CHRNB@A@ , and CHRNA@A@B@ ) were studied .


Frequency of binge drinking and other correlated alcohol consumption measures were significantly associated with SNPs in CHRNA@ ( p-values ranged from @ to @ ) , but not with SNPs in other CHRNs .


This association was independent of smoking status in our cohort .


Variants in CHRNA@ may contribute to risk of binge drinking in young adults in this cohort .


Results will need to be confirmed in independent samples .


Informal caregivers ( family and friends ) of people with cancer are often unprepared for their caregiving role , leading to increased burden or distress .


Comprehensive Health Enhancement Support System ( CHESS ) is a Web-based lung cancer information , communication , and coaching system for caregivers .


This randomized trial reports the impact on caregiver burden , disruptiveness , and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites .


A total of @ informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that received Internet and CHESS .


Caregivers were provided a computer and Internet service if needed .


Written surveys were completed at pretest and during the intervention period bimonthly for up to @ months .


Analyses of covariance ( ANCOVAs ) compared the intervention 's effect on caregivers ' disruptiveness and burden ( CQOLI-C ) , and negative mood ( combined Anxiety , Depression , and Anger scales of the POMS ) at @ months , controlling for blocking variables ( site , caregiver 's race , and relationship to patient ) and the given outcome at pretest .


Caregivers randomized to CHESS reported lower burden , t ( @ ) = @ , p = @ , d = @ , and negative mood , t ( @ ) = @ , p = @ , d = @ , than those in the Internet group .


The effect on disruptiveness was not significant .


Although caring for someone with a terminal illness will always exact a toll on caregivers , eHealth interventions like CHESS may improve caregivers ' understanding and coping skills and , as a result , ease their burden and mood .


Krill is an increasingly popular source of marine n-@ ( -@ ) PUFA that is seen as a premium product .


However , to our knowledge , the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported .


We assessed whether supplementation with a blend of krill and salmon ( KS ) oil -LSB- which is rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) -RSB- affects insulin sensitivity in overweight men .


The design was a randomized , double-blind , controlled crossover trial .


A total of @ men with a mean SD age of @ @ y , who were overweight -LSB- body mass index ( in kg/m ( @ ) ) from @ to @ -RSB- but otherwise healthy , received @ @-g capsules of KS oil or a control ( canola oil ) for @ wk and crossed over to another treatment after an @-wk washout period .


The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test .


Secondary outcomes included lipid profiles , inflammatory markers , @-h ambulatory blood pressure , and carotid artery intimamedia thickness .


Unexpectedly , insulin sensitivity ( per the Matsuda index ) was @ % lower with the KS oil than with the control oil ( P = @ ) .


A mediation analysis showed that , after controlling for the likely positive effects of blood EPA and DHA ( i.e. , the omega-@ index ) , the reduction in insulin sensitivity after KS-oil supplementation was more marked -LSB- @ % lower than with the control oil ( P = @ ) -RSB- .


Supplementation with a blend of KS oil is associated with decreased insulin sensitivity .


Thus , krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease .


This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN@ .


To observe the clinical efficacy of Tongfu Mixture ( TM ) for post-ERCP pancreatitis ( PEP ) .


Totally @ PEP patients were randomly assigned to the control group ( treated by routine therapy , @ cases ) and the TM treatment group ( treated by TM , @ cases ) .


Clinical indices including the alleviation time of abdominal pain/distention , gastrointestinal function recovery time , and the post-surgical length of stay were observed .


Blood amylase ( AMY ) , C-reactive protein ( CRP ) , plasma endotoxin ( PLS ) , TNF-alpha , and IL-@ were detected before surgery , @ h , @ h , and @ h after surgery .


The alleviation time of abdominal pain/distention , the gastrointestinal function recovery time , and the post-surgical length of stay were obviously shorter in the TM treatment group than those in the control group ( P < @ ) .


The recovery of AMY and CRP were better in the TM treatment group than in the control group at post-operative @ h and @ h ( P < @ ) .


The levels of LPS , TNF-alpha , and IL-@ were lower in the TM group than in the control group at post-operative @ h ( P < @ ) .


TM showed better clinical efficacy and could significantly decrease the post-surgical length of stay .


post-ERCP pancreatitis ; integrative medicine ; Tongfu Mixture


Preventive health checks may identify individuals with an unhealthy lifestyle and motivate them to change behaviour .


However , knowledge about the impact of the different components included in preventive health checks is deficient .


The aim of this trial is to evaluate whether including cardiorespiratory fitness testing in preventive health checks @ ) increases cardiorespiratory fitness level and motivation to change physical activity behaviour and @ ) reduces physical inactivity prevalence and improves self-rated health compared with preventive health checks without fitness testing .


An open-label , household-cluster , randomized controlled trial with a two-group parallel design is used .


The trial is embedded in a population-based health promotion program , `` Check your Health Preventive Program '' , in which all @-@ year-old citizens in a Danish municipality are offered a preventive health check .


In each arm of the trial , @ citizens will be recruited ( @,@ in total ) .


The primary outcome is cardiorespiratory fitness level assessed by submaximal cycle ergometer testing after one year .


An intermediate outcome is the percentage of participants increasing motivation for physical activity behaviour change between baseline and two-weeks follow-up assessed using the Transtheoretical Model 's stages of change .


Secondary outcomes include changes from baseline to one-year follow-up in physical inactivity prevalence measured by a modified version of the questions developed by Saltin and Grimby , and in self-rated health measures using the Short-Form @ , Health Survey , version @ .


This trial will contribute to a critical appraisal of the value of fitness testing as part of preventive health checks .


The conduction in real-life community and general practice structures makes the trial findings applicable and transferable to other municipalities providing support to decision-makers in the development of approaches to increase levels of physical activity and improve health .


Patients who are critically ill can develop so-called intensive-care unit acquired weakness , which delays rehabilitation .


Reduced muscle mass , quality , or both might have a role .


The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients ( EPaNIC ) trial ( registered with ClinicalTrials.gov , number NCT@ ) showed that tolerating macronutrient deficit for @ week in intensive-care units ( late parenteral nutrition -LSB- PN -RSB- ) accelerated recovery compared with early PN .


The role of weakness was unclear .


Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres .


In this prospectively planned subanalysis of the EPaNIC trial , weakness ( MRC sum score ) was assessed in @ awake , cooperative patients .


Skeletal muscle biopsies , harvested from @ patients @ days after randomisation and from @ matched healthy controls , were studied for autophagy and atrophy .


We determined the significance of differences with Mann-Whitney U , Median , Kruskal-Wallis , or ( @ ) ( exact ) tests , as appropriate .


With late PN , @ ( @ % ) of @ patients had weakness on first assessment ( median day @ post-randomisation ) compared with @ ( @ % ) of @ patients given early PN ( absolute difference -@ % , @ % CI -@ to -@ ; p = @ ) .


Weakness recovered faster with late PN than with early PN ( p = @ ) .


Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls , similarly with early PN and late PN .


The LC@ ( microtubule-associated protein light chain @ ) II to LC@I ratio , related to autophagosome formation , was higher in patients given late PN than early PN ( p = @ ) , reaching values almost double those in the healthy control group ( p = @ ) , and coinciding with less ubiquitin staining ( p = @ ) .


A higher LC@II to LC@I ratio was independently associated with less weakness ( p = @ ) .


Expression of mRNA encoding contractile myofibrillary proteins was lower and E@-ligase expression higher in muscle biopsies from patients than in control participants ( p@ ) , but was unaffected by nutrition .


Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting , but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness .


SH@-containing inositol-@ ' - phosphatase @ ( SHIP@ ) is an endogenous inhibitor of the phosphoinositide-@-kinase pathway that is involved in the activation and chemotaxis of inflammatory cells .


AQX-@ is a first-in-class , oral SHIP@ activator with a novel anti-inflammatory mode of action .


To evaluate the effects of AQX-@ on airway responses to allergen challenge in mild-to-moderate asthmatic patients .


A randomized , double-blind , placebo-controlled , two-way crossover study was performed in @ steroid-nave mild-to-moderate asthmatics with a documented late-phase response to inhaled allergen ( LAR ) .


AQX-@ ( @ mg daily ) or placebo was administered orally for @ days .


Allergen challenge was performed on day @ ( @ h postdose ) , followed by methacholine challenge ( day @ ) , and induced sputum collection and fractional exhaled nitric oxide ( FeNO ) .


AQX-@ significantly attenuated the late-phase response compared with placebo ( FEV@ @-@ h : mean difference @ mL , @ % ; P = @ ) and significantly increased the minimum FEV@ during LAR ( mean difference @ mL ; P = @ ) .


AQX-@ had no effect on the early-phase response .


AQX-@ showed a trend in reduction of sputum eosinophils , neutrophils and macrophages although this did not achieve significance as there were only @ paired samples for analysis .


There was no effect on methacholine responsiveness or FeNO .


Pharmacokinetic data showed AQX-@ was rapidly absorbed with geometric mean Cmax and AUC@-@ h values of @ ng/mL and @ @ h ng/mL , respectively .


AQX-@ was well tolerated , but mild GI side-effects ( dyspepsia , nausea and abdominal pain ) were described in @/@ subjects on active treatment .


These side-effects were mild self-limiting , required no further treatment and did not lead to discontinuation of therapy .


AQX-@ , a novel oral SHIP@ activator , significantly reduces the late response to allergen challenge , with a trend to reduce airway inflammation .


AQX-@ was safe and well tolerated and merits further investigation in inflammatory disorders .


Endoscopic submucosal dissection ( ESD ) allows en bloc resection of superficial colorectal tumors regardless of size .


However , ESD is technically difficult , hazardous , and time consuming .


New devices may help overcome these drawbacks .