Furthermore , lenalidomide had no significant effect on blood C max and AUC of temsirolimus and its active metabolite sirolimus ( also a P-gp inhibitor/substrate ) .


The C max of digoxin was slightly higher ( +@ % ) when administered with lenalidomide versus placebo .


There were no other changes in digoxin pharmacokinetics upon co-administration with lenalidomide .


No remarkable safety findings were observed .


There are no clinically significant pharmacokinetic interactions between lenalidomide and substrates or inhibitors of P-gp .


To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions .


A total of @ patients were randomized and participated in the study .


Patients received either cream @ ( the natural oil-based emulsion containing allantoin ) or cream @ ( aqueous cream ) .


Skin toxicity , pain , itching , and skin-related quality of life scores were collected for up to @ weeks after radiation treatment .


Patients who received cream @ had a significantly lower average level of Common Terminology Criteria for Adverse Events at week @ ( P < @ ) but had statistically higher average levels of skin toxicity at weeks @ , @ , and @ ( all P < @ ) .


Similar results were observed when skin toxicity was analyzed by grades .


With regards to pain , patients in the cream @ group had a significantly higher average level of worst pain ( P < @ ) and itching ( P = @ ) compared with the cream @ group at week @ ; however , these differences were not observed at other weeks .


In addition , there was a strong trend for cream @ to reduce the incidence of grade @ or more skin toxicity in comparison with cream @ ( P = @ ) .


Overall , more participants in the cream @ group were required to use another topical treatment at weeks @ ( P = @ ) and @ ( P = @ ) .


The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week @ ; however , it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion ( week @ and beyond ) .


There were no major differences in pain , itching , and skin-related quality of life .


In light of these results , clinicians and patients can base their decision on costs and preferences .


Overall , aqueous cream seems to be a more preferred option .


Problem-based learning ( PBL ) is well established in medical education and beyond , and continues to be developed and explored .


Challenges include how to connect the somewhat abstract nature of classroom-based PBL with clinical practice and how to maintain learner engagement in the process of PBL over time .


A study was conducted to investigate the efficacy of decision-PBL ( D-PBL ) , a variant form of PBL that replaces linear PBL cases with virtual patients .


These Web-based interactive cases provided learners with a series of patient management pathways .


Learners were encouraged to consider and discuss courses of action , take their chosen management pathway , and experience the consequences of their decisions .


A Web-based application was essential to allow scenarios to respond dynamically to learners ' decisions , to deliver the scenarios to multiple PBL classrooms in the same timeframe , and to record centrally the paths taken by the PBL groups .


A randomized controlled trial in crossover design was run involving all learners ( N = @ ) in the second year of the graduate entry stream for the undergraduate medicine program at St George 's University of London .


Learners were randomized to study groups ; half engaged in a D-PBL activity whereas the other half had a traditional linear PBL activity on the same subject material .


Groups alternated D-PBL and linear PBL over the semester .


The measure was mean cohort performance on specific face-to-face exam questions at the end of the semester .


D-PBL groups performed better than linear PBL groups on questions related to D-PBL with the difference being statistically significant for all questions .


Differences between the exam performances of the @ groups were not statistically significant for the questions not related to D-PBL .


The effect sizes for D-PBL-related questions were large and positive ( > @ ) except for @ question that showed a medium positive effect size .


The effect sizes for questions not related to D-PBL were all small ( @ ) with a mix of positive and negative values .


The efficacy of D-PBL was indicated by improved exam performance for learners who had D-PBL compared to those who had linear PBL .


This suggests that the use of D-PBL leads to better midterm learning outcomes than linear PBL , at least for learners with prior experience with linear PBL .


On the basis of tutor and student feedback , St George 's University of London and the University of Nicosia , Cyprus have replaced paper PBL cases for midstage undergraduate teaching with D-PBL virtual patients , and @ more institutions in the ePBLnet partnership will be implementing D-PBL in Autumn @ .


The optimal dietary approach for weight loss and improving insulin sensitivity in adolescents is unknown .


This study aimed to explore the association between the estimated insulin demand of the diet , as measured by glycemic and insulin load , weight loss , percentage body fat and insulin sensitivity index ( ISI ) in obese adolescents with clinical features of insulin resistance and/or prediabetes after a @ month lifestyle and metformin intervention .


Secondary data analysis of @ adolescents ( median age @ years ( range @-@ @ ) participating in a randomized controlled trial , known as RESIST ; ACTRN@ .


Weight change between baseline and @ months was measured by BMI expressed as percentage of the @th centile ( BMI % @ ) .


Body composition was measured by dual energy X-ray absorptiometry and ISI was determined by an oral glucose tolerance test .


Higher dietary glycemic load and insulin load were associated with less weight loss ( BMI % @ ) , adjusted for sex and pubertal stage , = @ , P = @ and = @ , P = @ , respectively .


Inclusion of total energy intake in the model explained observed associations between dietary glycemic load and insulin load and change in BMI % @ .


Neither dietary glycemic load nor insulin load were associated with changes in percentage body fat or ISI .


Dietary glycemic index and macronutrient content ( % of total energy ) were not associated to changes in BMI % @ , percentage body fat or ISI .


Reduced energy diet contributes to weight loss in obese , insulin resistant adolescents .


Diets with a lower insulin demand were associated with a lower energy intake and may hence assist with weight loss .


To investigate the safety of combining a @-Hz primed low-frequency repetitive transcranial magnetic stimulation ( rTMS ) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy ( mCIMT ) program in children with congenital hemiparesis .


Phase @ randomized , double-blinded , placebo-controlled pretest/posttest trial .


University academic facility and pediatric specialty hospital .


Subjects ( N = @ ; age range , @-@ y ) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia .


No subject withdrew because of adverse events .


All subjects included completed the study .


Subjects were randomized to @ of @ groups : either real rTMS plus mCIMT ( n = @ ) or sham rTMS plus mCIMT ( n = @ ) .


Adverse events , physician assessment , ipsilateral hand function , stereognosis , cognitive function , subject report of symptoms assessment , and subject questionnaire .


No major adverse events occurred .


Minor adverse events were found in both groups .


The most common events were headaches ( real : @ % , sham : @ % ; P = @ ) and cast irritation ( real : @ % , sham : @ % ; P = @ ) .


No differences between groups in secondary cognitive and unaffected hand motor measures were found .


Primed rTMS can be used safely with mCIMT in congenital hemiparesis .


We provide new information on the use of rTMS in combination with mCIMT in children .


These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis .


Persons with serious mental illnesses ( SMI ) are more likely to die earlier than the general population , primarily due to increased medical burden , particularly from cardiovascular disease ( CVD ) .


Life Goals Collaborative Care ( LG-CC ) is designed to improve health outcomes in SMI through self-management , care management , and provider support .


This single-blind randomized controlled effectiveness study will determine whether patients with SMI receiving LG-CC compared to usual care ( UC ) experience improved physical health in @ months .


Patients diagnosed with SMI and at least one CVD risk factor receiving care at a VA mental health clinic were randomized to LG-CC or UC .


LG-CC included five self-management sessions covering mental health symptom management reinforced through health behavior change , care coordination and health monitoring via a registry , and provider feedback .


The primary outcome is change in physical health-related quality of life score ( VR-@ ) from baseline to @ months .


Secondary outcomes include changes in mental health-related quality of life , CVD risk factors ( blood pressure , BMI ) , and physical activity from baseline to @ months later .


Out of @ enrolled , @ were randomized to LG-CC and @ to UC .


Among patients completing baseline assessments ( N = @ ) ; the mean age was @ ( SD = @ ; range @-@ years ) , @ % were women , the majority ( @ % ) were diagnosed with depression , and the majority ( @ % ) were diagnosed with hypertension or were overweight ( BMI mean SD = @ @ ) .


Baseline VR-@ physical health component score was below population norms ( @ SD = @ ) at @ @ .


Findings from this trial may inform initiatives to improve physical health for SMI patient populations .


Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program ( CB group ) and CB bibliotherapy , relative to an educational brochure control condition and to one another , in a school-based effectiveness randomized controlled prevention trial .


@ adolescents ( M age = @ , @ % female ) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest , posttest , and @-month follow-up .


We tested the moderating effect of three individual ( baseline depressive symptoms , negative attributional style , substance use ) , three environmental ( negative life events , parental support , peer support ) , and two sociodemographic ( sex , age ) characteristics .


Baseline depressive symptoms interacted with condition and time .


Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest ( but not @-month follow-up ) relative to the control condition , but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy .


Specifically , CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated , but not average or low baseline symptoms .


We found no interaction effect for other putative moderators .


Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline .


The fact that no study variable moderated the effects of CB group , which had a significant main effect in reducing depressive symptoms relative to the control condition , suggests that this indicated prevention intervention is effective for a wide range of adolescents .


Vitamin D deficiency is a common problem worldwide .


Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome .


No previous study has compared the efficacy and safety of ergocalciferol at @,@ versus @,@ IU/week in patients with metabolic syndrome .


To evaluate the efficacy of ergocalciferol supplementation on serum @-hydroxyvitamin D -LSB- @ ( OH ) D -RSB- concentrations and to examine safety parameters in metabolic syndrome patients .


Outpatient department of Phramongkutklao Hospital , Bangkok , Thailand .


A randomized , double-blinded , parallel study was conducted in metabolic syndrome patients with vitamin D deficiency -LSB- @ ( OH ) D < @ ng/mL -RSB- .


Ninety patients were randomly assigned into three groups of @ patients each .


Group @ was given two capsules of placebo/week , group @ was given ergocalciferol @,@ IU/week , and group @ was given ergocalciferol @,@ IU/week for @ weeks .


serum @ ( OH ) D concentrations , serum calcium , safety , and corrected QT ( QTc ) interval .


Of the @ patients enrolled , @ patients completed the study .


At the end of the study , the mean serum @ ( OH ) D in groups @ and @ significantly increased from the baseline ( @ and @ to @ and @ ng/mL , respectively ) .


The increase in serum @ ( OH ) D in groups @ and @ were comparable and significantly greater than that of the placebo group .


The percentage number of patients achieving normal vitamin D levels in groups @ , @ and @ were @ , @ , and @ % , respectively , which were significantly different between groups ( p < @ ) .


Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group ( p > @ ) .


Serum calcium levels did not change within and between groups of treatment .


No significant change in QTc was observed in any patient .


Both @,@ and @,@ IU/week of ergocalciferol supplementation for @ weeks were able to increase serum @ ( OH ) D concentrations significantly .


However , more patients in the ergocalciferol @,@ IU/week treatment group achieved a normal serum @ ( OH ) D level than in the group which received @,@ IU/week .


Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients .


Cross-cultural translation , adaptation , and psychometric testing .


To cross-culturally translate and adapt the Roland-Morris Disability Questionnaire ( RMDQ ) into Modern Standard Arabic and examine its validity with Arabic-speaking patients with low back pain ( LBP ) .


The English RMDQ is valid , reliable , and commonly used to assess LBP disability in clinical practice and research .


There is no valid and reliable version of the RMDQ in Modern Standard Arabic .


The RMDQ was forward translated and back translated .


An expert committee of musculoskeletal physiotherapists reviewed the translation .


Eight patients with LBP evaluated item-by-item comprehensibility .


Ten patients piloted the RMDQ for overall comprehensibility and acceptability .


Seventeen bilingual patients tested the agreement of the Arabic and English RMDQs .


Two-hundred one patients completed the RMDQ and the visual analogue scale .


Sixty-four patients were followed-up for test-retest reliability .


Translation of most items was uncontroversial .


The expert committee found the Arabic RMDQ clinically and culturally appropriate .


They reviewed item @ , addressing bending and kneeling , because this has a clinical significance and cultural/religious implication regarding prayer positions .


All patients reported that it was easy to understand and complete .


The Arabic RMDQ had high overall agreement with the English RMDQ for the global score ( intraclass correlation coefficient -LSB- ICC -RSB- = @ ; @-@ @ ) .


Kappa statistics showed good item-by-item agreement ( none @ ) .


Mean ( SD ) RMDQ and visual analog scale scores of @ patients were @ ( @ ) and @ ( @ ) , respectively .


The RMDQ had a low correlation against pain intensity ( r = @ ; P < @ ) .


A Cronbach of @ showed high internal consistency .


Test-retest reliability of the Arabic RMDQ was good ( ICC = @ ; @ % confidence interval , @-@ @ ) .


Kappa statistics were high for @ items and fair for @ .


The Arabic version of the RMDQ has good comprehensibility and acceptability , high internal consistency and reliability , low correlation against pain intensity , and good agreement with the English RMDQ .


We recommend its use with Arabic-speaking patients with LBP .


Biologic drugs are expensive treatments used in rheumatoid arthritis ( RA ) .


Switching among them is common practice in patients who have had an inadequate response or intolerable adverse events .


The National Institute of Health and Clinical Excellence ( NICE ) UK , which aims to curtail postcode prescribing , has provided guidance on the sequential prescription of these drugs .


This study sought to evaluate the extent to which rheumatology centres across the Midlands were complying with NICE guidance on the switching of biologic drugs in RA , as well as analyse the various prescribing patterns of these drugs .


Data was collected via a web-based tool on RA patients who had undergone at least one switch of a biologic drug during @ .


The standards specified in NICE technology appraisals ( TA@ , TA@ , TA@ , TA@ , and TA@ ) were used to assess compliance with NICE guidance .


Descriptive statistical analysis was performed .


There were @ biologic drug switches in @ patients .


The most common reason given for switching to a drug was NICE guidelines ( @ , @ % ) , followed by Physician 's choice ( @ , @ % ) .


Lack of effect was the most common reason for discontinuing a drug ( @ , @ % ) .


For patients on Rituximab , Methotrexate was used in @ switches ( @ % of the time ) .


Overall NICE compliance for all units was @ % ( range @ to @ % ) , with anti-TNF to anti-TNF switches for inefficacy making up the majority of non-compliant switches .


This study draws attention to the enigma and disparity of commissioning and prescribing of biologic drugs in RA .


Currently the evidence would not support switching of a biologic drug for non-clinical purposes such as economic pressures .


Flexibility in prescribing should be encouraged : biologic therapy should be individualised based on the mode of action and likely tolerability of these drugs .


Further work should focus on the evidence for using particular sequences of biologic drugs .


To determine whether infusions with intravenous immunoglobulin ( IVIg ) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo .


A single-centre , randomised , double-blind , placebo-controlled trial .


A tertiary centre for recurrent miscarriage in Copenhagen , Denmark .


A group of @ women with unexplained secondary recurrent miscarriage and at least four miscarriages .


Women were randomly assigned to repeated infusions with IVIg or placebo ( albumin ) from the time of positive pregnancy test to gestational week @ or pregnancy loss .


Primary outcome was birth with neonatal survival in all randomised women .


In the intention-to-treat analyses , live birth rates were @/@ ( @ % ) in the IVIg and @/@ ( @ % ) in the placebo group , relative risk @ ( @ % CI @-@ @ ) .


In a per protocol analysis , almost identical results were found .


The median gestational length at delivery was higher in the IVIg than the placebo group ( @ versus @ days , P = @ ) but the mean birthweight was not significantly increased .


In this trial , which is the largest so far , IVIg did not increase the live birth rate in patients with secondary recurrent miscarriage and the treatment can not be recommended in clinical practice .


Hypertension , hyperlipidemia , and diabetes are significant , but often preventable , contributors to cardiovascular disease ( CVD ) risk .


Medication and behavioral nonadherence are significant barriers to successful hypertension , hyperlidemia , and diabetes management .


Our objective was to describe the theoretical framework underlying a tailored behavioral and educational pharmacist-administered intervention for achieving CVD risk reduction .


Adults with poorly controlled hypertension and/or hyperlipidemia were enrolled from three outpatient primary care clinics associated with the Durham Veterans Affairs Medical Center ( Durham , NC ) .


Participants were randomly assigned to receive a pharmacist-administered , tailored , @-year telephone-based intervention or usual care .


The goal of the study was to reduce the risk for CVD through a theory-driven intervention to increase medication adherence and improve health behaviors .


Enrollment began in November @ and is ongoing .


The target sample size is @ patients .


The Cardiovascular Intervention Improvement Telemedicine Study ( CITIES ) intervention has been designed with a strong theoretical underpinning .


The theoretical foundation and intervention are designed to encourage patients with multiple comorbidities and poorly controlled CVD risk factors to engage in home-based monitoring and tailored telephone-based interventions .


Evidence suggests that clinical pharmacist-administered telephone-based interventions may be efficiently integrated into primary care for patients with poorly controlled CVD risk factors .


Dose-dense weekly paclitaxel ( Taxol ) and carboplatin ( dd-TC ) improved survival compared with conventional tri-weekly paclitaxel and carboplatin ( c-TC ) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group @ trial .


We report the quality-of-life ( QoL ) results from this trial .


A total of @ patients were randomly assigned to receive c-TC or dd-TC ( c-TC , n = @ ; dd-TC , n = @ ) and were asked to complete a QoL assessment at baseline , just after the third and sixth chemotherapy cycles , and at @ months after randomization .


QoL was assessed using Functional Assessment of Cancer Therapy ( FACT ) - general ( FACT-G ) , FACT-taxane subscale ( FACT-T ) , and FACT-ovary subscale ( FACT-Ov ) .


The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time .


Baseline QoL assessment was completed by @ out of @ ( @ % ) and @ out of @ ( @ % ) patients in the c-TC and dd-TC groups , respectively .


In these groups , the compliance rates with regard to QoL assessment were @ % and @ % , respectively , after three chemotherapy cycles ; @ % and @ % , respectively , after six chemotherapy cycles ; and @ % and @ % , respectively , at @ months after randomization .


The overall QoL did not differ significantly between the two treatment groups up to @ months after randomization ( P = @ ) .


However , QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group ( P = @ ) .


dd-TC does not decrease overall QoL compared with c-TC .


The accuracy of physical examination techniques in detecting liver disease is unclear .


We sought to determine the perceived location of the lower liver border via scratch , percussion , palpation and ballottement with novice medical student examiners , compared with ultrasound localisation .


Five novice medical students learnt four liver examination techniques and measured the lower liver border in @ healthy volunteers .


The difference between the examination technique and ultrasound ( bias ) and limits of agreement of each method were estimated by mixed linear models and shown using Bland-Altman - like plots .


All techniques had similar bias for the lower liver border , between @ and @ cm superior to the ultrasound measurement .


Percussion had the smallest variability with increasing liver size .


Limits of agreement were wide for all techniques , smallest for palpation ( @ cm ) and largest for scratch ( @ cm ) compared to the mean liver distance of @ cm .


Conclusion There was no difference in bias between the scratch , percussion , palpation and ballottement techniques regarding the lower liver border .


All techniques had very wide limits of agreement , although palpation had the smallest .


Liver size examination by novice medical students in healthy subjects is unreliable .


Further research is needed using examiners with a different level of expertise and participants of varying body habitus and confirmed liver disease .


To evaluate the dose-response relationship of a novel recombinant human FSH ( rhFSH ; FE @ ) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment ; and prospectively study the influence of initial antimllerian hormone ( AMH ) concentrations .


Randomized , controlled , assessor-blinded , AMH-stratified ( low : @-@ @ pmol/L -LSB- @ - < @ ng/mL -RSB- ; high : @-@ @ pmol/L -LSB- @-@ @ ng/mL -RSB- ) trial .


Seven infertility centers in four countries .


Two hundred sixty-five women aged @ years .


Controlled ovarian stimulation with either @ , @ , @ , @ , or @ g of rhFSH , or @ g ( @ IU ) of follitropin alfa in a GnRH antagonist cycle .


Number of oocytes retrieved .


The number of oocytes retrieved increased in an rhFSH dose-dependent manner , from @ @ oocytes with @ g/d to @ @ with @ g/d .


The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata , demonstrating that a @ % increase in dose resulted in @ ( @ % confidence interval @-@ @ ) and @ ( @ % confidence interval @-@ @ ) more oocytes in the low and high AMH stratum , respectively .


Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata .


No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata .


Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum .


Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner .


The availability of blastocysts is less influenced by the rhFSH dose and AMH level .


The aim of this study was to evaluate the feasibility and safety of nonoperative treatment of acute nonperforated appendicitis with antibiotics in children .


A pilot randomized controlled trial was performed comparing nonoperative treatment with antibiotics versus surgery for acute appendicitis in children .


Patients with imaging-confirmed acute nonperforated appendicitis who would normally have had emergency appendectomy were randomized either to treatment with antibiotics or to surgery .


Follow-up was for @ year .


Fifty patients were enrolled ; @ were randomized to surgery and @ to nonoperative treatment with antibiotics .


All children in the surgery group had histopathologically confirmed acute appendicitis , and there were no significant complications in this group .


Two of @ patients in the nonoperative treatment group had appendectomy within the time of primary antibiotic treatment and @ patient after @ months for recurrent acute appendicitis .


Another @ patients have had an appendectomy due to recurrent abdominal pain ( n = @ ) or parental wish ( n = @ ) during the follow-up period ; none of these @ patients had evidence of appendicitis on histopathological examination .


Twenty-two of @ patients ( @ % ) treated with antibiotics had initial resolution of symptoms .


Of these @ , only @ patient ( @ % ) had recurrence of acute appendicitis during follow-up .


Overall , @ % of patients have not had an appendectomy during the follow-up period .


This pilot trial suggests that nonoperative treatment of acute appendicitis in children is feasible and safe and that further investigation of nonoperative treatment is warranted .


The prevalence of sleep disorders increases with age .


Sleep disorders may have serious health implications and may be related to serious underlying diseases .


Many older people use hypnotics , like benzodiazepines , although these medications have serious side effects and often lead to habituation .


Acetaminophen is one of the most frequently used off-label drugs for sleep disorders , although little is known about its effects .


Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people .


Participants , aged @ years or older ( n = @ ) , who have sleep disorders will be randomized for treatment with either acetaminophen @ mg or placebo , once daily at bedtime in a double-blind design .


Eligible patients should be able to give informed consent , should not be cognitively impaired ( Minimal Mental State Examination ( MMSE ) score@ ) , should not have pain , and should not use acetaminophen on a regular basis because of pain complaints .


The study will take three weeks to complete .


During these three weeks , the participants register their sleep behavior in a sleep diary .


The participants will use the study medication during the second and third week .


The primary endpoint will be the self-reported sleep disorders at the end of week three , as measured by means of the Insomnia Severity Index ( ISI ) .


To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern , we will measure the periods of wakefulness and sleep in a subgroup of participants , using an actigraph worn on the wrist during the entire study period .


The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population .


There is a need for treatments for sleep disorders without serious adverse effects .


Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people .


Modified vaccinia virus Ankara ( MVA ) is a promising viral vector platform for the development of an H@N@ influenza vaccine .


Preclinical assessment of MVA-based H@N@ vaccines showed their immunogenicity and safety in different animal models .


We aimed to assess the safety and immunogenicity of the MVA-haemagglutinin-based H@N@ vaccine MVA-H@-sfMR in healthy individuals .


In a single-centre , double-blind phase @/@a study , young volunteers ( aged @-@ years ) were randomly assigned with a computer-generated list in equal numbers to one of eight groups and were given one injection or two injections intramuscularly at an interval of @ weeks of a standard dose ( @ ( @ ) plaque forming units -LSB- pfu -RSB- ) or a ten times lower dose ( @ ( @ ) pfu ) of the MVA-H@-sfMR ( vector encoding the haemagglutinin gene of influenza A/Vietnam/@ / @ virus -LSB- H@N@ subtype -RSB- ) or MVA-F@-sfMR ( empty vector ) vaccine .


Volunteers and physicians who examined and administered the vaccine were masked to vaccine assignment .


Individuals who received the MVA-H@-sfMR vaccine were eligible for a booster immunisation @ year after the first immunisation .


Primary endpoint was safety .


Secondary outcome was immunogenicity .


The trial is registered with the Dutch Trial Register , number NTR@ .


@ of @ individuals who were enrolled completed the study .


No serious adverse events were identified .


@ individuals reported severe headache and lightheadedness , erythema nodosum , respiratory illness ( accompanied by influenza-like symptoms ) , sore throat , or injection-site reaction .


Most of the volunteers had one or more local ( itch , pain , redness , and swelling ) and systemic reactions ( rise in body temperature , headache , myalgia , arthralgia , chills , malaise , and fatigue ) after the first , second , and booster immunisations .


Individuals who received the @ ( @ ) dose had fewer systemic reactions .


The MVA-H@-sfMR vaccine at @ ( @ ) pfu induced significantly higher antibody responses after one and two immunisations than did @ ( @ ) pfu when assessed with haemagglutination inhibition geometric mean titre at @ weeks against H@N@ A/Vietnam/@ / @ ( @ -LSB- SD @ -RSB- vs @ -LSB- @ -RSB- and @ -LSB- @ -RSB- vs @ -LSB- @ -RSB- ) .


@ of @ eligible individuals were enrolled in the booster immunisation study .


A single shot of MVA-H@-sfMR @ ( @ ) pfu prime immunisation resulted in higher antibody responses after the booster immunisation than did two shots of MVA-H@-sfMR at the ten times lower dose .


The MVA-based H@N@ vaccine was well tolerated and immunogenic and therefore the vaccine candidates arising from the MVA platform hold great promise for rapid development in response to a future influenza pandemic threat .


However , the immunogenicity of this vaccine needs to be compared with conventional H@N@ inactivated non-adjuvanted vaccine candidates in head-to-head clinical trials .


This two-part phase @ study evaluated the efficacy and safety of panitumumab , a fully human anti-epidermal growth factor receptor monoclonal antibody , combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer .


In part @ , patients were sequentially enrolled to receive paclitaxel @ mg/m ( @ ) and carboplatin ( area under the concentration-versus-time curve , @ mg/min/ml ) plus panitumumab ( @ , @ , or @ mg/kg ) .


In part @ , patients were randomized @:@ to receive paclitaxel/carboplatin with ( arm A ) or without ( arm B ) the maximum tolerated dose of panitumumab identified in part @ .


Primary endpoints in parts @ and @ were the incidence of dose-limiting toxicities and time to progression ( TTP ) , respectively .


In part @ , four of @ patients had dose-limiting toxicities : three at @ mg/kg ( fatigue , pain in extremity , dyspepsia ) and one at @ mg/kg ( rash ) .


The maximum tolerated dose was not reached ; panitumumab @ mg/kg was selected for part @ .


In part @ , TTP was @ weeks ( @ % confidence interval -LSB- CI -RSB- , @-@ @ ) in arm A and @ weeks ( @ % CI , @-@ @ ) in arm B ( hazard ratio , @ ; @ % CI , @-@ @ ; p = @ ) .


Progression-free survival in arms A and B was @ weeks and @ weeks , respectively , and the objective response rate was @ % and @ % .


Adverse events occurring more frequently in arm A than in arm B included skin toxicity , diarrhea , stomatitis , vomiting , and dizziness .


Exploratory analyses did not demonstrate associations between potential biomarkers and outcomes .


Although toxicity was predictable and manageable , the addition of panitumumab to paclitaxel/carboplatin did not improve TTP in patients with previously untreated advanced non-small-cell lung cancer .


Lung volume reduction surgery improves quality of life , exercise capacity , and survival in selected patients but is accompanied by significant morbidity .


Bronchoscopic approaches may provide similar benefits with less morbidity .


In a randomized , sham procedure controlled , double-blind trial , @ subjects were enrolled at @ centers .


Patients had emphysema , airflow obstruction , hyperinflation , and severe dyspnea .


The primary effectiveness measure was a significant improvement in disease-related quality of life ( St. George 's Respiratory Questionnaire ) and changes in lobar lung volumes .


The primary safety measure was a comparison of serious adverse events .


There were @/@ ( @ % ) responders in the treatment group at @ months , significantly > @/@ ( @ % ) in the control group -LSB- Bayesian credible intervals ( BCI ) , @ % , @ % -RSB- .


Lobar volume changes were significantly different with an average decrease in the treated lobes of -@ mL compared with -@ mL for the control group ( BCI , -@ , -@ ) .


The proportion of responders in St. George 's Respiratory Questionnaire was not greater in the treatment group .


There were significantly more subjects with a serious adverse event in the treatment group ( n = @ or @ % ) compared with the control group ( n = @ or @ % ) ( BCI , @ , @ ) , but most were neither procedure nor device related .


This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results .


Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies .


Further studies need to focus on improved patient selection and a different treatment algorithm .


Lung volume reduction surgery improves survival in selected patients with emphysema , and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality .


Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis .


We did a single-centre , double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax .


We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in @ s ( FEV@ ) of less than @ % predicted , significant hyperinflation ( total lung capacity > @ % and residual volume > @ % ) , a restricted exercise capacity ( @ min walking distance < @ m ) , and substantial breathlessness ( MRC dyspnoea score @ ) .


Participants were randomised ( @:@ ) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion ( bronchoscopic lung volume reduction ) or a bronchoscopy with sham valve placement ( control ) .


Patients and researchers were masked to treatment allocation .


The study was powered to detect a @ % improvement in the primary endpoint , the FEV@ @ months after the procedure .


Analysis was on an intention-to-treat basis .


The trial is registered at controlled-trials .


com , ISRCTN@ .


@ patients ( @ % male , FEV@ -LSB- % predicted -RSB- mean @ % -LSB- SD @ -RSB- ) were enrolled to receive valves ( n = @ ) or sham valve placement ( control , n = @ ) between March @ , @ , and Sept @ , @ .


In the bronchoscopic lung volume reduction group , FEV@ increased by a median @ % ( IQR @-@ ) versus @ % ( @-@ ) in the control group ( Mann-Whitney p = @ ) .


There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax .


Unilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function .


There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery .


To determine the effects of decreased ankle-foot dorsiflexion ( A-Fdf ) range of motion ( ROM ) on gait kinematics in children with spastic cerebral palsy ( SCP ) .


All participants were children with spastic cerebral palsy ( n = @ ) who walked with knee flexion in midstance .


Data were collected over @-@ sessions , at @-monthly intervals .


A-Fdf ROM was quantified using a custom-designed hand-held ankle dynamometer that exerted @ Nm at the ankle .


Ankle-foot and knee angles during gait were quantified on sagittal video recordings .


Linear regression ( cross-sectional analysis ) and General Estimation Equation analysis ( longitudinal analysis ) were performed to assess relationships between ( change in ) A-Fdf ROM and ( change in ) ankle-foot and knee angle during gait .


Cross-sectional analysis showed a positive relationship between A-Fdf ROM and both ankle-foot angle in midstance and terminal swing .


Longitudinal analysis showed a positive relationship between individual decreases in A-Fdf ROM and increases of knee flexion during gait ( lowest knee angle in terminal stance and angle in terminal swing ) .


For this subgroup of SCP children , our results indicate that while changes in ankle angles during gait are unrelated to changes in A-Fdf ROM , changes in knee angles are related to changes in A-Fdf ROM .


After stroke , pneumonia is a relevant medical complication that can be precipitated by aspiration of saliva , liquids , or solid food .


Swallowing difficulty and aspiration occur in a significant proportion of stroke survivors .


Cough , an important mechanism protecting the lungs from inhaled materials , can be impaired in stroke survivors , and the likely cause for this impairment is central weakness of the respiratory musculature .


Thus , respiratory muscle training in acute stroke may be useful in the recovery of respiratory muscle and cough function , and may thereby reduce the risk of pneumonia .


The present study is a pilot study , aimed at investigating the validity and feasibility of this approach by exploring effect size , safety , and patient acceptability of the intervention .


Adults with moderate to severe stroke impairment ( National Institutes of Health Stroke Scale ( NIHSS ) score @ to @ at the time of admission ) are recruited within @weeks of stroke onset .


Participants must be able to perform voluntary respiratory maneuvers .


Excluded are patients with increased intracranial pressure , uncontrolled hypertension , neuromuscular conditions other than stroke , medical history of asthma or chronic obstructive pulmonary disease , and recent cardiac events .


Participants are randomized to receive inspiratory , expiratory , or sham respiratory training over a @-week period , by using commercially available threshold resistance devices .


Participants and caregivers , but not study investigators , are blind to treatment allocation .


All participants receive medical care and stroke rehabilitation according to the usual standard of care .


The following assessments are conducted at baseline , @weeks , and @weeks : Voluntary and reflex cough flow measurements , forced spirometry , respiratory muscle strength tests , incidence of pneumonia , assessments of safety parameters , and self-reported activity of daily living .


The primary outcome is peak expiratory cough flow of voluntary cough , a parameter indicating the effectiveness of cough .


Secondary outcomes are incidence of pneumonia , peak expiratory cough flow of reflex cough , and maximum inspiratory and expiratory mouth pressures .


Various novel pharmacologic and nonpharmacologic approaches for preventing stroke-associated pneumonia are currently being researched .


This study investigates a novel strategy based on an exercise intervention for cough rehabilitation .


Bleeding after percutaneous coronary intervention ( PCI ) is more common in women than in men .


However , the relationship of sex and bleeding with outcomes is less well studied .


We examined the sex-related differences in the incidence of bleeding and its association with in-hospital outcomes among @,@ patients undergoing PCI enrolled in the BMC@ registry ( @-@ ) .


Women had higher bleeding rate than did men ( @ % vs @ % ) and thus received more blood transfusions ( @ % vs @ % ) .


Both men ( odds ratio -LSB- OR -RSB- @ , @ % CI @-@ @ ) and women ( OR @ , @ % CI @-@ @ ) who bled had higher risk-adjusted death compared with their counterparts without bleeding .


Although there was no difference in adjusted mortality between women and men without bleeding ( OR @ , @ % CI @-@ @ ) , among patients who bled , adjusted death was higher in women ( OR @ , @ % CI @-@ @ ) .


Among patients with bleeding , transfusion was associated with similar increased risk of death in both men ( OR @ , @ % CI @-@ @ ) and women ( OR @ , @ % CI @-@ @ ) compared with their counterparts without transfusion ( s ) .


Post-PCI bleeding was more common and associated with higher-than-expected in-hospital death in women compared with men with bleeding .


This trend for higher death in women with bleeding was independent of transfusion .


Quality efforts geared toward reducing bleeding in general , with a special focus on women , need to be explored to help reduce post PCI-bleeding and mortality and decrease sex-related disparity in adverse events .


This randomized , double-blind study evaluates the efficacy and tolerability of agomelatine , using fluoxetine as an active comparator , in Asian patients suffering from moderate to severe major depressive disorder ( MDD ) .


Patients were randomly assigned to receive either agomelatine ( @-@mg / day , n = @ ) or fluoxetine ( @-@mg / day , n = @ ) during an @-week treatment period .


The main outcome measure was the change in Hamilton Depression Rating Scale @ items ( HAM-D@ ) scores .


Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness ( CGI-S ) and Improvement of illness ( CGI-I ) , patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire ( LSEQ ) and anxiety using the Hamilton Anxiety Rating Scale ( HAM-A ) scores .


Tolerability and safety evaluations were based on emergent adverse events .


Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population .


Mean changes over @ weeks were clinically relevant and similar in both groups ( -@ and -@ on HAM-D@ scale in agomelatine and fluoxetine groups , respectively ) .


The between-group difference reached statistical significance on non-inferiority test ( p = @ ) .


Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups .


The two treatments were equally effective on the symptoms of both anxiety and sleep .


The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population .


Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients .


Icotinib , an oral epidermal growth factor receptor tyrosine kinase inhibitor , has proved effectiveness in xenografted nude mice .


Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time , including dose proportionality , food effect , and tolerability .


Two studies were conducted in total of @ healthy subjects : a randomized , two-Latin-square crossover , dose proportional study ( n = @ ) and a randomized two-way crossover food-effect study ( n = @ ) .


Plasma concentration of Icotinib reached peak at a median Tmax of @-@ @ h after single dose and then declined with a mean t@/@ of @-@ @ h. Over the dose range of @-@ mg , AUC values were proportional to dose and Cmax showed a slight saturation when dose increases .


Only @ % of the dose was excreted through kidney in unchanged Icotinib .


After dosing @ mg of Icotinib with high-fat and high-calorie meal , mean Cmax and AUC were significantly increased by @ and @ % , respectively .


Three subjects experienced four adverse events ( rash , increase in AST and ALT , and external injury ) .


Rash and increased levels of AST and ALT were considered as drug-related .


No serious adverse events were reported .


The current work demonstrated that Icotinib was well tolerated in healthy male subjects ( n = @ ) over the dose range of @-@ mg with or without food .


Icotinib exposure , expressed in AUC , was proportionally increased with dose over the above dose range .


Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects .


To compare safety and efficacy of insulin glargine and liraglutide in patients with type @ diabetes ( T@DM ) .


This randomized , multinational , open-label trial included subjects treated for T@DM with metforminsulphonylurea , who had glycated haemoglobin ( HbA@c ) levels of @-@ % .


Subjects were assigned to @weeks of insulin glargine , titrated to target fasting plasma glucose of @-@ @ mmol/L or liraglutide , escalated to the highest approved clinical dose of @ mg daily .


The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA@c < @ % .


The mean -LSB- standard deviation ( s.d. ) -RSB- age of the participants was @ ( @ ) years , the duration of diabetes was @ ( @ ) years , body mass index was @ ( @ ) kg/m ( @ ) and HbA@c level was @ ( @ ) % .


Equal numbers ( n = @ ) were allocated to glargine and liraglutide .


Similar numbers of subjects in both groups attained an HbA@c level of < @ % ( @ vs. @ % ) ; therefore , superiority of glargine over liraglutide was not observed ( p = @ ) .


Subjects treated with glargine had greater reductions of HbA@c -LSB- -@ % ( @ ) and -@ % ( @ ) ; p = @ -RSB- and fasting plasma glucose -LSB- @ ( @ ) and @ ( @ ) mmol/L ; p < @ -RSB- than those receiving liraglutide .


The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events ( p < @ ) .


The mean ( s.d. ) weight change was +@ ( @ ) kg for glargine and -@ ( @ ) kg for liraglutide ( p < @ ) .


Symptomatic hypoglycaemia was more common with glargine ( p < @ ) .


A greater number of subjects in the liraglutide arm withdrew as a result of adverse events ( p < @ ) .


Adding either insulin glargine or liraglutide to subjects with poorly controlled T@DM reduces HbA@c substantially , with nearly half of subjects reaching target levels of @ % .


The lung volume reduction ( LVR ) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema .


We investigated the feasibility , safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema .


Patients were treated in @ centres .


Safety was evaluated by recording all adverse events , efficacy by the St George 's Respiratory Questionnaire ( SGRQ ) as primary endpoint , and pulmonary function testing , modified Medical Research Council dyspnoea score ( mMRC ) and @-min walk distance ( @MWD ) up to @months after the final treatment .


Sixty patients ( @ years , forced expiratory volume in @s ( FEV ( @ ) ) @ % pred ) were bronchoscopically treated with coils ( @ bilateral , @ unilateral ) , with a median of @ ( range @-@ ) coils per lobe .


Within @days post-treatment , seven chronic obstructive pulmonary disease exacerbations ( @ % ) , six pneumonias ( @ % ) , four pneumothoraces ( @ % ) and one haemoptysis ( @ % ) occurred as serious adverse events .


At @ and @months , respectively , SGRQ was -@ and -@ points , @MWD was +@ m and +@ m , FEV ( @ ) was +@ L and +@ L , and RV ( residual volume ) was -@ L and -@ L ( all p < @ ) .


Post hoc analyses showed significant responses for SGRQ , @MWD and RV in patients with both heterogeneous and homogeneous emphysema .


LVR coil treatment results in significant clinical improvements in patients with severe emphysema , with a good safety profile and sustained results for up to @year .


Whole grain ( WG ) options are often limited in schools , which may impact rural , low-income students who rely on school meals for a substantial portion of their food intake .


This study examined the changes in the availability and quantity of WG and refined grain foods offered in schools participating in the Creating Healthy , Active and Nurturing Growing-up Environments ( CHANGE ) study , a randomized , controlled intervention among rural communities ( @ intervention and @ control ) .


Foods were assessed using production records , recipes , and nutrition labels from breakfast and lunch over @ week during fall @ and spring @ .


Key informant interviews were conducted with school food service directors in the spring @ .


The CHANGE intervention schools significantly increased the average percent of school days WGs were offered ( p = @ ) and the amount of WGs offered/food item ( ounces ) at lunch compared with control schools ( p = @ ) .


There was a significant decrease in the percent of students with access to refined grains at lunch compared with control schools ( p = @ ) , although there were no significant differences in WG availability during breakfast .


The CHANGE schools improved WG availability , enabling student 's WG consumption to be closer to national recommendations .


To evaluate the clinical value of iodine -LSB- @I -RSB- metuximab infusion combined with transcatheter arterial chemoembolization ( TACE ) for treating cases of post-intervention relapse of mid or advanced stage hepatocellular carcinoma ( HCC ) .


Sixty patients who were diagnosed between March @ and June @ with relapse of mid or advanced stage HCC following previous intervention with various standard clinical methods were recruited for study .


The patients were randomly and equally divided into a control treatment group ( CG ; receiving TACE therapy alone ) and an experimental treatment group ( TG ; receiving TACE combined with iodine -LSB- @I -RSB- metuximab injection ) .


For all patients , licartin was first perfused into the tumor feeding artery and then the TACE procedure was performed @ min later .


Liver function markers and routine blood parameters , including alpha-fetoprotein ( AFP ) and clotting time , were examined at one week and one month after the treatment .


Enhanced computed tomography or magnetic resonance imaging of the liver was performed at one month after treatment and thereafter on a bi-monthly follow-up schedule .


The World Health Organization 's tumor evaluation standard was used to assess the therapeutic effects in each group .


Results of laboratory tests ( pre - and post-treatment ) , reported complications , and side-effects were evaluated for their contributions to time of tumor progression ( TTP ) and survival time .


Patients in the TG and CG groups had similar blood cell counts at pre-operative and @-week postoperative time points .


The TG group showed a significantly reduced level of AFP following treatment , but it was not significantly different from the level in the CG group .


The TG group did however show significantly different levels of liver functional parameters ( all P less than @ ) and significantly higher TTP ( @ + / -@ vs. CG : @ + / -@ months ; t = -@ , P less than @ ) and average survival time ( @ vs. @ months ; x@ = @ , P = @ ) .


The rates of partial response ( PR ) , slight remission ( MR ) , unchanged status ( SD ) and progressive disease ( PD ) were @ % , @ % , @ % and @ % in the TG group , and @ % , @ % , @ % and @ % in the CG group .


The therapeutic effect rate ( CR + PR + MR ) and reaction rate ( CR + PR + MR + SD ) was significantly different between the two groups ( P = @ ) .


No serious adverse effects were reported .


TACE combined with iodine -LSB- @I -RSB- metuximab injection is a safe and effective procedure for prolonging the survival and TTP of patients with HCC relapse following prior therapeutic intervention .


Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation .


First efficacy results of the nicotine vaccine @ ' - AmNic-rEPA ( NicVAX ) showed that only a subgroup of the top @ % antibody responders achieved higher abstinence rates than placebo .


The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention .


Randomized placebo-controlled trial .


Two research centres ( Maastricht University Medical Centre and Slotervaart Hospital ) in the Netherlands .


A total of @ smokers were assigned randomly to six injections with NicVAX ( n = @ ) or placebo ( n = @ ) both co-administered with open label varenicline and behavioural support .


Outcomes were prolonged carbon monoxide-validated abstinence from weeks @ to @ ( primary ) and weeks @ to @ ( secondary ) .


We also performed a pre-planned subgroup analysis in the top @ % antibody responders .


There was no difference in abstinence rates between NicVAX and placebo from weeks @ to @ -LSB- @ versus @ % , odds ratio ( OR ) = @ , @ % confidence interval ( CI ) = @-@ @ -RSB- or weeks @ to @ ( @ versus @ % , OR = @ , @ % CI = @-@ @ ) .


The top @ % antibody responders , compared to the placebo group , showed a non-significant tendency towards higher abstinence rates from weeks @ to @ ( @ versus @ % , OR = @ , @ % CI = @-@ @ ) .


The nicotine vaccine , NicVAX , does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support .


Acting coherently upon stimuli requires some kind of integration of stimulus and response features across various distinct cortical feature maps ( one aspect of the binding problem ) .


Although the process of feature binding proper seems rather automatic , recent studies revealed that the management of stimulus-response bindings is less efficient in populations with impaired cognitive-control processes .


Here , we investigated whether the cognitive control of stimulus-response feature bindings ( `` event files '' ) in healthy participants is affected by non-invasive brain stimulation ( tDCS ) of the dorsolateral prefrontal cortex ( DLPFC ) - a main component of the cognitive-control network .


In different sessions , participants received anodal , cathodal , or sham tDCS ( @ mA , @ min ) while performing an audio-visual event-file task assessing the creation and retrieval of stimulus-stimulus and stimulus-response feature bindings .


The general findings from this task indicate that performance suffers when some , but not all of the features are repeated ( the so-called partial repetition cost ) .


Stimulation over the right , but not the left DLPFC reduced control of stimulus-response bindings and produced outcome patterns similar to those previously observed in autistic children , people with lower fluid intelligence , and older adults .


This finding provides empirical support for a role of the right DLPFC in feature-binding management , which might consist in preventing the stimulus-induced activation of previously created , but now task-irrelevant , episodic bindings .


From a methodological perspective , the finding may suggest that tDCS could be used as a temporary , reversible `` brain lesion '' generator in healthy subjects , enabling experimental investigation of how the brain works .


To assess in a randomized study the patient-centred outcome of two guided surgery systems ( mucosa or bone supported ) compared to conventional implant placement , in fully edentulous patients .


Fifty-nine patients ( @ jaws ) with edentulous maxillas and / or mandibles , were consecutively recruited and randomly assigned to one of the treatment groups .


Outcome measures were the Dutch version of the McGill Pain Questionnaire ( MPQ-DLV ) , the Health-related quality of life instrument ( HRQOL ) , visual analogue scales ( VAS ) , the duration of the procedure , and the analgesic doses taken each day .


Three hundred and fourteen implants were placed successfully .


No statistical differences could be shown between treatment groups on pain response ( MPQ-DLV ) , treatment perception ( VAS ) or number or kind of pain killers .


For the HRQOLI-instrument , a significant difference was found between the Materialise Mucosa and Materialise Bone group at day @ ( p = @ ) and day @ ( p = @ ) .


For the duration of the surgery , a statistical difference ( p = @ ) was found between the Materialise mucosa and the Mental group , in favour of the first .


In this study little difference could be found in the patient outcome variables of the different treatment groups .


However there was a tendency for patients treated with conventional flapped implant placement to experience the pain for a longer period of time .


The snatch-farrowed porcine-colostrum-deprived ( SF-pCD ) pig model , in which neonates are raised on commercially available bovine colostrum , is an alternative model for porcine infectious disease research .


It is not known if SF-pCD pigs possess growth performance and immunity comparable to conventional , farm-raised pigs .


The current experiment compared growth performance and immune responses of SF-pCD pigs to their farm-raised siblings following Mycoplasma hyopneumoniae ( Mhyo ) vaccination .


Twelve SF-pCD and @ farm-raised siblings were vaccinated on day @ ( D@ ) and D@ of age .


Body weights were measured once or twice weekly and average daily gain ( ADG ) was calculated .


Peripheral blood mononuclear cells ( PBMC ) were isolated on D@ .


Cytokine secretion from PBMC stimulated with Mhyo antigen or phorbol myristate acetate plus ionomycin ( PMA/Iono ) was assessed using a multiplexed fluorescent microsphere immunoassay ( FMIA ) .


Additionally , interferon gamma ( IFN ) secretion from stimulated PBMC was assessed using ELISPOT .


Mhyo IgG titers were measured by an ELISA in D@ sera .


Growth performance did not differ between groups before weaning , but SF-pCD pigs had higher ADG after weaning .


In response to Mhyo stimulation , numbers of IFN secreting PBMC and levels of interleukin @ ( IL@ ) and IL@ in PBMC supernatants were significantly higher in SF-pCD pigs , as were Mhyo antibody levels in sera , and levels of IL@ , IL@ and IL@ in supernatants of PMA/Iono stimulated PBMC .


Under the conditions of this experiment , SF-pCD pigs demonstrated superior growth performance and enhanced humoral and cell-mediated immunity following vaccination .


Whether or not this reflects greater resistance or tolerance to infection is unknown but the ability to react positively to the vaccination provides evidence that SF-pCD pigs are a suitable alternative model for swine disease research .


Physical exercise is associated with enhanced production of reactive oxygen species , which if uncontrolled can result in tissue injury .


Phosphodiesterase type @ inhibitors ( PDE@i ) exhibit protective effect against oxidative stress , both in animals and healthy/unhealthy humans .


However , the effect of a chronic administration of PDE@i , particularly combined with physical exercise , has never been investigated .


The present study was designed to evaluate the effect of the long-acting PDE@i tadalafil on oxidative status and muscle damage after exhaustive exercise in healthy males included in a double-blind crossover trial .


Tadalafil , having a putative antioxidant activity , may reduce oxidative damage after strenuous exercise .


Each volunteer randomly received two tablets of placebo or tadalafil ( @ mg/day ) with @ h of interval before performing exhaustive exercise .


After @ weeks of washout , the volunteers were crossed over .


Blood samples were collected immediately before exercise , immediately after , and during recovery ( @ , @ , @ min ) .


Plasma total antioxidant status , glutathione homeostasis ( GSH/GSSG ) , malondialdehyde ( MDA ) , protein carbonyls , creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) and the inflammatory cytokine interleukin @ were assessed .


Tadalafil administration per se affected redox homeostasis ( GSH/GSSG -@ % ; p < @ ) , cellular ( CK +@ % and LDH +@ % ; p < @ ) and oxidative damage ( MDA +@ % and protein carbonyls +@ % ; p < @ ) markers .


The exhaustive exercise increased all the above-reported biochemical parameters , with subjects from the tadalafil group showing significantly higher values with respect to the placebo group .


A prolonged exposure to tadalafil decreases antioxidant capacity at resting condition , therefore making subjects more susceptible to the oxidative stress induced by an exhaustive bout of exercise .


To compare the clinical efficacy difference between electroacupuncture ( EA ) at qijie area combined with spine balance-regulating massage and medication for posterior circulation ischemia ( PCI ) .


One hundred cases of PCI were randomly divided into a treatment group ( @ cases ) and a medication group ( @ cases ) .


The treatment group was treated with EA at Baihui ( GV @ ) , Sishencong ( EX-HN @ ) , Fengchi ( GB @ ) , Shenshu ( BL @ ) , Danzhong ( CV @ ) , etc. in qijie area combined with spine muscle-relieving massage and comprehensive chiropractic .


The medication group was treated with oral administration of nimodipine ( @ mg per time , three treatments per day ) and vinpocetine injection with @ mL of glucose injection or intravenous drip of @ mL @ % sodium chloride injection , once a day .


Ten treatments were taken as one course in both groups , and two courses were given .


The symptom score , mean resistance index ( RI ) of vertebral artery ( VA ) and basilar artery ( BA ) , mean velocity of blood flow ( Vm ) and comprehensive clinical efficacy were compared before and after treatment in two groups .


The cured and markedly effective rate was @ % ( @/@ ) in the treatment group , which was superior to @ % ( @/@ ) in the medication group ( P < @ ) .


The symptom score was both significantly improved after treatment in two groups ( both P < @ ) , which was more obvious in the treatment group ( P < @ ) .


The RI of VA and BA , Vm of VA and BA were significantly improved after treatment in two groups ( all P < @ ) , which were more obvious in the treatment group ( all P < @ ) .


The electroacupuncture combined with spine balance-regulating massage has superior effect on improving mean velocity of blood flow and resistance index of vertebral artery and basilar artery as well as symptom score to medication , and is believed to be a safe and effective treatment for posterior circulation ischemia .


To determine the safety and effectiveness of intralesional tetracycline @ % injection for the treatment of lower eyelid festoons .


The authors retrospectively reviewed the charts of all patients undergoing tetracycline @ % injection of lower eyelid festoons at the Cole Eye Institute from August @ to August @ .


Charts were reviewed for patient demographic data , dose and number of tetracycline injections , follow-up interval , the presence of preinjection and postinjection photographs , and complications .


Charts without preinjection and postinjection photographs were excluded from review .


The preinjection and postinjection photographs were randomized , masked , and graded by @ independent examiners .


Photographs were graded on a scale of @ ( no festoon ) to @ ( severe festoon ) .


Student t test was used for statistical analysis .


Eleven patients met inclusion criteria .


Each patient underwent bilateral injection .


Average follow up was @ days ( range , @-@ days ) .


Patients received up to @ ml ( mean , @ ml ) of tetracycline @ % per side .


Average preinjection grade was @ ( standard deviation , @ ; range , @-@ ) , and average postinjection grade was @ ( standard deviation , @ ; range , @-@ ; p < @ ) .


Three patients had follow up less than @ days ( mean , @ days ) , with an average preinjection grade of @ and postinjection grade of @ ( p < @ ) .


Five patients had follow up between @ and @ days ( mean , @ days ) , with an average preinjection grade of @ and postinjection grade of @ ( p < @ ) .


Three patients had follow up longer than @ days ( mean , @ days ) , with an average preinjection grade of @ and postinjection grade of @ ( p < @ ) .


Complications other than pain and bruising were not identified in any patient .


Intralesional tetracycline @ % injection may offer a safe option to treat lower eyelid festoons .


Complications such as cutaneous ischemia or necrosis were not identified in any patient .


Further study may determine optimal treatment doses and intervals and detect infrequent but significant complications .


The Quality and Outcomes Framework in the United Kingdom ( UK ) National Health Service previously highlighted case finding of depression amongst patients with diabetes or coronary heart disease .


However , depression in older people remains under-recognized .


Comprehensive data for analyses of the association of depression in older age with other health and functional measures , and demographic factors from community populations within England , are lacking .


Secondary analyses of cross-sectional baseline survey data from the England arm of a randomised controlled trial of health risk appraisal for older people in Europe ; PRO-AGE study .


Data from @ community-dwelling non-disabled people aged @ years or more from three group practices in suburban London contributed to this study .


Depressed mood was ascertained from the @-item Mental Health Inventory Screening test .


Exploratory multivariable logistic regression was used to identify the strongest associations of depressed mood with a previous diagnosis of a specified physical/mental health condition , health and functional measures , and demographic factors .


Depressed mood occurred in @ % ( @/@ ) of participants .


A previous diagnoses of depression ( OR @ ; P < @ ) and poor vision as determined from a Visual Function Questionnaire ( OR @ ; P = @ ) were amongst the strongest factors associated with depressed mood that were independent of functional impairment , other co-morbidities , and demographic factors .


A subgroup analyses on those without a previous diagnosis of depression also indicated that within this group , poor vision ( OR @ ; P = @ ) was amongst the strongest independent factors associated with depressed mood .


Previous case-finding strategies in primary care focussed on heart disease and diabetes but health-related conditions other than coronary heart disease and diabetes are also associated with an increased risk for depression .


Complex issues of multi-morbidity occur within aging populations .


` Risk ' factors that appeared stronger than those , such as , diabetes and coronary heart disease that until recently prompted for screening in the UK due to the QOF , were identified , and independent of other morbidities associated with depressed mood .


From the health and functional factors investigated , amongst the strongest factors associated with depressed mood was poor vision .


Consideration to case finding for depressed mood among older people with visual impairment might be justified .


To examine the association between preoperative quality of life ( QoL ) and postoperative adverse events in women treated for endometrial cancer .


@ women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery .


This analysis includes women with preoperative QoL measurements , from the Functional Assessment of Cancer Therapy-General ( FACT-G ) questionnaire , and who were followed up for at least @ weeks after surgery ( n = @ ) .


The outcomes for this study were defined as ( @ ) the occurrence of moderate to severe adverse events within @ months ( Common Toxicology Criteria ( CTC ) grade@ ) ; and ( @ ) any serious adverse event ( SAE ) .


The association between preoperative QoL and the occurrence of AE was examined , after controlling for baseline comorbidity and other factors .


After adjusting for other factors , odds of occurrence of AE of CTC grade@ were significantly increased with each unit decrease in baseline FACT-G score ( OR = @ , @ % CI @-@ @ , p = @ ) , which was driven by physical well-being ( PWB ) ( OR = @ , @ % CI @-@ @ , p = @ ) and functional well-being subscales ( FWB ) ( OR = @ , @ % CI @-@ @ , p = @ ) .


Similarly , odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score ( OR = @ , @ % CI @-@ @ , p = @ ) , baseline PWB ( OR = @ , @ % CI @-@ @ , p < @ ) or baseline FWB subscales ( OR = @ , @ % CI @-@ @ , p = @ ) .


Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery .


Since there is a lack of current evidence to support the compatibility of the most commonly used arterial blood gas syringes with the latest multi-parameter analyzers , the objective of this study was to assess the agreement of analyte values between three heparinized arterial blood gas syringes using three different analyzers .


Venous blood from @ healthy volunteers was drawn into the study syringes ( BD Drihep A-Line , PICO@ , and Portex Line Draw Plus ) by four clinician volunteers in a random order ( @ total ) and immediately ( < @ minutes ) analyzed ( ABL@ FLEX , RAPIDPoint @ , i-STAT System ) in a randomized order .


The Bland-Altman method was used to assess agreement of analyte values between the syringes for each analyzer .


The results by analyte and analyzer were compared across syringes using one-way ANOVA , and Tukey 's approach was used to identify statistically significant differences between pairs of syringes .


Comparison of the syringes ' mean differences and standard deviations showed close agreement for all three analyzers .


There were no statistically significant differences between syringes in @ of the analytes for any of the analyzers ( p > @ ) .


For RAPIDPoint and i-STAT , the Ca ( @ + ) value was significantly less for A-Line than for the other syringes .


The value for Na ( + ) was significantly greater for the PICO@ than the A-Line and Line Draw syringes with the i-STAT .


Both results were within two standard deviations of the mean of the other two syringes and are not considered clinically significant ; however , comparisons were not made between the values from the different analyzers .


Dry-balanced lithium heparin ABG syringes used for blood draws should provide reliable results , regardless of syringe type , provided that the clinicians use proper pre-analytical techniques .


Pancreaticoduodenectomy ( PD ) is associated with a high incidence of postoperative complications including pancreatic fistula .


This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux-en-Y ( IsoRY ) and conventional reconstruction ( CR ) methods .


Patients admitted for PD between June @ and September @ in a single centre were assigned randomly to CR or IsoRY .


The primary endpoint was the incidence of pancreatic fistula ( grade A-C ) defined according to the International Study Group on Pancreatic Fistula .


Secondary endpoints were complication rates , mortality and hospital stay .


Multiple logistic regression analysis was performed to identify factors associated with pancreatic fistula .


Some @ patients were randomized , @ to CR and @ to IsoRY ; two patients from the IsoRY group were excluded after randomization .


Pancreatic fistula occurred in @ patients ( @ per cent ) in the CR group and @ ( @ per cent ) in the IsoRY group ( P = @ ) .


The number of patients with a clinically relevant pancreatic fistula ( grade B or C ) was similar in the two groups ( @ and @ patients respectively ; P = @ ) , as were complication rates ( @ versus @ per cent ; P = @ ) and mortality ( none in either group ; P = @ ) .


Soft pancreas was the only independent risk factor for pancreatic fistula ( odds ratio @ , @ per cent confidence interval @ to @ ; P < @ ) .


This study showed that IsoRY reconstruction does not reduce the incidence of pancreatic fistula compared with CR .


Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function .


We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease .


In this randomised , double-blind , placebo-controlled trial , boys from three centres in the USA aged @ years or older with Duchenne muscular dystrophy , myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone @ mg or placebo orally , every other day for the first month and once daily thereafter , in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors ( ACEI ) or angiotensin receptor blockers ( ARB ) .


Computer-generated randomisation was done centrally using block sizes of four and six , and only the study statistician and the investigational pharmacy had the preset randomisation assignments .


The primary outcome was change in left ventricular circumferential strain ( Ecc ) at @ months , a measure of contractile dysfunction .


Safety was established through serial serum potassium levels and measurement of cystatin C , a non-creatinine measure of kidney function .


This trial is registered with ClinicalTrials.gov , number NCT@ .


Between Jan @ , @ , and July @ , @ , @ boys were screened and @ were enrolled .


@ were randomly assigned to receive eplerenone and @ to receive placebo , of whom @ in the eplerenone group and @ in the placebo group completed baseline , @-month , and @-month visits .


After @ months , decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo ( median Ecc @ -LSB- IQR @-@ -RSB- vs @ -LSB- @-@ -RSB- ; p = @ ) .


Cystatin C concentrations remained normal in both groups , and all non-haemolysed blood samples showed normal potassium concentrations .


One @-year-old patient in the placebo group died of fat embolism , and another patient in the placebo group withdrew from the trial to address long-standing digestive issues .


All other adverse events were mild : short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone , flushing occurred in one patient given placebo , and anxiety occurred in another patient given placebo .


In boys with Duchenne muscular dystrophy and preserved ejection fraction , addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function .


Early use of available drugs warrants consideration in this population at high risk of cardiac death , but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy .


To monitor corneal epithelial healing under bandage contact lens ( BCL ) using ultrahigh-resolution optical coherence tomography ( UHR-OCT ) after pterygium surgery .


Thirty-nine eyes of @ patients undergoing pterygium excision and conjunctival autografting were randomly allocated into @ groups : @ eyes were covered with silicone hydrogel BCLs at the end of surgery and @ eyes served as a control .


Ultrahigh-resolution optical coherence tomography scans of the cornea were performed sequentially at @ , @ , and @ days , and then every other day until the end of re-epithelialization after surgery .


Complete epithelial healing was verified with fluorescein staining examination after removal of BCLs .


Postsurgery pain was evaluated using the visual analog scale .


All BCLs were successfully fit without any contact lens-related complications .


Ultrahigh-resolution optical coherence images clearly revealed the architectural features of postoperative cornea with BCL in situ and showed epithelial healing process .


Ultrahigh-resolution optical coherence tomography imaging agreed with the fluorescein staining examinations in detecting corneal epithelial defect .


Based on the assessment by UHR-OCT , the average time course of re-epithelialization in the BCL group was @ days , whereas in the control group , it was @ days ( P = @ ) .


Visual analog scale scoring showed lower pain levels in the BCL group comparing with the control group at each point of time ( all P < @ ) .


Ultrahigh-resolution optical coherence tomography is an excellent tool in monitoring corneal epithelial healing under BCLs and determining the appropriate time for lens removal .


Silicone hydrogel BCL is recommended as an adjuvant therapy after pterygium surgery for its efficacy in improving re-epithelialization and postoperative comfort .


The Zwolle Risk Score ( ZRS ) identifies ST-elevation myocardial infarction ( STEMI ) patients treated with primary percutaneous coronary intervention ( PPCI ) eligible for early discharge .


We aimed to investigate whether baseline N-terminal pro-brain natriuretic peptide ( NT-proBNP ) is also able to identify these patients and could improve future risk strategies .


PPCI patients included in the Ongoing Tirofiban in Myocardial Infarction Evaluation ( On-TIME ) II study were candidates ( N = @ ) .


We analyzed whether ZRS and baseline NT-proBNP predicted @-day mortality and assessed the occurrence of major adverse cardiac events ( MACEs ) and major bleeding .


Receiver operating characteristic curve analysis was used to assess discriminative accuracy for ZRS , NT-pro-BNP , and their combination .


After multiple imputation , @ patients were included .


Both ZRS > @ ( hazard ratio -LSB- HR -RSB- = @ ; P < @ ) and log NT-pro-BNP ( HR = @ ; P < @ ) values were associated with @-day mortality .


On multivariate analysis , both the ZRS ( HR = @ ; @ % confidence interval -LSB- CI -RSB- = @ to @ ; P < @ ) and log NT-proBNP ( HR = @ ; @ % CI = @ to @ ; P < @ ) independently predicted death at @ days .


The area under the curve for @-day mortality for combined ZRS/NT-proBNP was @ ( @ % CI = @ to @ ) , with optimal predictive values of a ZRS @ and a NT-proBNP value of @ pg/mL .


Using these cut-off values , @ % of the study population could be identified as very low risk with zero mortality at @ days follow-up and low occurrence of MACEs and major bleeding between @ hours and @ days ( @ % and @ % , respectively ) .


Baseline NT-proBNP identifies a large group of low-risk patients who may be eligible for early ( @ - to @-hour ) discharge , whereas optimal predictive accuracy is reached by the combination of both baseline NT-proBNP and ZRS .


Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm .


To evaluate the clinical effectiveness of a perioperative , cardiac output-guided hemodynamic therapy algorithm .


OPTIMISE was a pragmatic , multicenter , randomized , observer-blinded trial of @ high-risk patients aged @ years or older undergoing major gastrointestinal surgery at @ acute care hospitals in the United Kingdom .


An updated systematic review and meta-analysis were also conducted including randomized trials published from @ to February @ .


Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope ( dopexamine ) infusion during and @ hours following surgery ( n = @ ) or to usual care ( n = @ ) .


The primary outcome was a composite of predefined @-day moderate or major complications and mortality .


Secondary outcomes were morbidity on day @ ; infection , critical care-free days , and all-cause mortality at @ days ; all-cause mortality at @ days ; and length of hospital stay .


Baseline patient characteristics , clinical care , and volumes of intravenous fluid were similar between groups .


Care was nonadherent to the allocated treatment for less than @ % of patients in each group .


The primary outcome occurred in @ % of intervention and @ % of usual care participants ( relative risk -LSB- RR -RSB- , @ -LSB- @ % CI , @-@ @ -RSB- ; absolute risk reduction , @ % -LSB- @ % CI , -@ % to @ % -RSB- ; P = @ ) .


There was no significant difference between groups for any secondary outcomes .


Five intervention patients ( @ % ) experienced cardiovascular serious adverse events within @ hours compared with none in the usual care group .


Findings of the meta-analysis of @ trials , including data from this study , suggest that the intervention is associated with fewer complications ( intervention , @/@ -LSB- @ % -RSB- vs control , @/@ -LSB- @ % -RSB- ; RR , @ -LSB- @ % CI , @-@ @ -RSB- ) and a nonsignificant reduction in hospital , @-day , or @-day mortality ( intervention , @/@ deaths -LSB- @ % -RSB- vs control , @/@ deaths -LSB- @ % -RSB- ; RR , @ -LSB- @ % CI , @-@ @ -RSB- ) and mortality at longest follow-up ( intervention , @/@ deaths -LSB- @ % -RSB- vs control , @/@ deaths -LSB- @ % -RSB- ; RR , @ -LSB- @ % CI , @-@ @ -RSB- ) .


In a randomized trial of high-risk patients undergoing major gastrointestinal surgery , use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and @-day mortality .


However , inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates .


The Nurse-Family Partnership delivered by nurses has been found to produce long-term effects on maternal and child health in replicated randomized trials .


A persistent question is whether paraprofessional home visitors might produce comparable effects .


To examine the impact of prenatal and infancy/toddler home visits by paraprofessionals and by nurses on child development at child ages @ and @ years .


Randomized trial in public and private care settings in Denver , Colorado , of @ low-income women and their first-born children ( @ % of the mothers were unmarried ; @ % were Hispanic , @ % were non-Hispanic white , @ % were African American , and @ % were American Indian/Asian ) .


Home visits provided from pregnancy through child age @ years delivered in one group by paraprofessionals and in the other by nurses .


Reports of children 's internalizing , externalizing , and total emotional/behavioral problems , and tests of children 's language , intelligence , attention , attention dysfunction , visual attention/task switching , working memory , and academic achievement .


We hypothesized that program effects on cognitive-related outcomes would be more pronounced among children born to mothers with low psychological resources .


We report paraprofessional-control and nurse-control differences with P < @ given similar effects in a previous trial , earlier effects in this trial , and limited statistical power .


There were no significant paraprofessional effects on emotional/behavioral problems , but paraprofessional-visited children born to mothers with low psychological resources compared with control group counterparts exhibited fewer errors in visual attention/task switching at age @ years ( effect size = -@ , P = @ ) .


There were no statistically significant paraprofessional effects on other primary outcomes .


Nurse-visited children were less likely to be classified as having total emotional/behavioral problems at age @ years ( relative risk -LSB- RR -RSB- = @ , P = @ ) , internalizing problems at age @ years ( RR = @ , P = @ ) , and dysfunctional attention at age @ years ( RR = @ , P = @ ) .


Nurse-visited children born to low-resource mothers compared with control-group counterparts had better receptive language averaged over ages @ , @ , and @ years ( effect size = @ , P = @ ) and sustained attention averaged over ages @ , @ , and @ years ( effect size = @ , P = @ ) .


There were no significant nurse effects on externalizing problems , intellectual functioning , and academic achievement .


Children born to low-resource mothers visited by paraprofessionals exhibited improvement in visual attention/task switching .


Nurse-visited children showed improved behavioral functioning , and those born to low-resource mothers benefited in language and attention but did not improve in intellectual functioning and academic achievement .


Inhaler mishandling is a common issue among patients suffering from asthma and is associated with poor clinical outcomes and greater consumption of health-care resources .


Ease of use can improve inhaler technique and , possibly , patients ' preference for their inhaler device , which in turn may lead to better adherence to therapy .


This study investigated usability characteristics of NEXThaler ( ) versus two other dry powder inhalers ( DPIs ; Diskus ( ) and Turbuhaler ( ) ) .


Sixty-six adult patients with asthma ( mean age @ years ) and with no previous experience of using a DPI were included in a randomized crossover comparison of the three devices .


The main measures of usability were the number of steps failed for each device and the number of people who were able to use the device successfully ( effectiveness ) , the time it took patients to set up the device and the time to read the instructions for use ( IFU ; efficiency ) , and patient preferences ( satisfaction ) .


Inhaler technique was evaluated after the IFU leaflet was read .


NEXThaler was found to be superior to the other two DPIs in terms of the number of device use failures ( p < @ ) , time to set up ( p < @ ) , and time to read IFU ( p < @ ) .


Additionally , the proportion of participants who completed a successful inhalation without any errors at all was significantly higher for NEXThaler than for Diskus and Turbuhaler ( p < @ ) .


Patients rated NEXThaler as the easiest to use and most preferred inhaler to own ( p < @ ) .


NEXThaler displayed better usability compared with Diskus and Turbuhaler .


The improved usability and higher satisfaction with the device may contribute to increased patient adherence to asthma treatment .


Randomized data support shorter radiotherapy courses for management of cancer-related symptoms in the palliative setting .


The purpose of this study was to evaluate the length of palliative radiotherapy before hospice enrollment among the elderly U.S. population , with a further focus on factors that influence the duration of radiation and the length of survival on hospice , including whether the duration of radiation was associated with length of survival on hospice .


A total of @ patients with breast , prostate , lung , or colorectal cancer who received a course of radiotherapy within @days before hospice enrollment were identified within the Surveillance , Epidemiology , and End Results-Medicare linked database .


The primary end points included the duration of palliative radiotherapy and the time from hospice enrollment through death ( hospice duration ) .


Multivariate linear regression and multivariate Cox models evaluated factors associated with the length of radiotherapy course and hospice duration .


The median length of palliative radiotherapy was @days , and the median hospice duration was @days .


The course of palliative radiotherapy was longer than hospice duration in @ % of the patients .


Breast and lung cancer were associated with longer courses of radiotherapy and shorter stays on hospice .


Patients treated in freestanding radiation centers had longer courses of radiotherapy .


For these groups , a longer radiotherapy course was not associated with longer hospice duration .


This study found relatively long courses of radiotherapy before short lengths of survival on hospice .


Future research is needed to identify barriers to shorter radiotherapy courses .


The once-daily oral factor Xa inhibitor , edoxaban , is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate-high stroke risk .


Limited data regarding cerebrovascular events with edoxaban were reported previously .


We analyzed the subtypes of cerebrovascular events in @ @ patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction @ ( ENGAGE AF-TIMI @ ) comparing outcomes among patients randomized to warfarin versus @ edoxaban regimens ( high dose , low dose ) .


The primary end point for this prespecified analysis of cerebrovascular events was all stroke ( ischemic plus hemorrhagic ) , defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting @ hours or fatal in < @ hours .


Independent stroke neurologists unaware of treatment adjudicated all cerebrovascular events .


Patients randomized to high-dose edoxaban had fewer strokes on-treatment ( hazard ratio , @ ; @ % confidence interval , @-@ @ ) than warfarin ( median time-in-therapeutic range , @ % ) ; patients in the low-dose edoxaban group had similar rates ( hazard ratio , @ versus warfarin ; @ % confidence interval , @-@ @ ) .


Rates of ischemic stroke or transient ischemic attack were similar with high-dose edoxaban ( @ % per year ) and warfarin ( @ % per year ; P = @ ) , but more frequent with low-dose edoxaban ( @ % per year ; P < @ ) .


Both edoxaban regimens significantly reduced hemorrhagic stroke and other subtypes of intracranial bleeds .


In patients with atrial fibrillation , once-daily edoxaban was as effective as warfarin in preventing all strokes , with significant reductions in various subtypes of intracranial bleeding .


Ischemic cerebrovascular event rates were similar with high-dose edoxaban and warfarin , whereas low-dose edoxaban was less effective than warfarin .


The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids , alone or in conjunction with drotrecogin-alfa ( activated ) ( DrotAA ) , on the outcomes in septic shock patients .


We performed a sub-study of the PROWESS-Shock trial ( septic shock patients who received fluids and vasopressors above a predefined threshold for at least @ hours were randomized to receive either DrotAA or placebo for @ hours ) .


A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression .


Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids , alone or in conjunction with DrotAA , on @-day and @-day all-cause mortality .


A total of @ patients were enrolled of which @ % received intravenous steroids for treatment of septic shock at baseline ( DrotAA + steroids N = @ ; DrotAA + no steroids N = @ ; placebo + steroids N = @ ; placebo + no steroids N = @ ) .


The propensity weighted risk of @-day as well as @-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo ( interaction p-value = @ and p = @ , respectively ) nor was a difference detected within each randomized treatment .


Similarly , the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy .


In patients with lung infection ( N = @ ) , abdominal infection ( N = @ ) , Gram-positive sepsis ( N = @ ) and Gram-negative sepsis ( N = @ ) , the propensity weighted risk of @-day as well as @-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment .


In the present study of septic shock patients , after adjustment for treatment selection bias , we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo .


Fibrin sealant ( FS ) is a biologically derived tissue adhesive for securing flaps .


The aim of the present randomized controlled clinical trial was to compare early wound healing by assessing interleukin-@ ( IL-@ ) and interleukin-@ ( IL-@ ) levels from gingival crevicular fluid ( GCF ) after using FS and suture for periodontal flap closure .


Thirty selected quadrants in @ periodontitis patients were randomly assigned to either a test ( fibrining ) or control group ( suturing ) for flap closure .


IL-@ and IL-@ were assessed in GCF using enzyme-linked immunosorbent assay ( ELISA ) before and eight days after surgery .


Patients were recalled at @ , @ , @days and @months after surgery for clinical assessment .


There was a statistically significant decrease in IL-@ ( @ , @ pg/l ) and IL-@ ( @ , @ pg/l ) levels in the test side after fibrining while there was an increase in the control side ( IL-@ @ , @ ; IL-@ @ , @ pg/l ) ( p < @ ) .


The change in concentration of IL-@ and IL-@ following intervention correlated significantly in both the sites .


Clinical parameters differed significantly only on the seventh day with less plaque and bleeding on the test sites .


Fibrin sealant enhances early wound healing by reducing inflammation after periodontal flap surgery .


Continuous lumbar plexus block ( LPB ) is a well-accepted technique for regional analgesia after THA .


However , many patients experience considerable quadriceps motor weakness with this technique , thus impairing their ability to achieve their physical therapy goals .


We asked whether L@ paravertebral block ( PVB ) provides better postoperative analgesia ( defined as decreased postoperative opioid consumption and lower pain scores ) , better preservation of motor function , and decreased length of hospital stay ( LOS ) compared to LPB in patients undergoing THA .


Sixty patients undergoing minimally invasive THA under standardized spinal anesthesia were enrolled in this randomized controlled study .


After exclusions , @ patients were randomized into the L@ PVB ( n = @ ) and LPB ( n = @ ) groups .


Patient-controlled analgesia was available for @ hours .


Motor and pain assessments were performed in the recovery room and at the end of @ hours .


LOS was also noted .


Postoperative opioid consumption during the first @ hours was less in the LPB group ( mean SD : @ @ mg morphine ) than in the L@ PVB group ( @ @ mg morphine ; p = @ ) ; however , postoperative pain scores were not different between groups .


Postoperative motor and rehabilitation outcomes and LOS were also similar .


Our study demonstrates that use of a LPB results in slightly less morphine consumption but comparable pain scores when compared with continuous L@ PVB .


No difference was noted in terms of motor preservation or LOS .


Although the difference in morphine consumption was only slightly in favor of the LPB group , the advantage of L@ PVBs noted by previous authors as preservation of motor function , was not seen .


At our institute where LPBs have been performed for years , there seems to be no real advantage in switching to L@ PVBs .


However , L@ PVB could be a reasonable alternative for operators who are wary of LPBs due to their high potential for complications and/or requiring advanced skills for its placement .


But , since L@ PVBs are relatively new , not much is known about their complication profile .


We recommend a thorough understanding of both techniques before attempting to place them .


Level I , therapeutic study .


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


Annually approximately @ patients undergo a laparotomy in the Netherlands .


About @,@ of these patients will develop an incisional hernia .


Both open and laparoscopic surgical repair have been proven to be safe .


However , the most effective treatment of incisional hernias remains unclear .


This study , the ` INCH-trial ' , comparing cost-effectiveness of open and laparoscopic incisional hernia repair , is therefore needed .


A randomized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias .


Patients with a symptomatic incisional hernia , eligible for laparoscopic and open incisional hernia repair .


Only surgeons , experienced in both open and laparoscopic incisional hernia repair , will participate in the INCH trial .


During incisional hernia repair , a mesh is placed under or on top of the fascia , with a minimal overlap of @ cm .


Primary endpoint is length of hospital stay after an incisional hernia repair .