We also calculated average values of the following electrophysiological parameters : @ ) area and @ ) duration of the rectified EMG signal from the suprahyoid/submental muscles related to the sucking and swallowing phases ; @ ) EMG peak amplitude for the sucking and swallowing phases ; @ ) area and peak amplitude of the laryngeal-pharyngeal mechanogram ; @ ) oropharyngeal delay .


The volume of the ingested bolus significantly increased ( by an average of about @ % compared with the baseline value ) both at @ and at @ min after the end of anodal tDCS .


The electrophysiological evaluation after anodal tDCS showed a significant increase in area and duration of the sucking phase-related EMG signal .


Anodal tDCS leads to stronger sucking of a liquid bolus in healthy subjects , likely by increasing recruitment of cortical areas of the swallowing network .


This finding might open up interesting perspectives for the treatment of patients suffering from dysphagia due to various pathological conditions .


The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual ( CAU ) for patients with anxiety , depressive or stress-related disorders within a primary health care context .


To compare the effects of cognitive-based-behavioural therapy ( CBT ) and multimodal intervention ( MMI ) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre .


Patients ( n = @ ) , aged @-@ years , were referred to the study by the GPs and @ were randomized to CAU or one of two group interventions in addition to CAU : ( i ) group CBT administered by psychologists and ( ii ) group MMI administered by assistant nurses .


The primary outcome measure was the Mental Component Summary score of short form @ .


Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes .


The data were analysed using intention-to-treat with a linear mixed model .


On the primary outcome measure , the mean improvement based on mixed model analyses across post - and follow-up assessment was significantly larger for the MMI group than for the CBT ( @ ; P = @ ) and CAU ( @ ; P = @ ) groups .


Participants receiving CBT were significantly more improved than those in the CAU group .


On four of the secondary outcome measures , the MMI group was significantly more improved than the CBT and CAU groups .


The course of improvement did not differ between the CBT group and the CAU group on these measures .


Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting .


The group format and transdiagnostic approach fit well with the requirements of primary care .


The present study examines the role of comorbid anxiety on depression outcomes for those receiving cognitive behavioral therapy ( CBT ) for depression by telephone ( T-CBT ) or face-to-face ( FtF-CBT ) .


Three hundred twenty-five participants were randomized to T-CBT or FtF-CBT .


Comorbid anxiety was measured using the Mini International Neuropsychiatric Interview and Generalized Anxiety Disorder @ .


Depression was measured using the Hamilton Rating Scale for Depression and Patient Health Questionnaire @ .


A hierarchical model including the two-way interaction of treatment assignment and anxiety status indicated a significant effect for all outcome variables ( Ps < @ ) .


Post hoc t tests indicated T-CBT participants with comorbid anxiety disorders had significantly higher symptom severity over time compared to their T-CBT counterparts without anxiety ( Ps < @ ) and FtF-CBT counterparts with comorbid anxiety ( Ps < @ ) .


There were no significant differences in outcomes between those with and without comorbid anxiety disorders receiving FtF-CBT , or between T-CBT and FtF-CBT among those without comorbid anxiety disorders .


The findings indicate that the presence of baseline anxiety impacts the overall effect of T-CBT for the treatment of depression .


Cardiac rehabilitation ( CR ) is a secondary prevention program that offers education and support to assist patients with coronary heart disease ( CHD ) make lifestyle changes .


Despite the benefits of CR , attendance at centre-based sessions remains low .


Mobile technology ( mHealth ) has potential to reach more patients by delivering CR directly to mobile phones , thus providing an alternative to centre-based CR .


The aim of this trial is to evaluate if a mHealth comprehensive CR program can improve adherence to healthy lifestyle behaviours ( for example , physically active , fruit and vegetable intake , not smoking , low alcohol consumption ) over and above usual CR services in New Zealand adults diagnosed with CHD .


A two-arm , parallel , randomised controlled trial will be conducted at two Auckland hospitals in New Zealand .


One hundred twenty participants will be randomised to receive a @-week evidence - and theory-based personalised text message program and access to a supporting website in addition to usual CR care or usual CR care alone ( control ) .


The primary outcome is the proportion of participants adhering to healthy behaviours at @months , measured using a composite health behaviour score .


Secondary outcomes include overall cardiovascular disease risk , body composition , illness perceptions , self-efficacy , hospital anxiety/depression and medication adherence .


This study is one of the first to examine an mHealth-delivered comprehensive CR program .


Strengths of the trial include quality research design and in-depth description of the intervention to aid replication .


If effective , the trial has potential to augment standard CR practices and to be used as a model for other disease prevention or self-management programs .


Use of TIPSS is associated with increases in ammonia concentration and hepatic encephalopathy ( HE ) risk .


L-ornithine-L-aspartate ( LOLA ) is effective in reducing ammonia concentration .


To evaluate the effects of LOLA on venous ammonia concentration after TIPSS .


The included patients were randomised to receive LOLA or no-LOLA treatment for @ days .


Fasting and post-prandial venous ammonia levels were the primary outcomes .


Psychometric performance , post-TIPSS HE , and liver and renal function were assessed as secondary outcomes .


Of @ cirrhotic patients who received successful TIPSS between November @ and June @ , @ met the inclusion criteria and were randomised to the LOLA ( n = @ ) or control ( n = @ ) groups .


Change in fasting ammonia significantly favoured the LOLA group at days @ ( P = @ ) and @ ( P = @ ) .


Changes in post-prandial ammonia concentration significantly favoured the LOLA group at days @ , @ and @ as well .


During the study period , patients in the LOLA group had better improvement in psychometric tests than those in the control group .


Overt HE during treatment was observed in one patient in the LOLA group and three patients in the control group ( P = @ ) .


There were no differences in complications , adverse events or mortality between the two groups .


Prophylactic use of LOLA infusion after TIPSS is safe and effective in significantly reducing the increase of venous ammonia concentration , and can benefit the patient 's mental status as well .


Median sternotomy , sternal spreading , and sternal wiring are the main causes of pain during the early recovery phase following cardiac surgery .


This study was designed to evaluate the analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after parasternal block following cardiac surgery .


The total of @ patients ( American Society of Anesthesiologist status II , III ) , @-@ years old , undergoing coronary-artery bypass grafting were enrolled in this prospective , randomized , double-blind study .


A presternal catheter was inserted with continuous infusion of @ mL/h bupivacaine @ % ( Group B ) or normal saline ( Group C ) during the first @ postoperative hrs .


Primary outcomes were postoperative morphine requirements and pain scores , secondary outcomes were extubation time , postoperative respiratory parameters , incidence of wound infection , Intensive Care Unit ( ICU ) and hospital stay duration , and bupivacaine level in blood .


Student 's t-test was used to analyze the parametric data and Chi-square test for categorical variables .


During the postoperative @ h , there was marked reduction in morphine requirements in Group B compared to Group C , ( @ @ mg vs. @ @ mg respectively , P = @ ) , lower postoperative pain scores , shorter extubation time ( @ @ min vs. @ @ min , respectively , P = @ ) , better respiratory parameters ( PaO @ / FiO @ , PaCO @ and pH ) , with no incidence of wound infection , no differences in ICU or hospital stay duration .


The plasma concentration of bupivacaine remained below the toxic threshold ( at T@ , @ ug/ml @ and T@ h @ @ ug/ml ) .


Continuous presternal bupivacaine infusion has resulted in better postoperative analgesia , reduction in morphine requirements , shorter time to extubation , and better postoperative respiratory parameters than the control group .


We investigated the efficacy and safety of the sodium glucose cotransporter @ inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type @ diabetes mellitus ( T@DM ) .


Patients inadequately controlled on MDI insulin metformin ( mean HbA@c @ % -LSB- @ mmol/mol -RSB- ; BMI @ kg/m ( @ ) ; insulin dose @ international units/day ) were randomized and treated with once-daily empagliflozin @ mg ( n = @ ) , empagliflozin @ mg ( n = @ ) , or placebo ( n = @ ) for @ weeks .


Insulin dose was to remain stable in weeks @-@ , adjusted to meet glucose targets in weeks @-@ , then stable in weeks @-@ .


The primary end point was change from baseline in HbA@c at week @ .


Secondary end points were changes from baseline in insulin dose , weight , and HbA@c at week @ .


Adjusted mean SE changes from baseline in HbA@c were -@ @ % ( -@ @ mmol/mol ) for placebo versus -@ @ % ( -@ @ mmol/mol ) and -@ @ % ( -@ @ mmol/mol ) for empagliflozin @ mg and empagliflozin @ mg , respectively , at week @ ( both P < @ ) .


At week @ , further reductions with insulin titration resulted in changes from baseline in HbA@c of -@ @ % ( -@ @ mmol/mol ) , -@ @ % ( -@ @ mmol/mol ) , and -@ @ % ( -@ @ mmol/mol ) with placebo , empagliflozin @ mg , and empagliflozin @ mg , respectively , and final HbA@c of @ % ( @ mmol/mol ) , @ % ( @ mmol/mol ) , and @ % ( @ mmol/mol ) , respectively .


More patients attained HbA@c < @ % ( < @ mmol/mol ) with empagliflozin ( @-@ % ) versus placebo ( @ % ; both P < @ ) .


Empagliflozin @ mg and empagliflozin @ mg reduced insulin doses ( -@ to -@ international units/day ) and weight ( -@ to -@ kg ) versus placebo ( all P < @ ) at week @ .


In obese , difficult-to-treat patients with T@DM inadequately controlled on high MDI insulin doses , empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements .


At present , school-age children suffer high levels of chronic stress that could produce potentially long-lasting effects .


The aim of this pilot study was to evaluate the effects of mind-body integration practices and cooperative activities on stress levels and social interaction in @ - to @-year-old children .


We performed an intervention program once a week during @ months in which children performed mind-body integration practices and cooperative activities .


Our findings showed that these practices reduced cortisol levels and increased social connectedness .


Moreover , we found that most of the children used the learned mind-body integration practices in stressful situations in their homes , even @ months after the intervention .


Our results demonstrated the positive impact of these helpful tools and the great plasticity of children 's behavior , which enabled them to incorporate healthy habits .


Overall , the intervention enhanced health at an individual level and favored social network diversity at a group level .


Our research illustrates how children can incorporate techniques that help them cope with stressful moments and reveals the effectiveness of this experience in reducing cortisol levels .


This study contributes to the understanding of how mind-body integration practices and social connectedness can be helpful in reducing chronic stress , a topic that , to the best of our knowledge , has been little studied in children .


Interactions between the microbial flora of the intestine and the human host play a critical role inmaintaining intestinal health and in the pathophysiology of a wide variety of disorders such as antibiotic associated diarrhea , Clostridium difficile infection , and inflammatory bowel disease .


Prebiotics can confer health benefits by beneficial effects on the intestinal microbiome , whereas antibiotics can disrupt the microbiome leading to diarrhea andother side effects .


To compare the effects of the prebiotic , polysaccharopeptide from Trametes versicolor , to those of the antibiotic , amoxicillin , on the human gut microbiome


Twenty-four healthy volunteers were randomized to receive PSP , amoxicillin , or no treatment ( control ) .


Stool specimens were analyzed using bTEFAP microbial ecology methods on seven occasions over @ weeks from each participant in the active treatment groups and on three occasions for the controls .


Twenty-two of @ participants completed the protocol .


PSP led to clear and consistent microbiome changes consistent with its activity as a prebiotic .


Despite the diversity of the human microbiome we noted strong microbiome clustering among subjects .


Baseline microbiomes tended to remain stable and to overshadow the treatment effects.Amoxicillin treatment caused substantial microbiome changes most notably an increase in Escherichia/Shigella .


Antibiotic associated changes persisted to the end of the study , @ days after antibiotic therapy ended .


The microbiomes of healthy individuals show substantial diversity but remain stable over time.The antibiotic amoxicillin alters the microbiome and recovery from this disruption can take several weeks .


PSP from T. versicolor acts as a prebiotic to modulate human intestinal microbiome composition .


To determine the feasibility and clinical efficacy of ultrasound-guided facet joint injection and nerve block in lumbar facet joint for the treatment of facet-joint related low back pain .


@ patients with facet-joint pain were randomized into two groups received block blindly ( B group ) or guided by ultrasound ( US group ) respectively .


The location of needle tip was confirmed by CT in both groups , and the accuracy was computed afterwards .


VAS score , puncture time and one-time puncture success rate ( % ) were recorded .


VAS scores and pain remission rates in both groups were recorded at @ min , @ d , @ d , @ weeks after the block .


The VAS scores were @ + / - @ in US group and @ + / - @ in B group ( P < @ ) .


The puncture time was ( @ + / - @ ) s in US group while ( @ + / - @ ) s in B group ( P < @ ) .


There were @ facet joint blocks guided by ultrasound , in which @ were correctly targeted with the first puncture .


The success rate is @ % .


There were @ facet joint blocks blindly , in which @ were correctly targeted with the first puncture .


The difference of one-time puncture success rate between the two groups was significant ( P < @ ) .


Differences of VAS and pain remission rate at half an hour after facet joint injection between B group and US group were significant ( P < @ ) .


There were @ , @ , @ , and @ patients in US group obtaining a reduction in VAS scores > or = @ at @ min , @ d , @ d and @ weeks after the procedure respectively , while the numbers of such patients were @ , @ , @ , @ in B group ( P > @ ) .


After @ weeks of follow-up , the overall remission rates were ( @ + / - @ ) % in US group , and ( @ + / - @ ) % in B group , there was no significant difference between the two groups ( P > @ ) .


The ultrasound-guided lumbar facet joint injection technique had a high feasibility and accuracy , and had better clinical efficacy than block blindly .


Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury ( SCI ) .


Antidepressants are used routinely to treat depression , yet no placebo-controlled trials have been published in this population to our knowledge .


To determine the efficacy and tolerability of venlafaxine hydrochloride extended-release ( XR ) for major depressive disorder ( MDD ) or dysthymic disorder in persons with chronic SCI .


Multisite , randomized ( @:@ ) , double-blind , placebo-controlled Project to Improve Symptoms and Mood After SCI ( PRISMS ) trial .


All research staff conducting screening , intervention , and outcome procedures were blinded to randomization status .


We screened @ patients from outpatient clinics at @ SCI treatment centers in the United States and randomized @ participants into the trial .


Participants were @ to @ years old and at least @ month after SCI , with MDD or dysthymic disorder .


Seventy-four percent of participants were male , and participants were on average @ years old and @ years after SCI .


Forty-seven percent had cervical injuries , @ % had American Spinal Injury Association injury severity A ( complete injury ) SCI , @ % had at least @ prior MDD episodes , and @ % had current MDD .


Common comorbidities included chronic pain ( @ % ) , significant anxiety ( @ % ) , and history of substance dependence ( @ % ) .


Twelve-week trial of venlafaxine XR vs placebo using a flexible-dose algorithm .


The Hamilton Depression Rating Scale ( HAM-D @-item version and Maier subscale , which focuses on core depression symptoms and excludes somatic symptoms ) over @ weeks .


Mixed-effects models revealed a significant difference between the venlafaxine XR and placebo groups in improvement on the Maier subscale from baseline to @ weeks ( treatment effect , @ ; @ % CI , @-@ @ ; P = @ ) but not on the HAM-D @-item version ( treatment effect , @ ; @ % CI , -@ to @ ; P = @ ) .


Participants receiving venlafaxine XR reported significantly less SCI-related disability on the Sheehan Disability Scale at @ weeks compared with placebo ( treatment effect , @ ; @ % CI , @-@ @ ; P = @ ) .


Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine XR group compared with the placebo group over @ weeks .


Venlafaxine XR was well tolerated by most patients and an effective antidepressant for decreasing core symptoms of depression and improving SCI-related disability .


Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic SCI .


Epidemiological evidence suggests that physical activity benefits cognition , but results from randomized trials are limited and mixed .


To determine whether a @-month physical activity program results in better cognitive function , lower risk of mild cognitive impairment ( MCI ) or dementia , or both , compared with a health education program .


A randomized clinical trial , the Lifestyle Interventions and Independence for Elders ( LIFE ) study , enrolled @ community-living participants at @ US centers from February @ until December @ .


Participants were sedentary adults aged @ to @ years who were at risk for mobility disability but able to walk @ m.


A structured , moderate-intensity physical activity program ( n = @ ) that included walking , resistance training , and flexibility exercises or a health education program ( n = @ ) of educational workshops and upper-extremity stretching .


Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding ( DSC ) task subtest of the Wechsler Adult Intelligence Scale ( score range : @-@ ; higher scores indicate better function ) and the revised Hopkins Verbal Learning Test ( HVLT-R ; @-item word list recall task ) assessed in @ participants ( @ % ) .


Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at @ months .


At @ months , DSC task and HVLT-R scores ( adjusted for clinic site , sex , and baseline values ) were not different between groups .


The mean DSC task scores were @ points for the physical activity group vs @ for the health education group ( mean difference , -@ points -LSB- @ % CI , -@ to @ points -RSB- , P = @ ) .


The mean HVLT-R delayed recall scores were @ for the physical activity group vs @ for the health education group ( mean difference , -@ words -LSB- @ % CI , -@ to @ words -RSB- , P = @ ) .


No differences for any other cognitive or composite measures were observed .


Participants in the physical activity group who were @ years or older ( n = @ ) and those with poorer baseline physical performance ( n = @ ) had better changes in executive function composite scores compared with the health education group ( P = @ for interaction for both comparisons ) .


Incident MCI or dementia occurred in @ participants ( @ % ) in the physical activity group and @ participants ( @ % ) in the health education group ( odds ratio , @ -LSB- @ % CI , @ to @ -RSB- ) .


Among sedentary older adults , a @-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function .


To evaluate the effect of expert guided mentorship on technical score and time for a set of robotic training drills .


Prospective randomized controlled trial ( Canadian Task Force classification I ) .


Academic institution .


Fifty trainees in robotic surgery .


Inexperienced trainees underwent either a @-minute expert guided mentorship session or no intervention .


The primary outcomes were technical score and time-to-drill completion for a set of dry lab robotic training drills evaluated at an initial and final skills assessment .


The t-test , including paired analyses , was used to evaluate outcomes .


Forty-nine of @ trainees ( @ % ) completed the study .


There were no significant differences in participant characteristics or initial performance between the @ groups .


During the final skills assessment , the intervention group demonstrated significantly better performance on @ of @ objective measures .


They had a higher mean score for the bead transfer drill when compared with the control group ( @ vs @ ; p = @ ) .


No differences in time-to-drill completion were noted between the @ groups .


Regardless of randomization , all participants had significantly improved scores for each of the drills on the final compared with the initial skills assessment ( p < @ ) .


Although expert guided mentorship in a dry lab simulation environment seems feasible , further investigation is warranted before its widespread use because it may be more resource intensive than other teaching methods , without consistent objective improvements in technical performance .


Lithium has been widely used to treat bipolar affective disorder for over @years .


Still , its acute effects in human cerebral cortex are poorly understood .


This study aimed at investigating the acute effects of lithium on motor cortex excitability as measured by transcranial magnetic stimulation ( TMS ) .


Ten healthy young adults participated in a double-blind placebo-controlled randomized crossover study with four sessions , where a single oral dose of lithium carbonate ( @mg , @mg , or @mg ) or placebo was tested .


Focal TMS of the hand area of left motor cortex was used to test resting and active motor thresholds , motor evoked potential input-output curve ( MEP IO-curve ) , slope of the MEP IO-curve and paired-pulse measures of intracortical inhibition and facilitation before , and two and four hours after drug administration .


Two hours post drug administration , @mg of lithium carbonate increased the slope of the MEP IO-curve while @mg tended to decrease it .


Lithium had no effect on motor thresholds , or intracortical inhibition or facilitation .


The acute effects of lithium on MEP IO-curve , a marker of corticospinal excitability , are consistent with an inverted U-shaped dose-response relationship .


Findings are important for our understanding of the therapeutic and toxic effects of lithium on the human central nervous system .


The rising number of children in daycare nurseries increases opportunities for the transmission of infectious diseases .


Pathogens may be transmitted directly from child to child via sneezing , coughing and touching , or indirectly via the environment .


Toys are among the fomites with the highest pathogen load , but their role in disease transmission is unknown .


To determine if washing and disinfection of toys can reduce sickness absence and microbial pathogen load in the nursery environment .


Twelve nurseries ( caring for @ children ) were randomized to intervention and control groups .


The intervention consisted of washing and disinfection of toys and linen every two weeks for three months by a commercial cleaning company .


The extent and causes of sickness absence among the children were recorded in both groups before and after introduction of the intervention .


Ten sampling points in each nursery were examined for bacteria and respiratory viruses .


The presence of respiratory virus DNA/RNA was widespread , but very few pathogenic bacteria were found in the environment .


The intervention reduced the presence of adenovirus -LSB- odds ratio ( OR ) @ , @ % confidence interval ( CI ) @-@ @ -RSB- , rhinovirus ( OR @ , @ % CI @-@ @ ) and respiratory syncytial virus ( OR @ , @ % CI @-@ @ ) compared with the control group , but the intervention had no effect on sickness absence or disease patterns in the nurseries .


Although cleaning and disinfection of toys every two weeks can decrease the microbial load in nurseries , it does not appear to reduce sickness absence among nursery children .


Acute kidney injury ( AKI ) remains a deadly condition .


Tissue inhibitor of metalloproteinases ( TIMP ) -@ and insulin-like growth factor binding protein ( IGFBP ) @ are two recently discovered urinary biomarkers for AKI .


We now report on the development , and diagnostic accuracy of two clinical cutoffs for a test using these markers .


We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease : Improving Global Outcomes Stages @-@ AKI within @ h using data from a previously published multicenter cohort ( Sapphire ) .


Next , we verified these cutoffs in a new study ( Opal ) enrolling @ critically ill adults from six sites in the USA .


One hundred subjects ( @ % ) in Sapphire and @ ( @ % ) in Opal met the primary end point .


The results of the Opal study replicated those of Sapphire .


Relative risk ( @ % CI ) in both studies for subjects testing at @ versus > @-@ were @ ( @-@ ) and @ ( @-@ @ ) , or @ ( @-@ ) and @ ( @-@ ) for @ versus > @ .


For the @ cutoff , sensitivity was @ % in both studies , and specificity @ and @ % .


For @ , sensitivity was @ and @ % , and specificity @ and @ % .


Urinary -LSB- TIMP-@ -RSB- -LSB- IGFBP@ -RSB- values of @ or greater identify patients at high risk and those > @ at highest risk for AKI and provide new information to support clinical decision-making .


To study the effect of somatostatin in patients with advanced gastric cancer who received D@ lymphadenectomy and vagina vasorum dissection .


Using a prospective , single-blind , placebo-controlled design , patients with advanced gastric cancer were randomized into a study group ( n = @ ) and a control group ( n = @ ) .


Patients in the study group were given somatostatin for @-@ d starting @ h after the operation , and patients in the control group were given normal saline .


Preoperative and nonoperative complications in the perioperative period , as well as different types of postoperative drainage in the two groups were compared .


There was no significant difference between the study group and the control group for preoperative clinicopathological indicators .


We found no significant difference between the two groups for the overall incidence of complications , but a lower percentage of peritoneal effusion was observed in the treatment group ( @ % vs @ % , P < @ ) .


There were no significant differences between the two groups in the incidence of postoperative pancreatic dysfunction and chylous fistula .


However , there were significant differences in the amylase concentration in drainage fluid , volume and duration of drainage , volume and duration of chylous fistula and peritoneal drainage , and volume and duration of gastric tube drainage .


The study group did not show any increase in mean hospitalization cost and the cost reduced when the postoperative complications occurred .


Postoperative somatostatin reduces volume and duration of surgical drainage and related complications .


Somatostatin may improve safety of gastric cancer surgery , reducing postoperative complications and promoting recovery .


mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss , by sensitising PTEN-deficient tumours to trastuzumab .


The BOLERO-@ study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER@-positive advanced breast cancer .


In this phase @ , randomised , double-blind trial , patients were enrolled across @ sites in @ countries .


Eligible patients were aged @ years or older , with locally assessed HER@-positive advanced breast cancer , with Eastern Cooperative Oncology Group ( ECOG ) performance status of @-@ , who had not received previous trastuzumab or chemotherapy for advanced breast cancer within @ months of randomisation , had measurable disease as per Response Evaluation Criteria in Solid Tumors ( RECIST ) or bone lesions in the absence of measurable disease , without previous systemic treatment for advanced disease except endocrine therapy .


Patients were randomly assigned ( @:@ ) with an interactive voice and web response system to receive either @ mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at @ mg/kg loading dose on day @ with subsequent weekly doses of @ mg/kg of each @ week cycle plus paclitaxel intravenously at a dose of @ mg/m ( @ ) on days @ , @ , and @ of each @ week cycle .


Randomisation was stratified according to previous use of trastuzumab and visceral metastasis .


Patients and investigators were masked to the assigned treatments .


Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging , labelling , appearance , and administration schedule .


The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline ; the latter was added during the course of the study , before unmasking based on new clinical and biological findings from other studies .


All efficacy analyses were based on the intention-to-treat population .


Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here .


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


Between Sept @ , @ , and Dec @ , @ , @ patients were randomly assigned to receive everolimus ( n = @ ) or placebo ( n = @ ) .


Median follow-up was @ months ( IQR @-@ ) .


In the full population , median progression-free survival was @ months ( @ % CI @-@ ) with everolimus versus @ months ( @-@ ) with placebo ( hazard ratio @ , @ % CI @-@ ; p = @ ) .


In the HR-negative subpopulation ( n = @ ) , median progression-free survival with everolimus was @ months ( @ % CI @-@ ) versus @ months ( @-@ ) with placebo ( hazard ratio @ , @ % CI @-@ ; p = @ ) ; however , the protocol-specified significance threshold ( p = @ ) was not crossed .


The most common adverse events with everolimus were stomatitis ( @ -LSB- @ % -RSB- of @ patients in the everolimus group vs @ -LSB- @ % -RSB- of @ patients in the placebo group ) , diarrhoea ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- patients ) , and alopecia ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) .


The most frequently reported grade @ or @ adverse events in the everolimus group versus the placebo group were neutropenia ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) , stomatitis ( @ -LSB- @ % -RSB- vs three -LSB- @ % -RSB- ) , anaemia ( @ -LSB- @ % -RSB- vs six -LSB- @ % -RSB- ) and diarrhoea ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- ) On-treatment adverse event-related deaths were reported in @ ( @ % ) patients in the everolimus group and none in the placebo group .


Although progression-free survival was not significantly different between groups in the full analysis population , the @ months prolongation we noted with the addition of everolimus in the HR-negative , HER@-positive population warrants further investigation , even if it did not meet prespecified criteria for significance .


The safety profile was generally consistent with what was previously reported in BOLERO-@ .


Proactive monitoring and early management of adverse events in patients given everolimus and chemotherapy is crucial .


To explore the selective retention of the great saphenous vein trunk below the knee to prevent saphenous nerve injury during varicose vein surgery .


This research was a single-center prospective randomized trial .


From January @ to January @ , @ patients of varicose veins in the great saphenous vein were treated and divided into two groups of @ cases each .


In the observation group , the vascular trunk of the great saphenous vein was stripped to below the knee level whilst that in the control group , it was stripped to the ankle level .


Patients in both groups were treated with a transilluminated powered phlebectomy ( TIPP ) and foam sclerotherapy .


Primary end points were postoperative pain , saphenous nerve injury , quality of life and recurrence rate .


After one month follow-up : @ % of patients in the observation group had neurological symptoms , while @ % of patients had neurological symptoms in the control group .


The saphenous nerve injury between the two groups was statistically significant .


Postoperative follow-up of one year , @ % patients had symptoms of neurological disorders in the observation group , while @ % patients had symptoms of neurological disorders in the control group .


Therefore , selective retention of great saphenous vein below-knee can prevent saphenous nerve injury .


The main outcome measures were postoperative pain , missing saphenous nerve , improvement of symptoms and the incidence of recurrence .


The follow-up after one month showed that the percentage of neurological symptoms in the observation group and the control group was @ % and @ % respectively , and the saphenous nerve injury showed a statistical difference .


The follow-up after one year showed @ % of abnormal sensation in the observation group and @ % of dysesthesia or paresthesia in the control group in surgical limb according to subjects ' claims , and there existed a statistical difference in the saphenous nerve injury .


The selective retention of the great saphenous vein trunk below the knee can prevent the saphenous nerve injury .


Shared decision making is a promising model for patient-centred medicine , resulting in better clinical outcomes overall .


In the mental health field , interventions that consider the patient-centred perspective -- such as patient quality of life , involvement in the treatment , treatment satisfaction , and working alliance -- have increased and better clinical outcomes discovered for patients with schizophrenia .


However , few studies have examined the efficacy of shared decision making for schizophrenia treatment .


The objective of this study is to evaluate the effect of a shared decision making intervention compared to treatment as usual on patient satisfaction at discharge for first-admission patients with schizophrenia .


This is a randomised , parallel-group , two-arm , open-label , single-centre study currently being conducted in an acute psychiatric ward of Numazu Chuo Hospital , Japan .


We are recruiting patients between @ and @ years old who are admitted to the ward with a diagnosis of schizophrenia without prior experience of psychiatric admission .


Fifty-eight participants are being randomised into a shared decision making intervention group or a treatment as usual control group in a @:@ ratio .


The intervention program was developed based on a shared decision making model and is presented as a weekly course lasting the duration of the patients ' acute psychiatric ward stay .


The primary outcome measure is patient satisfaction at discharge as assessed by the Client Satisfaction Questionnaire .


Due to the study 's nature , neither the patient nor staff can be blinded .


This is the first randomised controlled trial to evaluate the efficacy of shared decision making for patients with early-treatment-stage schizophrenia .


The intervention program in this study is innovative in that it includes both of the patient and staff who are involved in the treatment .


Orbital inflammation is a potentially blinding and disfiguring disease process that is often treated with systemic corticosteroids and immunosuppression ; better treatments are needed .


To determine whether rituximab , a monoclonal antibody against the B-lymphocyte antigen CD@ , is effective in the treatment of refractory orbital inflammation .


A dose-ranging , randomized , double-masked phase @/@ clinical trial was conducted at a tertiary referral ophthalmology clinic .


Ten individuals with orbital inflammation refractory to systemic corticosteroids and at least @ other immunosuppressive agent were enrolled from January @ to March @ .


Rituximab infusions were administered on study days @ and @ at doses of either @ mg or @ mg .


Initial responders with recurrent inflammation after week @ were permitted reinfusion with an additional cycle of @ open-label @-mg rituximab infusions .


The primary outcomes were reduction of inflammation measured with a validated orbital disease grading scale and corticosteroid dose reduction by at least @ % .


The secondary outcomes were visual acuity , reduction in pain , and participant - and physician-reported global health assessment .


Of @ enrolled patients , @ demonstrated improvement on the orbital disease grading scale at the @-week end point with rituximab therapy .


Of these @ individuals , @ were receiving corticosteroids at study inception and all achieved successful dose reduction .


For the secondary outcome measures in the @ participants , @ patients and @ patients improved in self-rated and physician global health scores , respectively , and @ patients had reduction in pain by @ % or more at @ weeks .


Four patients who were positive responders at the week @ end point experienced breakthrough inflammation after week @ and received reinfusions between @ and @ weeks .


Vision remained stable in all participants .


Three of @ patients had short-term objective or subjective worsening @ to @ weeks after receiving rituximab infusions , which was averted in subsequent patients with oral corticosteroids administered during the infusion and did not affect the eventual positive treatment outcome .


No significant differences with regard to efficacy , toxicity , or likelihood of retreatment were noted between the dosing arms .


Rituximab was safe and effective in @ of @ patients with noninfectious orbital disease , although @ required reinfusion with rituximab to maintain control of orbital inflammation .


Substantial toxicity was not noted .


Rituximab should be considered in the treatment of refractory orbital inflammation .


The most prevalent phenotype of asthma is characterized by eosinophil-dominated inflammation that is driven by a type @ helper T cell ( Th@ ) .


Therapeutic targeting of GATA@ , an important transcription factor of the Th@ pathway , may be beneficial .


We evaluated the safety and efficacy of SB@ , a novel DNA enzyme ( DNAzyme ) that is able to cleave and inactivate GATA@ messenger RNA ( mRNA ) .


We conducted a randomized , double-blind , placebo-controlled , multicenter clinical trial of SB@ involving patients who had allergic asthma with sputum eosinophilia and who also had biphasic early and late asthmatic responses after laboratory-based allergen provocation .


A total of @ patients could be evaluated ; @ were assigned to receive @ mg of SB@ , and @ were assigned to receive placebo , with each study drug administered by means of inhalation once daily for @ days .


An allergen challenge was performed before and after the @-day period .


The primary end point was the late asthmatic response as quantified by the change in the area under the curve ( AUC ) for forced expiratory volume in @ second ( FEV@ ) .


After @ days , SB@ attenuated the mean late asthmatic response by @ % , as compared with the baseline response , according to the AUC for FEV@ , whereas placebo was associated with a @ % increase in the AUC for FEV@ ( P = @ ) .


The early asthmatic response with SB@ was attenuated by @ % as measured by the AUC for FEV@ , whereas the early response with placebo was increased by @ % ( P = @ ) .


Inhibition of the late asthmatic response by SB@ was associated with attenuation of allergen-induced sputum eosinophilia and with lower levels of tryptase in sputum and lower plasma levels of interleukin-@ .


Allergen-induced levels of fractional exhaled nitric oxide and airway hyperresponsiveness to methacholine were not affected by either SB@ or placebo .


Treatment with SB@ significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma .


Biomarker analysis showed an attenuation of Th@-regulated inflammatory responses .


( Funded by Sterna Biologicals and the German Federal Ministry of Education and Research ; ClinicalTrials.gov number , NCT@ . )


Odanacatib is a cathepsin K inhibitor in development for the treatment of osteoporosis .


Evaluation of therapies to ensure that treatment effects are relevant regardless of sex is clinically important .


In this double-blind , randomized controlled trial , older men ( aged @-@ years ) and postmenopausal women ( aged @-@ years ) were given odanacatib @ mg once weekly or placebo for @ weeks .


Pharmacodynamic ( PD ) evaluation measured weighted average inhibition ( WAI ) of urine amino-terminal cross-linked telopeptide of type I collagen/creatinine ( uNTx/Cr ) after odanacatib administration .


Pharmacokinetic ( PK ) parameter data were collected , and an analysis of sex as a factor in the PK/PD relationship was conducted .


Adverse events were monitored .


The hypotheses were that WAI of uNTx/Cr would be > @ % ( including > @ % for the lower limit of the @ % confidence intervals -LSB- CIs -RSB- ) for older men and postmenopausal women , that there would be no important differences in area under the curve from @ to @ hours ( AUC@-@ h ) between men and women , and that odanacatib would be safe and well tolerated .


A total of @ subjects ( @ men and @ women ) were randomized .


The least squares mean WAI ( uNTx/Cr ) at week @ was @ % ( @ % CI , @ % -@ % ) for men and @ % ( @ % CI , @ % -@ % ) for women ; mean values were > @ % , but lower bounds were < @ % as prespecified in the primary hypothesis .


The differences among men and women in PD parameters were not meaningful ( @ ; @ % CI , -@ to @ ) .


PK parameters for both groups were comparable ( geometric mean ratio of AUC@-@ h , @ ; @ % CI , @-@ @ ) .


A PK/PD analysis found that the EC@ and maximum fractional inhibition were similar in male and female subjects .


There were no notable or serious adverse events in this study .


Although the primary hypothesis was not met , there were no clinically meaningful differences in PD , PK , or PK/PD parameters between older men and postmenopausal women , supporting further research on odanacatib ( @ mg once weekly ) as a treatment for male osteoporosis .


Odanacatib was generally well tolerated .


To explore relationships between baseline and changes in fatigue during treatment with outcomes in patients with major depressive disorder ( MDD ) receiving citalopram monotherapy .


Secondary analyses of data from the Sequenced Treatment Alternatives to Relieve Depression ( STAR * D ) Level @ treatment phase ( @ weeks citalopram monotherapy ) .


Fatigue was assessed with item @ on energy level from the @-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR@ ; scored @-@ : @ = no fatigue , @ = maximal fatigue ) ; prospective fatigue : assessment of fatigue at Level @ entry and exit ( no fatigue , treatment-emergent fatigue , remitted fatigue , or residual fatigue ) .


Http://clinicaltrials.gov , NCT@ .


Remission of depressive symptoms ( @-item Hamilton Rating Scale for Depression @ or QIDS-SR@ @ ) ; Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form ; Short-Form Health Survey Mental and Physical subscales ; and Work and Social Adjustment Scale ( WSAS ) .


At baseline , of @ patients included in the analyses , @ % had a QIDS-SR@ item @ score of @ ; @ % , a score of @ ; @ % , a score of @ ; and @ % , a score of @ .


During Level @ treatment , @ % of patients had no prospective fatigue , @ % had treatment-emergent fatigue , @ % had fatigue remitting during treatment , and @ % had residual fatigue .


Female gender , unemployment , fewer years of education , and lower monthly income were significantly associated with higher rates of baseline fatigue ( all P < @ ) .


Higher levels of baseline or prospective fatigue were associated with reduced likelihood of remission , decreased overall satisfaction ( P < @ ) , and reduced mental and physical function at outcome ( P@ @ ) .


Patients with higher baseline or prospective fatigue reported higher WSAS total scores ( P < @ ) , indicative of more severe functional impairment .


Lower baseline fatigue and remission of fatigue during antidepressant treatment in patients with MDD are associated with higher rates of remission of depressive symptoms and better function and quality of life .


Study limitations include use of the STAR * D Level @ sample ( citalopram as only antidepressant ) , use of a proxy measure of energy/fatigue ( item @ from the QIDS-SR@ ) , and the secondary post-hoc analysis design .


Increased left ventricular mass ( LVM ) , low ventricular ejection fraction ( EF ) , and high pulse-wave velocity ( PWV ) relate to overall and cardiovascular mortality in patients with ESRD .


The aim of this study was to determine the effect of online hemodiafiltration ( HDF ) versus low-flux hemodialysis ( HD ) on LVM , EF , and PWV .


Echocardiography was used to assess LVM and EF in @ patients in the CONvective TRAnsport STudy followed for up to @ years .


PWV was measured in @ patients for up to @ years .


Effect of HDF versus HD on LVM , EF , and PWV was evaluated using linear mixed models .


Patients had a mean age of @ years , and @ % were male .


At baseline , median LVM was @ g ( interquartile range -LSB- IQR -RSB- , @-@ g ) , and median EF was @ % ( IQR , @ % -@ % ) .


Median PWV was @ m/s ( IQR , @-@ @ m/s ) .


There was no significant difference between the HDF and HD treatment groups in rate of change in LVM ( HDF : change , -@ g/yr -LSB- @ % confidence interval ( @ % CI ) , -@ to @ g -RSB- ; HD : change , @ g/yr -LSB- @ % CI , -@ to @ g -RSB- ; P for difference = @ ) , EF ( HDF : change , -@ % / yr -LSB- @ % CI , -@ % to @ % -RSB- ; HD : change , -@ % / yr -LSB- @ % CI , -@ % to -@ % -RSB- ; P = @ ) , or PWV ( HDF : change , -@ m/s per year -LSB- @ % CI , -@ to @ m/s ) ; HD : change , @ m/s per year -LSB- @ % CI , -@ to @ m/s -RSB- ; P = @ ) .


No differences in rate of change between treatment groups were observed for subgroups of age , sex , residual kidney function , dialysis vintage , history of cardiovascular disease , diabetes , or convection volume .


Treatment with online HDF did not affect changes in LVM , EF , or PWV over time compared with HD .


The progressive changes in lung morphology observed in cystic fibrosis ( CF ) can potentially affect the statistical distribution of computed tomography ( CT ) density values .


This study aimed to characterize the lung CT density distributions by quantifying indices of the kurtosis and skewness of the lung density distribution and to compare these indices to radiologic scores and lung function parameters in children and young adults with CF.


CT scans and lung function of @ patients with CF were retrospectively examined .


The Bhalla radiologic scoring was performed separately , in random order , by two expert radiologists , blinded to the patient 's identity , age , clinical status , results of lung function tests , and the other paired observer 's score .


Positive relations were evidenced between the log indices of lung density distribution kurtosis ( iKurtosis ) and the overall radiologic scores ( RS ) of both observers ( R = @ ; P < @ vs RS@ and R = @ ; P < @ vs RS@ ) .


A similar relationship was evidenced with the log index of the degree of distribution asymmetry ( iSkewness ; R = @ ; P < @ vs RS@ and R = @ ; P < @ vs RS@ ) .


Log-iKurtosis and log-iSkewness were related to FEV@ ( R = -@ ; P < @ ( -@ ) and R = -@ ; P < @ ( -@ ) ) and to residual volume ( R = @ ; P < @ and R = @ ; P < @ , respectively ) .


Both radiologic scores showed significant relation with lung function .


The correlation between RS@ and RS@ was excellent ( R = @ ) , with a Cohen weighted kappa of @ .


Characteristic indices of lung CT density distribution are correlated to lung function and radiologic scores in patients with CF and merit further evaluation as part of more comprehensive automated methods for quantifying CF lung CT data .


To compare the tissue reaction produced by @ gauges of implanted polyglactin @ ( Vicryl ) suture material in human skin .


A prospective , double masked , parallel randomized IRB approved clinical trial .


Consecutive patients with involutional entropion and horizontal eyelid laxity were randomly allocated to @/@ or @/@ gauge test suture groups .


Symptoms were alleviated during the wait for definitive surgery by placement of eyelid everting sutures .


After @ days , surgical entropion correction including eyelid wedge excision was achieved .


Histological analysis was carried out , masked to the suture gauge used , on the excised eyelid containing one of the temporary everting sutures .


Both patient and analyst were masked to the suture group .


The four primary outcome measurements were granuloma outer diameter , central cellular diameter , giant cell number and area of fibrous coat and a statistical comparison made between suture gauge groups .


@ patients were allocated to each group , and histological analysis was possible in @ patients .


Significant suture-related granulomatous inflammatory reactions were found in all specimens .


Medians of the measurements for @/@ and @/@ gauge sutures , respectively , were @ mm versus @ mm granuloma outer diameter ( p = @ ) ; @ mm versus @ mm central cellular element diameter ( p = @ ) ; @ mm ( @ ) versus @ mm ( @ ) fibrous coat area ( p = @ ) and @ versus @ giant cell number ( p = @ ) .


Polyglycolic acid sutures elicit a significant foreign body inflammatory response proportional to suture gauge .


This reaction may be minimized by early suture removal .


The study validates a novel and ethical approach to the examination of human skin response to implanted suture material .


Ulcerative colitis ( UC ) is difficult to treat , and standard therapy does not always induce remission .


Fecal microbiota transplantation ( FMT ) is an alternative approach that induced remission in small series of patients with active UC .


We investigated its safety and efficacy in a placebo-controlled randomized trial .


We performed a parallel study of patients with active UC without infectious diarrhea .


Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT ( @ mL , via enema , from healthy anonymous donors ; n = @ ) or placebo ( @ mL water enema ; n = @ ) once weekly for @ weeks .


Patients , clinicians , and investigators were blinded to the groups .


The primary outcome was remission of UC , defined as a Mayo score @ with an endoscopic Mayo score of @ , at week @ .


Patients provided stool samples when the study began and during each week of FMT for microbiome analysis .


The trial was stopped early for futility by the Data Monitoring and Safety Committee , but all patients already enrolled in the trial were allowed to complete the study .


Seventy patients completed the trial ( @ dropped out from the placebo group and @ from the FMT group ) .


Nine patients who received FMT ( @ % ) and @ who received placebo ( @ % ) were in remission at @ weeks ( a statistically significant difference in risk of @ % ; @ % confidence interval , @ % -@ % ) .


There was no significant difference in adverse events between groups .


Seven of the @ patients in remission after FMT received fecal material from a single donor .


Three of the @ patients with UC @ year entered remission , compared with @ of @ of those with UC > @ year ( P = @ , Fisher 's exact test ) .


Stool from patients receiving FMT had greater microbial diversity , compared with baseline , than that of patients given the placebo ( P = @ , Mann-Whitney U test ) .


FMT induces remission in a significantly greater percentage of patients with active UC than placebo , with no difference in adverse events .


Fecal donor and time of UC appear to affect outcomes .


ClinicalTrials.gov Number : NCT@ .


Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia .


Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation .


Therefore , we compared argatroban and lepirudin in critically ill surgical patients .


Following institutional review board approval and written informed consent , critically ill surgical patients more than or equal to @ years with suspected heparin-induced thrombocytopenia , were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time ( aPTT ) of @ to @ times baseline .


In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters .


We evaluated in all patients the incidence of bleeding and thrombembolic events .


We identified @ patients with suspected heparin-induced thrombocytopenia , including @ requiring renal replacement therapy .


Mean filter lifetimes did not differ between groups ( argatroban @ hours ( n = @ ) versus lepirudin @ hours ( n = @ ) , mean difference @ hours , @ % CI -@ to @ , P = @ ) .


Among all @ patients , relevant bleeding occurred in four argatroban - versus eleven lepirudin-patients ( OR @ , @ % CI @ to @ , P = @ ) .


In the argatroban-group , three thromboembolic events occurred compared to two in the lepirudin group ( OR @ , @ % CI @ to @ , P = @ ) .


The incidence of confirmed heparin-induced thrombocytopenia was @ % ( n = @ ) in our study population .


This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy , but suggests fewer bleeds in surgical patients with argatroban anticoagulation .


This study sought to assess the prognostic value of physical examination in a modern treated heart failure population .


The physical examination is the cornerstone of the evaluation and monitoring of patients with heart failure .


Yet , the prognostic value of congestive signs ( i.e. , peripheral edema , jugular venous distension , a third heart sound , and pulmonary rales ) has not been assessed in the current era .


A post-hoc analysis was conducted on all @,@ patients , @ % male , mean age @ @ years , with symptomatic left ventricular systolic dysfunction enrolled in the AF-CHF ( Atrial Fibrillation and Congestive Heart Failure ) trial .


The prognostic value of baseline physical examination findings was assessed in univariate and multivariate Cox regression analyses .


Peripheral edema was observed in @ ( @ % ) , jugular venous distension in @ ( @ % ) , a third heart sound in @ ( @ % ) , and pulmonary rales in @ ( @ % ) patients .


Death from cardiovascular causes occurred in @ ( @ % ) patients over a mean follow-up of @ @ months .


All @ physical examination findings were associated with cardiovascular mortality in univariate analyses ( all p values < @ ) .


In multivariate analyses , taking all @ signs as potential covariates , only rales ( hazard ratio @ ; @ % confidence interval : @ to @ ; p = @ ) and peripheral edema ( hazard ratio : @ ; @ % confidence interval : @ to @ ; p = @ ) were associated with cardiovascular mortality , independent of other variables .


In the modern era , congestive signs on the physical examination ( i.e. , peripheral edema , jugular venous distension , a third heart sound , and pulmonary rales ) continue to provide important prognostic information in patients with congestive heart failure .


Gastric cancers may harbor a subset of cells with cancer stem cell ( CSC ) properties , including chemotherapy resistance , and CD@ is a gastric CSC marker .


The Hedgehog ( HH ) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis .


Here , we examine the role of HH signaling in CD@ ( + ) gastric cancer cells .


Gastric cancer cell lines , tumor xenografts , and patient tumors were examined .


Gastric cancer cell lines AGS , MKN-@ , and NCI-N@ grown as spheroids or sorted for CD@ ( + ) were found to have upregulation of HH pathway proteins .


HH inhibition using Smoothened ( Smo ) shRNA or vismodegib ( VIS ) decreased spheroid formation and colony formation .


CD@ ( + ) cells , compared with unselected cells , were also resistant to @-fluorouracil and cisplatin chemotherapy , and this resistance was reversed in vitro and in xenografts with Smo shRNA or VIS .


CD@ ( + ) cells also had significantly more migration , invasion , and anchorage-independent growth , and these properties could all be blocked with HH inhibition .


Clinical tumor samples from a phase II trial of chemotherapy with or without VIS for advanced gastric cancer were analyzed for CD@ expression .


In the chemotherapy alone group , high CD@ expression was associated with decreased survival , whereas in the chemotherapy plus VIS group , high CD@ expression was associated with improved survival .


HH signaling maintains CSC phenotypes and malignant transformation phenotypes in CD@ ( + ) gastric cancer cells , and HH inhibition can reverse chemotherapy resistance in CD@ ( + ) cells .


Gastric cancer is a heterogeneous disease , and the strategy of combining chemotherapy with HH inhibition may only be effective in tumors with high CD@ levels .


We compared @ strategies for disseminating an evidence-based skin cancer prevention program .


We evaluated the effects of @ strategies ( basic vs enhanced ) for dissemination of the Pool Cool skin cancer prevention program in outdoor swimming pools on ( @ ) program implementation , maintenance , and sustainability and ( @ ) improvements in organizational and environmental supports for sun protection .


The trial used a cluster-randomized design with pools as the unit of intervention and outcome .


The enhanced group received extra incentives , reinforcement , feedback , and skill-building guidance .


Surveys were collected in successive years ( @-@ ) from managers of @ pools in @ metropolitan areas across the United States participating in the Pool Cool Diffusion Trial .


Both treatment groups improved their implementation of the program , but pools in the enhanced condition had significantly greater overall maintenance of the program over @ summers of participation .


Furthermore , pools in the enhanced condition established and maintained significantly greater sun-safety policies and supportive environments over time .


This study found that more intensive , theory-driven dissemination strategies can significantly enhance program implementation and maintenance of health-promoting environmental and policy changes .


Future research is warranted through longitudinal follow-up to examine sustainability .


This study sought to test @ hypotheses : @ ) fibroblast growth factor ( FGF ) -@ identifies patients with stable ischemic heart disease ( SIHD ) at high risk of cardiovascular events independent of clinical factors , renal function , and established cardiovascular biomarkers ; and @ ) FGF-@ identifies patients who derive greater clinical benefit from angiotensin-converting enzyme inhibitor therapy .


FGF-@ is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease .


Data in patients with SIHD are more sparse .


FGF-@ levels were measured in @,@ patients with SIHD randomly assigned to trandolapril or placebo within the PEACE ( Prevention of Events With Angiotensin-Converting Enzyme ) trial and followed up for a median of @ years .


After adjustment for clinical risk predictors , left ventricular ejection fraction , markers of renal function , and established cardiovascular biomarkers , FGF-@ concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo ( quartile @ hazard ratio : @ ; @ % confidence interval , @ to @ ; p = @ ) and significantly improved metrics of discrimination .


Furthermore , among patients in the top quartile of FGF-@ levels , trandolapril significantly reduced cardiovascular death or incident heart failure ( hazard ratio : @ ; @ % confidence interval : @ to @ ) , whereas there was no clinical benefit in the remaining patients ( hazard ratio : @ ; @ % confidence interval : @ to @ ; p interaction = @ ) .


This interaction was independent of and additive to stratification based on renal function .


Elevated levels of FGF-@ are associated with cardiovascular death and incident heart failure in patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function .


( Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy -LSB- PEACE -RSB- : NCT@ ) .


One of the most common symptoms observed in patients with dementia is agitation , and several non-pharmacological treatments have been used to control this symptom .


However , because of limitations in research design , the benefit of non-pharmacological treatments has only been demonstrated in certain cases .


The purpose of this study was to compare aroma-acupressure and aromatherapy with respect to their effects on agitation in patients with dementia .


In this experimental study , the participants were randomly assigned to three groups : @ patients were included in the aroma-acupressure group , @ patients in the aromatherapy group , and @ patients in the control group who received daily routine as usual without intervention .


The Cohen-Mansfield Agitation Inventory ( CMAI ) scale and the heart rate variability ( HRV ) index were used to assess differences in agitation .


The CMAI was used in the pre-test , post-test and post-three-week test , and the HRV was used in the pre-test , the post-test and the post-three-week test as well as every week during the four-week interventions .


The CMAI scores were significantly lower in the aroma-acupressure and aromatherapy groups compared with the control group in the post-test and post-three-week assessments .


Sympathetic nervous activity was significantly lower in the fourth week in the aroma-acupressure group and in the second week in the aromatherapy group , whereas parasympathetic nervous activity increased from the second week to the fourth week in the aroma-acupressure group and in the fourth week in the aromatherapy group .


Aroma-acupressure had a greater effect than aromatherapy on agitation in patients with dementia .


However , agitation was improved in both of the groups , which allowed the patients with dementia to become more relaxed .


Future studies should continue to assess the benefits of aroma-acupressure and aromatherapy for the treatment of agitation in dementia patients .


Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action .


This study compared injections of recombinant human insulin ( rHI ) formulated with recombinant human hyaluronidase -LSB- rHuPH@ -RSB- ( INSULIN-PH@ ) to insulin lispro for prandial treatment in subjects with type @ diabetes ( T@D ) .


After a @-month run-in period using twice-daily insulin glargine ( or usual basal insulin therapy for pump users ) with prandial lispro , @ subjects with T@D ( @ @ years ; body mass index : @ @ kg/m ( @ ) ; A@c : @ @ % ) were assigned to INSULIN-PH@ or lispro in a random sequence for two consecutive , @-week periods as the prandial insulin in an intensive treatment regimen .


The mean glycaemic excursion for INSULIN-PH@ ( @ @ mmol/l ) was comparable ( p = @ ) to lispro ( @ @ mmol/l ) .


The @-point self-monitored blood glucose profiles were also comparable in the two groups .


Good glycaemic control ( A@c ) was maintained for both treatments at @ weeks ( INSULIN-PH@ : @ @ % ; lispro : @ @ % ) .


Overall rates of hypoglycaemia ( @ mmol/l ) were @ events per patient per @ weeks for INSULIN-PH@ and @ events for lispro .


There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated .


Unlike commercially available formulations of regular human insulin , a formulation of rHI with rHuPH@ was comparable to lispro for postprandial glucose excursions in a basal-bolus treatment regimen for T@D patients .


Glycaemic control , safety and tolerability profiles were comparable for both treatments .


To observe practicality and safety of CT-RIDC for the patients with presaccular lacrimal obstruction and study the related factors .


To provide guidance for the diagnosis and treatment of the patients with presaccular lacrimal obstruction .


Fifty-four patients ( @ eyes ) with presaccular lacrimal obstruction , including @ cases ( @ eyes ) of upper and lower lacrimal punctum atresia , @ cases ( @ eyes ) of superior and inferior canalicular obstruction , @ cases ( @ eyes ) of common canaliculus obstruction , @ cases ( @ eyes ) of old laceration of superior and inferior canalicular , were recruited .


All patients underwent the examination by using @ and @ ear endoscope and the imaging characteristics of the inferior orifice of nasolacrimal duct were obtained .


Fifty-three cases ( @ eyes ) with the opening inferior orifice were randomly divided into four groups ( @ eyes , @ eyes , @ eyes , @ eyes ) according to different angle of head hypsokinesis in the supine position .


The OM lines back along the sagittal plane of the head back @ , @ , @ , @ were measured .


The angles of head hypsokinesis were set in accordance with the OM line measurement results.Intubation was successful when the intubation guided needle within the set of epidural anesthetic catheter aided with endoscopy was inserted into the inferior orifice of nasolacrimal duct and then the epidural anesthetic catheter was inserted into the lacrimal duct @ mm .


The angle ( ) between the long axis of the curved part of the intubation guided needle and the long axis of the guided needle was measured .


The numbers of intubation success cases in each group were recorded .


test was used to compare intubation success rate under the different angle of head hypsokinesis.Scheffe method was used to compare intubation success rate between each group .


Contrast medium was then injected into lacrimal duct through the epidural anesthetic catheter for patients with successful intubation and CT scan was carried out .


@D model of lacrimal passage was reconstructed with CT axial scanning .


The intubation guided needle was successfully inserted into the inferior orifice of nasolacrimal duct in @ eyes among @ eyes with the opening orifice .


The number of successful intubation cases were @ eyes , @ eyes , @ eyes , @ eyes and the intubation success rate was @ % , @ % , @ % , @ % according the angle of head hypsokinesis @ group ( @ eyes ) , @ group ( @ eyes ) , @ group ( @ eyes ) , @ group ( @ eyes ) .


The intubation success rate of head hypsokinesis @ group was significantly lower than that of the other groups .


Multiple Comparison by Scheffe Test demonstrated that there was a remarkable difference ( P < @ ) in the intubation success rate between head hypsokinesis @ group and the other three groups .


There were no significant differences in the intubation success rate among head hypsokinesis @ group , head hypsokinesis @ group and head hypsokinesis @ group .


The mean of was @ with a range of @-@ @ by measuring the angle of the successful intubation cases .


According to the frequency distribution plot , most was in @-@ .


The successful intubation cases ( @ eyes ) underwent CT scan in the same position immediately after injected contrast medium ( Optiray ) through the epidural anesthetic catheter .


CT images of @ eyes showed retained contrast medium in the nasolacrimal duct and lacrimal sac .


The findings from CT-DCG images were basically agreed with the operation .


CD-RIDC may apply to pre-operative examination for the patients with the opening orifice and presaccular lacrimal obstruction.It provideed imaging evidence for diagnosis and therapy and it was safe and practical .


Many factors could affect CD-RIDC .


The main verified facors were the shape of the inferior orifice of nasolacrimal duct , head position of the patient and the bending angle of the tip of intubation guided needle .


Existing psychological therapies for bipolar disorders have been found to have mixed results , with a consensus that they provide a significant , but modest , effect on clinical outcomes .


Typically , these approaches have focused on promoting strategies to prevent future relapse .


An alternative treatment approach , termed ` Think Effectively About Mood Swings ' ( TEAMS ) addresses current symptoms , including subclinical hypomania , depression and anxiety , and promotes long-term recovery .


Following the publication of a theoretical model , a range of research studies testing the model and a case series have demonstrated positive results .


The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial .


A target number of @ patients with a diagnosis of bipolar I or II disorder , or bipolar disorder not-otherwise-specified are screened , allocated to a baseline assessment and randomized to either @ sessions of TEAMS therapy plus treatment-as-usual ( TAU ) or TAU .


Patients complete self-report inventories of depression , anxiety , recovery status and bipolar cognitions targeted by TEAMS .


Assessments of diagnosis , bipolar symptoms , medication , access to services and quality of life are conducted by assessors blind to treatment condition at @ , @ , @ and @ months post-randomization .


The main aim is to evaluate recruitment and retention of participants into both arms of the study , as well as adherence to therapy , to determine feasibility and acceptability .


It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization .


The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety , reduce bipolar cognitions , improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up .


The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach .


The design will provide preliminary evidence of efficacy , feasibility , acceptability , uptake , attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual .


Annular stabilization is important during bicuspid aortic valve ( BAV ) repair to obtain the best long-term results .


This report describes the early outcomes of a novel bicuspid annuloplasty ring for this purpose .


Under regulatory supervision ( NCT@ ) , a geometric bicuspid annuloplasty ring was used during valve repair in @ patients .


Three patients had Sievers type @ valves , @ had Sievers type @ , and @ had Sievers type @ .


Thirteen patients had left - / right-coronary cusp fusion , @ had right - / noncoronary cusp fusion , and @ had both .


Moderate to severe aortic insufficiency ( AI ) was present in @ of @ patients , and @ had mild AI with aortic aneurysms .


Ascending aortic aneurysms , root aneurysms , or both were replaced in @ of @ patients .


The Dacron-covered titanium ring had circular base geometry and two outwardly flaring subcommissuralposts positioned opposite on the circumference .


The ring was implanted into the annulus beneath the valve , and then leaflet repair was performed .


Immediate postrepair echocardiograms showed grade @ residual AI in all patients , with good cusp mobility and effective height , and satisfactory gradients .


There were no in-hospital or late mortalities .


Two patients experienced leaflet tears from long annular suture tails , requiring late valve replacement .


After implementation of a lateral suture fixation technique , no more failures occurred .


At a mean follow-up time of @ months , the remaining @ patients were in New York Heart Association class I , with predominant grade @ AI .


As a technique for BAV repair , internal ring annuloplasty produces major annular remodeling and stabilization .


Annular reduction and reshaping to a @/@ % symmetric circular geometry facilitates leaflet repair and enhances cusp coaptation .


Geometric ring annuloplasty could have useful applications in BAV repair .


To develop a CSF metabolomics signature for motor neuron disease ( MND ) using ( @ ) H-NMR spectroscopy and to evaluate the predictive value of the profile in a separate cohort .


We collected CSF from patients with MND and controls and analyzed the samples using ( @ ) H-NMR spectroscopy .


We divided the total patient sample in a @:@ ratio into a training cohort and a test cohort .


First , a metabolomics signature was created by statistical modeling in the training cohort , and then the analyses tested the predictive value of the signature in the test cohort .


We conducted @ independent trials for each step .


Finally , we identified the compounds that contributed most consistently to the metabolome profile .


Analysis of CSF from @ patients and @ controls identified a diagnostic profile for MND ( R ( @ ) X > @ % , R ( @ ) Y > @ % , Q ( @ ) > @ % ) .


The best model selected the correct diagnosis with mean probability of @ % in the training cohort .


The profile discriminated between diagnostic groups with @ % sensitivity and @ % specificity in the test cohort .


Metabolites linked to pathophysiologic pathways in MND ( i.e. , threonine , histidine , and molecules related to the metabolism of branched amino acids ) were among the discriminant compounds .


CSF metabolomics using ( @ ) H-NMR spectroscopy can detect a reproducible metabolic signature for MND with reasonable performance .


To our knowledge , this is the first metabolomics study that shows that a validation in separate cohorts is feasible .


These data should be considered in future biomarker studies .


This study provides Class III evidence that CSF metabolomics accurately distinguishes MNDs from other neurologic diseases .


The purpose of this study was to determine the efficacy of pre-emptive analgesia with pregabalin and celecoxib on narcotic consumption and perceived pain in adult patients undergoing maxillomandibular advancement surgery for obstructive sleep apnea .


This was a prospective , randomized , double-blinded , placebo-controlled study of adult patients undergoing elective maxillomandibular advancement surgery for obstructive sleep apnea .


The groups received a masked @-time preoperative oral dose of pregabalin @ mg and celecoxib @ mg ( experimental group ) or lactose powder @ g ( placebo group ) .


In the postoperative period , pain management consisted of intravenous morphine patient-controlled analgesia and oral oxycodone @ mg and acetaminophen @ mg .


Patients completed a daily pain and narcotic log .


Statistical significance between group means was determined by the @-tailed independent t test .


There were statistically significant differences between the pregabalin plus celecoxib and placebo groups in average intravenous morphine consumption per @-hour interval ( @ @ vs @ @ mg ; P < @ ) , mean daily narcotic pill consumption ( @ @ vs @ @ pills ; P < @ ) , and mean daily visual analog scale scores ( @ @ vs @ @ ; P < @ ) .


Within the limitations of this study , a @-time preoperative oral dose of pregabalin and celecoxib before adult maxillomandibular advancement surgery for obstructive sleep apnea decreased mean intravenous morphine consumption , mean daily narcotic pill consumption , and mean patient perceived pain .


Few well-designed randomized controlled trials ( RCT ) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease -LSB- COPD ) have been conducted .


We assessed the effectiveness of a pharmaceutical care program for patients with COPD .


The PHARMACOP-trial was a single-blind @-month RCT , conducted in @ community pharmacies in Belgium , enrolling patients prescribed daily COPD medication , aged > or = @ years , and with a smoking history > or = @ pack-years .


A computer-generated randomization sequence allocated patients to intervention ( n = @ ) , receiving protocol-defined pharmacist care , or control group ( n = @ ) , receiving usual pharmacist care @:@ ratio , stratified by center ) .


Interventions , focusing on inhalation technique and adherence to maintenance therapy , were carried out at start of the trial and at one month follow-up .


Primary outcomes were inhalation technique and medication adherence .


Secondary outcomes were exacerbation rate , dyspnea , COPD specific and generic health status and smoking behavior .


From December @ to April @ , @ patients were enrolled .


@ patients ( @ % ) were lost to follow-up .


At the end of the trial , inhalation score ( Mean estimated difference -LSB- delta -RSB- , @ % ; @ % Confidence Interval -LSB- CI -RSB- , @-@ @ ; P < @ -RSB- and medication adherence -LSB- ( delta , @ % ; @ % CI , @-@ @ ; P < @ ) were significantly higher in the intervention group compared to the control group .


In the intervention group , a significantly lower hospitalization rate was observed ( @ vs @ hospitalizations ; Rate Ratio , @ ; @ % CI , @-@ @ ; P = @ ) .


No other significant between-group differences were observed .


The PHARMACOP-trial demonstrates that pragmatic pharmacist care programs improve both inhalation technique and medication adherence in patients with COPD and could reduce hospitalization rates .


The protocolled intervention used in this trial was specifically designed for and evaluated in ( Belgian ) community pharmacies .


This may facilitate future implementation in the Belgian context .


Self-monitoring of blood pressure with self-titration of antihypertensives ( self-management ) results in lower blood pressure in patients with hypertension , but there are no data about patients in high-risk groups .


To determine the effect of self-monitoring with self-titration of antihypertensive medication compared with usual care on systolic blood pressure among patients with cardiovascular disease , diabetes , or chronic kidney disease .


A primary care , unblinded , randomized clinical trial involving @ patients who were aged at least @ years with a history of stroke , coronary heart disease , diabetes , or chronic kidney disease and with baseline blood pressure of at least @/@ mm Hg being treated at @ UK primary care practices was conducted between March @ and January @ .


Self-monitoring of blood pressure combined with an individualized self-titration algorithm .


During the study period , the office visit blood pressure measurement target was @/@ mm Hg and the home measurement target was @/@ mm Hg .


Control patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary .


The primary outcome was the difference in systolic blood pressure between intervention and control groups at the @-month office visit .


Primary outcome data were available from @ patients ( @ % ) .


The mean baseline blood pressure was @ / @ mm Hg in the intervention group and @ / @ mm Hg in the control group .


After @ months , the mean blood pressure had decreased to @ / @ mm Hg in the intervention group and to @ / @ mm Hg in the control group , a difference of @ mm Hg ( @ % CI , @-@ @ ) in systolic and @ mm Hg ( @ % CI , @-@ @ ) in diastolic blood pressure following correction for baseline blood pressure .


Multiple imputation for missing values gave similar results : the mean baseline was @ / @ mm Hg in the intervention group vs @ / @ mm Hg in the control group , and at @ months , the mean was @ / @ mm Hg in the intervention group vs @ / @ mm Hg in the control group , with a difference of @ mm Hg ( @ % CI , @-@ @ ) for systolic and @ mm Hg ( @ % CI , @-@ @ ) for diastolic blood pressure between groups .


These results were comparable in all subgroups , without excessive adverse events .


Among patients with hypertension at high risk of cardiovascular disease , self-monitoring with self-titration of antihypertensive medication compared with usual care resulted in lower systolic blood pressure at @ months .


The incidence of vulvodynia in American women has been reported to be between @ % and @ % .


However , there is no consistently effective standardized treatment for vulvodynia .


To determine the feasibility and potential effects of using a standardized acupuncture protocol for the treatment of women with vulvodynia .


The primary outcome was vulvar pain , and sexual function was the secondary outcome .


Pain was assessed by the Short-Form McGill Pain Questionnaire , and function was measured by the Female Sexual Function Index ( FSFI ) .


Thirty-six women with vulvodynia met inclusion criteria .


The women were randomly assigned either to the acupuncture group or to the wait-list control group .


The @ subjects assigned to the acupuncture group received acupuncture two times per week for @ weeks for a total of @ sessions .


Reports of vulvar pain and dyspareunia were significantly reduced , whereas changes in the aggregate FSFI scores suggest significant improvement in sexual functioning in those receiving acupuncture vs. those who did not .


Acupuncture did not significantly increase sexual desire , sexual arousal , lubrication , ability to orgasm or sexual satisfaction in women with vulvodynia .


This was the first randomized controlled pilot study to examine the use of acupuncture for the treatment of vulvodynia .


The acupuncture protocol was feasible and in this small sample appeared to reduce vulvar pain and dyspareunia with an increase in overall sexual function for women with vulvodynia .


This study should be replicated in a larger double-blinded randomized controlled trial .


Patients with type @ diabetes ( T@D ) are prone to develop preclinical myocardial dysfunction , but no single strategy to prevent progression to heart failure has been established .


We aimed to assess whether intensified global cardiovascular ( CV ) risk factor control would improve left ventricular ( LV ) systolic and diastolic function as compared with standard of care .


A total of @ patients with @ CV risk factor ( @ % female , mean SD age @ @ years , LV ejection fraction @ @ % , @ % with LV diastolic dysfunction ) were randomized to @ years of intensified CV risk multi-intervention ( INT , n = @ ) or standard care ( STAND , n = @ ) .


Echocardiography , including tissue Doppler imaging , and maximum exercise test were performed at baseline and study end .


Multi-intervention comprised lifestyle intervention and pharmacologic treatment to reach strict prespecified CV risk factor goals , whereas STAND group received current guideline care .


Greater reductions were observed for hemoglobin A@c and total cholesterol in the INT group ( P < @ and P = @ , respectively ) , whereas blood pressure reduction was similar .


Work capacity increased in INT and decreased in STAND ( P = @ ) .


There was no significant between-group difference in the change in any of the echocardiographic parameters .


Two years of intensified multi-intervention in patients with T@D improved work capacity and glycemic and lipid control and had no significant benefit or harm on resting cardiac function .


Transient receptor potential vanilloid type @ ( TRPV@ ) is a non-selective cation channel widely expressed in skin tissues , and peripheral sensory nerve fibres .


Activation of TRPV@ releases neuropeptides ; the resulting neurogenic inflammation is believed to contribute to the development of pruritus .


A TRPV@ antagonist has the potential to perform as an anti-pruritic agent .


SB@ is a TRPV@ antagonist that has demonstrated in vitro activity against cloned TRPV@ human receptors and when orally administered has demonstrated pharmacodynamic activity in animal models and clinical studies .


To select a topical dose of SB@ using the TRPV@ agonist capsaicin ; to confirm engagement of the TRPV@ antagonistic action of SB@ and assess whether the dose selected has an effect on itch induced by two challenge agents .


A clinical study was conducted in @ healthy volunteers to assess the effects of @ doses of SB@ on skin flare induced by capsaicin .


Subjects with a robust capsaicin response were chosen to determine if the selected topical formulation of SB@ had an effect on challenge agent induced itch .


Following capsaicin challenge the greatest average reduction in area of flare was seen for the @ % formulation .


This dose was selected for further investigation .


Itch intensity induced by two challenge agents ( cowhage and histamine ) was assessed on the Computerised Visual Analogue Scale .


The difference in average itch intensity ( Weighted Mean Over @ Mins ) between the @ % dose of SB@ and placebo for the cowhage challenge was -@ , whilst the histamine challenge showed on average a -@ point change .


The @ % topical formulation of SB@ cream was clinically well tolerated and had target specific pharmacodynamic activity .


However there were no clinically significant differences on pruritus induced by either challenge agent in comparison to placebo .


SB@ is unlikely to be of symptomatic benefit for histaminergic or non-histaminergic induced itch .


The type @ Diabetes Mellitus treatment is currently effective but still not ideal .


A therapy based on the incretins , which represents a significant qualitative progress , is close to an ideal .


The first completed mortality study with dipeptidyl peptidase ( DPP@ ) inhibitors is the study called SAVOR as presented in Amsterdam during the European Cardiology Congress in @ .


SAVOR ( Saxagliptin and Cardiovascular Outcomes in Patients with Type @ Diabetes Mellitus ) randomised @,@ patients with Type @ Diabetes Mellitus and a high-risk of cardiovascular events treated with current per oral antidiabetics and patients treated with saxagliptin or placebo .


Eight thousand eight hundred and twenty patients were randomised to be treated with saxagliptin and @,@ were randomised to be treated with placebo .


The average monitored period was @ years .


The primary goal ( cardiovascular death , nonfatal myocardial infarction and nonfatal CMP ) occurred in @ % ( @ ) patients treated with saxagliptin and in @ % ( @ ) patients treated with placebo ( HR @ , p < @ for non inferiority ) .


The main secondary goal ( cardiovascular death , myocardial infarction , vascular stroke , hospitalisation for a heart failure or angina pectoris and myocardial revascularisation ) occurred in @ % ( @,@ ) patients treated with saxagliptin and in @ % ( @,@ ) patients treated with placebo .


The number of hospitalisations for heart failure was @ ( @ % ) in the group treated with saxagliptin and @ ( @ % ) in the group treated with placebo ( p = @ ) .


DPP@ inhibitor saxagliptin did not increase the occurrence of ischemic cardiovascular events but it inclined to an increased hospitalisation for heart failure in patients with the already present heart failure .


It did not increase the occurrence of pancreatitis .


Simultaneously it significantly improved the Diabetes Mellitus control , which could signal a future improvement in cardiovascular goals .


Patients with antiplatelet and antithrombotic therapy ( AP/AT ) represent a substantial proportion of ear , nose and throat ( ENT ) patients .


Despite the ubiquitous consideration of bleeding and ischemic/thrombembolic risk , no detailed assessment of the perioperative setting in an ENT cohort is available in the literature .


The goal of the present work is to give a detailed assessment of patients with AP/AT in an ENT cohort resulting in ENT-specific recommendations for daily routine .


In all , @ randomized patients were asked regarding analgetic therapy in acute pain .


Medical data of @patients who underwent head and neck surgery were analyzed for AP/AT therapy .


Therapeutic strategies , the perioperative AP/AT therapy , duration of intensive care treatment and hospitalization ( ICT/H ) , application of erythrocytes and internistic/neurolocigal complication data were analyzed in patients with/without AP/AT .


Nearly @ % of our patients were taking AP/AT due to coronary heart disease ( CHD ) , peripheral arterial disease ( PAD ) , cardiac arrhythmia , or cardiovascular disease ( CVD ) .


Patients ' questionnaire revealed that @ % of our patients use acetylsalicylic acid in acute pain , which represents @ % of the overall AP/AT cohort .


Head and neck surgery in patients with AP/AT showed an elevated bleeding frequency ( p = @ ) without an elevated risk for internistic/neurological complications .


ICT/H were remarkably prolonged ( p = @ ; p = @ ) .


Head and neck surgery in patients with AP/AT can be routinely performed .


Indication for intensive care , endotracheal intubation , and tracheostomy should be made generously due to high requirements of airway management in ENT .


Ischemic/thrombembolic and bleeding risk requires careful assessment in an interdisciplinary setting .


The mechanism of reflux protection may involve a ` flap valve ' at the oesophago-gastric junction ( OGJ ) .


To assess the effects of baclofen , a gamma-aminobutyric acid receptor type-B ( GABA-B ) agonist known to suppress reflux events , on the ` functional anatomy ' of the OGJ and proximal stomach after a large test meal .


Twelve healthy volunteers ( HVs ) and @ patients with gastro-oesophageal reflux disease ( GERD ) ; with erosive oesophagitis or pathological oesophageal acid exposure completed a randomised , double-blind , cross-over study .


On @ test days participants received @-mg baclofen or placebo before ingestion of a large test meal .


OGJ structure and function were assessed by high-resolution manometry ( HRM ) and magnetic resonance imaging ( MRI ) using validated methods .


Measurements of the oesophago-gastric angle were derived from three-dimensional models reconstructed from anatomic MRI images .


Cine-MRI and HRM identified postprandial reflux events .


Mixed model analysis and Wilcoxon rank signed tests assessed differences between participant groups and treatment conditions .


In both HVs and GERD patients , baclofen reduced the frequency of postprandial reflux events .


The oesophago-gastric insertion angle in GERD patients was reduced ( -@ @ , P = @ ) , but was unchanged in healthy controls .


In both study groups , baclofen augmented lower oesophageal sphincter ( LES ) pressure ( HVs : +@ @ mmHg , P < @ , GERD : +@ @ mmHg , P < @ ) and increased LES length ( HVs : +@ @ cm , P < @ , GERD : +@ @ cm , P < @ ) .


Baclofen inhibits transient LES relaxations and augments LES pressure and length .


Additionally , baclofen has effects on the ` functional anatomy ' of the OGJ and proximal stomach in GERD patients , which may suppress reflux by means of a ` flap valve ' mechanism .


The aim of the current study is to compare the accuracy of the ultrasound ( US ) versus clinical assessment for determination of the spinal level , using X-ray as the Gold Standard for control .


@ patients were randomized into two equal groups .


Patients in the Clinical Group were examined by landmarks to assess the Assumed Clinical Tuffier 's Line , and then by fluoroscopy to determine the True Clinical Tuffier 's Line .


Patients in the Ultrasound Group were examined by the ultrasound to determine the Ultrasound Tuffier 's Line .


The results of both groups were compared in relation to the plain X-ray , done for each patient , which determined the Radiological Tuffier 's Line .


In the Clinical Group , the True Clinical Tuffier 's line met the Assumed Tuffier 's line in only @ % of the patients .


In the remaining patients , wrong leveling ranged from one space above in @ % to @ spaces above in @ % and in @ % of patients the line was at L@ .


In the Ultrasound Group , wrong leveling occurred in @ % of patients .


The Ultrasound misidentification was less than one level in @ % and one level in @ % of patients .


Ultrasound examination had a true limitation of @ % of patients .


Ultrasound examination of the spine is recommended in patients planned for spinal anesthesia , as it is superior to clinical assessment in identification of the interspinous levels .


This will decrease the hazard of spinal cord trauma .


The purpose of this study was to evaluate the clinical outcomes of cografting of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects on the extremities .


In this prospective randomized study , @ consecutive patients with full-thickness skin defects on the extremities following trauma underwent grafting using either cograft of acellular dermal matrix with autologous split-thickness skin graft ( nine patients , group A ) or autologous split-thickness skin graft alone ( @ patients , group B ) from June of @ to December of @ .


The postoperative evaluations included observation of complications ( including graft necrosis , graft detachment , or seroma formation ) and Vancouver Scar Scale score .


No statistically significant difference was found regarding complications , including graft necrosis , graft detachment , or seroma formation .


At week @ , significantly lower Vancouver Scar Scale scores for vascularity , pliability , height , and total score were found in group A compared with group B.


At week @ , lower scores for pliability and height and total scores were identified in group A compared with group B.


For cases with traumatic full-thickness skin defects on the extremities , a statistically significant better result was achieved with cograft of acellular dermal matrix with autologous split-thickness skin graft than with autologous split-thickness skin graft alone in terms of Vancouver Scar Scale score .


Therapeutic , II .


If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present standard .


Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects .


We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects .


Patients with T@-@ primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised , multicentre , open-label , phase @ non-inferiority EORTC @-@ AMAROS trial .


Patients were randomly assigned ( @:@ ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution .


The primary endpoint was non-inferiority of @-year axillary recurrence , considered to be not more than @ % for the axillary radiotherapy group compared with an expected @ % in the axillary lymph node dissection group .


Analyses were by intention to treat and per protocol .


The AMAROS trial is registered with ClinicalTrials.gov , number NCT@ .


Between Feb @ , @ , and April @ , @ , @ patients were enrolled at @ centres from nine European countries , of whom @ were eligible for randomisation .


@ patients were randomly assigned to receive axillary lymph node dissection and @ to receive axillary radiotherapy .


Of the @ patients with a positive sentinel node , @ had been randomly assigned to axillary lymph node dissection and @ to axillary radiotherapy ; these patients constituted the intention-to-treat population .


Median follow-up was @ years ( IQR @-@ ) for the patients with positive sentinel lymph nodes .


In the axillary lymph node dissection group , @ ( @ % ) of @ patients who underwent axillary lymph node dissection had additional positive nodes .


Axillary recurrence occurred in four of @ patients in the axillary lymph node dissection group and seven of @ in the axillary radiotherapy group .


@-year axillary recurrence was @ % ( @ % CI @-@ ) after axillary lymph node dissection versus @ % ( @-@ ) after axillary radiotherapy .


The planned non-inferiority test was underpowered because of the low number of events .


The one-sided @ % CI for the underpowered non-inferiority test on the hazard ratio was @-@ , with a non-inferiority margin of @ .


Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at @ year , @ years , and @ years .