These results suggest that a nutritional approach may be a useful part of migraine treatment , but that methodologic issues necessitate further research .


Clinicaltrials.gov , NCT01699009 and NCT01547494 .


The purpose of this study was to determine if educating parents with visual aids after their child 's treatment under general anesthesia would improve attendance at follow-up appointments , oral health outcomes , and treatment satisfaction .


Fifty-four parent-child dyads were recruited and randomly assigned to two groups .


The control group received verbal education , and the intervention group received verbal and visual education .


Oral health was measured using the Gingival Index and the Simplified Oral Hygiene Index ( OHI-S ) before and after the treatment .


Parent surveys were administered before and after treatment .


MResults : Seventy-eight percent of the intervention group and 52 percent of the control group returned for follow-up appointments ( P = .04 ) .


The plaque index decreased ( P < .01 ) ; the reported brushing frequency increased for all children from baseline to follow-up visit ( P = .02 ) .


The satisfaction increased only for parents in the intervention group over time ( P = .04 ) .


Using visual aids had a positive impact on patient attendance at follow-up and parents ' treatment satisfaction .


There was an improvement in oral hygiene , as measured by the OHI-S , and an increase in brushing frequency for all children , regardless of whether their parents were educated with or without a visual aid .


To evaluate the association between adolescent and young-adult hearing loss and nonverbal intelligence in rural Nepal .


Cross-sectional assessment of hearing loss among a population cohort of adolescents and young adults .


Sarlahi District , southern Nepal .


Seven hundred sixty-four individuals aged 14 to 23 years .


Evaluation of hearing loss , defined by World Health Organization criteria of pure-tone average greater than 25 decibels ( 0.5 , 1 , 2 , 4 kHz ) , unilaterally and bilaterally .


Nonverbal intelligence , as measured by the Test of Nonverbal Intelligence , 3rd Edition standardized score ( mean , 100 ; standard deviation , 15 ) .


Nonverbal intelligence scores differed between participants with normal hearing and those with bilateral ( p = 0.04 ) but not unilateral ( p = 0.74 ) hearing loss .


Demographic and socioeconomic factors including male sex ; higher caste ; literacy ; education level ; occupation reported as student ; and ownership of a bicycle , watch , and latrine were strongly associated with higher nonverbal intelligence scores ( all p < 0.001 ) .


Subjects with bilateral hearing loss scored an average of 3.16 points lower ( 95 % confidence interval , -5.56 to -0.75 ; p = 0.01 ) than subjects with normal hearing after controlling for socioeconomic factors .


There was no difference in nonverbal intelligence score based on unilateral hearing loss ( 0.97 ; 95 % confidence interval , -1.67 to 3.61 ; p = 0.47 ) .


Nonverbal intelligence is adversely affected by bilateral hearing loss even at mild hearing loss levels .


Socio economic well-being appears compromised in individuals with lower nonverbal intelligence test scores .


Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome ( MFS ) , a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1 .


There are approximately 18,000 patients in the UK with MFS .


Current treatment includes careful follow-up , beta blockers , and prophylactic surgical intervention ; however , there is no known treatment which effectively prevents the rate of aortic dilatation in MFS .


Preclinical , neonatal , and pediatric studies have indicated that angiotensin receptor blockers ( ARBs ) may reduce the rate of aortic dilatation .


This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome .


The Aortic Irbesartan Marfan Study ( AIMS ) is an investigator-led , prospective , randomized , placebo-controlled , double-blind , phase III , multicenter trial .


Currently , 26 centers in the UK will recruit 490 clinically confirmed MFS patients ( aged 6 to 40 years ) using the revised Ghent diagnostic criteria .


Patients will be randomized to irbesartan or placebo .


Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter .


The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography .


The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months .


This is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS .


Not only will this provide useful information on the safety and efficacy of ARBs in MFS , it will also provide a rationale basis for potentially lifesaving therapy for MFS patients .


ISRCTN , 90011794 .


Asteatotic eczema ( AE ) is characterized by itchy , dry , rough , and scaling skin .


The treatments for AE are mainly emollients , usually containing urea , lactic acid , or a lactate salt .


N-palmitoylethanolamine ( PEA ) and N-acetylethanolamine ( AEA ) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases .


The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE .


A monocentric , randomized , double-blind , comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients .


The level of skin dryness among the subjects ranged from mild to moderate .


The subjects ' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology .


The results showed that , although some aspects were improved in both groups , the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance .


However , the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days , with a significant difference between values at baseline and after 14 days .


A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group .


Compared with traditional emollients , regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously .


To compare health outcomes during 14-year observational follow-up in women initially randomised to unopposed estrogen or placebo .


At recruitment to the Estrogen for the Prevention of Re-Infarction Trial ( ESPRIT ) women were assigned to estradiol valerate : 2mg or placebo treatment for 2years .


Women were recruited from 35 hospitals in the northwest of England and Wales in July 1996-February 2000 .


Women aged 50-69 surviving their first myocardial infarction .


All women were followed by data linkage to UK mortality and cancer records ; mean follow-up 14.1 and 12.6 years , respectively .


In an intention-to-treat analysis , hazard ratios ( HRs ) were computed , overall and stratified by age at recruitment .


Death ( all-cause , cardiac disease , stroke or cancer ) and cancer incidence ( any , breast or endometrium ) .


There were 418 deaths in 1017 women randomised .


The all-cause mortality HR of 1.07 ( 95 % CI 0.88-1 .29 ) indicated no significant difference between treatment groups .


Women aged 50-59years at recruitment had lower HRs than women aged 60-69years for all outcomes except ischaemic heart disease .


Among 149 incident cancers there were seven cases of breast cancer in the intervention arm and 15 in the placebo ; HR 0.47 ( 95 % CI 0.19-1 .15 ) .


There were no deaths from endometrial cancer but three incident cases , one in the active arm and two in placebo .


These results suggest that unopposed estrogen may be used safely by women with an intact uterus surviving a first myocardial infarction .


CHA2DS2-VASc and CHADS2 scores were derived and validated for stroke-risk stratification in patients who have a diagnosis of atrial fibrillation ( AF ) .


We hypothesized that these scores would predict adverse cardiovascular events even in the absence of AF .


The CHA2DS2-VASc and CHADS2 scores for 2010 patients with sick sinus syndrome who underwent pacemaker implantation and were enrolled in the Mode Selection Trial ( MOST ) were calculated .


The association of these risk scores with main trial end points , including the composite of death and stroke , were evaluated to determine whether the associations differed by history of AF .


Of the 2010 patients , 12 % had a CHA2DS2-VASc score of 0-1 , 16 % had a score of 2 , 41 % had a score of 3-4 , and 31 % had a score 5 ( the distribution for CHADS2 was similar ) ; 42 % had a clinical history of AF .


Both scores were associated with death or stroke ( hazard ratio [ HR ] , 1.14 ; 95 % confidence interval [ CI ] , 1.05-1 .23 for each 1-point increase in CHA2DS2-VASc ; P = 0.001 ; HR , 1.11 ; 95 % CI , 1.02-1 .21 for each 1-point increase in CHADS2 ; P = 0.016 ) .


Association of scores with outcomes of death , stroke , and heart failure hospitalization were not different for patients with vs those without a history of AF ( interaction P 0.55 for CHA2DS2-VASc and 0.30 for CHADS2 ) .


Both CHA2DS2-VASc and CHADS2 scores predict risk of death or stroke in patients with sick sinus syndrome , regardless of AF history .


These scores could be risk-stratification tools for clinical events that might respond to new therapiesie , anticoagulation or other interventionseven in the absence of AF .


Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration , which may persist for several days .


Such acute kidney injury is associated with lower long-term kidney function .


However , it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function .


To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later .


The Coronary Artery Bypass Grafting Surgery Off - or On-pump Revascularisation Study ( CORONARY ) enrolled 4752 patients undergoing first isolated coronary artery bypass graft ( CABG ) surgery at 79 sites in 19 countries .


Patients were randomized to receive CABG surgery either with a beating-heart technique ( off-pump ) or with cardiopulmonary bypass ( on-pump ) .


From January 2010 to November 2011 , 2932 patients ( from 63 sites in 16 countries ) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year .


The last 1-year serum creatinine concentration was recorded on January 18 , 2013 .


Acute kidney injury within 30 days of surgery ( 50 % increase in serum creatinine concentration from prerandomization concentration ) and loss of kidney function at 1 year ( 20 % loss in estimated glomerular filtration rate from prerandomization level ) .


Off-pump ( n = 1472 ) vs on-pump ( n = 1460 ) CABG surgery reduced the risk of acute kidney injury ( 17.5 % vs 20.8 % , respectively ; relative risk , 0.83 [ 95 % CI , 0.72-0 .97 ] , P = .01 ) ; however , there was no significant difference between the 2 groups in the loss of kidney function at 1 year ( 17.1 % vs 15.3 % , respectively ; relative risk , 1.10 [ 95 % CI , 0.95-1 .29 ] , P = .23 ) .


Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss , and in the subgroup with baseline chronic kidney disease .


Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury , without evidence of better preserved kidney function with off-pump CABG surgery at 1 year .


In this setting , an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function .


clinicaltrials.gov Identifier : NCT00463294 .


Osteoarthritis ( OA ) of the knee is the most frequent form of arthritis and a cause of pain and disability .


Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach , but no evidence supports the recommendation .


To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee .


We performed a randomized , blinded , placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1 , 2012 , through April 2 , 2014 .


The participants had radiographic confirmation of clinical OA of the knee , clinical signs of localized inflammation in the knee , and knee pain during walking ( score > 4 on a scale of 0 to 10 ) .


Participants were randomly allocated ( 1:1 ) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate ( Depo-Medrol ) , 40 mg/mL , dissolved in 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( corticosteroid group ) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( placebo group ) .


Two weeks after the injections , all participants started a 12-week supervised exercise program .


The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) questionnaire ( range , 0-100 ; higher scores indicate greater improvement ) at week 14 .


Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation .


Outcomes were measured at baseline , week 2 ( exercise start ) , week 14 ( exercise stop ) , and week 26 ( follow-up ) .


One hundred patients were randomized to the corticosteroid group ( n = 50 ) or the placebo group ( n = 50 ) ; 45 and 44 patients , respectively , completed the trial .


The mean ( SE ) changes in the KOOS Pain subscale score at week 14 were 13.6 ( 1.8 ) and 14.8 ( 1.8 ) points in the corticosteroid and placebo groups , respectively , corresponding to a statistically insignificant mean difference of 1.2 points ( 95 % CI , -3.8 to 6.2 ; P = .64 ) .


We found no statistically significant group differences in any of the secondary outcomes at any time point .


No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee .


Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments .


clinicaltrialsregister.eu Identifier : 2012-002607-18 ; clinicaltrials.gov Identifier : NCT01945749 .


To assess whether a suture technique in upper blepharoplasty may be the cause of differences in the occurrence of suture abscess formation and focal inflammation .


A Level I , randomized controlled trial .


The upper blepharoplasty wound was closed with a running intradermal suture .


External intradermal suturing implied that this suture was started by initially passing it through the intact skin adjacent to the wound .


In contrast , internal intradermal suturing meant the intradermal suture was not started in the adjacent skin but simply within the wound itself .


One week and 6 weeks after surgery , the presence of suture abscesses and focal inflammation was assessed at the entrance and exit of the sutures .


After 1 week , 12 abscesses ( 40.0 % ) were found at the medial side of the externally sutured upper eyelids and 4 abscesses ( 13.3 % ) in the internally sutured upper eyelids ( p = .02 ) .


The presence of erythema and edema after 1 week was also significantly lower in internally sutured upper eyelids ( p = .02 ) .


In this series , the method of starting the suture ( internal vs external ) at the medial side of an upper blepharoplasty wound was associated with a statistically significant reduction in the incidence of medial wound inflammation and suture abscess formation at a 1-week follow-up .


Adverse skin reactions as a local side effect of nicotine patches sometimes interfere with smoking cessation therapy .


We studied the effects of semipermeable membrane dressings ( SMD ) used under nicotine patches ( NP ) on nicotine absorption , as assessed according to the urinary cotinine levels , and skin symptoms .


First , the urinary cotinine levels were compared in eight nonsmokers that applied NP over SMD and NP without SMD ( Study 1 ) .


The urinary cotinine levels were measured using a highly sensitive competitive enzyme immunoassay .


Second , 28 subjects undergoing NP therapy for diagnosed nicotine dependence were randomly assigned into two groups in a crossover design to receive NP over SMD and NP without SMD .


The urinary cotinine levels and skin symptoms were compared between the two treatment groups .


During the follow-up period of 48 weeks , the smoking cessation rate was evaluated ( Study 2 ) .


No statistical differences were observed in the urinary cotinine levels between the NP over SMD and NP without SMD groups .


In Study 2 , the skin symptoms improved with the use of SMD in 42.8 % ( 6/14 ) of the patients and worsened in 28.5 % ( 4/14 ) of the patients .


No serious skin disorders were reported .


The subjects followed in Study 2 exhibited smoking cessation rates of 92.8 % , 78.5 % and 64.2 % at 12 , 24 and 48 weeks , respectively .


The use of NP over SMD is a safe and effective alternative application to NP treatment for preventing the skin symptoms caused by NP without interfering with nicotine absorption .


Metal-on-metal ( MOM ) total hip arthroplasties were reintroduced because of the problems with osteolysis and aseptic loosening related to polyethylene wear of early metal-on-polyethylene ( MOP ) arthroplasties .


The volumetric wear rate has been greatly reduced with MOM arthroplasties ; however , because of nano-size wear particles , the absolute number has been greatly increased .


Thus , a source of metal ion exposure with the potential to sensitize patients is present .


We hypothesized that higher amounts of wear particles result in increased release of metal ions and ultimately lead to an increased incidence of metal allergy .


52 hips in 52 patients ( median age 60 ( 51-64 ) years , 30 women ) were randomized to either a MOM hip resurfacing system ( ReCap ) or a standard MOP total hip arthoplasty ( Mallory Head/Exeter ) .


Spot urine samples were collected preoperatively , postoperatively , after 3 months , and after 1 , 2 , and 5 years and tested with inductively coupled plasma-sector field mass spectrometry .


After 5 years , hypersensitivity to metals was evaluated by patch testing and lymphocyte transformation assay .


In addition , the patients answered a questionnaire about hypersensitivity .


A statistically significant 10 - to 20-fold increase in urinary levels of cobalt and chromium was observed throughout the entire follow-up in the MOM group .


The prevalence of metal allergy was similar between groups .


While we observed significantly increased levels of metal ions in the urine during the entire follow-up period , no difference in prevalence of metal allergy was observed in the MOM group .


However , the effect of long-term metal exposure remains uncertain .


To investigate the effect of pancreatic duct stent internal versus external drainage with pancreaticojejunostomy on the early curative effect after pancreaticoduodenectomy ( PD ) .


The study was a prospective controlled trial .


A total of 219 patients undergoing PD from January 2010 to March 2013 were randomly divided into external drainage group ( n = 110 ) and internal drainage group ( n = 109 ) .


The pancreatic duct stent was put in the jejunum during the operation in the internal drainage group , while that in the external drainage group was placed outside the body through the jejunum and abdominal wall .


The intra-operative blood loss , operative duration , post-operative hospital stay , mortality rate , and the morbidity of pancreatic fistula as well as other complications were compared between the two groups .


Compared with internal drainage group , pancreatic duct stent external drainage obviously reduced the morbidity of pancreatic fistula ( 13.6 % vs. 22.6 % ) , delayed gastric emptying ( 10.0 % vs. 27.5 % ) , abdominal infection ( 6.4 % vs. 19.3 % ) , intestinal obstruction ( 8.2 % vs. 20.2 % ) along with the overall complications ( 24.5 % vs. 41.3 % ) after PD ( ( 2 ) = 5.735 8 to 11.047 7 , P < 0.05 ) , and shortened the healing duration of pancreatic fistula ( ( 11.5 2.9 ) d vs. ( 20.1 5.7 ) d , t = 5.07 , P < 0.01 ) , while there was no significant difference in the intra-operative blood loss , operative duration , post-operative hospital stay and mortality rate , etc between the two groups ( P > 0.05 ) .


Pancreatic duct stent external drainage can effectively reduce the morbidity of pancreatic fistula and the overall complications after PD , which is safe and feasible .


The method is worthy of popularization and application clinically .


Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels , but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown .


This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults .


We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D ( 700IU/day ) and calcium ( 500mg/day ) intervention trial carried out in men and women aged 65 years .


Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay .


In the men , sclerostin levels increased over 2 years by 4.111.81 ng/l ( 13.1 % ) in the vitamin D plus calcium-supplemented group and decreased by 3.161.78 ng/l ( 10.9 % ) in the placebo group ( P = 0.005 for difference in change ) .


Adjustments for the season of measurement , baseline physical activity levels , baseline serum sclerostin levels , and total body bone mineral content did not substantially alter the changes .


In the women , there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments .


In both the sexes , vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels .


Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation .


The reason for this difference remains to be determined .


The research tested the accuracy of the VIVO Harvester software in identifying publications authored by faculty members affiliated with a National Institutes of Health Clinical and Translational Sciences Award ( CTSA ) site .


Health sciences librarians created `` gold standard '' lists of references for the years 2001 to 2011 from PubMed for twenty-five randomly selected investigators from one CTSA site .


These gold standard lists were compared to the same twenty-five investigators ' reference lists produced by VIVO Harvester .


The authors subjected the discrepancies between the lists to sensitivity and specificity analyses .


The VIVO Harvester correctly identified only about 65 % of the total eligible PubMed references for the years 2001-2011 for the CTSA-affiliated investigators .


The identified references produced by VIVO Harvester were precise yet incomplete .


The sensitivity rate was 0.65 , and the specificity rate was 1.00 .


While the references produced by VIVO Harvester could be confirmed in PubMed , the VIVO Harvester retrieved only two-thirds of the required references from PubMed .


National Institutes of Health CTSA sites will need to supplement VIVO Harvester-produced references with the expert searching skills of health sciences librarians .


Health sciences librarians with searching skills need to alert their CTSA sites about these deficiencies and offer their skills to advance their sites ' missions .


The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics ( PK ) ; the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitisC virus ( HCV ) drug 's prescribing information alone .


This was a single-centre , randomized , open-label , two-cohort , two-period , one-way study in healthy adult subjects .


Dolutegravir 50mg once daily was administered for 5 days in Period1 , and dolutegravir 50mg once daily was coadministered with either boceprevir 800mg every 8h ( Cohort1 ) or telaprevir 750mg every 8h ( Cohort2 ) for 10days in Period2 .


No deaths or serious adverse events were reported during the study .


Four subjects were withdrawn from the study because of adverse events ( elevated alanine aminotransferase , cellulitis , increased serum creatinine and dizziness ) .


One subject became pregnant during the study .


Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration-time curve ( AUC ) and maximal plasma concentration ( Cmax ) and caused a small increase in concentration at the end of the dosing interval ( C ; 8 % ) .


Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone ; AUC0 - , Cmax and C increased by 25 , 19 and 37 % , respectively .


Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK .


Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data , indicating no effect of dolutegravir on boceprevir or telaprevir exposure .


Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment .


The blood/gas partition coefficient of a certain volatile anesthetic is of clinical importance because it determines its velocity of uptake into and elimination from the body of a patient and thus its pharmacokinetic behavior .


To date , the blood/gas partition coefficients of isoflurane , sevoflurane , and desflurane have been measured in small numbers of subjects or in particular study groups , for example , healthy volunteers , patients experiencing a common kind of disease , or mothers immediately after giving birth .


The objective of this study was to determine the blood/gas partition coefficients of these volatile anesthetics at 37C in a larger clinically relevant and adult patient population .


Furthermore , we tested whether age , gender , body mass index , hemoglobin concentration , or hematocrit had an influence on the coefficients .


Blood samples were taken from 120 fasting operative patients with ASA physical status I to III and aged 19 to 86 years .


All subjects were randomly enrolled in study groups for the separate determinations of the blood/gas partition coefficients of isoflurane ( n = 41 ) , sevoflurane ( n = 41 ) , and desflurane ( n = 38 ) by headspace gas chromatography .


To check the quality of the measurements , we determined the distilled water/gas partition coefficients of those anesthetics and compared them with previously published values .


We found a blood/gas partition coefficient of 1.45 0.12 ( mean SD ) for isoflurane , 0.74 0.06 for sevoflurane , and 0.57 0.04 for desflurane .


Values of this study are 5.07 % , 12.12 % , and 7.55 % higher for isoflurane , sevoflurane , and desflurane , respectively , than the previously published mean values ( all P 0.001 ) .


There were only trends for small correlations between the blood/gas partition coefficient of isoflurane and hemoglobin concentration ( Pearson r = 0.32 ; P = 0.041 ) and hematocrit ( r = 0.37 ; P = 0.016 ) .


We found no other potentially significant correlations of the partition coefficients with patient age , body mass index , hemoglobin concentration , or hematocrit ( all remaining P > 0.069 ) .


Furthermore , the coefficients did not differ significantly between female and male patients .


The evaluation of the distilled water/gas partition coefficients of isoflurane ( 0.59 0.04 ) , sevoflurane ( 0.37 0.04 ) , and desflurane ( 0.27 0.03 ) proved the validity of the gas chromatography method used in this study .


The blood/gas partition coefficients of the modern volatile anesthetics , in particular , those of sevoflurane and desflurane , may be higher than that has been hitherto reported .


Therefore , their uptake and elimination may occur more slowly in some patients than has been supposed .


The blood/gas partition coefficients of isoflurane , sevoflurane , and desflurane measured in this study appear to be representative because they were determined in a clinically and numerically relevant patient cohort .


Physical activity is a key factor for healthy ageing , yet many older people lead a sedentary lifestyle .


Traditional physical activity interventions do not consider the specific needs and views of older adults .


As views on ageing are known to be related to health behaviours , the current study evaluates the effectiveness of prompting positive views on ageing within a physical activity intervention .


Randomised controlled trial with three groups aged 65 + : Intervention for physical activity with ` views-on-ageing ' - component ( n = 101 ; IGVoA ) , and without ` views-on-ageing ' - component ( n = 30 ; IG ) , and active control intervention for volunteering ( n = 103 ; CG ) .


Attitudes towards older adults and physical activity were assessed five weeks before intervention , two weeks , six weeks and 8.5 months after the intervention .


Compared to the IG and CG , positive attitudes towards older adults increased in the IGVoA after the intervention .


For IGVoA , the indirect intervention effect on change in activity via change in attitudes towards older adults was reliable .


A ` views-on-ageing ' - component within a physical activity intervention affects change in physical activity via change in views on ageing .


Views on ageing are a promising intervention technique to be incorporated into future physical activity interventions for older adults .


Evaluate a selective obesity prevention program promoting use of cognitive reappraisals to reduce reward region response and increase inhibitory region response to high-fat/high-sugar foods and reduce intake of fat and sugar to prevent blunted reward region response to intake of such foods .


Young adults at risk for future weight gain by virtue of weight concerns ( N = 148 ) were randomized to this new prevention program ( Minding Health ) , an alternative prevention program promoting participant-driven gradual reductions in caloric intake and increases in physical activity ( Healthy Weight ) , or an obesity education video control condition , completing assessments at pre - , post - , and 6-month follow-up .


A subset of Minding Health and control participants completed an fMRI scan at pre - and post-assessing neural response to images of high-fat/sugar foods and to receipt and anticipated receipt of a high-fat/sugar food .


Minding Health participants showed significantly greater reductions in body fat than controls and caloric intake from fat and sugar than Healthy Weight participants .


Minding Health participants also showed greater activation of an inhibitory control region and reduced activation of an attention/expectation region in response to palatable food images relative to pretest and controls .


However , Healthy Weight participants showed greater reductions in BMI and eating disorder symptoms than Minding Health participants .


Although the Minding Health intervention produced some of the hypothesized effects , it did not produce lasting reductions in body fat or BMI and showed limited effects on neural responsivity , implying it will be vital to increase the efficacy of this new prevention program .


Sixty-two percent of patients would like their doctor to recommend a specific web site to find health information , but only 3 % of patients receive such recommendations .


We investigated whether providing patients with an Internet web-site link recommended by their physician would improve patient knowledge and satisfaction .


Our hypothesis was that directing patients to a reliable web site would improve both .


Sixty patients with a new diagnosis of carpal tunnel syndrome were prospectively randomized into two groups .


Twenty-three patients in the control group had a traditional physician office visit and received standard care for carpal tunnel syndrome .


Thirty-seven patients in the treatment group received a handout that directed them to the American Society for Surgery of the Hand ( ASSH ) web page on carpal tunnel syndrome in addition to the standard care provided in the office visit .


Patients later completed a ten-question true-or-false knowledge questionnaire and a six-item satisfaction survey .


Differences in scores were analyzed using two-sample t tests .


Less than half ( 48 % ) of the patients who were given the Internet directive reported that they had visited the recommended web site .


The mean scores on the knowledge assessment ( 6.84 of 10 for the treatment group and 6.96 of 10 for the control group ) and the satisfaction survey ( 4.49 of 5 for the treatment group and 4.43 of 5 for the control group ) were similar for both groups .


The mean score for knowledge was similar for the patients who had used the ASSH web site and for those who had not ( 6.89 and 6.97 respectively ) .


Moreover , compared with patients who had not used the Internet at all to learn about carpal tunnel syndrome , patients who used the Internet scored 6.6 % better ( mean score , 7.14 for those who used the Internet compared with 6.70 for those who had not ; p > 0.05 ) .


Regardless of Internet usage , most patients scored well on the knowledge assessment and reported a high level of satisfaction .


Whether the patient was given a handout or had visited the ASSH or other Internet web sites , the knowledge and satisfaction scores for all patients were similar .


Since the physician was the common denominator in both groups , the results indicate that the patient-physician relationship may be more valuable than the Internet in providing patient education .


Effective communication between patients and practitioners is at the cornerstone of delivering excellent care and building trusting relationships .


This study examines whether reliable Internet information should be embraced as a tool to enhance patient-surgeon communication in a clinical context .


Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis .


We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease .


Between Nov 12 , 2008 , and Dec 23 , 2010 , we enrolled Indigenous Australian , Maori , and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre , double-blind , randomised , parallel-group , placebo-controlled trial .


Eligible children had had at least one pulmonary exacerbation in the previous 12 months .


Children were randomised ( 1:1 ratio , by computer-generated sequence with permuted block design , stratified by study site and exacerbation frequency [ 1-2 vs 3 episodes in the preceding 12 months ] ) to receive either azithromycin ( 30 mg/kg ) or placebo once a week for up to 24 months .


Allocation concealment was achieved by double-sealed , opaque envelopes ; participants , caregivers , and study personnel were masked to assignment until after data analysis .


The primary outcome was exacerbation ( respiratory episodes treated with antibiotics ) rate .


Analysis of the primary endpoint was by intention to treat .


At enrolment and at their final clinic visits , children had deep nasal swabs collected , which we analysed for antibiotic-resistant bacteria .


This study is registered with the Australian New Zealand Clinical Trials Registry ; ACTRN12610000383066 .


45 children were assigned to azithromycin and 44 to placebo .


The study was stopped early for feasibility reasons on Dec 31 , 2011 , thus children received the intervention for 12-24 months .


The mean treatment duration was 207 months ( SD 57 ) , with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group .


Compared with the placebo group , children receiving azithromycin had significantly lower exacerbation rates ( incidence rate ratio 050 ; 95 % CI 035-071 ; p < 00001 ) .


However , children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria ( 19 of 41 , 46 % ) than those receiving placebo ( four of 37 , 11 % ; p = 0002 ) .


The most common adverse events were non-pulmonary infections ( 71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group ) and bronchiectasis-related events ( episodes or investigations ; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group ) ; however , study drugs were well tolerated with no serious adverse events being attributed to the intervention .


Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease .


However , this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria , the clinical consequences of which are uncertain , and will need careful monitoring and further study .


National Health and Medical Research Council ( Australia ) and Health Research Council ( New Zealand ) .


To examine whether insulin glargine can lead to better control of glycated haemoglobin ( HbA1c ) than that achieved by neutral protamine Hagedorn ( NPH ) insulin , using a protocol designed to limit nocturnal hypoglycaemia .


The present study , the Least One Oral Antidiabetic Drug Treatment ( LANCELOT ) Study , was a 36-week , randomized , open-label , parallel-arm study conducted in Europe , Asia , the Middle East and South America .


Participants were randomized ( 1:1 ) to begin glargine or NPH , on background of metformin with glimepiride .


Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels 5.5 mmol/l , while limiting values 4.4 mmol/l .


The efficacy population ( n = 701 ) had a mean age of 57 years , a mean body mass index of 29.8 kg/m , a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2 % ( 66mmol/mol ) .


At treatment end , HbA1c values and the proportion of participants with HbA1c < 7.0 % ( < 53mmol/mol ) were not significantly different for glargine [ 7.1 % ( 54mmol/mol ) and 50.3 % ] versus NPH [ 7.2 % ( 55mmol/mol ) and 44.3 % ] .


The rate of symptomatic nocturnal hypoglycaemia , confirmed by plasma glucose 3.9 or 3.1 mmol/l , was 29 and 48 % less with glargine than with NPH insulin .


Other outcomes were similar between the groups .


Insulin glargine was not superior to NPH insulin in improving glycaemic control .


The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins .


This study confirms , in a globally heterogeneous population , the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH , even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels .


Vaccines against norovirus , the leading cause of acute gastroenteritis , should protect against medically significant illness and reduce transmission .


In this randomized , double-blind , placebo-controlled trial , 18 - to 50-year-olds received 2 injections of placebo or norovirus GI .1 / GII .4 bivalent vaccine-like particle ( VLP ) vaccine with 3-O-desacyl-4 ' - monophosphoryl lipid A ( MPL ) and alum .


Participants were challenged as inpatients with GII .4 virus ( 4400 reverse transcription polymerase chain reaction [ RT-PCR ] units ) , and monitored for illness and infection .


Per protocol , 27 of 50 ( 54.0 % ) vaccinees and 30 of 48 ( 62.5 % ) controls were infected .


Using predefined illness and infection definitions , vaccination did not meet the primary endpoint , but self-reported cases of severe ( 0 % vaccinees vs. 8.3 % controls ; P = .054 ) , moderate or greater ( 6.0 % vs. 18.8 % ; P = .068 ) , and mild or greater severity of vomiting and/or diarrhea ( 20.0 % vs. 37.5 % ; P = .074 ) were less frequent .


Vaccination also reduced the modified Vesikari score from 7.3 to 4.5 ( P = .002 ) .


Difficulties encountered were low norovirus disease rate , and inability to define illness by quantitative RT-PCR or further antibody rise in vaccinees due to high vaccine-induced titers .


By day 10 , 11 of 49 ( 22.4 % ) vaccinees were shedding virus compared with 17 of 47 ( 36.2 % ) placebo recipients ( P = .179 ) .


Bivalent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea ; field efficacy studies are planned .


Clinical Trials Registration .


NCT01609257 .


Amphetamine challenge in rodent prepulse inhibition ( PPI ) studies has been used to model potential dopamine involvement in effects that may be relevant to schizophrenia , though similar studies in healthy humans have failed to report replicable or robust effects .


The present study investigated dexamphetamine effects on PPI in healthy humans with an increased dose and a range of startling stimulus intensities to determine participants ' sensitivity and range of responses to the stimuli .


A randomised , placebo-controlled dexamphetamine ( 0.45 mg/kg , per os . )


, double-blind , counterbalanced , within-subject design was used .


PPI was measured in 64 participants across a range of startling stimulus intensities , during two attention set conditions ( ATTEND and IGNORE ) .


Startle magnitudes for pulse-alone and prepulse-pulse magnitudes were modelled using the startle reflex magnitude ( sigmoid ) function .


Parameters were extracted from these fits , including the upper limit of the asymptote ( maximum startle reflex capacity , R MAX ) , intensity threshold , stimulus intensity that elicits a half-maximal response ( ES50 ) and the maximum rate of change of startle response magnitude to an increase in stimulus intensity .


Dexamphetamine increased the threshold and ES50 of the response to pulse-alone trials in both sexes and reduced R MAX exclusively in females .


Dexamphetamine modestly increased PPI of the R MAX across both attention conditions .


PPI of R MAX was reduced during the ATTEND condition compared to the IGNORE condition .


Results indicate that sex differences exist in motor , but not sensory , components of the startle reflex .


Findings also reveal that administration of 0.45 mg/kg dexamphetamine to healthy humans does not mimic PPI effects observed in schizophrenia .


Corticosteroid withdrawal ( CW ) after pediatric kidney transplantation potentially improves growth while avoiding metabolic and other adverse events .


We have recently reported the results of a 196 subject randomized controlled trial comparing early CW ( tacrolimus , mycophenolate mofetil ( MMF ) , daclizumab , and corticosteroids until day 4 ) with tacrolimus , MMF , and corticosteroid continuation ( CC ) .


At 6 months , CW subjects showed better growth with no adverse impact on acute rejection or graft survival ( Am J Transplant 2010 ; 10 : 828-836 ) .


This 2-year investigator-driven follow-up study aimed to determine whether improved growth persisted in the longer term .


Data regarding growth , graft outcomes and adverse events were collected at 1 year ( 113 patients ) and 2 years ( 106 patients ) after transplantation .


The primary endpoint , longitudinal growth calculated as delta height standard deviation score , was analyzed using a mixed model repeated measures model .


Corticosteroid withdrawal subjects grew better at 1 year ( difference in adjusted mean change , 0.25 ; 95 % confidence interval , 0.10 , 0.40 ; P = 0.001 ) .


At 2 years , growth remained numerically better in CW subjects ( 0.20 ( -0.01 , 0.41 ) ; P = 0.06 ) , and significantly better in prepubertal subjects ( 0.50 ( 0.16 , 0.84 ) ; P = 0.004 ) .


Bacterial and viral infection was significantly more common in CW subjects at 1 year only .


Corticosteroid withdrawal and CC subjects received similar exposure to both tacrolimus and MMF at 1 and 2 years .


No significant difference in patient or graft survival , rejection , estimated glomerular filtration rate , or other adverse events was detected .


Early CW effectively and safely improves growth up to 2 years after transplantation , particularly in prepubertal children .


Persistent eosinophilic airway inflammation in asthma increases the risk of exacerbations .


In a phase 2b dose-ranging study , we aimed to assess the efficacy and safety of benralizumab , an anti-interleukin 5 receptor monoclonal antibody that depletes blood and airway eosinophils , in adults with uncontrolled eosinophilic asthma .


We did a randomised , controlled , double-blind , dose-ranging phase 2b study .


Eligible participants were adults aged 18-75 years with uncontrolled asthma using medium-dose or high-dose inhaled corticosteroids and longacting agonists , with two to six exacerbations in the past year .


Current or former smokers were excluded .


We used the ELEN index ( an algorithm to predict elevated sputum eosinophils ) or baseline fraction of exhaled nitric oxide to stratify patients by eosinophilic status , and with an interactive web-voice response system randomly assigned eosinophilic individuals in a 1:1:1:1 ratio to receive placebo , 2 mg benralizumab , 20 mg benralizumab , or 100 mg benralizumab , and non-eosinophilic individuals in a 1:1 ratio to receive placebo or 100 mg benralizumab .


Study drugs were given as two subcutaneous injections every 4 weeks for the first three doses , then every 8 weeks , for 1 year .


Patients , treating physicians , and study investigators were masked to treatment allocation .


The primary endpoint was annual exacerbation rate in eosinophilic individuals after 1 year of follow-up .


Analysis was by modified intention to treat .


This study was designed with a two-sided of 02 and powered at 78 % for the primary outcome in the eosinophilic population .


This study is registered with ClinicalTrials.gov , number NCT01238861 .


Between Jan 3 , 2011 , and March 6 , 2012 , we randomly assigned 324 eosinophilic individuals to placebo ( n = 80 ) or benralizumab 2 mg dose ( n = 81 ) , 20 mg dose , ( n = 81 ) , or 100 mg dose ( n = 82 ) , and 285 non-eosinophilic individuals to 100 mg benralizumab ( n = 142 , 140 included in analysis ) or placebo ( n = 143 , 142 included in analysis ) .


In eosinophilic individuals , benralizumab reduced exacerbation rates compared with placebo in the 100 mg group ( 034 vs 057 , reduction 41 % , 80 % CI 11 to 60 , p = 0096 ) but not in the 2 mg group ( 065 vs 057 , difference -9 % , 80 % CI -59 to 26 , p = 0781 ) or the 20 mg group ( 037 vs 057 , reduction 36 % , 80 % CI 3 to 58 , p = 0173 ) .


In patients with a baseline blood eosinophil cutoff of at least 300 cells per L , exacerbation rates in the benralizumab 20 mg group ( n = 70 ) and 100 mg group ( n = 97 ) were lower than in the placebo group ( n = 83 ; 030 vs 068 , reduction 57 % , 80 % CI 33 to 72 , p = 0015 for 20 mg dose ; 038 vs 068 , difference 43 % , 80 % CI 18 to 60 , p = 0049 for 100 mg dose ) .


Our findings suggested that benralizumab 20 mg and 100 mg resided at the dose-response plateau .


Treatment-emergent adverse events occurred in 277 ( 72 % ) of 385 participants receiving any benralizumab dose compared with 143 ( 65 % ) of 221 receiving placebo .


Nasopharyngitis ( 44 [ 11 % ] patients receiving benralizumab vs 13 [ 6 % ] patients receiving placebo ) and injection site reactions ( 60 [ 16 % ] vs eight [ 4 % ] ) occurred more frequently with benralizumab than with placebo .


Benralizumab at 20 mg and 100 mg doses seemed to reduce asthma exacerbations in adults with uncontrolled eosinophilic asthma and baseline blood eosinophils of at least 300 cells per L , possibly due to targeting of the interleukin 5 receptor rather than interleukin 5 ligand .


Further investigation of benralizumab treatment in phase 3 studies is warranted .


MedImmune .


We evaluated 3 methods of integrating interventions for depression ( Adolescent Coping With Depression Course ; CWD ) and substance use disorders ( Functional Family Therapy ; FFT ) , examining ( a ) treatment sequence effects on substance use and depression outcomes and ( b ) whether the presence of major depressive disorder ( MDD ) moderated effects .


Participants were 170 adolescents ( ages 13-18 ; 22 % female ; 61 % non-Hispanic White ) with comorbid depressive disorder ( 54 % MDD , 18 % dysthymia ) and substance use disorders who were randomized to ( a ) FFT followed by CWD ( FFT/CWD ) , ( b ) CWD followed by FFT ( CWD/FFT ) , or ( c ) coordinated FFT and CWD ( CT ) .


Acute treatment ( 24 treatment sessions provided over 20 weeks ) and 6 - and 12-month follow-up effects are presented for substance use ( percentage of days of substance use ; Timeline Followback ) and depression ( Children 's Depression Rating Scale-Revised ) .


FFT/CWD achieved better substance use outcomes than CT at posttreatment , and 6 - and 12-month follow-ups ; substance use effects for CWD/FFT were intermediate .


For participants with baseline MDD , the CWD/FFT sequence resulted in lower substance use than either FFT/CWD or CT. .


Depressive symptoms decreased significantly in all 3 treatment sequences with no evidence of differential effectiveness during or following treatment .


Attendance was lower for the second of both sequenced interventions .


A large proportion of the sample received treatment outside the study , which predicted better outcomes in the follow-up .


Depression reductions occurred early in all 3 treatment sequences .


Of the examined treatment sequences , FFT/CWD appeared most efficacious for substance use reductions but addressing depression early in treatment may improve substance use outcomes in the presence of MDD .


Drug development in chronic obstructive pulmonary disease ( COPD ) has been characterised by unacceptably high failure rates .


In addition to the poor sensitivity in forced expiratory volume in one second ( FEV1 ) , numerous causes are known to contribute to this phenomenon , which can be clustered into drug - , disease - and design-related factors .


Here we present a model-based approach to describe disease progression , treatment response and dropout in clinical trials with COPD patients .


Data from six phase II trials lasting up to 6 months were used .


Disease progression ( trough FEV1 measurements ) was modelled by a time-varying function , whilst the treatment effect was described by an indirect response model .


A time-to-event model was used for dropout


All relevant parameters were characterised with acceptable precision .


Two parameters were necessary to model the dropout patterns , which was found to be partly linked to the treatment failure .


Disease severity at baseline , previous use of corticosteroids , gender and height were significant covariates on disease baseline whereas disease severity and reversibility to salbutamol/salmeterol were significant covariates on Emax for salmeterol active arm .


Incorporation of the various interacting factors into a single model will offer the basis for patient enrichment and improved dose rationale in COPD .


To evaluate the efficacy and safety of domestically produced Salbutamol Sulfate metered dose inhaler ( MDI ) without chloro-fluro-carbon ( CFC ) in the treatment of asthmatic patients .


A muticenter , randomized , double-blind , positive controlled clinical trial was conducted in asthmatic patients .


The participants were randomized divided into trial group treated with domestically produced Salbutamol Sulfate Aerosol MDI ( 200 microg single-dose ) and control group treated with imported Salbutamol Sulfate Aerosol MDI ( 200 microg single-dose ) .


The lung function was measured by spirometry and a scoring questionaire before medications and 15 , 30 , 120 and 240 min post medications .


A total of 238 patients were enrolled in the trial .


Compared with baselines , the forced expiratory volume in 1 s ( FEV1 ) of the participants in both groups increased significantly 15 , 30 , 120 and 240 min after medications ( P < 0.05 ) .


There was no significant difference in the changes of FEV1 between the two groups ( P > 0.05 ) .


Similarly , the forced vital capacity ( FVC ) and asthma symptomatic scores of the participants in both groups improved significantly after administration of medications ( P < 0.05 ) .


There was no significant difference in the ratio of adverse reactions between the two groups ( P > 0.05 ) .


In both groups , drugs were well tolerated .


The domestically produced Salbutamol Sulfate Aerosol MDI without CFC is effective and safe for treating asthma .


The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized .


In this investigation , we examined the effect of 2 commonly used doses of dexamethasone ( 4 and 8 mg at induction of anesthesia ) on blood glucose concentrations during the first 24 hours after administration .


Two hundred women patients were randomized to 1 of 6 groups : Early-control ( saline ) ; Early-4 mg ( 4 mg dexamethasone ) ; Early-8 mg ( 8 mg dexamethasone ) ; Late-control ( saline ) ; Late-4 mg ( 4 mg dexamethasone ) ; and Late-8 mg ( 8 mg dexamethasone ) .


Blood glucose concentrations were measured at baseline and 1 , 2 , 3 , and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups .


The incidence of hyperglycemic events ( the number of patients with at least 1 blood glucose concentration > 180 mg/dL ) was determined .


Blood glucose concentrations increased significantly over time in all control and dexamethasone groups ( from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL , all P < 0.001 ) .


Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone ( either 4 or 8 mg ) and those receiving saline at any measurement time .


The incidence of hyperglycemic events did not differ in any of the early ( 21 % -28 % , P = 0.807 ) or late ( 13 % -24 % , P = 0.552 ) groups .


Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations , these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia .


Nausea and vomiting can occur in Parkinson 's disease ( PD ) patients initiated on apomorphine subcutaneous injections and antiemetic prophylaxis is recommended per product labeling .


Data suggest long-term antiemetic prophylaxis may not be needed , although this has not been systematically studied .


We evaluated coadministered trimethobenzamide with apomorphine in 182 PD subjects using a randomized , double-blind , placebo-controlled design , with phased withdrawal of subjects from trimethobenzamide to placebo .


Evaluations included presence/absence of nausea and vomiting ; Index of Nausea , Vomiting , and Retching ( INVR ) ; subject evaluation of medication ; Unified Parkinson 's Disease Rating Scale ( UPDRS ) motor score ; `` on '' response post-injection ; and safety assessments .


Incidence of nausea and/or vomiting on Day 1 of apomorphine initiation ( primary endpoint ) was not significantly different between trimethobenzamide and placebo .


Over a longer period , a significantly lower incidence was found for trimethobenzamide during Period 1 ( Days 1-28 , p = 0.025 ) and Period 2 ( Days 29-56 , p = 0.005 ) , with no difference during Period 3 ( Days 57-84 ) .


INVR results were generally more favorable with trimethobenzamide than placebo in Period 1 and significantly more favorable in Period 2 .


The majority of subjects in both groups achieved an `` on '' response after apomorphine injection at all assessments .


No significant differences were found between groups for UPDRS motor scores .


No added safety risk with concomitant use of trimethobenzamide and apomorphine was found .


Our data suggest that trimethobenzamide helps reduce nausea/vomiting during the first 8 weeks of apomorphine therapy , but is generally not needed thereafter .


Trimethobenzamide did not worsen parkinsonism nor affect `` on '' response after apomorphine injection .


To evaluate the association between outdoor and nearwork activities at baseline and myopia stabilisation by age 15 in the Correction of Myopia Evaluation Trial ( COMET ) .


Correction of Myopia Evaluation Trial enrolled 469 children ( ages : 6-11years ) with spherical equivalent myopia between -1.25 and -4.50 D , who were randomised to progressive addition or single vision lenses and followed for 5years in their original lenses .


At baseline , families recorded the child 's outdoor and nearwork activities for 3days within a week .


Weekly hours spent in nearwork and outdoor activities were calculated for each participant .


Refractions collected over 11years were fit using the Gompertz function to determine each participant 's myopia stabilisation age .


Myopia for each child was then categorized as stable/not stable by age 15 .


Half ( 233/469 ) of participants had usable baseline activity diaries and refraction data that could be fit with the Gompertz function , 59.7 % ( 139/233 ) had stable myopia by age 15 and 40.3 % had myopia that was not yet stable .


The frequency of stable myopia was similar for the two categories ( median split ) of outdoor activities : 60 % ( 71/118 ) for 9.0 hours/week ( -1 ) and 59 % ( 68/115 ) for > 9.0 hours/week ( -1 ) .


56 % ( 64/114 ) of children reporting > 21.0 h of baseline weekly nearwork activity had stable myopia by age 15 compared to 63 % ( 75/119 ) with 21.0 h of near work ( adjusted OR = 0.74 ; 95 % CI : 0.43-1 .29 ) .


Using baseline nearwork as a continuous variable , the multivariable odds ratio for the association between baseline nearwork hours and stabilisation by age 15 is 0.98 : 95 % CI : 0.96-1 .00 , a result trending towards significance .


While time spent in outdoor activities in childhood does not appear to be related to myopia stabilisation by age 15 , less near work activity might potentially be associated with myopia stabilisation by that age .


The long-term safety and therapeutic response of sodium oxybate ( SXB ) in fibromyalgia syndrome ( FM ) patients were assessed for a combined period of up to 1 year in a prospective , multicenter , open-label , extension study in patients completing 1 of 2 phase 3 randomized , double-blind , controlled , 14-week trials that examined the efficacy and safety of SXB 4.5 g , SXB 6 g , and placebo for treatment of FM .


This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries .


Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged 18 years met the American College of Rheumatology 1990 criteria for FM , had a body mass index ( BMI ) < 40 kg/m2 , and had a score 50 on a 100-mm pain visual analog scale ( VAS ) at baseline .


All patients began treatment in the extension study with SXB 4.5 g/night ( administered in 2 equally divided doses ) for at least 1 week , followed by possible serial 1.5 g/night dose increases to 9 g/night ( maximum ) or reductions to 4.5 g/night ( minimum ) .


Of the 560 FM patients enrolled in this extension study , 319 ( 57.0 % ) completed the study .


The main reason for early discontinuation was adverse events ( AEs ; 23.0 % of patients ) .


Patients were primarily middle-aged ( mean 46.910.8 years ) , female ( 91.1 % ) , white ( 91.4 % ) , with a mean duration of FM symptoms of 9.98.7 years .


Serious AEs were experienced by 3.6 % of patients .


The most frequently reported AEs ( incidence 5 % at any dose or overall ) were nausea , headache , dizziness , nasopharyngitis , vomiting , sinusitis , diarrhea , anxiety , insomnia , influenza , somnolence , upper respiratory tract infection , muscle spasms , urinary tract infection , and gastroenteritis viral .


Maintenance of SXB therapeutic response was demonstrated with continued improvement from controlled-study baseline in pain VAS , Fibromyalgia Impact Questionnaire ( FIQ ) total scores , and other measures .


Responder analyses showed that 68.8 % of patients achieved 30 % reduction in pain VAS and 69.7 % achieved 30 % reduction in FIQ total score at study endpoint .


The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials .


Improvement in pain and other FM clinical domains was maintained during long-term use .


ClinicalTrials.gov NCT00423605 .


To evaluate the efficacy of the stair-step protocol using clomiphene citrate ( CC ) and to assess the uterine and systemic side effects in patients with polycystic ovary syndrome ( PCOS ) .


A total of 60 PCOS patients who failed to respond to 50mg/day for 5days of CC treatment within the cycle were randomly allocated to the control ( traditional protocol ) and study ( stair-step protocol ) groups .


In the stair-step protocol , patients were treated with CC 50mg/day for 5days and then in nonresponsive patients , the dosage was increased to 100mg/day for 5days in the same cycle .


Patients who failed the 50mg/day CC treatment in the previous cycle were stimulated with 100mg/day CC and were accepted as the control group .


Ovulation and pregnancy rates , duration of treatment and uterine and systemic side effects were evaluated .


Ovulation and pregnancy rates were similar between the stair-step and the control group ( 43.3 vs. 33.3 % , respectively ) ( 16.7 vs. 10 % , respectively ) .


The duration of treatment was significantly shorter in stair-step compared to traditional protocol ( 20.52.0 vs. 48.62.4 days , respectively ) .


There were no significant differences in the systemic side effects between the groups .


Uterine side effects were evaluated with endometrial thickness and uterine artery Doppler ultrasound ; no significant differences were observed in stair-step compared to traditional protocol .


The stair-step protocol was determined to have a significantly shorter treatment period without any detrimental effect on the ovulation and pregnancy rates .


Patient blood management combines the use of several transfusion alternatives .


Integrated use of erythropoietin , cell saver , and/or postoperative drain reinfusion devices on allogeneic erythrocyte use was evaluated using a restrictive transfusion threshold .


In a factorial design , adult elective hip - and knee-surgery patients with hemoglobin levels 10 to 13 g/dl ( n = 683 ) were randomized for erythropoietin or not , and subsequently for autologous reinfusion by cell saver or postoperative drain reinfusion devices or for no blood salvage device .


Primary outcomes were mean allogeneic intra - and postoperative erythrocyte use and proportion of transfused patients ( transfusion rate ) .


Secondary outcome was cost-effectiveness .


With erythropoietin ( n = 339 ) , mean erythrocyte use was 0.50 units ( U ) / patient and transfusion rate 16 % while without ( n = 344 ) , these were 0.71 U/patient and 26 % , respectively .


Consequently , erythropoietin resulted in a nonsignificant 29 % mean erythrocyte reduction ( ratio , 0.71 ; 95 % CI , 0.42 to 1.13 ) and 50 % reduction of transfused patients ( odds ratio , 0.5 ; 95 % CI , 0.35 to 0.75 ) .


Erythropoietin increased costs by 785 per patient ( 95 % CI , 262 to 1,309 ) , that is , 7,300 per avoided transfusion ( 95 % CI , 1,900 to 24,000 ) .


With autologous reinfusion , mean erythrocyte use was 0.65 U/patient and transfusion rate was 19 % with erythropoietin ( n = 214 ) and 0.76 U/patient and 29 % without ( n = 206 ) .


Compared with controls , autologous blood reinfusion did not result in erythrocyte reduction and increased costs by 537 per patient ( 95 % CI , 45 to 1,030 ) .


In hip - and knee-replacement patients ( hemoglobin level , 10 to 13 g/dl ) , even with a restrictive transfusion trigger , erythropoietin significantly avoids transfusion , however , at unacceptably high costs .


Autologous blood salvage devices were not effective .


The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis ( UC ) has been reported up to week 52 from the placebo-controlled trials ULTRA ( Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab ) 1 and 2 .


Up to 4 years of data for adalimumab-treated patients from ULTRA 1 , 2 , and the open-label extension ULTRA 3 are presented .


Remission per partial Mayo score , remission per Inflammatory Bowel Disease Questionnaire ( IBDQ ) score , and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208 .


Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline .


Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing , respectively .


As observed , last observation carried forward ( LOCF ) and nonresponder imputation ( NRI ) were used to report efficacy .


Adverse events were reported for any adalimumab-treated patient .


A total of 600/1 ,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies .


Of these , 199 patients remained on adalimumab after 4 years of follow-up .


Rates of remission per partial Mayo score , remission per IBDQ score , mucosal healing , and corticosteroid discontinuation at week 208 were 24.7 % , 26.3 % , 27.7 % ( NRI ) , and 59.2 % ( observed ) , respectively .


Of the patients who were followed up in ULTRA 3 ( 588/1 ,094 ) , a total of 360 patients remained on adalimumab 3 years later .


Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6 % and 59.9 % of patients , respectively ( NRI ) .


Adverse event rates were stable over time .


Remission , mucosal healing , and improved quality of life were maintained in patients with moderately to severely active UC with long-term adalimumab therapy , for up to 4 years .


No new safety signals were reported .


Robotic thyroidectomy ( RoT ) is frequently performed due to its excellent cosmesis and recovery features .


However , postoperative pain in the operating field after RoT remains a concern due to extensive tissue dissection and tension during the operation .


The aim of this study was to evaluate the anterior chest pain and the effect of levobupivacaine spraying on postoperative pain control after bilateral axillo-breast approach ( BABA ) RoT .


We randomized 55 adult patients scheduled for BABA RoT into the control group ( group C , n = 27 ) or the levobupivacaine group ( group L , n = 28 ) .


At the end of surgery , patients in groups C and L were sprayed with the same volume ( 30 ml ) of normal saline and 0.25 % levobupivacaine , respectively , on the flap dissection area .


Pain scores , the consumption of patient-controlled analgesia ( PCA ) , and other adverse effects were assessed at 1 , 6 , 24 , and 48 h postoperatively .


Patients in group L showed lower pain scores than those of group C at 1 h ( 50 [ 0-100 ] vs. 80 [ 20-100 ] ; p = 0.004 ) , 6 h ( 30 [ 0-90 ] vs. 70 [ 30-90 ] ; p < 0.001 ) , 24 h ( 30 [ 0-80 ] vs. 50 [ 10-80 ] ; p = 0.016 ) and 48 h ( 10 [ 0-80 ] vs. 30 [ 10-80 ] ; p < 0.001 ) postoperatively .


PCA consumption of group L was less than that of group C at 6 , 24 , and 48 h after surgery .


There were no significant differences in postoperative nausea-vomiting , headache , or dizziness .


Local anesthetic-related adverse effects were not reported .


Levobupivacaine spray on the operative field at the end of BABA RoT reduced postoperative pain and PCA consumption without adverse events .


In dental applications , as in all other medical applications , pain needs to be prevented or at least controlled .


The use of the tooth as a model for studying pain mechanisms is well established .


In the current study , we aimed to evaluate and compare the analgesic effects of gabapentin and lornoxicam , respectively , vs a placebo for postendodontic treatment pain .


Clinical research was planned as prospective , randomized , and placebo controlled .


Each subject was given 600mg gabapentin ( group G : N = 30 ) , 8mg lornoxicam ( group L : N = 30 ) , or a placebo ( group C : N = 30 ) 30 min prior to endodontic treatment .


At 4 ( T ( 3 ) ) , 8 ( T ( 4 ) ) , 12 ( T ( 5 ) ) , and 24 ( T ( 6 ) ) h after preoperative ( T ( 0 ) ) time points , the analgesic efficacies of the agents were evaluated by using the visual analog scale ( VAS ) .


In group G , VAS values were significantly greater at T ( 0 ) time point than at T ( 5 ) or T ( 6 ) .


T ( 0 ) time point VAS value in group L was lower than at T4 time point and greater than at T ( 6 ) .


In group C , T ( 0 ) time point VAS values were significantly lower at T ( 3 ) and T ( 5 ) time points and greater than at T ( 6 ) time point .


VAS values in group G at T ( 5 ) time point were significantly lower than in group C or group L ( P < 0.05 ) .


Based on the obtained data , prophylactic lornoxicam controlled postendodontic treatment pain more effectively than did the placebo drugs , and gabapentin was more effective in controlling the pain than either lornoxicam or the placebo .


To compare the outcomes of the nasal obstruction , the main symptom of the patients who underwent radiofrequency and lateral displacement of the inferior turbinate and patients who were treated with radiofrequency alone .


The prospective randomised study was conducted at the Department of Otorhinolaryngology and Head-Neck Surgery , Balikesir University Medical School , Balikesir , Turkey , between July and December 2012 .


It included 60 patients , diagnosed with allergic or non-allergic chronic rhinitis with inferior turbinate hypertrophy which was refractory to medical therapy .


Half of the patients were treated with radiofrequency , and the rest with radiofrequency and lateral displacement .


The main symptom of the patients was nasal obstruction .


The frequency and degree of nasal obstruction were evaluated by patients ' self-assessments using the standard 10-cm visual analogue scale .


The evaluations were performed first pre-operatively and on the 1st , 3rd , 5th and 7th days postoperatively as well as at the end of the 4th week .


SPSS 18 was used for statistical analysis .


Nasal obstruction frequency and severity scores in patients treated with both radiofrequency and lateral displacement on post-operative days 3 , 5 and 7 were found to be significantly lower ( p < 0.001 ) compared to the patients treated with only radiofrequency .


The study demonstrated that radiofrequency and lateral displacement together is an effective method to prevent inferior turbinate oedema in the early post-operative period .


Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A antagonist that inhibits platelet aggregation and vasoconstriction .


The aim of this study was to compare the pharmacokinetics of a sarpogrelate controlled-release formulation ( CR ) with those of the immediate-release formulation ( IR ) .


The effect of food on the pharmacokinetics of CR sarpogrelate was also evaluated .


A randomized , open-label , 3-period , 3-treatment crossover study was conducted in 50 healthy male subjects .


Subjects were allocated into one of six sequence groups .


In one period , a 100-mg IR formulation was administered three times at 6-h intervals , and in the other two periods , a 300-mg CR formulation was administered once to fasting and once to fed subjects .


Each period was separated by a 7-day washout period .


Serial blood samples were collected up to 24h after the first drug administration in each period .


The plasma concentrations of sarpogrelate were analysed by liquid chromatography-tandem mass spectrometry .


Pharmacokinetic parameters were calculated by non-compartmental methods .


After the administration of the IR formulation , the plasma concentration reached a peak at 048h and the drug was eliminated with a half-life ( t1/2 ) of 07h .


After administration of the CR formulation , the plasma concentration reached a peak at 05h and the drug was eliminated with a t1/2 of 323h .


The geometric mean ratios ( CR/IR ) for sarpogrelate area under the plasma concentration-time curve ( AUC ) and the maximum plasma drug concentration ( Cmax ) were 12040 ( 90 % confidence interval ( CI ) : 10992-13188 ) and 09462 ( 90 % CI : 08504-10529 ) .


When CR was administered to fed subjects , the time to peak concentration was prolonged to 397h and t1/2 was shortened to 145h .


The geometric mean ratios ( fasting/fed ) for sarpogrelate AUC and Cmax were 08573 ( 90 % CI : 07687-09561 ) and 06452 ( 90 % CI : 05671-07341 ) .


After the administration of CR and IR formulations of the same daily dose of sarpogrelate hydrochloride , the overall systemic exposure was slightly higher for the CR than for the IR formulation , whereas peak concentration was comparable between the two formulations .


Food reduced the bioavailability of sarpogrelate CR .


With increasing numbers of type 2 diabetes ( DM2 ) and hypertension patients , there is a pressing need for effective , time-efficient and sustainable strategies to help physicians support their patients to achieve higher physical activity levels .


SMARTER will determine whether physician-delivered step count prescriptions reduce arterial stiffness over a one-year period , compared with usual care , in sedentary overweight/obese adults with DM2/hypertension .


Randomized , allocation-concealed , assessor-blind , multisite clinical trial .


The primary outcome is change in arterial stiffness over one year .


The secondary outcomes include changes in physical activity , individual vascular risk factors , medication use , and anthropometric parameters .


Assessments are at baseline and one year .


Participants are sedentary/low active adults with 25BMI < 40 kg/m2 followed for DM2/hypertension by a collaborating physician .


The active arm uses pedometers to track daily step counts and review logs with their physicians at 3 to 4-month intervals .


A written step count prescription is provided at each visit , aiming to increase counts by 3,000 steps/day over one year , with an individualized rate increase .


The control arm visits physicians at the same frequency and receives advice to engage in physical activity 30-60 minutes/day .


SMARTER will enroll 364 individuals to detect a 105 % difference in arterial stiffness change between arms .


Arterial stiffness is assessed noninvasively with carotid femoral pulse wave velocity using applanation tonometry .


The importance of SMARTER lies not simply in the use of pedometer-based monitoring but also on its integration into a prescription-based intervention delivered by the treating physician .


Equally important is the measurement of impact of this approach on a summative indicator of arterial health , arterial stiffness .


If effectiveness is demonstrated , this strategy has strong potential for widespread uptake and implementation , given that it is well-aligned with the structure of current clinical practice .


ClinicalTrials.gov ( NCT01475201 ) .


To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus ( MRSA ) .


Parallel , open label , randomised controlled trial .


Four acute care hospitals in Israel .


Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin .


Patients with left sided endocarditis , meningitis , chronic haemodialysis , and prolonged neutropenia were excluded .


Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication .


The primary efficacy outcome was treatment failure assessed at day 7 , consisting of death , persistence of haemodynamic instability or fever , stable or worsening Sequential Organ Failure Assessment score , and persistence of bacteraemia .


The primary safety outcome was all cause mortality at day 30 .


Non-inferiority was defined by a difference of less than 15 % for treatment failure .


252 patients were included in the trial , of whom 91 ( 36 % ) had bacteraemia .


No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole ( 51/135 , 38 % ) versus vancomycin ( 32/117 , 27 % ) - risk ratio 1.38 ( 95 % confidence interval 0.96 to 1.99 ) .


However , trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion-absolute difference 10.4 % ( 95 % confidence interval -1.2 % to 21.5 % ) .


For patients with bacteraemia , the risk ratio was 1.40 ( 0.91 to 2.16 ) .


In a multivariable logistic regression analysis , trimethoprim-sulfamethoxazole was significantly associated with treatment failure ( adjusted odds ratio 2.00 , 1.09 to 3.65 ) .


The 30 day mortality rate was 32/252 ( 13 % ) , with no significant difference between arms .


Among patients with bacteraemia , 14/41 ( 34 % ) treated with trimethoprim-sulfamethoxazole and 9/50 ( 18 % ) with vancomycin died ( risk ratio 1.90 , 0.92 to 3.93 ) .


High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to vancomycin in the treatment of severe MRSA infections .


The difference was particularly marked for patients with bacteraemia .


Trial registration Clinical trials NCT00427076 .


The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD .


A multicenter , double-blind , double-dummy , and randomized controlled trial ( RCT ) was conducted .


All groups were treated with additional conventional medicines .


There were a 6-month treatment and a 12-month follow-up for 5 times .


Primary outcomes included lung function test , exacerbation frequency , score of SGRQ .


Second outcomes consisted of 6MWD , BODE index , psychological field score , inflammatory factors and cortisol .


A total of 331 patients were randomly divided into two active treatment groups ( Bushen Yiqi ( BY ) granule group , n = 109 ; Bushen Fangchuan ( BF ) tablet group , n = 109 ) and a placebo group ( n = 113 ) .


Finally 262 patients completed the study .


BY granule & BF tablet increased the values of VC , FEV1 ( % ) and FEV1/FVC ( % ) , compared with placebo .


BY granule improved PEF .


Both treatments reduced acute exacerbation frequency ( P = 0.067 ) , BODE index and psychological field score , while improved 6MWD .


In terms of descent rang of SGRQ score , both treatments increased ( P = 0.01 ) .


Both treatments decreased inflammatory cytokines , such as IL-8 , and IL-17 ( P = 0.0219 ) .


BY granule obviously descended IL-17 ( P < 0.05 ) , IL-1 ( P = 0.05 ) , IL-6 , compared with placebo .


They improved the level of IL-10 and cortisol .


BY granule raised cortisol ( P = 0.07 ) and decreased TNF - .


Both treatments slightly descended TGF-1 .


In terms of safety , subject compliance and drug combination , there were no differences ( P > 0.05 ) among three groups .


BY granule and BF tablet were positively effective for the treatment of COPD , and the former performed better in general .


Chinese Clinical Trial Register center ChiCTR-TRC-09000530 .


Adjuvant endocrine therapy compromises bone health in patients with breast cancer , causing osteopenia , osteoporosis , and fractures .


Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects .


In this trial , we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal , aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer .


In this prospective , double-blind , placebo-controlled , phase 3 trial , postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden .


Patients were assigned by an interactive voice response system .


The randomisation schedule used a randomly permuted block design with block sizes 2 and 4 , stratified by type of hospital regarding Hologic device for DXA scans , previous aromatase inhibitor use , and baseline bone mineral density .


Patients , treating physicians , investigators , data managers , and all study personnel were masked to treatment allocation .


The primary endpoint was time from randomisation to first clinical fracture , analysed by intention to treat .


As an additional sensitivity analysis , we also analysed the primary endpoint on the per-protocol population .


Patients were treated until the prespecified number of 247 first clinical fractures was reached .


This trial is ongoing ( patients are in follow-up ) and is registered with the European Clinical Trials Database , number 2005-005275-15 , and with ClinicalTrials.gov , number NCT00556374 .


Between Dec 18 , 2006 , and July 22 , 2013 , 3425 eligible patients were enrolled into the trial , of whom 3420 were randomly assigned to receive denosumab 60 mg ( n = 1711 ) or placebo ( n = 1709 ) subcutaneously every 6 months .


Compared with the placebo group , patients in the denosumab group had a significantly delayed time to first clinical fracture ( hazard ratio [ HR ] 050 [ 95 % CI 039-065 ] , p < 00001 ) .


The overall lower number of fractures in the denosumab group ( 92 ) than in the placebo group ( 176 ) was similar in all patient subgroups , including in patients with a bone mineral density T-score of -1 or higher at baseline ( n = 1872 , HR 044 [ 95 % CI 031-064 ] , p < 00001 ) and in those with a bone mineral density T-score of less than -1 already at baseline ( n = 1548 , HR 057 [ 95 % CI 040-082 ] , p = 0002 ) .


The patient incidence of adverse events in the safety analysis set ( all patients who received at least one dose of study drug ) did not differ between the denosumab group ( 1366 events , 80 % ) and the placebo group ( 1334 events , 79 % ) , nor did the numbers of serious adverse events ( 521 vs 511 [ 30 % in each group ] ) .


The main adverse events were arthralgia and other aromatase-inhibitor related symptoms ; no additional toxicity from the study drug was reported .


Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel , no cases of osteonecrosis of the jaw were reported .


93 patients ( 3 % of the full analysis set ) died during the study , of which one death ( in the denosumab group ) was thought to be related to the study drug .


Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors , and can be administered without added toxicity .


Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab , this treatment should be considered for clinical practice .


Amgen .


Fractalkine ( CX3CL1 ) is a chemokine associated with atherosclerosis and inflammation .


There is limited knowledge of fractalkine levels during acute myocardial infarction ( AMI ) and stem cell treatment .


We aimed to investigate the time profile of circulating fractalkine and gene expression of its receptor CX3CR1 during AMI , and the influence of intracoronary autologous bone marrow stem cell ( mBMC ) transplantation ( given 6 days after AMI ) on fractalkine levels .


We examined fractalkine levels at different time points by enzyme-linked immunosorbent assay ( ELISA ) in 20 patients with AMI , and 10 patients with stable angina pectoris ( AP ) undergoing percutaneous coronary intervention ( PCI ) , and in 100 patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction ( ASTAMI ) trial .


Patients with AMI had significantly elevated levels 3 - and 12 h after PCI compared to patients with stable AP .


After 12 h levels were similar in the two groups .


An inverse pattern was observed in gene expression levels .


No correlation between fractalkine levels and myocardial injury or infarct size was seen .


We could not demonstrate any influence of autologous mBMC transplantation on fractalkine levels .


Fractalkine levels are elevated the first 12 h after PCI in patients with AMI , however , not correlated to infarct size .


The inverse pattern in gene expression of fractalkine receptor ( CX3CR1 ) might be a compensatory mechanism .


No effect of autologous mBMC transplantation given 6 days after AMI on fractalkine levels was observed .


This prospective comparative study was done to evaluate the effectiveness of implants of different design ( titanium elastic intramedullary nail versus anatomical precontoured dynamic compression plate ) in treatment of displaced midshaft clavicular fractures .


Sixty-six patients between 18 and 65years of age were included in this study .


They were randomized in two groups to be treated with either elastic intramedullary nail ( EIN ) or plate .


Clinical and radiological assessments were performed at regular intervals .


Outcomes and complications of both groups over 2years of follow-up time were compared .


Length of incision , operation time , blood loss and duration of hospital stay were significantly less for the EIN group .


American Shoulder and Elbow Surgeons ( ASES ) and Constant Shoulder scores were significantly higher ( p < 0.05 ) in the plating group than the EIN group for the first 2months but there was no significant difference found between the two groups regarding functional and radiological outcome at the 2-year follow-up .


Significantly higher rates of refracture after implant removal ( p = 0.045 ) in the plating group was observed .


Infection and revision surgery rates were also higher in the plate group , but this difference was insignificant ( p > 0.05 ) .


EIN is a safe , minimally invasive surgical technique with a lower complication rate , faster return to daily activities , excellent cosmetic and comparable functional results , and can be used as an equally effective alternative to plate fixation in displaced midshaft clavicle fractures .


Level 2 .


Adjuvant therapy with an aromatase inhibitor improves outcomes , as compared with tamoxifen , in postmenopausal women with hormone-receptor-positive breast cancer .


In two phase 3 trials , we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years .


Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin , oophorectomy , or ovarian irradiation .


The primary analysis combined data from 4690 patients in the two trials .


After a median follow-up of 68 months , disease-free survival at 5 years was 91.1 % in the exemestane-ovarian suppression group and 87.3 % in the tamoxifen-ovarian suppression group ( hazard ratio for disease recurrence , second invasive cancer , or death , 0.72 ; 95 % confidence interval [ CI ] , 0.60 to 0.85 ; P < 0.001 ) .


The rate of freedom from breast cancer at 5 years was 92.8 % in the exemestane-ovarian suppression group , as compared with 88.8 % in the tamoxifen-ovarian suppression group ( hazard ratio for recurrence , 0.66 ; 95 % CI , 0.55 to 0.80 ; P < 0.001 ) .


With 194 deaths ( 4.1 % of the patients ) , overall survival did not differ significantly between the two groups ( hazard ratio for death in the exemestane-ovarian suppression group , 1.14 ; 95 % CI , 0.86 to 1.51 ; P = 0.37 ) .


Selected adverse events of grade 3 or 4 were reported for 30.6 % of the patients in the exemestane-ovarian suppression group and 29.4 % of those in the tamoxifen-ovarian suppression group , with profiles similar to those for postmenopausal women .


In premenopausal women with hormone-receptor-positive early breast cancer , adjuvant treatment with exemestane plus ovarian suppression , as compared with tamoxifen plus ovarian suppression , significantly reduced recurrence .


( Funded by Pfizer and others ; TEXT and SOFT ClinicalTrials.gov numbers , NCT00066703 and NCT00066690 , respectively . )


urgent development of effective interventions to prevent rapidly rising childhood obesity in China is needed .


Between May 2010 and December 2013 , a cluster randomized controlled trial was conducted among 4th graders in eight urban primary schools randomly assigned to intervention or control groups in Nanjing , China .


A multi-component intervention program was implemented within the treatment group , while students in the control group followed their usual health education curriculum without additional intervention .


At baseline , 638 and 544 students were enrolled in the intervention and control group , respectively .


The prevalence of excess body weight was 26.8 % , with 27.4 % in the intervention group and 26.1 % in the control group ( p = 0.61 ) .


The mean ( SD ) BMI and WC was 18.7 ( 3.0 ) and 63.0 ( 9.2 ) for participants in intervention schools , and 18.5 ( 2.9 ) and 63.6 ( 8.7 ) for students in control group , separately ( p = 0.24 and 0.41 , respectively ) .


Compared to those who were not aware of what lifestyle/behavior factors were unhealthy , students who were aware of the unhealthy lifestyle / behavior factors consumed fewer fried snacks ( 0.460.76 serves/week vs 0.650.91 serves/week ; p < 0.01 ) , soft drinks ( 160194 ml/week vs 199227 ml/week ; p < 0.01 ) , but larger amount of meat ( 502429 g/week vs 449344 g/week ; p = 0.03 ) , and reported less screen time ( 214232 minutes/week vs 252264 minutes/week ; p < 0.01 ) .


Moreover , there was no difference within physical activity time between these two groups ( 257341 minutes/week vs 218324 minutes/week ; p = 0.13 ) .


Main characteristics of participants were balanced at baseline within intervention and control schools , but a gap existed between healthy lifestyle knowledge and actual healthy behavior in students .


ChiCTR-ERC-11001819 .


To explore experiences of mild-stroke survivors in the context of early supported discharge .


The meanings patients attributed to activities and participation in the home recovery process were our main interest .


Eight participants ( 45-80 years ) from a randomised controlled study were selected for this sub-study .


This purposive sample had received rehabilitation in their homes in the post-stroke acute phase of recovery as part of the larger study .


Extensive interview data were analysed using an interpretive strategy and systematic text condensation .


Coping theory was included in later stages of analysis .


The mild-stroke survivors ' stories revealed that life had changed profoundly .


Differences and similarities in experienced changes were related to : self-perceived health , the body , practical activities , taking part in society , and self-perception .


The findings showed the ways in which life changed for mild-stroke survivors , experienced challenges , and survivors ' thoughts about the future .


Mild-stroke rehabilitation should focus more strongly on basic concerns related to self-perceived health , self-perception , and body , since these dimensions seem to complicate daily activities and close relationships .


Professionals should also be aware of patients who experience an uncertain situation and unresolved rehabilitation needs , which still can be present 6-8 months after the stroke .


When living with mild stroke , entrance to practical and social activities seemed founded on the patients ' perception of the body and self as comprehensible or not .


Comprehending their own changed body and sense of self seem to be a long-term process when living with mild stroke .


It is suggested that long-term follow-up be incorporated in home rehabilitation service , also in the context of early supported discharge .


This may contribute to help patient cope more optimally with activities and participation of importance to them .


To show that albiglutide , a glucagon-like peptide-1 receptor agonist , is an effective and generally safe treatment to improve glycaemic control in patients with type 2 diabetes mellitus whose hyperglycaemia is inadequately controlled with pioglitazone ( with or without metformin ) .


In this 3-year , randomized , double-blind , placebo-controlled study , 310 adult patients on a regimen of pioglitazone ( with or without metformin ) were randomly assigned to receive additional treatment with albiglutide [ 30 mg subcutaneous ( s.c. ) once weekly , n = 155 ] or matching placebo ( n = 155 ) .


The primary efficacy endpoint was change from baseline to week 52 ( intention-to-treat ) in glycated haemoglobin ( HbA1c ) .


The model-adjusted change from baseline in HbA1c at week 52 was significantly better with albiglutide than with placebo ( -0.8 % , 95 % confidence interval -1.0 , -0.6 ; p < 0.0001 ) .


Change from baseline fasting plasma glucose was -1.3 mmol/l in the albiglutide group and +0.4 mmol/l in the placebo group ( p < 0.0001 ) ; a significantly higher percentage of patients reached the HbA1c goals with albiglutide ( p < 0.0001 ) , and the rate of hyperglycaemia rescue up to week 52 for albiglutide was 24.4 versus 47.7 % for placebo ( p < 0.0001 ) .


Albiglutide plus pioglitazone had no impact on weight , and severe hypoglycaemia was observed rarely ( n = 2 ) .


With few exceptions , the results of safety assessments were similar between the groups , and most adverse events ( AEs ) were mild or moderate .


The 52-week incidence rates for gastrointestinal AEs for albiglutide and placebo were : 31.3 and 29.8 % , respectively ( diarrhoea : 11.3 and 8.6 % ; nausea : 10.7 and 11.3 % ; vomiting : 4.0 and 4.0 % ) .


Albiglutide 30 mg administered once weekly as an add-on to pioglitazone ( with or without metformin ) provided effective and durable glucose lowering and was generally well tolerated .


The recently published SARA study was a prospective , multi-centre randomized controlled trial that compared CA to antiarrhythmic drug therapy ( ADT ) in 146 patients with persistent atrial fibrillation ( AF ) .


The study found that recurrence of AF or atrial flutter occurred significantly less often in the CA arm compared to the ADT arm ( 29.6 % vs. 56.3 % , p = 0.002 ) .


Despite this clear superiority in terms of efficacy , the authors were not able to demonstrate a corresponding Quality of Life ( QoL ) improvement .


We sought to investigate this apparent disparity using alternative analytical methods .


We were able to show that a high coefficient of variation existed for all QoL measures at each time point which may explain the lack of statistical difference originally reported .


We reanalyzed the raw QoL data from the SARA study using paired sample t-tests for the change in QOL for individual patients between baseline and 12 month ( final ) follow up .


For patients randomized to ADT the difference in QoL after 12 months was not significant for any of the four QoL domains ( global , physical , psychological and sexual ) whereas for patients randomized to CA all comparisons were significant ( global , p < 0.001 ; physical , p = 0.001 ; psychological , p < 0.001 ; sexual , p = 0.003 ) .


In the SARA study , after 12 months ' follow up , CA significantly improved QoL for patients with persistent AF whereas medical therapy had no appreciable effect .


The aim of this study was to investigate the influence on fertility and pregnancy outcome in cervical intraepithelial neoplasia ( CIN ) patients after a loop electrosurgical excision procedure ( LEEP ) or cold-knife conization ( CKC ) .


269 patients with CIN-II-III who wanted to conceive were prospectively enrolled in this randomized clinical trial to receive either the LEEP or CKC procedure .


Fertility , neonatal and maternal outcomes were observed and compared .


244 evaluable patients were divided into two groups .


There were 124 in the LEEP group and 120 in the CKC group .


The preterm premature rupture of membranes ( 16 vs. 8 % ; p = 0.03 ) , preterm delivery rate ( 11 vs. 5 % ; p = 0.04 ) and low birth weight infants rate ( < 2,500 g ) ( 10 vs. 6 % ; p = 0.04 ) were higher in the CKC group than in the LEEP group , but there was no difference in mean birth weight , cesarean delivery , labor induction , or neonatal intensive care unit admission .


There was no case of neonatal mortality .


In a prospective evaluation the findings of this study demonstrate that LEEP is safer for future pregnancies when compared to CKC .


LEEP should be an appropriate choice for patients with CIN who want to become pregnant later in life .


Current neonatal resuscitation guidelines recommend tracheal suctioning of nonvigorous neonates born through meconium-stained amniotic fluid .


We evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping .


Tracheal suctioning at birth ( n = 15 ) decreased amount of meconium in distal airways ( 53 29 particles/mm ( 2 ) lung area ) compared to no suction ( 499 109 particles/mm ( 2 ) ; n = 14 ; P < 0.001 ) .


Three lambs in the suction group had cardiac arrest during suctioning , requiring chest compressions and epinephrine .


Onset of ventilation was delayed in the suction group ( 146 11 vs. 47 3 s in no-suction group ; P = 0.005 ) .


There was no difference in pulmonary blood flow , carotid blood flow , and pulmonary or systemic blood pressure between the two groups .