No significant differences in baseline VAS or VRS were found with regard to age or sex .


After 10 minutes , all 3 groups experienced a significant decrease in VAS and VRS scores , with the most drastic decrease occurring in group II .


After 30 minutes , there was a significantly higher decrease in group III than in group I ( P = .001 ) .


After 60 minutes , mean VAS scores of groups I and III ( P = .753 ) were similar .


The mean VAS score of group III was lower than that of group II ( P = .013 ) .


After 120 minutes , the difference in the VAS scores was ( P = .000 ) between groups I and II and between groups II and III .


Yet , the VAS evaluation made after 120 minutes revealed statistically similar outcomes for groups I and III ( P = .488 ) .


The statistical findings for VRS evaluations made after 10 , 30 , 60 , and 120 were similar to those for VAS .


In renal colic patients with a possible nonsteroidal anti-inflammatory drug and acetaminophen side effect risk , acupuncture emerges as an alternative treatment modality .


The aim of this study was to compare a highly structured planned rest protocol that includes visitor and healthcare personnel restrictions with a simple planned rest period that encourages patients to rest during a designated time without restriction of visitors and healthcare personnel .


Many hospitals acute care have begun to restrict visitors and nonessential health team interventions during specific times despite the lack of experimentally designed studies .


Using a convenience sample of 52 intermediate care unit patients , a randomized experimental design study compared a highly structured planned rest protocol with restriction of visitors/healthcare personnel to a simple planned rest period without restrictions .


The primary outcome variable was the patient 's perceived quality of rest after a 2-hour rest period .


Intermediate care patients ' perception of rest and sleep during a designated rest period was similar whether elaborate rest strategies were used , including visitor and healthcare personnel restrictions , or if it was only suggested they rest and the door to their room closed .


The restriction of visitors and healthcare personnel during a 2-hour rest period did not improve the patient 's perception of rest or how long it took them to go to sleep .


To observe the efficacy of encephalopathy therapeutic tongue acupoint apparatus ( ETTAA ) in the treatment of autism .


Eighty-four children of autism were randomly divided into a tongue acupuncture group ( group A ) and a conventional training group ( group B ) , 42 cases in each group .


The behavior training and sensory integration training were carried out in group B and the ETTAA was added in group A.


The apparatus was switched on for 20 min every time and 3 times a day .


Treatment of two months were carried out in both groups .


The score of childhood autism rating scale ( CARS ) and clinical efficacy in both groups were observed before and after treatment .


After treatment , the CARS in both groups were significantly reduced ( 42.39 + / - 6.86 vs 32.15 + / - 5.12 , P < 0.001 ; 44.58 + / - 6.76 vs 39.72 + / - 7.11 , P < 0.05 ) , which was more significant in group A ( P < 0.01 ) .


The totally effective rate in group A [ 90.5 % ( 38/42 ) ] was superior to that in group B [ 66.7 % ( 28/42 ) , P < 0.01 ] .


The clinical efficacy in tongue acupuncture group is apparently superior to that in conventional training group , ETTAA combined with conventional training have a better curative effect in the treatment of autism .


To evaluate the effect of tobacco cessation brief-intervention ( BI ) training for lay `` health influencers , '' on knowledge , self-efficacy and the proportion of participants reporting BI delivery post-training .


Randomized , community-based study comparing In-person or Web-based training , with mailed materials .


In-person and Web-training groups had significant post-training cessation knowledge and self-efficacy gains .


All groups increased the proportion of individuals reporting BIs at follow-up , with no significant between-group differences .


Irrespective of participants ' prior intervention experience , 80 % -86 % reported BIs within the past 90 days ; 71 % -79 % reported > 1 in the past 30 .


Web and In-person training significantly increase health influencer cessation knowledge and self-efficacy .


With minimal prompting and materials , even persons without BI experience can be activated to encourage tobacco cessation .


Chronic sinonasal disease is common in asthmatic patients and associated with poor asthma control ; however , there are no long-term trials addressing whether chronic treatment of sinonasal disease improves asthma control .


We sought to determine whether treatment of chronic sinonasal disease with nasal corticosteroids improves asthma control , as measured by the Childhood Asthma Control Test and Asthma Control Test in children and adults , respectively .


A 24-week multicenter , randomized , placebo-controlled , double-blind trial of placebo versus nasal mometasone in adults and children with inadequately controlled asthma was performed .


Treatments were randomly assigned , with concealment of allocation .


Two hundred thirty-seven adults and 151 children were randomized to nasal mometasone versus placebo , and 319 participants completed the study .


There was no difference in the Childhood Asthma Control Test score ( difference in change with mometasone - change with placebo [ M - P ] , -0.38 ; 95 % CI , -2.19 to 1.44 ; P = .68 ; age 6-11 years ) or the Asthma Control Test score ( M - P , 0.51 ; 95 % CI , -0.46 to 1.48 ; P = .30 ; age 12 years ) in those assigned to mometasone versus placebo .


In children and adolescents ( age 6-17 years ) there was no difference in asthma or sinus symptoms but a decrease in episodes of poorly controlled asthma defined by a decrease in peak flow .


In adults there was a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index ( M - P , 0.06 ; 95 % CI , 0.01 to 0.11 ; P < .01 ) and in nasal symptoms ( sinus symptom score M - P , -3.82 ; 95 % CI , -7.19 to -0.45 ; P = .03 ) but no difference in asthma quality of life , lung function , or episodes of poorly controlled asthma in adults assigned to mometasone versus placebo .


Treatment of chronic sinonasal disease with nasal corticosteroids for 24 weeks does not improve asthma control .


Treatment of sinonasal disease in asthmatic patients should be determined by the need to treat sinonasal disease rather than to improve asthma control .


The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) significantly improved overall survival , progression-free survival , and objective response in the first-line treatment of patients with KRAS codon 12/13 ( exon 2 ) wild-type metastatic colorectal cancer ( mCRC ) .


Outcome was reassessed in subgroups defined by extended RAS mutation testing .


Existing DNA samples from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons ( exons 3 and 4 ) and six NRAS codons ( exons 2 , 3 , and 4 ) using beads , emulsion , amplification , and magnetics technology .


No tissue microdissection was performed .


A 5 % mutant allele cutoff was used to call mutations .


Mutation status was evaluable in 430 ( 64.6 % ) of 666 patients with KRAS exon 2 wild-type tumors .


Other RAS mutations were detected in 63 ( 14.7 % ) of 430 patients .


In those with RAS wild-type tumors , a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI .


In patients with other RAS tumor mutations , no difference in efficacy outcomes between treatment groups was seen .


The safety profile in RAS subgroups was similar and in line with expectations .


In the first-line treatment of mCRC , patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI ; patients with RAS tumor mutations did not .


Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy , thereby allowing the further tailoring of cetuximab administration to maximize patient benefit .


Chronic stimulation and dysregulation of the neuroendocrine system by stress may cause metabolic abnormalities .


We estimated how much cortisol and psychosocial outcomes improved with a restorative yoga ( relaxation ) versus a low impact stretching intervention for individuals with the metabolic syndrome .


We conducted a 1-year multi-center randomized controlled trial ( 6-month intervention and 6-month maintenance phase ) of restorative yoga vs. stretching .


Participants completed surveys to assess depression , social support , positive affect , and stress at baseline , 6 months and 12 months .


For each assessment , we collected saliva at four points daily for three days and collected response to dexamethasone on the fourth day for analysis of diurnal cortisol dynamics .


We analyzed our data using multivariate regression models , controlling for study site , medications ( antidepressants , hormone therapy ) , body mass index , and baseline cortisol values .


Psychosocial outcome measures were available for 171 study participants at baseline , 140 at 6 months , and 132 at 1 year .


Complete cortisol data were available for 136 of 171 study participants ( 72 in restorative yoga and 64 in stretching ) and were only available at baseline and 6 months .


At 6 months , the stretching group had decreased cortisol at waking and bedtime compared to the restorative yoga group .


The pattern of changes in stress mirrored this improvement , with the stretching group showing reductions in chronic stress severity and perseverative thoughts about their stress .


Perceived stress decreased by 1.5 points ( -0.4 ; 3.3 , p = 0.11 ) at 6 months , and by 2.0 points ( 0.1 ; 3.9 , p = 0.04 ) at 1 year in the stretching compared to restorative yoga groups .


Post hoc analyses suggest that in the stretching group only , perceived increases in social support ( particularly feelings of belonging ) , but not changes in stress were related to improved cortisol dynamics .


We found significant decreases in salivary cortisol , chronic stress severity , and stress perception in the stretching group compared to the restorative yoga group .


Group support during the interactive stretch classes may have contributed to these changes .


Part of the myocardial damage occurring during cardiac surgery is a consequence of reperfusion injury .


Cyclosporine , a potent inhibitor of the opening of the mitochondrial permeability transition pore , attenuates reperfusion injury in patients with acute ST-segment elevation myocardial infarction .


This study investigated whether the administration of cyclosporine just before the aortic cross-unclamping would reduce myocardial injury in patients undergoing aortic valve surgery .


This study was a monocentric , prospective , randomized , single-blinded , controlled trial .


Sixty-one patients , scheduled for elective aortic valve surgery , were randomly assigned ( computer-generated randomization sequence ) to receive either an intravenous bolus of cyclosporine ( 2.5 mg/kg , cyclosporine group , n = 30 ) or normal saline ( control group , n = 31 ) 10 min before aortic cross-unclamping .


The primary endpoint was the 72-h area under the curve for cardiac troponin I.


Both groups were similar with respect to baseline characteristics and aortic cross-clamping duration .


A significant 35 % reduction of area under the curve for cardiac troponin I was observed in the cyclosporine group compared with the control group ( 242 225 vs. 155 71 arbitrary units , mean SD ; mean difference , -86.2 42.5 ; 95 % CI , -172.3 to -0.1 ; P = 0.03 ) .


Cyclosporine beneficial effect remained significant after adjustment for aortic cross-clamping duration in each group ( mean difference , -88 34 , 95 % CI , -157 to -19 ; P = 0.01 ) .


None of the treated patients had significant side effects ( odds ratio , 0.64 ; 95 % CI , 0.16 to 2.55 ; P = 0.52 ) .


Cyclosporine administration at the time of reperfusion protects against reperfusion injury in patients undergoing aortic valve surgery .


The clinical benefit of this protection requires confirmation in a larger clinical trial .


Recent work has shown no difference in change of LVEF between RV apical ( RVA ) pacing and non-RVA pacing in patients with normal LV function .


We hypothesised that a more sensitive marker ( global longitudinal strain , GLS ) could identify a detrimental effect of RVA and that assessment of deformation could identify whether dyssynchrony , contraction inefficiency and regional LV impairment were responsible for functional changes .


In this substudy of Protect-PACE ( The Protection of Left Ventricular Function During Right Ventricular Pacing .


Does Right Ventricular High-septal Pacing Improve Outcome Compared With Right Ventricular Apical Pacing ? )


, a randomised controlled trial of RVA and non-RVA pacing in pacemaker-dependent patients with preserved EF , 145 patients ( 76 with RVA ) with echocardiograms of sufficient quality underwent measurement of LV longitudinal strain ( GLS ) from speckle tracking just after implantation and at 2 years .


LV dyssynchrony , discoordination and regional apical longitudinal strain were also measured .


Pacing was associated with reduced GLS after 2 years , although 2-year GLS was lower in RVA ( -13.9 4.1 vs -15.5 4.6 , p = 0.02 ) .


RVA was an independent correlate of GLS , although there was a minor difference in GLS between the RVA and non-RVA groups ( -1.8 3.6 vs -0.8 3.4 % , p = 0.07 ) , reflecting impairment of GLS at baseline in RVA .


Apical strain was significantly lower in RVA than those in non-RVA at baseline and 2 years ( both p < 0.01 ) .


Dyssynchrony and discoordination parameters at 2 years also showed significant deterioration in RVA .


Apical strain , dyssynchrony and discoordination parameters at 2 years were significantly associated with GLS .


Inefficient dyssynchronous contraction and the decrease in apical strain appear to be associated with global LV impairment in RVA .


PROTECT-PACE ClinicalTrials.gov number NCT00461734 .


Left ventricular hypertrophy ( LVH ) is common in kidney transplant ( KT ) recipients .


LVH is associated with a worse outcome , though m-TOR therapy may help to revert this complication .


We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up .


We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor ( CNI ) to m-TOR therapy .


A control group received immunosuppressive therapy based on CNIs .


Two echocardiograms were done during the follow-up .


Nineteen patients were switched to SRL and 11 to EVL .


The m-TOR group showed a significant reduction in LVMi after 1 year ( from 62 22 to 55 20 g/m2 .7 ; P = 0.003 , paired t-test ) .


A higher proportion of patients showing LVMi reduction was observed in the m-TOR group ( 53.3 versus 29.3 % , P = 0.048 ) at the study end .


In addition , only 56 % of the m-TOR patients had LVH at the study end compared to 77 % of the control group ( P = 0.047 ) .


A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group ( P = 0.019 ) .


Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH , independently of blood pressure changes and follow-up time .


This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass .


This bioequivalence study aimed to compare rate and extent of absorption of a generic medicinal product of ibandronic acid 150-mg film-coated tablet versus Bonviva ( ) .


This was a single-centre , open-label , randomized , three-way , three-sequence , reference-replicated , crossover bioequivalence study , under fasting conditions .


A single oral dose of ibandronic acid as one 150-mg film-coated tablet was administered in each study period .


Each washout period lasted 14 days .


Blood samples were collected according to a predefined sampling schedule and up to 48.0 hours after administraton in each period .


Plasma concentrations of ibandronic acid were measured using a liquid chromatograph-mass spectrometry/mass spectrometry method .


Bioequivalence between generic and reference medicinal products is acceptable if the 90 % confidence intervals ( CI ) of ratio of least-squares means between the test and the reference product of ln-transformed area under the serum concentration-time curve from time zero to time of last measurable concentration ( AUC0-t ) is within the 80.00-125 .00 % interval .


Prospectively , a scaled average bioequivalence approach for maximum serum concentration ( C max ) was established .


153 healthy volunteers were enrolled and randomized .


After the test formulation ( T ) and first and second Bonviva ( ) ( R ) dosing , the C max was 96.71 90.19 ng/mL , 92.67 91.48 ng/mL and 87.94 60.20 ng/mL and the AUC0-t was 390.83 287.27 ngh/mL , 388.54 356.76 ngh/mL and 383.53 246.72 , respectively .


Ratios of T/R and 90 % CI were 100.92 % ( 94.35-107 .94 ) for AUC0-t , 100.90 % ( 94.37-107 .88 ) for AUC0-inf and 102.56 % ( 95.05-110 .67 ) for C max .


Test formulation of ibandronic acid is bioequivalent in rate and extent of absorption to Bonviva ( ) following a 150-mg dose , under fasting conditions .


Cognitive stimulation therapy ( CST ) is a widely used , evidence-based intervention for people with dementia ( PwD ) .


Although designed as a 14 session , twice weekly intervention , many services in the UK deliver CST once a week for 14 weeks .


However , this method of delivery has yet to be evaluated .


In addition , CST does not include any formal carer training .


This study aimed to evaluate the effectiveness of once weekly CST and determine any additional impact when enhanced with a carer training program .


A single blind , randomized controlled trial was conducted .


Sixty eight PwD and their carers were recruited through three community Memory Assessment Services .


PwD and their carers were randomized to one of three conditions : CST plus carer training , CST only , or a wait list control .


PwD were administered standardized measures of cognition , quality of life , and quality of relationship with carer at baseline and the 15 week follow-up .


There were no baseline differences across the three groups .


At follow-up , there were no significant differences between PwD in the three groups on any outcomes .


Weekly CST with or without carer training may not be an effective form of delivery .


Several possible explanations for the outcomes are proposed .


Weekly CST may not offer the necessary `` dose '' required to combat decline , and equally the carer training may have been too brief to have made a difference .


Services currently offering weekly CST should collect routine outcome data to support its use and provide practice-based evidence .


Intranasal steroids are recognized as an effective treatment for allergic rhinitis ( AR ) although their effect on nasal patency has never been evaluated with an objective instrument such as anterior rhinomanometry in children .


Moreover this effect has been widely assessed with total Nasal Symptom Scores ( NSS ) including all symptoms of allergic rhinitis and not with scores specifically focused on nasal obstruction such as the Nasal Obstruction Symptom Evaluation score ( NOSE ) .


Sixty children ( 42 males and 18 female ) aged 6-10 years , affected by persistent AR , were randomized and divided in two groups of 30 children to be included in an unblinded trial : one group treated with intranasal budesonide and isotonic nasal saline for 2 weeks and the other group treated only with isotonic nasal saline for 2 weeks .


Each child underwent rhinomanometry and completed the NSS and the NOSE scores before and after treatment .


At the baseline nasal patency and NSS total score , NOSE total scores were correlated ( r = -0.29 , p < 0.001 ; r = -60 , p < 0.001 ) .


After 2 weeks of treatment improvements in nasal patency , NSS and NOSE were seen ( NSS 4.13 1.38 vs 1.33 1.93 , p < 0.001 ; NOSE 34 17.97 vs 9 18.21 , p < 0.001 ; nasal patency -26.13 25.25 vs -11.83 11.31 , p < 0.001 ) .


Correlations were found between rhinitis duration and nasal patency and NOSE ( r = -0.84 , p < 0.001 ; r = 0.43 , p < 0.01 ) .


Intranasal budesonide is effective in increasing nasal patency in children .


Moreover the NOSE score was strongly correlated with nasal flow and , hence , this score should be regarded as a valid and reliable instrument in children .


Sleep hygiene recommendations are widely disseminated despite the fact that few systematic studies have investigated the empirical bases of sleep hygiene in the home environment .


For example , studies have yet to investigate the relative effects of a given dose of caffeine administered at different times of day on subsequent sleep .


This study compared the potential sleep disruptive effects of a fixed dose of caffeine ( 400 mg ) administered at 0 , 3 , and 6 hours prior to habitual bedtime relative to a placebo on self-reported sleep in the home .


Sleep disturbance was also monitored objectively using a validated portable sleep monitor .


Results demonstrated a moderate dose of caffeine at bedtime , 3 hours prior to bedtime , or 6 hours prior to bedtime each have significant effects on sleep disturbance relative to placebo ( p < 0.05 for all ) .


The magnitude of reduction in total sleep time suggests that caffeine taken 6 hours before bedtime has important disruptive effects on sleep and provides empirical support for sleep hygiene recommendations to refrain from substantial caffeine use for a minimum of 6 hours prior to bedtime .


Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 ( HIV-1 ) vaccines represents a current research priority for the HIV-1 vaccine field .


In particular , it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans .


In this double-blind , randomized , placebo-controlled clinical trial , we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 ( Ad26 ) vectored HIV-1 envelop ( Env ) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers .


Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed .


Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects .


Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative .


We also observed no increase in activated total or vector-specific mucosal CD4 + T lymphocytes following vaccination by either histopathology or flow cytometry .


These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans .


Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation .


NCT01103687 .


C-reactive protein ( CRP ) is a marker of systemic inflammation that has been associated with the incidence and prognosis for a number of different cancers .


Recent data suggest that CRP may be a prognostic factor for liver cancer and cirrhosis .


However , few long-term studies are available .


We prospectively examined associations between serum CRP and subsequent risk of liver cancer incidence or chronic liver disease mortality in a nested case-control study performed in the Linxian Nutrition Intervention Trials cohort .


Baseline serum CRP was measured for 220 incident liver cancer cases , 276 participants who died of chronic liver disease , and 1,018 age - , sex - , and trial-matched controls .


Unconditional logistical regression models were used to estimate ORs and 95 % confidence intervals ( CI ) .


Compared with the lowest quartile , subjects in the fourth quartile of serum CRP had a higher risk of liver cancer incidence ( OR , 1.63 ; 95 % CI , 1.06-2 .51 ) , with a significant Ptrend across quartiles ( P = 0.01 ) .


The association with liver cancer was only significant among men ( Q4 vs. Q1 ; OR , 2.00 ; 1.10-3 .62 ) , but not among women ( Q4 vs. Q1 ; OR , 1.15 ; 0.60-2 .22 ) .


For chronic liver disease deaths , the corresponding risk estimate in men and women was 2.95 ( 1.90-4 .57 ) , with a monotonic trend ( P < 0.001 ) .


Higher serum CRP concentrations at baseline were associated with subsequent incidence of liver cancer and death from chronic liver disease .


Our findings suggest that levels of systemic inflammation may serve as a long-term marker of liver cancer and liver disease .


Spinal anaesthesia for caesarean delivery is frequently associated with adverse effects such as maternal hypotension and bradycardia .


Prophylactic administration of ondansetron has been reported to provide a protective effect .


We studied the effect of different doses of ondansetron in obstetric patients .


This prospective double-blind , randomised , placebo-controlled study included 128 healthy pregnant women scheduled for elective caesarean delivery under spinal anaesthesia .


Women were randomly allocated into four groups ( n = 32 ) to receive either placebo or ondansetron 2 , 4 or 8 mg intravenously before induction of spinal anaesthesia .


Demographic , obstetric , intraoperative timing and anaesthetic variables were assessed at 16 time points .


Anaesthetic variables assessed included blood pressure , heart rate , oxygen saturation , nausea , vomiting , electrocardiographic changes , skin flushing , discomfort or pruritus and vasopressor requirements .


There were no differences in the number of patients with hypotension in the placebo ( 43.8 % ) and ondansetron 2mg ( 53.1 % ) , 4 mg ( 56.3 % ) and 8 mg ( 53.1 % ) groups ( P = 0.77 ) , nor the percentage of time points with systolic hypotension ( 7.3 % in the placebo group and 11.1 % , 15.7 % and 12.6 % in the ondansetron 2 , 4 and 8 mg groups , respectively , P = 0.32 ) .


There were no differences between groups in ephedrine ( P = 0.11 ) or phenylephrine ( P = 0.89 ) requirements and the number of patients with adverse effects .


In our study , prophylactic ondansetron had little effect on the incidence of hypotension in healthy parturients undergoing spinal anaesthesia with bupivacaine and fentanyl for elective caesarean delivery .


To determine the stability of beliefs of patients with Type 2 diabetes about their diabetes over 3 years , following diagnosis .


Data were collected as part of a multicentre cluster randomized controlled trial of a 6-h self-management programme , across 207 general practices in the UK .


Participants in the original trial were eligible for follow-up with biomedical data ( HbA1c levels , blood pressure , weight , blood lipid levels ) collected at the practice , and questionnaire data collected by postal distribution and return .


Psychological outcome measures were depression ( Hospital Anxiety and Depression Scale ) and diabetes distress ( Problem Areas in Diabetes scale ) .


Illness beliefs were assessed using the Illness Perceptions Questionnaire-Revised and the Diabetes Illness Representations Questionnaire scales .


At 3-year follow-up , all post-intervention differences in illness beliefs between the intervention and the control group remained significant , with perceptions of the duration of diabetes , seriousness of diabetes and perceived impact of diabetes unchanged over the course of the 3-year follow-up .


The control group reported a greater understanding of diabetes during the follow-up , and the intervention group reported decreased responsibility for diabetes outcomes during the follow-up .


After controlling for 4-month levels of distress and depression , the perceived impact of diabetes at 4 months remained a significant predictor of distress and depression at 3-year follow-up .


Peoples ' beliefs about diabetes are formed quickly after diagnosis , and thereafter seem to be relatively stable over extended follow-up .


These early illness beliefs are predictive of later psychological distress , and emphasize the importance of initial context and provision of diabetes care in shaping participants ' future well-being .


Atopic dermatitis ( AD ) primarily affects infants and young children .


Although topical corticosteroids ( TCSs ) are often prescribed , noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects .


In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD , pimecrolimus 1 % cream ( PIM ) was compared with TCSs .


A total of 2418 infants were enrolled in this 5-year open-label study .


Infants were randomized to PIM ( n = 1205 ; with short-term TCSs for disease flares ) or TCSs ( n = 1213 ) .


The primary objective was to compare safety ; the secondary objective was to document PIM 's long-term efficacy .


Treatment success was defined as an Investigator 's Global Assessment score of 0 ( clear ) or 1 ( almost clear ) .


Both PIM and TCSs had a rapid onset of action with > 50 % of patients achieving treatment success by week 3 .


After 5 years , > 85 % and 95 % of patients in each group achieved overall and facial treatment success , respectively .


The PIM group required substantially fewer steroid days than the TCS group ( 7 vs 178 ) .


The profile and frequency of adverse events was similar in the 2 groups ; in both groups , there was no evidence for impairment of humoral or cellular immunity .


Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system .


PIM was steroid-sparing .


The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children .


To date , no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids .


This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 ( IGF-1 ) therapy in comparison to intratympanic corticosteroid therapy .


We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear ( 62 patients ) or four intratympanic injections with dexamethasone ( Dex ; 58 patients ) .


The primary outcome was the proportion of patients showing hearing improvement ( 10 decibels or greater in pure-tone average hearing thresholds ) 8 weeks after treatment .


The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events .


In the IGF-1 group , 66.7 % ( 95 % confidence interval [ CI ] , 52.9-78 .6 % ) of the patients showed hearing improvement compared to 53.6 % ( 95 % CI , 39.7-67 .0 % ) of the patients in the Dex group ( P = 0.109 ) .


The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant ( P = 0.003 ) .


No serious adverse events were observed in either treatment group .


Tympanic membrane perforation did not persist in any patient in the IGF-1 group , but did persist in 15.5 % ( 95 % CI , 7.3-27 .4 % ) of the patients in the Dex group ( P = 0.001 ) .


The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness .


UMIN Clinical Trials Registry Number UMIN000004366 , October 30th , 2010 .


Findings from the randomised phase 3 NeoALTTO trial in women with HER2-positive early breast cancer showed that the combination of lapatinib and trastuzumab significantly improved rates of pathological complete response compared with either drug alone .


Here , we report data for the prespecified secondary endpoints of event-free and overall survival , and assess the association between these outcomes and pathological complete response .


We enrolled women with HER2-positive early breast cancer and randomly assigned them to receive oral lapatinib ( 1500 mg ) , intravenous trastuzumab ( 4 mg/kg loading dose followed by 2 mg/kg ) , or lapatinib ( 1000 mg ) plus trastuzumab ( same dose as for single agent ) in combination for 6 weeks , followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel ( 80 mg/m ( 2 ) ) .


Definitive surgery was done 4 weeks after the last dose of paclitaxel .


After surgery , women received three cycles of FEC ( fluorouracil 500 mg/m ( 2 ) plus epirubicin 100 mg/m ( 2 ) plus cyclophosphamide 500 mg/m ( 2 ) ) given intravenously every 3 weeks , followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy .


The primary endpoint was pathological complete response .


Secondary endpoints included event-free and overall survival ( intention-to-treat analysis ) , and the association between pathological complete response and event-free or overall survival ( analysed by landmark analysis at 30 weeks after randomisation ) .


Follow-up is ongoing , and the trial is registered with ClinicalTrials.gov , number NCT00553358 .


455 patients were enrolled : 154 ( 34 % ) were assigned to the lapatinib group , 149 ( 33 % ) to the trastuzumab group , and 152 ( 33 % ) to the lapatinib plus trastuzumab group .


At an event follow-up of 377 years ( IQR 350-422 ) , 3-year event-free survival was 78 % ( 95 % CI 70-84 ) in the lapatinib group , 76 % ( 68-82 ) in the trastuzumab group , and 84 % ( 77-89 ) in the combination group .


Event-free survival did not differ between the lapatinib and trastuzumab groups ( HR 106 , 95 % CI 066-169 , p = 081 ) , nor between the combination and trastuzumab groups ( 078 , 047-128 , p = 033 ) .


Median survival follow-up was 384 years ( IQR 360-424 ) , and 3-year overall survival was 93 % ( 95 % CI 87-96 ) for lapatinib , 90 % ( 84-94 ) for trastuzumab , and 95 % ( 90-98 ) for combination therapy .


Overall survival did not significantly differ between the lapatinib and trastuzumab groups ( HR 086 , 95 % CI 045-163 , p = 065 ) , nor between the combination and trastuzumab groups ( 062 , 030-125 , p = 019 ) .


Landmark analyses showed that 3-year event-free survival was significantly improved for women who achieved pathological complete response compared with those who did not ( HR 038 , 95 % CI 022-063 , p = 00003 ) , as was 3-year overall survival ( 035 , 015-070 , p = 0005 ) .


Adverse events occurred in 149 ( 99 % ) patients receiving lapatinib , 142 ( 96 % ) patients receiving trastuzumab , and 147 ( 99 % ) patients receiving combination therapy .


The most common adverse events were diarrhoea , rash or erythema , hepatic adverse events , and neutropenia ( not related to FEC administration ) , and were consistent with known safety profiles of lapatinib and trastuzumab .


Three primary and eight secondary cardiac events occurred , with no significant difference in incidence between treatment groups for primary or any cardiac events .


Although event-free survival or overall survival did not differ between treatment groups , findings from our study confirm that patients who achieve pathological complete response after neoadjuvant anti-HER2 therapy have longer event-free and overall survival than do patients without pathological complete response .


GlaxoSmithKline .


The anti-oxidant and proangiogenic protein haptoglobin ( Hp ) is believed to be important for implantation and pregnancy , although its specific role is not known .


The three phenotypes ( 1-1 , 2-1 and 2-2 ) differ in structure and function .


Hp 2-2 is associated with increased vascular stiffness in other populations .


We examined whether Hp phenotype is associated with abnormal uterine artery Doppler ( UAD ) in pregnancy .


We conducted a secondary analysis of a preeclampsia prediction cohort nested within a larger placebo-controlled randomized clinical trial of antioxidants for prevention of preeclampsia .


We determined Hp phenotype in 2184 women who completed UAD assessments at 17 weeks gestation .


Women with notching were re-evaluated for persistent notching at 24 weeks ' gestation .


Logistic regression was used to assess differences in UAD indices between phenotype groups .


Hp phenotype did not significantly influence the odds of having any notch ( p = 0.32 ) , bilateral notches ( p = 0.72 ) , or a resistance index ( p = 0.28 ) or pulsatility index ( p = 0.67 ) above the 90th percentile at 17 weeks ' gestation .


Hp phenotype also did not influence the odds of persistent notching at 24 weeks ( p = 0.25 ) .


Hp phenotype is not associated with abnormal UAD at 17 weeks ' gestation or with persistent notching at 24 weeks .


Nitrous oxide ( N2O ) offers both hypnotic and analgesic characteristics .


We therefore tested the hypothesis that N2O administration decreases the amount of propofol and remifentanil given by a closed-loop automated controller to maintain a similar bispectral index ( BIS ) .


In a randomized multicentre double-blind study , patients undergoing elective surgery were randomly assigned to breathe 60 % inspired N2O ( N2O group ) or 40 % oxygen ( AIR group ) .


Anaesthesia depth was evaluated by the proportion of time where BIS was within the range of 40-60 ( BIS40-60 ) .


The primary outcomes were propofol and remifentanil consumption , with reductions of 20 % in either being considered clinically important .


A total of 302 patients were randomized to the N2O group and 299 to the AIR group .


At similar BIS40-60 [ 79 ( 67-86 ) % vs 76 ( 65-85 ) % ] , N2O slightly decreased propofol consumption [ 4.5 ( 3.7-5 .5 ) vs 4.8 ( 4.0-5 .9 ) mg kg ( -1 ) h ( -1 ) , P = 0.032 ] , but not remifentanil consumption [ 0.17 ( 0.12-0 .23 ) vs 0.18 ( 0.14-0 .24 ) g kg ( -1 ) min ( -1 ) ] .


For the subgroups of men , at similar BIS40-60 [ 80 ( 72-88 ) % vs 80 ( 70-87 ) % ] , propofol [ 4.2 ( 3.4-5 .3 ) vs 4.4 ( 3.6-5 .4 ) mg kg ( -1 ) h ( -1 ) ] and remifentanil [ 0.19 ( 0.13-0 .25 ) vs 0.18 ( 0.15-0 .23 ) g kg ( -1 ) min ( -1 ) ] consumptions were similar in the N2O vs AIR group , respectively .


For the subgroups of women , at similar BIS40-60 [ 76 ( 64-84 ) % vs 72 ( 62-82 ) % ] , propofol [ 4.7 ( 4.0-5 .8 ) vs 5.3 ( 4.5-6 .6 ) mg kg ( -1 ) h ( -1 ) , P = 0.004 ] and remifentanil [ 0.18 ( 0.13-0 .25 ) vs 0.20 ( 0.15-0 .27 ) g kg ( -1 ) min ( -1 ) , P = 0.029 ] consumptions decreased with the co-administration of N2O .


With automated drug administration titrated to comparable BIS , N2O only slightly reduced propofol consumption and did not reduce remifentanil consumption .


There was a minor gender dependence , but not by a clinically important amount .


Clinical trial registration This study was registered at ClinicalTrials.gov , number NCT00547209 .


Pain control in pediatric patients undergoing tonsillectomy remains a dilemma .


Tramadol and ketamine are reported to be an effective analgesic .


To evaluate the effect of peritonsillar infiltration of tramadol in combination with ketamine versus peritonsillar infiltration of tramadol posttonsillectomy .


Specialty hospital in Jordan .


Sixty children , aged 7-12 years , selected for tonsillectomy were enrolled in the study .


We divided the patients into two groups 30 of each , Group I : received peritonsillar saline and peritonsillar infiltration of tramadol 2 mg/kg , Group II : received peritonsillar infiltration of ketamine 1.0 mg/kg added to peritonsillar tramadol 2 mg/kg .


Hemodynamic stability , pain scale , first request of analgesia , total analgesics consumption and post-operative nausea and vomiting ( PONV ) side effects were recorded 24 h after surgery .


The analysis of data showed that Group II had significantly lower face pain scale , longer time for first request of analgesia , and better hemodynamic stability than GI ( p < 0.001 ) .


On the other hand the total analgesics requirements , time of surgery , and PONV showed no significant differences between the two groups .


Combined use of peritonsillar infiltration of ketamine 1.0 mg/kg with tramadol 2 mg/kg provided prolong analgesic effects , less pain with no side effect , and better hemodynamic stability compared with using tramadol alone in patients undergoing tonsillectomy .


Pediatric patients with acute lymphoblastic leukemia ( ALL ) are treated with oral 6-mercaptopurine ( 6MP ) for nearly 2 years , but no pediatric formulation has been available .


In this study , an oral 6MP liquid suitable for pediatric use was developed and tested in the target population .


A randomized cross-over study was performed in 20 pediatric ALL patients ( age 1.9 - 14.6 years ) , comparing pharmacokinetics and pharmacodynamics of a newly developed 6MP liquid formulation to 6MP capsules , both taken orally for 4 weeks .


Based upon trough levels of the principal active metabolite,6-thioguanine nucleotides ( 6-TGN ) , a relative bioavailability of the liquid vs. capsules of 1.01 was found ( 90 % CI 0.86 - 1.20 ) , demonstrating bioequivalence .


This was supported by the similarly observed 6MP dosages needed for leucocyte depletion , for both formulations ( 35 mg/day ( range 10 - 115 mg ) ) .


75 % of the parents/patients ( p = 0.005 ) preferred the oral liquid over the capsules because of the ease of administration .


We conclude that the novel 6MP liquid is a promising treatment for ALL .


To analyse treatment effects of eccentric vs. concentric graded exercise in chronic tennis elbow .


Randomized controlled trial .


Primary care in Uppsala County , Sweden .


A total of 120 subjects with tennis elbow lasting more than three months were recruited from primary care and by advertisement .


Eccentric ( n = 60 ) or concentric exercise ( n = 60 ) , by lowering or lifting a weight , at home daily , for three months with gradually increasing load .


Pain during muscle contraction and muscle elongation , as well as strength , was assessed at baseline and after one , two , three , six , and 12 months .


Function and quality of life was assessed at baseline and after three , six and 12 months .


The eccentric exercise group had faster regression of pain , with an average of 10 % higher responder rate at all levels of pain reduction , both during muscle contraction and elongation , ( p < 0.0001 and p = 0.006 , respectively ) .


Significant differences were found in Cox 's analysis from two months onwards ( HR 0.78 , 95 % confidence interval ( CI ) 0.63-0 .96 , p < 0.02 ) .


This represents an absolute pain reduction of 10 % in the eccentric vs. the concentric group and a number-needed-to-treat of 10 .


The eccentric group also had a greater increase of muscle strength than the concentric ( p < 0.02 ) .


The differences persisted throughout the follow-up period .


There were no significant differences between the groups regarding function or quality of life measures .


Eccentric graded exercise reduced pain and increased muscle strength in chronic tennis elbow more effectively than concentric graded exercise .


A randomized , double-blind , controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design .


Twenty-one twin pairs ( n = 42 ) were enrolled in a gingivitis study with oral hygiene promotion ( 14 days ) and gingivitis induction ( 21 days ) .


During the gingivitis induction phase , one member of the twin pair was randomly assigned to a 2 % typified propolis rinse , and the other was assigned a color-matched 0.05 % sodium fluoride plus 0.05 % cetylpyridinium chloride rinse ( positive control ) .


Patients rinsed twice daily with 20mL for 30 seconds for 21 days .


Gingivitis was measured on days -14 ( baseline ) , 0 ( after hygiene phase ) , and 21 ( after no-hygiene phase ) by using the Papillary Bleeding Score ( PBS ) and by standard digital imaging of the gum tissues ( G-parameter ) .


The 38 persons who completed the study ( age 13-22 years ) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase .


After 21 days without oral hygiene , the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter .


Use of a 2 % typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period .


To report results of a randomized phase II trial ( Radiation Therapy Oncology Group RTOG-0234 ) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck ( SCCHN ) with high-risk pathologic features .


Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases .


Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m ( 2 ) or docetaxel 15 mg/m ( 2 ) once per week .


Between April 2004 and December 2006 , 238 patients were enrolled .


With a median follow-up of 4.4 years , 2-year overall survival ( OS ) was 69 % for the cisplatin arm and 79 % for the docetaxel arm ; 2-year disease-free survival ( DFS ) was 57 % and 66 % , respectively .


Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors .


Grade 3 to 4 myelosuppression was observed in 28 % of patients in the cisplatin arm and 14 % in the docetaxel arm ; mucositis was observed in 56 % and 54 % , respectively .


DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial ( Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck ) , which had a hazard ratio of 0.76 for the cisplatin arm versus control ( P = .05 ) and 0.69 for the docetaxel arm versus control ( P = .01 ) , reflecting absolute improvement in 2-year DFS of 2.5 % and 11.1 % , respectively .


The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity .


The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial .


To evaluate the efficacy and safety of the Xiaoyao pill for treatment of functional dyspepsia ( FD ) associated with perimenopausal depression .


This was a double-blind , randomized , controlled trial including 180 patients with FD accompanied by depression that were divided into two groups of 90 .


Patients in the treatment group received oral administration of the Xiaoyao pill for soothing the liver and activating the spleen , and patients in the control group received a placebo .


This trial included an 8-wk therapy period with a follow-up period of 6 mo. .


The total efficacy and degree of depression , as assessed by the Hamilton Rating Scale for Depression ( HRSD ) , were evaluated .


Plasma levels of motilin and gastrin were measured and a gastric emptying test was conducted in each participant .


The Xiaoyao pill had a good therapeutic effect and improved the symptoms in patients with perimenopausal FD as assessed by the HRSD score , motilin and gastrin levels , and rate of gastric emptying .


The total effective rate of the Xiaoyao pill in the treatment group was significantly superior to that of the placebo in the control group .


In the control group , the initial HRSD score was 12.12 2.29 and decreased to 7.14 1.67 after therapy ( P < 0.01 ) .


In the treatment group , the initial HRSD score was 11.44 2.15 , which significantly decreased to 6.20 2.08 after therapy ( P < 0.01 ) .


Moreover , the HRSD score in the treatment group was significantly lower than in control group after 8 wk ( P < 0.01 ) .


Motilin and gastrin levels in both groups were significantly increased after the 8-wk therapy ( P < 0.05 ) .


The gastric emptying rate was also improved in both groups after therapy ( P < 0.05 ) , and the improvement was significantly better in the treatment group compared to the controls ( P < 0.05 ) .


These results confirm the therapeutic effects of the Xiaoyao pill in perimenopausal FD patients and indicate that it is worthy of clinical promotion .


The Xiaoyao pill is effective and safe for the treatment of perimenopausal women with FD associated with depression .


Delay in diagnosis of anaemia during preoperative assessment poses logistic problems , leading to multiple clinic visits , inadequate preoperative management , and unnecessary delay of surgery .


Therefore , we tested an instant spectrophotometric haemoglobin ( SpHb ) measurement technique to facilitate this assessment .


We evaluated portable instant SpHb vs standard laboratory screening of anaemia between March 2012 and December 2013 .


Paired Hb measurements were performed on 726 patients using SpHb ( Pronto-7 , Masimo Corporation , Irvine , CA , USA ) and Hb measured on the same day using an automated analyser .


The results were obtained from a group of 638 patients from the pre-anaesthetic clinic with expected normal Hb values , and 88 patients from the oncology clinic with known low Hb .


Median ( range ) SpHb was 129.5 ( 67-171 ) compared with 136 g litre ( -1 ) ( 63-178 ) Hb measured using the automated system .


Identifying Hb below a threshold of 130 g litre ( -1 ) for males had a high sensitivity ( 93 % ) , while identifying a threshold of 120 g litre ( -1 ) for females had lower sensitivity ( 75 % ) .


The specificity for males ( 77 % ) and females ( 81 % ) was similar .


Mean measurement bias and agreement : tolerability interval ratio was -8.1 g litre ( -1 ) and 2.78 for men and -3.1 g litre ( -1 ) and 2.44 for women .


SpHb was sensitive as a preliminary screening tool for detecting true low Hb values in males , but less sensitive in females .


Instant SpHb measurement may enable prompt routine preoperative anaemia management , but its precision was lower than expected .


This study is approved by the Tasmanian Human Ethics Committee , Australia and was registered prospectively in the Australian and New Zealand Clinical Trials Registry ( http://www.ANZCTR.org.au/ ACTRN12611001256965 ) and the World Health Organization Clinical Trials Registry ( http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12611001256965 ) .


Hyperhomocysteinemia is a well-known risk factor for vascular disease .


However , its action , mechanism , and role in the acute phase of stroke have not been determined .


We tried to determine whether an association existed between elevated serum homocysteine levels and early neurological deterioration ( END ) in patients with acute ischemic stroke .


We performed a secondary analysis from the Cilostazol in Acute Ischemic Stroke Treatment ( CAIST ) trial , which was a double-blinded , randomized , multicenter trial , assessing the noninferiority of cilostazol over aspirin within 48 hours of an acute ischemic stroke .


END was defined as an increase of 1 point in motor power or an increase of 2 points in the total National Institute of Health Stroke Scale score within 7 days .


The mean ( SD ) serum homocysteine level was 11.44.7 mol/L .


Of the 396 patients studied , 57 ( 14.4 % ) patients worsened during the 7 days after inclusion .


Most ( 68 % ) of the END cases occurred within the first 24 hours after treatment .


High levels ( > 10.3 mol/L ) of serum homocysteine were independent predictors for END ( third quartile odds ratio , 3.45 ; 95 % confidence intervals , 1.25-9 .50 ; P = 0.016 ; fourth quartile odds ratio , 3.36 ; 95 % confidence intervals 1.18-9 .52 ; P = 0.023 ) in multivariate analysis .


Patients with acute stroke with elevated serum homocysteine levels are at an increased risk for END .


Obesity amongst children is a growing problem worldwide .


In contrast to adults , little is known on the effects of controlled weight loss on components of the metabolic syndrome in children .


The primary aim of the study was to evaluate the effects of a 20-week exercise and diet guidance intervention on body mass index ( BMI ) in a group of overweight children .


Our hypothesis was an observed reduction in BMI and secondarily in body fat content , insulin insensitivity , and other components of the metabolic syndrome in the intervention group .


School children from Copenhagen were randomly allocated to an intervention group ( n = 19 ) or a control group ( n = 19 ) .


Anthropometric assessment , whole body dual-energy X-ray absorptiometry scan , two hours oral glucose tolerance test , steps measured by pedometer , and fitness tests were measured at baseline and at 20weeks .


Thirty-seven children ( 30 girls ) participated at baseline , aged 8.70.9 years with a BMI of 21.83.7 kg/m2 ( meanSD ) , and 36 children completed the study .


The intervention group decreased their BMI ( the intervention effect is the difference in change between the groups adjusted for the respective baseline values ( DELTA ) = -2.0 kg/m2 , 95 % CI : -2.5 ; -1.5 , P < 0.001 ) , total body mass ( DELTA = -4.0 kg , 95 % CI : -4.9 ; -3.0 , P < 0.001 ) , and fat mass ( DELTA = -3.3 kg , 95 % CI : -4.2 ; -2.7 , P < 0.001 ) compared to the control group after the intervention .


The intervention group displayed decreased waist , hip and waist-to-height ratio ( WHtR ) ( all three variables ; P < 0.001 ) , area under curve for plasma insulin ( P < 0.05 ) , and increased mean and minimum steps/day ( P < 0.05 and P < 0.01 , respectively ) .


The multicomponent intervention had significant favorable effects on BMI , weight , WHtR , mean and minimum steps/day , and fat mass .


In addition , similar beneficial metabolic effects were found in the children as shown in adults , e.g. increase in peripheral insulin sensitivity .


Clinicaltrials.gov Identifier number NCT01660789 .


Hyperaminotransferasemia is an important problem in obese patients .


We decide to examine the changes in hyperaminotransferasemia after weight reduction in obese patients with and without NAFLD secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets .


A population of 306 obese patients was randomly allocated to two groups : Diet M ( high monounsaturated fat hypocaloric diet ) and Diet P ( high polyunsaturated fat hypocaloric diet ) .


Patients were classified as group I ( obese subjects ; n = 262 ) when serum ALT activity was normal or group II ( NAFLD patients ; n = 44 ) when serum ALT activity was ( 43 UI/L ) .


In NAFLD group with diet M , BMI , weight , fat mass , waist circumference , systolic blood pressure , total cholesterol , LDL cholesterol ) , insulin and HOMA-R decreased .


In NAFLD group with diet P , BMI , weight , fat mass , waist circumference , systolic blood pressure , total cholesterol , LDL cholesterol ) , insulin and HOMA-R decreased , too .


In NAFLD group , alanine aminotransferase [ ( diet M ) -20.319.2 UI/L vs. ( diet P ) -14.220.1 UI/L ] , aspartate aminotransferase [ ( diet M ) -11.312.2 UI/L vs. ( diet P ) -11.110.1 UI/L ] , and gammaglutamyl transferase [ ( diet M ) -18.112.2 UI/L vs. ( diet P ) -10.920.1 UI/L ] improved with both diets .


We showed that weight reduction secondary to two hypocaloric diets was associated with improvement in hypertransaminasemia and insulin resistance in NAFLD patients .


To assess whether customised mobile phone reminders would improve adherence to therapy and thus decrease virological failure among HIV infected patients starting antiretroviral treatment ( ART ) .


Randomised controlled trial among HIV infected patients initiating antiretroviral treatment .


Three diverse healthcare delivery settings in south India : two ambulatory clinics within the Indian national programme and one private HIV healthcare clinic .


631 HIV infected , ART nave , adult patients eligible to initiate first line ART were randomly assigned to mobile phone intervention ( n = 315 ) or standard care ( n = 316 ) and followed for 96 weeks .


The intervention consisted of customised , interactive , automated voice reminders , and a pictorial message that were sent weekly to the patients ' mobile phones for the duration of the study .


The primary outcome was time to virological failure ( viral load > 400 copies/mL on two consecutive measurements ) .


Secondary outcomes included ART adherence measured by pill count , death rate , and attrition rate .


Suboptimal adherence was defined as mean adherence < 95 % .


Using an intention-to-treat approach we found no observed difference in time to virological failure between the allocation groups : failures in the intervention and standard care arms were 49/315 ( 15.6 % ) and 49/316 ( 15.5 % ) respectively ( unadjusted hazard ratio 0.98 , 95 % confidence interval 0.67 to 1.47 , P = 0.95 ) .


The rate of virological failure in the intervention and standard care groups were 10.52 and 10.73 per 100 person years respectively .


Comparison of suboptimal adherence was similar between both groups ( unadjusted incidence rate ratio 1.24 , 95 % CI 0.93 to 1.65 , P = 0.14 ) .


Incidence proportion of patients with suboptimal adherence was 81/300 ( 27.0 % ) in the intervention arm and 65/299 ( 21.7 % ) in the standard care arm .


The results of analyses adjusted for potential confounders were similar , indicating no significant difference between the allocation groups .


Other secondary outcomes such as death and attrition rates , and subgroup analysis also showed comparable results across allocation groups .


In this multicentre randomised controlled trial among ART nave patients initiating first line ART within the Indian national programme , we found no significant effect of the mobile phone intervention on either time to virological failure or ART adherence at the end of two years of therapy.Trial registration Current Controlled Trials ISRCTN79261738 .


To investigate the changes of B and T lymphocyte attenuator ( BTLA ) , reactive oxygen species ( ROS ) , reactive nitrogen species ( RNS ) , malondialdehyde ( MDA ) , superoxide dismutase ( SOD ) , catalase ( CAT ) , total antioxidative capacity ( TAOC ) in the patients with ankylosing spondylitis ( AS ) and the effect of Xinfeng capsule ( XFC ) on them .


AS patients ( n = 140 ) were randomly divided into two groups , XFC group ( 3 tablets each time , tid , n = 70 ) and salicylazosulfapyridine ( SASP ) group ( 4 pills each time , bid , n = 70 ) .


Continuous treatment lasts 3 months .


The study also enrolled 60 healthy volunteers as a control group .


Flow cytometry was used to test BTLA expression .


ELISA was performed to detect the oxidative stress indicators ( ROS , RNS , MDA , SOD , CAT , TAOC ) and cytokines ( IL-4 , IL-10 , IL-1 , TNF - ) .


Western blotting was adopted to examine the blood sedimentation ( ESR ) .


HITACHI 7060 automatic biochemical analyzer was used to determine the level of high sensitive C-reactive protein ( Hs-CRP ) .


Clinical efficacy of XFC group was significantly better than that of SASP group ( P < 0.01 ) .


Compared with the healthy control group , AS patients had significantly lower BTLA expression in CD3 ( + ) T cells and CD4 ( + ) T cells from the peripheral blood ( P < 0.01 or P < 0.05 ) , the decreased levels of SOD , CAT and TAOC , and significantly increased ROS , RNS and MDA values ( P < 0.01 or P < 0.05 ) .


In addition , the levels of serum IL-1 , TNF - , ESR and Hs-CRP were significantly higher ( P < 0.01 ) and IL-4 , IL-10 were significantly lower in AS patients ( P < 0.01 or P < 0.05 ) .


Compared with pre-treatment , both XFC and SASP significantly elevated the expressions of BTLA ( + ) CD3 ( + ) T , BTLA ( + ) CD4 ( + ) T , BTLA , SOD , TAOC , IL-4 , SF-36 ( PF , SF , RP , RE , BP , MH , VT , GH ) eight dimension scores , and reduced ROS , MDA , TNF - , ESR , Hs-CRP , VAS , BASDAI , BASFI and BAS-G in the peripheral blood ( P < 0.01 or P < 0.05 ) .


The differences between XFC group and SASP group were statistically significant ( P < 0.01 or P < 0.05 ) .


Pearson correlation analysis showed that BTLA expression level in the peripheral blood was positively correlated with SOD , RP , BP , SF and RE .


BTLA ( + ) CD3 ( + ) T cells and BTLA * CD4 ( + ) T cells were significantly negatively correlated with ROS , MDA , IL-1 , TNF - , ESR , VAS and BASDAI , and they were positively correlated with TAOC , IL-4 and IL-10 .


BTLA ( + ) CD3 ( + ) T cells were significantly negatively correlated with RNS , Hs-CRP and BASFI ; BTLA ( + ) CD4 ( + ) T cells were positively correlated with CAT .


XFC can improve BTLA expression in the peripheral blood of AS patients and regulate negatively the activation and proliferation of T cells .


Hemolysis , occurring during cardiopulmonary bypass , is associated with lipid peroxidation and postoperative acute kidney injury .


Acetaminophen inhibits lipid peroxidation catalyzed by hemeproteins and in an animal model attenuated rhabdomyolysis-induced acute kidney injury .


This pilot study tests the hypothesis that acetaminophen attenuates lipid peroxidation in children undergoing cardiopulmonary bypass .


Single-center prospective randomized double-blinded study .


University-affiliated pediatric hospital .


Thirty children undergoing elective surgical correction of a congenital heart defect .


Patients were randomized to acetaminophen ( OFIRMEV [ acetaminophen ] injection ; Cadence Pharmaceuticals , San Diego , CA ) or placebo every 6 hours for four doses starting before the onset of cardiopulmonary bypass .


Markers of hemolysis , lipid peroxidation ( isofurans and F2-isoprostanes ) , and acute kidney injury were measured throughout the perioperative period .


Cardiopulmonary bypass was associated with a significant increase in free hemoglobin ( from a prebypass level of 9.8 6.2 mg/dL to a peak of 201.5 42.6 mg/dL postbypass ) .


Plasma and urine isofuran and F2-isoprostane concentrations increased significantly during surgery .


The magnitude of increase in plasma isofurans was greater than the magnitude in increase in plasma F2-isoprostanes .


Acetaminophen attenuated the increase in plasma isofurans compared with placebo ( p = 0.02 for effect of study drug ) .


There was no significant effect of acetaminophen on plasma F2-isoprostanes or urinary makers of lipid peroxidation .


Acetaminophen did not affect postoperative creatinine , urinary neutrophil gelatinase-associated lipocalin , or prevalence of acute kidney injury .


Cardiopulmonary bypass in children is associated with hemolysis and lipid peroxidation .


Acetaminophen attenuated the increase in plasma isofuran concentrations .


Future studies are needed to establish whether other therapies that attenuate or prevent the effects of free hemoglobin result in more effective inhibition of lipid peroxidation in patients undergoing cardiopulmonary bypass .


Propofol , a short-acting hypnotic drug , is increasingly administered by a diverse group of specialists ( e.g. , cardiologists , gastroenterologists ) during diagnostic and therapeutic procedures .


Standard monitoring during sedation comprises continuous pulse oximetry with visual assessment of the patient 's breathing pattern .


Because undetected hypoventilation is a common pathway for complications , capnographic monitoring of exhaled carbon dioxide has been advocated .


We examined whether the use of capnography reduces the incidence of hypoxemia during nonanesthesiologist-administered propofol sedation in patients who did not receive supplemental oxygen routinely .


An open , stratified , randomized controlled trial was conducted in 427 healthy adult women during minor gynecology procedures in an outpatient clinic in the Netherlands .


Patients were randomly assigned to receive either standard respiratory monitoring ( standard care ) or standard respiratory monitoring combined with capnography ( capnography group ) .


To replicate usual clinical practice , capnography monitoring was performed by the same medical team that provided sedation .


The primary end point was the incidence of hypoxemia , defined as oxygen saturations < 91 % .


From April 2010 to January 2011 , 427 patients were enrolled .


In the capnography group , 206 patients and in the standard care group , 209 patients were analyzed .


The percentage of patients with a hypoxemic episode was 25.7 % ( 53 of 206 ) in the capnography group and 24.9 % ( 52 of 209 ) in the standard care group , resulting in an absolute difference of 0.8 % ( -7.5 to 9.2 % ) .


We were unable to confirm an additive role for capnography in preventing hypoxemia during elective nonanesthesiologist-administered propofol ( monotherapy ) sedation in healthy women in whom supplemental oxygen is not routinely administered .


Based on the confidence interval , the benefit of adding capnography is at most an absolute hypoxemia reduction of 7.5 % , suggesting that adding it in this practice setting to the routine monitoring strategy does not necessarily improve patient safety in daily practice .


Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol ( the 25-hydroxyvitamin D3 metabolite ) is not well studied .


Additionally , it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25 ( OH ) D3 plasma concentrations considered desirable for fracture prevention ( 30 ng/mL ) .


We therefore investigated plasma pharmacokinetics of 25 ( OH ) D3 during different vitamin D3 and calcifediol supplementation regimens .


In this seven-arm , randomized , double-blind , controlled parallel-group study , 35 healthy females aged 5070 years ( 5 per group ) received 20 g calcifediol or vitamin D ( 3 ) daily , 140 g calcifediol or vitamin D ( 3 ) weekly , for 15 weeks , or a single bolus of either 140 g calcifediol , or vitamin D ( 3 ) , or both .


25 ( OH ) D3 plasma concentrations were quantified using LCMS/MS in 14 clinical visits among all participants .


For daily ( weekly ) dosing , the area under the concentrationtime curve ( AUC024h ) , which is the measure for exposure , was 28 % ( 67 % ) higher after the first dose of calcifediol than after the first dose of vitamin D3 .


After 15 weeks , this difference was 123 % ( 178 % ) .


All women in the daily and weekly calcifediol groups achieved 25 ( OH ) D3 concentrations > 30 ng/mL ( mean , 16.8 days ) , but only 70 % in the vitamin D3 daily or weekly groups reached this concentration ( mean , 68.4 days ) .


A single dose of 140 g calcifediol led to 117 % higher 25 ( OH ) D3 AUC096h values than 140 g vitamin D3 , while the simultaneous intake of both did not further increase exposure .


Calcifediol given daily , weekly , or as a single bolus is about 23 times more potent in increasing plasma 25 ( OH ) D3 concentrations than vitamin D3 .


Plasma 25 ( OH ) D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol .


Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy .


However , the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects .


Mepolizumab , a humanized monoclonal antibody that binds to and inactivates interleukin-5 , has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma .


In a randomized , double-blind trial involving 135 patients with severe eosinophilic asthma , we compared the glucocorticoid-sparing effect of mepolizumab ( at a dose of 100 mg ) with that of placebo administered subcutaneously every 4 weeks for 20 weeks .


The primary outcome was the degree of reduction in the glucocorticoid dose ( 90 to 100 % reduction , 75 to less than 90 % reduction , 50 to less than 75 % reduction , more than 0 to less than 50 % reduction , or no decrease in oral glucocorticoid dose , a lack of asthma control during weeks 20 to 24 , or withdrawal from treatment ) .


Other outcomes included the rate of asthma exacerbations , asthma control , and safety .


The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group ( 95 % confidence interval , 1.25 to 4.56 ; P = 0.008 ) .


The median percentage reduction from baseline in the glucocorticoid dose was 50 % in the mepolizumab group , as compared with no reduction in the placebo group ( P = 0.007 ) .


Despite receiving a reduced glucocorticoid dose , patients in the mepolizumab group , as compared with those in the placebo group , had a relative reduction of 32 % in the annualized rate of exacerbations ( 1.44 vs. 2.12 , P = 0.04 ) and a reduction of 0.52 points with respect to asthma symptoms ( P = 0.004 ) , as measured on the Asthma Control Questionnaire 5 ( in which the minimal clinically important difference is 0.5 points ) .


The safety profile of mepolizumab was similar to that of placebo .


In patients requiring daily oral glucocorticoid therapy to maintain asthma control , mepolizumab had a significant glucocorticoid-sparing effect , reduced exacerbations , and improved control of asthma symptoms .


( Funded by GlaxoSmithKline ; SIRIUS ClinicalTrials.gov number , NCT01691508 . )


Longer duration of first-line chemotherapy for patients with metastatic breast cancer is associated with prolonged overall survival and improved progression-free survival .


We investigated capecitabine added to maintenance bevacizumab after initial treatment with bevacizumab and docetaxel in this setting .


We did this open-label randomised phase 3 trial at 54 hospitals in Brazil , China , Egypt , France , Hong Kong , India , Italy , Poland , Spain , and Turkey .


We enrolled patients with HER2-negative measurable metastatic breast cancer ; each received three to six cycles of first-line bevacizumab ( 15 mg/kg ) and docetaxel ( 75-100 mg/m ( 2 ) ) every 3 weeks .


Progression-free patients were randomly assigned with an interactive voice-response system by block ( size four ) randomisation ( 1:1 ) to receive either bevacizumab and capecitabine or bevacizumab only ( bevacizumab 15 mg/kg on day 1 ; capecitabine 1000 mg/m ( 2 ) twice per day on days 1-14 , every 3 weeks ) until progression , stratified by oestrogen receptor status ( positive vs negative ) , visceral metastases ( present vs absent ) , response status ( stable disease vs response vs non-measurable ) , and lactate dehydrogenase concentration ( 15 vs > 15upper limit of normal ) .


Neither patients nor investigators were masked to allocation .


The primary endpoint was progression-free survival ( from randomisation ) in the intention-to-treat population .


This trial is registered with ClinicalTrials.gov , NCT00929240 .


Between July 16 , 2009 , and March 7 , 2011 ( when enrolment was prematurely terminated ) , 284 patients received initial bevacizumab and docetaxel ; 185 ( 65 % ) were randomly assigned ( 91 to bevacizumab and capecitabine versus 94 to bevacizumab only ) .


Progression-free survival was significantly longer in the bevacizumab and capecitabine group than in the bevacizumab only group ( median 119 months [ 95 % CI 98-154 ] vs 43 months [ 39-68 ] ; stratified hazard ratio 038 [ 95 % CI 027-055 ] ; two-sided log-rank p < 00001 ) , as was overall survival ( median 390 months [ 95 % CI 323-not reached ] vs 237 months [ 185-317 ] ; stratified HR 043 [ 95 % CI 026-069 ] ; two-sided log-rank p = 00003 ) .


Results for time to progression were consistent with those for progression-free survival .


78 ( 86 % ) patients in the bevacizumab and capecitabine group and 72 ( 77 % ) in the bevacizumab only group had an objective response .


Clinical benefit was recorded in 92 ( 98 % ) patients in the bevacizumab alone group and 90 ( 99 % ) in the bevacizumab and capecitabine group .


Mean change from baseline in global health score did not differ significantly between groups .


Grade 3 or worse adverse events during the maintenance phase were more common with bevacizumab and capecitabine than with bevacizumab only ( 45 [ 49 % ] of 91 patients vs 25 [ 27 % ] of 92 patients ) .


The most common grade 3 or worse events were hand-foot syndrome ( 28 [ 31 % ] in the bevacizumab and capecitabine group vs none in the bevacizumab alone group ) , hypertension ( eight [ 9 % ] vs three [ 3 % ] ) , and proteinuria ( three [ 3 % ] vs four [ 4 % ] ) .


Serious adverse events were reported by ten ( 11 % ) patients in the bevacizumab and capecitabine group and seven ( 8 % ) patients in the bevacizumab only group .


Despite prematurely terminated accrual and the lack of information about post-progression treatment , both progression-free survival and overall survival were significantly improved with bevacizumab and capecitabine compared with bevacizumab alone as maintenance treatment .


These results might inform future maintenance trials and current first-line treatment strategies for HER2-negative metastatic breast cancer .


F Hoffmann-La Roche .


Facial exercises are a noninvasive alternative to medical approaches to facial rejuvenation .


Logopedists could be involved in providing these exercises .


Little research has been conducted , however , on the effectiveness of exercises for facial rejuvenation .


This study assessed the effectiveness of 4 exercises purportedly reducing wrinkles and sagging of the facial skin .


A control group study was conducted with 18 participants , 9 of whom ( the experimental group ) underwent daily training for 7 weeks .


Pictures taken before and after 7 weeks of 5 facial areas ( forehead , nasolabial folds , area above the upper lip , jawline and area under the chin ) were evaluated by a panel of laypersons .


In addition , the participants of the experimental group evaluated their own pictures .


Evaluation included the pairwise presentation of pictures before and after 7 weeks and scoring of the same pictures by means of visual analogue scales in a random presentation .


Only one significant difference was found between the control and experimental group .


In the experimental group , the picture after therapy of the upper lip was more frequently chosen to be the younger-looking one by the panel .


It can not be concluded that facial exercises are effective .


More systematic research is needed .


Reactive oxygen species are markedly increased after ischemia and play important roles in the mechanism of ischemia-reperfusion injury .


Regulating the oxidative stress response after brain ischemia provides a potential therapeutic strategy .


Quercetin is a natural flavonoid that exhibits antioxidant properties .


However , the mechanisms by which it protects cells are not fully understood .


Exercise training also reduces oxidative stress and enhances brain recovery .


The purpose of this study was to determine whether combined exercise training with quercetin treatment could result in better neuroprotection and functional recovery in rats subjected to brain ischemia .


Rats were randomly assigned to the following groups : middle cerebral artery occlusion ( MCAO ) with rest control , MCAO with quercetin , MCAO with exercise , or MCAO with exercise and quercetin .


To determine the effect of PI3K/Akt pathway in quercetin and exercise-mediated neuroprotection , two additional groups , a group of MCAO with quercetin and PI3K/Akt inhibitor ( LY294002 ) and a group of MCAO with exercise , quercetin , and PI3K/Akt inhibitor , were added in this study .


Motor function was examined at the 24th hour and 14th day post-MCAO .


Brain samples were used to measure the expression of antioxidative and antiapoptotic proteins as well as to measure the infarct volume .


Treatment with either exercise or quercetin significantly decreased oxidative stress and infarct volume , increased antioxidative and antiapoptotic signaling , and improved motor function .


Exercise training combined with quercetin treatment resulted in better outcomes than either treatment alone .


PI3K/Akt inhibition eliminated the protective effects of exercise training and quercetin treatment .


Quercetin enhances exercise-mediated functional recovery after brain ischemia via up-regulation of PI3K/Akt activity to promote antioxidative and antiapoptotic signaling .


Diclofenac dosing in children for analgesia is currently extrapolated from adult data .


Oral diclofenac 1.0 mgkg ( -1 ) is recommended for children aged 1-12years .


Analgesic effect from combination diclofenac/acetaminophen is unknown .


Children ( n = 151 ) undergoing tonsillectomy ( c. 1995 ) were randomized to receive acetaminophen elixir 40mgkg ( -1 ) before surgery and 20mgkg ( -1 ) rectally at the end of surgery with diclofenac suspension 0.1 mgkg ( -1 ) , 0.5 mgkg ( -1 ) , or 2.0 mgkg ( -1 ) before surgery or placebo .


A further 93 children were randomized to receive diclofenac 0.1 mgkg ( -1 ) , 0.5 mgkg ( -1 ) , or 2.0 mgkg ( -1 ) only .


Postoperative pain was assessed ( visual analogue score , VAS 0-10 ) at half-hourly intervals from waking until discharge .


Data were pooled with those from a further 222 children and 30 adults .


One-compartment models with first-order absorption and elimination described the pharmacokinetics of both medicines .


Combined drug effects were described using a modified EMAX model with an interaction term .


An interval-censored model described the hazard of study dropout .


Analgesia onset had an equilibration half-time of 0.496 h for acetaminophen and 0.23 h for diclofenac .


The maximum effect ( EMAX ) was 4.9 .


The concentration resulting in 50 % of EMAX ( C50 ) was 1.23 mgl ( -1 ) for diclofenac and 13.3 mgl ( -1 ) for acetaminophen .


A peak placebo effect of 6.8 occurred at 4h .


Drug effects were additive .


The hazard of dropping out was related to pain ( hazard ratio of 1.35 per unit change in pain ) .


Diclofenac 1.0 mgkg ( -1 ) with acetaminophen 15mgkg ( -1 ) achieves equivalent analgesia to acetaminophen 30mgkg ( -1 ) .


Combination therapy can be used to achieve similar analgesia with lower doses of both drugs .


The FIRIS study previously demonstrated non-inferiority of IRIS ( irinotecan plus S-1 ) to FOLFIRI ( 5-fluorouracil/leucovorin with irinotecan ) for progression-free survival as the second-line chemotherapy for metastatic colorectal cancer ( mCRC ) as the primary endpoint .


The overall survival ( OS ) data were immature at the time of the primary analysis .


Between 30 January 2006 and 29 January 2008 , 426 patients with mCRC who failed in first-line chemotherapy were randomly assigned to receive either FOLFIRI or IRIS .


After the primary analysis , the follow-up survey was cut off on 29 July 2010 , and the final OS data were analysed .


With a median follow-up of 39.2 months , the median OS was 17.4 months in the FOLFIRI group and 17.8 months in the IRIS group [ hazard ratio ( HR ) 0.900 ; 95 % confidence interval ( CI ) 0.728-1 .112 ] .


In the pre-planned subgroup of patients who received prior chemotherapy containing oxaliplatin , the median OS was 12.7 months in the FOLFIRI group and 15.3 months in the IRIS group ( HR 0.755 ; 95 % CI 0.580-0 .983 ) .


IRIS is non-inferior to FOLFIRI for OS as second-line chemotherapy for mCRC .


IRIS can be an option for second-line chemotherapy of mCRC .


( ClinicalTrials.gov Number : NCT00284258 ) .


Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management ; however , acetaminophen presents potential hepatotoxicity to patients and thus dose limitations .


These opioid medications are also widely abused .


Once-daily , single-entity hydrocodone ( Hysingla ER tablets [ HYD ] ) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic , hydrocodone .


This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics ( 23-31 % of the study populations ) .


Data were analyzed from two Phase III trials , a 12-week randomized , placebo-controlled trial ( RCT ) and an open-label , 52-week trial .


In both trials , a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind ( randomized controlled trial [ RCT ] ) or open-label , flexible-dose maintenance treatment .


Pain intensity was assessed using a numerical rating scale ( 0-10 , 0 = no pain ) .


For the RCT , primary and sensitivity analyses of pain scores used different approaches to handle missing data .


Safety data for both studies were summarized .


In the RCT , the mean baseline pain score was 7.3 .


Pain relief was greater with HYD than placebo during double-blind treatment .


In the open-label , flexible-dose trial , the majority of patients were maintained on their titrated dose .


Mean baseline pain score was 6.3 , about 57 % of patients completed the 1-year maintenance period , and mean pain scores were between 3.6 and 4.1 during the maintenance period .


Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD .


Adverse events in both trials were typical of those associated with opioid analgesics .


In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets , single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase .


HYD 's safety and tolerability profiles were similar to other opioid analgesics .


Stability between internal and external biological regulators are essential to stable mood states .


However , the literature needs studies investigating the effect of brief psychotherapies in the biological rhythm regularization .


To verify the capacity regulation of biological rhythms in two models of brief psychotherapy for the remission of depressive symptoms .


We conducted a randomized clinical trial with young adults aged 18-29 years old who met diagnostic criteria for depression according to the Structured Clinical Interview for DSM ( SCID ) .


In order to evaluate the biological rhythm the Biological Rhythm of assessment in Neuropsychiatry ( BRIAN ) interview was used ; whereas the severity of depression was assessed by the Hamilton Depression Rating Scale ( HDRS ) .


The psychotherapy models consisted of two cognitive psychotherapies : Cognitive Narrative Therapy ( CNT ) and Cognitive-Behavioral Therapy ( CBT ) .


The sample consisted of 97 randomized into two models of brief psychotherapy .


The patients regulated the biological rhythm from baseline to post-intervention ( p = .001 ) and follow up ( p = .003 ) .


We also found a positive moderate correlation between biological rhythm regularization and remission of the depressive symptoms ( r = .594 ; p < .001 ) .


The two models of brief psychotherapies were effective in the remission of depressive symptoms as well as the regulation of biological rhythms in the follow-up of 6 months .


We did not assess genetic , hormonal and neurochemical factors .


Also , we did not include patients in pharmaceutical treatment , and with severe symptomatology .


Obesity and overweight are becoming progressively more prevalent worldwide and are independently associated with a significant increase in the risk of cardiovascular diseases .


Systemic arterial hypertension is frequently found in association with obesity and contributes significantly to increased cardiovascular risk .


We hypothesise that Roux-en-Y gastric bypass ( RYGB ) surgery , a procedure that effectively reduces body weight , can also positively impact blood pressure control in obese and hypertensive individuals .


A unicentric , randomised , controlled , unblinded clinical trial .


Sixty obese ( body mass index between 30 and 39.9 ) and moderately well controlled hypertensive patients , in use of at least two antihypertensive medications at maximum doses or more than two in moderate doses , will be randomly allocated , using an online , electronic and concealed method , to receive either RYGB plus optimised clinical treatment ( OCT ) or OCT alone .


The primary end point is the reduction of antihypertensive medication at 1 and 2 years of follow-up .


Data analysis will primarily be conducted on an intention-to-treat basis .


The study was approved by the local institutional review board that works in total compliance with the latest version of the Helsinki Declaration , the Good Clinical Practices ( GCP ) , the ` America 's Document ' and the national regulatory laws .


Before the beginning of any study-related activities , each study participant is asked to provide a signed informed consent .


NCT01784848 .


We showed in a previous study that pylorus-resecting pancreaticoduodenectomy ( PrPD ) , which divides the stomach adjacent to the pylorus ring , preserves more than 95 % of the stomach and significantly reduced the incidence of delayed gastric emptying ( DGE ) compared with pylorus-preserving pancreaticoduodenectomy ( PpPD ) .


However , long-term outcomes of PrPD and the adverse effect of early postoperative DGE on long-term outcomes remain unclear .


A total of 130 patients enrolled in a previous study were followed for 24 months after surgery .


Primary endpoint was whether PrPD is a better surgical procedure than PpPD regarding long-term outcomes .


Weight loss > grade 2 ( Common Terminology Criteria for Adverse Events , Version 4.03 ) at 24 months after surgery was significantly better in group PrPD ( 16.2 % ) than in group PpPD ( 42.2 % ) ( p = 0.011 ) .


Nutritional status and late postoperative complications were similar for the two groups .


The incidence of weight loss > grade 2 at 24 months was 63.6 % in DGE patients with DGE and 25.3 % in non-DGE patients ( p = 0.010 ) .


T max ( time to peak ( 13 ) CO2 content in ( 13 ) C-acetate breath test ) at 24 months in DGE patients was significantly delayed compared with that in non-DGE patients ( 27.9 22.7 vs. 16.5 10.1 min , p = 0.023 ) .


Serum albumin level at 24 months was higher in non-DGE patients than in those with DGE ( 3.7 0.6 vs. 4.1 0.4 g/dl , p = 0.013 ) .


PrPD offers long-term outcomes similar to those of PpPD .


DGE may be associated with weight loss and poor nutritional status in patients with long-term outcomes .


We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin ( ) ( Theracurmin ; Theravalues , Tokyo , Japan ) .


The area under the blood concentration-time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder .


We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment .


Fifty patients with knee osteoarthritis of Kellgren-Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized , double-blind , placebo-controlled , prospective clinical study .


Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks .


To monitor adverse events , blood biochemistry analyses were performed before and after 8 weeks of each intervention .


The patients ' knee symptoms were evaluated at 0 , 2 , 4 , 6 , and 8 weeks by the Japanese Knee Osteoarthritis Measure , the knee pain visual analog scale ( VAS ) , the knee scoring system of the Japanese Orthopedic Association , and the need for nonsteroidal anti-inflammatory drugs .


At 8 weeks after treatment initiation , knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group , except in the patients with initial VAS scores of 0.15 or less .


Theracurmin lowered the celecoxib dependence significantly more than placebo .


No major side effects were observed with Theracurmin treatment .


Theracurmin shows modest potential for the treatment of human knee osteoarthritis .


In recent years the video game industry has surpassed both the music and video industries in sales .


Currently violent video games are among the most popular video games played by consumers , most specifically First-Person Shooters ( FPS ) .


Technological advancements in game play experience including the ability to play online has accounted for this increase in popularity .


Previous research , utilising the General Aggression Model ( GAM ) , has identified that violent video games increase levels of aggression .


Little is known , however , as to the effect of playing a violent video game online .


Participants ( N = 101 ) were randomly assigned to one of four experimental conditions ; neutral video game -- offline , neutral video game -- online , violent video game -- offline and violent video game -- online .


Following this they completed questionnaires to assess their attitudes towards the game and engaged in a chilli sauce paradigm to measure behavioural aggression .


The results identified that participants who played a violent video game exhibited more aggression than those who played a neutral video game .


Furthermore , this main effect was not particularly pronounced when the game was played online .


These findings suggest that both playing violent video games online and offline compared to playing neutral video games increases aggression .


Mindfulness Based Stress Reduction ( MBSR ) is a secular form of meditation training .


The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons .


Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention .


We used a visual continuous performance task ( CPT ) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program ( HEP ) , a structurally equivalent , active control condition in a randomized , longitudinal design ( ClinicalTrials.gov , NCT01301105 ) focusing on a non-clinical population typical of MBSR participants .


Researchers were blind to group assignment .


63 community participants were randomized to either MBSR ( n = 31 ) or HEP ( n = 32 ) .


CPT analyses were conducted on 29 MBSR participants and 25 HEP participants .


We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP , with more home practice associated with greater improvements .


Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research .


Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance .


One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable .


Attentional sensitivity is not affected by mindfulness practice as taught in MBSR , but it is unclear whether mindfulness might positively affect another aspect of attention , vigilance .


These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples .


ClinicalTrials.gov , NCT01301105 .


There is scarce and inconsistent information about gender-related differences in the hydration of sports persons , as well as about the effects of hydration on performance , especially during indoor sports .


To determine the physiological differences between genders during in indoor physical exercise , with and without hydration .


21 spinning sportspeople ( 12 men and 9 women ) participated in three controlled , randomly assigned and non-sequential hydration protocols , including no fluid intake and hydration with plain water or a sports drink ( volume adjusted to each individual every 15 min ) , during 90 min of spinning exercise .


The response variables included body mass , body temperature , heart rate and blood pressure .


During exercise without hydration , men and women lost ~ 2 % of body mass , and showed higher body temperature ( ~ 0.2 C ) , blood pressure ( ~ 4 mmHg ) and heart rate ( ~ 7 beats/min ) compared to exercises with hydration .


Body temperature and blood pressure were higher for men than for women during exercise without hydration , differences not observed during exercise with hydration .


Between 42-99 % of variance in body temperature , blood pressure and heart rate could be explained by the physical characteristics of subjects and the work done .


During exercise with hydration ( either with water or sport drink ) , the physiological response was similar for both genders .


Exercise without hydration produced physical stress , which could be prevented with either of the fluids ( plain water was sufficient ) .


Gender differences in the physiological response to spinning ( body temperature , mean blood pressure and heart rate ) can be explained in part by the distinct physical characteristics of each individual .


Higher serum urate concentrations predict more favorable prognosis in individuals with Parkinson disease ( PD ) .


The purpose of this study was to test the causality of this association using a Mendelian randomization approach .


The study was conducted among participants in DATATOP and PRECEPT , 2 randomized trials among patients with early PD .


The 808 patients with available DNA were genotyped for 3 SLC2A9 single nucleotide polymorphisms ( SNPs ) that identify an allele associated with lower urate concentrations , and for selected SNPs in other genes encoding urate transporters that have modest or no effect on serum urate levels .


An SLC2A9 score was created based on the total number of minor alleles at the 3 SLC2A9 loci .


Primary outcome was disability requiring dopaminergic treatment .


Serum urate concentrations were 0.69 mg/dl lower among individuals with 4 SLC2A9 minor alleles as compared to those with 2 ( p = 0.0002 ) .


The hazard ratio ( HR ) for progression to disability requiring dopaminergic treatment increased with increasing SLC2A9 score ( HR = 1.16 , 95 % confidence interval [ CI ] = 1.00-1 .35 , p = 0.056 ) .


In a comparative analysis , the HR was 1.27 ( 95 % CI = 1.00-1 .61 , p = 0.0497 ) for a 0.5 mg/dl genetically conferred decrease in serum urate , and 1.05 ( 95 % CI = 1.01-1 .10 , p = 0.0133 ) for a 0.5 mg/dl decrease in measured serum urate .


No associations were found between polymorphisms in other genes associated with urate that do not affect serum urate and PD progression .


This Mendelian randomization analysis adds to the evidence of a causal protective effect of high urate levels .


To examine the relationship between perceived discrimination and medication adherence among black people with hypertension and the role of stress and depressive symptoms in this relationship .


Perceived racial discrimination has been associated with poor health outcomes in blacks ; its relationship to medication adherence among hypertensive patients remains untested .


We measured perceived racial discrimination at baseline , stress and depressive symptoms at 6 months , and medication adherence at 12 months among patients enrolled in a 30-site cluster-randomized controlled trial testing a patient and physician-targeted intervention to improve blood pressure .


A mediational method with bootstrapping ( stratified by site ) confidence intervals was used to estimate the indirect association between perceived discrimination and medication adherence through stress and depression .


Of 1056 patients from 30 sites enrolled in the trial , 463 had complete data on all four measures at 6 and 12 months and were included in the analyses .


Adjusting for clustering , perceived discrimination was associated with poor medication adherence ( B = 0.138 , p = .011 ) at 12 months , and with stress ( B = 2.24 , p = .001 ) and depression ( B = 1.47 , p = .001 ) at 6 months .


When stress and depression were included in the model , there was a 65 % reduction in the total association of perceived discrimination with medication adherence , and the relationship was no longer significant ( B = 0.049 , p = .35 ) .


Perceived discrimination is associated with poor medication adherence among hypertensive blacks , and stress and depressive symptoms may account for this relationship .


clinicaltrials.gov Identifier : NCT00233220 .


The objective was to evaluate a configural vital signs ( CVS ) display designed to support rapid detection and identification of physiological deterioration by graphically presenting patient vital signs data .


Current display technology in the intensive care unit ( ICU ) is not optimized for fast recognition and identification of physiological changes in patients .


To support nurses more effectively , graphical or configural vital signs displays need to be developed and evaluated .


A CVS display was developed based on findings from studies of the cognitive work of ICU nurses during patient monitoring .


A total of 42 ICU nurses interpreted data presented either in a traditional , numerical format ( n = 21 ) or on the CVS display ( n = 21 ) .


Response time and accuracy in clinical data interpretation ( i.e. , identification of patient status ) were assessed across four scenarios .


Data interpretation speed and accuracy improved significantly in the CVS display condition ; for example , in one scenario nurses required only half of the time for data interpretation and showed up to 1.9 times higher accuracy in identifying the patient state compared to the numerical display condition .


Providing patient information in a configural display with readily visible trends and data variability can improve the speed and accuracy of data interpretation by ICU nurses .


Although many studies , including this one , support the use of configural displays , the vast majority of ICU monitoring displays still present clinical data in numerical format .


The introduction of configural displays in clinical monitoring has potential to improve patient safety .


This study aims to observe the impact of the temperature of blood transfusion and infusion toward the perioperative cerebral oxygen metabolism and the postoperative cognitive recovery .