614 adult female patients will be recruited from four primary care research networks ( Wales , England , Spain , the Netherlands ) and individually randomised to either POCT guided care or the guideline-informed ` standard care ' arm .


Urine and stool samples ( where possible ) will be obtained at presentation ( day 1 ) and two weeks later for microbiological analysis .


All participants will be followed up on the course of their illness and their quality of life , using a 2 week self-completed symptom diary .


At 3 months , a primary care notes review will be conducted for evidence of further evidence of treatment failures , recurrence , complications , hospitalisations and health service costs .


Although the Flexicult POCT is used in some countries in routine primary care , it 's clinical and cost effectiveness has never been evaluated in a randomised clinical trial .


If shown to be effective , the use of this POCT could benefit individual sufferers and provide evidence for health care authorities to develop evidence based policies to combat the spread and impact of the unprecedented rise of infections caused by antibiotic resistant bacteria in Europe .


ISRCTN65200697 ( Registered 10 September 2013 ) .


During clinical development of the licensed Japanese encephalitis chimeric virus vaccine ( JE-CV ) , the neutralization capacity of vaccine-induced antibodies was assessed against the vaccine virus and against well characterized wild-type ( wt ) viruses isolated between 1949-1991 .


We assessed whether JE-CV-induced antibodies can also neutralize more recent wt Japanese encephalitis virus ( JEV ) isolates including a genotype 1 isolate .


Sera from 12-18month-old children who received a single dose of JE-CV in a phase III study in Thailand and the Philippines ( ClinicalTrials.gov NCT00735644 ) were randomly selected and pooled according to neutralization titer against JE-CV into eight samples .


Neutralization was assessed by plaque reduction neutralization tests ( PRNT50 ) against three recent isolates from JEV genotypes 1 and 3 in addition to four JEV previously tested .


Neutralization titers against the three recent JEV strains were comparable to those observed previously against other strains and the vaccine virus .


The observed differences between responses to genotype 1 and 3 viruses were within assay variability for the PRNT50 .


The results were consistent with previously generated data on the neutralization of wt JEV isolates , immune responses induced by JE-CV neutralize recently isolated virus from southeast ( SE ) Asia and India .


Evidence regarding what comprises effective education for acne vulgaris patients is lacking .


Internet-based education may improve patient knowledge of this condition .


Our objective was to compare the effectiveness of standard web-based education and an automated counseling website in improving acne knowledge .


In a randomized trial , participants visited either a standard website or an automated counseling website to learn about acne .


Multiple-choice questions were administered at baseline and after 12weeks to assess change in acne knowledge .


A total of 97 high school students were enrolled , and 95 completed the study .


The standard website group had a significant increase in knowledge from baseline ( 3.611.22 ) to 12-week follow-up ( 5.461.31 , p < 0.001 ) .


Similarly , the automated counseling website group had a significant increase in knowledge between both time points ( 3.531.50 vs. 6.491.06 , p < 0.001 ) .


After 12 weeks , mean improvement in knowledge was higher in the automated counseling group ( 2.961.85 ) than in the standard website group ( 1.851.46 , d = 0.67 , p = 0.002 ) .


The number of website visits was positively correlated with improvement in knowledge in both groups .


Finally , the automated counseling website group rated their educational material more useful ( p = 0.004 ) and more enjoyable to view ( p = 0.003 ) than did the standard website group .


This study is limited to adolescents with mild-to-moderate acne vulgaris .


Internet-based patient education appears to be an effective method of improving acne knowledge among adolescents .


Neuropeptide Y is a key peptide affecting adiposity and has been related to obesity risk .


However , little is known about the role of NPY variations in diet-induced change in adiposity .


The objective was to examine the effects of NPY variant rs16147 on central obesity and abdominal fat distribution in response to dietary interventions .


We genotyped a functional NPY variant rs16147 among 723 participants in the Preventing Overweight Using Novel Dietary Strategies trial .


Changes in waist circumference ( WC ) , total abdominal adipose tissue , visceral adipose tissue , and subcutaneous adipose tissue ( SAT ) from baseline to 6 and 24 mo were evaluated with respect to the rs16147 genotypes .


Genotype-dietary fat interaction was also examined .


The rs16147 C allele was associated with a greater reduction in WC at 6 mo ( P < 0.001 ) .


In addition , the genotypes showed a statistically significant interaction with dietary fat in relation to WC and SAT ( P-interaction = 0.01 and 0.04 ) : the association was stronger in individuals with high-fat intake than in those with low-fat intake .


At 24 mo , the association remained statistically significant for WC in the high-fat diet group ( P = 0.02 ) , although the gene-dietary fat interaction became nonsignificant ( P = 0.30 ) .


In addition , we found statistically significant genotype-dietary fat interaction on the change in total abdominal adipose tissue , visceral adipose tissue , and SAT at 24 mo ( P = 0.01 , 0.05 , and 0.04 ) : the rs16147 T allele appeared to associate with more adverse change in the abdominal fat deposition in the high-fat diet group than in the low-fat diet group .


Our data indicate that the NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions , and the effects of the rs16147 single-nucleotide polymorphism on central obesity and abdominal fat distribution were modified by dietary fat .


To compare clinical and subjective quality-of-life ( QoL ) data for teenagers wearing daily disposable contact lenses or spectacles .


This open-label study randomized subjects ( aged 13 to 19 years ) with no previous contact lens wear experience to nelfilcon A ( DAILIES AquaComfort Plus ) contact lenses or spectacles for 6 months .


A full clinical workup , as well as subjective QoL measures using the Pediatric Refractive Error Profile and Quality of Life Impact of Refractive Correction questionnaires , was conducted at baseline and at week 4 and months 3 and 6 , with an additional study visit at week 2 for subjects randomized to wear contact lenses .


A total of 110 teenagers were enrolled in the study ; 13 discontinued before study completion , 10 ( 17.5 % ) from the contact lens group and 3 ( 5.7 % ) from the spectacle group ( p = 0.04 ) .


Visual acuity was good for both groups at all study visits .


Biomicroscopy assessments were similar at baseline for both groups .


Significant differences in Pediatric Refractive Error Profile responses were noted between vision correction groups across visits for appearance ( p < 0.001 ) , satisfaction ( p < 0.001 ) , activities ( p < 0.001 ) , peer perception ( p = 0.003 ) , and overall score ( p < 0.001 ) .


For Quality of Life Impact of Refractive Correction , the contact lens group gave more favorable responses than the spectacle group ( p = 0.02 ) .


After 6 months of wearing contact lenses , teenagers had a more positive attitude toward comfort , vision , and safety with contact lenses .


No serious adverse events were reported during the study .


The daily disposable lenses used in this study are suitable for vision correction for teenagers , offering improvements in QoL measures during the first month of wear , including appearance , satisfaction , activities , and peer perceptions , without negatively impacting vision or eye health .


Teenagers were able to handle contact lenses with the same amount of confidence as spectacles .


Severe deficiencies of testosterone ( T ) and GH are associated with low bone mineral density ( BMD ) and increased fracture risk .


Replacement of T in hypogonadal men improves several bone parameters .


Replacement of GH in GH-deficient men improves BMD .


Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism .


This randomized , prospective , 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism .


Subjects were randomized to receive T alone ( n = 15 ) or T and GH ( n = 17 ) for 2 years .


We evaluated magnetic resonance microimaging-derived structural ( bone volume fraction [ BVF ] and trabecular thickness ) and mechanical ( axial stiffness [ AS ] , a measure of bone strength ) properties of the distal tibia at baseline and after 1 and 2 years of treatment .


Treatment with T and GH did not affect BVF , thickness , or AS differently from T alone .


T treatment in all subjects for 2 years increased trabecular BVF by 9.6 % ( P < .0001 ) , trabecular thickness by 2.6 % ( P < .001 ) , and trabecular AS by 9.8 % ( P < .001 ) .


In contrast , testosterone treatment in all subjects significantly increased cortical thickness by 2.4 % ( P < .01 ) but decreased cortical BVF by -4.7 % ( P < .01 ) and cortical AS by -6.9 % ( P < .01 ) .


Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone .


However , testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone , illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone .


Traumatic brain injury ( TBI ) is the leading cause of death and disability in the US .


Approximately 70-90 % of the TBI cases are classified as mild , and up to 25 % of them will not recover and suffer chronic neurocognitive impairments .


The main pathology in these cases involves diffuse brain injuries , which are hard to detect by anatomical imaging yet noticeable in metabolic imaging .


The current study tested the effectiveness of Hyperbaric Oxygen Therapy ( HBOT ) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments .


The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome ( PCS ) .


The HBOT effect was evaluated by means of prospective , randomized , crossover controlled trial : the patients were randomly assigned to treated or crossover groups .


Patients in the treated group were evaluated at baseline and following 40 HBOT sessions ; patients in the crossover group were evaluated three times : at baseline , following a 2-month control period of no treatment , and following subsequent 2-months of 40 HBOT sessions .


The HBOT protocol included 40 treatment sessions ( 5 days/week ) , 60 minutes each , with 100 % oxygen at 1.5 ATA .


`` Mindstreams '' was used for cognitive evaluations , quality of life ( QOL ) was evaluated by the EQ-5D , and changes in brain activity were assessed by SPECT imaging .


Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period .


SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements .


HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage .


ClinicalTrials.gov NCT00715052 .


The Grip on Challenging Behavior care program was developed using the current guidelines and models on managing challenging behavior in dementia in nursing homes .


It was hypothesized that the use of the care program would lead to a decrease in challenging behavior and in the prescription of psychoactive drugs without increase in use of restraints .


A randomized controlled trial was undertaken using a stepped-wedge design to implement the care program and to evaluate the effects .


An assessment of challenging behavior and psychoactive medication was undertaken every 4 months on all participating units followed by the introduction of the care program in a group of 3 to 4 units .


A total of 6 time assessments took place over 20 months .


Seventeen dementia special care units of different nursing homes .


A total of 659 residents of dementia special care units .


All residents with dementia on the unit were included .


Units were assigned by random allocation software to 1 of 5 groups with different starting points for the implementation of the care program .


A care program consisting of various assessment procedures and tools , which ensure a multidisciplinary approach and which structure the process of managing challenging behavior in dementia .


Challenging behavior was measured using the Cohen-Mansfield Agitation Inventory ( CMAI ) and the Neuropsychiatric Inventory .


Research assistants ( blinded for intervention status of the unit ) interviewed nurses on the units about challenging behavior .


Data on psychoactive drugs and restraints were retrieved from resident charts .


A total of 2292 assessments took place involving 659 residents ( 1126 control measurements , 1166 intervention measurements ) .


The group of residents who remained in the intervention condition compared with the group in the control condition differed significantly in the CMAI change scores between successive assessments [ -2.4 CMAI points , 95 % confidence interval ( CI ) -4.3 to -0.6 ] .


No significant effects were found for the control-to-intervention group compared with the group who remained in the control group ( 0.0 CMAI points , 95 % CI -2.3 to 2.4 ) .


Significant effects were found on 5 of the 12 Neuropsychiatric Inventory items and on the use of antipsychotics ( odds ratio 0.54 , 95 % CI 0.37 - 0.80 ) and antidepressants ( odds ratio 0.65 , 95 % CI 0.44-0 .94 ) .


No effect on use of restraints was observed .


The Grip on Challenging behavior program was able to diminish some forms of challenging behavior and the use of psychoactive drugs .


HIV-infected prisoners have a high prevalence of alcohol use disorders and commonly relapse to alcohol soon after release to the community which is linked to high morbidity , poor antiretroviral therapy ( ART ) adherence and increased sexual risk-taking behaviors .


Extended-release naltrexone ( XR-NTX ) effectively reduces relapse to alcohol in alcohol dependent persons , yet it remains unexamined among criminal justice system ( CJS ) populations transitioning to the community .


A randomized double-blind , placebo-controlled trial of XR-NTX to improve HIV treatment outcomes via reducing relapse to alcohol use after prison release for HIV-infected hazardous drinking and alcohol dependent prisoners is discussed .


Acceptability of study participation is high with 86 % of those referred who met eligibility criteria and 85 % of those who were able to receive injections prior to release accepted injections , yet important implementation issues are identified and addressed during the study and are discussed in this paper .


Medication-assisted therapies for prevention of relapse to alcohol use for CJS populations transitioning to the community , especially for HIV-infected patients , are urgently needed in order to reduce alcohol relapse after release and improve HIV treatment outcomes and contribute to improved individual and public health .


To examine whether the consumption of a Mediterranean diet ( MedDiet ) , compared with a low-fat diet , interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene ( rs1800629 , rs1799964 ) in order to improve triglycerides ( TG ) , glycemic control , and inflammation markers .


Genotyping , biochemical measurements , dietary intervention , and oral fat load test meal were determined in 507 metabolic syndrome ( MetS ) patients selected from all the subjects included in CORDIOPREV clinical trial ( n = 1002 ) .


At baseline , G/G subjects ( n = 408 ) at the rs1800629 polymorphism , showed higher fasting and postprandial TG ( p = 0.003 and p = 0.025 , respectively ) , and high sensitivity C-reactive protein ( hsCRP ) ( p = 0.003 ) plasma concentrations than carriers of the minor A-allele ( G/A + A/A ) ( n = 99 ) .


After 12 months of MedDiet , baseline differences between genotypes disappeared .


The decrease in TG and hsCRP was statistically significant in G/G subjects ( n = 203 ) compared with carriers of the minor A-allele ( p = 0.005 and p = 0.034 , respectively ) ( n = 48 ) .


No other gene-diet interactions were observed in either diet .


These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects .


Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS .


We investigated real-life oral anticoagulation ( OAC ) treatment after surgical ablation and examined its adherence to current recommendations .


We also explored factors related to OAC use preoperatively and at follow-up .


One hundred and fifteen patients with atrial fibrillation ( AF ) were evaluated during 12-month follow-up after surgery .


Patients were divided into two categories according to the congestive heart failure , hypertension , age 75 years , diabetes and prior stroke [ or transient ischaemic attack or thromboembolism ] ( CHADS2 ) score : 60 patients were assigned to the high-risk group ( CHADS2 score 2 ) and 55 to the low-risk group ( CHADS2 score 1 ) .


OAC use was defined as guideline adherent , undertreatment or overtreatment .


Baseline overall guideline adherence was 62 % .


OAC was underprescribed in high-risk patients and overprescribed in low-risk patients ( both , P < 0.001 ) .


The only factor associated with OAC use after logistic regression analysis were age > 75 years ( P = 0.01 ) and preoperative AF > paroxysmal ( P = 0.013 ) .


Overall guideline adherence at 12-month follow-up showed a trend towards a better adherence in the sinus rhythm ( SR ) subgroup ( 74 % vs 55 % , P = 0.02 ) .


OAC was underprescribed in high-risk patients and overprescribed in low-risk patients ( both P < 0.001 ) .


After logistic regression analysis , preoperative OAC use ( P = 0.007 ) and other indications for OAC ( P = 0.01 ) were predictors of anticoagulation treatment .


Real-life OAC prescription in AF patients showed a moderate guideline adherence , with high-risk patients being undertreated and low-risk patients being overtreated .


These findings stress the importance that antithrombotic treatment in patients undergoing AF surgery needs to be critically re-evaluated .


Memory T-cells are mediators of transplant injury , and no therapy is known to prevent the development of cross-reactive memory alloimmunity .


Activated vitamin D is immunomodulatory , and vitamin D deficiency , common in hemodialysis patients awaiting transplantation , is associated with a heightened alloimmune response .


Thus , we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients .


We performed a 12-month single-center pilot randomized , controlled trial of 50,000 IU/week of cholecalciferol ( D3 ) versus no supplementation in 96 hemodialysis patients with serum 25 ( OH ) D < 25 ng/mL , measuring effects on serum 25 ( OH ) D and phenotypic and functional properties of T-cells .


Participants were randomized 2:1 to active treatment versus control .


D3 supplementation increased serum 25 ( OH ) D at 6 weeks ( 13.5 [ 11.2 ] ng/mL to 42.5 [ 18.5 ] ng/mL , p < 0.001 ) and for the duration of the study .


No episodes of sustained hypercalcemia occurred in either group .


Results of IFN ELISPOT-based panel of reactive T-cell assays ( PRT ) , quantifying alloreactive memory , demonstrated greater increases in the controls over 1 year compared to the treatment group ( delta PRT in treatment 104.8 + / -330.8 vs 252.9 + / -431.3 in control ) , but these changes in PRT between groups did not reach statistical significance ( p = 0.25 ) .


D3 supplements are safe , effective at treating vitamin D deficiency , and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients , but their effects on alloimmunity need to be confirmed in larger studies .


These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients .


Clinicaltrials.gov NCT01175798 .


To investigate the timing and value of noninvasive ventilation ( NIV ) as a weaning tool immediately after early extubation in patients with acute respiratory distress syndrome ( ARDS ) .


A prospective randomized controlled trial was conducted .


The ARDS patients with surgical diseases admitted to Department of Respiratory Intensive Care Unit ( RICU ) of the First Affiliated Hospital of Xinjiang Medical University were enrolled .


The patients were randomly divided into sequential group and control group .


All patients underwent endotracheal intubation and were mechanically ventilated .


Every 12 hours during the first 3 days , the lung recruitment maneuver was performed during pressure control ventilation ( PCV ) .


After lung recruitment , all patients were ventilated with synchronized intermittent mandatory ventilation ( SIMV ) + pressure support ventilation ( PSV ) + positive end-expiratory pressure ( PEEP ) or assistant/control ventilation ( A/C ) .


The objects in sequential group who met the following criteria including those with oxygen index ( PaO2/FiO2 ) reaching 200-250 mmHg ( 1 mmHg = 0.133 kPa ) under PEEP of 8 cmH2O ( 1 cmH2O = 0.098 kPa ) , and pressure support of 12 cmH2O , and most acute infiltrating lesions having resolved on chest imaging , received noninvasive ventilation ( NIV ) immediately after extubation , and patients in control group continued to have invasive mechanical ventilation via intubation or tracheostomy with an endotracheal tube .


The baseline data in both groups and the number of re-intubation in the sequential group were recorded .


The duration of invasive mechanical ventilation and total duration of mechanical ventilation , ICU length of stay , the incidence of ventilator-associated pneumonia ( VAP ) , and mortality rate were compared between the two groups .


53 consecutive adult patients were enrolled , including 26 in sequential group and 27 cases in control group .


The period of endotracheal intubation was 7.0 ( 6.8 , 9.5 ) days , and 7.7 % ( 2/26 ) patients underwent re-intubation in sequential group .


There were significant difference in respiratory and circulatory indicators before extubation spontaneous breathing trial ( SBT ) 10 minutes in sequential group , indicating that the patients were still in the early stage of extubation sequential NIV .


There was no significant difference in indices reflecting respiratory function and circulation between the two groups , except that respiratory rate at 1 hour was slightly increased in sequential group as compared with that of control group , indicating that sequential NIV could maintain invasive ventilation function .


There was significant difference in duration of invasive mechanical ventilation [ 7.0 ( 6.8 , 9.5 ) days vs. 21.0 ( 17.0 , 25.0 ) days , Z = -6.048 , P = 0.000 ] , duration of total mechanical ventilation ( 18.04.1 days vs. 22.07.3 days , t = -2.805 , P = 0.008 ) , and length of ICU stay ( 21.04.1 days vs. 28.08.1 days , t = -4.012 , P = 0.000 ) between sequential group and control group , but there was no significant differences in the incidence of VAP [ 15.4 % ( 4/26 ) vs. 29.6 ( 8/27 ) , ( 2 ) = 1.535 , P = 0.215 ] and mortality rate [ 7.7 % ( 2/26 ) vs. 18.5 % ( 5/27 ) , P = 0.420 ] .


When PaO2/FiO2 reached 200-250 mmHg under the condition of low ventilation , sequential NIV facilitates the early discontinuation of mechanical ventilation in ARDS patients with surgical diseases , with shortening of duration of invasive mechanical ventilation , total mechanical ventilation , and the length of ICU stay .


Low serum 25-hydroxyvitamin D levels ( 25 ( OH ) D ) have been associated with a higher likelihood of seasonal affective disorder ( SAD ) and poor mental well-being , yet firm evidence for either remains lacking .


Thus , vitamin D supplementation may alleviate symptoms associated with SAD .


This study was a randomized , single-centre , double-blind , placebo-controlled trial including healthcare professionals employed in psychiatric and somatic hospitals .


3345 healthcare professionals were invited to participate , 50 participants were screened , and 34 were able to complete the study .


The main inclusion criterion was 8 points or more on question no. 2 of the Seasonal Pattern Assessment Questionnaire ( SPAQ-SAD ) .


During a 3-month period , the participants received a daily dose of 70g vitamin D or placebo .


The primary outcome was the sum of the self-reported questionnaire Structured Interview Guide for the Hamilton Depression Rating Scale , Seasonal Affective Disorders ( SIGH-SAD ) .


The secondary outcome was World Health Organization-Five Well-Being Index ( WHO-5 ) of the healthcare professionals during the winter period and the exploratory outcome measures were weight , waist circumference , blood pressure , absenteeism from work and 25 ( OH ) D.


There were no significant between-group differences in SIGH-SAD sums at 12weeks ( p = 0.7 ( CI : - 3.27 to 4.81 ) ) .


However , there was a significant improvement of primary SIGH-SAD over time from inclusion ( autumn-winter ) to the completion of the study ( winter-spring ) for all participants .


The secondary and exploratory outcome measures were all insignificant between groups.The sums of the SIGH-SAD at 12weeks were not significantly different [ p = 0.701 ( CI : 4.81-3 .27 ) ] between the groups .


There was , however , a significant improvement in primary SIGH-SAD sums over time from inclusion ( autumn-winter ) to the completion of the study ( winter-spring ) in both groups .


The secondary and explorative outcome measures were not significantly different between groups .


There were no significant between-group differences in the primary ( SIGH-SAD ) and secondary ( WH0-5 ) as well as the exploratory outcome measures ( weight , waist circumference , blood pressure , absenteeism from work and 25 ( OH ) D. Thus , the study failed to demonstrate an effect of vitamin D on SAD symptoms , but our findings may be limited by confounders .


Furthermore , the study was underpowered and did not allow us to assess the ability of vitamin D to improve mood in those with low 25 ( OH ) D.


( http://www.clinicaltrials.gov registration number : NCT01462058 ) .


Secondary hyperparathyroidism is a common consequence of chronic kidney disease .


Cinacalcet ( Sensipar ( ) ) is often prescribed in combination to reduce elevated levels of parathyroid hormone , calcium and phosphorus .


The objective of this study was to assess the effects of concomitantly administered therapies of calcium carbonate ( CaCO ( 3 ) ; TUMS ( ) ) , sevelamer hydrochloride ( HCl ; Renagel ( ) ) and pantoprazole sodium ( Protonix ( ) ) on the pharmacokinetics and safety of cinacalcet in healthy subjects .


Three randomized , open-label , two-way crossover pharmacokinetic studies were conducted in healthy subjects .


Participants received single doses of cinacalcet alone or in combination with either CaCO ( 3 ) , sevelamer HCl or pantoprazole .


The pharmacokinetic profile of cinacalcet was characterized .


Safety assessments including adverse event reporting , changes in vital signs and clinical laboratory measurements were conducted throughout the studies .


The 90 % confidence intervals for the area under the concentration-time curve from time zero to the last quantifiable concentration ( AUC ( last ) ) , area under the concentration-time curve from time zero to infinity ( AUC ( 0 - ) ) and maximum plasma concentration ( C ( max ) ) of cinacalcet were within the accepted range of 80-125 % for both CaCO ( 3 ) and sevelamer HCl co-administration with cinacalcet .


No severe or serious adverse events or clinically relevant changes in physical or laboratory findings occurred during the studies .


The pharmacokinetic parameters of cinacalcet were not affected by co-administration of CaCO ( 3 ) , sevelamer HCl or pantoprazole .


Co-administration of these agents with cinacalcet does not require an adjustment of the dose of cinacalcet .


We examined the efficacy of a community-based , culturally relevant intervention to promote healthy eating and physical activity among African American ( AA ) women between the ages of 45-65 years , residing in rural Alabama .


We conducted a group randomized controlled trial with counties as the unit of randomization that evaluated two interventions based on health priorities identified by the community : ( 1 ) promotion of healthy eating and physical activity ; and ( 2 ) promotion of breast and cervical cancer screening .


A total of 6 counties with 565 participants were enrolled in the study between November 2009 and October 2011 .


The overall retention rate at 24-month follow-up was 54.7 % .


Higher retention rate was observed in the `` healthy lifestyle '' arm ( 63.1 % ) as compared to the `` screening '' arm ( 45.3 % ) .


Participants in the `` healthy lifestyle '' arm showed significant positive changes compared to the `` screening '' arm at 12-month follow-up with regard to decrease in fried food consumption and an increase in both fruit/vegetable intake and physical activity .


At 24-month follow-up , these positive changes were maintained with healthy eating behaviors , but not engagement in physical activity .


A culturally relevant intervention , developed in collaboration with the target audience , can improve ( and maintain ) healthy eating among AA women living in rural areas .


To compare local infiltration of dexamethasone to intravenous injection for postoperative pain and recovery after tonsillectomy .


Prospective , randomized study .


Second Affiliated Hospital of Harbin Medical University .


Children ( n = 240 , American Society of Anesthesiologists [ ASA ] classes I-II , aged 5-10 y ) scheduled for tonsillectomy were randomly and equally assigned to 3 groups : DEX-IV , for intravenous injection of dexamethasone ( 0.5 mg/kg , maximum dose 24 mg ) ; DEX-INF , given the same amount of dexamethasone by local infiltration to the upper middle and lower poles of the tonsils ; and a control group not given dexamethasone .


Postoperative pain was scored at intervals from 30 minutes to 24 hours .


The time to first administration of analgesic and average consumption of analgesic , times to first oral water and solid food intake , and incidence rates of nausea and vomiting were evaluated .


From postoperative 1 to 16 hours , the DEX-INF group had significantly lower pain scores than did the DEX-IV group , and the time to first analgesic and average consumption of analgesic were also significantly lower .


The times to first oral water and food intake in the DEX-INF group were significantly shorter than in the DEX-IV group .


The incidence of nausea and vomiting in the DEX-INF group was higher than that of the DEX-IV group .


Local infiltration of dexamethasone was more effective than systemic administration to decrease pain and time to food intake , but the antiemetic effect was less .


ChiCTR-TRC-13003535 .


A vicious circle of decreased physical fitness , early fatigue , and low physical activity levels ( PAL ) is thought to affect children with cerebral palsy ( CP ) .


However , the relationship of changes in physical fitness to changes in PAL and fatigue is unclear .


The objective of this study was to investigate the associations among changes in physical fitness , walking-related PAL , and fatigue in children with CP .


This study was a secondary analysis of a randomized controlled trial with measurements at baseline , 6 months ( after the intervention period ) , and 12 months .


Twenty-four children with bilateral spastic CP and 22 with unilateral spastic CP , aged 7 to 13 years , all walking , participated in this study .


Physical fitness was measured by aerobic capacity , anaerobic threshold , anaerobic capacity , and isometric and functional muscle strength .


Walking-related PAL was measured using an ankle-worn activity monitor for 1 week .


Fatigue was determined with the Pediatric Quality of Life ( PedsQL ) Multidimensional Fatigue Scale .


Longitudinal associations were analyzed by random coefficient regression analysis .


In children with bilateral CP , all fitness parameters showed a positive , significant association with walking-related PAL , whereas no associations between physical fitness and walking-related PAL were seen in children with unilateral CP .


No clinically relevant association between physical fitness and fatigue was found .


Although random coefficient regression analysis can be used to investigate longitudinal associations between parameters , a causal relationship can not be determined .


The actual direction of the association between physical fitness and walking-related PAL , therefore , remains inconclusive .


Children with bilateral spastic CP might benefit from improved physical fitness to increase their PAL or vice versa , although this is not the case in children with unilateral CP .


There appears to be no relationship between physical fitness and self-reported fatigue in children with CP .


Interventions aimed at improving PAL may be differently targeted in children with either bilateral or unilateral CP .


Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed .


Mathematical modelling and the HIV Prevention Trials Network ( HPTN ) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment ( ART ) should substantially reduce incidence and may eliminate HIV as a public health problem .


We describe the rationale and design of a trial to evaluate this hypothesis .


A rigorously-designed trial of universal testing and treatment ( UTT ) interventions is needed because : i ) it is unknown whether these interventions can be delivered to scale with adequate uptake ; ii ) there are many uncertainties in the models such that the population-level impact of these interventions is unknown ; and ii ) there are potential adverse effects including sexual risk disinhibition , HIV-related stigma , over-burdening of health systems , poor adherence , toxicity , and drug resistance.In the HPTN 071 ( PopART ) trial , 21 communities in Zambia and South Africa ( total population 1.2 m ) will be randomly allocated to three arms .


Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing , promotion of medical male circumcision for HIV-negative men , and offer of immediate ART for those testing HIV-positive ; Arm B will receive the full package except that ART initiation will follow current national guidelines ; Arm C will receive standard of care .


A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence .


Based on model projections , the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes .


Trial results , combined with modelling and cost data , will provide short-term and long-term estimates of cost-effectiveness of UTT interventions .


Importantly , the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT .


ClinicalTrials.gov NCT01900977 .


Bright light treatment is effective for seasonal affective disorder ( SAD ) , although the mechanisms of action are still unknown .


We investigated whether transcranial bright light via the ear canals has an antidepressant effect in the treatment of SAD .


During the four-week study period , 89 patients ( 67 females ; 22 males , aged 22-65 , mean SD age : 43.2 10.9 years ) suffering from SAD were randomized to receive a 12-min daily dose of photic energy of one of three intensities ( 1 lumen/0 .72 mW/cm ( 2 ) ; 4 lumens/2 .881 mW/cm ( 2 ) ; 9 lumens/6 .482 mW/cm ( 2 ) ) via the ear canals .


The light was produced using light-emitting diodes .


The severity of depressive symptoms was assessed with the Hamilton Depression Rating Scale - Seasonal Affective Disorder ( SIGH-SAD ) , the Hamilton Anxiety Rating Scale ( HAMA ) , and the Beck Depression Inventory ( BDI ) .


Cognitive performance was measured by the Trail Making Test ( TMT ) .


The within-group and between-group changes in these variables throughout the study were analysed with a repeated measures analysis of variance ( ANOVA ) , whereas gender differences at baseline within the light groups were analysed using Student 's t-tests .


Patients in all three groups showed significant decreases in their BDI , HAMA , and SIGH-SAD scores .


Response rates , i.e. , an at least 50 % decrease of symptoms as measured by the BDI , were 74 % -79 % in the three treatment groups .


Corresponding variations for the SIGH-SAD and the HAMA were 35-45 % and 47-62 % , respectively .


No intensity-based dose-response relationships in the improvement of anxiety and depressive symptoms or cognitive performance between treatment groups were observed .


Approximately one in four patients experienced mild adverse effects , of which the most common were headache , insomnia , and nausea .


These results suggests that transcranial bright light treatment may have antidepressant and anxiolytic effect in SAD patients , as both self - and psychiatrist-rated depressive and anxiety symptoms decreased in all treatment groups .


These improvements are comparable to findings of earlier bright light studies that used conventional devices .


The lack of dose response may be due to a saturation effect above a certain light intensity threshold .


Further studies on the effects of transcranial bright light with an adequate placebo condition are needed .


NCT01293409 , ClinicalTrials.gov .


Suppressive therapy with levothyroxine is the main step in treatment of differentiated thyroid cancer ( DTC ) .


However , subclinical hyperthyroidism is associated with deleterious effects on cardiovascular and skeletal systems .


Metformin may have a suppressive effect on TSH level .


We performed a single blind randomized controlled trial on the effect of short term Metformin therapy on 50 non-diabetic patients with DTC ( mean age of 39.68 8.7 years ) under suppressive therapy with levothyroxine .


Metformin ( 500 mg ) or placebo was added to the drug regimen of the patients and levothyroxine dose decreased by 33 % .


TSH and thyroid hormone values were measured at the beginning of the study and 3 months after treatment .


Forty-six patients had papillary and 4 had follicular carcinoma .


The mean dose of levothyroxine was 2.20.48 g/kg .


The mean TSH level at the beginning of the study was 0.05.04 mIU/L .


The mean age , weight and baseline TSH level was not significantly different between metformin and placebo groups ( P > 0.2 ) .


In the metformin group , the mean ( SD ) TSH level was significantly increased from 0.030.04 to 3.15.7 mIU/L after 3 months of intervention ( P = 0.01 ) and the mean thyroid hormone levels were significantly decreased ( P < 0.001 ) .


In the placebo group , the mean TSH level increased from 0.040.04 to 3.14.7 mIU/L after 3 months ( P = 0.003 ) .


Delta TSH was 3.05.6 mIU/L and 3.14.7 mIU/L in metformin and placebo groups , respectively ( P = 0.9 ) .


Adding 500 mg of metformin to drug regimen was not useful to compensate for 33 % of levothyroxine dose reduction in patients with DTC .


Vocal local ( VL ) is a non-pharmacological pain management technique for gynecological procedures .


In Africa , it is usually used in combination with pharmacological analgesics .


However , analgesics are associated with side-effects , and can be costly and subject to frequent stock-outs , particularly in remote rural settings .


We compared the effectiveness of VL + local anesthesia + analgesics ( the standard approach ) , versus VL + local anesthesia without analgesics , on pain and satisfaction levels for women undergoing tubal ligations in rural Kenya .


We conducted a site-randomised non-inferiority trial of 884 women receiving TLs from 40 Marie Stopes mobile outreach sites in Kisii and Machakos Districts .


Twenty sites provided VL + local anesthesia + analgesics ( control ) , while 20 offered VL + local anesthesia without additional analgesics ( intervention ) .


Pain was measured using a validated 11-point Numeric Rating Scale ; satisfaction was measured using 11-point scales .


A total of 461 women underwent tubal ligations with VL + local anesthesia , while 423 received tubal ligations with VL + local anesthesia + analgesics .


The majority were aged 30 years ( 78 % ) , and had > 3 children ( 99 % ) .


In a multivariate analysis , pain during the procedure was not significantly different between the two groups .


The pain score after the procedure was significantly lower in the intervention group versus the control group ( by 0.40 points ; p = 0.041 ) .


Satisfaction scores were equally high in both groups ; 96 % would recommend the procedure to a friend .


VL + local anesthesia is as effective as VL + local anesthesia + analgesics for pain management during tubal ligation in rural Kenya .


Avoiding analgesics is associated with numerous benefits including cost savings and fewer issues related to the maintenance , procurement and monitoring of restricted opioid drugs , particularly in remote low-resource settings where these systems are weak .


Pan-African Clinical Trials Registry PACTR201304000495942 .


To evaluate the radiation dose , image quality , and influence on visual contrast of low tube voltage abdominal computed tomography ( CT ) and the effects of display setting optimization .


One hundred and fifty-seven patients were randomly assigned to one of three protocols .


Fifty-two patients underwent a 120 kVp protocol , and 53 and 52 patients underwent low-dose protocols with 100 and 80 kVp , respectively .


The effective dose ( ED ) , image noise , CT attenuation , and signal-to-noise ratio ( SNR ) of each organ of each protocol were compared using Dunnett 's test .


Qualitative analysis between the protocols was also performed .


The ED of the 100 and 80 kVp protocols were 22 % and 37 % reduced , respectively .


There were no significant differences in the SNR between the protocols ( 120 kVp : 13.8 3.5 ; 100 kVp : 13.9 3.3 ; 80 kVp : 13.5 2.9 ; p > 0.05 ) .


However , there were significant differences in contrast familiarity between the 120 kVp images and all the other images , except 100 kVp images , with optimized display settings ( p < 0.05 ) .


In abdominal CT , an 80 kVp setting offers greater radiation dose reduction than a 100 kVp setting without significant deterioration of the SNR ; however , the visual contrast between the organs might be changed .


Chronic fatigue syndrome ( CFS ) is a disabling condition with unknown disease mechanisms and few treatment options .


To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function .


Participants were enrolled from a single referral center recruiting nationwide in Norway .


A referred sample of 176 adolescents with CFS was assessed for eligibility ; 120 were included ( 34 males and 86 females ; mean age , 15.4 years ) .


A volunteer sample of 68 healthy adolescents serving as controls was included ( 22 males and 46 females ; mean age , 15.1 years ) .


The CSF patients and healthy controls were assessed cross-sectionally at baseline .


Thereafter , patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks ; double-blinding was provided .


Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents : Pathophysiology and Intervention Trial .


Clonidine hydrochloride capsules ( 25 g or 50 g twice daily for body weight < 35 kg or > 35 kg , respectively ) vs placebo capsules for 9 weeks .


Number of steps per day .


At baseline , patients with CFS had a lower number of steps per day ( P < .001 ) , digit span backward score ( P = .002 ) , and urinary cortisol to creatinine ratio ( P = .001 ) , and a higher fatigue score ( P < .001 ) , heart rate responsiveness ( P = .02 ) , plasma norepinephrine level ( P < .001 ) , and serum C-reactive protein concentration ( P = .04 ) compared with healthy controls .


There were no significant differences regarding blood microbiology evaluation .


During intervention , the clonidine group had a lower number of steps per day ( mean difference , -637 steps ; P = .07 ) , lower plasma norepinephrine level ( mean difference , -42 pg/mL ; P = .01 ) , and lower serum C-reactive protein concentration ( mean ratio , 0.69 ; P = .02 ) compared with the CFS placebo group .


Adolescent CFS is associated with enhanced sympathetic nervous activity , low-grade systemic inflammation , attenuated hypothalamus-pituitary-adrenal axis function , cognitive impairment , and large activity reduction , but not with common microorganisms .


Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity ; thus , sympathetic and inflammatory enhancement may be compensatory mechanisms .


Low-dose clonidine is not clinically useful in CFS .


clinicaltrials.gov Identifier : NCT01040429 .


Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy ( CRT ) for locally advanced rectal cancer .


Between March 2005 and November 2008 , 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT ( 50.4 Gy in 28 fractions , per oral tegafur-uracil and L-leucovorin ) alone or the same CRT schedule plus a brachytherapy boost ( 10 Gy in 2 fractions ) .


The primary trial endpoint was pathologic complete response ( pCR ) at the time of surgery ; secondary endpoints included overall survival ( OS ) , progression-free survival ( PFS ) , and freedom from locoregional failure .


Results for the primary endpoint have previously been reported .


This analysis presents survival data for the 224 patients in the Danish part of the trial .


In all , 221 patients ( 111 control arm , 110 brachytherapy boost arm ) had data available for analysis , with a median follow-up time of 5.4 years .


Despite a significant increase in tumor response at the time of surgery , no differences in 5-year OS ( 70.6 % vs 63.6 % , hazard ratio [ HR ] = 1.24 , P = .34 ) and PFS ( 63.9 % vs 52.0 % , HR = 1.22 , P = .32 ) were observed .


Freedom from locoregional failure at 5 years were 93.9 % and 85.7 % ( HR = 2.60 , P = .06 ) in the standard and in the brachytherapy arms , respectively .


There was no difference in the prevalence of stoma .


Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration .


Despite increased pathologic tumor regression at the time of surgery , we observed no benefit on late outcome .


Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery .


The goals of this study were to investigate the difference in responses between a scuba dive preceded by aerobic exercise ( EX ) and a nonexercise control dive ( CON ) and to further evaluate the potential relation between venous gas emboli ( VGE ) and microparticles ( MP ) .


We hypothesized that exercise would alter the quantity and subtype of annexin V-positive MP and VGE .


Nineteen divers performed two dives to 18 m seawater for 41 min separated by at least 3 d , one of which was preceded by 60 min of treadmill interval exercise .


Blood was obtained before exercise , before diving , and 15 min , 2 h , 4 h , and 24 h after surfacing .


Intravascular bubbles were quantified by transthoracic echocardiography at 15 , 40 , 80 , and 120 min .


The median VGE remained unchanged between the two dives ; however , there was a significant increase in VGE in the exercise dive at 40 and 80 min at rest .


MP were significantly elevated by approximately 2 times at all time points after CON compared with those after EX .


Markers of neutrophil and platelet activation were elevated by both dives , and these elevations were attenuated in the EX dive .


We conclude that some of the differences observed between the EX and CON related to MP and platelet and neutrophil activation provide additional insight into the potential protective benefits of exercise ; however , further study is needed to understand the mechanism and true potential of these benefits .


Although previous randomized clinical trials established a basis for lipid guidelines worldwide , they employed fixed doses of statins throughout trials ( fire-and-forget approach ) .


In the real clinical setting , however , statin doses are titrated to achieve target low-density lipoprotein cholesterol ( LDL-C ) levels ( treat-to-target approach ) .


The major objective was to investigate whether intensive lipid-lowering therapy using the treat-to-target approach yielded greater regression of aortic plaques .


We therefore performed a prospective , randomized trial comparing the effects of standard ( achieve LDL-C levels recommended by the Japanese guidelines ) and intensive ( achieve 30 % lower LDL-C levels than standard ) rosuvastatin therapy for 1 year in 60 hypercholesterolemic patients with a primary endpoint of aortic atherosclerotic plaques evaluated by non-invasive magnetic resonance imaging ( MRI ) .


Average doses were 2.9 3.1 and 6.5 5.1 mg/day for standard ( n = 29 ) and intensive therapy group ( n = 31 ) , respectively .


Although both therapies significantly reduced LDL-C and high-sensitivity C-reactive protein ( hsCRP ) levels , LDL-C reduction was significantly greater in the intensive group ( -46 vs. -34 % ) .


MRI study showed that thoracic aortic plaques were significantly regressed in both groups , with greater regression of thoracic plaque in the intensive group ( -9.1 vs. -3.2 % , p = 0.01 ) .


Multivariate analyses revealed that thoracic plaque regression was significantly correlated with hsCRP reduction , but not with changes in serum lipids , endothelial function , or doses of rosuvastatin .


Intensive statin therapy with titration targeting lower LDL-C levels resulted in greater thoracic aortic plaque regression compared to standard therapy , which was correlated with hsCRP reduction , suggesting that intensive statin therapy could provide better clinical outcomes .


To evaluate the efficacy and tolerability of pregabalin in postoperative pain management after laparoscopic cholecystectomy ( LC ) .


A prospective , randomized , placebo , controlled , double-blinded study was conducted at Anesthesia Department , Laparoscopy Surgery Unit , Ain Shams University Hospital .


Ninety patients with ASA physical status I-II scheduled for elective LC under general anesthesia were included .


Patients were randomly assigned to the following groups ( n = 30 each ) : pregabalin group ( P ) , received 150 mg pregabalin capsules 2 hours preoperatively , 12 hours postoperatively , and twice daily for 2 days ; gabapentin group ( G ) , received 1200 mg gabapentin capsules ( 400 mg , 3 ) 2 hours preoperatively , 12 hours postoperatively , and 400 mg three times daily for 2 days ; and control group ( C ) , received placebo capsules .


Postoperative pain scores were recorded on a visual analogue scale .


The following data were recorded : total daily pethidine and diclofenac consumption , numeric sedation score , and the postoperative nausea , vomiting , and dizziness scores .


The 24-hour pethidine consumption was significantly lower ( P < 0.001 ) in both pregabalin and gabapentin groups versus control .


Both groups had significantly less ( P < 0.001 ) patients with postoperative nausea , vomiting , sedation , and dizziness versus control .


Overall patient satisfaction with pain management was significantly higher ( P < 0.001 ) in pregabalin group versus gabapentin or control groups .


Gabapentin 1200 mg and pregabalin 150 mg are effective and safe analgesics for reducing postoperative pain in LC .


The perioperative oral administration of pregabalin 150 mg in patients undergoing LC is an effective and safe method of analgesia with a low incidence of adverse effects and reduces postoperative pethidine consumption .


The aim of the study was to investigate the influence of different driving scenarios ( urban , rural , highway ) on the timing required by drivers from a two-stage warning system , based on car-to-car communication .


Car-to-car communication systems are designed to inform drivers of potential hazards at an early stage , before they are visible to them .


Here , questions arise as to how drivers acknowledge early warnings and when they should be informed ( first stage ) and warned ( second stage ) .


Hence , optimum timing for presenting the information was tested .


A psychophysical method was used to establish the optimum timing in three driving scenarios at different speed limits ( urban : 50 km/h , rural : 100 km/h , highway : 130 km/h ) .


A total of 24 participants ( 11 female , 13 male ; M = 29.1 years , SD = 11.6 years ) participated in the study .


The results showed that the optimum timing did not differ among the three scenarios.The first and second stages should ultimately be presented at different timings at each speed limit ( first stage : 26.5 s , second stage : 12.1 s before a potential hazard ) .


The results showed that well-selected timing for activating information and warning is crucial for the acceptance of these systems .


Appropriate timing for presenting the information and warning can be derived for these systems .


The findings will be integrated in further development of assistance systems based on car-to-x technology within the Car2X-Safety project of the Niederschsisches Forschungszentrum Fahrzeugtechnik in Germany.This study was also supported by Chalmers University of Technology in Sweden .


Conducting randomized controlled trials on traditional Chinese non-drug therapies has been limited by factors such as patient preference to specific treatment modality .


The aim of this study is to investigate the feasibility of applying a partially randomized patient preference ( PRPP ) trial model in evaluating the efficacy of two types of traditional Chinese medicine therapies , acupuncture and cupping , for fibromyalgia while accounting for patients ' preference of either therapeutic modality .


This protocol was approved by the Institutional Ethics Committee of affiliated Dongfang Hospital , Beijing University of Chinese Medicine ( approval number : 2013052104-2 ) .


One hundred participants with fibromyalgia will be included in this study .


Diagnosis of fibromyalgia will be based on the American College of Rheumatology criteria .


Before treatment , participants will be interviewed for their preference toward acupuncture or cupping therapy .


Fifty participants with no preference will be randomly assigned to one of the two groups and another 50 participants with strong preference to either acupuncture or cupping will receive what they choose .


For acupuncture and cupping therapy , the main acupoints used will be tender points ( Ashi ) .


Treatment will be three times a week for 5 consecutive weeks with a follow-up period of 12weeks .


Outcome measures will be qualitative ( patient expectation and satisfaction ) and quantitative ( pain intensity , quality of life , depression assessment ) .


NCT01869712 ( in clinicaltrials.gov , on 22nd May 2013 ) .


Adequate postoperative analgesia may enhance recovery .


The efficacy of continuous wound infusion vs intermittent epidural ropivacaine for postoperative analgesia was investigated .


Prospective randomized , observer blind trial .


Aretaieio University Hospital .


Patients scheduled for open abdominal hysterectomy or myomectomy .


Patients received 10 mL of 0.75 % ropivacaine along the skin incision before skin closure , followed by wound infusion 2 mL/hour of 0.375 % ropivacaine or epidurally 10 mL of 0.75 % ropivacaine in the beginning of surgery followed by 10 mL of 0.2 % ropivacaine 6 hourly .


The epidural injections or the wound infusion of ropivacaine lasted 48 hours .


Rescue analgesia consisted of patient-controlled analgesia morphine up to 48 hours and acetaminophen/codeine tablets the next 24 hours .


Analgesic consumption and visual analog scale pain at rest and during cough were assessed 2 , 4 , 8 , 24 , 48 , and 72 hours postoperatively .


One and three months later , patients were interviewed by phone for analgesic consumption at home and presence of pain .


The subcutaneous group consumed more morphine during the first 2 , 4 , and 8 hours postoperatively ( P < 0.001 , P < 0.001 , and P < 0.001 , respectively ) .


Subsequent morphine and acetaminophen/codeine requirements did not differ between the two groups .


Pain intensity during cough was higher only 2 hours after surgery in the subcutaneous group ( P = 0.002 ) .


Three months postoperatively , the two groups did not differ in the analgesic requirements and presence of persisting and/or burning pain .


Based on our results , there is no clinical significant difference between the epidural ropivacaine and the subcutaneous ropivacaine group or a clear superiority to one management strategy .


An 18-month randomized , controlled prospective study evaluated , in an intra-individual comparison , the clinical performance of two-step etch-and-rinse adhesives in non-carious cervical lesions ( NCCL ) .


35 subjects , with at least two similar sized NCCL participated in this study .


After sample size calculation , 70 restorations were placed , according to one of the following groups : Adper Single Bond 2 ( SB ) and Ambar ( AM ) .


The restorations were placed incrementally using a resin composite ( Opallis ) .


The restorations were evaluated at baseline and after 6 and 18 months according to the FDI criteria .


The differences in the ratings of the two materials after 6 and 18 months were tested with Fisher 's exact test ( = 0.05 ) , and the performance of the each material at baseline and after 6 and 18 months was evaluated by Wilcoxon test ( = 0.05 ) .


All subjects attended the 18-month recall .


No significant differences were observed between the materials for any criteria evaluated .


Only four restorations ( two from each material ) were lost after 18 months .


Thus , the retention rates of both materials at 18 months were 94.2 % ( 95 % CI 81-98 % ) .


Nine restorations ( four Ambar and five Adper Single Bond 2 ) showed marginal discoloration which was solved with a polishing procedure .


Both adhesive systems showed acceptable clinical retention rates after 18 months .


The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men .


A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources .


The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India .


This study protocol is for parallel group , randomized controlled trials ( Healthy Activity Program for moderate to severe depression , Counselling for Alcohol Problems for harmful and dependent drinking ) in eight primary health centres in Goa , India .


Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and , in men only , the Alcohol Use Disorders Identification Test for drinking problems .


Screen-positive attendees will be invited to participate ; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial .


Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence , stratified by primary health centre and , for depression , by sex .


The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results .


Psychological treatments will be delivered by lay counsellors , over a maximum period of three months .


Primary outcomes are severity of disorder and remission rates at three months post-enrolment and , for the Counselling for Alcohol Problems trial , drinking and the impact of drinking on daily lives .


Secondary outcomes include severity of disorder and remission rates at 12months , disability scores , suicidal behaviour and economic impact , and cost-effectiveness at three and 12months .


500 participants with depression and 400 participants with harmful drinking will be recruited .


Primary analyses will be intention-to-treat .


These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors .


Both trials are registered with the International Society for the Registration of Clinical Trials ( Healthy Activity Programme registration number ISRCTN95149997 ; Counselling for Alcohol Problems registration number ISRCTN76465238 ) .


To compare WHO first-line antiretroviral therapy ( ART ) with nonnucleoside reverse transcriptase inhibitors ( NNRTI ) - based regimen with a boosted protease inhibitor ( bPI ) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations ( DRMs ) .


Treatment-naive adults were randomized to nevirapine ( NVP ) or ritonavir-boosted lopinavir ( LPV/r ) regimens each in combination with tenofovir ( TDF ) / emtricitabine ( FTC ) or zidovudine ( ZDV ) / lamivudine ( 3TC ) .


Primary endpoint was the incidence of therapeutical ( clinical and/or virologic ) failure at week 48 with follow-up till week 96 .


Four hundred and twenty-five patients ( 120 men ; 305 women ) received at least one dose of the study drug .


mITT analysis showed no difference in proportion of therapeutical failure between treatment arms [ 67/209 ( 32 % ) in NVP vs. 63/216 ( 29 % ) LPV/r at week 48 ( P = 0.53 ) ; 88/209 ( 42 % ) in NVP vs. 83/216 ( 38 % ) in LPV/r at week 96 ( P = 0.49 ) ] .


Per-protocol analysis demonstrated significantly more virologic failure with NVP than with LPV/r regimens [ at week 48 : 19/167 ( 11 % ) vs. 7/166 ( 4 % ) , P = 0.014 ; at week 96 : 27/158 ( 17 % ) vs. 13/159 ( 8 % ) , P = 0.019 ) ] .


Drug resistance mutations to NNRTI were detected in 19 out of 22 ( 86.3 % ) and dual-class resistance to nucleoside reverse transcriptase inhibitor ( NRTI ) and NNRTI in 15 out of 27 ( 68.2 % ) of NVP failing patients .


K65R mutation was present in seven out of 14 patients failing NVP-TDF/FTC regimen .


No major protease inhibitor-DRM was detected among LPV/r failing patients .


Discontinuation for adverse events was similar between treatment groups .


In resource-limited settings , first-line NNRTI-NRTI regimen as compared with bPI-based regimen provides similar outcome but is associated with a significantly higher number of virologic failure and resistance mutations in both classes that jeopardize future options for second-line therapy .


We carried out an open randomized controlled study to explore the changes in the rate of speech recovery and BDNF concentrations in patients with left-hemisphere stroke and carbohydrate metabolism disorders ( diabetes mellitus type2 or prediabetes ) who received cerebrolysin .


A study included 60 inpatients of the Center of Speech Pathology and Neurorehabilitation .


Neuropsychological examination was performed at baseline and after the treatment was completed .


We determined aphasia type and quantitatively assessed speech in scores which reflected the severity of speech impairment .


BDNF serum concentrations were measured .


Clinical efficacy of cerebrolysin ( intravenously in dose 20 ml in 100 ml of physiological solution , 5 days a week , during 4 weeks ) used in addition to standard neurorehabilitation measures in patients with post stroke aphasia of different severity was demonstrated .


This treatment was most effective in patients with very marked and marked speech impairment that was confirmed by the maximal possible improvement of speech during the first course of neurorehabilitation measures , in particular in a subgroup of patients without carbohydrate metabolism disorders .


A significant increase in BDNF concentrations was an additional evidence of this improvement .


The use of cerebrolysin in the complex treatment of patients with post stroke aphasia of different severity improves the prognosis of their rehabilitation .


Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites , data for the best possible dose fractionation schedules are lacking .


We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy .


We did a multicentre , non-blinded , randomised , controlled trial in nine countries worldwide .


We enrolled patients 18 years or older who had radiologically confirmed , painful ( ie , pain measured as 2 points using the Brief Pain Inventory ) bone metastases , had received previous radiation therapy , and were taking a stable dose and schedule of pain-relieving drugs ( if prescribed ) .


Patients were randomly assigned ( 1:1 ) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment , stratified by previous radiation fraction schedule , response to initial radiation , and treatment centre .


Patients , caregivers , and investigators were not masked to treatment allocation .


The primary endpoint was overall pain response at 2 months , which was defined as the sum of complete and partial pain responses to treatment , assessed using both Brief Pain Inventory scores and changes in analgesic consumption .


Analysis was done by intention to treat .


This study is registered with ClinicalTrials.gov , number NCT00080912 .


Between Jan 7 , 2004 , and May 24 , 2012 , we randomly assigned 425 patients to each treatment group .


19 ( 4 % ) patients in the 8 Gy group and 12 ( 3 % ) in the 20 Gy group were found to be ineligible after randomisation , and 140 ( 33 % ) and 132 ( 31 % ) patients , respectively , were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis .


In the intention-to-treat population , 118 ( 28 % ) patients allocated to 8 Gy treatment and 135 ( 32 % ) allocated to 20 Gy treatment had an overall pain response to treatment ( p = 021 ; response difference of 400 % [ upper limit of the 95 % CI 92 , less than the prespecified non-inferiority margin of 10 % ] ) .


In the per-protocol population , 116 ( 45 % ) of 258 patients and 134 ( 51 % ) of 263 patients , respectively , had an overall pain response to treatment ( p = 017 ; response difference 600 % [ upper limit of the 95 % CI 132 , greater than the prespecified non-inferiority margin of 10 % ] ) .


The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite ( 201 [ 56 % ] of 358 assessable patients who received 8 Gy vs 229 [ 66 % ] of 349 assessable patients who received 20 Gy ; p = 0011 ) and diarrhoea ( 81 [ 23 % ] of 357 vs 108 [ 31 % ] of 349 ; p = 0018 ) .


Pathological fractures occurred in 30 ( 7 % ) of 425 patients assigned to 8 Gy and 20 ( 5 % ) of 425 assigned to 20 Gy ( odds ratio [ OR ] 154 , 95 % CI 085-275 ; p = 015 ) , and spinal cord or cauda equina compressions were reported in seven ( 2 % ) of 425 versus two ( < 1 % ) of 425 , respectively ( OR 354 , 95 % CI 073-1715 ; p = 0094 ) .


In patients with painful bone metastases requiring repeat radiation therapy , treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions ; however , as findings were not robust in a per-protocol analysis , trade-offs between efficacy and toxicity might exist .


Canadian Cancer Society Research Institute , US National Cancer Institute , Cancer Council Australia , Royal Adelaide Hospital , Dutch Cancer Society , and Assistance Publique-Hpitaux de Paris .


The combination of midazolam and opioid has been widely used as a standard sedative regimen for endoscopic retrograde cholangiopancreatography ( ERCP ) .


Following recent evidence that dexmedetomidine may exert a synergistic effect in combination with midazolam , this study compared the sedative effect and adverse events of midazolam-meperidine-dexmedetomidine ( MMD ) and midazolam-meperidine during ERCP .


A total of 110 patients who were scheduled for ERCP were prospectively enrolled and randomly assigned , in a double-blind manner , to the MMD ( n = 53 ) or midazolam-meperidine ( n = 57 ) groups .


Each patient received an intravenous ( IV ) bolus dose of midazolam and meperidine ( 0.06 mg/kg and 50mg , 30 % reduction and 25mg for patients aged 65 years , respectively ) .


To this dose , a continuous IV infusion of dexmedetomidine ( 1g/kg/h ; MMD group ) or the same volume of normal saline ( midazolam-meperidine group ) was added .


The sedation level ( Ramsay Sedation Scale [ RSS ] ) as well as hemodynamic and respiratory changes were assessed .


Adequate sedation ( RSS3 ) was maintained during ERCP in 75.5 % and 36.8 % of the MMD and midazolam-meperidine group , respectively ( P < 0.001 ) .


RSS scores were significantly higher in the MMD group ( P < 0.001 ) .


Intraoperative bispectral index scores were significantly lower in the MMD group ( P < 0.001 ) than in the midazolam-meperidine group.Lower additional ( P = 0.001 ) and total ( P = 0.003 ) doses of midazolam were required in the MMD group.Patients in the MMD group showed lower pain scores ( P < 0.001 ) and higher satisfaction scores ( P < 0.001 ) .


Desaturation occurred more frequently in the midazolam-meperidine group ( 11 vs. 1 ; P = 0.003 ) .


The addition of dexmedetomidine to the midazolam-meperidine regimen provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam-meperidine regimen.This trial was registered at ClinicalTrials.gov Identifier ( NCT01404689 ) .


The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis .


Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults .


Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults .


Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed .


After repeated infusion of capsaicin-contained red pepper sauce , the threshold volume to activate secondary peristalsis was significantly increased during slow ( p < 0.001 ) and rapid air injections ( p = 0.004 ) .


Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception ( p < 0.001 ) , but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion ( p = 0.007 ) .


Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow ( p = 0.003 ) and rapid air injections ( p = 0.01 ) , but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow ( p = 0.0005 ) and rapid air injections ( p = 0.003 ) .


Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults .


These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus .


This study was conducted to determine if intravenous dexamethasone combined with caudal block was able to prolong post-operative analgesia in pediatric daycare surgeries .


Sixty four ASA I or II children aged 3 to 10 year old scheduled for daycare open unilateral herniotomy received general anesthesia and caudal block using 0.25 % levobupivacaine 0.75 mg.kg ( -1 ) with suppository paracetamol 30 mg.kg ( -1 ) .


After anesthesia induction , they were randomized to receive either intravenous dexamethasone 0.5 mg.kg ( -1 ) ( Group I ) or same volume intravenous normal saline ( Group II ) .


Postoperatively , pain scores were assessed using Wong - Baker faces scale .


At home , their parents assessed and recorded the pain scores , time to first oral paracetamol served and frequency of paracetamol given in two consecutive days post surgery .


On the third postoperative day , these information were gathered from the parents via a phone call .


There were statistically significant differences between Group I and Group II in the median time to first paracetamol ( 800 vs 520 min , p = 0.01 ) , mean pain scores postoperative day 1 ( 1.9 2.0 vs 3.5 2.2 , p = 0.05 ) , mean pain score-postoperative day 2 ( 0.8 1.6 vs 2.3 2.0 , p = 0.03 ) and mean frequencies of paracetamol given on postoperative day 2 ( 0.3 0.8 vs 1.1 1.0 , p = 0.02 ) .


A single intravenous dexamethasone dose when combined with caudal block reduces postoperative pain , decreases paracetamol requirement and prolongs analgesic duration in children after open herniotomy .


The liver is an important organ for various aspects of glucose metabolism , including glucose uptake , storage , and synthesis .


It is a major organ in the metabolic process with perfusion provided by both the portal vein and hepatic artery .


In diabetic patients organ perfusion is reduced and this is linked to atherosclerosis , and as a result complications occur .


In this study , we aimed to evaluate liver perfusion by scintigraphic methods in diabetic patients .


We retrospectively investigated 1,100 myocardial perfusion scintigraphies taken between January 2011 and December 2012 at Canakkale Onsekiz Mart University Medical Faculty Nuclear Medicine Department .


A total of 66 patients who were diagnosed with diabetes mellitus and had myocardial perfusion scintigraphies were included in the study .


The control subjects included 127 patients without diabetes mellitus who were chosen at random .


Patients with chronic liver disease were not included in the study .


The values from liver regions of interest ( liver-ROI ) rates and heart regions of interest ( heart-ROI ) rates were compared between the patients and controls .


Patients were grouped according to the presence of diabetes .


In the diabetes mellitus group , the liver-ROI average was lower ( p = 0.66 ) than in the controls .


In the control group , the average liver-ROI/heart-ROI ratios were higher than the ratio in the diabetes mellitus group ( p = 0.019 ) .


Multivariate variance analysis showed that the diabetes mellitus liver-ROI/heart-ROI ratio was independent of other risk factors ( p = 0.003 ; F : 9.6 ) .


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This study shows that liver perfusion in diabetic patients is reduced compared with those without diabetes .


Prospective studies with larger patient groups are required .


There is no consensus on the importance of visit-to-visit glycemic variability in diabetes .


Therefore , we assessed the effects of visit-to-visit variability ( VVV ) in HbA1c and fasting glucose on major outcomes in the ADVANCE ( Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ) trial .


ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes .


VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3-24 months after randomization .


Outcomes were combined macro - and microvascular events and all-cause mortality occurring post 24 months .


Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group .


Among 4,399 patients in the intensive group , an increase in VVV of HbA1c was associated with an increased risk of vascular events ( P = 0.01 ) and with mortality ( P < 0.001 ) : highest versus lowest tenth hazard ratio ( 95 % CI ) 1.64 ( 1.05-2 .55 ) and 3.31 ( 1.57-6 .98 ) , respectively , after multivariable adjustment .


A clear association was also observed between VVV of fasting glucose and increased risk of vascular events ( P < 0.001 ; 2.70 [ 1.65-4 .42 ] ) .


HbA1c variability was positively associated with the risk of macrovascular events ( P = 0.02 for trend ) , whereas glucose variability was associated with both macro - and microvascular events ( P = 0.005 and P < 0.001 for trend , respectively ) .


Sensitivity analyses using other indices , and patients in the standard glucose treatment group , were broadly consistent with these results .


Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes .


Insulin initiation and titration in primary care is necessary to respond to the growing epidemic of type 2 diabetes ( T2D ) .


The INITIATION study aims to evaluate the impact of implementing a new model of care with Primary Care Physician and Practice Nurse ( PN ) teams supported by a Credentialed Diabetes Educator-Registered Nurse ( CDE-RN ) and endocrinologist in initiating and titrating basal and prandial insulin for T2D patients in the Australian healthcare system over 24weeks .


This study also explores the feasibility and efficacy of retrospective continuous glucose monitoring ( r-CGM ) in comparison with self-monitoring of blood glucose ( SMBG ) among people with T2D in primary care .


The study employs a before and after design with a nested exploratory trial of SMBG and r-CGM .


A total of 102 insulin nave T2D patients with a glycated haemoglobin ( HbA1c ) level of > 7.5 % in the previous 6months while treated with maximal oral therapy will be recruited and screened from 22 primary care practices in Melbourne , Australia .


All patients will be commenced on a basal insulin regimen following randomization into one of the two blood glucose monitoring arms , with intensification to a `` basal plus '' regimen if required .


The outcomes of the new model of care will be benchmarked with data collected over the same period from a specialist setting in Melbourne , Australia .


This article describes the study protocol and insulin treatment algorithm employed in the first study to explore r-CGM use among T2D in primary care .


Findings from the INITIATION study will inform development of a larger randomized controlled trial .


ACTRN12610000797077 .


Integrative neuromuscular training ( INT ) has successfully enhanced physical fitness and reduced abnormal biomechanics , which appear to decrease injury rates in adolescent female athletes .


If not addressed at the proper time , low levels of physical fitness and abnormal mechanics may predispose female athletes to an increased risk of musculoskeletal injuries .


To evaluate sex-specific effects of INT on selected measures of health - and skill-related fitness in children during physical education ( PE ) .


Cohort study .


Public primary school .


Forty children ( 16 boys , 24 girls ; age = 7.6 0.3 years , height = 124.5 6.4 cm , mass = 29.5 7.6 kg ) from 2 second-grade PE classes .


The classes were randomized into the PE-plus-INT group ( 10 boys , 11 girls ) or the control group ( 6 boys , 13 girls ) that participated in traditional PE .


The INT was performed 2 times per week during the first approximately 15 minutes of each PE class and consisted of body weight exercises .


Push-up , curl-up , standing long jump , single-legged hop , single-legged balance , sit-and-reach flexibility test , shuttle run , and 0.8-km run .


At baseline , the boys demonstrated higher levels of performance in most of the fitness measurements as evidenced by greater performance on the push-up , standing long jump , single-legged hop , shuttle run , and 0.8-km run ( P < .05 ) .


In the evaluation of the training effects , we found intervention effects in the girls for enhanced INT-induced gains in performance relative to the control group on the curl-up , long jump , single-legged hop , and 0.8-km run ( P < .05 ) after controlling for baseline .


Boys did not demonstrate similar adaptations from the INT program ( P .05 ) .


These data indicate that INT is an effective and time-efficient addition to PE for enhancing motor skills and promoting physical activity in children .


Seven-year-old girls appeared to be more sensitive to the effects of INT than 7-year-old boys .


Future research is warranted to confirm these effects in larger cohorts of children .


To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema ( DME ) .


A phase IIIb , 18-month , prospective , open-label , multicenter , single-arm study in the United Kingdom .


Participants ( N = 109 ) with visual impairment due to DME .


Participants received 3 initial monthly ranibizumab 0.5 mg injections ( day 0 to month 2 ) , followed by individualized best-corrected visual acuity ( BCVA ) and optical coherence tomography-guided re-treatment with monthly ( months 3-5 ) and subsequent bimonthly follow-up ( months 6-18 ) .


Laser was allowed after month 6 .


Mean change in BCVA from baseline to month 12 ( primary end point ) , mean change in BCVA and central retinal thickness ( CRT ) from baseline to month 18 , gain of 10 and 15 letters , treatment exposure , and incidence of adverse events over 18 months .


Of 109 participants , 100 ( 91.7 % ) and 99 ( 90.8 % ) completed the 12 and 18 months of the study , respectively .


The mean age was 63.7 years , the mean duration of DME was 40 months , and 77.1 % of the participants had received prior laser treatment ( study eye ) .


At baseline , mean BCVA was 62.9 letters , 20 % of patients had a baseline BCVA of > 73 letters , and mean baseline CRT was 418.1 m , with 32 % of patients having a baseline CRT < 300 m.


The mean change in BCVA from baseline to month 6 was +6.6 letters ( 95 % confidence interval [ CI ] , 4.9-8 .3 ) , and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters ( 95 % CI , 2.9-6 .7 ; P < 0.001 ) and +6.5 letters ( 95 % CI , 4.2-8 .8 ) at month 18 .


The proportion of participants gaining 10 and 15 letters was 24.8 % and 13.8 % at month 12 and 34.9 % and 19.3 % at month 18 , respectively .


Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months , respectively .


No new ocular or nonocular safety findings were observed during the study .


The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment .


The highest risk for invasive meningococcal disease ( IMD ) is in infants aged < 1 year .


Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A , C , W and Y.


This phase 3b , multinational , open-label , randomized , parallel-group , multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM , a quadrivalent meningococcal conjugate vaccine , concomitantly administered with routine vaccinations to healthy infants .


Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2 , 4 , 6 and 12 months .


Adverse events ( AEs ) that were medically attended and serious adverse events ( SAEs ) were collected from all subjects from enrollment through 18 months of age .


In a subset , detailed safety data ( local and systemic solicited reactions and all AEs ) were collected for 7 days post vaccination .


The primary objective was a non-inferiority comparison of the percentages of subjects with 1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone ( criterion : upper limit of 95 % confidence interval [ CI ] of group difference < 6 % ) .


A total of 7744 subjects were randomized with 1898 in the detailed safety arm .


The percentage of subjects with severe systemic reactions was 16 % after MenACWY-CRM plus routine vaccines and 13 % after routine vaccines alone ( group difference 3.0 % ( 95 % CI -0.8 , 6.4 % ) .


Although the non-inferiority criterion was not met , post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone ( group difference -0.1 % [ 95 % CI -4.9 % , 4.7 % ] ) .


Rates of solicited AEs , medically attended AEs , and SAEs were similar across groups .


In a large multinational safety study , a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone .


Endoscopic papillary balloon dilation ( EPBD ) was associated with a higher rate of endoscopic retrograde cholangiopancreatography ( ERCP ) pancreatitis ( PEP ) .


The purpose of this study was to determine whether placement of an endoscopic nasobiliary drainage ( ENBD ) catheter can also prevent PEP after EPBD .


A total of 93 patients , who with proven common bile duct ( CBD ) stones , received EPBD were enrolled this trial .


They were randomly divided into ENBD group ( n = 45 ) and no-ENBD group ( n = 48 ) according whether undergone an ENBD procedure after EPBD .


Their demographics , laboratory , procedural data were collected , and pancreaticobiliary complications were followed .


The number of patients with serum amylase levels above the normal upper limit ( > 180 U/L ) did not differ between groups .


However , compared with ENBD group , more patients in No-ENBD group had levels greater than three times the normal limit ( > 540 U/L ) ( 11/48 vs 3/45 , P = 0.0285 ) , and more patients developed to PEP ( 7/48 vs 0/45 , P = 0.0250 ) .


During follow-up , the numbers of patients undergone cholecystectomy , cholangitis and recurrence of CBD stones were similar .


There was also no significant difference in the cumulative rate of recurrent pancreaticobiliary complications between the two groups ( P = 0.452 ) .


EPBD followed by insertion of an ENBD catheter can prevent PEP , and routine ENBD catheter placement is recommended after an EPBD procedure .


Use of pneumococcal conjugate vaccines ( PCVs ) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond .


Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood , however data are scarce .


The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood .


We did an open-label , randomised , parallel group , controlled trial in healthy infants aged 40-60 days from Kathmandu , Nepal .


Participants were randomly allocated ( 4:4:5 ratio ) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost ( 2 +1 ) , three-dose prime ( 3 +0 ) , or two doses after completion of the initial study phase ( 0 +2 ) .


We used a computer generated randomisation list with randomly varying block sizes .


We followed up participants at age 2-4 years together with a group of unvaccinated controls .


Sera were analysed for opsonophagocytic activity , protein D , and PCV10 serotype-specific IgG .


Laboratory staff was masked to intervention group assignment .


The primary outcome measure was to determine the proportion of participants in the 2 +1 group at age 10 months with specific IgG for serotypes 1 , 5 , and 14 of at least 02 g/mL in the per-protocol population .


The secondary outcomes were non-inferiority ( within 10 % levels ) at age 18 weeks for the proportion of participants in the 2 +1 group compared with the 3 +0 group with serotypes 1 , 5 , and 14 specific IgG of at least 02 g/mL ; the proportion of participants with PCV10 serotype-specific IgG of at least 02 g/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months ; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study group .


In the follow-up study , the primary outcome measure was the proportion of participants with IgG of at least 02 g/mL for PCV10 serotypes at age 2-4 years in children previously immunised with a 3 +0 schedule compared with a 2 +1 schedule .


The trial is registered with Current Controlled Trials , registration number ISRCTN56766232 .


Between May 10 , 2010 , and Jan 7 , 2011 , 390 children were randomly assigned to each group : 119 to the 2 +1 group , 120 to the 3 +0 group , and 151 to the 0 +2 group .


At age 10 months , the proportions of 2 +1 participants with IgG of at least 02 g/mL were 990 % ( 95 % CI 942-1000 ) for serotype 1 , 100 % ( 962-1000 ) for serotype 5 , and 979 % ( 925-997 ) for serotype 14 .


At age 18 weeks , non-inferiority ( within 10 % levels ) of the 2 +1 group was shown compared with the 3 +0 group , and there was no difference between the 2 +1 and 3 +0 groups for the proportion with IgG of at least 02 g/mL for any of the PCV10 serotypes .


At age 10 months , proportions with IgG of at least 02 g/mL for serotypes 1 , 5 , 6B , and 23F , were higher in the 2 +1 group than in the 3 +0 group .


At age 18 weeks , there were no differences in opsonophagocytic activity between the 2 +1 and 3 +0 groups for reciprocal titres of at least 8 , but at age 10 months , proportions with an opsonophagocytic reciprocal titre of at least 8 for serotypes 1 , 4 , 5 , 6B , 18C , 19F and 23F were higher in the 2 +1 group than in the 3 +0 group .


At age 2-4 years , there were higher proportions in the 2 +1 group versus the 3 +0 group with IgG of at least 02 g/mL for serotypes 1 , 5 , 6B , and 18C .


Use of a 2 +1 PCV schedule with booster at age 9 months in a resource-poor setting improved antibody persistence through early childhood without compromising antibody responses in early infancy .


This schedule is now recommended by WHO for progressive introduction across Nepal , with PCV10 introduction having commenced on Jan 18 , 2015 .


Concurrent pre-implementation and post-implementation surveillance is being done by a GAVI Alliance funded study .


This study was supported by funding from the National Institute for Public Health and the Environment , The Netherlands ; Oxford Vaccine Group , University of Oxford , UK ; and GlaxoSmithKline Biologicals , Belgium .


To determine the safety and efficacy of intraoperative cell salvage system in decreasing the need for allogeneic transfusions in a cohort of scoliosis patients undergoing primary posterior spinal fusion with segmental spinal instrumentation .


A total of 110 consecutive scoliosis patients undergoing posterior instrumented spinal fusion were randomized into two groups according to whether a cell saver machine for intraoperative blood salvage was used or not .


Data included age , body mass index , perioperative hemoglobin levels , surgical time , levels fused , perioperative estimated blood loss , perioperative transfusions and incidence of transfusion-related complications .


A Chi-square test and t tests were performed for intraoperative and perioperative allogeneic transfusion between groups .


A regression analysis was performed between selected covariates to investigate the predictive factors of perioperative transfusion .


Perioperative allogenic blood transfusion rate was lower in the cell saver group ( 14.5 versus 32.7 % , p = 0.025 ) .


Mean intraoperative red blood cell transfusion requirement was also lower ( 0.21 U/pt versus 0.58 U/pt , p = 0.032 ) .


A multivariate analysis demonstrated that no .


of fused segments ( OR : 1.472 ; p = 0.005 ) , preoperative hemoglobin level ( OR : 0.901 ; p = 0.001 ) , and the use of cell saver system ( OR : 0.133 ; p = 0.003 ) had a trend toward significance in predicting likelihood of transfusion .


Cell saver use significantly reduces the need for allogeneic blood in spine deformity surgery , particularly in patients with low preoperative hemoglobin or longer operation time .


This study confirms the utility of routine cell saver use during PSF with segmental spinal instrumentation for scoliosis patients .


To compare the incidence and intensity of posterior capsular opacification ( PCO ) and neodymium : yttrium-aluminium-garnet ( Nd : YAG ) capsulotomy rates between two microincision intra-ocular lenses ( IOLs ) 3 years after surgery .


Sixty-five patients randomly received a Y-60H IOL ( HOYA Surgical Optics , Singapore ) in one eye and a Micro AY IOL ( PhysIOL , Lige , Belgium ) in the contralateral eye during same-day bilateral cataract surgery .


Eyes were examined 1 week , 20 months and 3 years after surgery .


The amount of PCO ( score : 0-10 ) was assessed subjectively at the slit lamp and objectively using automated image analysis software ( aqua ) .


Additionally , the Nd : YAG capsulotomy rate was noted .


Three years postoperatively , the objective PCO score of Y-60H IOLs was 1.9 1.7 compared to PCO score of 1.7 2.2 for the Micro AY IOLs ( p = 0.66 ) .


Thirty-four percentage of the Y-60H eyes had undergone Nd : YAG capsulotomy , compared to 49 % of the Micro AY eyes ( p = 0.04 ) .


Significantly , more capsular folds were observed in the Y-60H IOL group ( p = 0.001 ) .


There was no significant difference in best-corrected visual acuity , rhexis/IOL overlap and anterior capsule opacification 3 years after surgery .


Both microincision IOLs showed high YAG rates and comparable PCO scores 3 years after surgery .


In the light of this unsatisfying PCO performance , the advantage of the present microincision IOLs over conventional IOLs must be questioned .


Medications are an effective intervention for managing and preventing health problems but their benefit can be undermined by non-adherence or adverse drug events ( ADEs ) .


Since these issues may be interconnected , efforts to improve non-adherence should also include reduction of ADEs .


We have developed the ISTOP-ADE system ( Information Systems-enabled Outreach for Preventing Adverse Drug Events ) , which enables timely monitoring and managing of ADEs .


The objectives of this study are to determine whether the ISTOP-ADE system , compared to routine care , will reduce : a ) the probability of discontinuing the use of prognosis-altering medications ; b ) the probability of a patient experiencing a severe ADE ; c ) the proportion of patients experiencing ADEs , preventable ADEs and ameliorable ADEs ; and d ) health services utilization .


We will randomly assign 2,200 adult ambulatory patients in the province of Qubec who have been prescribed an incident medication for the management or prevention of a chronic health condition , to routine care or the ISTOP-ADE system .


The ISTOP-ADE system consists of an interactive voice response system ( IVRS ) paired with pharmacist support .


The IVRS will call patients at 3 and 17days post-prescription to determine if they are experiencing any problems and connect them with a pharmacist when required or desired by the patient .


We will evaluate medication persistence at 180days and health-care utilization using provincial administrative data .


Two blinded physicians will ascertain ADE status through a case review .


We expect the ISTOP-ADE intervention to be feasible and to improve the quality of patient care through improved medication adherence , reduced ADE duration and reduced number of ADEs resulting in an emergency department or inpatient encounter .


This in turn could lower health-care utilization , saving costs and lowering the burden on emergency departments and family practices .


The success of ISTOP-ADE would present opportunities to implement this intervention through health systems , health insurance agents and commercial pharmacies .


ClinicalTrials.gov Identifier : NCT02059044 .


Date registered : 10 January 2014 .


Entering primary school is an important childhood milestone , marking the beginning of a child 's formal education .


Yet the change creates a time of vulnerability for the child , the parents and the parent-child relationship .


Failure to adjust to the transition may place the family in a psychologically devastating position .


The aims of this study were to test the effectiveness of a parental training programme in enhancing the parent-child relationship and decreasing parental stress by reducing harsh parenting in preparing children for the transition to primary school .


A randomised controlled trial incorporating a two-group pre-test and repeated post-test was conducted in one of the largest public housing estates in Hong Kong .