A double-blinded , randomised , controlled trial was conducted .


Children under the age of 16 years with recurrent abdominal pain associated with dyspepsia and diagnosed with H. pylori by histology were randomly allocated either to a 10-day sequential treatment regimen or to a 10-day conventional triple therapy .


Analysis of the outcome of this study was based on clinical improvement and confirmed H. pylori eradication based on stool H. pylori antigen detection and/or repeat endoscopy .


Of the 71 patients included in the analysis , 45 ( 63.4 % ) were given the 10-day conventional treatment while 26 ( 36.6 % ) received the 10-day sequential treatment .


There was no difference in clinical improvement after treatment in the two therapies .


However , there was a significant difference in the eradication of H. pylori between the conventional v. sequential regimens ( 48.8 % v. 84.6 % , respectively ; p = 0.02 , odds ratio 0.19 ) .


The sequential treatment had a significantly higher H. pylori eradication rate than the conventional treatment .


Wavefront-guided ( WFG ) and wavefront-optimized ( WFO ) platforms for refractive surgery are designed for improved visual outcomes .


It is unclear which treatment profile is superior for patients undergoing photorefractive keratectomy ( PRK ) .


To compare the safety , efficacy , predictability , stability , and higher-order aberrations in eyes undergoing WFG and WFO PRK .


A prospective , randomized , fellow-eye-controlled clinical trial was conducted at the Byers Eye Institute at Stanford with enrollment between April 2009 and March 2011 ; 1 year of follow-up was included .


Of 90 patients screened , 71 patients ( 142 eyes ) with less than 12.00 diopters ( D ) of spherical myopia and less than 3.00 D of astigmatism were enrolled consecutively .


One eye was randomized to undergo WFG PRK treatment ( Visx CustomVue Star S4 IR excimer laser system ; Abbott Medical Optics ) , and the fellow eye received WFO PRK treatment ( WaveLight Allegretto Wave Eye-Q 400 Hz excimer laser system ; Alcon Surgical ) .


Data on the manifest refraction , uncorrected visual acuity , best-corrected visual acuity , 5 % and 25 % contrast best-corrected visual acuity , and higher-order aberrations were collected preoperatively and at the 1 - , 3 - , 6 - , and 12-month follow-up visits .


Eyes undergoing both treatments had improved best-corrected visual acuity ( WFG : mean , 0.05 [ 95 % CI , 0.03-0 .07 ] ; WFO : mean , 0.04 [ 95 % CI , 0.02-0 .06 ] ) and less sphere ( WFG : mean , -4.79 [ 95 % CI , -5.31 to -4.26 ] ; WFO : mean , -4.61 [ 95 % CI , -5.18 to -4.03 ] ) , cylinder ( WFG : mean , 0.66 [ 95 % CI , 0.49-0 .82 ] ; WFO : mean , 0.52 [ 95 % CI , 0.35-0 .69 ] ) , and spherical equivalents ( WFG : mean , -4.45 [ 95 % CI , -4.99 to -3.91 ] ; WFO : mean , -4.34 [ 95 % CI , -4.92 to -3.76 ] ) ( P < .001 ) but higher levels of spherical aberration ( WFG : mean , -0.11 [ 95 % CI , -0.15 to -0.06 ] ; WFO : mean , -0.11 [ 95 % CI , -0.14 to -0.07 ] ) ( P < .001 ) and higher-order root-mean-square aberrations ( WFO : mean , -0.07 [ 95 % CI , -0.12 to -0.02 ] ; WFO : mean , -0.12 [ 95 % CI , -0.17 to -0.70 ] ) ( P = .005 in WFG eyes and P < .001 in WFO eyes ) at 12 months compared with preoperative measurements .


A total of 93.0 % of the eyes in the WFG group and 94.4 % in the WFO had an uncorrected visual acuity of 20/20 or better at 12 months , with 56.3 % in the WFG group and 43.7 % in the WFO group gaining 1 or more lines of best-corrected visual acuity .


The stability of the refractive correction was excellent for both groups .


A difference in uncorrected visual acuity or contrast acuity between eyes undergoing WFG or WFO treatment at 3 months and beyond could not be identified .


This lack of difference suggests that both systems can be used to provide excellent improvement in vision for persons with myopia .


clinicaltrials.gov Identifier : NCT01135719 .


This study investigated the short-term efficacy of low-level laser therapy ( LLLT ) in patients with mild to moderate carpal tunnel syndrome ( CTS ) , lasting for < 1 year .


Seventy-nine patients with CTS were included in this double-blind , placebo-controlled study , and randomly divided in two treatment groups : Experimental group ( EG ) , active laser group ( 40 patients ) ; and control group ( CG ) , placebo ( sham ) laser group ( 39 patients ) .


A GaAlAs diode laser [ 780 nm , 30 mW continuous wave ( CW ) , 0.785 cm ( 2 ) , 38.2 mW/cm ( 2 ) ] was applied in contact with four points perpendicularly to the skin over the carpal tunnel area for 90 sec per point ( 2.7 J , 3.4 J/cm ( 2 ) / point ) .


Both groups were treated five times per week , once a day over 2 weeks , followed by 10 treatments every other day for 3 weeks , that is , for a total of 20 treatments .


Clinical assessment , including visual analogue scale ( VAS ) pain rating , Tinel 's sign , and median nerve conduction studies ( NCSs ) were evaluated before , and 3 weeks after , the last LLLT treatment .


Significant reduction in pain , reduction in the percentage of patients with a positive Tinel 's sign , and shortening of sensory and motor latency time in the NCS examination was observed in the experimental LLLT group ( but not in the control group ) .


This study has observed and documented the statistically significant short-term effects of LLLT on CTS patients in comparison with a placebo group .


The results support this conclusion , especially if the LLLT is applied in the earlier stages of CTS , and with mild to moderate cases .


To compare dentin tubule occlusion by dentifrices containing either nanohydroxyapatite ( 10 % nHAP and 15 % nHAP ) , sodium monofluorophosphate ( Na-MFP ) or NovaMin ( NovaMin ) .


All 80 participants wore four intraoral appliances bearing dentin blocks while using one of the four test dentifrices ( n = 20/dentifrice ) twice daily for 14 days .


The four appliances were removed in pairs after 7 and 14 days .


One treated block from each of the test periods ( 7 and 14 days ) and their untreated controls were examined with SEM to determine the level of tubule occlusion .


The remaining two treated blocks and their controls were used to determine tubule permeability to dye solution .


Effectiveness was compared statistically ( ANOVA/Tukey 's ) based on % area covered by deposited precipitate layer ( % DPL ) , % dye penetration inhibition ( % DPI ) and percentage of fully-open ( % FOT ) , partially-occluded ( % POT ) and completely-occluded ( % COT ) tubules in each block calculated relative to the number of tubules in their control blocks .


SEM showed increased % COT and % DPL overtime .


After 7 and 14 days , % COT , % POT , % DPL and % DPI were significantly lower with Na-MFP when compared to 10 % nHAP ( P < 0.01 ) , NovaMin ( P < 0.05 ) and 15 % nHAP ( P < 0.001 ) , the three of which were not significantly different from each other in those four variables .


A reverse trend was observed with % FOT ( P < 0.001 ) .


Within the same dentifrice , no difference in % COT , % POT , % FOT , % DPI and % DPL after 7 and 14 days , except with Na-MFP in which % DPL significantly ( P < 0.05 ) increased with usage .


In conclusion , nanohydroxyapatite-containing and NovaMin-containing toothpastes showed equal and more effectiveness in occluding dentin tubules than Na-MFP toothpaste .


Imiquimod 3.75 % and 2.5 % creams were studied for the treatment of actinic keratosis ( AK ) of the full face or balding scalp , to determine comparable efficacy and tolerability to imiquimod 5 % cream .


In two identical multicenter , randomized , double-blind , placebo controlled studies .


Adult subjects with 5 to 20 visible lesions , or palpable AKs in an area that exceeded 25 cm on either the face or balding scalp were randomized to imiquimod 3.75 % , 2.5 % or vehicle cream ( 1:1:1 ) applied once daily for two 2-week treatment cycles , with a 2-week , no-treatment interval between cycles .


Efficacy was assessed 8 weeks posttreatment ( End of Study Visit [ EOS ] ) .


Primary efficacy was rate of complete clearance of AK lesions .


Secondary efficacy endpoints were rate of partial clearance at EOS ( 75 % reduction in number of AK lesions compared to baseline ) and median percent decrease from baseline lesion count .


Safety assessments included visual assessment of local skin reactions ( LSRs ) , number and duration of study treatment rest periods required due to intolerant LSRs , adverse events ( AEs ) and clinical laboratory tests .


Overall 479 patients were randomized to imiquimod 3.75 % , 2.5 % , or vehicle .


Complete clearance rates were 35.6 % , 30.6 % , and 6.3 % respectively ( both P < .001 versus vehicle ) .


The difference in complete clearance rates ( imiquimod minus vehicle ) was 29.3 % and 24.3 % , respectively .


Partial clearance rates were 59.4 % , 48.1 % , and 22.6 % respectively ( both P < .001 versus vehicle ) .


Median % reductions in AK lesions were 81.8 % , 71.8 % , and 25.0 % respectively ( P < .001 versus vehicle ) .


All primary and secondary efficacy endpoints were greater in Study 1 .


Photodamage in the treatment area was ` much improved ' with imiquimod 3.75 % .


Both active creams were well tolerated with few treatment-related discontinuations .


In two well-controlled Phase 3 studies , both imiquimod 3.75 % and 2.5 % creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK .


Reduction in AK lesions was comparable to that reported with imiquimod 5 % with fewer local AEs .


Cannabis is the most consumed illegal substance in France .


General practitioners ( GPs ) are the health professionals who are most consulted by adolescents .


Brief intervention ( BI ) is a promising care initiative for the consumption of cannabis , and could be a tool for GPs in caring for adolescents who consume cannabis .


The aim of the CANABIC study is to measure the impact of a BI carried out by a GP on the consumption of cannabis by adolescents of 15 to 25years of age .


A randomized clustered controlled trial , stratified over three areas ( Auvergne , Languedoc-Roussillon , and Rhne - Alpes ) , comparing an intervention group , which carries out the BI in consultation , and a control group , which ensures routine medical care .


The main assessment criterion is the consumption of cannabis by amount of joints per month , at 12months .


The amount necessary to highlight a significant difference between the two groups of 30 % of consumption at 12months is 250 patients ( 50 GPs , 5 patients per GP ; risk = 5 % ; power = 90 % ; intra-cluster correlation coefficient = 0.2 ; Hawthorne effect = 15 % ; lost to follow-up rates for GPs = 10 % and for patients = 20 % ) .


This plan is replicated for the three areas , and therefore a total of 750 patients are expected.The secondary criteria for judgment are the associated consumption of tobacco and alcohol , the perception of the consequences of consumption , and the driving of a vehicle following consumption .


Research about BI for young cannabis users is underway .


The aim of the CANABIC study is to validate a BI suited to adolescents who consume cannabis , which may be performed in the general practice .


This would provide a tool for their treatment by a GP , which could be widely distributed during initial or further medical training .


CANABIC is a randomized clustered trial ( NCT01433692 , registered 2011 Sept 12 ) , PHRC funded : Clinical Research Hospital Program ( Governmental Fund , Health Ministry ) .


Date first patient randomized : March 2012 .


To evaluate the safety and effect of L-carnitine combined with tadalafil in the treatment of late-onset hypogonadism ( LOH ) with erectile dysfunction ( ED ) .


We randomly divided 140 cases of LOH with ED aged 40 -70 years into a treatment and a control group to receive L-carnitine + tadalafil and testosterone undecanoate + tadalafil , respectively .


After 8 weeks of treatment , we obtained the scores on IIEF-5 and Aging Male Symptoms ( AMS ) , observed changes in the levels of sex hormones , analyzed the results of the routine blood test and PSA level , and evaluated the safety of medication .


Finally , 110 cases were included , 60 in the treatment group and 50 in the control .


After 8 weeks of medication , the IIEF-5 and AMS scores were significantly improved as compared with the baseline both in the treatment group ( 17.7 + / - 3.5 vs 10.2 + / - 2.7 and 36.2 + / - 6.5 vs 48.8 + / - 5.8 ) and in the control group ( 16.7 + / - 2.6 vs 9.3 + / - 2.4 and 35.8 + / - 6.6 vs 50.7 + / - 5.0 ) ( both P < 0.05 ) , with no significant differences between the two groups ( P > 0.05 ) .


As for the safety of medication , there were no significant differences between the two groups before and after treatment ( P > 0.05 ) .


Two patients in the control group showed a PSA level > 4 microg/L , which was confirmed to be caused by prostatitis during follow-up .


L-carnitine combined with tadalafil is safe and effective for the treatment of LOH with ED .


Coronary artery disease is highly prevalent in patients with stroke , but because revascularization does not improve major clinical outcomes in patients with stable coronary artery disease relative to intensive medical therapy , routine evaluation for this disease is not warranted in stroke patients .


However , it might be warranted in patients destined to undergo vigorous physical therapy .


The Locomotor Experience Applied Post-Stroke study , a randomized controlled trial of 408 participants that tested the relative efficacy of two rehabilitation techniques on functional walking level , provided the opportunity to address this question .


The study aims to test the efficacy of screening for cardiovascular disease and an exercise tolerance test in assuring safety among patients undergoing vigorous rehabilitation for gait impairment .


All participants were screened for serious cardiovascular and pulmonary conditions .


At six-weeks poststroke , they also completed a cardiovascular screening inventory and underwent an exercise tolerance test involving bicycle ergometry .


Participants received 36 , 90-min sessions of a prescribed physical therapy ( three per week ) , initiated at either two-months or six-months poststroke .


Twenty-nine participants were excluded on the basis of the cardiac screening questionnaire , and 15 failed the exercise tolerance test for cardiovascular reasons .


No participant experienced a cardiac event during a treatment session .


Two participants experienced myocardial infarctions , but continued in the trial .


In three additional participants , myocardial infarctions caused or contributed to death .


The combination of a negative cardiac screen and the absence of exercise tolerance test failure appeared to have a high negative predictive value for cardiac events during treatment , despite the likelihood of a high prevalence of coronary artery disease in our population .


To compare the effects of massage therapy ( moderate pressure stroking ) and exercise ( flexion and extension of limbs ) on preterm infants ' weight gain and to explore potential underlying mechanisms for those effects .


Weight gain and parasympathetic nervous system activity were assessed in 30 preterm infants randomly assigned to a massage therapy group or to an exercise group .


Infants received 10min of moderate pressure massage or passive flexion and extension of the limbs 3 times per day for 5days , and EKGs were collected during the first session to assess vagal activity .


Both massage and exercise led to increased weight gain .


However , while exercise was associated with increased calorie consumption , massage was related to increased vagal activity .


Taken together , these findings suggest that massage and exercise lead to increased preterm infant weight gain via different underlying mechanisms .


Studies have shown that cannabis intake increases the risk of traffic accidents .


Controlled experiments support these findings and have shown a positive dose-effect relationship .


In this retrospective cross-sectional study of data from a roadside survey , we investigated whether a police officer 's judgment regarding signs of impairment is related to the concentration of delta-9-tetrahydrocannabinol ( THC ) in the oral fluid ( OF ) .


We investigated 2,632 cases from a representative sample of 3,302 Spanish drivers : 253 drivers positive for THC only , 32 positive for THC and ethanol , 201 with only ethanol detected in their breath , and 2,146 drivers who tested negative for ethanol in breath and drugs in OF .


Recorded data comprised breath alcohol concentrations , THC concentrations in the OF , and the 31 observed signs of impairment .


Subject groups were compared using the chi-square test , and logistic regression was used to examine the risk of being categorized as exhibiting signs of impairment .


A relationship was found between the OF THC concentration and some observed signs of impairment .


Eye signs were noticeable from a THC concentration > 3.0 ng/ml in OF , and > 25 ng/ml was related to behavior , facial expression , and speech signs .


Alcohol and THC contribute to impairment independently and , when taken simultaneously , the effects are comparable to the sum of the effects when consumed separately .


The observation of signs of impairment due to cannabis occurs in an OF concentration-related manner but , as a clinical test , OF has low sensitivity and specificity in a random roadside survey .


Long-term effects of different weightbearing ( WB ) modalities after matrix-associated autologous chondrocyte implantation ( MACI ) on changes in knee articular cartilage and clinical outcomes are needed to establish more evidence-based recommendations for postoperative rehabilitation .


There will be no differences between accelerated WB compared with delayed WB regarding knee articular cartilage or patient self-reported knee function or activity level 5 years after MACI .


Furthermore , significant correlations between magnetic resonance imaging ( MRI ) - based outcomes and patient-reported outcome measures 5 years postoperatively will exist .


Randomized controlled trial ; Level of evidence , 1 .


After MACI , 31 patients ( 23 male , 8 female ) were randomly assigned to the accelerated WB group ( AWB group ) or to the delayed WB group ( DWB group ) .


With the exception of time and increase to full WB , both groups underwent the same rehabilitation program .


The AWB group was allowed full WB after 6 weeks and the DWB group after 10 weeks .


Assessments were performed 3 months , 2 years , and 5 years postoperatively , but this long-term follow-up study only included changes from 2 to 5 years postoperatively .


The magnetic resonance observation of cartilage repair tissue ( MOCART ) score ( primary outcome ) , the MRI-based variables of bone edema and effusion , the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and the Tegner scale were included .


In addition , the association between MRI-based outcomes and the KOOS at 5 years postoperatively was investigated .


There was a significant decrease in the MOCART score and a significant increase in bone edema 2 and 5 years postoperatively but no significant group differences .


The only significant correlation between the MRI-based variables and the KOOS was found for bone edema and the KOOS subscale of pain ( r = -0.435 , P < .05 ) at 5-year follow-up .


There were no significant differences in the MRI-based or clinical outcomes between the AWB group and DWB group 5 years after MACI .


While the clinical outcomes remained stable , a decline of the MRI-based findings was observed between 2 and 5 years postoperatively .


Furthermore , a significant association between bone edema and pain was found .


No occurrence of unintended effects was observed .


To determine the effects of rivastigmine patch associated with physical exercise versus rivastigmine patch alone in quality of life ( QOL ) , cognition , activities of daily living ( ADL ) and functional mobility in Alzheimer 's disease ( AD ) subjects .


A randomized , controlled , single-blinded trial was conducted in 40 patients with mild to moderate stages of AD .


All patients were daily treated with rivastigmine transdermal patch at a stable dose of 4.6 mg and randomized into two groups : physical exercises or control .


The exercise program consisted of aerobic , flexibility , strength and balance movements , twice a week for 6 months .


Main outcomes were Quality of Life in Alzheimer 's disease scale ( QOL ) , Activities of Daily Living Questionnaire ( ADL ) , Mini-Mental State Examination ( MMSE ) and `` Time Up and Go Test '' .


Thirty-four patients completed the study .


After 6 months , there was a significant improvement in QOL of patients randomized to physical exercise group ( P < 0.05 ) .


In both groups , there was an improvement on caregivers QOL ( P > 0.05 ) .


When considering cognitive functions , there was no difference between groups .


The ability to perform ADL worsened in the group enrolled to RTP alone .


There was an improvement in functional mobility in the group treated with RTP .


Our results suggest that the association between physical exercises and RTP improves QOL in patients with AD .


Cognition remained unchanged in both groups .


Regarding the effect of physical exercises in ADL , further trials are necessary to confirm these results .


Immobilization of the spine of patients with trauma at risk of spinal damage is usually performed using a rigid long spineboard or vacuum mattress , both during prehospital and in-hospital care .


However , disadvantages of these immobilization devices in terms of discomfort and tissue-interface pressures have guided the development of soft-layered long spineboards .


We compared tissue-interface pressures between awake and anaesthetized ( unconscious ) patients during immobilization on a rigid spineboard and a soft-layered long spineboard .


In this comparative study , 30 anaesthetized patients were randomized to immobilization on either the rigid spineboard or the soft-layered spineboard for the duration of their elective surgery .


Tissue-interface pressures measured using an Xsensor pressure-mapping device were compared with those of 30 healthy volunteers who were immobilized sequentially on the rigid spineboard and the soft-layered spineboard .


Redness of the sacrum was also recorded for the anaesthetized patients immediately after the surgery .


For both anaesthetized patients and awake volunteers , tissue-interface pressures were significantly lower on the soft-layered spineboard than on the rigid spineboard , both at start and after 15min .


On the soft-layered spineboard , tissue interface pressure and peak pressure index ( PPI ) for the sacrum were significantly lower for anaesthetized patients than for awake volunteers .


Peak pressures and PPI on the rigid spineboard were equal for both groups .


Tissue-interface pressures did not change significantly over time .


Redness of the sacrum was significantly more pronounced on the rigid spineboard than on the soft-layered spineboard .


This prospective randomized controlled trial shows that using a soft-layered spineboard compared to a rigid spineboard for spinal immobilization resulted in lower tissue-interface pressures in both awake volunteers and anaesthetized patients .


Moreover , tissue-interface pressures on the soft-layered spineboard were lower in anaesthetized patients than in awake volunteers .


These findings show the importance of using a soft-layered spineboard to reduce tissue-interface pressure , especially for patients who can not relieve pressure themselves by changing position .


Few studies have designed and tested the use of continuous quality improvement approaches in community based substance use treatment settings .


Little is known about the feasibility , costs , efficacy , and sustainment of such approaches in these settings .


A group-randomized trial using a modified stepped wedge design is being used .


In the first phase of the study , eight programs , stratified by modality ( residential , outpatient ) are being randomly assigned to the intervention or control condition .


In the second phase , the initially assigned control programs are receiving the intervention to gain additional information about feasibility while sustainment is being studied among the programs initially assigned to the intervention .


By using this design in a pilot study , we help inform the field about the feasibility , costs , efficacy and sustainment of the intervention .


Determining information at the pilot stage about costs and sustainment provides value for designing future studies and implementation strategies with the goal to reduce the time between intervention development and translation to real world practice settings .


One of the main priorities of Dutch organisations providing shelter services is to develop evidence-based interventions in the care for abused women and homeless people .


To date , most of these organisations have not used specific intervention models and the interventions which have been implemented rarely have an empirical and theoretical foundation .


The present studies aim to examine the effectiveness of critical time intervention ( CTI ) for abused women and homeless people .


In two multi-centre randomised controlled trials we investigate whether CTI , a time-limited ( nine month ) outreach intervention , is more effective than care-as-usual for abused women and homeless people making the transition from shelter facilities to supported or independent housing .


Participants were recruited in 19 women 's shelter facilities and 22 homeless shelter facilities across The Netherlands and randomly allocated to the intervention group ( CTI ) or the control group ( care-as-usual ) .


They were interviewed four times in nine months : once before leaving the shelter , and then at three , six and nine months after leaving the shelter .


Quality of life ( primary outcome for abused women ) and recurrent loss of housing ( primary outcome for homeless people ) as well as secondary outcomes ( e.g. care needs , self-esteem , loneliness , social support , substance use , psychological distress and service use ) were assessed during the interviews .


In addition , the model integrity of CTI was investigated during the data collection period .


Based on international research CTI is expected to be an appropriate intervention for clients making the transition from institutional to community living .


If CTI proves to be effective for abused women and homeless people , shelter services could include this case management model in their professional standards and improve the ( quality of ) services for clients .


NTR3463 and NTR3425 .


Eye irritation is a constant hazard for migrant and seasonal farmworkers , but there are few studies of the problem or how to address it .


Researchers evaluated the effect of a community-based participatory eye health intervention on farmworker eye symptoms in the Hudson Valley , NY .


A randomized pre-post intervention with 2 , 4-week follow-up periods was implemented with a sample of 97 farmworkers .


Five eye symptoms were measured , along with utilization of protective eyewear and eye drops .


Leading baseline eye symptoms were redness ( 49 % ) , blurred vision ( 43 % ) , itching ( 43 % ) , and eye pain ( 29 % ) .


Significant reductions in eye pain ( P = 0.009 ) , and non-significant reductions in redness were observed for the intervention group while controls experienced increases in both .


The intervention was effective in significantly reducing eye pain , and to a lesser extent , redness .


Future eyewear promotion programs should offer a range of eye wear , tailor offerings to local climate and tasks , evaluate eyewear durability , and include eye drops .


Treatments for papulopustular rosacea ( PPR ) are limited .


To demonstrate the efficacy and safety of once-daily ivermectin 1 % cream in subjects with moderate to severe PPR .


Two identically designed , randomized , double-blind , controlled studies of ivermectin 1 % cream ( IVM 1 % ) or vehicle once daily for 12 weeks were conducted in subjects with moderate to severe PPR .


Efficacy assessments were Investigator 's Global Assessment ( IGA ) of disease severity and inflammatory lesion counts .


Safety assessments included incidence of adverse events ( AEs ) and local tolerance parameters .


Subjects evaluated their rosacea and completed satisfaction and quality of life ( QoL ) questionnaires .


In both studies , a greater proportion of subjects in the IVM 1 % group achieved treatment success ( IGA `` clear '' or `` almost clear '' ) : 38.4 % and 40.1 % vs 11.6 % and 18.8 % for vehicle ( both P < .001 ) , respectively .


Ivermectin was superior to vehicle in terms of reduction from baseline in inflammatory lesion counts ( 76.0 % and 75.0 % vs 50.0 % for both vehicle groups , respectively ) .


For all endpoints , starting at week 4 and continuing through week 12 , IVM 1 % was statistically significantly superior ( P < .001 ) .


Fewer subjects treated by IVM 1 % reported dermatologic AEs , and a higher proportion of subjects were observed to have no skin dryness or itching compared to vehicle .


Significantly more subjects receiving IVM 1 % reported having an `` excellent '' or `` good '' improvement , along with an improved QoL .


Ivermectin 1 % cream was effective and safe in treating inflammatory lesions of papulopustular rosacea .


To determine whether a novel endpoint of time to prerandomization monthly seizure count could be used to differentiate efficacious and nonefficacious therapies in clinical trials of new add-on antiepileptic drugs ( AEDs ) .


This analysis used data from 3 randomized , double-blind , placebo-controlled phase III trials of perampanel as an add-on therapy in patients with epilepsy who were experiencing refractory partial seizures : studies 304 ( ClinicalTrials.gov identifier NCT00699972 ) , 305 ( NCT00699582 ) , and 306 ( NCT00700310 ) .


Time to prerandomization monthly seizure count was evaluated post hoc for each trial , and findings were compared with the original primary outcomes ( median percent change in seizure frequency and 50 % responder rate ) .


Outcomes were assessed for all partial-onset seizures , secondarily generalized ( SG ) tonic-clonic seizures only , and complex partial plus SG ( CP + SG ) seizures .


Perampanel 4-12 mg significantly prolonged median time to prerandomization monthly seizure count , generally by more than 1 week , compared with placebo , across all 3 studies , consistent with the original primary outcomes .


Analysis of SG seizures only , and CP + SG seizures , also indicated a significantly prolonged median time to prerandomization monthly seizure count with perampanel 8 mg and 12 mg compared with placebo .


Time to prerandomization monthly seizure count is a promising novel alternative to the standard endpoints of median percent change in seizure frequency and 50 % responder rates used in trials of add-on AEDs .


Use of this endpoint could reduce exposure to placebo or ineffective treatments , thereby facilitating trial recruitment and improving safety .


Patients are at risk of drug-related problems ( DRPs ) at transition points during hospitalization .


The community pharmacist ( CP ) is often the first healthcare professional patients visit after discharge .


CPs lack sufficient information about the patient and so they may be unable to identify problems in medications , which may lead to dispensing the wrong drugs or dosage , and/or giving wrong information .


We aim to assess the impact of a complex intervention comprising of medication reconciliation performed at discharge by a hospital pharmacist ( HP ) with communication between the HP and CP on DRPs during the seven days following discharge .


The study is a cluster randomized crossover trial involving 46 care units ( each unit corresponding to a cluster ) in 22 French hospitals during two consecutive 14-day periods , randomly assigned as ` experimental ' or ` control ' ( usual care ) periods .


We will recruit patients older than 18 years of age and visiting the same CP for at least three months .


We will exclude patients with a hospital length of stay of more than 21 days , who do not return home or those in palliative care .


During the experimental period , the HP will perform a medications reconciliation that will be communicated to the patient .


The HP will inform the patient 's CP about the patient 's drug therapy ( modification in home medication , acute drugs prescribed , nonprescription treatments , and/or lab results ) .


The primary outcome will be a composite outcome of any kind of drug misuse during the seven days following discharge assessed at day seven ( 2 ) post-discharge by a pharmacist in charge of the study who will contact both patients and CPs by phone .


The secondary outcome will be unplanned hospitalizations assessed by phone contact at day 35 ( 5 ) after discharge .


We plan to recruit 1,176 patients .


This study will assess the impact of a reconciliation of medications performed at patient discharge followed by communication between the HP and the patient 's CP .


It will allow for identifying the type of patients in France for which the intervention is most relevant .


This study was registered with ClinicalTrials.gov ( number : NCT02006797 ) on 5 December 2013 .


The current efforts of intensivists focused on individual antibiotic treatment in patients suffering from sepsis has inspired us to conduct an open prospective clinical study to assess the relationship between body fluid retention ( > 10 L/24 hours ) and the efficiency of hydrophilic time-dependent antibiotics used in critically ill patients .


Polytrauma and abdominal catastrophes are the most frequent causes of systemic inflammatory response syndrome ( SIRS ) .


Consequent body liquid retention is taken for a pathophysiological covariate modifying the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of hydrophilic time-dependent antibiotics ( betalactams and carbapenems ) .


Not only body fluid retention but also changes in renal clearance are thought to be responsible for failure in PK/PD target attainment necessary for effective antimicrobial activity .


To describe the importance of the pathophysiological covariates for the individual kinetic variables of a representative antibiotic ( piperacillin ) is the primary goal of this kinetic observational study .


Three patients with polytrauma and SIRS admitted at the ICU of the Surgical Department , Teaching Hospital Hradec Krlov , whose condition was characterized by cumulative body fluid retention ( > 10 L ) , were eligible for enrolment .


As per standard hospital protocol , the patients were administered with 4 g of piperacillin in combination with tazobactam 0.5 g intravenously by 1-hour ( h ) infusion every 8 h.


A series of blood samples were taken 1 , 2.5 , and 5 h after the termination of the infusion .


Urine was collected over each dosing interval and for 24 h. Piperacillin was detected using a previously validated HPLC method .


Individual pharmacokinetic variables were estimated using non-compartmental pharmacokinetic analysis .


Cumulative body fluid retention was calculated as the difference between fluid intake and output .


Creatinine clearance ( Cl ) was used for renal function evaluation .


PK/PD target attainment was analysed according to Carlier ( 2013 ) .


In three patients with polytrauma and SIRS , great interindividual and intraindividual differences in extravascular volume expansion , i.e. cumulative body fluid retention 2030 L and changes in renal function , were recorded .


In 2/3 patients these pathophysiological changes as well as the clinical interventions administered resulted in augmented piperacillin clearance and an increase in distribution volume ( Vd ) ( > 20 L ) with a maximum at Day 28 after initiation of therapy .


In such patients treated with a standard dose of piperacillin , only minimum PK/PD target attainment ( 50 % Ft > MIC ) was obtained .


In contrast , a patient suffering from renal dysfunction attained both minimum ( 50 % ft > MIC ) and maximum PK/PD target ( 100 % ft > MIC ) .


In three critically ill patients with polytrauma and SIRS , pathophysiological changes ( covariates ) had a profound effect on the key determinants of the pharmacokinetics ( Cl and Vd ) , resulting in significant intraindividual variability in pharmacodynamic / pharmacokinetic target attainment necessary for therapeutic time-dependent antibacterial activity of piperacillin .


Consequently , patients with augmented clearance of piperacillin may be at risk for treatment failure , and/or bacterial resistance without dose up-titration .


A subsequent clinical study will be conducted to describe personalised kinetically guided antibiotic therapy .


Intracranial atherosclerosis represents a relatively unexplored , but potentially important , cause of stroke in a white population .


To investigate the relationship between intracranial carotid artery calcification ( ICAC ) as a marker of intracranial atherosclerosis and the risk of stroke in whites .


A population-based cohort study in the general community with 6 years of follow-up was conducted ( the Rotterdam Study ) .


Between 2003 and 2006 , a random sample of 2323 stroke-free persons ( mean age , 69.5 years ) underwent computed tomography scanning to quantify ICAC volume .


All participants were continuously monitored for the occurrence of stroke until January 1 , 2012 .


Atherosclerotic calcification in the intracranial internal carotid arteries .


Incident stroke .


During 14,055 person-years of follow-up , 91 participants had a stroke , of which 74 were ischemic .


Larger ICAC volume was related to a higher risk of stroke , independent of cardiovascular risk factors , ultrasound carotid plaque score , and calcification in other vessels ( fully adjusted hazard ratio per an increase of 1 SD in ICAC volume , 1.43 [ 95 % CI , 1.04-1 .96 ] ) .


Intracranial carotid artery calcification contributed to 75 % of all strokes ; for aortic arch and extracranial carotid artery calcification this incidence was only 45 % and 25 % , respectively .


Our findings establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the proportion of all strokes may be greater than that of large-artery atherosclerosis in more proximally located vessel beds .


Transient esophageal ulceration is a common finding after sclerotherapy of varices .


These ulcers sometimes cause pain , ulcer bleeding , and stricture formation .


Gastroesophageal reflux ( GER ) after Endoscopic injection sclerotherapy ( EIS ) is a known cause of worsening ulcer formation .


Therefore , an efficient drug for GER is desirable to improve the quality of life of patients with esophageal varices .


We randomized 18 Japanese cirrhotic patients who had risky esophageal varices .


The patients were randomly allocated into two groups , and during EIS sessions , one group was administered proton pump inhibitor ( PPI ) ( Rabeprazole 20 mg a person once a day ) , while the other received histamine H2 receptor antagonist ( H2-blocker ) ( famotidine 20 mg a person , twice a day ) .


Gastroesophageal reflux was monitored by a 24-h pH-monitoring catheter introduced into the distal esophagus .


Ulcer formation was evaluated using an endoscopic examination .


The subjective and objective symptoms were also compared between the two groups .


All patients in the H2-blocker group showed an increased percentage of time with pH < 4.0 after EIS sessions , but no patients in the PPI group showed an increased such symptoms .


The H2-blocker group also experienced a significantly higher number of days of heartburn and dysphasia than did the PPI group ( p = 0.017 , p = 0.042 ) .


The rate of ulcer improvement was found to be faster in Rabeprazole group than in H2 blocker group ( p = 0.008 ) .


These results suggest that Rabeprazole treatment prevents EIS-associated gastroesophageal reflux and promotes ulcer healing .


Rabeprazole also improve the subjective symptoms following EIS .


To evaluate the efficacy and safety of gatifloxacin 0.5 % ophthalmic solution administered twice daily for treatment of acute bacterial conjunctivitis .


Two identically designed , double-masked , multicenter studies in the United States and India enrolled patients 1 year or older with acute bacterial conjunctivitis .


Patients were randomized to gatifloxacin 0.5 % or vehicle treatment for 5 days .


Clinical success in clearing conjunctival hyperemia and discharge at day 6 ( primary endpoint ) and day 4 and microbiological cure were determined .


Isolates from positive conjunctival samples were tested for sensitivity and susceptibility .


Safety measures included adverse events ( AEs ) .


Data from these 2 studies were pooled for these analyses .


Of the 1437 randomized patients , 658 constituted the modified intent-to-treat population .


Patient characteristics were similar between the pooled treatment groups .


Clinical success occurred for 58.0 % of gatifloxacin 0.5 % - treated versus 45.5 % vehicle-treated patients at day 6 ( P = 0.001 ) and for 23.7 % versus 15.4 % in the respective groups at day 4 ( P = 0.007 ) .


Microbiological cure was higher with gatifloxacin 0.5 % than vehicle at days 4 and 6 ( P < 0.001 for both time points ) .


The combined minimum inhibitory concentration required to inhibit 90 % of isolates for gatifloxacin 0.5 % was 2.0 g/mL for gram-positive and gram-negative organisms .


AEs were reported by 11.6 % and 13.3 % of patients in the gatifloxacin 0.5 % and vehicle safety populations , respectively .


One patient in each treatment group experienced a serious AE ; neither was treatment related .


The 0.5 % concentration of gatifloxacin ophthalmic solution was safe and effective for treatment of acute bacterial conjunctivitis with twice-daily administration for 5 days .


Reduced postoperative pain is considered one of the benefits of laparoscopic inguinal hernia repair ( LHR ) .


We investigated the need for intravenous flurbiprofen axetil ( FA ) before emergence from anesthesia in patients who had undergone LHR .


Forty adult patients who were prepared for LHR were randomly divided into the FA group ( FA 1 mg x kg ( -1 ) administered at the end of surgery , n = 20 ) and the control group ( no FA administration , n = 20 ) .


Postoperative pain was evaluated by the Prince Henry Pain Score ( PHPS ) as well as by the frequency of on-demand use of nonsteroidal antiinflammatory drugs ( NSAIDs ) .


The PHPS on arrival at the ward was significantly lower in the FA group than the control group .


Additionally , none of the patients of the FA group required NSAIDs in the first two hours of postoperative period , compared with 6 patients ( 30 % ) of the control group .


However , at 4 hours postoperatively , none of the patients of both groups suffered pain at rest and the PHPS was similar in the two groups .


Although postoperative pain after LHR is mild and disappears rapidly , FA administration before emergence from anesthesia is necessary for management of pain during the immediate postoperative period .


The aim of this study was to evaluate the efficacy and safety of combinations of lercanidipine ( L ) and enalapril ( E ) at different doses on office and home blood pressure ( BP ) in patients with Stage 2 hypertension .


This was a randomized , double-blind , placebo-controlled , factorial study conducted in 100 centres from seven countries .


Patients with office DBP 100-109mmHg and home DBP at least 85mmHg at the end of a 2-week placebo run-in period were randomized to a 10-week treatment with placebo , L ( 10 or 20mg ) , E ( 10 or 20mg ) or the four L-E combinations .


The efficacy parameters were office DBP at trough ( primary ) , SBP at trough and home SBP and DBP .


Office BP was measured at each visit in both the sitting and the standing position , while home BP was measured twice in the morning and twice in the evening for at least 3 days before treatment and at study end .


Safety parameters included adverse events , laboratory tests and 12-lead ECG .


A total of 1039 patients were randomized ( 48 % men , mean age 54 years , mean BMI 30kg/m , 40 % obese patients ) .


Baseline BP was similar in all groups and lower for home than for office values ( 149/95 and 159/103mmHg , respectively ) .


A marked placebo effect was observed on office but not on home BP .


Combination therapy was superior to placebo at all doses for both office and home BP .


The greatest effect was observed in the L20/E20 group , in which the SBP/DBP fall amounted to -19.2 / -15.2 and -13.2 / -7.5 mmHg for sitting office and home BP , respectively .


Similar reductions were observed on standing office BP .


The L20/E20 combination was associated with less cough , palpitations and leg oedema than monotherapies , with no increased rate of dizziness or hypotension .


In Stage 2 hypertension , a fixed-dose combination of L and E ensures a control of both office and out-of-office BP , with a favourable tolerability profile .


Successful preventive therapy for ischemic priapism , a disorder of penile erection with major physical and psychologic consequences , is limited .


We conducted a randomized , double-blind , placebo-controlled clinical trial to assess the efficacy and safety of sildenafil by a systematic dosing protocol to prevent recurrent ischemic priapism associated with sickle cell disease .


Thirteen patients with sickle cell disease reporting priapism recurrences at least twice weekly were randomized to receive sildenafil 50 mg or placebo daily , unassociated with sleep or sexual activity , for 8 weeks , followed by open-label use of this sildenafil regimen for an additional 8 weeks .


Priapism frequency reduction by 50 % did not differ between sildenafil and placebo groups by intention-to-treat or per protocol analyses ( P = 1.0 ) .


However , during open-label assessment , 5 of 8 patients ( 62.5 % ) by intention-to-treat analysis and 2 of 3 patients ( 66.7 % ) by per protocol analysis met this primary efficacy outcome .


No significant differences were found between study groups in rates of adverse effects , although major priapism episodes were decreased 4-fold in patients monitored `` on-treatment . ''


Sildenafil use by systematic dosing may offer a strategy to prevent recurrent ischemic priapism in patients with sickle cell disease .


Goal of the presented study is to evaluate whether alcohol-dependent patients given additional individual psychotherapy after a heavy relapse during pharmacotherapy remain abstinent for longer than those who continue with pharmacotherapy alone .


In a randomized , multicenter study , 109 alcohol-dependent patients who had suffered a heavy relapse either while receiving anticraving medication or placebo were randomized into 2 groups .


One group received medication , medical management , and additional individual , disorder-specific , cognitive-behavioral psychotherapy , while the control group received medication and medical management only .


Main outcome was defined as days until first heavy relapse .


Fifty-four patients were randomized to the psychotherapy group , 55 to the control group .


Intention-to-treat and completer analyses found no differences between groups , whereas as-treated analyses ( patients who actually received psychotherapy compared with those who did not ) found a significant effect of psychotherapy .


Our data indicate that patients that are willing to attend psychotherapy benefit from receiving psychotherapy in addition to pharmacotherapy .


We suggest that it may be beneficial to consider patients ' preferences concerning psychotherapy at an earlier stage during treatment .


Nonalcoholic fatty liver disease ( NAFLD ) is the most common cause of chronic liver injury .


Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production ; antioxidant therapy is one of the main therapeutic lines in NAFLD .


In the current study we aimed to investigate the effect of coenzyme Q10 ( coQ10 ) therapy on several adipocytokines and insulin resistance in patients with NAFLD .


In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled .


After randomization into two groups , 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks .


BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , fasting serum glucose ( FSG ) , insulin resistance ( IR ) , vaspin , chemerin , pentraxin 3 ( PTX3 ) and markers of oxidative stress including total antioxidant capacity ( TAC ) and malondialdehyde ( MDA ) .


After 4 weeks of coQ10 supplementation , waist circumference ( WC ) and serum AST and TAC concentrations significantly decreased in intervention group ( p < 0.05 ) but no significant changes occurred in placebo-treated group .


In stepwise multivariate linear regression model , change in serum FSG was a significant predictor of changes in serum vaspin , chemerin and pentraxin 3 ( p < 0.001 ) .


The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD .


Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit .


Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers , when supervised by specialists , in low-income and middle-income countries .


We did the COmmunity care for People with Schizophrenia in India ( COPSI ) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care .


We did a multicentre , parallel-group , randomised controlled trial at three sites in India between Jan 1 , 2009 and Dec 31 , 2010 .


Patients aged 16-60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases , Diagnostic Criteria for Research ( ICD-10-DCR ) were randomly assigned ( 2:1 ) , via a computer-generated randomisation list with block sizes of three , six , or nine , to receive either collaborative community-based care plus facility-based care or facility-based care alone .


Randomisation was stratified by study site .


Outcome assessors were masked to group allocation .


The primary outcome was a change in symptoms and disabilities over 12 months , as measured by the positive and negative syndrome scale ( PANSS ) and the Indian disability evaluation and assessment scale ( IDEAS ) .


Analysis was by modified intention to treat .


This study is registered as an International Standard Randomised Controlled Trial , number ISRCTN 56877013 .


187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group ; 253 ( 90 % ) participants completed follow-up to month 12 .


At 12 months , total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group ( PANSS adjusted mean difference -3.75 , 95 % CI -7.92 to 0.42 ; p = 0.08 ; IDEAS -0.95 , -1.68 to -0.23 ; p = 0.01 ) .


However , no difference was shown in the proportion of participants who had a reduction of more than 20 % in overall symptoms ( PANSS 85 [ 51 % ] in the intervention group vs 44 [ 51 % ] in the control group ; p = 0.89 ; IDEAS 75 [ 48 % ] vs 28 [ 35 % ] ) .


We noted a significant reduction in symptom and disability outcomes at the rural Tamil Nadu site ( -9.29 , -15.41 to -3.17 ; p = 0.003 ) .


Two patients ( one in each group ) died by suicide during the study , and two patients died because of complications of a road traffic accident and pre-existing cardiac disease .


18 ( 73 % ) patients ( 17 in the intervention group ) were admitted to hospital during the course of the trial , of whom seven were admitted because of physical health problems , such as acute gastritis and vomiting , road accident , high fever , or cardiovascular disease .


The collaborative community-based care plus facility-based care intervention is modestly more effective than facility-based care , especially for reducing disability and symptoms of psychosis .


Our results show that the study intervention is best implemented as an initial service in settings where services are scarce , for example in rural areas .


Wellcome Trust .


Complications with IV patient-controlled analgesia include programming errors , invasive access , and impairment of mobility .


This study evaluated an investigational sufentanil sublingual tablet system ( SSTS ) for the management of pain after knee or hip arthroplasty .


This prospective , randomized , parallel-arm , double-blind study randomized postoperative patients at 34U .


S. sites to receive SSTS 15 g ( n = 315 ) or an identical placebo system ( n = 104 ) and pain scores were recorded for up to 72h .


Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible .


Patients were excluded if they were opioid tolerant .


The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48h .


Secondary endpoints included total pain relief , patient and healthcare professional global assessments , and patient and nurse ease-of-care questionnaires .


Summed pain intensity difference ( standard error ) was higher ( better ) in the SSTS group compared with placebo ( 76 [ 7 ] vs. -11 [ 11 ] , difference 88 [ 95 % CI , 66 to 109 ] ; P < 0.001 ) .


In the SSTS group , more patients and nurses responded `` good '' or `` excellent '' on the global assessments compared with placebo ( P < 0.001 ) .


Patient and nurse ease-of-care ratings for the system were high in both groups .


There was a higher incidence of nausea and pruritus in the SSTS group .


SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals .


Adherence to pharmacological or non-pharmacological treatment of diabetes type 2 is fundamental in order to delay the onset of complications .


To measure the effect of nursing educational support on compliance with treatment in patients with type 2 diabetes attending Regional Hospital Universitario of Colima , Mexico .


An experimental , randomized study including outpatients with type 2 diabetes attending a Regional Hospital who agreed in writing to participate in the study .


Nursing educational intervention sessions of three hours on two days a week for three months were provided .


Adherence to treatment was assessed before and after intervention using the Scale for treatment adherence in type 2 diabetes ( EATDM-III ( ) ) .


We performed two-proportion Z and p ; Risk Ratio and confidence interval 95 % and attributable fraction exposed .


e experimental group had 32 members , the same as the control .


After the intervention it was found that 16 members ( 50 % ) in the experimental group showed treatment adherence , unlike the control group where no one showed adherence to treatment , obtaining an independent two-proportion Z = 4.62 , P = .0000 , Risk Ratio = 65 ; Confidence Interval 95 % = 3.67 to 1152.38 ; exposed attributable fraction = 98.46 % .


The intervention was effective for the adherence of treatment .


We report the main results , among adults , of a cluster-randomised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods .


The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants .


The trial was part of a multicomponent process/outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants .


Twenty matched pairs of neighbourhoods in London were randomised to intervention/control condition .


Primary outcomes ( five portions fruit/vegetables/day ; 530m of moderate intensity physical activity/week , abnormal General Health Questionnaire ( GHQ ) -12 score and Warwick-Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention questionnaire survey , among 3986 adults in a random sample of households across neighbourhoods .


There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR :1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR :1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : -1.52 , 95 % CI -3.93 to 0.88 ) .


There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : -0.14 , 95 % CI -0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) .


The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes .


Low participation rates and population churn likely compromised any impact of the intervention .


Imprecise estimation of outcomes and sampling bias may also have influenced findings .


There is a need for greater investment in refining such programmes before implementation ; new methods to understand , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway .


Two phase I studies in healthy Chinese ( NCT01458743 ) and Western ( NCT01612507 ) subjects evaluated the pharmacokinetics ( PK ) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours ( q8h or q12h ) .


Each study enrolled subjects sequentially into 1 of 2 cohorts ( cohort 1 : 60-minute infusions ; cohort 2 : 120-minute infusions ) .


All subjects in the Chinese ( n = 26 ) study received open label ceftaroline fosamil ; in the Western study , subjects ( n = 41 ) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions .


Single infusions were administered on days 1 and 8 .


On days 2 - 7 ( 3 - 7 for Chinese study , cohort 1 ) subjects received q12h or q8h infusions .


Plasma and urine were collected on days 1 and 8 for PK analysis .


Ceftaroline PK was linear and time-independent following single and multiple doses of ceftaroline fosamil .


The magnitude and timing of peak plasma concentrations of ceftaroline ( active metabolite ) , ceftaroline fosamil ( prodrug ) , and ceftaroline M-1 ( inactive metabolite ) varied according to the ceftaroline fosamil dosing schedule ( q12h or q8h ) and infusion duration ( 60 minutes or 120 minutes ) , but overall plasma ceftaroline exposures within the respective dosing intervals were broadly similar across cohorts .


The most frequent adverse events were rash/drug eruption , most of which were of mild-moderate intensity and considered related to treatment .


Ceftaroline PK was broadly similar in healthy Chinese and Western subjects receiving equivalent dose regimens .


The tolerability profile of ceftaroline fosamil in Chinese and Western subjects was consistent with previous clinical trials .


Pharmacologic treatment options for posttraumatic stress disorder ( PTSD ) are limited in number and effectiveness .


Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders , such as major depression .


Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone ( CRH ) - containing circuits are involved in the pathophysiology of the disease .


This Phase II trial aims to evaluate the efficacy of a CRH type 1 receptor ( CRHR1 ) antagonist in the treatment of PTSD .


Currently untreated adult women , ages 18 to 65years , with a primary psychiatric diagnosis of PTSD of at least 3months ' duration , are being enrolled in a parallel-group , double-blind , placebo-controlled , randomized clinical trial evaluating the efficacy and safety of GSK561679 , a novel CRHR1 receptor antagonist .


GSK561679 ( or matching placebo ) is prescribed at a fixed dose of 350mg nightly for six weeks .


The primary trial hypothesis is that GSK561679 will reduce symptoms of PTSD , as measured by the Clinician-Administered PTSD Scale ( CAPS ) , significantly more than placebo after six weeks of treatment .


Putative biological markers of PTSD which may influence treatment response are measured prior to randomization and after five weeks ' exposure to the study medication , including : fear conditioning and extinction using psychophysiological measures ; variants of stress-related genes and gene expression profiles ; and indices of HPA axis reactivity .


In addition , the impact of PTSD and treatment on neuropsychological performance and functional capacity are assessed at baseline and after the fifth week of study medication .


After completion of the six-week double blind treatment period , subjects enter a one-month follow-up period to monitor for sustained response and resolution of any adverse effects .


Considerable preclinical and human research supports the hypothesis that alterations in central nervous system CRH neuronal activity are a potential mediator of PTSD symptoms .


This study is the first to assess the efficacy of a specific antagonist of a CRH receptor in the treatment of PTSD .


Furthermore , the biological and neuropsychological measures included in this trial will substantially inform our understanding of the mechanisms of PTSD .


Clinicaltrials.gov Identifier : NCT01018992.Registered 6 November 2009 .


First patient randomized 14 January 2010 .


This study evaluates the impact of the duration of pre-existing peripheral neuropathic pain on the therapeutic response to the capsaicin 8 % cutaneous patch .


The non-interventional QUEPP ( QUTENZA - safety and effectiveness in peripheral neuropathic pain ) study evaluated the effectiveness of Qutenza ( TM ) in 1044 non-diabetic patients with peripheral neuropathic pain , who received a single application .


Follow-up visits were scheduled at weeks 1-2 , 4 , 8 and 12 .


A pre-defined co-analysis of changes in average pain intensity was performed based on the duration of pre-existing pain .


In patients with pre-existing pain for < 6 months , the mean relative change of the numeric pain rating scale score on days 7-14 to week 12 versus baseline was -36.6 % [ 4.6 standard error of the mean ( SEM ) ; n = 105 ] , -25.1 % ( 1.9 SEM ; n = 311 ) in patients with pain duration of 6 months to 2 years , -22.3 % ( 1.6 SEM ; n = 391 ) in patients with pain for > 2-10 years , and -19.2 % ( 2.6 SEM ; n = 99 ) in patients with pain for > 10 years .


Thirty percent and 50 % responder rates were 61.7 % and 39.3 % in patients with pre-existing pain for < 6 months , 42.3 % and 23.3 % in patients with pain for 6 months to 2 years , 40.9 % and 21.6 % in patients with pain for > 2-10 years , and 32.3 % and 14.1 % in patients with pain for > 10 years .


The highest treatment response to the capsaicin 8 % cutaneous patch was observed in patients with a history of pre-existing peripheral neuropathic pain of less than 6 months , suggesting that early initiation of topical treatment might be indicated .


Longitudinal evidence linking diabetic retinopathy with changes in brain structure and cognition is sparse .


We used data from the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial to determine whether diabetic retinopathy at baseline predicted changes in brain structure or cognition 40 months later .


Participants from the ACCORD-MIND and ACCORD-Eye substudies were included in analyses of cognition ( n = 1,862 ) and MRI-derived brain variables ( n = 432 ) .


Retinopathy was categorized as none , mild nonproliferative , or moderate/severe .


Tests of cognition included the Mini-Mental State Examination ( MMSE ) , Digit Symbol Substitution Test ( DSST ) , Rey Auditory Verbal Learning Test , and Stroop test .


Primary brain outcomes were gray matter and abnormal white matter volumes .


Baseline retinopathy was associated with lower gray matter volume ( adjusted means of 470 , 466 , and 461 cm ( 3 ) for none , mild , and moderate/severe retinopathy , respectively ; P = 0.03 ) .


Baseline retinopathy also predicted a greater change in MMSE and DSST scores at 40 months in each retinopathy category ( MMSE : -0.20 , -0.57 , and -0.42 , respectively [ P = 0.04 ] ; DSST : -1.30 , -1.84 , and -2.89 , respectively [ P = 0.01 ] ) .


Diabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes .


Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline , patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline .


The superiority of conventional polyethylene glycol ( PEG ) solution over sodium picosulfate with magnesium citrate ( SPMC ) for bowel preparation remains controversial .


Therefore , this study compared the efficacy , safety , and tolerability of different regimens of SPMC and PEG solution in Koreans , who consume a traditional high-fiber diet .


A total of 200 outpatients undergoing elective colonoscopy were randomized into four groups receiving different bowel-preparation regimens in a prospective study : 4 L PEG in the morning on the day of colonoscopy , two 2 L split doses of PEG , split doses of 2 SPMC sachets , and split doses of 3 SPMC sachets .


Bowel cleansing efficacy was assessed based on the Ottawa bowel preparation scale and the Aronchick scale by endoscopists blinded to treatment , and patients filled out a questionnaire to determine satisfaction .


There was no difference among groups with respect to bowel cleansing grade ( Ottawa scale , p = 0.314 ) .


Patients in the SPMC groups were less likely to have abdominal fullness , pain , nausea , or vomiting than patients in the PEG groups ( p < 0.05 ) .


Patients reported SPMC was more palatable than PEG .


There were no significant differences among groups with respect to polyp detection rate .


SPMC is as effective as conventional high-volume PEG-electrolyte solution in Korean patients .


SPMC groups reported superior palatability and tolerability compared to PEG groups .


Information and behaviour can spread through interpersonal ties .


By targeting influential individuals , health interventions that harness the distributive properties of social networks could be made more effective and efficient than those that do not .


Our aim was to assess which targeting methods produce the greatest cascades or spillover effects and hence maximise population-level behaviour change .


In this cluster randomised trial , participants were recruited from villages of the Department of Lempira , Honduras .


We blocked villages on the basis of network size , socioeconomic status , and baseline rates of water purification , for delivery of two public health interventions : chlorine for water purification and multivitamins for micronutrient deficiencies .


We then randomised villages , separately for each intervention , to one of three targeting methods , introducing the interventions to 5 % samples composed of either : randomly selected villagers ( n = 9 villages for each intervention ) ; villagers with the most social ties ( n = 9 ) ; or nominated friends of random villagers ( n = 9 ; the last strategy exploiting the so-called friendship paradox of social networks ) .


Participants and data collectors were not aware of the targeting methods .


Primary endpoints were the proportions of available products redeemed by the entire population under each targeting method .


This trial is registered with ClinicalTrials.gov , number NCT01672580 .


Between Aug 4 , and Aug 14 , 2012 , 32 villages in rural Honduras ( 25-541 participants each ; total study population of 5773 ) received public health interventions .


For each intervention , nine villages ( each with 1-20 initial target individuals ) were randomised , using a blocked design , to each of the three targeting methods .


In nomination-targeted villages , 951 ( 743 % ) of 1280 available multivitamin tickets were redeemed compared with 940 ( 662 % ) of 1420 in randomly targeted villages and 744 ( 610 % ) of 1220 in indegree-targeted villages .


All pairwise differences in redemption rates were significant ( p < 001 ) after correction for multiple comparisons .


Targeting nominated friends increased adoption of the nutritional intervention by 122 % compared with random targeting ( 95 % CI 69-179 ) .


Targeting the most highly connected individuals , by contrast , produced no greater adoption of either intervention , compared with random targeting .


Introduction of a health intervention to the nominated friends of random individuals can enhance that intervention 's diffusion by exploiting intrinsic properties of human social networks .


This method has the additional advantage of scalability because it can be implemented without mapping the network .


Deployment of certain types of health interventions via network targeting , without increasing the number of individuals targeted or the resources used , could enhance the adoption and efficiency of those interventions , thereby improving population health .


National Institutes of Health , The Bill & Melinda Gates Foundation , Star Family Foundation , and the Canadian Institutes of Health Research .


Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy ( ART ) .


We hypothesized that short-course , high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality .


The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza , Tanzania , and Lusaka , Zambia .


Participants were 1,815 ART-nave non-pregnant adults with body mass index ( BMI ) < 18.5 kg/m who were referred for ART based on CD4 count < 350 cells/L or WHO stage 3 or 4 disease .


The intervention was a lipid-based nutritional supplement either without ( LNS ) or with additional vitamins and minerals ( LNS-VM ) , beginning prior to ART initiation ; supplement amounts were 30 g/day ( 150 kcal ) from recruitment until 2 weeks after starting ART and 250 g/day ( 1,400 kcal ) from weeks 2 to 6 after starting ART .


The primary outcome was mortality between recruitment and 12 weeks of ART .


Secondary outcomes were serious adverse events ( SAEs ) and abnormal electrolytes throughout , and BMI and CD4 count at 12 weeks ART .


Follow-up for the primary outcome was 91 % .


Median adherence was 66 % .


There were 181 deaths in the LNS group ( 83.7 / 100 person-years ) and 184 ( 82.6 / 100 person-years ) in the LNS-VM group ( rate ratio ( RR ) , 0.99 ; 95 % CI , 0.80-1 .21 ; P = 0.89 ) .


The intervention did not affect SAEs or BMI , but decreased the incidence of low serum phosphate ( RR , 0.73 ; 95 % CI , 0.55-0 .97 ; P = 0.03 ) and increased the incidence of high serum potassium ( RR , 1.60 ; 95 % CI , 1.19-2 .15 ; P = 0.002 ) and phosphate ( RR , 1.23 ; 95 % CI , 1.10-1 .37 ; P < 0.001 ) .


Mean CD4 count at 12 weeks post-ART was 25 cells/L ( 95 % CI , 4-46 ) higher in the LNS-VM compared to the LNS arm ( P = 0.02 ) .


High-dose vitamin and mineral supplementation in LNS , compared to LNS alone , did not decrease mortality or clinical SAEs in malnourished African adults initiating ART , but improved CD4 count .


The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients .


PACTR201106000300631 , registered on 1st June 2011 .


Eicosapentaenoic acid ( EPA ) , abundant in oily fish , is reported to reduce skin inflammation and provide photoprotection , potential mechanisms include competition with arachidonic acid ( AA ) for metabolism by cyclooxygenases/lipoxygenases to less pro-inflammatory mediators .


We thus examine impact of EPA intake on levels of AA , EPA and their resulting eicosanoids in human skin with or without ultraviolet radiation ( UVR ) challenge .


In a double-blind randomised controlled study , 79 females took 5 g EPA-rich or control lipid for 12 wk .


Pre - and post-supplementation , red blood cell and skin polyunsaturated fatty acids were assessed by GC , and eicosanoids from unexposed and UVR-exposed skin by LC-MS/MS .


Active supplementation increased red blood cell and dermal EPA versus control ( both p < 0.001 ) , lowering relative AA : EPA content ( 4:1 versus 15:1 and 5:1 versus 11:1 , respectively ; both p < 0.001 ) .


Pre-supplementation , UVR increased PGE2 , 12-hydroxyeicosatetraenoic acids , 12-HEPE ( all p < 0.001 ) and PGE3 ( p < 0.05 ) .


Post-EPA , PGE2 was reduced in unchallenged skin ( p < 0.05 ) while EPA-derived PGE3 ( non-sign ) and 12-HEPE ( p < 0.01 ) were elevated post-UVR .


Thus , post-EPA , PGE2 : PGE3 was lower in unchallenged ( 12:1 versus 28:1 ; p < 0.05 ) and UVR exposed ( 12:1 versus 54:1 ; p < 0.01 ) skin ; 12-hydroxyeicosatetraenoic acids :12 - HEPE was lower in UVR-exposed skin ( 3:1 versus 11:1 ; p < 0.001 ) .


Dietary EPA augments skin EPA : AA content , shifting eicosanoid synthesis towards less pro-inflammatory species , and promoting a regulatory milieu under basal conditions and in response to inflammatory insult .


We compared the efficacies of cold knife excision and carbon dioxide ( CO2 ) laser fiber excision of oral cavity leukoplakia .


Between August 2009 and June 2011,45 patients who underwent excision of oral cavity leukoplakia were assessed for operative time , use of bipolar cautery , blood loss , and number of intraoperative margins needed .


Patients were assigned randomly to either a cold knife group ( 23 procedures ) or a CO2 laser fiber group ( 24 procedures ) at the time of the procedure .


The times of excision were similar in the CO2 laser fiber group ( 1.64 min/cm2 ) and the cold knife group ( 1.70 min/cm2 ) .


There were large differences between the CO2 laser fiber group and the cold knife group in the categories of bipolar cautery uses per square centimeter ( 0.34 uses versus 3.32 uses ) and blood loss ( 0.19 g/cm2 versus 2.55 g/cm2 ) .


The average number of margins needed to clear a specimen by frozen section was 1.21 for the CO2 laser fiber group and 1.83 for the cold knife group .


The CO2 laser fiber did not show an advantage in operative time .


The CO2 laser fiber did show better outcomes in the areas of blood loss , bipolar cautery use , and intraoperative margins needed .


Research has shown that auditory training improves auditory sensory skills ; however , it is unclear whether this improvement is transferred to top-down skills , such as memory , attention , and language , and whether it depends on group characteristics in regard to memory and attention skills .


The primary goal of this research was to investigate the generalization of learning from auditory sensory skills to top-down skills such as memory , attention , and language .


We also aimed to compare whether this generalization process occurs in the same way among typically developing children and children with speech sound disorder .


This study was a randomized controlled trial .


Typically developing 7 - to 12-yr-old children and children with speech sound disorder were separated into four groups : a trained control group ( TDT ; n = 10 , age 9.6 2.0 yr ) , a nontrained control group ( TDNT ; n = 11 , age 8.2 1.6 yr ) , a trained study group ( SSDT ; n = 10 , age 7.7 1.2 yr ) , and a nontrained study group ( SSDNT ; n = 8 , age 8.6 1.2 yr ) .


Both trained groups underwent a computerized , nonverbal auditory training that focused on frequency discrimination , ordering , and backward-masking tasks .


The training consisted of twelve 45 min sessions , once a week , for a total of 9 hr of training , approximately .


Near-transfer ( Gap-In-Noise [ GIN ] and Frequency Pattern Test ) and far-transfer measures ( auditory and visual sustained attention tests , phonological working memory and language tests ) were applied before and after training .


The results were analyzed using a 2 2 2 mixed-model analysis of variance with the group and training as the between-group variables and the period as the within-group variable .


The significance threshold was p 0.05 .


There was a group period training interaction for GIN [ F ( 1.35 ) = 7.18 , p = 0.011 ] , indicating a significant threshold reduction only for the TDT group ( Tukey multiple comparisons ) .


There was a significant group period interaction [ F ( 1.35 ) = 5.52 , p = 0.025 ] and a training period interaction for visual reaction time [ F ( 1.35 ) = 4.20 , p = 0.048 ] , indicating improvement in the SSDT group and worsening in both nontrained groups .


There was also a significant group training period interaction [ F ( 1.35 ) = 4.27 , p = 0.046 ] for the auditory false alarms , with a significant improvement after training only for the SSDT group .


Analysis of variance also revealed that all groups exhibited approximately the same level of gains for all measures , except for GIN [ F ( 3,38 ) = 4.261 , p = 0.011 ] and visual response time [ F ( 3.38 ) = 4.069 , p = 0.014 ] .


After training , the TDT group demonstrated a significant improvement for GIN and the SSDT exhibited the same for sustained attention , indicating learning generalization from an auditory sensory training to a top-down skill .


For the other measures , all groups exhibited approximately the same level of gains , indicating the presence of a test-retest effect .


Our findings also show that the memory span was not related to the learning generalization process given that the SSDT exhibited a more pronounced gain in attention skills after the sensory training .


Although meditation therapies such as the Transcendental Meditation ( TM ) technique are commonly used to assist with stress and stress-related diseases , there remains a lack of rigorous clinical trial research establishing the relative efficacy of these treatments overall and for populations with psychiatric illness .


This study uses a comparative effectiveness design to assess the relative benefits of TM to those obtained from a gold-standard cognitive behavioral therapy for posttraumatic stress disorder ( PTSD ) in a Veteran population .


This paper describes the rationale and design of an in progress randomized controlled trial comparing TM to an established cognitive behavioral treatment - Prolonged Exposure ( PE ) - and an active control condition ( health education [ HE ] ) for PTSD .


This trial will recruit 210 Veterans meeting DSM-IV criteria for PTSD , with testing conducted at 0 and 3 months for PTSD symptoms , depression , mood disturbance , quality of life , behavioral factors , and physiological/biochemical and gene expression mechanisms using validated measures .


The study hypothesis is that TM will be noninferior to PE and superior to HE on changes in PTSD symptoms , using the Clinician Administered PTSD Scale ( CAPS ) .


The described study represents a methodologically rigorous protocol evaluating the benefits of TM for PTSD .


The projected results will help to establish the overall efficacy of TM for PTSD among Veterans , identify bio-behavioral mechanisms through which TM and PE may improve PTSD symptoms , and will permit conclusions regarding the relative value of TM against currently established therapies for PTSD .


Autism spectrum disorder ( ASD ) is a neurodevelopmental disorder characterized by social communication impairments and restricted , repetitive behaviors .


Whereas current pharmacological interventions for ASD focus primarily on psychiatric symptoms , including agitation and obsessive behaviors , few agents target core symptomatology .


It has been previously hypothesized that abnormalities in facial scanning , such as reduced eye contact or increased mouth fixation , contribute to social communication deficits in ASD .


In addition , previous reports have suggested elevated stress and anxiety in ASD , symptoms that are believed to impact facial scanning patterns .


The present pilot study sought to explore the effects of pharmacological intervention via propranolol , a nonselective - adrenergic antagonist and known anxiolytic , on facial scanning in ASD .


Specifically , we wished to determine whether there is an increase in eye contact and a decrease in mouth fixation with administration of propranolol .


A sample of 14 participants with ASD and 14 matched controls participated in two study sessions in which propranolol and placebo were administered in a counterbalanced , double-blinded manner .


At each session , ocular fixation data were collected during presentation of video stimuli of 16 human faces .


Fixation time on the eye , nose , and mouth regions of the face stimuli was analyzed .


The baseline fixation patterns for the ASD and control groups did not significantly differ ; however , administration of propranolol was associated with a significant reduction in mouth fixation for the ASD group .


Additionally , mouth fixation was positively related to nonverbal communication impairment in the ASD group .


Although eye fixation in ASD appears typical in the present study , the effect of propranolol in reducing mouth fixation suggests an important focus for further research .


Future studies are needed to better characterize the relationship between stress and anxiety and facial scanning in ASD , as well as the effects of pharmacological intervention .


Does the initiation of corifollitropin alfa administration on cycle day 4 instead of cycle day 2 result in a reduced total rFSH consumption in a GnRH antagonist protocol ?


Initiation of corifollitropin alfa on cycle day 4 compared with day 2 results in significantly reduced total rFSH consumption at the end of the follicular phase .


In vitro fertilization treatment is associated with significant physical , psychological and emotional stress in infertile patients .


This notion has fuelled the search for simplified treatment approaches that may reduce the treatment burden .


The introduction of corifollitropin alfa has provided a more patient-friendly treatment protocol because it obviates the need for daily hormonal injections .


In addition , postponing the initiation of hormonal stimulation should also reduce the total gonadotrophin consumption and the number of injections needed .


A prospective randomized controlled pilot study was conducted in a university centre in Belgium .


Between December 2011 and March 2013 , 59 patients were randomized in the study and 52 of these patients received the allocated intervention .


All patients were randomly assigned to the control group ( CD2 ) , with initiation of corifollitropin alfa on cycle day 2 , or to the study group ( CD4 ) with initiation of stimulation on day 4 .


The GnRH antagonist was administered from cycle day 7 onwards in both treatment arms .


The main outcome measure was the total rFSH consumption at the end of the follicular phase after corifollitropin alfa treatment .


The total dose of rFSH at the end of the follicular phase was significantly reduced in the CD4 group compared with the CD2 group ( 324 ( 276 ) IU in the CD2 group versus 173 ( 255 ) IU in the CD4 group , P = 0.015 , mean difference -151 , 95 % confidence interval ( CI ) -301 to -1 ) .


A significant reduction of total duration of rFSH stimulation in the CD4 group was also observed ( 8.6 ( 1.4 ) days in CD2 group versus 7.8 ( 1.2 ) days in the CD4 group , P = 0.008 , mean difference -0.8 , 95 % CI -1.6 to -0.1 ) .


The number of cumulus-oocyte-complexes was comparable in both treatment groups ( 12.8 ( 7.3 ) in CD2 group versus 14.7 ( 8.8 ) in the CD4 group , P = 0.461 , mean difference 1.8 , 95 % CI -2.7 to 6.4 ) .


Ongoing pregnancy rates of 48 % in the CD2 group and 41 % in the CD4 group were achieved ( P = 0.60 , relative risk ( RR ) 0.85 , 95 % CI 0.46-1 .56 ) .


Final oocyte maturation was triggered with GnRH agonist instead of hCG in two patients in the CD2 group and in eight patients in the CD4 group , because of an increased risk of ovarian hyperstimulation syndrome ( P = 0.078 , RR 3.7 ( 95 % CI 0.88-15 .8 ) .


Before general implementation can be advised , this trial should be validated in a much larger randomized trial .


WIDER IMPLICATIONS OF THE FINDINGS If the approach of starting ovarian stimulation on Day 4 of the cycle could be implemented in a large population of infertile patients , it would result in a significant reduction of gonadotrophin consumption .


No external finance was involved in this study .


C.B and N.P.P. have received fees from MSD .


Otherwise the authors declare no conflict of interest regarding this study .


The trial was registered at clinicaltrials.gov ( NCT01633580 ) .


The pandemic potential of avian influenza A/H5N1 should not be overlooked , and the continued development of vaccines against these highly pathogenic viruses is a public health priority .


This open-label extension booster study followed a Phase III study of 1206 adults who had received two 3.75 g doses of primary AS03A-adjuvanted or non-adjuvanted H5N1 split-virus vaccine ( A/Vietnam/1194 / 2004 ; clade 1 ) ( NCT00449670 ) .


The aim of the extension study was to evaluate different timings for heterologous AS03A-adjuvanted booster vaccination ( A/Indonesia/5 / 2005 ; clade 2.1 ) given at Month 6 , 12 , or 36 post-primary vaccination .


Immunogenicity was assessed 21days after each booster vaccination and the persistence of immune responses against the primary vaccine strain ( A/Vietnam ) and the booster strain ( A/Indonesia ) was evaluated up to Month 48 post-primary vaccination .


Reactogenicity and safety were also assessed .


After booster vaccination given at Month 6 , HI antibody responses to primary vaccine , and booster vaccine strains were markedly higher with one dose of AS03A-H5N1 booster vaccine in the AS03A-adjuvanted primary vaccine group compared with two doses of booster vaccine in the non-adjuvanted primary vaccine group .


HI antibody responses were robust against the primary and booster vaccine strains 21days after boosting at Month 12 or 36 .


At Month 48 , in subjects boosted at Month 6 , 12 , or 36 , HI antibody titers of 1:40 against the booster strain persisted in 39.2 % , 61.2 % , and 95.6 % of subjects , respectively .


Neutralizing antibody responses and cell-mediated immune responses also showed that AS03A-H5N1 heterologous booster vaccination elicited robust immune responses within 21days of boosting at Month 6 , 12 , or 36 post-primary vaccination .


The booster vaccine was well tolerated , and no safety concerns were raised .


In Asian adults primed with two doses of AS03A-adjuvanted H5N1 pandemic influenza vaccine , strong cross-clade anamnestic antibody responses were observed after one dose of AS03A-H5N1 heterologous booster vaccine given at Month 6 , 12 , or 36 after priming , suggesting that AS03A-adjuvanted H5N1 vaccines may provide highly flexible prime-boost schedules .


Although immunogenicity decreased with time , vaccinated populations could potentially be protected for up to three years after vaccination , which is likely to far exceed the peak of the a pandemic .


Labor is one of the most painful experiences a woman may face during her lifetime .


One of the most effective methods used for eliminating this pain is epidural analgesia .


The aim of this study to determine the impact of adding morphine to low-dose bupivacaine epidural anesthesia on labor and neonatal outcomes , and maternal side effects .


This is a prospective randomized double-blind study comparing two regimens of anesthetic agents used for epidural anesthesia in labor .


A total of 120 pregnant women were randomized into two groups with 60 subjects in each study arm .


A catheter was inserted , and 0.1 % bupivacaine + 2 g/mL fentanyl in 15 mL saline were given to Group bupivacaine-fentanyl ( Group BF ) , while 0.0625 % bupivacaine + 2 g/ml fentanyl + 2 mg morphine in 15 mL saline were given to Group bupivacaine-fentanyl-morphine ( Group BFM ) with no test dosing from the needle .


No morphine was added to the subsequent epidural injections in Group BFM .


The total dose of bupivacaine was significantly lower in Group BFM relative to Group BF ( P = 0.0001 ) .


The visual analogu scalescores at 15 , 30 , and 45 min were significantly lower in Group BF compared to thosein Group BFM ( P = 0.0001 , P = 0.001 , and P = 0.006 , respectively ) .


The second stage of labor was significantly shorter in Group BFM relative to Group BF ( P = 0.027 and P = 0.003 , respectively ) .


The satisfaction with analgesia following the first dose was higher in the nonmorphine group ( P = 0.0001 ) .


However , maternal postpartum satisfaction was similar in both groups .


Either nausea or vomiting was recorded in eight patients in Group BFM .


We believe that epidural analgesia comprised of a low-dose local anaesthetic and 2 mg morphine provides a painless labor that significantly reducesthe use of local anesthetic without changing the efficiency of the analgesic , ensuring the mother 's satisfaction without leading to an adverse effect on the mother or foetus , while mildly ( but significantly ) shortening the second stage of labor .


This phase III study assessed the safety and immunogenicity of MenACWY-CRM , a quadrivalent meningococcal conjugate vaccine , administered with routine vaccines starting at 2 months of age .


Healthy infants received MenACWY-CRM in a two - or three-dose primary infant series plus a single toddler dose .


In addition , a two-dose toddler catch-up series was evaluated .


Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement ( hSBA ) .


Reactogenicity and safety results were collected systematically .


After a full infant/toddler series or two-dose toddler catch-up series , MenACWY-CRM elicited immune responses against the four serogroups in 94-100 % of subjects .


Noninferiority of the two - versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups .


Following the three-dose infant primary series , 89-98 % of subjects achieved an hSBA 8 across all serogroups .


Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone , except for pertactin after the two-dose infant series .


Noninferiority criteria were met for all concomitant antigens after the three-dose infant series .


MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated .


No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed .


Teacher training may improve teaching effectiveness , but it might also have paradoxical effects .


Research on expertise development suggests that the integration of new strategies may result in a temporary deterioration of performance until higher levels of competence are reached .


In this study , the impact of a clinical teacher training on teaching effectiveness was assessed in an intensive course in emergency medicine .


As primary study outcome students ' practical skills at the end of their course were chosen .


The authors matched 18 clinical teachers according to clinical experience and teaching experience and then randomly assigned them to a two-day-teacher training , or no training .


After 14 days , both groups taught within a 12-hour intensive course in emergency medicine for undergraduate students .


The course followed a clearly defined curriculum .


After the course students were assessed by structured clinical examination ( SCE ) and MCQ .


The teaching quality was rated by students using a questionnaire .


Data for 96 students with trained teachers , and 97 students with untrained teachers were included .


Students taught by untrained teachers performed better in the SCE domains ` alarm call ' ( p < 0.01 ) and ` ventilation ' ( p = 0.01 ) , while the domains ` chest compressions ' and ` use of automated defibrillator ' did not differ .


MCQ scores revealed no statistical difference .


Overall , teaching quality was rated significantly better by students of untrained teachers ( p = 0.05 ) .


At the end of a structured intensive course in emergency medicine , students of trained clinical teachers performed worse in 2 of 4 practical SCE domains compared to students of untrained teachers .


In addition , subjective evaluations of teaching quality were worse in the group of trained teachers .


Difficulties in integrating new strategies in their teaching styles might be a possible explanation .


Nivolumab , a programmed death 1 ( PD-1 ) checkpoint inhibitor , was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma .


This randomized , open-label , phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment .


A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned ( in a 1:1 ratio ) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily .


The primary end point was overall survival .


The secondary end points included the objective response rate and safety .


The median overall survival was 25.0 months ( 95 % confidence interval [ CI ] , 21.8 to not estimable ) with nivolumab and 19.6 months ( 95 % CI , 17.6 to 23.1 ) with everolimus .


The hazard ratio for death with nivolumab versus everolimus was 0.73 ( 98.5 % CI , 0.57 to 0.93 ; P = 0.002 ) , which met the prespecified criterion for superiority ( P0 .0148 ) .


The objective response rate was greater with nivolumab than with everolimus ( 25 % vs. 5 % ; odds ratio , 5.98 [ 95 % CI , 3.68 to 9.72 ] ; P < 0.001 ) .


The median progression-free survival was 4.6 months ( 95 % CI , 3.7 to 5.4 ) with nivolumab and 4.4 months ( 95 % CI , 3.7 to 5.5 ) with everolimus ( hazard ratio , 0.88 ; 95 % CI , 0.75 to 1.03 ; P = 0.11 ) .


Grade 3 or 4 treatment-related adverse events occurred in 19 % of the patients receiving nivolumab and in 37 % of the patients receiving everolimus ; the most common event with nivolumab was fatigue ( in 2 % of the patients ) , and the most common event with everolimus was anemia ( in 8 % ) .


Among patients with previously treated advanced renal-cell carcinoma , overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus .


( Funded by Bristol-Myers Squibb ; CheckMate 025 ClinicalTrials.gov number , NCT01668784 . )


To study changes of plasma ADMA levels of patients with non-ST elevation myocardial infarction ( NSTEMI ) undergoing percutaneous coronary intervention ( PCI ) and to explore the effect of Salvia Miltiorrhiza ( SM ) on them .


Totally 52 patients with confirmed NSTEMI undergoing PCI were randomly assigned to the SM treated group and the control group , 26 in each group .


Patients in the SM treated group received the conventional therapy plus SM ( 1 g each time , three times per day till one month after PCI ) .


Those in the control group only received the conventional therapy .


Plasma ADMA levels were measured before PCI , and at day 1 and 30 after PCI .


Plasma ADMA levels in both group obviously decreased at day 30 after PCI with statistical difference ( P < 0.01 ) .


The decrement was more obviously seen in the SM treated group , with statistical difference when compared with the control group ( P < 0.01 ) .


Patients with NSTEMI undergoing PCI could have plasma ADMA levels decreased .


Administration of SM just before PCI might be associated with negative regulating plasma ADMA levels .


To assess treatment outcomes via acoustic voice laboratory measurements before and after intervention in patients with common voice problems and Determine if outcome sensitivity of certain voice laboratory measures varies with disorder type .


Retrospective and single-blinded .


In this study , 40 patients with a single voice disorder diagnosis of either benign vocal fold lesions ( lesions ) , primary muscle tension dysphonia ( MTD-1 ) , vocal fold atrophy ( atrophy ) or unilateral vocal fold paralysis ( UVFP ) underwent baseline testing , a single intervention-type ( phonosurgery/voice therapy ) , and follow-up testing at uniform time points .


Ten patients per diagnosis group were analyzed before and after treatment .


Time - and frequency-based acoustic measures taken from vowels and sentences as well as patient-perceptual analysis ( Voice Handicap Index-10 ) were reviewed .


Statistically significant improvements were observed for three of four groups .


Patients with muscle tension dysphonia displayed an improvement in Cepstral Spectral Index of Dysphonia speech ( CSID ) ( P < 0.05 ) .


Patients with lesions had improved Voice Handicap Index-10 ( P < 0.05 ) , cepstral peak prominence ( CPP ) vowel standard deviation ( P < 0.05 ) , and CPP speech ( P < 0.05 ) .


Patients with atrophy did not demonstrate significant improvement in any measure .


Patients with unilateral vocal fold paralysis showed an improvement in CSID speech ( P < 0.05 ) and CPP speech ( P < 0.05 ) .


In addition , strong effect sizes were observed for many of the acoustic parameters studied .


For all groups except atrophy , treatment was successful in improving patient perception of voice handicap and/or some acoustic voice parameters .


A disorder-specific response to frequency-based acoustic measures was found .


Breakthrough cancer pain ( BTcP ) is recognized as a clinically significant complication of chronic cancer pain with most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30min .