Secondary variables included 24-h ambulatory and seated BP measurements as well as BP normalization .


Of 600 patients enrolled , 486 were randomized ( 244 to OLM/AML 40/10 mg , 242 to PER/AML 8/10 mg ) .


The reduction in CSBP was larger with OLM/AML ( 14.5 0.83 mmHg ) than with PER/AML ( 10.4 0.84 mmHg ) .


The between-group difference was -4.2 1.18 mmHg with 95 % confidence intervals ( -6.48 to -1.83 mmHg ) within the predefined non-inferiority margin ( 2 mmHg ) .


An integrated superiority test confirmed that OLM/AML was superior to PER/AML ( p < 0.0001 ) in reducing CSBP .


The superiority of OLM/AML over PER/AML was also established for the majority of secondary efficacy variables ; at the final examination , 75.6 % of OLM/AML recipients achieved BP normalization ( mean seated systolic BP/diastolic BP < 140/90 mmHg ) compared with 57.5 % of PER/AML recipients ( p < 0.0001 ) .


The combination of OLM/AML was superior to PER/AML in reducing CSBP and other efficacy measures , including a significantly higher rate of BP normalization .


The objective of this study was to compare the effectiveness of using a virtual environment ( VE ) versus traditional paper floor plans ( FPs ) to prepare nurses for wayfinding in a new hospital building .


This study was designed to control for variables such as task complexity and individual ability that have been missed in other media comparison studies .


Thirty nurses were assigned to the VE or FP condition using a randomized block experimental design .


Subjects were blocked by alternate ranks on spatial/navigational ability and computer attitude/experience and randomly assigned to conditions .


Nurses received instruction with either a VE or FP condition .


Wayfinding tasks were then completed with trained observers at the new hospital under construction .


The investigators found no significant differences between the wayfinding performance or postintervention confidence levels of subjects .


Instruction using both media improved wayfinding and navigation skills .


Qualitative findings suggest that interactions of the instructional style , media , and learner influence information retention and transfer .


Although the virtual media did not prove to be more effective than FPs , it was equally effective for learning wayfinding and navigation skills in a new hospital .


Nursing leaders may want to consider use of 3-dimensional VEs as an early method to provide repetitive practice for learning how to navigate a new large-scale space .


PSA and PSA velocity ( PSAV , rate of PSA change over time ) are biomarkers for diagnosis and prognosis of prostate cancer .


Men who are at high risk for prostate cancer also have associated comorbidities for which they are taking NSAIDs and statins for long periods ; therefore , it is important to understand the effect of these medications on markers used to assess prostate cancer risk .


Using a population of 699 men , multiple linear regressions were used to investigate the associations between PSA and concomitant medications , and mixed-effects models were used to investigate these associations with PSAV .


After adjusting for selenium use , age , race , body mass index , and pack-years of smoking , aspirin , other NSAIDs , or statins did not demonstrate statistically significant associations with PSA ( P = 0.79 , 0.68 , and 0.79 , respectively ) or PSAV ( P = 0.23 , 0.43 , and 0.84 , respectively ) .


Results were not altered upon stratifying the sample between men who developed prostate cancer during the course of the study and those who did not .


Results from this study indicate that chronic use of aspirin , other NSAIDs , or statins did not affect PSA levels or PSAV in men at high risk for prostate cancer .


Larger prospective studies designed to investigate these relationships are needed to confirm this result .


Long-term use of NSAIDs or statins in men at high risk for prostate cancer may not interfere with the diagnosis or prognosis of this disease , and supports appropriate use of these medications with regard to prostate cancer risk .


Exogenous GLP-1 slows gastric emptying in health and diabetes leading to diminished glycemic excursions .


Gastric emptying is markedly accelerated by hypoglycemia .


The primary objective was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycemia .


Ten healthy volunteers were studied on four separate days in a randomized double-blind fashion .


Blood glucose was stabilized using a glucose/insulin clamp at hypoglycemia ( 2.6 mmol/L on two occasions [ hypo ] ) or euglycemia ( 6.0 mmol/L on two occasions [ eu ] ) between T = -15 and 45 min before clamping at 6.0 mmol/L until 180 min .


During hypoglycemia and euglycemia , subjects received intravenous GLP-1 ( 1.2 pmol/kg/min ) or placebo .


At T = 0 min , subjects ingested 100 g beef mince labeled with 20 MBq ( 99m ) Tc-sulfur-colloid and 3 g of 3-O-methyl-glucose ( 3-OMG ) , a marker of glucose absorption .


Gastric emptying was measured scintigraphically from T = 0 to 180 min and serum 3-OMG taken at 15-min intervals .


The areas under the curve for gastric emptying and 3-OMG concentration were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests .


Gastric emptying was accelerated during hypoglycemia ( hypo/placebo vs. eu/placebo ; P < 0.001 ) , as was glucose absorption ( P < 0.03 ) .


GLP-1 slowed emptying during euglycemia ( eu/placebo vs. eu/GLP -1 ; P < 0.001 ) .


However , hypoglycemia-induced acceleration of gastric emptying on placebo was markedly diminished by GLP-1 ( hypo/placebo vs. hypo/GLP -1 ; P < 0.008 ) , as was glucose absorption ( P < 0.01 ) .


Acute administration of exogenous GLP-1 attenuates , but does not abolish , the acceleration of gastric emptying by insulin-induced hypoglycemia in healthy subjects .


For future etiologic cohort studies in runners it is important to identify whether ( hyper ) pronation of the foot , decreased ankle joint dorsiflexion ( AJD ) and the degree of the extension of the first Metatarsophalangeal joint ( MTP1 ) are risk factors for running injuries and to determine possible sex differences.These parameters are frequently determined with the navicular drop test ( NDT ) Stance and Single Limb-Stance , the Ankle Joint Dorsiflexion-test , and the extension MTP1-test in a healthy population .


The aim of this clinimetric study was to determine the reproducibility of these three orthopaedic tests in runners , using minimal equipment in order to make them applicable in large cohort studies .


Furthermore , we aimed to determine possible sex differences of these tests .


The three orthopaedic tests were administered by two sports physiotherapists in a group of 42 ( 22 male and 20 female ) recreational runners .


The intra-class correlation ( ICC ) for interrater and intrarater reliability and the standard error of measurement ( SEM ) were calculated .


Bland and Altman plots were used to determine the 95 % limits of agreements ( LOAs ) .


Furthermore , the difference between female and male runners was determined .


The ICC 's of the NDT were in the range of 0.37 to 0.45 , with a SEM in the range of 2.5 to 5 mm .


The AJD-test had an ICC of 0.88 and 0.86 ( SEM 2.4 and 8.7 ) , with a 95 % LOA of -6.0 to 6.3 and -5.3 to 7.9 , and the MTP1-test had an ICC of 0.42 and 0.62 ( SEM 34.4 and 9.9 ) , with a 95 % LOA of -30.9 to 20.7 and -20 to 17.8 for the interrater and intrarater reproducibility , respectively.Females had a significantly ( p < 0.05 ) lower navicular drop score and higher range of motion in extension of the MTP1 , but no sex differences were found for ankle dorsiflexion ( p 0.05 ) .


The reproducibility for the AJD test in runners is good , whereas that of the NDT and extension MTP1 was moderate or low .


We found a difference in NDT and MTP1 mobility between female and male runners , however this needs to be established in a larger study with more reliable test procedures .


There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy .


We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women .


We did an open-label , randomised controlled trial , in seven academic hospitals and 44 non-academic hospitals in the Netherlands .


Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h ( immediate delivery ) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation ( expectant monitoring ) .


The primary outcomes were a composite of adverse maternal outcomes ( thromboembolic disease , pulmonary oedema , eclampsia , HELLP syndrome , placental abruption , or maternal death ) , and neonatal respiratory distress syndrome , both analysed by intention-to-treat .


This study is registered with the Netherlands Trial Register ( NTR1792 ) .


Between March 1 , 2009 , and Feb 21 , 2013 , 897 women were invited to participate , of whom 703 were enrolled and randomly assigned to immediate delivery ( n = 352 ) or expectant monitoring ( n = 351 ) .


The composite adverse maternal outcome occurred in four ( 11 % ) of 352 women allocated to immediate delivery versus 11 ( 31 % ) of 351 women allocated to expectant monitoring ( relative risk [ RR ] 036 , 95 % CI 012-111 ; p = 0069 ) .


Respiratory distress syndrome was diagnosed in 20 ( 57 % ) of 352 neonates in the immediate delivery group versus six ( 17 % ) of 351 neonates in the expectant monitoring group ( RR 33 , 95 % CI 14-82 ; p = 0005 ) .


No maternal or perinatal deaths occurred .


For women with non-severe hypertensive disorders at 34-37 weeks of gestation , immediate delivery might reduce the already small risk of adverse maternal outcomes .


However , it significantly increases the risk of neonatal respiratory distress syndrome , therefore , routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered .


ZonMw .


Evaluate the impact of concomitant enzyme ( CYP3A4 ) - inducer antiepileptic drugs ( EIAEDs ) on the efficacy and safety of perampanel in patients from the 3 phase-III clinical trials .


Patients with pharmacoresistant partial-onset seizures in the 3 phase-III clinical studies were aged 12 years and older and receiving 1 to 3 concomitant antiepileptic drugs .


Following 6-week baseline , patients were randomized to once-daily , double-blind treatment with placebo or perampanel 8 or 12 mg ( studies 304 and 305 ) or placebo or perampanel 2 , 4 , or 8 mg ( study 306 ) .


Treatment response assessed by median percent reduction in seizure frequency and responder rates improved with perampanel compared with placebo .


However , at 8 and 12 mg , the treatment response was significantly greater in patients receiving non-EIAEDs .


The treatment effect ( perampanel-placebo ) also demonstrated a dose-dependent increase in all patients .


The overall incidence of treatment-emergent adverse events was similar regardless of the presence of EIAEDs .


Occurrence of some adverse events , such as fatigue , somnolence , dizziness , irritability , was greater in patients receiving non-EIAEDs , as was discontinuation because of adverse events .


Perampanel shows efficacy and safety in the presence and absence of EIAEDs .


As systemic exposure to perampanel increases , so does efficacy .


Given the extensive metabolism of perampanel , systemic exposure is clearly reduced with concomitant administration of CYP3A4 inducers .


This supports the strategy of dosing perampanel to clinical effect .


Recognition of these pharmacokinetic interactions will be important in the optimization of this novel medication .


This study provides Class II evidence that 2 to 12 mg/d doses of perampanel reduced seizure frequency and improved responder rate in the presence and absence of EIAEDs .


Optimum duration of dual antiplatelet treatment ( DAPT ) after coronary stenting remains uncertain , with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice .


We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial .


This analysis was a planned extension of the previously published ARCTIC-Monitoring trial , in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent ( DES ) .


We recruited patients ( aged 18 years or older ) scheduled for planned DES implantation at 38 centres in France .


After 1 year of follow-up , patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study ( ARCTIC-Interruption ) .


Using a computer-generated randomisation sequence ( 1:1 ; stratified by centre ) , we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained ( interruption group ) or a strategy of DAPT continuation for 6-18 months ( continuation group ) .


The primary endpoint was the composite of death , myocardial infarction , stent thrombosis , stroke , or urgent revascularisation , analysed by intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT00827411 .


Between Jan 4 , 2011 , and March 3 , 2012 , 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption : 624 to the interruption group and 635 to the continuation group .


After a median follow-up of 17 months ( IQR 15-18 ) , the primary endpoint occurred in 27 ( 4 % ) patients in the interruption group and 24 ( 4 % ) patients in the continuation group ( hazard ratio [ HR ] 117 [ 95 % CI 068-203 ] ; p = 058 ) .


STEEPLE major bleeding events occurred more often in the continuation group ( seven [ 1 % ] patients ) compared with the interruption group ( one [ < 05 % ] patient ; HR 015 [ 002-120 ] ; p = 0073 ) .


Major or minor bleedings were also more common in the continuation group compared with the interruption group ( 12 [ 2 % ] patients vs three [ 1 % ] patients ; HR 026 [ 007-091 ] ; p = 004 ) .


Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting .


No conclusion can be drawn for high-risk patients who could not be randomised .


The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment .


Allies in Cardiovascular Trials Initiatives and Organized Networks ( ACTION Study Group ) , Fondation de France , Sanofi-Aventis , Cordis , Medtronic , Boston Scientific , Fondation SGAM .


To evaluate the effect of different bracket types on the levels of Streptococcus mutans ( SM ) and Lactobacillus ( LB ) in saliva , in plaque , and on the periodontal condition .


Forty patients aged 14 to 16 years , who had Angle Class I malocclusion with minimal crowding , were nonsmokers , were without systematic disease , and did not use antibiotics or oral mouth rinses during the 3-month period before the study were randomly selected .


The patients were subdivided into two groups with random allocation of bracket type : conventional brackets ( CB ; Avex Mx , OPAL orth . )


with steel wire ligature or self-ligating brackets ( SLB ; F1000 , Leone S.p.A. ) .


Microbial and periodontal records were obtained before bonding ( T1 ) and 1 month after bonding ( T2 ) .


Microbial samples were collected from the stimulated saliva and the plaque from the labial surfaces of the upper and lower lateral incisors .


To estimate the number of colony-forming units of SM and LB , Dentocult SM and LB kits were used .


The plaque index ( PI ) , gingival index ( GI ) , and pocket depth ( PD ) values were recorded to evaluate the periodontal condition .


Paired t-test and Mann-Whitney U-test were used to compare the groups statistically .


No significant differences occurred in SM or LB colonization between the groups .


In the SLB group , PI , GI , and PD values increased significantly ( P < .05 ) .


A greater increase was found in PD value in the SLB group ( 0.98 mm ) compared with the CB group ( 0.04 mm ; P < .05 ) .


The F1000 SLB do not have an advantage over Avex Mx CB with respect to periodontal status and colonization of SM and LB .


Autophagy has been reported to be essential for pre-implantation development and embryo survival .


However , its role in placental development and regulation of autophagy during pregnancy remain unclear .


The aims of this study were to ( 1 ) study autophagy by characterizing changes in levels of beclin-1 , DRAM , and LC3B in human placenta throughout gestation ; ( 2 ) determine whether autophagy is involved in regulation of trophoblast invasion in JEG-3 cells ( a choriocarcinoma cell line ) ; ( 3 ) examine the effects of reduced oxygen and glucose on the autophagic changes ; and ( 4 ) investigate the effect of reoxygenation and supplementation of glucose after oxygen-glucose deprivation ( OGD ) on the autophagic changes in primary cytotrophoblasts obtained from normal term pregnancy .


An analysis of 40 placental samples representing different gestational stages showed ( 1 ) no significant differences in beclin-1 , DRAM , and LC3B-II levels in placentas between early and mid-gestation , and late gestation with vaginal delivery ; ( 2 ) placentas from late gestation with cesarean section had lower levels of LC3B-II compared to early and mid-gestation , and late gestation with vaginal delivery ; levels of DRAM were also lower compared to placentas from early and mid-gestation ; and ( 3 ) using explant cultures , villous tissues from early and late gestation had similar rates of autophagic flux under physiological oxygen concentrations .


Knockdown of BECN1 , DRAM , and LC3B had no effects on viability and invasion activity of JEG-3 cells .


On the other hand , OGD caused a significant increase in the levels of LC3B-II in primary cytotrophoblasts , while re-supplementation of oxygen and glucose reduced these changes .


Furthermore , there were differential changes in levels of beclin-1 , DRAM , and LC3B-II in response to changes in oxygen and glucose levels .


Our results indicate that autophagy is involved in development of the human placenta and that changes in oxygen and glucose levels participate in regulation of autophagic changes in cytotrophoblast cells .


It is known that increased potassium and reduced sodium intakes can improve postprandial endothelial function .


However , the effect of increasing potassium in the presence of high sodium in the postprandial state is not known .


We aimed to determine the effect of high potassium and high sodium on postprandial endothelial function as assessed by using flow-mediated dilatation ( FMD ) and arterial compliance as assessed by using pulse wave velocity ( PWV ) and central augmentation index ( AIx ) .


Thirty-nine healthy , normotensive volunteers [ 21 women and 18 men ; mean SD age : 37 15 y ; BMI ( in kg/m ( 2 ) ) : 23.0 2.8 ] received a meal with 3 mmol K and 65 mmol Na ( low-potassium , high-sodium meal ( LKHN ) ] , a meal with 38 mmol K and 65 mmol Na [ high-potassium , high-sodium meal ( HKHN ) ] , and a control meal with 3 mmol K and 6 mmol Na ( low-potassium , low-sodium meal ) on 3 separate occasions in a randomized crossover trial .


Brachial artery FMD , carotid-femoral PWV , central AIx , and blood pressure ( BP ) were measured while participants were fasting and at 30 , 60 , 90 , and 120 min after meals .


Compared with the LKHN , the addition of potassium ( HKHN ) significantly attenuated the postmeal decrease in FMD ( P-meal by time interaction < 0.05 ) .


FMD was significantly lower after the LKHN than after the HKHN at 30 min ( P < 0.01 ) .


AIx decreased after all meals ( P < 0.05 ) .


There were no significant differences in AIx , PWV , or BP between treatments over time .


The addition of potassium to a high-sodium meal attenuates the sodium-induced postmeal reduction in endothelial function as assessed by FMD .


This trial was registered at http://www.anzctr.org.au/ as ACTRN12613000772741 .


Antiretroviral preexposure prophylaxis ( PrEP ) , using daily oral combination tenofovir disoproxil fumarate plus emtricitabine , is an effective human immunodeficiency virus ( HIV ) prevention strategy for populations at high risk of HIV acquisition .


Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity , nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses , hypothesized to result from aborted HIV infections providing a source of immunologic priming .


We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans .


Within a PrEP clinical trial among high-risk heterosexual African men and women , we detected HIV-specific CD4 ( + ) and CD8 ( + ) peripheral blood T-cell responses in 10 % -20 % of 247 subjects evaluated .


The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo , and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function .


We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals .


These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine .


The extralevator abdominoperineal excision ( ELAPE ) has been proposed as oncologically superior to standard abdominoperineal excision ( SAPE ) .


However , little is known regarding comparative margins achieved in ELAPE and SAPE .


The purpose of this study was to compare patterns of tissue removal between these two groups that can aid patient selection .


Twenty APE specimens , comprising 10 SAPEs and 10 ELAPEs , were selected randomly from a single UK centre .


Transverse slices of pathological specimens were matched to corresponding axial MRI images obtained from conventional pelvic MRI imaging .


Measurements from the muscularis propria to the resection margin [ muscularis to margin ( MTM ) distance ] were recorded by height ( from anal verge ) and quadrant for each surgical group .


MTM distances achieved on histopathological assessment were also compared to MRI assessed distances necessary to achieve a clear CRM .


ELAPE specimens had a greater mean MTM distance than for SAPE ( 7.75 vs. 5.61 mm , p = 0.02 ) .


ELAPE had significantly greater MTM distances in lateral and posterior quadrants ( p < 0.05 ) than SAPE at 30-49 mm .


There was no significant difference in mean anterior distances ( 1.57 vs. 1.16 mm , p = 0.507 ) with the smallest difference at a height of 60-69 mm .


Two ( 2 % ) of pathological MTM distances within ELAPE group failed to achieve the minimum MRI assessed distance compared with 30 ( 23 % ) in the SAPE group , which had higher CRM positivity .


ELAPE appears to confer oncological benefit over SAPE but with notable exceptions , including tumours located above and below the puborectalis sling and anteriorly at the level of prostate where exenteration may be more appropriate .


In bariatric surgery , non - or mini-invasive modalities for cardiovascular monitoring are addressed to meet individual variability in hydration needs .


The aim of the study was to compare conventional monitoring to an individualized goal-directed therapy ( IGDT ) regarding the need of perioperative fluids and cardiovascular stability .


Fifty morbidly obese patients were consecutively scheduled for laparoscopic bariatric surgery ( ClinicalTrials.gov Identifier : NCT01873183 ) .


The intervention group ( IG , n = 30 ) was investigated preoperatively with transthoracic echocardiography ( TTE ) and rehydrated with colloid fluids if a low level of venous return was detected .


During surgery , IGDT was continued with a pulse-contour device ( FloTrac ) .


In the control group ( CG , n = 20 ) , conventional monitoring was conducted .


The type and amount of perioperative fluids infused , vasoactive/inotropic drugs administered , and blood pressure levels were registered .


In the IG , 213 204 mL colloid fluids were administered as preoperative rehydration vs. no preoperative fluids in the CG ( p < 0.001 ) .


During surgery , there was no difference in the fluids administered between the groups .


Mean arterial blood pressures were higher in the IG vs. the CG both after induction of anesthesia and during surgery ( p = 0.001 and p = 0.001 ) .


In morbidly obese patients suspected of being hypovolemic , increased cardiovascular stability may be reached by preoperative rehydration .


The management of rehydration should be individualized .


Additional invasive monitoring does not appear to have any effect on outcomes in obesity surgery .


To explore the effect of body position ( sitting vs supine ) on intraocular pressure ( IOP ) in children , as assessed by the Icare PRO and the Tono-Pen .


Prospective clinical study .


Children with known or suspected glaucoma and those without glaucoma were recruited from the Duke Eye Center pediatric clinic .


Subjects underwent tonometry in both eyes while upright ( sitting ) , after instillation of topical anesthetic , with either the Icare PRO or the Tono-Pen first , and then the second instrument ( order randomized ) .


Goldmann applanation tonometry ( GAT ) was then performed by a clinician masked to the previous measurements .


The subjects were then placed in the supine position for 5 minutes , and tonometry using the Icare PRO and the Tono-Pen was obtained , in the same order used when they were the sitting position .


Enrolled were 47 children ( 94 eyes ) .


Mean seated IOP for GAT , Icare PRO and Tono-Pen were 16.4 4.2 , 17.5 3.5 , and 18.0 3.9 mm Hg , respectively .


The mean supine IOP for the Icare PRO and Tono-Pen were 18.4 4.5 and 18.8 4.2 mm Hg , respectively .


This rise was +0.9 2.3 mm Hg for Icare PRO ( P = 0.01 ) and +0.7 1.8 mm Hg for Tono-Pen ( P = 0.009 ) , respectively .


In children , Icare PRO tonometry correlates well with GAT in the sitting position , and with the Tono-Pen in both the sitting and supine positions .


IOP rises when a child changes position from sitting to supine when measured by the Icare PRO or the Tono-Pen .


However , the increase , which is less than 1 mm Hg , seems clinically insignificant and is unlikely to alter glaucoma management in children .


To investigate the influence of the overall intraocular lens ( IOL ) diameter on posterior capsule opacification ( PCO ) formation .


In this prospective randomized clinical trial , 124 eyes of 62 patients with bilateral age-related cataract were included .


Each patient received a Corneal A501D IOL in one eye and a Corneal J501D IOL in the fellow eye .


Best corrected visual acuity ( BCVA ) and digital slitlamp photographs were taken a 1h , 1 week , 1 , 3 , 6 and 12 months postoperatively .


The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image-analysis software .


We found a mean BCVA of 0.810.2 for the Corneal A501D group and 0.790.21 for the Corneal J501D group .


There was no significant difference 12 months after surgery between the two IOLs ( p > 0.05 ) .


Objective PCO assessment resulted in a mean PCO score ( scale 0-10 ) of 1.651.71 was found for the Corneal J501D group and a score of 1.541.64 was found for the Corneal A501D group ( p > 0.05 ) .


The subjective PCO assessment at 1 year resulted in a mean PCO score of 2.01.74 in the Corneal J501D group and 2.131.64 in the Corneal A501D group ( p > 0.05 ) .


Both investigated IOLs showed good clinical performance regarding PCO and BCVA .


Our study suggests that the use of an IOL with variable total diameter seems not to influence the rate of PCO formation .


To assess the efficacy of two antimicrobial prophylaxis regimens , a short cycle and the standard one , on the prevalence of acute postoperative infection in orthopedic surgery for acute and chronic disease of a thoracic and a pelvic limb .


Prospective , observational , experimental randomized , double-blind trial in patients undergoing orthopedic surgery due to acute or chronic disease , between April and September 2009 .


The sample size was determined using the formula to calculate the finite population .


Two groups were formed : one was given cefalotin for 24 hours plus ten additional days of dicloxacillin , the standard regimen and a second one that received cefalotin for 24 hours and placebo for ten days .


The wound was assessed during hospitalization and it was checked on days 5 , 8 , 14 and 30 .


A statistical software was used for the statistical analysis , which included Student 's t-test and chi2 , and descriptive statistics for percentages , frequencies , means and standard deviations .


The protocol was approved by the local health research committee .


One hundred and thirty-one patients were included .


Group I included 62 patients with cefalotin/dicloxacillin and Group II 69 patients with cafalotin/placebo for 10 days .


In Group I one patient had infection and in Group II there were 3 cases , with p = 0.50 when chi2 was applied .


Antimicrobial prophylaxis with 24 hour-cefalotin has the same effect on the prevalence of postoperative infection than a prolonged cycle of cefalotin plus dicloxacillin , according to the chi2 test .


It is clear that there is no considerable benefit in giving antibiotics indiscriminately and for long periods of time compared with protection from infection in clean wounds .


In the multi-site Prescription Opioid Addiction Treatment Study ( POATS ) , conducted within the National Drug Abuse Clinical Trials Network , participants randomly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes .


However , research with other substance-dependent populations shows that subgroups of participants may benefit from a treatment although the entire population does not .


We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management , either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence .


Problem severity was measured by a history of heroin use , higher Addiction Severity Index drug composite score , and chronic pain .


Adequate treatment adherence was defined a priori as attending at least 60 % of all offered sessions .


Patients who had ever used heroin and received drug counseling were more likely to be successful ( i.e. , abstinent or nearly abstinent from opioids ) than heroin users who received medical management alone , but only if they were adherent to treatment and thus received adequate exposure to counseling ( OR = 3.7 , 95 % CI = 1.1-11 .8 , p = 0.03 ) .


The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score .


These findings emphasize the importance of treatment adherence , and suggest that patients with prescription opioid dependence are a heterogeneous group , with different optimal treatment strategies for different subgroups .


The most effective approach for long-standing persistent atrial fibrillation ( LPAF ) ablation remained undetermined .


Our goal was to explore the heterogeneous left atrial substrate in patients with LPAF and to evaluate the effectiveness of a novel individualized substrate modification ( ISM ) approach in LPAF ablation .


One hundred and twenty-four patients with LPAF were randomized to ISM group ( n = 64 ) or stepwise ablation ( SA ) group ( n = 60 ) .


After pulmonary vein isolation , ISM was performed in the ISM group and SA was applied in the SA group .


The clinical effectiveness after a single and a repeated procedure was compared .


The total procedural time was significantly shorter in ISM than that in SA .


In the ISM group , mild left atrial substrate was observed in 17 ( 27.4 % ) , moderate in 26 ( 41.9 % ) and severe in 19 ( 30.6 % ) patients after successful cardioversion of the 62 patients .


The intention-to-treat analysis showed that sinus rhythm was maintained in 65.5 % of patients in the ISM group and in 45.0 % of patients in the SA group after a single procedure , P = 0.04 .


Atrial tachycardia ( AT ) recurred in 5 of 22 in the ISM group and in 20 of 33 in the SA group , P = 0.01 .


After a repeated procedure , 75 % of patients in the ISM group and 63.3 % of patients in the SA group were free of further recurrence , P = 0.16 .


Left atrial substrate varied noticeably in patients with LPAF .


The ISM approach was superior to SA approach in terms of procedural time , recurrence rate of AT and clinical effectiveness after a single procedure .


However , they yielded comparable outcomes after a repeated procedure .


Relaxin is a peptide hormone that exerts specific effects on cardiovascular system and human brain , leading to the hypothesis that this hormone may play a protective role against CVD and integration and modulation of behavioral activation .


We aimed to demonstrate the efficacy of Relaxin on functional recovery of post-stroke patients .


Patients admitted within a Rehabilitation Unit suffering from stroke have been evaluated .


Patients have been randomized to RLX ( 40 mcg/d ) plus rehabilitation vs a control group that underwent only rehabilitation .


A preliminary analysis of 36 patients at 20 and 40 days was made using the mRS for global function , the Functional Independent Measure ( FIM ) for daily activity and Trail Making Test ( TMT ) for cognitive function .


Eighteen patients ( age 72 ( 64-79 ) , M 56 % ) randomized to RLX plus rehabilitation were compared to 18 patients ( age 68 ( 64-78 ) , M 50 % ) that underwent only rehabilitation .


There was no difference between the two groups in terms of risk factors , stroke syndromes and etiology .


At admission the two groups showed the same characteristics in terms of functional aspects ( mRS , FIM ; p ns ) and cognitive function ( TMT ; p ns ) .


After 20 days ( T1 ) the treatment group ( RLX + rehabilitation ) showed no differences between the two groups ( FIM 78 vs 69 ; p ns ) , while after 40 days ( T2 ) patients treated with RLX+R showed an excellent recovery ( FIM 96 vs 75 ; p0 .001 ) .


In terms of cognitive function patients RLX+R revealed a better performance at T1 ( TMT 3.5 vs 2 ; p 0.002 ) and still better at T2 ( TMT 4 vs 2 ; p 0.001 ) .


These results have been confirmed in terms of global function both at T1 ( mRS 2.5 vs 3 ; p0 .001 ) and T2 ( mRS 2 vs 3 ; p < 0.001 ) .


Relaxin showed in this analysis a positive effects on stroke patient 's recovery , thus offering the broad therapeutic potential role of RLX as new drug in post-stroke patients .


Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life ( HRQoL ) .


We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients .


For this open-labelled , multicentre trial , we recruited patients aged 18 years or older from 30 UK centres .


Patients were eligible if they had an advanced , histologically confirmed adenocarcinoma of the oesophagus , oesophagogastric junction , or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination .


Patients could have an Eastern Cooperative Oncology Group performance status of 0-2 .


We randomly assigned patients using a central , computerised minimisation procedure to receive docetaxel plus active symptom control , or active symptom control alone ( 1:1 ; stratified by disease status , disease site , duration of response to previous chemotherapy , and performance status ) .


Docetaxel was given at a dose of 75 mg/m ( 2 ) by intravenous infusion every 3 weeks for up to six cycles .


The primary endpoint was overall survival , analysed by intention to treat .


This is the report of the planned final analysis .


This study is an International Standardised Randomised Controlled Trial , number ISRCTN13366390 .


Between April 21 , 2008 , and April 26 , 2012 , we recruited 168 patients , allocating 84 to each treatment group .


After a median follow-up of 12 months [ IQR 10-21 ] ) and 161 ( 96 % ) deaths ( 80 in the docetaxel group , 81 in the active symptom control group ) , median overall survival in the docetaxel group was 5.2 months ( 95 % CI 4.1-5 .9 ) versus 3.6 months ( 3.3-4 .4 ) in the active symptom control group ( hazard ratio 0.67 , 95 % CI 0.49-0 .92 ; p = 0.01 ) .


Docetaxel was associated with higher incidence of grade 3-4 neutropenia ( 12 [ 15 % ] patients vs no patients ) , infection ( 15 [ 19 % ] patients vs two [ 3 % ] patients ) , and febrile neutropenia ( six [ 7 % ] patients vs no patients ) .


Patients receiving docetaxel reported less pain ( p = 0.0008 ) and less nausea and vomiting ( p = 0.02 ) and constipation ( p = 0.02 ) .


Global HRQoL was similar between the groups ( p = 0.53 ) .


Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia ( p = 0.02 ) and abdominal pain ( p = 0.01 ) .


Our findings suggest that docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine .


Cancer Research UK .


The purpose of this study was to identify characteristics of peer coaches associated with improvement in diabetes control among low-income patients with type 2 diabetes .


Low-income patients with type 2 diabetes who spoke English or Spanish from 6 urban clinics in San Francisco , California , were invited to participate in the study .


Twenty participants received training and provided peer coaching to 109 patients over a 6-month peer coaching intervention .


Primary outcome was average change in patient glycosylated hemoglobin ( A1C ) .


Characteristics of peer coaches included age , gender , years with diabetes , A1C , body mass index ( BMI ) , levels of diabetes-related distress , self-efficacy in diabetes self-management , and depression .


Patient improvement in A1C was associated with having a coach with a lower sense of self-efficacy in diabetes management ( P < .001 ) , higher level of diabetes-related distress ( P = .01 ) , and lower depression score ( P = .03 ) .


Coach characteristics are associated with patient success in improving A1C .


`` Better '' levels of coach diabetes self-efficacy and distress were not helpful and , in fact , were associated with less improvement in patient A1C , suggesting that some coach uncertainty about his or her own diabetes might foster improved patient self-management .


These coach characteristics should be considered when recruiting peer coaches .


Although protein-rich plant foods have recently been touted as an equivalent to animal products , limited data exist regarding the effects of animal vs. plant proteins on appetite , satiety , and subsequent food intake .


The objective was to determine whether a high-protein beef lunch alters the appetitive , hormonal , and neural signals controlling food intake regulation vs. a macronutrient and fiber-matched ( MF ) or serving size-matched ( SS ) soy lunch in healthy adults .


A randomized , double-blind , crossover design study was completed in 21 adults ( aged 23 1 y ; body mass index : 23.8 0.6 kg/m ; mean SEM ) to compare 400-kcal MF and SS lunches varying in protein quality .


The MF lunches contained 24-g beef protein or 24-g soy protein , whereas the SS lunches contained 1 serving of beef ( 24-g protein/1-g fiber ) or soy ( 14-g protein/5-g fiber ) .


Pre - and postlunch appetite questionnaires and blood sampling were completed over an 8-h period until dinner was voluntarily requested .


In addition , pre - and postlunch functional MRI brain scans were completed to assess neural activation in response to food stimuli .


On average , dinner was requested at 250 20 min postlunch with no differences between beef vs. soy within the MF and SS conditions .


Furthermore , no differences in hunger , fullness , peptide YY , or glucagon-like peptide-1 responses were observed after the beef vs. soy lunches within the MF and SS conditions .


The SS beef meal led to reductions in anterior cingulate activation ( -22 6 % ) vs. soy ( +7 9 % ; P < 0.01 ) and greater reductions in insular activation ( -30 6 % ) vs. SS soy ( -7 10 % ; P < 0.01 ) .


The participants consumed 945 78 kcal after the MF meals and 910 74 kcal after the SS meals with no differences between beef vs. soy .


When comparing 2 high-quality protein sources , such as beef and soy , the type of protein consumed within a mixed meal elicited very little effect on appetite , satiety , and food intake in healthy adults .


Primary progressive aphasia ( PPA ) is an untreatable neurodegenerative disorder that disrupts language functions .


Previous studies have demonstrated transcranial direct current stimulation ( tDCS ) may improve language symptoms in patients with post stroke aphasia or neurodegenerative diseases .


The present study investigated whether the application of anodal tDCS ( AtDCS ) to the scalp overlying the left dorsolateral prefrontal cortex ( DLPFC ) , which may increase cortical excitability , in combination with individualized speech therapy would improve naming accuracy in the agrammatic variant of PPA ( avPPA ) .


Sixteen avPPA patients were randomly allocated into two subgroups : AtDCS ( n = 8 ) or placebo tDCS ( PtDCS ) .


tDCS was applied over the left DLPFC ( BA 8/9 ) 25 minutes per day for two weeks ( 10 days ) .


Each patient underwent 25 minutes of individualized speech therapy with either AtDCS or PtDCS during each treatment session .


Neuropsychological assessment , experimental naming , and linguistic abilities in daily living were assessed at baseline ( T0 ) , after two weeks of intervention ( T1 ) and at a 12-week follow-up ( T2 ) .


Significant improvement in experimental naming was observed in both groups at T1 and T2 , but this effect was significantly greater in AtDCS than PtDCS patients .


Naming correctness , as assessed using the Aachener Aphasie Test , increased selectively in the AtDCS group from T0 to T1 , and this effect remained significant at T2 .


The analysis of daily living language abilities improved selectively in AtDCS group .


Our results support the beneficial effect of targeted language training in combination with brain stimulation in avPPA patients .


tDCS should be considered a useful tool for the improvement of language functions in patients with neurodegenerative diseases in future trials .


To evaluate transcutaneous electrical nerve stimulation ( TENS ) used to relieve uterine contraction pain during breast-feeding in multiparous women .


A controlled and randomized clinical trial was performed with 32 post-partum multiparous women who were breast-feeding .


The participants were randomized into an experimental ( EG , n = 16 ) and a control group ( CG , n = 16 ) .


Pain was assessed using the Numerical Rating Scale and the descriptors of the Present Pain Intensity ( PPI - McGill ) during two sequential feeds .


In the first assessment , the post-partum women in the EG and CG were monitored while breast-feeding and questioned regarding the degree of uterine contraction pain .


In the second assessment , which was performed at the next feed , the EG used TENS while the CG was monitored , with pain being reassessed following .


In the EG , the TENS electrodes were placed between T10-L1 and S2-S4 , with a frequency of 100 Hz , a pulse duration of 75 s and amplitude adjusted to produce a strong and tolerable sensation for 40 min .


A descriptive analysis of the data and comparative intra - and intergroup analyses were performed by means of a non-parametrical test , with a significance level P 0.05 .


The level of basal pain was 5.56 in the EG and 5.50 in the CG .


In the intragroup analysis , the EG ( P < 0.0001 ) and CG ( P = 0.04 ) presented significant pain reduction .


In the intergroup analysis , the EG had significant pain reduction ( P < 0.01 ) in comparison to the CG .


In the PPI analysis , a non-significant decrease in pain intensity was observed in the EG .


TENS was found to be effective in reducing post-partum uterine contraction pain during breast-feeding .


Cold-induced increases in aortic blood pressure ( BP ) may cause adverse cardiac events in hypertensives by increasing ventricular afterload .


L-citrulline supplementation reduces BP at baseline and during the cold pressor test ( CPT ) , but the effect on wave reflection ( augmentation pressure ( AP ) and index ( AIx ) ) is controversial .


Our aim was to assess the effect of L-citrulline-rich watermelon supplementation on aortic hemodynamic responses to CPT in hypertensive adults .


Brachial systolic BP ( bSBP ) and aortic systolic BP ( aSBP ) , AP , AIx , AIx adjusted to 75 beats/min ( AIx75 ) , reflection time ( Tr ) , first ( P1 ) and second systolic peak ( P2 ; wave reflection magnitude ) , heart rate ( HR ) , and systolic time index ( STI ; myocardial oxygen demand ) at baseline and during CPT and magnitude of the response from baseline to CPT were evaluated in 13 individuals ( 10 women ; 571 year ; bSBP 1515 mm Hg ) .


Participants were randomized to a 6-week watermelon or placebo supplementation in a crossover design .


Watermelon reduced ( P < 0.05 ) bSBP , aSBP , P1 , and P2 at baseline and CPT compared with placebo ; thus , increases from baseline to CPT were unaffected .


Watermelon did not affect AP , AIx , AIx75 , and STI at baseline but decreased ( P < 0.05 ) AP and STI during CPT and the increases in AP ( ~ 5mm Hg ) and AIx75 ( ~ 7.3 % ) from baseline to CPT .


Watermelon supplementation reduced aortic BP and myocardial oxygen demand during CPT and the magnitude of the cold-induced increase in wave reflection in obese adults with hypertension .


Watermelon may provide cardioprotection by attenuating cold-induced aortic hemodynamic responses .


Clinicaltrial.gov register , NCT01185041 .


The aim of this study is to determine whether laparoscopic repair ( LR ) of inguinal hernia is superior to open repair ( OR ) in bilateral cases .


Sixty-two boys older than 6 years with bilateral hernias were included in our prospective , randomized , single-blinded clinical trial .


All patients were administered morphine via patient-controlled analgesia for 24 hours .


Pain scores were evaluated by the patients using a visual analog scale ( VAS ) at 1 , 2 , 4 , 12 , and 24 hours postoperatively .


Operative time , pain scores , analgesic doses , and first mobilization attempt were evaluated .


Parents also provided assessments of their children 's recovery and wound appearance .


Operative time was found to be slightly higher in OR compared with LR .


VAS scores were higher in OR than in LR at 1 hour postoperatively ( 6.78 versus 3.88 , respectively ; P < .05 ) .


At the other times , VAS scores showed no significant differences .


Although OR patients requested and delivered analgesics more frequently than LR patients , the difference was not significant .


The scores given by parents for wound appearance were significantly higher in the bilateral LR group than in the bilateral OR group ( 894.23 and 786.7 , respectively ; P < .05 ) .


This trial demonstrates that LR in bilateral cases offers benefits compared with OR in terms of lower pain scores and analgesic requirements and of reduced operative and patient recovery times .


However , the only significant difference was better wound cosmesis in bilateral LR cases .


The purpose of this randomized , controlled , crossover clinical trial was to evaluate and compare the behavioral differences resulting from the sedative effects of atomized buccal ( transmucosal ) and atomized intranasal ( parenteral ) midazolam ( 0.3 mg/kg ) as a method for sedation of pediatric dental patients .


Twenty-five 36 - to 72-month-old patients were randomly selected and divided into two groups that were sedated with either atomized buccal in the first visit or intranasal midazolam in the second visit ( 0.3 mg/kg ) .


Patient be - havior was rated , and drug acceptance by method of administration was determined .


There were no statistically significant differences between both groups in maximum working time .


There were significant differences between both groups in drug acceptance ( P = .008 ) and onset time ( P = .00 ) .


The statistical differences between the two groups were not significant in all behavior rating scales , except for the crying rating scale , since the buccal group showed more crying .


Atomized buccal and intranasal midazolam are both effective for sedation of pediatric dental patients and have the same maximum working time .


However , atomized intranasal is more acceptable by children , has faster onset time , and children demonstrate less crying .


Both the amount and the rate of absorption of ethanol ( EtOH ) from alcoholic beverages are key determinants of the peak blood alcohol concentration ( BAC ) and exposure of organs other than gut and liver .


Previous studies suggest EtOH is absorbed more rapidly in the fasting than in the postprandial state .


The concentration of EtOH and the type of beverage may determine gastric emptying/absorption of EtOH .


The pharmacokinetics of EtOH were measured in 15 healthy men after consumption of 0.5 g of EtOH/kg body weight .


During this 3-session crossover study , subjects consumed in separate sessions , beer ( 5.1 % v/v ) , white wine ( 12.5 % v/v ) , or vodka/tonic ( 20 % v/v ) over 20 minutes following an overnight fast .


BAC was measured by gas chromatography at multiple points after consumption .


Peak BAC ( Cmax ) was significantly higher ( p < 0.001 ) after vodka/tonic ( 77.4 17.0 mg/dl ) than after wine ( 61.7 10.8 mg/dl ) or beer ( 50.3 9.8 mg/dl ) and was significantly higher ( p < 0.001 ) after wine than beer .


The time to Cmax occurred significantly earlier ( p < 0.01 ) after vodka/tonic ( 36 10 minutes ) compared to wine ( 54 14 minutes ) or beer ( 62 23 minutes ) .


Six subjects exceeded a Cmax of 80 mg/dl after vodka/tonic , but none exceeded this limit after beer or wine .


The area under the concentration-time curve ( AUC ) was significantly greater after drinking vodka/tonic ( p < 0.001 ) than after wine or beer .


Comparison of AUCs indicated the relative bioavailability of EtOH was lower after drinking beer .


Findings indicate that BAC is higher after drinking vodka/tonic than beer or wine after fasting .


A binge pattern is significantly more likely to result in BAC above 80 mg/dl after drinking vodka/tonic than beer or wine .


Men drinking on an empty stomach should know BAC will vary depending on beverage type and the rate and amount of EtOH .


This study was conducted to determine whether treatment with motavizumab , an anti-respiratory syncytial virus ( RSV ) monoclonal antibody , would decrease viral load and improve clinical outcomes in previously healthy term infants hospitalized with RSV lower respiratory tract infection .


Infants hospitalized with lower respiratory tract infection and a positive RSV test performed locally were randomized to receive 1 intravenous dose of motavizumab ( 30 or 100 mg/kg ) or placebo .


Nasal wash samples were tested by real-time reverse transcriptase polymerase chain reaction at a central laboratory to determine viral load .


Clinical data were collected during RSV hospitalization and at 12-month follow up .


Of 118 infants , 112 were confirmed RSV positive by real-time reverse transcriptase polymerase chain reaction .


In each study group , median ( range ) RSV load ( log10 copies/mL ) decreased at a similar rate from baseline to study day 7 [ motavizumab 30 mg/kg : 8.35 ( 2.5-9 .5 ) to 5.03 ( 2.5-6 .8 ) ; motavizumab 100 mg/kg : 8.22 ( 5.5-9 .7 ) to 4.25 ( 2.5-8 .0 ) ; placebo : 8.02 ( 6.7-9 .8 ) to 5.17 ( 2.5-7 .3 ) ] .


Median ( range ) duration of hospitalization was 3.05 ( 0.8-16 .0 ) , 2.99 ( 1.0-25 .0 ) and 2.88 ( 0.8-11 .7 ) days for the motavizumab 30 mg/kg , motavizumab 100 mg/kg and placebo groups , respectively .


Six ( 8 % ) motavizumab and 0 placebo recipients were admitted to the intensive care unit and 4 required mechanical ventilation .


The incidence of wheezing episodes during the 12-month follow up was comparable for all 3 groups .


Motavizumab had no appreciable effect on RSV viral load measured in the upper respiratory tract of children hospitalized for RSV lower respiratory tract infection .


No differences were observed for duration of hospitalization , severity of illness measures or wheezing episodes during 12-month follow up in children treated with motavizumab or placebo .


New-onset diabetes after transplantation ( NODAT ) is one of the most common complications after kidney transplantation .


Patients were randomly assigned to receive cyclosporine A-based or tacrolimus-based immunosuppression .


Fasting and oral glucose tolerance tests were performed , and the patients were assigned to one of the following 3 groups , on the basis of the results : normal , impaired fasting glucose/impaired glucose tolerance , or NODAT .


NODAT developed in 14 % of patients receiving cyclosporine A-based immunosuppression and in 26 % of patients taking tacrolimus ( P = .0002 ) .


Albumin levels were similar , but uric acid level ( P = .002 ) and the age of the recipient ( P = .003 ) were significantly different between the diabetic and the normal groups .


Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group .


Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation ( P = .05 ) .


The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier , before the development of any sign of functional impairment .


To compare the visual and refractive outcomes and the corneal structural changes in myopic patients after surface refractive treatments ( ie , photorefractive keratectomy [ PRK ] with adjuvant mitomycin-C [ MMC ] and epithelial laser in situ keratomileusis [ epi-LASIK ] ) .


University of Crete , Heraklion , Crete , Greece .


Prospective comparative case series .


One eye of consecutive myopic patients was randomly assigned to PRK-MMC , and the fellow eye was treated with epi-LASIK .


Visual and refractive outcomes and corneal confocal microscopy findings were evaluated .


All patients were examined preoperatively and 1 , 3 , 6 , 12 , and 24 months postoperatively .


Twenty-six eyes ( 13 patients ) were included .


The mean follow-up was 2.47 years 0.35 ( SD ) ( range 1.64 to 2.93 years ) .


In the PRK-MMC group , the mean preoperative spherical equivalent refraction was -3.84 1.59 diopters ( D ) ( range -1.5 to -8.7 D ) and -0.21 0.44 D ( range -0.5 to 1.0 D ) at the last follow-up and in the epi-LASIK group , -3.91 1.48 D ( range -1.5 to -8.5 D ) and -0.18 0.36 ( range +0.5 to -0.5 D ) , respectively .


Qualitative analysis of the subepithelial nerve plexus , haze development , and keratocyte distribution were similar in the 2 groups .


There was no statistically significant difference in endothelial cell density between the groups throughout the follow-up ( P > .05 ) .


Epithelial LASIK and PRK-MMC gave similar visual , refractive , and corneal structural outcomes in patients with myopia for up to 2 years postoperatively .


No author has a financial or proprietary interest in any material or method mentioned .


The need to respond quickly to potential influenza pandemics is important .


Immunologic priming ( initial presentation of an antigen to allow antibody responses on revaccination ) with vaccine directed toward an older avian influenza H5 strain might lead to secondary antibody responses to a single dose of more current H5 avian influenza vaccine .


To assess priming with the older avian influenza A/Vietnam/1203 / 2004 ( H5N1 ) ( Vietnam ) vaccine and to conduct dose-response studies with vaccine directed against the more contemporary H5N1 avian influenza virus , influenza A/Anhui/01 / 2005 ( Anhui ) .


Multicenter US randomized clinical trial beginning in June 2010 with follow-up continuing through October 2011 enrolling 72 healthy adults who were vaccinated 1 year previously with the Vietnam vaccine and 565 vaccine-naive adults .


Participants who were previously vaccinated with 90 g of unadjuvanted Vietnam vaccine were randomly assigned to receive 3.75 g of avian influenza Anhui vaccine with or without MF59 adjuvant , stratified by 1 vs 2 previous doses ( 1 dose : n = 18 with MF59 and n = 17 without ; 2 doses : n = 19 with MF59 and n = 18 without ) .


Vaccine-naive individuals were randomly assigned to receive Ahnui vaccine with or without MF59 adjuvant in 1 of 5 doses ( 3.75 g [ n = 55 with MF59 and n = 59 without ] , 7.5 g [ n = 51 with MF59 and n = 57 without ] , 15 g [ n = 48 with MF59 and n = 44 without ] , 45 g [ n = 47 with MF59 and n = 47 without ] , or 90 g [ n = 57 without adjuvant ] ) or placebo ( n = 100 ) given at days 0 and 28 .


The primary immunogenicity outcome was hemagglutination inhibition assay ( HAI ) titer against each vaccine antigen 1 month ( day 28 ) and 6 months ( day 180 ) after last vaccination .


The primary safety outcomes were local and systemic adverse events on days 0 to 7 after each vaccination and serious adverse events .


Previously vaccinated participants manifested secondary antibody responses after receipt of low-dose Anhui vaccine ( `` boosting '' ) ; by day 28 , 21 % to 50 % developed HAI responses of 1:40 or greater .


Use of adjuvant was not associated with increased HAI responses .


Among vaccine-naive participants ( n = 565 ) , the optimum dose was 7.5 g of antigen with adjuvant ( geometric mean titer [ GMT ] , 63.3 ; 95 % CI , 43.0-93 .1 ) .


The greatest response to unadjuvanted antigen was seen at the highest dose , 90 g ( GMT , 28.5 ; 95 % CI , 19.7-41 .2 ) .


Local or systemic reactions occurred , respectively , in 40 ( 78 % ) and 25 ( 49 % ) of 51 participants who received 7.5 g plus adjuvant vs 50 ( 88 % ) and 29 ( 51 % ) of 57 who received 90 g of unadjuvanted vaccine .


In general , antibodies were short-lived , and by day 180 , HAI titers had decreased to less than 1:20 in all treatment groups .


Previous receipt of a single dose of influenza A ( H5N1 ) Vietnam vaccine was associated with sufficient immunologic priming to facilitate antibody response to a different H5N1 antigen using low-dose Anhui ( booster ) vaccine .


In participants who had not previously received H5 vaccine , low-dose Anhui vaccine plus adjuvant was more immunogenic compared with higher doses of unadjuvanted vaccine .


clinicaltrials.gov Identifier : NCT00680069 .


Most patients with asthma take fewer than half of prescribed doses of controller medication .


Interventions to improve adherence have typically been costly , impractical , and at best only minimally successful .


To test a speech recognition ( SR ) intervention to improve adherence to pediatric asthma controller medication .


The Breathe Well study was a 24-month pragmatic randomized clinical trial .


The study was conducted within Kaiser Permanente Colorado , a large , group-model health maintenance organization .


A total of 1187 children aged 3 to 12 years with a persistent asthma diagnosis and prescription for an inhaled corticosteroid were randomized to the computerized SR intervention or usual care condition and followed up for 24 months between October 2009 and February 2013 .


Speech recognition telephone calls to parents in the intervention condition were triggered when an inhaled corticosteroid refill was due or overdue .


Calls were automatically tailored with medical and demographic information from the electronic health record and from parent answers to questions in the call regarding recent refills or a desire to receive help refilling , learn more about asthma control , or speak with an asthma nurse or pharmacy staff member .


Adherence to pediatric asthma controller medication , measured as the medication possession ratio over 24 months .


In the intention-to-treat analysis , inhaled corticosteroid adherence was 25.4 % higher in the intervention group than in the usual care group ( 24-month mean [ SE ] adherence , 44.5 % [ 1.2 % ] vs 35.5 % [ 1.1 % ] , respectively ; P < .001 ) .


Asthma-related urgent care events did not differ between the 2 groups .


The intervention effect was consistent in subgroups stratified by age , sex , race/ethnicity , body mass index , and disease-related characteristics .


The intervention 's significant impact on adherence demonstrates strong potential for low-cost SR adherence programs integrated with an electronic health record .


The absence of change in urgent care visits may be attributable to the already low number of asthma urgent care visits within Kaiser Permanente Colorado .


Application of electronic health record-leveraged SR interventions may reduce health care utilization when applied in a population with less-controlled asthma .


clinicaltrials.gov Identifier : NCT00958932 .


Whether acupuncture is effective for relieving perimenopausal syndrome has been controversial recently .


In this article , we report the protocol of a randomized controlled trial using acupuncture to treat perimenopausal syndrome , aiming to answer this controversy .


A multicenter randomized controlled trial with two parallel arms is underway in China .


Two hundred and six women with perimenopausal syndrome will be randomly assigned to a treatment group using acupuncture plus auricular acupressure ( AA group ) and a control group using Climen ( Bayer Healthcare Company Limited , Guangzhou , China ) , a 28-day sequential hormone replacement therapy , in a 1:1 ratio .


Participants in the AA group will receive three acupuncture sessions per week in the first 4 weeks and two sessions per week in the following 8 weeks , for a total of 28 sessions over 12 weeks .


Auricular points will be plastered by Semen Vaccariae twice per week for a consecutive 12 weeks , with both ears used alternately .


The Climen control group is prescribed a tablet containing estradiol valerate 2 mg/day for the first 11 days , and a tablet containing estradiol valerate 2 mg/day plus cyroterone acetate 1 mg/day for the following 10 days .


The total treatment period of the control group is three cycles .


The post-treatment follow-up period will last 24 weeks .


The primary outcome is the Menopause Rating Scale ( MRS ) assessed at baseline and 4 , 12 , 16 , 24 and 36 weeks after randomization .


The secondary outcomes are Menopause-Specific Quality of Life , average hot flash score during 24 hours , serum estradiol , follicle-stimulating hormone and luteinizing hormone level .


The first two secondary outcomes are measured at the same point as the MRS. Other secondary outcomes are measured at baseline and 12 , 24 weeks after randomization .


The results of this trial , which will be available in 2015 , will clarify whether acupuncture is effective to relieve perimenopausal syndrome .


ClinicalTrials.gov NCT01933204 ( registered 9 August 2013 ) .


Carpal tunnel decompression with division of the transverse carpal ligament has been a highly successful procedure for the treatment of carpal tunnel syndrome .


The standard longitudinal incision technique , with a long curvilinear incision , has been the optimal treatment procedure for surgical decompression of the median nerve , for many surgeons .


The aim of this study was to compare the traditional open carpal tunnel release ( TOCTR ) technique with the minimal-access carpal tunnel release ( MACTR ) technique for the treatment of carpal tunnel syndrome ( CTS ) , presenting our experience .


A total of 120 patients eligible for carpal tunnel decompression were recruited into the study .


The patients were randomised for treatment allocation , at a 1:1 ratio , resulting in 60 patients in group A , treated by standard TOCTR , and 60 patients in group B , treated by MACTR .


To evaluate patients ' outcomes we used the Boston Carpal Tunnel ( BCT ) questionnaire ; the formed scar was evaluated according to the Vancouver scale and short - and long-term complications .


Statistical analysis was performed by the chi-squared test and analysis of variance ( ANOVA ) ; Excel was the program used .


In our series , there was no complication related to the surgical intervention of any injury to nerve , artery or tendon structures .


In each section of the BCT questionnaire , patients in group B had significantly better results than patients in group A at both 6 and 12 months ' follow-up ( p < 0.001 ) .


For the Vancouver scar scale , there was a significant difference between two groups ' scores ; group B patients had significant improvements compared with group A patients .


In our perspective randomised study , MACTR showed statistically significant improvement compared to TOCTR .


The patient tolerance is reasonably high and the procedure is compatible with the current minimal invasive trend in surgery .


To investigate the efficacy and safety of a bilayer combination oxycodone ( OC ) and acetaminophen ( APAP ) analgesic with both immediate-release and extended-release ( ER ) components ( OC/APAP ER ) in patients with moderate to severe pain using an established acute pain model .


This was a randomized , double-blind , placebo-controlled trial .


Adult patients were included in the study if they had a pain intensity score4 on a 0-10 numerical rating scale after bunionectomy surgery , and were randomized ( 1:1 ) to receive four doses ( two tablets q12h ) of OC/APAP ER or placebo .


NCT01484652 .


The primary efficacy endpoint was the summed pain intensity difference over the first 48 hours ( SPID48 ) .


Secondary endpoints included SPIDs and total pain relief ( TOTPAR ) over the dosing intervals ; time to perceptible , meaningful , and confirmed pain relief ; and the proportion of patients with 30 % reduction in pain intensity scores .


A total of 329 patients were enrolled , of whom 266 ( OC/APAP ER , n = 135 ; placebo , n = 131 ) completed the study .


The mean ( SE ) SPID48 was 114.9 ( 7.6 ) in the OC/APAP ER group and 66.9 ( 7.6 ) in the placebo group ( P < 0.0001 ) .


SPID and TOTPAR values were significantly greater with OC/APAP ER than with placebo over all time periods analyzed , and the median times to perceptible , meaningful , and confirmed pain relief were significantly shorter .


More patients showed 30 % reduction in pain intensity scores with OC/APAP ER than with placebo at all times after 0.5 hours .


OC/APAP ER was generally well tolerated .


A limitation of this study was the lack of an active comparator .


OC/APAP ER was efficacious and generally well tolerated in an established model of moderate to severe acute pain , providing an onset of analgesia in approximately 30 minutes and sustained pain relief over the 12 hour dosing period .


Double-blind study comparing efficacy and safety of the topically acting corticosteroid beclomethasone dipropionate ( BDP ) to prednisone ( PD ) in patients with active , mild-to-moderate ulcerative colitis ( UC ) .


Overall , 282 patients were randomized to receive BDP-prolonged release tablets 5mg once daily for 4 weeks and then every other day for an additional 4 weeks or oral PD 40mg once daily for the initial 2 weeks tapered of 10mg every 2 weeks during the 8-week study period .


Efficacy end point was the non-inferiority of BDP vs. PD in terms of Disease Activity Index ( DAI ) score < 3 or reduction by at least 3 points for patients with a baseline DAI 7 at week 4 .


Safety end point was the proportion of patients with steroid-related adverse events ( AEs ) and cortisol < 150nmol/l at week 4 .


DAI response rates at week 4 were 64.6 % and 66.2 % with BDP and PD , respectively , demonstrating non-inferiority of BDP vs. PD ( delta : -1.56 ; 95 % confidence interval ( CI ) -13.00 -9.88 , P = 0.78 ) .


Patients with steroid-related AEs and cortisol < 150nmol/l at week 4 were 38.7 % in the BDP group and 46.9 % in the PD group ( P = 0.17 between groups ) .


No safety signals were observed in both the groups .


BDP was non-inferior to PD in the treatment of active UC , with a good safety profile in both the groups .


Micronutrient deficiencies and in utero exposure to HIV may impair infant neurodevelopment .


To evaluate the effect of daily multivitamin supplementation on the cognitive , language and motor development of HIV-exposed Tanzanian infants .


A total of 2387 infants were randomized to receive daily oral supplementation of multivitamins ( B-complex , C and E ) or placebo from age 6 weeks for 24 months .


The cognitive , language and motor scales of the Bayley Scales of Infant and Toddler Development , third edition , were administered to a subset of 206 infants at age 15 months .


Multivitamin supplementation did not improve measures of cognitive development , expressive or receptive language or gross motor capabilities .


There was a trend toward improved fine motor skills among infants randomized to the multivitamin group ( difference in mean score = 0.38 ; 95 % CI = -0.01 , 0.78 , p = 0.06 ) .


Daily provision of multivitamins to HIV-exposed infants does not substantially improve developmental outcomes at age 15 months .


Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) is the most effective treatment for morbid obesity .


The additional benefit of placing a nonadjustable band around the pouch remains to be determined .


The objective of this study was to compare outcomes between banded and nonbanded LRYGB patients in a single bariatric center .


A matched cohort analysis was performed between patients who had undergone banded and nonbanded ( standard ) LRYGB .


In the banded bypass cohort , an 8 F , 6.5 cm silastic ring was placed around the proximal gastric pouch .


Both cohorts were matched for age , body mass index ( BMI ) , and anastomotic technique .


Endpoints included percentage excess weight loss ( % EWL ) , postoperative morbidity , and band-related complications .


Between January 2007 and July 2010 , 134 banded LRYGB were performed ( 55 % female , mean age 45 years ) .


They were compared with a matched cohort of 134 concurrent nonbanded LRYGB patients ( 67 % female , mean age 45.4 years ) .


Mean preoperative BMI was 54.6 and 52.8 kg/m ( 2 ) , respectively ( P = .084 ) .


At 24 months postoperatively , the average % EWL was 58.6 % in banded bypass patients and 51.4 % in the nonbanded group ( P = .015 ) .


The difference in EWL was more pronounced in super-obese patients than in those with BMI < 50 ( among super-obese , 57.5 % versus 47.6 % , P = .003 ; among those with BMI < 50 , 62.9 % versus 57.9 % , P = .406 ] .


There was no difference in early ( 19.4 % versus 19.4 % ) or late complications ( 10.4 % versus 13.4 % , P = .451 ) between banded and nonbanded LRYGB patients .


Banding the pouch during LRYGB can be performed safely and may provide better weight loss , particularly in super-obese patients .


Further prospective and long-term comparative studies of this technique are warranted .


The mitogen-activated protein kinase ( MAPK ) pathway has been implicated in the molecular pathogenesis of human cancers , including metastatic colorectal cancer ( mCRC ) .


This provides a rationale for the development of MAPK-targeted agents such as pimasertib .


Patients with KRAS mutant mCRC were treated in the second-line setting with FOLFIRI ( 5-fluorouracil/folinic acid/irinotecan ) plus pimasertib .


The primary objective of the safety run-in phase was to determine the maximum-tolerated dose ( MTD ) and the recommended phase II dose of pimasertib combined with FOLFIRI .


Sixteen patients were enrolled in the trial .


Ten and six patients were treated daily with 45 and 60mg of pimasertib plus FOLFIRI , respectively .


The MTD was considered to be 45mg per day .


The most common treatment-emergent adverse events were diarrhoea , nausea , vomiting , asthenia and skin/rash event .


Of the 15 patients in the efficacy analysis group , two patients had partial response , nine patients had stable disease , three patients had progressive disease as their best overall response and one patient could not be evaluated .


Dose escalation of pimasertib in combination with FOLFIRI was limited by toxicity .


At the MTD of 45mg per day , pimasertib was adequately tolerated in patients with mCRC and no unexpected or new safety signals or concerns were identified .


Maternal micronutrient deficiencies may adversely affect fetal and infant health , yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia .


To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes .


Cluster randomized , double-masked trial in Bangladesh , with pregnancy surveillance starting December 4 , 2007 , and recruitment on January 11 , 2008 .


Six-month infant follow-up ended August 30 , 2012 .


Surveillance included 127,282 women ; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants .


Median gestation at enrollment was 9 weeks ( interquartile range , 7-12 ) .


Women were provided supplements containing 15 micronutrients or iron-folic acid alone , taken daily from early pregnancy to 12 weeks postpartum .


The primary outcome was all-cause infant mortality through 6 months ( 180 days ) .


Prespecified secondary outcomes in this analysis included stillbirth , preterm birth ( < 37 weeks ) , and low birth weight ( < 2500 g ) .


To maintain overall significance of = .05 , a Bonferroni-corrected = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes ( .05 / 5 ) .


Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group , there were 14,374 and 14,142 live-born infants , respectively , included in the analysis .


At 6 months , multiple micronutrients did not significantly reduce infant mortality ; there were 764 deaths ( 54.0 per 1000 live births ) in the iron-folic acid group and 741 deaths ( 51.6 per 1000 live births ) in the multiple micronutrient group ( relative risk [ RR ] , 0.95 ; 95 % CI , 0.86-1 .06 ) .


Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths ( 43.1 vs 48.2 per 1000 births ; RR , 0.89 ; 95 % CI , 0.81-0 .99 ; P = .02 ) and significant reductions in preterm births ( 18.6 vs 21.8 per 100 live births ; RR , 0.85 ; 95 % CI , 0.80-0 .91 ; P < .001 ) and low birth weight ( 40.2 vs 45.7 per 100 live births ; RR , 0.88 ; 95 % CI , 0.85-0 .91 ; P < .001 ) .


In Bangladesh , antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight .


clinicaltrials.gov Identifier : NCT00860470 .


To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion ( RVO ) or diabetic macular edema ( DME ) .


A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration .


Patients with RVO ( n = 441 ) and DME ( n = 435 ) from 4 large , randomized , phase 3 clinical trials of monthly ranibizumab intravitreal administration .


A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration ( AMD ) was fitted separately to RVO and DME data .


Population pharmacokinetic parameters and interindividual variability were estimated for each model .


Baseline covariates were evaluated for potential effects on systemic pharmacokinetics .


Model performance was validated using general diagnostic plots and a visual predictive check .


Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients .


The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients .


Most observed data points were within the simulated 90 % confidence interval , indicating that systemic ranibizumab concentrations were comparable among AMD , RVO , and DME patients .


No disease-related covariates were identified by the population pharmacokinetics analysis .


The systemic pharmacokinetics of ranibizumab were similar among patients with AMD , RVO , or DME .


Disease-related differences and patient demographics , measured in this study , did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration .


In all disease processes tested , ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation , thus minimizing systemic exposure .


WAKE-UP is a randomized , placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion 's visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery ( FLAIR ) sequences as its main imaging inclusion criterion .


Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement .


We therefore sought to improve rating homogeneity by incorporating quantitative signal intensity measurements .


One hundred forty-three data sets of patients with acute ischemic stroke were visually rated by 8 raters with respect to WAKE-UP study inclusion and exclusion criteria , and inter-rater agreement was calculated .


A subanalysis was performed on 45 cases to determine a threshold value of relative signal intensity ( rSI ) between the ischemic lesion and contralateral healthy tissue which best corresponded to a visually established verdict of FLAIR positivity .


The usefulness of this threshold in improving inter-rater agreement was evaluated in an additional sample of 50 patients .


Inter-rater agreement for inclusion into the WAKE-UP trial was 73 % with a free-marginal of 0.46 .


A threshold of rSI which best correlated with the visual rating of lesions as FLAIR positive was 1.20 .


The addition of rSI measurements to visual evaluation did not change the inter-rater agreement .


Introducing a semiquantitative measure for FLAIR rSI did not improve the agreement between individual raters .


However , enhancing visual assessment with rSI measurements can provide reassurance to local investigators in cases of uncertainty .


Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus ( HCV ) genotype 2 or 3 infection produces a sustained virologic response ( SVR ) in 70 % -80 % of patients .


We performed a randomized , double-blind , phase 2b study to assess whether adding daclatasvir , a nonstructural protein 5A ( NS5A ) inhibitor that is active against these genotypes , improves efficacy and shortens therapy .


Patients with HCV genotype 2 or 3 infection ( n = 151 ) , enrolled at research centers in North America , Europe , or Australia , were assigned randomly to groups given 12 or 16 weeks of daclatasvir ( 60 mg once daily ) , or 24 weeks of placebo , each combined with peginterferon alfa-2a and ribavirin .


Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response .


The primary end point was SVR at 24 weeks after treatment ( SVR24 ) .


Baseline characteristics were similar among patients within each HCV genotype group .


However , the 80 patients with HCV genotype 3 , compared with the 71 patients with HCV genotype 2 , were younger ( mean age , 45 vs 53 y , respectively ) , and a larger proportion had cirrhosis ( 23 % vs 1 % , respectively ) .


Among patients with HCV genotype 2 infection , an SVR24 was achieved by 83 % , 83 % , and 63 % of those in the daclatasvir 12-week group , the daclatasvir 16-week group , or the placebo group , respectively ; among patients with HCV genotype 3 infection , an SVR24 was achieved by 69 % , 67 % , and 59 % of patients in these groups , respectively .


Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3 .


In both daclatasvir arms for both HCV genotypes , the lower bound of the 80 % confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20 % , establishing noninferiority .


Safety findings were similar among groups , and were typical of those expected from peginterferon alfa and ribavirin therapy .


Twelve or 16 weeks of treatment with daclatasvir , in combination with peginterferon alfa-2a and ribavirin , is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections .


Daclatasvir-containing regimens could reduce the duration of therapy for these patients .


Clinicaltrials.gov number : NCT01257204 .


In patients with chronic lymphoid leukemia ( CLL ) or small lymphocytic lymphoma ( SLL ) , a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome .


We evaluated the efficacy of ibrutinib , a covalent inhibitor of Bruton 's tyrosine kinase , in patients at risk for a poor outcome .


In this multicenter , open-label , phase 3 study , we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab .


The primary end point was the duration of progression-free survival , with the duration of overall survival and the overall response rate as secondary end points .


At a median follow-up of 9.4 months , ibrutinib significantly improved progression-free survival ; the median duration was not reached in the ibrutinib group ( with a rate of progression-free survival of 88 % at 6 months ) , as compared with a median of 8.1 months in the ofatumumab group ( hazard ratio for progression or death in the ibrutinib group , 0.22 ; P < 0.001 ) .


Ibrutinib also significantly improved overall survival ( hazard ratio for death , 0.43 ; P = 0.005 ) .


At 12 months , the overall survival rate was 90 % in the ibrutinib group and 81 % in the ofatumumab group .


The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group ( 42.6 % vs. 4.1 % , P < 0.001 ) .


An additional 20 % of ibrutinib-treated patients had a partial response with lymphocytosis .


Similar effects were observed regardless of whether patients had a chromosome 17p13 .1 deletion or resistance to purine analogues .


The most frequent nonhematologic adverse events were diarrhea , fatigue , pyrexia , and nausea in the ibrutinib group and fatigue , infusion-related reactions , and cough in the ofatumumab group .


Ibrutinib , as compared with ofatumumab , significantly improved progression-free survival , overall survival , and response rate among patients with previously treated CLL or SLL .


( Funded by Pharmacyclics and Janssen ; RESONATE ClinicalTrials.gov number , NCT01578707 . )


Prior evidence suggests that high-calcium intake influences postprandial appetite and insulinemia , possibly due to elevated incretins .


In vitro and ex vivo models demonstrate that extracellular calcium and protein synergistically enhance secretion of incretins .


This is yet to be shown in humans .


This study was designed to assess energy intake compensation in response to protein and calcium ingestion .


Twenty healthy adults ( 13 men ; 7 women ) completed 4 trials in a randomized , double-blind crossover design separated by 48 h.


During the trials , each participant consumed a low-calcium and low-protein control preload [ ( CON ) ; 4 g and 104 mg , respectively ] , a high-protein preload ( PRO ; 29 g ) , a high-calcium preload ( CAL ; 1170 mg ) , or a high-protein and high-calcium preload ( PROCAL ) .


Blood samples were collected at baseline and 15 , 30 , 45 , and 60 min after preload ingestion to determine insulin and incretin hormone concentrations .


Energy intake was assessed by a homogenous test meal 60 min after the preload .


Visual analog scales were completed immediately before blood sampling to assess subjective appetite sensations .


Relative to the CON , the PRO produced 100 % ( 95 % CI : 85 % , 115 % ) energy compensation , whereas the CAL produced significant overcompensation [ 118 % ( 95 % CI : 104 % , 133 % ) ] , which was significantly more positive than with the PRO ( P < 0.05 ) .


The PROCAL resulted in energy compensation of 109 % ( 95 % CI : 95 % , 123 % ) , which tended to be greater than with the PRO ( P = 0.06 ) .


The mean difference in appetite sensations relative to the CON was not significantly different between the PRO ( -3 mm ; 95 % CI : -8 , 3 mm ) , CAL ( -5 mm ; 95 % CI : -9 , 0 mm ) , and PROCAL ( -5 mm ; 95 % CI : -10 , -1 mm ) ( P > 0.05 ) .


The addition of protein to a preload results in almost perfect energy compensation , whereas the addition of calcium , with or without protein , suppresses appetite and produces overcompensation of subsequent energy intake .


The role of circulating insulin and incretin concentrations in these responses , however , remains unclear .


This trial was registered at clinicaltrials.gov as NCT01986036 .


Chronic back pain ( CBP ) represents a significant public health problem .


As one of the most common causes of disability and sick leave , there is a need to develop cost-effective ways , such as Internet-based interventions , to help empower patients to manage their disease .


Research has provided evidence for the effectiveness of Internet-based interventions in many fields , but it has paid little attention to the reasons why they are effective .


This study aims to assess the impact of interactive sections of an Internet-based self-management intervention on patient empowerment , their management of the disease , and , ultimately , health outcomes .


A total of 51 patients were recruited through their health care providers and randomly assigned to either an experimental group with full access to the Internet-based intervention or a control group that was denied access to the interactive sections and knew nothing thereof .


The intervention took 8 weeks .


A baseline , a mid-term after 4 weeks , and a final assessment after 8 weeks measured patient empowerment , physical exercise , medication misuse , and pain burden .


All patients completed the study .


Overall , the intervention had a moderate effect ( F1 .52 = 2.83 , P = .03 , ( 2 ) = 0.30 , d = 0.55 ) .


Compared to the control group , the availability of interactive sections significantly increased patient empowerment ( midterm assessment : mean difference = +1.2 , P = .03 , d = 0.63 ; final assessment : mean difference = +0.8 , P = .09 , d = 0.44 ) and reduced medication misuse ( midterm assessment : mean difference = -1.5 , P = .04 , d = 0.28 ; final assessment : mean difference = -1.6 , P = .03 , d = -0.55 ) in the intervention group .


Both the frequency of physical exercise and pain burden decreased , but to equal measures in both groups .


Results suggest that interactive sections as part of Internet-based interventions can positively alter patients ' feelings of empowerment and help prevent medication misuse .


Detrimental effects were not observed .


ClinicalTrials.gov : NCT02114788 ; http://www.clinicaltrials.gov/ct2/show/NCT02114788 ( Archived by WebCite at http://www.webcitation.org/6ROXYVoPR ) .


The role of low-intensity pulsed ultrasound ( LIPUS ) in the management of fractures remains controversial .


The purpose of this study was to assess the feasibility of a definitive trial to determine the effect of LIPUS on functional and clinical outcomes in tibial fractures managed operatively .


We conducted a multicenter , concealed , blinded randomized trial of 51 skeletally mature adults with operatively managed tibial fractures who were treated with either LIPUS or a sham device .


All participating centers were located in Canada and site investigators were orthopedic surgeons specializing in trauma surgery .


The goals of our pilot study were to determine recruitment rates in individual centers , investigators ' ability to adhere to study protocol and data collection procedures , our ability to achieve close to 100 % follow-up rates , and the degree to which patients were compliant with treatment .


Patients were followed for one year and a committee ( blinded to allocation ) adjudicated all outcomes .


The committee adjudicators were experienced ( 10 or more years in practice ) orthopedic surgeons with formal research training , specializing in trauma surgery .


Our overall rate of recruitment was approximately 0.8 patients per center per month and site investigators successfully adhered to the study protocol and procedures .


Our rate of follow-up at one year was 84 % .


Patient compliance , measured by an internal timer in the study devices , revealed that 39 ( 76 % ) of the patients were fully compliant and 12 ( 24 % ) demonstrated a greater than 50 % compliance .


Based on patient feedback regarding excessive questionnaire burden , we conducted an analysis using data from another tibial fracture trial that revealed the Short Musculoskeletal Function Assessment ( SMFA ) dysfunction index offered no important advantages over the SF-36 Physical Component Summary ( PCS ) score .


No device-related adverse events were reported .


Our pilot study identified key issues that might have rendered a definitive trial unfeasible .


By modifying our protocol to address these challenges we have enhanced the feasibility of a definitive trial to explore the effect of LIPUS on tibial fracture healing .


The TRUST definitive trial was registered at ClinicalTrials.gov on 21 April 2008 ( identifier : NCT00667849 ) .


An inactivated poliovirus vaccine ( IPV ) based on attenuated poliovirus strains ( Sabin-1 , -2 and -3 ) was developed for technology transfer to manufacturers in low - and middle-income countries in the context of the global polio eradication initiative .


Safety and immunogenicity of Sabin-IPV ( sIPV ) was evaluated in a double-blind , randomized , controlled , dose-escalation trial in the target population .


Healthy infants ( n = 20/group ) aged 56-63 days , received a primary series of three intramuscular injections with low - , middle - or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains ( wIPV ) .


Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations .


The incidence of local and systemic reactions was comparable with the wIPV .


Seroconversion rates after three vaccinations were 100 % for type 2 and type 3 polioviruses ( both Sabin and wild strains ) and 95-100 % for type 1 polioviruses .


Median titers were high in all groups .


Titers were well above the log2 ( titer ) correlated with protection ( = 3 ) for all groups .


Median titers for Sabin-2 were 9.3 ( range 6.8-11 .5 ) in the low-dose sIPV group , 9.2 ( range 6.8-10 .2 ) in the low-dose adjuvanted sIPV group and 9.8 ( range 5.5-15 .0 ) in the wIPV group , Median titers against MEF-1 ( wild poliovirus type 2 ) were 8.2 ( range 4.8-10 .8 ) in the low-dose sIPV group , 7.3 ( range 4.5-10 .2 ) in the low-dose adjuvanted Sabin-IPV group and 10.3 ( range 8.5-17 .0 ) in the wIPV group .


For all poliovirus types the median titers increased with increasing dose levels .


sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels , and comparable with the wIPV .


EudraCTnr : 2011-003792-11 , NCT01709071 .


Laparoscopic magnetic sphincter augmentation ( MSA ) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease ( GERD ) .


Initial studies have demonstrated MSA to be safe and effective .


However , no direct comparison between MSA and laparoscopic Nissen fundoplication ( LNF ) , the gold standard surgical therapy for GERD , has been performed .


A single institution , case-control study was conducted of MSA performed from 2012 to 2013 and a cohort of LNF matched for age , gender , and hiatal hernia size .


MSA and LNF were both effective treatments for reflux with 75 and 83 % of patients , respectively , reporting resolution of GERD at short-term follow-up .


Dysphagia was common following both MSA and LNF , but severe dysphagia requiring endoscopic dilation was more frequent after MSA ( 50 vs. 0 % , p = 0.01 ) .


Need for dilation did not correlate with size of the LINX device or any other examined patient factors .


A trend toward decreased adverse GI symptoms of bloating , flatulence , and diarrhea was seen after MSA compared to LNF ( 0 vs. 33 % ) .


MSA had a shorter operative time ( 64 vs. 90 min , p < 0.01 ) but other peri-operative outcomes , including pain , morbidity , and re-admissions were equivalent to LNF .


MSA patients were more likely to be self-referred ( 58 vs. 0 % , p < 0.001 ) .


MSA and LNF are both effective and safe treatments for GERD ; however , severe dysphagia requiring endoscopic intervention is more common with MSA .


Other adverse GI side effects may be less frequent after MSA .


Consideration should be paid to these distinct post-operative symptom profiles when selecting a surgical therapy for reflux disease .


The aim of this trial was to compare the rates of patency achieved by cutting and conventional balloon angioplasty to treat hemodialysis access stenoses .


End-stage renal failure patients ( at three tertiary referral centers ) with significant hemodialysis access stenoses were prospectively randomized to have percutaneous transluminal angioplasty ( PTA ) by either cutting or conventional balloons .


Patients with more than one hemodynamically significant stenosis were excluded .


Kaplan-Meier method was used to compare the primary assisted patency rates for the two groups .


The study randomized 623 patients into two groups , and the duration of follow-up was 15 3 months .


In the cutting balloon angioplasty group , the clinical success rate was 89 % ( 282 of 316 stenoses ) .


In the conventional balloon angioplasty group , the clinical success rate was 86 % ( 265 of 307 stenoses ; P = .637 ) .


Assisted primary patency for cutting PTA was statistically significantly higher at 6 months and 1 year ( 86 % and 63 % ) than that for conventional PTA ( 56 % and 37 % , respectively ; P = .037 ) in the treatment of stenosis of the graft-to-vein anastomosis .


In the venous stenosis subgroup , equivalent primary assisted patency at 6 months and 1 year was observed for cutting PTA ( 84 % and 55 % ) and conventional PTA ( 70 % and 46 % , respectively ; P = .360 ) .


In the intragraft stenosis subgroup , primary assisted patency was equivalent at 6 months and 1 year for cutting PTA ( 67 % and 39 % ) and conventional PTA ( 62 % and 49 % , respectively ; P = .371 ) .


In the arterial anastomotic stenosis subgroup , assisted primary patency at 6 months and 1 year was equivalent for cutting PTA ( 70 % and 30 % ) and conventional PTA ( 75 % and 33 % , respectively ; P = .921 ) .


Cutting balloon angioplasty proved to be a safe and effective treatment of graft-to-vein anastomotic stenosis , with significantly higher patency than that of conventional balloon angioplasty .


There is strong evidence of an association between chronic kidney disease ( CKD ) and cardiovascular disease .


To date , however , proof that a reduction in glomerular filtration rate ( GFR ) is a causative factor in cardiovascular disease is lacking .


Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation , which invariably confound the association between CKD and cardiovascular disease .


There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis , rather than atherosclerotic disease , mediate the adverse cardiovascular effects of CKD .


The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion .


At the same time , the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group .


The reduction in GFR accompanying uninephrectomy causes ( 1 ) a pressure-independent increase in aortic stiffness ( aortic pulse wave velocity ) and ( 2 ) an increase in peripheral and central blood pressure .


This is a prospective , multicenter , longitudinal , parallel group study of 440 living kidney donors and 440 healthy controls .


All controls will be eligible for living kidney donation using current UK transplant criteria .


Investigations will be performed at baseline and repeated at 12 months in the first instance .


These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis , office blood pressure , 24-hour ambulatory blood pressure monitoring , and a series of biomarkers for cardiovascular and bone mineral disease .


These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease .


This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted .


In addition , this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease , namely , blood pressure and arterial stiffness .


If any adverse effects are detected , these may be potentially reversed with the early introduction of targeted therapy .