Risk of inflammatory and lens-induced adverse events also increase over time during CW .


Daily irrigation with sterile saline solution did not mitigate increases in epithelial permeability or decrease risk of adverse events .


We aimed to detail the effects of hydroxyethyl starch ( HES ) vs. Ringer 's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0 .42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock ( 6S ) trial .


In all 798 randomised patients , we assessed the incidence and effect on mortality of acute kidney injury ( AKI ) in the HES vs. Ringer 's acetate groups using the Kidney Disease : Improving Global Outcome criteria .


We also assessed the intervention effect on time to and duration of renal replacement therapy ( RRT ) .


At baseline , the intervention groups were similar .


The maximal AKI stage was higher in the HES vs. Ringer 's group within the first 5 days after randomisation ( P = 0.03 ) , the average difference being 0.2 points ( P < 0.01 ) .


An increase in AKI stage was associated with mortality ( hazard ratio ( HR ) 1.35 ; 95 % CI 1.22 to 1.49 ; P < 0.01 ) .


Significantly , more patients in the HES group received RRT within the first 5 days ( P = 0.01 ) , and the time to initiation of RRT was also shorter compared with the Ringer 's group ( HR 1.40 ; 95 % CI 1.01-1 .93 ; P = 0.04 ) .


The intervention effect of HES on mortality was reduced when adjusting for AKI stage as a time-dependent covariate ( P = 0.15 ) .


In patients with severe sepsis , HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days .


The increased mortality observed with HES may have been partly mediated through acute kidney impairment .


To compare the efficacy and safety of Tripterygium wilfordii Hook F ( TwHF ) with methotrexate ( MTX ) in the treatment of active rheumatoid arthritis ( RA ) .


Design : a multicentre , open-label , randomised controlled trial .


All patients were assessed by trained investigators who were unaware of the therapeutic regimen .


207 patients with active RA were randomly allocated ( 1:1:1 ) to treatment with MTX 12.5 mg once a week , or TwHF 20mg three times a day , or the two in combination .


At week 12 , if reduction of the 28-joint count Disease Activity Score ( DAS28 ) was < 30 % in the monotherapy groups , the patient was switched to MTX+T wHF .


The primary efficacy point was the proportion of patients achieving an American College of Rheumatology ( ACR ) 50 response at week 24 .


174/207 ( 84.1 % ) patients completed 24weeks of the trial .


In an intention-to-treat analysis , the proportion of patients reaching the ACR50 response criteria was 46.4 % ( 32/69 ) , 55.1 % ( 38/69 ) and 76.8 % ( 53/69 ) , respectively , in the MTX , TwHF and MTX+T wHF groups ( TwHF vs MTX monotherapy , p = 0.014 ; MTX+T wHF vs MTX monotherapy , p < 0.001 ) .


Similar statistically significant patterns at week 24 were found for ACR20 , ACR70 , clinical Disease Activity Index good responses , EULAR good response , remission rate and low disease activity rate .


Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm ( p < 0.05 ) , though no significant difference was found among the treatment arms ( p > 0.05 ) .


The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis .


Seven , three and five women in the TwHF , MTX and combination groups , respectively , developed irregular menstruation ( TwHF vs MTX monotherapy , p = 0.216 ) .


TwHF monotherapy was not inferior to , and MTX+T wHF was better than , MTX monotherapy in controlling disease activity in patients with active RA .


NCT01613079 .


Fibromyalgia is a chronic musculoskeletal pain syndrome characterized by a broad spectrum of manifestations .


Patients with fibromyalgia frequently suffer from manifestations similar to those experienced by patients with gluten-related disorders raising the possibility that some patients with fibromyalgia could suffer from underlying gluten sensitivity .


This study aims to assess whether avoiding gluten among patients with fibromyalgia and gluten sensitivity is beneficial .


Adult patients with fibromyalgia presenting gluten sensitivity symptoms are randomly allocated to receive gluten-free diet or hypocaloric diet for 24 weeks .


The primary outcome measure is the mean change in the number of experienced gluten sensitivity symptoms .


Secondary outcome measures include the mean changes in the body mass index , Revised Fibromyalgia Impact Questionnaire , Pittsburgh Sleep Quality Index , Brief Pain Inventory , Beck Depression Inventory-II , State-Trait Anxiety Inventory , Short-Form Health Survey and Patient Global Impression Scale of Severity .


Other secondary outcome measures include the frequency of potential adverse events and the proportion of responders according to the Patient Global Impression Scale of Improvement .


Previous studies assessing dietary interventions in fibromyalgia primarily evaluated their effects on the severity and impact of fibromyalgia symptoms and pain .


The current study is the first to evaluate the effects of gluten-free diet on the gluten sensitivity symptoms experienced by patients with fibromyalgia .


The results of this study will contribute to a better understanding of the potential role of gluten sensitivity in fibromyalgia .


Primary medication nonadherence ( PMN ) , defined as patients not picking up an initial prescription , can limit the effectiveness of therapy for chronic conditions .


Effective interventions to reduce PMN have not been widely studied or implemented .


To evaluate the ability of an additional nurse-directed telephone intervention to reduce PMN in a cohort of patients with persistent nonadherence after repeated pharmacy-based outreach .


Patients in the Geisinger Health System receiving new ( i.e. , initially prescribed ) prescriptions sent to CVS pharmacies for medications treating asthma , hypertension , diabetes , or hyperlipidemia were identified .


As part of existing programs , all patients received 2 automated and 1 live call from CVS pharmacies encouraging them to pick up their prescriptions ; those who had canceled their prescriptions or had not picked them up after the 3 pharmacy interventions were eligible for this study .


Patients were then randomized , and the intervention group received telephone outreach from a nursing call center to assess reasons for PMN and encourage pickup of prescriptions , with up to 3 attempts to reach each patient .


Medication pickup rates were compared across the intervention and control groups .


Initial PMN rates in the overall population were 6 % , lower than previously observed in other studies .


A total of 290 patients had not picked up their prescriptions after 3 calls from the pharmacy and were enrolled in the study : 142 in the intervention group and 148 controls .


The intervention did not change the rate at which patients picked up their prescriptions : 25 % of intervention patients did so compared with 24 % of control patients .


Multivariate models adjusting for patient characteristics and medication classes did not change the results .


In a population of patients who had not picked up new prescriptions after 3 calls from the pharmacy , additional nurse-directed outreach did not improve primary medication adherence .


Re-engagement with the prescribing clinician may be needed to improve adherence in this patient population .


The low rate of PMN in the overall population differed from prior studies in this setting and others and should be assessed in future research .


Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor ( G-CSF ) after acute myocardial infarction .


Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking .


Patients with left ventricular ejection fraction less than 45 % after anterior-wall myocardial infarction were treated with G-CSF ( 10 g/kg daily for 4 days ) or placebo .


After initial randomization of 86 patients , 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography .


Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups : 34.8 % ( 95 % confidence interval [ CI ] 32.6 % -37.0 % ) v. 36.4 % ( 95 % CI 33.5 % -39.2 % ) at baseline and 39.8 % ( 95 % CI 36.2 % -43.4 % ) v. 43.1 % ( 95 % CI 39.2 % -47.0 % ) at 6 weeks .


However , G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo ( 40.8 % [ 95 % CI 37.4 % -44.2 % ] v. 46.0 % [ 95 % CI 42.7 % -44.3 % ] ) .


Both groups had improved left ventricular function , but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo ( 5.7 [ 95 % CI 3.4-8 .1 ] percentage points v. 9.2 [ 95 % CI 6.3-12 .1 ] percentage points ) .


One or more of a composite of several major adverse cardiac events occurred in 8 patients ( 19 % ) within each group , with similar rates of target-vessel revascularization .


In patients with moderate left ventricular dysfunction following anterior-wall infarction , G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events .


Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety .


ClinicalTrials.gov , no .


NCT00394498 .


To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density ( ECD ) after penetrating keratoplasty ( PK ) in the Cornea Donor Study .


Multicenter , prospective , double-masked , controlled clinical trial .


One thousand ninety subjects undergoing PK for a moderate risk condition , principally Fuchs ' dystrophy or pseudophakic or aphakic corneal edema , were enrolled by 105 surgeons from 80 clinical sites in the United States .


Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors .


Donor and recipient diabetes status was determined from existing medical records .


Images of the central endothelium were obtained before surgery ( baseline ) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD .


Time to graft failure ( regraft or cloudy cornea for 3 consecutive months ) and ECD .


There was no statistically significant association of donor diabetes history with 10-year graft failure , baseline ECD , 10-year ECD , or ECD values longitudinally over time in unadjusted analyses , nor after adjusting for donor age and other significant covariates .


The 10-year graft failure rate was 23 % in the 199 patients receiving a cornea from a donor with diabetes versus 26 % in the 891 patients receiving a cornea from a donor without diabetes ( 95 % confidence interval for the difference , -10 % to 6 % ; unadjusted P = 0.60 ) .


Baseline ECD ( P = 0.71 ) , 10-year ECD ( P > 0.99 ) , and changes in ECD over 10 years ( P = 0.86 ) were similar comparing donor groups with and without diabetes .


The study results do not suggest an association between donor diabetes and PK outcome .


However , the assessment of donor diabetes was imprecise and based on historical data only .


The increasing frequency of diabetes in the aging population in the United States affects the donor pool .


Thus , the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty , or both , warrants further study with more precise measures of diabetes and its complications .


Although high-sensitivity cardiac troponin ( hs-cTn ) substantially improves the early detection of myocardial injury , it lacks specificity for acute myocardial infarction ( MI ) .


In suspected non-ST-elevation MI , invasive coronary angiography ( ICA ) remains necessary to distinguish between acute MI and noncoronary myocardial disease ( eg , myocarditis ) , unnecessarily subjecting the latter to ICA and associated complications .


This trial investigates whether implementing cardiovascular magnetic resonance ( CMR ) or computed tomography angiography ( CTA ) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease , thereby preventing unnecessary ICA .


In this prospective , single-center , randomized controlled clinical trial , 321 consecutive patients with acute chest pain , elevated hs-cTnT , and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies : ( 1 ) CMR , or ( 2 ) CTA early in the diagnostic process , or ( 3 ) routine clinical management .


In the 2 investigational arms of the study , results of CMR or CTA will guide further clinical management .


It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management , and unnecessary ICA will be prevented .


The primary end point is the total number of patients undergoing ICA during initial admission .


Secondary end points are 30-day and 1-year clinical outcome ( major adverse cardiac events and major procedure-related complications ) , time to final diagnosis , quality of life , and cost-effectiveness .


The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management , with no detrimental effect on clinical outcome .


Biomarkers can provide objective measures of dietary exposure , but their relationship with dietary intake in different populations needs to be characterized .


This study aimed to determine the association between C14 :0 , C15 :0 and C17 :0 and children 's dairy fat intake , and to ascertain whether these fatty acids can be used as biomarkers for detecting change in dairy fat intake .


Data from a randomized controlled trial ( 114 healthy children of 4-13 years of age ) was used .


The intervention was a replacement of regular-fat dairy foods with reduced-fat or low-fat items .


Serum fatty acid composition was measured and dairy intake was assessed via 3 24-hour diet recalls at baseline and at 12 weeks ( the end of the intervention ) .


Correlation analysis was used to evaluate the relationship between dietary intake and fatty acids at baseline and at week 12 , and for the change in biomarkers and diet between these time points .


Total dairy fat intake correlated with C14 :0 , C15 :0 and C17 :0 at baseline ( n = 114 ; r = 0.24 ; r = 0.42 ; r = 0.25 respectively , all p < 0.05 ) , but not at week 12 .


The change in the total amount of dairy fat ( g/day ) after 12 weeks was associated with a change in serum C15 :0 ( n = 59 ; r = 0.27 ; p = 0.04 ) .


C15 :0 is a useful biomarker of dairy fat intake in children and can detect short-term changes in the absolute intake of dairy fat .


The intravenous administration of scopolamine produces rapid antidepressant effects .


Generally , failing multiple previous antidepressant trials is associated with a poor prognosis for response to future medications .


This study evaluated whether treatment history predicts antidepressant response to scopolamine .


Treatment resistant patients ( 2 failed medication trials ) ( n = 31 ) and treatment nave patients ( no exposure to psychotropic medication ) ( n = 31 ) with recurrent major depressive or bipolar disorder participated in a double-blind , placebo-controlled , crossover clinical trial .


Following a placebo lead-in , participants randomly received P/S or S/P ( P = 3 placebo ; S = 3 scopolamine ( 4ug/kg ) sessions 3 to 5 days apart ) .


The Montgomery-Asberg Depression Rating Scale ( MADRS ) was the primary outcome measure .


A linear mixed model was used to examine the interaction between clinical response and treatment history , adjusting for baseline MADRS .


Treatment resistant and treatment nave subjects combined responded significantly to scopolamine compared to placebo ( F = 15.06 , p < 0.001 ) .


Reduction in depressive symptoms was significant by the first post-scopolamine session ( F = 42.75 , p < 0.001 ) .


A treatment history by scopolamine session interaction ( F = 3.37 , p = 0.04 ) indicated treatment nave subjects had lower MADRS scores than treatment resistant patients ; this was significant after the second scopolamine infusion ( t = 2.15 , p = 0.03 ) .


Post-hoc analysis : Also , we used a single regimen to administer scopolamine , and smokers were excluded from the sample , limiting generalizability .


Treatment nave and treatment resistant patients showed improved clinical symptoms following scopolamine , while those who were treatment nave showed greater improvement .


Scopolamine rapidly reduces symptoms in both treatment history groups , and demonstrates sustained improvement even in treatment resistant patients .


Heavy drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers , for whom tailored smoking cessation therapies are not yet available .


The present study used a double-blind , randomized , 22 medication design , testing varenicline alone ( VAR ; 1mg twice daily ) , naltrexone alone ( NTX ; 25mg once daily ) , varenicline plus naltrexone , and placebo for effects on neural activation to cigarette cues in a sample ( n = 40 ) of heavy drinking daily smokers ( 10 cigarettes/day ) .


All participants were tested after a 10-12-day titration period designed to reach steady state on the target medication .


Participants underwent functional neuroimaging ( fMRI ) for examination of brain responses to visual smoking-related ( vs. neutral ) cues .


Region of interest ( ROI ) analyses of brain responses to Cigarette vs. Neutral Cues indicated that the combination of VAR+NTX was associated with reduced activation of the bilateral anterior cingulate cortex as compared to placebo and to NTX alone .


Exploratory whole-brain analyses also indicated significant differences in brain activation during cigarette cues in the active medications versus placebo condition .


All medications suppressed left nucleus accumbens activation relative to placebo , suggesting the possibility that both medications , either alone or in combination , reduce neural signals associated with appetitive behavior .


Although preliminary , these neuroimaging findings indicate that clinical studies of the combination of VAR+NTX for heavy drinkers trying to quit smoking may be warranted .


Poor prognosis germ-cell tumours are only cured in about half of patients .


We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with germ-cell tumours .


In this phase 3 , multicentre , randomised trial , patients were enrolled from France ( 20 centres ) , USA ( one centre ) , and Slovakia ( one centre ) .


Patients were eligible if they were older than 16 years , had evidence of testicular , retroperitoneal , or mediastinal non-seminomatous germ cell tumours based on histological findings or clinical evidence and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor prognosis criteria .


After one cycle of BEP ( intravenous cisplatin [ 20 mg/m ( 2 ) per day for 5 days ] , etoposide [ 100 mg/m ( 2 ) per day for 5 days ] , and intramuscular or intravenous bleomycin [ 30 mg per day on days 1 , 8 , and 15 ] ) , patients ' human chorionic gonadotropin and alfa-fetoprotein concentrations were measured at day 18-21 .


Patients with a favourable decline in human chorionic gonadotropin and alfa-fetoprotein continued BEP ( Fav-BEP group ) for 3 additonal cycles , whereas patients with an unfavourable decline were randomly assigned ( 1:1 ) to receive either BEP ( Unfav-BEP group ) or a dose-dense regimen ( Unfav-dose-dense group ) , consisting of intravenous paclitaxel ( 175 mg/m ( 2 ) over 3 h on day 1 ) before BEP plus intravenous oxaliplatin ( 130 mg/m ( 2 ) over 3 h on day 10 ; two cycles ) , followed by intravenous cisplatin ( 100 mg/m ( 2 ) over 2 h on day 1 ) , intravenous ifosfamide ( 2 g/m ( 2 ) over 3 h on days 10 , 12 , and 14 ) , plus mesna ( 500 mg/m ( 2 ) at 0 , 3 , 7 and 11 h ) , and bleomycin ( 25 units per day , by continuous infusion for 5 days on days 10-14 ; two cycles ) , with granulocyte-colony stimulating factor ( lenograstim ) support .


Centrally blocked computer-generated randomisation stratified by centre was used .


The primary endpoint was progression-free survival and the efficacy analysis was done in the intention-to-treat population .


The planned trial accrual was completed in May , 2012 , and follow-up is ongoing .


This study is registered with ClinicalTrials.gov , number NCT00104676 .


Between Nov 28 , 2003 , and May 16 , 2012 , 263 patients were enrolled and 254 were available for tumour marker assessment .


Of these 51 ( 20 % ) had a favourable marker assessment , and 203 ( 80 % ) had an unfavourable tumour marker decline ; 105 were randomly assigned to the Unfav-dose-dense group and 98 to the Unfav-BEP group .


3-year progression-free survival was 59 % ( 95 % CI 49-68 ) in the Unfav-dose-dense group versus 48 % ( 38-59 ) in the Unfav-BEP group ( HR 066 , 95 % CI 044-100 , p = 005 ) .


3-year progression-free survival was 70 % ( 95 % CI 57-81 ) in the Fav-BEP group ( HR 066 , 95 % CI 049-088 , p = 001 for progression-free survival compared with the Unfav-BEP group ) .


More grade 3-4 neurotoxic events ( seven [ 7 % ] vs one [ 1 % ] ) and haematotoxic events occurred in the Unfav-dose-dense group compared with in the Unfav-BEP group ; there was no difference in grade 1-2 febrile neutropenia ( 18 [ 17 % ] vs 18 [ 18 % ] ) or toxic deaths ( one [ 1 % ] in both groups ) .


Salvage high-dose chemotherapy plus a stem-cell transplant was required in six ( 6 % ) patients in the Unfav-dose-dense group and 16 ( 16 % ) in the Unfav-BEP group .


Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline .


Institut National du Cancer ( Programme Hospitalier de Recherche Clinique ) .


Diminished diuretic response is common in patients with acute heart failure , although a clinically useful definition is lacking .


Our aim was to investigate a practical , workable metric for diuretic response , examine associated patient characteristics and relationships with outcome .


We examined diuretic response ( defined as weight kg/40 mg furosemide ) in 1745 hospitalized acute heart failure patients from the PROTECT trial .


Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response , following sensitivity analyses .


We investigated predictors of diuretic response and relationships with outcome .


The median diuretic response was -0.38 ( -0.80 to -0.13 ) kg/40 mg furosemide .


Poor diuretic response was independently associated with low systolic blood pressure , high blood urea nitrogen , diabetes , and atherosclerotic disease ( all P < 0.05 ) .


Worse diuretic response independently predicted 180-day mortality ( HR : 1.42 ; 95 % CI : 1.11-1 .81 , P = 0.005 ) , 60-day death or renal or cardiovascular rehospitalization ( HR : 1.34 ; 95 % CI : 1.14-1 .59 , P < 0.001 ) and 60-day HF rehospitalization ( HR : 1.57 ; 95 % CI : 1.24-2 .01 , P < 0.001 ) in multivariable models .


The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship .


Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components ( weight loss and diuretic dose ) in this population , while providing a less biased , more easily interpreted signal .


Worse diuretic response was associated with more advanced heart failure , renal impairment , diabetes , atherosclerotic disease and in-hospital worsening heart failure , and predicts mortality and heart failure rehospitalization in this post hoc , hypothesis-generating study .


Calcium pyrophosphate deposition ( CPPD ) may cause severe arthropathy , major joint destruction and treatment options are limited .


The aim of this study was to test the therapeutic efficacy of methotrexate ( MTX ) in chronic or recurrent CPPD arthropathy .


Patients with CPPD arthropathy were randomized to receive either weekly subcutaneous injections of 15 mg/week of MTX or placebo ( PBO ) for three months , in a double-blind , crossover randomized controlled trial .


Inclusion criteria comprised definite CPPD disease , recurrent arthritis or persistent polyarthritis , and an insufficient response to NSAIDs , glucocorticoids or colchicine .


The primary outcome was an improvement in the disease activity scores based on 44 joints ( DAS44 ) .


The analysis was performed on an intent-to-treat basis .


We randomized 26 patients , and compared 25 treatment periods on MTX with 21 treatment periods on PBO .


Baseline characteristics were balanced between the groups .


The evolution of the DAS44 was not statistically significantly different between groups ( median DAS44 decreased by -0.08 on MTX versus -0.13 on PBO , after three months , P = 0.44 ) .


Furthermore , pain levels remained stable in both groups ( median change in VAS Pain -1 unit on MTX and 0 on PBO , P = 0.43 ) , and none of the secondary outcomes was significantly different between the two groups .


Minor adverse events ( AE ) did not differ in frequency between the groups , but the only serious AE occurred on MTX ( bicytopenia ) .


The results of this trial with MTX in this older population with chronic or recurrent CPPD arthropathy suggest no strong effect of MTX on disease activity .


EudraCT No : 2007-003479-37 .


Registered 26 April 2008 .


Systolic hypertension is the most common form of hypertension in elderly patients .


There is increasing evidence that measurement of central aortic pressure ( CAP ) better accounts for cardiovascular risk than brachial blood pressure ( BP ) .


The Aliskiren for GEriatric LowEring of SyStolic hypertension ( AGELESS ) study in elderly patients with systolic hypertension showed that aliskiren-based therapy provided greater reductions in peripheral BP than ramipril-based therapy over 12 and 36 weeks of treatment .


Here , we present CAP results in a substudy of elderly patients from the AGELESS study .


This was a post hoc analysis of a 36-week , randomized , double-blind , parallel-group , active-controlled , optional-titration study in patients 65 years of age with systolic BP 140 mmHg .


Changes in both central and peripheral BP and pulse pressure ( PP ) and changes in systolic and PP amplification ratios from baseline to the week 36 end point with aliskiren-based versus ramipril-based therapy were analyzed .


Of the 901 patients randomized in the overall study , 154 patients ( aliskiren , n = 78 ; ramipril , n = 76 ) had CAP data .


Numerically comparable reductions were seen for central aortic systolic pressure ( CASP ) in aliskiren-based therapy ( baseline : 143.715.0 ; week 36 : -20.316.2 ) compared with ramipril-based therapy ( baseline : 147.911.9 ; week 36 : -20.714.6 ) .


However , for the change in central aortic diastolic pressure , the least squares mean between-treatment difference ( -3.6 mmHg [ 95 % confidence interval , -6.76 , -0.43 ; P = 0.0263 ] ) was in favor of aliskiren , while the other changes were comparable between the two groups with a trend in favor of aliskiren for CASP as well ( -2.6 mmHg [ 95 % confidence interval , -7.38 , 2.19 ; P = 0.2855 ) ] .


Correlation coefficients for change from baseline between CASP and systolic BP and between central aortic pulse pressure and PP ( r = 0.8 , P < 0.0001 ) were highly significant .


Aliskiren-based therapy provides comparable reductions in CASP to ramipril-based therapy .


Although the results did not reach statistical significance , these findings , when coupled with those of the main study , suggest that aliskiren may offer effective control of central BP in elderly patients with systolic hypertension and may be a good alternative to ramipril .


Conduct a pilot trial testing whether a brief cognitive-behavioral ( CB ) group reduced depressive symptoms and secondary outcomes relative to bibliotherapy and brochure controls in college students with elevated depressive symptoms .


82 college students ( M age = 19.0 , SD = 0.9 ; 70 % female , 80 % White ) with elevated self-assessed depressive symptoms were randomized to a 6-session CB group , bibliotherapy , or educational brochure control condition , completing assessments at pretest , posttest , and at 6 - and 12-month follow-up .


Planned contrasts found no significant effects for CB group on depressive symptoms compared to either bibliotherapy or brochure controls at posttest ( d = -.08 and .06 , respectively ) or over follow-up ( d = -.04 and -.10 , respectively ) .


There were no intervention effects for social adjustment and substance use , though CB group participants had improved knowledge of CB concepts at posttest , versus brochure controls .


Condition differences in major depression onset were nonsignificant but suggested support for CB interventions ( CB group = 7.4 % , bibliotherapy = 4.5 % , brochure control = 15.2 % ) .


Unexpectedly modest support was found for a brief CB group depression prevention intervention , compared to bibliotherapy or brochure control , when provided to self-selected college students , suggesting that alternative screening or interventions approaches are needed for this population .


Sexual dysfunction ( SD ) affects up to 80 % of multiple sclerosis ( MS ) patients and pelvic floor muscles ( PFMs ) play an important role in the sexual function of these patients .


The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS.


Thirty MS women were randomly allocated to one of three groups : pelvic floor muscle training ( PFMT ) with electromyographic ( EMG ) biofeedback and sham neuromuscular electrostimulation ( NMES ) ( Group I ) , PFMT with EMG biofeedback and intravaginal NMES ( Group II ) , and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation ( TTNS ) ( Group III ) .


Assessments , before and after the treatment , included : PFM function , PFM tone , flexibility of the vaginal opening and ability to relax the PFMs , and the Female Sexual Function Index ( FSFI ) questionnaire .


After treatment , all groups showed improvements in all domains of the PERFECT scheme .


PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II .


All groups improved in arousal , lubrication , satisfaction and total score domains of the FSFI questionnaire .


This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD .


To report pre-specified and exploratory results on the effect of different surgical approaches on erectile function ( EF ) after nerve-sparing radical prostatectomy ( nsRP ) obtained from the multicentre , randomised , double-blind , double-dummy REACTT trial of tadalafil ( once a day [ OaD ] or on-demand [ pro-re-nata , PRN ] ) vs placebo .


Patients aged < 68years with normal preoperative EF who underwent nsRP for localised prostate cancer ( Gleason 7 , prostate-specific antigen [ PSA ] < 10ng/mL ) were randomised after nsRP 1:1:1 to 9-month double-blind treatment with tadalafil 5mg OaD , tadalafil 20mg PRN , or placebo , followed by 6-week drug-free washout , and 3-month open-label OaD treatment ( all patients ) .


Recovery of EF was defined as an International Index of Erectile Function ( IIEF ) - EF domain score of 22 and normal orgasmic function was defined based on IIEF Question 10 .


Both parameters were analysed at the end of washout using logistic regression including terms for treatment , country , visit , visit-by-treatment interaction , age group , nerve-sparing score ( perfect = 2 , non-perfect > 2 ) , and surgical approach ( open surgery , robot-assisted laparoscopy , conventional laparoscopy , other ) .


Time to EF recovery was analysed post hoc with a Cox proportional-hazards model including terms for treatment , age-group , country , surgical approach and surgery-by-treatment interaction .


Of 422 patients treated , 189 underwent open surgery , 115 robot-assisted laparoscopy , 88 conventional laparoscopy and 30 surgery classified as ` other ' .


The odds of achieving EF recovery at the end of drug-free washout were about twice as high for the robot-assisted laparoscopy group compared with the open surgery group ( odds ratio 2.42 ; 95 % confidence interval [ CI ] 1.24 , 4.72 ; P = 0.029 ) .


Patients who underwent robot-assisted laparoscopy were significantly more likely to recover during double-blind treatment compared with patients who underwent open surgery ( hazard ratio 1.92 ; 95 % CI 1.17 , 3.15 ; P = 0.010 ) .


No favourable effect of conventional laparoscopy compared with open surgery could be seen .


These results may provide further insights into the role of surgery on EF recovery after nsRP .


However , the trial was not designed for these analyses and further prospective studies are needed .


To prospectively assess the contrast enhancement , image quality , radiation dose , and detectability of malignant pancreatic tumors with pancreatic computed tomography ( CT ) obtained at an 80-kilovolt ( peak ) ( kV [ p ] ) tube voltage setting and reduced iodine dose .


Institutional review board approval and written informed consent were obtained .


During a recent 10-month period , 136 patients ( 66 men and 70 women ; age range , 21-86 years ; mean SD age , 65.9 11.0 years ) with suspected pancreatic disease were randomized into 3 groups according to the following iodine-load and tube-voltage protocols : 600 mg of iodine per kilogram body weight ( mg/kg ) and 120 kV ( p ) ( 600-120 group ) , 500 mg/kg and 80 kV ( p ) ( 500-80 group ) , and 400 mg/kg and 80 kV ( p ) ( 400-80 group ) .


Analysis of variance was conducted to evaluate differences in CT number , background noise , signal-to-noise ratio , effective dose , lesion-to-pancreas contrast-to-noise ratio , and figure of merit .


Sensitivity , specificity , and area under the receiver-operating-characteristic curve were compared to assess the detectability of malignant pancreatic tumors .


The signal-to-noise ratios in vessels were greater ( P < 0.05 ) in the 400-80 and 500-80 groups than in the 600-120 group , and those in pancreas were comparable between the 400-80 and 600-120 groups .


No significant difference was found in effective dose , image quality , lesion-to-pancreas contrast-to-noise ratio , or figure of merit between the groups .


Sensitivity , specificity , and area under the receiver-operating-characteristic curve for detecting malignant pancreatic tumors were comparable between the groups .


Pancreatic CT with an 80-kV ( p ) setting and 400-mg iodine per kilogram contrast material load facilitates the reduction of iodine dose while maintaining image quality and the detectability of malignant pancreatic tumors .


Proponents of minimally invasive total knee arthroplasty argue that retracting rather than everting the patella results in quicker postoperative recovery and improved function .


We aimed to investigate this in patients undergoing knee arthroplasty through a standard medial parapatellar approach .


In a prospective randomized double-blinded study , sixty-eight patients undergoing total knee arthroplasty through a standard medial parapatellar approach were assigned to either retraction or eversion of the patella .


Postoperatively , at three months , and at one year after surgery , an independent observer assessed the primary outcome measure ( i.e. , knee flexion ) and secondary outcome measures ( i.e. , Oxford knee score , Short Form-12 [ SF-12 ] score , visual analog scale pain score , knee motion , and alignment and patellar height as measured on radiographs with use of the Insall-Salvati ratio ) .


Early ( three-month ) follow-up showed no significant difference between patellar eversion and subluxation in flexion ( mean and 95 % confidence interval [ CI ] , 101 5.37 versus 102 4.14 , respectively ) , Oxford knee scores ( 25 3 versus 27 2.69 , respectively ) , SF-12 , or visual analog scale pain scores ( 1.9 0.54 versus 1.1 0.44 , respectively ) .


A significant improvement in extension was found ( -3.9 1.12 versus -2.0 0.91 , respectively [ p = 0.034 ] ) , but this was not clinically significant .


There was no significant difference in any of the outcomes at one year .


There was a significant difference in implant malpositioning between the eversion group and the subluxation group , with an increased percentage of lateral tibial overhang in the subluxation group ( 0.45 0.39 versus 1.84 0.82 , respectively [ p = 0.005 ] ) , but this did not correlate with functional outcome .


There was no significant difference in alignment between the two groups ( 178.29 0.84 versus 178.18 0.78 ) .


At one year after surgery , there was no difference between the two groups in Insall-Salvati ratio ( 1.15 0.06 versus 1.12 0.06 ) although there was a correlation between the percentage reduction in the ratio and functional outcome .


There were two partial divisions of the patella tendon in the subluxation group , but no patella-related complications in the eversion group .


The results of this trial showed that retracting rather than everting the patella during total knee arthroplasty resulted in no significant clinical benefit in the early to medium term .


We observed no increase in patellar tendon shortening as a result of eversion rather than subluxation .


Our findings did suggest that , with subluxation , there may be an increased risk of damage to the patellar tendon and reduced visualization of the lateral compartment , leading to an increase in implant malpositioning with lateral tibial overhang .


Chronic anal fissure ( CAF ) is perpetuated by high sphincter pressures and secondary local ischemia .


Pharmacological approaches include topical nitrates and botulinum toxin ( BT ) , which both help to decrease the sphincter pressure .


The aims of the present study were to assess the efficacy and safety of BT injection and combined treatment with BT injection and lowered dose glyceryltrinitrate ( GTN ) cream for the treatment of CAF .


We hypothesised that combined treatment would have a synergistic effect on healing .


Forty-one consecutive patients with CAF were randomly assigned to receive one of the following treatments : Group A , injection of BT ( 20 U into internal anal sphincter ) and Group B , BT injection ( 20 units ) and subsequent thrice daily topical applications of half-dose 0.2 % GTN cream for 6 weeks .


Patients were followed up at 6 and 12 weeks and were assessed for healing of anal fissure , by means of visual inspection using fissure grades ; for faecal incontinence , using Cleveland Clinic incontinence scores ; and for fissure pain and headache using a numeric pain rating scale .


Fissure healing was similar in the two groups at both 6 ( 30 % in BT and GTN and 33 % in BT only ) and 12 weeks ( 50 % in BT and GTN vs 57 % in BT-only group ) .


Neither the change in pain score from 6 to 12 weeks , nor the overall level of pain was significantly different in the 2 groups .


Moderate or severe headaches were suffered by 58 % of patients using GTN .


Single-agent treatment by means of BT injection alone was well tolerated compared with combination treatment with BT injection and GTN cream , with no significant differences in healing of CAF observed in this small study .


The `` original '' traction-free Kocher 's method to perform the reduction of shoulder dislocation has been recently reviewed and some authors speculated that it can be self performed by patients under the guide of the physician .


In this way , as an `` assisted self-reduction '' technique , it is also effective and simple to perform .


The aim is to study the effectiveness of the assisted self-reduction technique , in comparison to the well known and largely used traction-countertraction method .


From a consecutive series of 237 uncomplicated anterior shoulder dislocations , a total of 61 were managed by the residents of our institution under the supervision of the senior authors using the assisted self-reduction method and 176 were managed by other orthopaedic consultants on duty in the Emergency Department using the traction-countertraction technique .


Only the senior authors used the assisted self-reduction technique , whereas the other orthopaedic consultants used the traction-countertraction method .


The need for intravenous sedation or general anaesthesia to perform the assisted self-reduction was considered a failure .


Recorded variables were demographic data , previous dislocation , traumatic mechanism and medication use during shoulder reduction , time to perform the reduction .


Ninety-eight percent of the acute dislocation treated with the assisted self-reduction technique and 81 % treated with the traction-countertraction method were reducible without recourse to intravenous sedation .


The assisted self-reduction technique is simple , effective and gentle .


Physicians on duty in the Emergency Departments should therefore be encouraged to use it .


Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation ( AF ) .


We sought to identify those most likely to have subclinical AF .


We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged 55 years in sinus rhythm , without known AF , enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event ( EMBRACE ) trial .


Participants underwent baseline 24-hour Holter ECG poststroke ; if AF was not detected , they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder .


Multivariable logistic regression assessed the association between baseline variables ( Holter-detected atrial premature beats [ APBs ] , runs of atrial tachycardia , age , and left atrial enlargement ) and subsequent AF detection .


Among 237 participants , the median baseline Holter APB count/24 h was 629 ( interquartile range , 142-1973 ) among those who subsequently had AF detected versus 45 ( interquartile range , 14-250 ) in those without AF ( P < 0.001 ) .


APB count was the only significant predictor of AF detection by 30-day ECG ( P < 0.0001 ) , and at 90 days ( P = 0.0017 ) and 2 years ( P = 0.0027 ) .


Compared with the 16 % overall 90-day AF detection rate , the probability of AF increased from < 9 % among patients with < 100 APBs/24 h to 9 % to 24 % in those with 100 to 499 APBs/24 h , 25 % to 37 % with 500 to 999 APBs/24 h , 37 % to 40 % with 1000 to 1499 APBs/24 h , and 40 % beyond 1500 APBs/24 h.


Among older cryptogenic stroke or transient ischemic attack patients , the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF .


Those with frequent APBs have a high probability of AF and represent ideal candidates for prolonged ECG monitoring for AF detection .


URL : http://www.clinicaltrials.gov .


Unique identifier : NCT00846924 .


Port-au-Prince , Haiti .


To determine long-term effects of early vs. delayed initiation of antiretroviral therapy ( ART ) on immune recovery and tuberculosis ( TB ) risk in human immunodeficiency virus ( HIV ) infected individuals .


Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm ( 3 ) vs. deferring ART until the CD4 count was < 200 cells/mm ( 3 ) .


The primary comparisons were CD4 counts over time and risk for incident TB , with 5 years of follow-up .


A total of 816 participants were enrolled , with 408 in each treatment arm .


The early treatment group started ART within 2 weeks , while the deferred treatment group started ART a median of 1.3 years after enrollment .


After 5 years , the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group ( 496 cells/mm ( 3 ) , 95 % confidence interval [ CI ] 477-515 vs. 373 cells/mm ( 3 ) , 95 % CI 357-389 ; P < 0.0001 ) .


TB risk was higher in the deferred treatment group ( unadjusted HR 2.41 , 95 % CI 1.56-3 .74 ; P < 0.0001 ) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis .


Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm ( 3 ) can result in long-term immune dysfunction and persistent increased risk for TB .


Elderly individuals with coronary heart disease are a population particularly burdened by disability .


However , to date many predictors of disability established in general populations have not been considered in studies examining disability in elderly acute myocardial infarction ( AMI ) survivors .


Our study explores factors associated with the ability to perform basic activities of daily living in elderly patients with AMI .


Baseline data from 333 AMI-survivors older than 64 years included within the randomized controlled KORINNA-study were utilized to examine disability assessed by the Stanford Health Assessment Questionare Disability Index ( HAQ-DI ) .


Numerous potential determinants including demographic characteristics , clinical parameters , co-morbidities , interventions , lifestyle , behavioral and personal factors were measured.Disability was defined as a HAQ-DI 0.5 .


After bi-variate testing the probability of disability was modeled with logistic regression .


Missing covariate values were imputed using a Markov Chain Monte Carlo method .


Disability was significantly more frequent in older individuals ( Odds Ratio ( OR ) : 1.10 , 95 % Confidence Interval ( CI ) : 1.05-1 .16 ) , patients with deficient nutrition ( OR : 3.38 , 95 % CI : 1.60-7 .15 ) , coronary artery bypass graft ( CABG ) ( OR : 3.26 , 95 % CI : 1.29-8 .25 ) , hearing loss in both ears ( OR : 2.85 , 95 % CI : 1.41-5 .74 ) , diabetes mellitus ( OR : 2.56 , 95 % CI : 1.39-4 .72 ) , and heart failure ( OR : 3.32 , 95 % CI : 1.79-6 .16 ) .


It was reduced in patients with percutaneous transluminal coronary angioplasty ( PTCA ) ( OR : 0.41 , 95 % CI : 0.21-0 .80 ) and male sex ( OR : 0.48 , 95 % CI : 0.27-0 .85 ) .


Effects of nutrition , hearing loss , and diametrical effects of PTCA and CABG on disability were identified as relevant for examination of causality in longitudinal trials .


ISRCTN02893746 .


Circulating progenitor cells ( CPCs ) improve cardiovascular function and organ perfusion by enhancing the capacities of endothelial repair and neovasculogenesis .


This study investigates whether exercise regimens with/without hypoxia affect cardiac and muscular hemodynamics by modulating CPCs and angiogenic factors .


Forty sedentary males were randomly divided into hypoxic ( HT , n = 20 ) and normoxic ( NT , n = 20 ) training groups .


The subjects were trained on a bicycle ergometer at 60 % VO ( 2max ) under 15 % ( HT ) or 21 % ( NT ) O2 conditions for 30 min daily , five days weekly for five weeks .


After the five-week interventions , the HT group exhibited a larger improvement in aerobic capacity than the NT group .


Furthermore , the HT regimen ( i ) enhanced cardiac output ( Q ( H ) ) and perfusion ( Q ( M ) ) / oxygenation of vastus lateralis during exercise ; ( ii ) increased levels of CD34 ( + ) / KDR ( + ) / CD117 ( + ) , CD34 ( + ) / KDR ( + ) / CD133 ( + ) , and CD34 ( + ) / KDR ( + ) / CD31 ( + ) cells in blood ; ( iii ) promoted the proliferative capacity of these CPC subsets , and ( iv ) elevated plasma nitrite/nitrate , stromal cell-derived factor-1 ( SDF-1 ) , matrix metalloproteinase-9 ( MMP-9 ) , and vascular endothelial growth factor-A ( VEGF-A ) concentrations .


Despite the lack of changes in Q ( H ) and the number or proliferative capacity of CD34 ( + ) / KDR ( + ) / CD117 ( + ) or CD34 ( + ) / KDR ( + ) / CD31 ( + ) cells , the NT regimen elevated both Q ( M ) and plasma nitrite/nitrate levels and suppressed the shedding of endothelial cells ( CD34 ( - ) / KDR ( + ) / phosphatidylserine ( + ) cells ) .


The HT regimen improves cardiac and muscular hemodynamic adaptations , possibly by promoting the mobilization/function of CPCs and the production of angiogenic factors .


Pharmacist - or nurse-led team care decreases patient blood pressure ( BP ) and cardiovascular disease ( CVD ) risk .


To evaluate whether a Web-based dietitian-led ( WD ) team care intervention was feasible and resulted in decreased BP , CVD risk , and weight compared to usual care ( UC ) .


Electronic health record ( EHR ) data identified patients aged 30-69 years with BMI > 26 , elevated BP , and 10 % -25 % 10-year Framingham CVD risk who were registered patient website users .


Patients with uncontrolled BP at screening were randomized to UC or WD , which included a home BP monitor , scale , and dietitian team care .


WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk .


Planned follow-up occurred via secure messaging to report BP , weight , and fruit and vegetable intake and receive ongoing feedback .


If needed , dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications .


Primary outcomes were change in systolic BP and weight loss 4 kg at 6 months .


Feasibility outcomes included intervention utilization and satisfaction .


Between 2010 and 2011 , a total of 90 of 101 participants completed 6-month follow-ups .


The WD group had higher rates of secure messaging utilization and patient satisfaction .


The WD group lost significantly more weight than the UC group ( adjusted net difference = -3.2 kg , 95 % CI = -5.0 , -1.5 , p < 0.001 ) and was more likely to lose 4 kg ( adjusted relative risk [ RRadj ] = 2.96 , 95 % CI = 1.16 , 7.53 ) .


BP control and CVD risk reduction were greater in WD than UC , but differences were not statistically significant .


WD intervention was feasible and resulted in decreased weight , BP , and CVD risk .


A larger trial is justified .


Trial Registration Number : NCT01077388 .


Adult attention-deficit/hyperactivity disorder ( ADHD ) is prevalent but often unrecognized , in part because it tends to co-occur with other disorders such as substance use disorders .


Cocaine use disorder is one such disorder with high co-occurrence of ADHD .


To examine whether treatment of co-occurring ADHD and cocaine use disorder with extended-release mixed amphetamine salts is effective at both improving ADHD symptoms and reducing cocaine use .


Thirteen-week , randomized , double-blind , 3-arm , placebo-controlled trial of participants meeting DSM-IV-TR criteria for both ADHD and cocaine use disorder conducted between December 1 , 2007 , and April 15 , 2013 , at 2 academic health center substance abuse treatment research sites .


One hundred twenty-six adults diagnosed as having comorbid ADHD and cocaine use disorder were randomized to extended-release mixed amphetamine salts or placebo .


Analysis was by intent-to-treat population .


Participants received extended-release mixed amphetamine salts ( 60 or 80 mg ) or placebo daily for 13 weeks and participated in weekly individual cognitive behavioral therapy .


For ADHD , percentage of participants achieving at least a 30 % reduction in ADHD symptom severity , measured by the Adult ADHD Investigator Symptom Rating Scale ; for cocaine use , cocaine-negative weeks ( by self-report of no cocaine use and weekly benzoylecgonine urine screens ) during maintenance medication ( weeks 2-13 ) and percentage of participants achieving abstinence for the last 3 weeks .


More patients achieved at least a 30 % reduction in ADHD symptom severity in the medication groups ( 60 mg : 30 of 40 participants [ 75.0 % ] ; odds ratio [ OR ] = 5.23 ; 95 % CI , 1.98-13 .85 ; P < .001 ; and 80 mg : 25 of 43 participants [ 58.1 % ] ; OR = 2.27 ; 95 % CI , 0.94-5 .49 ; P = .07 ) compared with placebo ( 17 of 43 participants [ 39.5 % ] ) .


The odds of a cocaine-negative week were higher in the 80-mg group ( OR = 5.46 ; 95 % CI , 2.25-13 .27 ; P < .001 ) and 60-mg group ( OR = 2.92 ; 95 % CI , 1.15-7 .42 ; P = .02 ) compared with placebo .


Rates of continuous abstinence in the last 3 weeks were greater for the medication groups than the placebo group : 30.2 % for the 80-mg group ( OR = 11.87 ; 95 % CI , 2.25-62 .62 ; P = .004 ) and 17.5 % for the 60-mg group ( OR = 5.85 ; 95 % CI , 1.04-33 .04 ; P = .04 ) vs 7.0 % for placebo .


Extended-release mixed amphetamine salts in robust doses along with cognitive behavioral therapy are effective for treatment of co-occurring ADHD and cocaine use disorder , both improving ADHD symptoms and reducing cocaine use .


The data suggest the importance of screening and treatment of ADHD in adults presenting with cocaine use disorder .


clinicaltrials.gov Identifier : NCT00553319 .


We previously reported on a randomized controlled trial ( RCT ) that examined the effect of adding tobramycin to bone cement after femoral stem migration .


The present study examined femoral head penetration into both conventional and highly crosslinked polyethylene acetabular liners in the same group of RCT patients , with a minimum of 5 years of postoperative follow-up .


Linear penetration of the femoral head into an X3 ( Stryker ) crosslinked polyethylene ( XLPE ) liner was measured in 18 patients ( 19 hips ) using radiostereometric analysis ( RSA ) .


Femoral head penetration was also measured in 6 patients ( 6 hips ) with a conventional polyethylene liner ( CPE ) , which served as a control group .


The median proximal femoral head penetration in the XLPE group after 5.5 years was 0.025 mm with a steady-state penetration rate of 0.001 mm/year between year 1 and year 5 .


The CPE liner showed a median proximal head penetration of 0.274 mm after 7.2 years , at a rate of 0.037 mm/year .


The Trident X3 sequentially annealed XLPE liner shows excellent in vivo wear resistance compared to non-crosslinked CPE liners at medium-term implantation .


The rate of linear head penetration in the XLPE liners after > 5 years of follow-up was 0.001 mm/year , which is in close agreement with the results of previous studies .


Lowering blood pressure ( BP ) after stroke remains a challenge , even in the context of clinical trials .


The Secondary Prevention of Small Subcortical Strokes ( SPS3 ) BP protocol , BP management during the study , and achieved BPs are described here .


Patients with recent symptomatic lacunar stroke were randomized to 1 of 2 levels of systolic BP ( SBP ) targets : lower : < 130mm Hg , or higher : 130-149mm Hg .


SBP management over the course of the trial was examined by race/ethnicity and other baseline conditions .


Mean SBP decreased for both groups from baseline to the last follow-up , from 142.4 to 126.7 mm Hg for the lower SBP target group and from 143.6 to 137.4 mm Hg for the higher SBP target group .


At baseline , participants in both groups used an average of 1.71.2 antihypertensive medications , which increased to a mean of 2.41.4 ( lower group ) and 1.81.4 ( higher group ) by the end-study visit .


It took an average of 6 months for patients to reach their SBP target , sustained to the last follow-up .


Black participants had the highest proportion of SBP 150mm Hg at both study entry ( 40 % ) and end-study visit ( 17 % ) , as compared with whites ( 9 % ) and Hispanics ( 11 % ) .


These results show that it is possible to safely lower BP even to a SBP goal < 130mm Hg in a variety of patients and settings , including private and academic centers in multiple countries .


This provides further support for protocol-driven care in lowering BP and consequently reducing the burden of stroke .


It is generally accepted that patients prefer to be told the truth by their physicians ; however , the practice of partial truth-telling is frequent with an existing ` norm of nondisclosure . '


Our primary objective was to determine what patients wanted to be told about their illness , and whether there might be differences between patients with either cancer or advanced chronic obstructive pulmonary disease ( COPD ) .


A second objective was to determine how these patients envisioned their participation , or lack thereof , in the treatment decision-making process .


Subjects were eligible for this prospective study if they were attending the oncology or pulmonary outpatient consultation services at the British Hospital or the Sanatorio Gemes Private Hospital in Buenos Aires , Argentina between June 2009 and May 2010 .


Ninety-nine patients were recruited .


Forty-four had a diagnosis of COPD , and 55 patients had cancer .


Seventeen of the patients expected their health to improve in the future , but a significantly higher proportion of patients with malignant disorders expected to get better in the near future as compared with those with COPD ( 98.2 % vs 62.8 % , P < 0.001 ) .


Most study participants expressed a desire to receive all the information available about their condition .


A majority of the participants expressed a preference for making treatment decisions in collaboration with their physician ( 40.4 % )


While they considered the role of their families relevant and wanted information to be shared so that family members might participate in decision-making , they did not want their families to have a right to withhold information , make final decisions .


We sought to determine if insulin detemir ( IDet ) is noninferior to insulin neutral protamine Hagedorn ( NPH ) for the treatment of gestational diabetes mellitus ( GDM ) and type 2 diabetes mellitus ( T2DM ) in pregnancy .


We conducted a randomized , controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014 .


Exclusion criteria were type 1 diabetes , age < 18 years , and insulin allergy .


Women who failed to achieve good glycemic control ( GC ) ( mean blood glucose [ BG ] < 100 mg/dL ) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH , with short-acting insulin aspart added as needed .


Patients were instructed to test BG 4 times a day ( fasting and 2-hour postprandial ) .


Targets of GC were fasting BG < 90 mg/dL and postprandial BG < 120 mg/dL , and insulin was adjusted as needed to achieve the targets .


The primary outcome was overall mean BG during insulin treatment ; secondary outcomes included overall mean postprandial and fasting BG , median number of weeks to achieve GC , percent of patients with overall GC , maternal weight gain , perinatal/neonatal outcomes , and number of hypoglycemic events .


Power analysis ( 90 % power ) determined that 88 patients would need to be randomized , assuming a maximal acceptable difference in overall mean BG of 7 mg/dL ( SD 10 mg/dL ) .


A per protocol analysis was performed .


In all , 105 women were randomized .


Eighteen women were excluded leaving 87 participants for analysis ( 45 NPH , 42 IDet ) .


Maternal characteristics were similar in both groups .


The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95 % confidence limit of 5.5 mg/dL ( less than the maximal acceptable difference of 7 mg/dL ; P = .2937 ) .


There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded .


The time to achieve GC was similar in both groups .


There were no differences in perinatal outcomes and maternal weight gain among the groups .


There were more hypoglycemic events per patient in the NPH group .


IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy .


Transfusion-related acute lung injury incidence remains the leading cause of posttransfusion mortality .


The etiology may be related to leukocyte antibodies or biologically active compounds in transfused plasma , injuring susceptible recipient 's lungs .


The authors have hypothesized that transfusion could have less severe effects that are not always appreciated clinically and have shown subtly decreased pulmonary oxygen gas transfer in healthy volunteers after transfusion of fresh and 21-day stored erythrocytes .


In this study , the authors tested the same hypothesis in surgical patients .


Ninety-one patients undergoing elective major spine surgery with anticipated need for erythrocyte transfusion were randomly allocated to receive their first transfusion of erythrocytes as cell salvage ( CS ) , washed stored , or unwashed stored .


Clinicians were not blinded to group assignment .


Pulmonary gas transfer and mechanics were measured 5 min before and 30 min after erythrocyte transfusion .


The primary outcome variable , gas transfer , as assessed by change of PaO2/FIO2 , with erythrocyte transfusion was not significant in any group ( mean SD ; CS : 9 59 ; washed : 10 26 ; and unwashed : 15 1 ) and did not differ among groups ( P = 0.92 ) .


Pulmonary dead space ( VD/VT ) decreased with CS transfusion ( -0.01 0.04 ; P = 0.034 ) but did not change with other erythrocytes ; the change from before to after erythrocyte transfusion did not differ among groups ( -0.01 to +0.01 ; P = 0.28 ) .


The authors did not find impaired gas exchange as assessed by PaO2/FIO2 with transfused erythrocytes that did or did not contain nonautologous plasma .


This clinical trial did not support the hypothesis of erythrocyte transfusion-induced gas exchange deficit that had been found in healthy volunteers .


Dentinal hypersensitivity is a common problem and there is a growing interest in herbal based formulations for the treatment of oral diseases .


This study was conducted to assess the efficacy of a commercially available novel herbal dentifrice in reduction of dentinal hypersensitivity .


A total of 73 subjects ( 38 males and 35 females ; aged 25-60years ) were randomly divided into two groups : Group 1 - a placebo dentifrice ( The Himalaya Drug Company Research and Development , Makali , Bangalore ) and Group 2 - ( test group ) , a commercially available herbal dentifrice ( Hi Ora K , The Himalaya Drug Company Research and Development , Makali , Bangalore ) .


Sensitivity scores for controlled air stimulus and cold water were recorded at baseline , 6weeks and 12weeks .


The test group was found to be significantly better compared to the placebo group at the end of 6 and 12weeks in reduction of dentinal hypersensitivity .


The novel herbal dentifrice can be recommended for treatment of dentinal hypersensitivity .


Peripheral neuropathic pain ( PNP ) associated with allodynia poses a significant clinical challenge .


The efficacy of ( 9 ) - tetrahydrocannabinol/cannabidiol ( THC/CBD ) oromucosal spray , a novel cannabinoid formulation , was investigated in this 15-week randomized , double-blind , placebo-controlled parallel group study .


In total , 303 patients with PNP associated with allodynia were screened ; 128 were randomized to THC/CBD spray and 118 to placebo , in addition to their current analgesic therapy .


The co-primary efficacy endpoints were the 30 % responder rate in PNP 0-10 numerical rating scale ( NRS ) score and the mean change from baseline to the end of treatment in this score .


Various key secondary measures of pain and functioning were also investigated .


At the 30 % responder level , there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis ( intention-to-treat ) dataset [ p = 0.034 ; 95 % confidence interval ( CI ) : 1.05-3 .70 ] .


There was also a reduction in mean PNP 0-10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group , but which failed to reach statistical significance .


Secondary measures of sleep quality 0-10 NRS score ( p = 0.0072 ) and Subject Global Impression of Change ( SGIC ) ( p = 0.023 ) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment .


These findings demonstrate that , in a meaningful proportion of otherwise treatment-resistant patients , clinically important improvements in pain , sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray .


THC/CBD spray was well tolerated and no new safety concerns were identified .


Cerebral palsy ( CP ) and brain injury ( BI ) are common conditions that have devastating effects on a child 's ability to use their hands .


Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills , both in isolation or concurrently .


The aim of this paper is to describe the method to be used to conduct two randomised controlled trials ( RCT ) investigating ( a ) the immediate effect of functional hand splints , and ( b ) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone , and to task-specific training alone in children with CP and BI .


The Cognitive Orientation to Occupational Performance ( CO-OP ) approach will be the task-specific training approach used .


Two concurrent trials ; a two group , parallel design , RCT with a sample size of 30 participants ( 15 per group ) ; and a three group , parallel design , assessor blinded , RCT with a sample size of 45 participants ( 15 per group ) .


age 4-15 years ; diagnosis of CP or BI ; Manual Abilities Classification System ( MACS ) level I - IV ; hand function goals ; impaired hand function ; the cognitive , language and behavioural ability to participate in CO-OP .


Participants will be randomly allocated to one of 3 groups ; ( 1 ) functional hand splint only ( n = 15 ) ; ( 2 ) functional hand splint combined with task-specific training ( n = 15 ) ; ( 3 ) task-specific training only ( n = 15 ) .


Allocation concealment will be achieved using sequentially numbered , sealed opaque envelopes opened by an off-site officer after baseline measures .


Treatment will be provided for a period of 2 weeks , with outcome measures taken at baseline , 1 hour after randomisation , 2 weeks and 10 weeks .


The functional hand splint will be a wrist cock-up splint ( + / - thumb support or supination strap ) .


Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children .


Primary outcome measures will be the Canadian Occupational Performance Measure ( COPM ) and the Goal Attainment Scale ( GAS ) .


Analysis will be conducted on an intention-to-treat basis .


This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI .


The nipple-areolar complex ( NAC ) has special histological properties with higher melanocyte concentration than breast skin .


To date , there are no data describing the late effects on the NAC following breast-conserving therapy ( BCT ) .


This study evaluated colour changes in the NAC in patients treated with breast-conserving surgery and adjuvant radiotherapy after 5 years .


Digital photographs obtained at 5 years following breast irradiation from the St. George and Wollongong ( SGW ) trial ( NCT00138814 ) were evaluated by five experts using an iPad ( Apple Inc. , Cupertino , CA , USA ) application specifically created for this study .


The SGW trial randomised 688 patients with Tis-2 , N0-1 , M0 carcinoma to the control arm of 50Gy in 25 fractions and boost arm of 45Gy in 25 fractions and 16Gy in 8 fractions electron boost .


A total of 141/372 ( 38 % ) patients had altered NAC ( 86 % lighter , 10 % darker ) .


Patients with Celtic skin type had increased likelihood of having an altered NAC ( odds ratio ( OR ) , 1.75 ( CI 1.1-2 .7 , P = 0.011 ) ) .


On subgroup analysis , those with Celtic skin type receiving biologically equivalent dose ( BED ) Gy3 80Gy had OR of 3.03 ( 95 % CI 1.2-7 .5 , P = 0.016 ) for having altered colour .


There was a dose response with more profound changes seen in the NAC compared with irradiated breast skin if BED Gy3 80Gy with OR of 2.42 ( 95 % CI 1.1-5 .6 , P = 0.036 ) .


In this Caucasian BCT population , over 30 % of patients developed lighter NAC and more commonly in women with Celtic skin type .


The degree of this effect increased with higher radiation dose .


Substantial progress has been made in identifying susceptibility variants for AMD in European populations ; however , few studies have been conducted to understand the role these variants play in AMD risk in diverse populations .


The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci .


Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism ( SNPs ) .


Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity .


Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography .


Populations included in this study were European Americans , African Americans , Mexican Americans , and Singaporeans from the Population Architecture using Genomics and Epidemiology ( PAGE ) study .


Index variants of AMD , rs1061170 ( CFH ) and rs10490924 ( ARMS2 ) , were associated with AMD at P = 3.0510 ( -8 ) and P = 6.3610 ( -6 ) , respectively , in European Americans .


In general , none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value < 0.05 .


Four lipid-associated SNPS ( LPL rs328 , TRIB1 rs6987702 , CETP rs1800775 , and KCTD10/MVK rs2338104 ) were associated with AMD in African Americans and Mexican Americans ( P < 0.05 ) , but these associations did not survive strict corrections for multiple testing .


While most associations did not generalize in the non-European populations , variants within lipid-related genes were found to be associated with AMD .


This study highlights the need for larger well-powered studies in non-European populations .


( 1 ) The primary objectives were ( 1 ) to assess the response to intravenous ( IV ) fluid in children presenting to the ED with migraine and ; ( 2 ) to assess the effect of treatment expectation on the response to I.


Despite a lack of evidence for the practice , many emergency department ( ED ) migraine treatment protocols include a bolus of IV fluid .


This study assessed the overall response to IV fluid hydration and the effect of expected medication treatment on the pain response among children and adolescents with migraine in an urban ED .


A single-blind , randomized parallel arm trial of 10mL/kg IV 0.9 % sodium chloride for children and adolescents aged 5-17 years presenting to a pediatric ED with migraine .


Patients were randomized into group A ( no expectation of medication in combination with IV fluid ) and group B ( expectation that medication may be given simultaneously ) .


All participants were treated with standard care following the 30-minute assessment .


Forty-seven participants were randomized and 2 were excluded ; mean age was 13.3 years and 31 ( 67.4 % ) were females .


Demographics and baseline characteristics were similar between groups .


Overall , there was no statistically significant difference for the primary outcome - change from baseline on the visual analog scale ( VAS ) at 30 minutes with a mean change of -12.3 mm ( standard deviation [ SD ] 17.9 ) in group A and -12.7 mm ( SD 13.2 ) in group B ( P = .936 ) .


The standardized difference between the 2 means ( Cohen 's d effect size ) was low at 0.024 ( 95 % confidence interval [ CI ] -0.56 to 0.61 ) .


Overall , complete headache relief was observed in only 1 participant ; 16 of 45 ( 35.6 % ; 95 % CI 21.8 to 51.2 ) had a reduction in headache of 33 % or more and 8 of 45 ( 17.8 % ; 95 % CI 6.1 to 29.4 % ) had a minimum clinical significant difference of 30mm or more on VAS with 4 in each group .


Thirteen of 39 patients with follow-up data ( 33.3 % ; 95 % CI 19.1 to 50.2 % ) reported a moderate or severe headache at the 24-hour follow up with no difference between groups ; only 3 patients returned to the ED .


One participant reported a minor IV-related adverse event .


The overall decrease in pain with IV fluid is small and clinically insignificant .


Treatment expectation did not significantly influence headache relief at 30 minutes with IV fluid hydration in children or adolescents with migraine in the ED .


The average relief of headache with IV fluid alone was small ; however , a clinically meaningful response was observed in 17.8 % .


Recurrence of headache is common in 33 % after ED discharge .


Combination diphtheria-tetanus-5 component acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine ( DTaP5-IPV-Hib-HepB ) administered either concurrently with 7-valent pneumococcal conjugate vaccine ( PCV7 ) or 1 month apart was generally safe and immunogenic at 2 , 4 and 6 months of age .


This study examined the effects of a booster dose at age 15 months .


Participants were randomized to DTaP5-IPV-Hib-HepB plus PCV7 , DTaP5-IPV-Hib-HepB with PCV7 administered 1 month later or a pentavalent DTaP5-IPV/Hib plus HepB plus PCV7 at 15 months of age in a randomized , open-label , phase IIb clinical trial .


Immunogenicity endpoints were rates of seroresponse to pertussis toxoid , filamentous hemagglutinin , pertactin and fimbriae types 2 and 3 ; rates of seroprotection against ( Hib ) polyribosylribitol phosphate capsular polysaccharide , hepatitis B surface antigen , diphtheria toxoid , tetanus toxoid and poliovirus types 1 , 2 and 3 ; and geometric mean titers to all vaccine antigens .


Safety endpoints included solicited injection-site reactions and systemic and serious adverse events .


Seroresponse/seroprotection rates for all antigens exceeded prespecified criteria in both groups that received the hexavalent DTaP5-IPV-Hib-HepB ; in the group that received the currently licensed pentavalent vaccine , seroresponse/seroprotection rates exceeded the criteria for all antigens except filamentous hemagglutinin .


Seroresponse rates were 88.9 % for pertussis antigens and seroprotection rates against polyribosylribitol phosphate capsular polysaccharide , hepatitis B surface antigen , diphtheria toxoid , tetanus toxoid and poliovirus antigens were 95.1 % in recipients of DTaP5-IPV-Hib-HepB .


DTaP5-IPV-Hib-HepB administered concomitantly with PCV7 or 1 month apart at 15 months of age following the infant series was well-tolerated and elicited antibody responses to all vaccine antigens , with no significant interference from concomitant PCV7 administration ( clinicaltrials.gov registration number NCT00362427 ) .


Treatment of patients with neurological manifestations of degenerative-dystrophic lesions of the spine must be integrated and optimized from the perspective of pathogenesis .


Antiedematous therapy is an important moment that takes into account the development of localized swelling affected the spinal structures .


We studied the efficacy of L-lysine aescinat in the treatment of patients with discogenic-venous lumbosacral radiculomyelopathy .


We analyzed the therapeutic efficacy of antitumor therapy with the drug L-lysine aescinat in 40 patients with discogenic-venous lumbosacral radiculomyelopathy in comparison with a control group of 40 patients treated with conventional therapy in a neurological hospital .


The age of the patients ranged from 30 to 60 years .


In total , there were 36 ( 45 % ) women and 44 ( 55 % ) men .


Herniated discs were visualized by MRI in all patients , attention was drawn to the condition of radicular veins of the cauda equina .


We assessed muscle strength of lumbosacral myotomes , their trophicity and state of segmental-conductor apparatus sensitivity with the quantitative determination of the time of vibration of a tuning fork .


The comparison of neurological status dynamics during treatment of inpatients has shown that neurological symptoms reduce more effectively in patients treated with L - lysine aescinat ( by 75 % during the first 3-5 days ) and in a greater number of the patients ( 77.5 % vs 55 % in the control group ) .


The authors ' experience has shown that venous micro - and macro-circulation disorders play an important role in the pathogenesis of lower lumbar disk hernia .


Clinical manifestations of these disorders are segmental and conductive spinal motor disorders in myotomes and sensitivity .


Quantitative determination of vibration sensitivity ( tuning fork test ) is pathognomonic for radiculomyeloischemia .


Vein tonics and antiedemics , including L - lysine aescinat as one of the most effective drugs , exert a pathogenetic effect on spondylic and discogenic nervous system disturbances .


Intracranial hemorrhage ( ICH ) is a life-threatening complication of anticoagulation .


We investigated the rate , outcomes , and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily , Oral , Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET AF ) .


Cox proportional hazards modeling was used .


During 1.94 years ( median ) of follow-up , 172 patients ( 1.2 % ) experienced 175 ICH events at a rate of 0.67 % per year .


The significant , independent predictors of ICH were race ( Asian : hazard ratio , 2.02 ; 95 % CI , 1.39-2 .94 ; black : hazard ratio , 3.25 ; 95 % CI , 1.43-7 .41 ) , age ( 1.35 ; 1.13-1 .63 per 10-year increase ) , reduced serum albumin ( 1.39 ; 1.12-1 .73 per 0.5 g/dL decrease ) , reduced platelet count below 21010 ( 9 ) / L ( 1.08 ; 1.02-1 .13 per 1010 ( 9 ) / L decrease ) , previous stroke or transient ischemic attack ( 1.42 ; 1.02-1 .96 ) , and increased diastolic blood pressure ( 1.17 ; 1.01-1 .36 per 10 mm Hg increase ) .


Predictors of a reduced risk of ICH were randomization to rivaroxaban ( 0.60 ; 0.44-0 .82 ) and history of congestive heart failure ( 0.65 ; 0.47-0 .89 ) .


The ability of the model to discriminate individuals with and without ICH was good ( C-index , 0.69 ; 95 % CI , 0.64-0 .73 ) .


Among patients with atrial fibrillation treated with anticoagulation , the risk of ICH was higher among Asians , blacks , the elderly , and in those with previous stroke or transient ischemic attack , increased diastolic blood pressure , and reduced platelet count or serum albumin at baseline .


The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin .


The external validity of these findings requires testing in other atrial fibrillation populations .


Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy .


In a Phase 3 , randomized , double-blind , double-dummy study ( NCT01644474 ) , patients ( low-density lipoprotein cholesterol [ LDL-C ] 100-190 mg/dL , 10-year risk of fatal cardiovascular events 1 % - < 5 % [ systemic coronary risk estimation ] ) were randomized to ezetimibe 10mg/day ( n = 51 ) or alirocumab 75 mg subcutaneously ( via 1-mL autoinjector ) every 2 weeks ( Q2W ) ( n = 52 ) , with dose up-titrated to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 LDL-C was 70 mg/dL .


Primary endpoint was mean LDL-C % change from baseline to 24 weeks , analyzed using all available data ( intent-to-treat approach , ITT ) .


Analyses using on-treatment LDL-C values were also conducted .


Mean ( SD ) baseline LDL-C levels were 141.1 ( 27.1 ) mg/dL ( alirocumab ) and 138.3 ( 24.5 ) mg/dL ( ezetimibe ) .


The 24-week treatment period was completed by 85 % of alirocumab and 86 % of ezetimibe patients .


Least squares mean ( SE ) LDL-C reductions were 47 ( 3 ) % with alirocumab versus 16 ( 3 ) % with ezetimibe ( ITT ; p < 0.0001 ) and 54 ( 2 ) % versus 17 ( 2 ) % ( on-treatment ; p < 0.0001 ) .


At week 12 , before up-titration , alirocumab 75 mg Q2W reduced LDL-C by 53 ( 2 ) % ( on-treatment ) .


Injection site reactions were infrequent ( < 2 % and < 4 % of alirocumab and ezetimibe patients , respectively ) .


Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide 50 % LDL-C reduction in the majority of the patients .


Adverse events were comparable between groups .


Diabetes is a chronic , potentially debilitating , and often fatal disease .


Dietary strategies to reduce postprandial glycemia are important in the prevention and treatment of diabetes .


Nuts are rich in mono - and polyunsaturated fatty acids , which may reduce hyperglycemia and improve metabolism .


To evaluate the effectiveness of pistachio nut supplementation on glycemic and inflammatory measures in patients with type 2 diabetes .


In this double-blind , randomized , placebo-controlled , crossover trial , 48 diabetic patients were equally assigned to groups A and B. Patients in group A received a snack of 25 g pistachio nuts twice a day for 12 weeks and group B received a control meal without nuts .


After 12 weeks of intervention , the patients had an 8-week washout .


Then the groups were displaced , and group B received the same amount of pistachios for 12 weeks .


With respect to the total change in variables over both phases , there was a marked decrease in HbA1c ( -0.4 % ) and fasting blood glucose ( FBG ) concentrations ( -16 mg/dl ) in the pistachio group compared with the control group ( p 0.001 for both ) .


There was no overall significant change in BMI , blood pressure , HOMA-IR , and C-reactive protein ( CRP ) concentrations .


Analysis of the two phases separately showed a decrease in FBG by 14 mg/dl and in HbA1c by 0.45 % in the treatment group ( A ) after 12 weeks , while no significant differences were seen in group B ( control group ) .


In the second phase , FBG decreased from 151.36 39.22 to 137.28 28.65 mg/dl ( -14 mg/dl ) and HbA1c decreased from 7.42 0.97 to 7.15 0.68 mg/dl ( -0.28 % , p = 0.013 and p = 0.033 , respectively ) in the pistachio group ( B ) .


Pistachio consumption reduced systolic blood pressure ( p = 0.007 ) , BMI ( p = 0.011 ) , and CRP ( p = 0.002 ) in patients from the treatment groups , but not insulin resistance .


Dietary consumption of pistachio nuts as a snack has beneficial effects on glycemic control , blood pressure , obesity , and inflammation markers in diabetic patients .


A hydrocodone extended-release ( ER ) formulation employing the CIMA ( ) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol .


This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release ( IR ) product .


In this four-period crossover study , healthy subjects aged 18-45 years were randomized to receive a single intact , oral 45-mg tablet of one of three hydrocodone ER prototypes ( low - , intermediate - , or high-level coating ) or an intact , oral tablet of hydrocodone IR/acetaminophen ( APAP ) 10/325 mg every 6 h until four tablets were administered , with each of the four treatments administered once over the four study periods .


Dosing periods were separated by a minimum 5-day washout .


Naltrexone 50 mg was administered to block opioid receptors .


Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose .


Parameters assessed included maximum observed plasma hydrocodone concentration ( C ( max ) ) , time to C ( max ) ( t ( max ) ) , and area under the concentration-time curve from time 0 to infinity ( AUC ( 0 - ) ) .


Mean C ( max ) values were 49.2 , 32.6 , and 28.4 ng/mL for the low - , intermediate - , and high-level coating hydrocodone ER tablet prototypes , respectively , and 37.3 ng/mL for the hydrocodone IR/APAP tablet ; respective median t ( max ) values were 5.9 , 8.0 , 8.0 , and 1.0 h. Total systemic exposure to hydrocodone ( AUC ( 0 - ) ) was comparable between hydrocodone ER tablet prototypes ( 640 , 600 , and 578 ngh/mL , respectively ) and hydrocodone IR/APAP ( 581 ngh/mL ) .


No serious adverse events or deaths were reported .


The most common adverse events included headache ( 26 % ) and nausea ( 18 % ) .


All three hydrocodone ER tablet prototypes ( low - , intermediate - , and high-level polymer coating ) demonstrated ER pharmacokinetic characteristics .


The hydrocodone ER tablet prototype with the high-level coating was selected for development because of its comparable exposure to the hydrocodone IR/APAP formulation and potentially increased ability to resist rapid drug release upon product tampering because of a higher polymer coating level .


All study medications were well tolerated in healthy naltrexone-blocked volunteers .


A low FODMAP ( Fermentable Oligosaccharides , Disaccharides , Monosaccharides And Polyols ) diet reduces symptoms of IBS , but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment .


The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded , randomised , cross-over trial .


Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets , differing only in FODMAP content ( mean ( 95 % CI ) low 3.05 ( 1.86 to 4.25 ) g/day vs Australian 23.7 ( 16.9 to 30.6 ) g/day ) , and then crossed over to the other diet with 21-day washout period .


Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled , and pH , short-chain fatty acid concentrations and bacterial abundance and diversity were assessed .


Faecal indices were similar in IBS and healthy subjects during habitual diets .


The low FODMAP diet was associated with higher faecal pH ( 7.37 ( 7.23 to 7.51 ) vs. 7.16 ( 7.02 to 7.30 ) ; p = 0.001 ) , similar short-chain fatty acid concentrations , greater microbial diversity and reduced total bacterial abundance ( 9.63 ( 9.53 to 9.73 ) vs. 9.83 ( 9.72 to 9.93 ) log10 copies/g ; p < 0.001 ) compared with the Australian diet .


To indicate direction of change , in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa ( median ratio 6.62 ; p < 0.001 ) and mucus-associated Akkermansia muciniphila ( 19.3 ; p < 0.001 ) , and reduced Ruminococcus torques .


Diets differing in FODMAP content have marked effects on gut microbiota composition .


The implications of long-term reduction of intake of FODMAPs require elucidation .


ACTRN12612001185853 .


As compared with individual tablets , saxagliptin/metformin extended-release ( XR ) fixed-dose combination ( FDC ) tablets offer the potential for increased patient compliance with the convenience of once daily dosing .


The aim of the present study was to show that the FDC of saxagliptin and metformin XR is bioequivalent to co-administration of the individual components when given to Chinese subjects residing in China .


This was a randomized , open-label , single-dose , two-period , cross-over pharmacokinetic study in two cohorts of healthy adult Chinese male subjects ( n = 32 in each cohort ) under fed conditions .


In cohort 1 , the pharmacokinetic properties of a saxagliptin/metformin XR 5/500mg FDC tablet were compared with those of co-administration of a 5mg saxagliptin tablet and a 500mg metformin XR tablet .


In cohort 2 , the pharmacokinetic properties of a saxagliptin/metformin XR 5/1 ,000 mg FDC tablet were compared with those of co-administration of a 5mg saxagliptin tablet and 2500mg metformin XR tablets .


The two cohorts were independent of each other with respect to treatment and results .


The pharmacokinetic properties of the active metabolite of saxagliptin ( 5-hydroxy-saxagliptin ) , as well as the safety and tolerability of each treatment , were also evaluated .


For both cohorts , saxagliptin and metformin in the FDCs were bioequivalent to the individual components , as the limits of the 90 % confidence intervals of the geometric least squares mean ratios were contained within the 80-125 % bioequivalence limits for the area under the plasma concentration-time curve parameters and within the 70-143 % bioequivalence limits for the maximum plasma concentration .


Similar exposures of 5-hydroxy-saxagliptin were observed with the two treatment regimens within each cohort .


Co-administration of saxagliptin and metformin XR was generally safe and well tolerated as the FDCs or as individual tablets .


Saxagliptin/metformin XR 5/500mg and saxagliptin/metformin XR 5/1 ,000 mg FDCs were bioequivalent to individual tablets of saxagliptin and metformin XR of the same strengths and were generally well tolerated .


These results in healthy Chinese subjects are consistent with those of previous assessments of saxagliptin/metformin XR FDC in the saxagliptin clinical development programme .


To test a virtual case-based Simulated Diabetes Education intervention ( SimDE ) developed to teach primary care residents how to manage diabetes .


Nineteen primary care residency programs , with 341 volunteer residents in all postgraduate years ( PGY ) , were randomly assigned to a SimDE intervention group or control group ( CG ) .


The Web-based interactive educational intervention used computerized virtual patients who responded to provider actions through programmed simulation models .


Eighteen distinct learning cases ( L-cases ) were assigned to SimDE residents over six months from 2010 to 2011 .


Impact was assessed using performance on four virtual assessment cases ( A-cases ) , an objective knowledge test , and pre-post changes in self-assessed diabetes knowledge and confidence .


Group comparisons were analyzed using generalized linear mixed models , controlling for clustering of residents within residency programs and differences in baseline knowledge .


The percentages of residents appropriately achieving A-case composite clinical goals for glucose , blood pressure , and lipids were as follows : A-case 1 : SimDE = 21.2 % , CG = 1.8 % , P = .002 ; A-case 2 : SimDE = 15.7 % , CG = 4.7 % , P = .02 ; A-case 3 : SimDE = 48.0 % , CG = 10.4 % , P < .001 ; and A-case 4 : SimDE = 42.1 % , CG = 18.7 % , P = .004 .


The mean knowledge score and pre-post changes in self-assessed knowledge and confidence were significantly better for SimDE group than CG participants .


A virtual case-based simulated diabetes education intervention improved diabetes management skills , knowledge , and confidence for primary care residents .


For many older people , long-term functional limitations persist after a hip fracture .


The efficacy of a home exercise program with minimal supervision after formal hip fracture rehabilitation ends has not been established .


To determine whether a home exercise program with minimal contact with a physical therapist improved function after formal hip fracture rehabilitation ended .


Randomized clinical trial conducted from September 2008 to October 2012 in the homes of 232 functionally limited older adults who had completed traditional rehabilitation after a hip fracture .


The intervention group ( n = 120 ) received functionally oriented exercises ( such as standing from a chair , climbing a step ) taught by a physical therapist and performed independently by the participants in their homes for 6 months .


The attention control group ( n = 112 ) received in-home and telephone-based cardiovascular nutrition education .


Physical function assessed at baseline , 6 months ( ie , at completion of the intervention ) , and 9 months by blinded assessors .


The primary outcome was change in function at 6 months measured by the Short Physical Performance Battery ( SPPB ; range 0-12 , higher score indicates better function ) and the Activity Measure for Post-Acute Care ( AM-PAC ) mobility and daily activity ( range , 23-85 and 9-101 , higher score indicates better function ) .


Among the 232 randomized patients , 195 were followed up at 6 months and included in the primary analysis .


The intervention group ( n = 100 ) showed significant improvement relative to the control group ( n = 95 ) in functional mobility ( mean SPPB scores for intervention group : 6.2 [ SD , 2.7 ] at baseline , 7.2 [ SD , 3 ] at 6 months ; control group : 6.0 [ SD , 2.8 ] at baseline , 6.2 [ SD , 3 ] at 6 months ; and between-group differences : 0.8 [ 95 % CI , 0.4 to 1.2 ] , P < .001 ; mean AM-PAC mobility scores for intervention group : 56.2 [ SD , 7.3 ] at baseline , 58.1 [ SD , 7.9 ] at 6 months ; control group : 56 [ SD , 7.1 ] at baseline , 56.6 [ SD , 8.1 ] at 6 months ; and between-group difference , 1.3 [ 95 % CI , 0.2 to 2.4 ] , P = .03 ; and mean AM-PAC daily activity scores for intervention group : 57.4 [ SD , 13.7 ] at baseline , 61.3 [ SD , 15.7 ] at 6 months ; control group : 58.2 [ SD , 15.2 ] at baseline , 58.6 [ SD , 15.3 ] at 6 months ; and between-group difference , 3.5 [ 95 % CI , 0.9 to 6.0 ] , P = .03 ) .


In multiple imputation analyses , between-group differences remained significant for SPPB and AM-PAC daily activity , but not for mobility .


Significant between-group differences persisted at 9 months for all functional measures with and without imputation .


Among patients who had completed standard rehabilitation after hip fracture , the use of a home-based functionally oriented exercise program resulted in modest improvement in physical function at 6 months after randomization .


The clinical importance of these findings remains to be determined .


clinicaltrials.gov Identifier : NCT00592813 .


To explore any differences in efficacy and safety outcomes between European ( EU ) ( n = 684 ) and North American ( NA ) ( n = 395 ) patients in the AFFIRM trial ( NCT00974311 ) .


Phase III , double-blind , placebo-controlled , multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer ( mCRPC ) after docetaxel .


Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160mg/day or placebo .


The primary end point was overall survival ( OS ) in a post hoc analysis .


Enzalutamide significantly improved OS compared with placebo in both EU and NA patients .


The median OS in EU patients was longer than NA patients in both treatment groups .


However , the relative treatment effect , expressed as hazard ratio and 95 % confidence interval , was similar in both regions : 0.64 ( 0.50 , 0.82 ) for EU and 0.63 ( 0.47 , 0.83 ) for NA .


Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions .


The tolerability profile of enzalutamide was comparable between EU and NA patients , with fatigue and nausea the most common adverse events .


Four EU patients ( 4/461 enzalutamide-treated , 0.87 % ) and one NA patient ( 1/263 enzalutamide-treated , 0.38 % ) had seizures .


The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry .


This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA - and EU-treated patients , although the median OS was higher in EU relative to NA patients .


Efficacy benefits were consistent across end points , with a comparable safety profile in both regions .


Although opioids are widely used as analgesics in general anaesthesia , they have unpleasant side-effects and can delay postoperative recovery .


Acupuncture and related techniques are effective for acute and chronic pain , and reduces some side-effects .


We assessed the effect of transcutaneous electric acupoint stimulation ( TEAS ) on intra-operative remifentanil consumption and the incidences of anaesthesia-related side-effects .


Sixty patients undergoing sinusotomy were randomly assigned to TEAS or control group .


TEAS consisted of 30 min of stimulation ( 6-9 mA , 2/10 Hz ) on the Hegu ( LI4 ) , Neiguan ( PC6 ) , and Zusanli ( ST36 ) before anaesthesia .


The patients in the control group had the electrodes applied , but received no stimulation .


Bispectral index was used to monitor the depth of anaesthesia .


Perioperative haemodynamics were recorded , and peripheral blood samples were collected to measure the levels of mediators of surgical stress .


The primary end point was intraoperative remifentanil consumption and the secondary endpoints were recovery quality and anaesthesia-related side-effects .


Patients in the TEAS group required 39 % less remifentanil during surgery than controls [ 0.0907 ( SD 0.026 ) g kg ( -1 ) min ( -1 ) vs 0.051 ( 0.018 ) g kg ( -1 ) min ( -1 ) ] .


There were no differences in intra-operative haemodynamics or surgical stress between groups .


However , the time to extubation and recall in the control group was 16.8 ( 6.8 ) min and 23.0 ( 5.0 ) min , respectively , significantly longer than that in the TEAS group ( P < 0.01 ) .


TEAS also decreased the incidence of dizziness and pruritus within the first 24 h after surgery ( P < 0.01 ) .


The use of TEAS significantly reduced intra-operative remifentanil consumption and alleviated postoperative side-effects in patients undergoing sinusotomy .


The trial was registered at clinicaltrials.gov ( NCT01700855 ) .


Radial-head subluxation is an easily identified and treated injury .


We investigated whether triage nurses in the emergency department can safely reduce radial-head subluxation at rates that are not substantially lower than those of emergency department physicians .


We performed an open , noninferiority , cluster-randomized control trial .