We evaluated factor V and von Willebrand factor ( vWF ) to determine endothelial dysfunction and creatinine kinase myocardial band ( CKMB ) - mass , troponin T to show myocardial ischemia preoperatively in the holding area ( T1 ) , after discontinuation of anesthetic gases ( T2 ) , and 24 hours after induction ( T3 ) .


Compared with baseline , homocysteine concentrations significantly decreased both in the nitrous oxide ( 22.3 16.3 vs 11.8 9.9 ; P < .00001 ) and nitrous oxide-free groups ( 21.5 15.3 vs 8.0 5.7 ; P < .0001 ) at postoperative hour 24 .


The nitrous oxide group had significantly higher mean plasma homocysteine concentrations than the nitrous oxide-free group ( P = .021 ) .


The actual homocysteine difference between groups was 3.8 mol/L .


This study shows that homocysteine levels markedly decrease within 24 hours after living-related donor kidney transplantation .


Patients receiving nitrous oxide have a lesser reduction , but this finding is unlikely to have a clinical relevance .


The effect of tranexamic acid ( TXA ) on bleeding and improvement of surgical field during functional endoscopic sinus surgery ( FESS ) is not clear yet .


This study was conducted to answer this question .


This trial was conducted on 60 patients with chronic sinusitis at Beasat Hospital , Hamadan , Iran , from April to November 2013 .


Thirty patients in the intervention group received three pledgets soaked with TXA 5 % and phenylephrine 0.5 % for 10 minutes in each nasal cavity before surgery .


Thirty patients in the control group received phenylephrine 0.5 % with the same way .


The amount of bleeding and the quality of surgical field were evaluated at 15 , 30 , and 45 minutes after the start of surgery using Boezaart grading .


The quality of the surgical field in the intervention group compared to the control group was significantly better in the first quarter ( P = 0.002 ) and the second quarter ( P = 0.003 ) but not in the third quarter ( P = 0.163 ) .


Furthermore , the amount of bleeding was much less during all periods in the intervention group than in the control group ( P = 0.001 ) .


Topical TXA can efficiently reduce bleeding and improve the surgical field in FESS in patients with rhinosinusitis .


Based on these findings , topical TXA may be a useful method for providing a suitable surgical field during the first 30 minutes after use .


Iranian Registry of Clinical Trials IRCT201212139014N15 .


The authors have reported in Part 1 of this study on a novel neuromonitoring test for the prevention of medial malpositioning of thoracic pedicle screws .


In the present paper they examine the impact of providing the results of the test as intraoperative feedback to the surgical team .


This is the second part of a 2-part report of a prospective , blinded and randomized neuromonitoring study designed to lower the incidence of medially malpositioned thoracic pedicle screws .


Details of the neuromonitoring technique and data supporting the alarm criteria used are contained in the companion article ( Part 1 ) .


For the majority of pedicle screw placements , intraoperative test results were withheld from the study team ( that is , the team members were blinded to the test results ) .


However , for a limited number of pedicle sites the authors provided one of 2 forms of testing feedback to the surgical team : 1 ) `` break the blind '' feedback , if testing suggested that screw placement would result in direct contact between screw and the dura mater ; and 2 ) `` planned '' feedback , beginning during the later stages of the study and provided for 50 % of pedicle sites .


Feedback gave the surgeon the opportunity to adjust the trajectory that the screw would ultimately take within the pedicle .


The final screw position relative to the pedicle 's medial wall for all sites in which feedback was withheld from the surgical team was compared with the screw position for those sites in which either form of feedback ( `` break the blind '' or `` planned '' ) was provided to and acted upon by the surgical team .


Of the 820 pedicle tracks tested among the 71 surgical cases included in this study , a total of 684 were operated upon without any form of feedback .


Planned feedback was provided for an additional 107 pedicle tracks , of which 15 triggered an intraoperative alarm ( evoked electromyogram response in leg muscles to stimulus intensity 10 mA ) leading to a warning to the surgical team of a medially biased pedicle track .


Finally , the blind was broken 29 times , in each case when testing revealed a particularly low threshold ( 4 mA ) for evoked responses in leg muscles when stimulating along the pedicle track with the ball-tipped probe .


As detailed in the companion paper to this one , there were 32 screws with threads lying at least 2 mm medial to the pedicle wall .


In all 32 instances ( 100 % ) , either these screws were in the `` no feedback '' category ( n = 29 ) or they were in a feedback category but the surgeon elected to not revise the pedicle-track trajectory .


Two patients returned to the operating room for revision of screw placements because the screws were encroaching upon the central canal ; the pedicle tracks for these screws had been in the `` no feedback '' category .


This is the first blinded and randomized study to prove that implementing a novel neuromonitoring strategy during placement of thoracic pedicle screws can significantly reduce the incidence of clinically relevant thoracic pedicle screw medial malpositioning .


The aim of the present study was twofold : 1 .


to compare the efficacy of three antipsychotics ( ziprasidone , olanzapine and perazine ) in schizophrenia 2 .


to compare the improvement in cognitive functioning between groups treated with the three different neuroleptics .


A total of 58 Caucasian patients diagnosed with paranoid schizophrenia were recruited into the study group .


We used the Polish version of the CIDI ( Composite International Diagnostic Interview ) to obtain ICD-10 diagnoses .


The intensity of psychopathological symptoms was examined using the PANSS .


The patients were randomly assigned to treatment with perazine , olanzapine or ziprasidone administered as monotherapy for 3 months .


The treatment efficacy was measured as a change in the PANSS ( Positive and Negative Syndrome Scale ) total score from baseline ( T0 ) to 3 months ( T1 ) .


The WCST ( The Wisconsin Card Sorting Test ) was used to measure working memory and executive functions in the evaluated patients .


Wilcoxon 's and Kruskal-Wallis tests were applied to compare changes in the PANSS scores between the treatment groups .


To analyze the cognitive functions , Kruskal-Wallis test for the WCST parameters was used .


The three antipsychotics similarly reduced the total PANSS score .


The WCST parameters in the 3 groups of examined patients using the Kruskal-Wallis test revealed some differences between the three administered antipsychotics .


Results suggest that the short-term efficacy of the atypical ( olanzapine , ziprasidone ) and typical ( perazine ) antipsychotic drugs did not differ .


Based on the analysis , a conclusion can be drawn that the three neuroleptics provided similar improvements in cognitive functioning .


Contextual factors , including the gender of researchers , influence experimental and patient pain reports .


It is currently not known how social stimuli influence pain percepts , nor which types of sensory modalities of communication , such as auditory , visual or olfactory cues associated with person perception and gender processing , produce these effects .


To determine whether exposure to two forms of social stimuli ( audio and visual ) from a virtual male or female stranger modulates cold pressor task ( CPT ) pain reports .


Participants with similar demographic characteristics conducted a CPT in solitude , without the physical presence of an experimenter or another person .


During the CPT , participants were exposed to the voice and image of a virtual male or female stranger .


The voices had analogous vocal prosody , provided no semantic information ( spoken in a foreign language ) and differed only in pitch ; the images depicted a middle-age male or female health care practitioner .


Male participants , but not females , showed higher CPT pain intensity when they were exposed to the female stimuli compared with the male stimuli .


Follow-up analyses showed that the association between the social stimuli and variability in pain sensitivity was not moderated by individual differences in subjective ( eg , self-image ) or objective measurements of one 's physical stature .


The findings show that exposure to virtual , gender-based auditory and visual social stimuli influences exogenous pain sensitivity .


Further research on how contextual factors , such as the vocal properties of health care examiners and exposure to background voices , may influence momentary pain perception is necessary for creating more standardized methods for measuring patient pain reports in clinical settings .


To compare early induction and expectant management regarding delivery outcomes and the experience of delivery in nulliparous women with prolonged latent phases .


Randomized controlled trial .


One delivery unit in a Swedish hospital .


Nulliparous women at term experiencing continuous contractions impeding rest ( women 's report ) and exceeding 18 h , a cervical dilation of less than 4 cm , intact membranes and with a singleton fetus in cephalic presentation .


The women were randomly allocated to either early induction ( n = 65 ) or expectant management ( n = 64 ) .


All participants received medication for therapeutic rest .


The early induction group was induced five hours after medication , and the expectant group awaited spontaneous onset of labor .


The Wijma Delivery Experience Questionnaire ( W-DEQ version B ) was filled in after delivery .


The primary outcome was mode of delivery .


Secondary outcomes included birth experience , duration of labor , postpartum hemorrhage , and neonatal outcomes .


The cesarean section rate was 15 of 65 ( 23.1 % ) in the early induction group and 24 of 64 ( 37.5 % ) in the expectant group ( p = 0.076 , OR 2.00 , 95 % CI 0.93-4 .31 ) .


No significant differences were shown regarding delivery , neonatal outcomes or birth experience .


No significant differences were shown between the two groups in the rate of cesarean sections or the experience of delivery .


According to the actual results , the power to detect a difference was only 45 % .


The cesarean section rate was high in both groups , regardless of intervention .


A double blind , randomized , unsupervised , parallel-group clinical trial was conducted on over 5,500 children in Sichuan Province , China .


This clinical trial compared the anti-caries efficacy of two test dentifrices to that of a control dentifrice .


The test dentifrices contained 1.5 % arginine , 1450 ppm fluoride as sodium monofluorophosphate ( MFP ) , and an insoluble calcium compound ( either dicalcium phosphate or calcium carbonate ) .


The positive control dentifrice contained 1450 ppm fluoride as sodium fluoride ( NaF ) , in a silica base .


The children were randomly assigned one of the toothpastes , and children residing in the same household were assigned the same dentifrice to use at home , twice a day .


Three calibrated dentists examined the children at baseline , as well as after one and two years of product use .


After one year of product use , there were no statistically significant differences among the three groups with respect to decayed , missing , and filled teeth ( DMFT ) or to decayed , missing , and filled surfaces ( DMFS ) .


After two years of product use , subjects in the two test groups using the dentifrices containing 1.5 % arginine , 1450 ppm fluoride as MFP , and an insoluble calcium compound had a statistically significant reduction in DMFT increments of 20.5 % and in DMFS increments of 19.6 % when compared to subjects in the group using the positive control dentifrice .


After two years , there were no statistically significant differences with respect to DMFT or DMFS between the two groups using the dentifrices containing 1.5 % arginine , 1450 ppm fluoride as MFP , and an insoluble calcium compound .


The use of the two test dentifrices demonstrated significant reductions in decayed , missing , and filled teeth and surfaces , however there was no statistically significant different between the two test dentifrices clinically after two years of using the toothpastes .


The results of this two-year clinical investigation support the conclusion that dentifrices containing 1.5 % arginine , an insoluble calcium compound , and 1450 ppm fluoride as MFP provide superior protection against caries lesion cavitation compared to a positive control dentifrice containing only 1450 ppm fluoride as NaF .


Although practice nurses are increasingly involved in hypertension management , there is little robust evidence of effectiveness .


To evaluate the effect of a specialist nurse-led hypertension clinic with consultant backup on change in systolic blood pressure .


Randomized trial .


Two inner city general practices .


Participants .


Three hundred and fifty-three patients , mean age 62 years ( range 18-99 ) , with last recorded blood pressure British Hypertension Society audit standard were randomly allocated to the nurse-led clinic or usual care .


Intervention .


Patients received a letter informing them that their last blood pressure was over target and inviting them to the clinic .


After assessment at the clinic , the nurse discussed any changes in anti-hypertensive treatment with a visiting consultant and the patient 's GP , and followed up the patient over 6 months until blood pressure targets were achieved .


Reduction in systolic blood pressure , assessed using two audits of the practices ' computerized records where blood pressure was measured independently by practice staff before and after the intervention period .


Follow-up was 89 % ( 313/353 ) .


There was greater reduction in systolic blood pressure in the clinic group ( n = 144 ) than usual care group ( n = 169 , adjusted difference 4.4 mmHg ; 95 % CI 0.7 to 8.2 ) .


Of 167 patients randomly selected for the clinic , 91 ( 55 % ) attended , 49 had blood pressure above target when measured according to protocol and 26 had their anti-hypertensive treatment intensified by their GP .


Invitation to a specialist nurse-led hypertension clinic with consultant back up was associated with reduced systolic blood pressure .


To evaluate the difference between a single preoperative dose versus an additional two-day postoperative course of oral amoxicillin in patients undergoing conventional dental implant placement .


Two dentists in two different private practices conducted this study .


One hour prior to surgery , patients had to take a single prophylactic antibiotic dose , consisting of 2 g of amoxicillin orally ; after implant placement , patients were randomly allocated to two different groups : protocol A ( no other antibiotic administration ) and protocol B , ( 1 g of amoxicillin in the evening of the day of surgery and 1 g twice a day for the 2 days after ) .


Outcome measures were prosthetic and implant failures , adverse events and early postoperative complications .


Patients were followed up to 6 months after functional loading .


Three hundred and sixty patients were randomised and treated ( 192 patients in one centre and 168 in the other ) .


Five hundred and sixty-seven implants were placed .


Protocol A was applied to 180 patients ( 278 implants ) and protocol B also to 180 patients ( 289 implants ) .


Data for 17 patients , 14 from protocol A and three from protocol B , were not available .


No statistically significant differences were found for the reported outcomes .


Two patients of protocol B experienced a prosthetic failure , losing four implants , while no prosthetic failures were reported for protocol A ( P = 0.4836 ; difference in proportions = -0.0110 ; 95 % CI : -0.0412 to 0.0119 ) .


Five patients ( 3.0 % ) of protocol A lost five implants versus 5 patients ( 2.8 % ) who lost eight implants in protocol B ( P = 1.0000 ; difference in proportions = 0.0020 ; 95 % CI : -0.0384 to 0.0438 ) .


Three adverse events were observed in the total population , all occurring in protocol B ( 1.69 % ) , with no statistically significant differences between the two groups ( P = 0.1199 ; difference in proportions = -0.0170 ; 95 % CI : -0.0487 to 0.0059 ) .


However , one patient experienced a severe allergic reaction requiring therapy discontinuation and hospital admission .


Early postoperative complications occurred in six patients of protocol A and in four patients of protocol B , with no statistically significant differences ( P = 0.5170 ; difference in proportions = 0.0130 ; 95 % CI : -0.0254 to 0.0568 ) .


No statistically significant differences were observed between 2 g of preoperative amoxicillin and an additional 2-day postoperative course , although adverse events were reported only in the additional 2-day postoperative group .


Based on these findings , it might be sufficient to routinely administer preoperatively 2 g of amoxicillin to patients undergoing routine dental implant placement procedures rather than administering additional postoperative doses .


Abnormal levels of CD8 T-cell activation persist in HIV-1-infected patients on suppressive antiretroviral therapy ( ART ) and may be deleterious .


CD8 T-cell activation ( % coexpressing CD38/HLA-DR ) was analyzed on blood specimens from 833 HIV-1-infected patients on ART for 96 weeks with concurrent plasma HIV RNA ( vRNA ) 200 copies per milliliter .


Factors associated with CD8 T-cell activation were assessed using generalized estimating equations to incorporate longitudinal measurements ( median 4/participant ) .


Participants were 84 % men , 47 % white , 28 % black , and 22 % Hispanic , with median pre-ART age 38 years and median ART exposure 144 weeks .


CD8 T-cell activation was higher at timepoints when vRNA was 51-200 versus 50 copies per milliliter [ mean CD8 T-cell activation 23.4 % vs. 19.7 % ; adjusted difference : 1.7 % ( 95 % confidence interval : 0.1 to 3.4 ) , P = 0.042 ] .


Restricting to vRNA 50 copies per milliliter , multivariable models showed the following factors associated with higher CD8 T-cell activation : older age [ 45 vs. 30 years : 3.6 % ( 1.4 to 5.7 ) , P = 0.004 ] , hepatitis C virus antibody positivity [ 3.6 % ( 0.9 to 6.2 ) , P = 0.032 ] , Hispanic vs. white [ 7.2 % ( 5.3 to 9.0 ) , P < 0.001 ] , lower concurrent CD4 count [ 200 vs. > 500 cells/mm : 2.2 % ( 0.7 to 3.7 ) , P < 0.001 ] , lower concurrent CD4/CD8 ratio [ -2.6 % ( -3.7 to -1.5 ) per 0.5 unit increase , P < 0.001 ] , and higher pre-ART CD8 T-cell activation [ 2.0 % ( 1.6 to 2.5 ) per 10 % higher , P < 0.001 ] .


In participants included in our analysis , residual low-level viremia between 51 and 200 copies per milliliter during ART was shown to be associated with greater CD8 T-cell activation than full suppression to < 50 copies per milliliter .


Older age , hepatitis C virus antibody positivity , race/ethnicity , higher pre-ART CD8 T-cell activation , and lower concurrent CD4/CD8 ratio and CD4 T-cell count also contribute to greater CD8 T-cell activation during suppressive ART .


Antiretroviral therapy ( ART ) is associated with improved kidney function ; however , the nucleotide reverse transcriptase inhibitor ( NRTI ) tenofovir disoproxil fumarate ( TDF ) has been associated with decreased kidney function and proteinuria .


We examined changes in urine protein : creatinine ( UPCR ) and urine albumin : creatinine ( UACR ) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI ( abacavir/lamivudine , ABC/3TC , n = 124 or TDF/emtricitabine , TDF/FTC , n = 121 ) with open-label protease inhibitor ( PI ) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor ( NNRTI ) efavirenz .


At baseline , 18 % of participants had clinically significant proteinuria ( UPCR 200 mg/g ) , and 11 % had clinically significant albuminuria ( UACR 30 mg/g ) .


The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups .


In intention-to-treat analyses , there was a significant effect of NRTI component on fold change in UPCR ( P = 0.011 ) and UACR ( P = 0.018 ) from baseline to week 96 , with greater improvements in participants randomized to ABC/3TC .


There was no significant effect of NNRTI/PI component on fold change in UPCR ( P = 0.23 ) or UACR ( P = 0.88 ) , and no significant interactions between NRTI and NNRTI/PI components .


In this prespecified secondary analysis , ART initiation was associated with improvements in proteinuria and albuminuria , with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC .


These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens .


Future studies should consider the long-term clinical significance of these findings .


This open-label , randomized study evaluated efficacy and safety of artemether-lumefantrine ( AL ) and dihydroartemisinin-piperaquine ( DP ) in treatment of uncomplicated falciparum malaria in children below five years of age , to build evidence on use of AL as first-line treatment and DP as second-line treatment in Kenya .


A total of 454 children aged six to 59 months with uncomplicated falciparum malaria were randomized ( 1:1 ) to receive AL dispersible or DP paediatric tablets and followed up for 42 days .


Primary efficacy variable was corrected adequate clinical and parasitological response ( ACPR ) rate on day 28 .


Secondary variables included corrected ( day 14 , 28 and 42 ) , uncorrected ( day 3 , 14 , 28 and 42 ) cure rates , parasitological failure at days 3 , 14 and 42 .


Acceptability and tolerability of both drugs were assessed by caregiver questionnaire .


On day 28 , corrected ACPR rates for AL dispersible and DP paediatric were 97.8 % ( 95 % CI : 94.9-99 .3 ) and 99.1 % ( 95 % CI : 96.8-99 .9 ) , respectively , in intention-to-treat population , with no significant treatment differences noted between AL dispersible and DP paediatric arms .


Additionally , no significant differences were observed for PCR corrected cure rates on days 14 and ACPR on day 42 for AL dispersible ( 100 % ; 96.8 % ) and DP paediatric ( 100 % ; 98.7 % ) .


Similarly , for PCR uncorrected cure rates , no significant differences were seen on days 3 , 14 , 28 , and 42 for AL dispersible ( 99.1 % ; 98.7 % ; 81.1 % ; 67.8 % ) and DP paediatric ( 100 % ; 100 % ; 87.7 % ; 70.5 % ) .


Parasite clearance was rapid , with approximately 90 % clearance achieved in 40 hours in both treatment arms .


Incidence of adverse events was related to underlying disease ; malaria being reported in both treatment arms .


One serious adverse event was noted in AL dispersible ( 0.42 % ) arm , not related to study drug .


Adherence to treatment regimen was higher for children treated with AL dispersible ( 93.6 % ) compared to DP paediatric ( 85.6 % ) .


Acceptability of AL dispersible regimen was assessed as being significantly better than DP paediatric .


AL and DP were both efficacious and well tolerated , and had similar effects at day 42 on risk of recurrent malaria .


No signs of Plasmodium falciparum tolerance to artemisinins were noted .


PACTR201111000316370 .


Tracheostomy facilitates respiratory care and the process of weaning from mechanical ventilatory support .


To compare the complications found in percutaneous dilatational tracheostomy ( PDT ) and surgical tracheostomy ( ST ) techniques .


This was a prospective randomized study to evaluate the complications of PDT and ST procedures in patients admitted to ICU unit of a teaching hospital during 2008 to 2011 .


We studied 40 patients in each group .


PDTs were performed with blue rhino technique at the bedside by a skilled clinician and all cases of STs performed by Charles G Durbin technique in operating room under general anesthesia .


Bronchoscopic examination through tracheostomy tube was performed to ensure the correct position of tracheostomy tube in the trachea lumen .


The duration of procedures and pre - and post-interventional complications were recorded .


The most common complications observed in the PDT group were minor bleeding ( n = 4 ) , hypoxemia , and cardiac dysrhythmias ( n = 3 ) whereas in the ST group , the most frequent complications were minor bleeding ( n = 5 ) and endotracheal tube puncture ( n = 3 ) .


The difference in overall complications between the two groups was insignificant ( P = 0.12 ) .


PDT with blue rhino technique is a safe , quick , and effective method while the overall complications in both groups were comparable .


To assess the influence of the surgical removal of partially impacted third molars ( 3Ms ) and compare the effects of a 3-cornered laterally rotated flap ( LRF ) with primary closure ( flap 1 ) and an envelope flap with secondary closure ( flap 2 ) on the short-term periodontal status of the adjacent second molars ( 2Ms ) .


We also assessed the postoperative complications after removal of the partially impacted 3M .


A split mouth , randomized clinical study was designed .


The study sample included patients with bilateral partially impacted 3Ms .


The primary predictor variable was the type of flap design ( flaps 1 and 2 ) .


The primary outcome variable was periodontal status ( gingival recession [ GR ] , probing depth [ PD ] , plaque index [ PI ] , and gingival index ) of the 2Ms measured preoperatively and 90 days postoperatively .


The secondary outcome variables were postoperative complications , including pain , facial swelling , alveolitis , and local wound infection .


The other variables included gender , position of the 3Ms , and surgical difficulty .


We performed descriptive , comparative , correlation , and multivariate analyses .


The sample included 28 patients aged 18 to 28 years .


The GR , PD , and PI values with the flap 2 design were greater than those with the flap 1 design ( P < .05 ) .


Facial swelling with the flap 1 design was significantly greater than with the flap 2 design on the second postoperative day ( P < .05 ) .


The pain levels with the flap 1 design were significantly greater than those with the flap 2 design on the first and second postoperative days ( P < .05 ) .


According to the multivariate regression analyses , flap design was closely related to the periodontal status of the 2Ms and postoperative discomfort .


The results of the present clinical study have shown that the flap design in partially impacted 3M surgery considerably influences the early periodontal health of the 2Ms and postoperative discomfort .


However , although the 3-cornered LRF design might cause more pain and swelling , it could be the method of choice for partially impacted 3M surgery because of the early periodontal healing .


Recent data suggest that intraoperative ( Phase I ) colloid ( human serum albumin [ HSA ] ) and a high fresh frozen plasma ( FFP ) / red blood cell ( RBC ) resuscitation will reduce postoperative ( Phase II ) fluid uptake .


This study compares a noncolloid ( balanced electrolyte solution [ BES ] ) plus low ( 0.35 ) FFP/RBC resuscitation ( Group A ) with an HSA plus high ( > 0.35 ) FFP/RBC resuscitation .


A previous randomized study of 94 patients included 48 BES patients and 46 HSA patients .


A Subgroup A of 25 BES patients with low FFP/RBC was compared with a Subgroup D of 21 HSA patients with high FFP/RBC .


Parameters monitored included Phase I vital signs and resuscitation needs ; Phase II duration , BES needs , weight gain , and hourly urine output ; and postoperative plasma volume ( PV ) by radioiodinated serum albumin ( RISA ) , extracellular fluid ( ECF ) volume by inulin space , and interstitial volume by ECF-PV .


Admission pulse ( 132 for A vs. 133 for D ) , systolic blood pressure ( SBP ) ( 74 for A vs. 74 for D ) and Phase I shock time ( SBP < 80 Torr ; 25 for A vs. 35 for D ) were similar .


Phase I RBC needs ( 12.5 1.3 for A vs. 14.9 1.7 for D ) and BES needs ( 8.4 0.6 L for A vs. 8.4 0.6 L for D ) were similar .


During Phase II , D patients had more RBC , comparable BES , and weight gain , with lower hourly urine output compared with Group A patients .


HSA with high FFP/RBC does not prevent Phase II fluid uptake and causes lower urine output despite increased PV .


Colloid reduces glomerular filtration , increases tubular reabsorption , and increases ECF , thus , prolonging Phase II .


Therapeutic study , level IV .


To compare two self-titration algorithms for initiating and escalating prandial insulin lispro in patients with type 2 diabetes inadequately controlled on basal insulin .


The trial was designed as two independent , multinational , parallel , open-label studies ( A and B ) , identical in design , to provide substantial evidence of efficacy and safety in endocrine and generalist settings .


Subjects were 18-85 years old ( study A : N = 528 ; study B : N = 578 ) , on basal insulin plus oral antidiabetic drugs for 3 months , and had an HbA1c 7.0 % to 12.0 % ( > 53.0 to 107.7 mmol/mol ) .


Once optimized on insulin glargine , subjects were randomized to one of two self-titration algorithm groups adjusting lispro either every day ( Q1D ) or every 3 days ( Q3D ) for 24 weeks .


The primary outcome was the change in HbA1c from baseline .


The primary and secondary objectives were evaluated for the overall population and subjects 65 years old .


Baseline HbA1c was similar ( study A : Q1D 8.3 % [ 67.2 mmol/mol ] vs. Q3D 8.4 % [ 68.3 mmol/mol ] , P = 0.453 ; study B : Q1D 8.3 % [ 67.2 mmol/mol ] vs. Q3D 8.4 % [ 68.3 mmol/mol ] , P = 0.162 ) .


Both algorithms had significant and equivalent reductions in HbA1c from baseline ( study A : Q3D -0.96 % [ -10.49 mmol/mol ] , Q1D -1.00 % [ -10.93 mmol/mol ] , Q3D-Q1D 0.04 % [ 0.44 mmol/mol ] [ 95 % CI -0.15 to 0.22 ( -1.64 to 2.40 ) ] ; study B : Q3D -0.92 % [ -10.06 mmol/mol ] , Q1D -0.98 % [ -10.71 mmol/mol ] , Q3D-Q1D 0.06 % [ 0.66 mmol/mol ] [ 95 % CI -0.12 to 0.24 ( -1.31 to 2.62 ) ] ) .


The incidence and rate of hypoglycemia were similar for Q3D and Q1D in both studies .


In general , no clinically relevant differences were found between the two algorithms in subjects 65 years old in either study .


Prandial insulin lispro can effectively and safely be initiated , by either of two self-titrated algorithms , in a variety of practice settings .


Interferon-free regimens are needed to treat hepatitis C virus ( HCV ) infections .


We investigated the efficacy of combined simeprevir and sofosbuvir .


We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon ( peginterferon ) and ribavirin or were treatment naive .


Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with ( group 1 ) or without ( group 2 ) ribavirin or for 12 weeks with ( group 3 ) or without ( group 4 ) ribavirin , in two cohorts : previous non-responders with METAVIR scores F0-F2 ( cohort 1 ) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 ( cohort 2 ) .


The primary endpoint was sustained virological response 12 weeks after stopping treatment ( SVR12 ) .


Analysis was done by intention to treat .


Safety data from cohorts 1 and 2 were pooled for analysis .


This study is registered with ClinicalTrials.gov , number NCT01466790 .


168 patients were enrolled and randomised , and 167 started treatment ( n = 80 in cohort 1 and n = 87 in cohort 2 ) .


SVR12 was achieved in 154 ( 92 % ) patients ( n = 72 [ 90 % , 95 % CI 81-96 ] in cohort 1 and n = 82 [ 94 % , 87-98 ] in cohort 2 ) .


The most common adverse events in the pooled groups were fatigue ( n = 52 [ 31 % ] ) , headache ( n = 33 [ 20 % ] ) , and nausea ( n = 26 [ 16 % ] ) .


Grade 4 adverse events were seen in one ( 2 % ) of 54 patients in each of groups 1 and 3 and in three ( 10 % ) of 31 patients in group 2 , whereas grade 3-4 events were reported in less than 5 % of all patients , except increased blood amylase concentration .


Serious adverse events were seen in four ( 2 % ) patients , all in groups 1 and 2 .


Four ( 2 % ) patients discontinued all study treatment because of adverse events , three before week 12 .


Combined simeprevir and sofosbuvir was efficacious and well tolerated .


Janssen .


We investigated the influences of the inner retinal sublayers and analytical areas in macular scans by spectral-domain optical coherence tomography ( OCT ) on the diagnostic ability of early glaucoma .


A total of 64 early ( including 24 preperimetric ) glaucomatous and 40 normal eyes underwent macular and peripapillary retinal nerve fiber layer ( pRNFL ) scans ( 3D-OCT-2000 ) .


The area under the receiver operating characteristics ( AUC ) for glaucoma diagnosis was determined from the average thickness of the total 100 grids ( 6 6 mm ) , central 44 grids ( 3.6 4.8 mm ) , and peripheral 56 grids ( outside of the 44 grids ) , and for each macular sublayer : macular RNFL ( mRNFL ) , ganglion cell layer plus inner plexiform layer ( GCL/IPL ) , and mRNFL plus GCL/IPL ( ganglion cell complex [ GCC ] ) .


Correlation of OCT parameters with visual field parameters was evaluated by Spearman 's rank correlation coefficients ( rs ) .


The GCC-related parameters had a significantly larger AUC ( 0.82-0 .97 ) than GCL/IPL ( 0.81-0 .91 ) , mRNFL-related parameters ( 0.72-0 .94 ) , or average pRNFL ( 0.88 ) in more than half of all comparisons .


The central 44 grids had a significantly lower AUC than other analytical areas in GCC and mRNFL thickness .


Conversely , the peripheral 56 grids had a significantly lower AUC than the 100 grids in GCL/IPL inferior thickness .


Inferior thickness of GCC ( rs , 0.45-0 .49 ) and mRNFL ( rs , 0.43-0 .51 ) showed comparably high correlations with central visual field parameters to average pRNFL thickness ( rs , 0.41 , 0.47 ) even in the central 44 grids .


The diagnostic ability of macular OCT parameters for early glaucoma differed by inner retinal sublayers and also by the analytical areas studied .


Use of an injection site modulation device ( InsuPad ) in intensive insulin treatment reduces frequency of hypoglycemia and prandial insulin requirements by enhancing subcutaneous microcirculation .


This meal tolerance test ( MTT ) investigation was performed as a sub-study during the real-world BARMER study to demonstrate non-inferiority of the reduced insulin doses observed in this study with respect to metabolic control .


The MTT was performed at baseline and after 3 months in insulin treated diabetes patients using the modulation device vs. a control group without device .


The dose used for the MTT was individually calculated based on the prandial insulin records from the patient diaries before the test .


Blood was drawn for determination of glucose , insulin , C-peptide , proinsulin , triglycerides , free fatty acids , nitrotyrosine , and asymmetric dimethyl-arginine ( ADMA ) at multiple time-points from 0 to 300min .


A total of 32 patients from one site were included into this MTT study ( 8 female , 7 type 1 diabetes , age : 49.912.5 yrs , HbA1c : 7.20.5 % ) .


During the BARMER study , mean HbA1c was treated to target ( < 6.5 % ) in both groups .


The prandial insulin dose decreased in the MTT modulation device group by -17.1 % , but remained unchanged in the control group ( -0.1 % , p < 0.001 ) .


No change was seen for the basal insulin dose in both treatment arms .


There were no differences between the groups with respect to the postprandial curves for glucose , C-peptide , intact proinsulin , free fatty acids , and triglycerides .


Insulin absorption was faster with the modulation device ( Tmax : 6028min vs. 9946min , p < 0.05 ) .


Key limitations are the small patient sample size and impossibility to determine the short-term effects of device use .


The results of this meal tolerance sub-study confirm that the observed prandial insulin dose reduction when using the injection site modulation device has no negative impact on postprandial metabolism .


This is the final report of a phase III randomized study to evaluate whole-brain radiotherapy ( WBRT ) in primary therapy of primary CNS lymphoma ( PCNSL ) after a median follow-up of 81.2 months .


Patients with newly diagnosed PCNSL were randomized to high-dose methotrexate ( HDMTX ) - based chemotherapy alone or followed by WBRT .


We hypothesized that the omission of WBRT would not compromise overall survival ( OS ; primary endpoint ) , using a noninferiority design with a margin of 0.9 .


In the per-protocol population ( n = 320 ) , WBRT nonsignificantly prolonged progression-free survival ( PFS ) ( median 18.2 vs 11.9 months , hazard ratio [ HR ] 0.83 [ 95 % confidence interval ( CI ) 0.65-1 .06 ] , p = 0.14 ) and significantly PFS from last HDMTX ( 25.5 vs 12.0 months , HR 0.65 [ 95 % CI 0.5-0 .83 ] , p = 0.001 ) , but without OS prolongation ( 35.6 vs 37.1 months , HR 1.03 [ 95 % CI 0.79-1 .35 ] , p = 0.82 ) .


In the intent-to-treat population ( n = 410 ) , there was a prolongation by WBRT of both PFS ( 15.4 vs 9.9 months , HR 0.79 [ 95 % CI 0.64-0 .98 ] , p = 0.034 ) and PFS from last HDMTX ( 19.4 vs 11.9 months , HR 0.72 [ 95 % CI 0.58-0 .89 ] , p = 0.003 ) , but not of OS ( 32.4 vs 36.1 months , HR 0.98 [ 95 % CI 0.79-1 .26 ] , p = 0.98 ) .


Although the statistical proof of noninferiority regarding OS was not given , our results suggest no worsening of OS without WBRT in primary therapy of PCNSL .


This study provides Class II evidence that in PCNSL HDMTX-based chemotherapy followed by WBRT does not significantly increase survival compared to chemotherapy alone .


The study lacked the precision to exclude an important survival benefit or harm from WBRT .


The antimetabolite 5-fluorouracil ( 5-FU ) is used for topical treatment of actinic keratosis .


Overall improvement in the skin is also observed .


Additionally , 5-FU was reported to be used for superficial peels .


To evaluate the efficacy and safety of 5 % 5-FU cream compared with peels for photodamaged forearms .


This interventional , randomized , comparative , evaluator-blind study included 32 patients with severe photoaging of forearms .


The regimens comprised either application of 5 % 5-FU cream everyday for 4 weeks on 1 forearm and 4 weekly peels on the other .


Efficacy assessment included : clinical photodamage scores , opinion of patients and investigators , and blind photographic evaluation by independent observers .


Skin biopsies were performed for histologic and immunohistochemical analysis .


Safety evaluation comprised observation of adverse events .


Clinical and histologic findings confirmed the benefits of topical 5 % 5-FU , in cream or peels , which improved skin appearance and decreased the dermal elastotic material .


Immunohistochemistry showed reduced levels of epidermal p53 and increase in the level of procollagen I. Results were maintained after 6 months .


Predictable adverse events occurred , with no differences between treatments .


Patients reported better tolerability to peels .


Five percent 5-FU cream or peels was safe and effective for the treatment of photodamaged forearms .


Decreased epidermal p53 levels and new dermal collagen were confirmed .


We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes .


The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle , metformin , or placebo interventions for 3.4 years .


Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing .


In addition to baseline testing , anthropometry was performed every 6 months ; fasting insulin yearly ; and hs-CRP , tissue plasminogen activator ( tPA ) , and fibrinogen at 1 year and end of study ( EOS ) .


CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS .


These reductions were not seen in those who developed diabetes over the course of the study despite intervention .


Fibrinogen was lower at 1 year in the lifestyle group .


Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group , but only partly in the placebo and metformin groups .


Weight , insulin sensitivity , and hyperglycemia differences each accounted for the influence of diabetes on the tPA response .


Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA .


Incident diabetes prevented these improvements , and this was accounted for by differences in weight , insulin resistance , and glucose levels .


A single-agent , extended-release formulation of hydrocodone ( HC ) has been developed for treatment of chronic moderate-to-severe pain .


This study was designed to examine the safety and efficacy of HC extended release in opioid-experienced adults with moderate-to-severe chronic low back pain ( CLBP ) .


This multicenter , enriched enrollment , randomized withdrawal study comprised an open-label conversion/titration phase ( 6 weeks ) followed by placebo-controlled , double-blind treatment ( 12 weeks ) .


During the conversion/titration phase , subjects ( N = 510 ) converted from their current opioid and were titrated to a stabilized dose of HC extended release ( 20-100mg every 12 hours ) .


During treatment , subjects ( N = 151 per group ) received HC extended release or placebo ; rescue medication was permitted .


The primary efficacy end point was mean change in average pain intensity from baseline to day 85 .


Response rates ( 30 % pain improvement ) and satisfaction ( Subject Global Assessment of Medication ) were assessed .


Demographic and baseline characteristics were similar between groups .


MeanSD change in average pain intensity score from baseline to day 85 was significantly lower in the HC extended-release treatment group vs placebo ( 0.481.56 vs 0.961.55 ; P = 0.008 ) .


Significantly more responders were in the treatment group ( 68 % vs 31 % ; P < 0.001 ) .


Mean Subject Global Assessment of Medication scores increased significantly ( 0.81.3 vs 0.01.4 ; P < 0.0001 ) , indicating greater satisfaction with HC extended release .


The adverse event profile was consistent with other opioids .


Extended-release HC is well tolerated and effective , without acetaminophen-associated risks of liver toxicity , for treatment of CLBP .


Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration .


To evaluate the safety and efficacy of ixmyelocel-T in 2 prospective randomized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy ( DCM ) stratified by ischemic or nonischemic status .


In IMPACT-DCM , patients were randomized to either ixmyelocel-T or standard-of-care control in a 3:1 ratio ( n = 39 ) ; ixmyelocel-T was administered intramyocardially via minithoracotomy .


In Catheter-DCM , patients were randomized to either ixmyelocel-T or standard of care control in a 2:1 ratio ( n = 22 ) ; ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter .


Only patients randomized to ixmyelocel-T underwent bone marrow aspiration and injections .


In the 2 studies , a total of 61 patients were randomized , and 59 were treated or received standard of care .


Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients .


A similar benefit was not seen in the nonischemic patients .


Heart failure exacerbation was the most common major adverse cardiovascular event .


Ixmyelocel-T treatment was associated with improved New York Heart Association class , 6-minute walk distance , and Minnesota Living with Heart Failure Questionnaire scores in the ischemic population relative to control ; a similar trend was not observed in the nonischemic population .


Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM .


To assess the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire , drug consumption , days of migraine , pain intensity and functional disability .


3-Armed randomized controlled trial setting : all patients admitted in the Department of Neurology of Ancona 's United Hospitals , Italy , with a diagnosis of migraine and without chronic illness , were considered eligible for the study .


Patients were randomly divided into three groups : ( 1 ) OMT + medication therapy , ( 2 ) sham + medication therapy and ( 3 ) medication therapy only .


Patients received 8 treatments in a study period of 6 months .


Changing from baseline HIT-6 score .


105 subjects were included .


At the end of the study , ANOVA showed that OMT significantly reduced HIT-6 score ( mean change scores OMT-conventional care : -8.74 ; 95 % confidence interval ( CI ) -12.96 to -4.52 ; p < 0.001 and OMT-sham : -6.62 ; 95 % CI -10.85 to -2.41 ; p < 0.001 ) , drug consumption ( OMT-sham : RR = 0.22 , 95 % CI 0.11-0 .40 ; OMT-control : RR = 0.20 , 95 % CI 0.10-0 .36 ) , days of migraine ( OMT-conventional care : M = -21.06 ; 95 % CI -23.19 to -18.92 ; p < 0.001 and OMT-sham : -17.43 ; 95 % CI -19.57 to -15.29 ; p < 0.001 ) , pain intensity ( OMT-sham : RR = 0.42 , 95 % CI 0.24-0 .69 ; OMT-control : RR = 0.31 , 95 % CI 0.19-0 .49 ) and functional disability ( p < 0.001 ) .


These findings suggest that OMT may be considered a valid procedure for the management of migraineurs .


The present trial was registered on www.ClinicalTrials.gov ( identifier : NCT01851148 ) .


The aim of this study was to assess the efficacy of strontium ranelate in improving symptoms in knee OA .


Symptoms were assessed over 3 years in patients with primary knee OA receiving strontium ranelate 2 g/day ( n = 454 ) , 1 g/day ( n = 445 ) or placebo ( n = 472 ) in the Strontium Ranelate Efficacy in Knee Osteoarthritis Trial .


Clinical response was evaluated using WOMAC subscores , minimal perceptible clinical improvement ( MPCI ) , minimal clinically important improvement ( MCII ) and a modified OMERACT-Osteoarthritis Research Society International ( OARSI ) responder definition .


Patients who withdrew prematurely from the study were considered non-responders .


There was no significant effect on symptoms for strontium ranelate 1 g/day .


At the dosage of 2 g/day , strontium ranelate was associated with greater response than placebo in terms of 20 % improvement in WOMAC pain from baseline to the last visit ( 58 % vs 47 % , P = 0.002 ) and 50 % improvement in WOMAC pain ( 42 % vs 36 % , P = 0.083 ) .


Significant differences were found in MPCI response for WOMAC pain ( 52 % vs 40 % , P < 0.001 ) , stiffness ( 47 % vs 39 % , P = 0.009 ) and physical function ( 46 % vs 37 % , P = 0.009 ) and in MCII response for WOMAC physical function ( 46 % vs 37 % , P = 0.013 ) .


There were also more OMERACT-OARSI-like responders with strontium ranelate ( 44 % vs 35 % , P = 0.004 ) .


The treatment-placebo difference in MPCI response for WOMAC pain was significant after 6 months ( P = 0.024 ) , while that in MPCI and MCII response for WOMAC physical function reached significance after 12 months ( P = 0.027 and P = 0.019 , respectively ) .


Treatment with strontium ranelate 2 g/day over 3 years is associated with a clinically meaningful improvement in pain from 6 months as well as physical function and stiffness as assessed by the number of responders above thresholds of clinical relevance .


Current Controlled Trials .


http://www.controlled-trials.com/ ( ISRCTN41323372 ) .


Eighty-five percent of institutionalized elderly people have osteoporosis and bone fracture rates 8 to 9 times higher than rates observed among community-dwelling elderly people .


Nevertheless , most of these persons are left untreated and are excluded from pivotal osteoporosis trials .


To determine the efficacy and safety of zoledronic acid to treat osteoporosis in frail elderly women in long-term care facilities .


We conducted a 2-year , randomized , placebo-controlled , double-blinded study from December 2007 through March 2012 .


Included were 181 women 65 or older with osteoporosis , including those with cognitive impairment , immobility , and multimorbidity , who were living in nursing homes and assisted-living facilities .


One 5-mg dose of zoledronic acid or placebo intravenously and daily calcium and vitamin D supplementation .


Hip and spine bone mineral density ( BMD ) at 12 and 24 months and adverse events .


There were no baseline differences in mean ( SE ) age ( 85.4 [ 0.6 ] years ) , BMD , or functional or cognitive status , but the treatment group included more participants with frailty , falls history , diabetes , and anticonvulsant medication use .


Values for BMD were available for 87 % of participants at 12 months and 73 % at 24 months .


Mean ( SE ) BMD changes were greater in the treatment group : 3.2 ( 0.7 ) and 3.9 ( 0.7 ) percentage-point differences in the total hip at 12 and 24 months , respectively ( P < .01 for both comparisons ) , and 1.8 ( 0.7 ) and 3.6 ( 0.7 ) percentage-point differences at the spine ( P < .01 ) ; adjusted analyses were similar .


The treatment and placebo groups ' fracture rates were 20 % and 16 % , respectively ( OR , 1.30 ; 95 % CI , 0.61-2 .78 ) ; mortality rates were 16 % and 13 % ( OR , 1.24 ; 95 % CI , 0.54-2 .86 ) .


Groups did not differ in the proportion of single fallers ( 28 % vs 24 % ; OR , 1.24 ; 95 % CI , 0.64-2 .42 ; P = .52 ) , but more participants in the treatment group had multiple falls ( 49 % vs 35 % ; OR , 1.83 ; 95 % CI , 1.01-3 .33 ; P = .047 ) ; however , this difference was no longer significant when adjusted for baseline frailty .


In this group of frail elderly women with osteoporosis , 1 dose of zoledronic acid improved BMD over 2 years .


The clinical importance of nonsignificant increases in fracture and mortality rates in the treatment group needs further study .


Since it is not known whether such therapy reduces the risk of fracture in this cohort , any change in nursing home practice must await results of larger trials powered to assess fracture rates .


clinicaltrials.gov Identifier : NCT00558012 .


Nutrition is an important aspect in the care of very low birth weight ( VLBW ) preterm infants .


Human milk fortified with human milk fortifiers ( HMF ) is best for enteral feeding of premature infants .


HMF is expensive and not easily available in Thailand .


Post discharge formula ( PDF ) has been routinely used to fortify human milk at Queen Sirikit National Institute of Child Health ( QSNICH ) but there is lack of supportive data regarding efficacy and safety .


To study and compare anthropometrics , biochemical markers and complications in VLBW infants fed human milk fortified with either HMF or PDF .


This was a prospective , randomized pilot study conducted in the neonatal unit of QSNICH from 1 March 2010 to 28 February 2011 .


Very low birth weight neonates , whose mothers had adequate breast milk within 96 hours of birth , were enrolled in the study and received parenteral nutrition and enteral feeding as per protocol .


Once the babies were feeding 100 cc/kg/day of human milk , they were randomly divided into two groups : the human milk fortified group ( HMF group ) and the post discharge formula fortified group ( PDF group ) .


Body weight was recorded daily while head circumference and length were recorded weekly .


Hematocrit , Blood Urea Nitrogen ( BUN ) , creatinine , electrolytes ( including phosphorus and calcium ) , alkaline phosphatase and albumin were checked at the beginning of the study ( feeding 100 cc/kg/day ) , 3 weeks later and when on full oral breast feeding or reached a weight of 2,000 grams , which ever came first .


Thirty-eight infants were enrolled in the study but eventually only 33 remained ( 18 in HMF group , 15 in PDF group ) .


Both groups had similar baseline demographic data , nutritional management , postnatal morbidities and length of stay .


There were no statistically significant differences in growth parameters and serum biochemical markers between the groups .


Definite NEC was not different between the groups .


Other complications of prematurity including osteopenia of prematurity were similar in both the groups .


The cost of breast milk fortification per person in the PDF and HMF group was 605 and 11,655 baht , respectively .


Human milk fortifiers are best for fortification of human milk in VLBW babies but using PDF as a fortifier may be considered as an alternative for VLBW infant in resource limited , developing countries .


However , it should always be additionally supplemented with multivitamins especially vitamin D , iron , calcium and phosphorus .


Complications like feeding intolerances and suspected NEC should be monitored closely .


Larger studies focusing on short and long-term outcomes are needed in the future .


Based on current evidence , there is a little agreement on the best timing for after birth umbilical cord clamping .


This study was designed to compare the impact of using two different times for cord clamping on hematocrit concentration and Apgar scores of the neonate .


Fifty-six healthy full-term vaginally born neonates were allocated to early ( 10 seconds after delivery ) and late ( 3 minutes after delivery ) umbilical cord clamping groups in this randomized clinical trial .


We recorded the length of the 3rd stage of labor and Apgar score at 5 minutes .


Infant 's hematocrit was measured at 2 and 18 hours of age .


Neonatal hematocrit differed between the two groups .


Late cord clamping group had greater hematocrit at 2 hours ( 45.5 4 vs. 49.5 4.4 , P = 0.0003 ) and 18 hours ( 47.7 5.5 vs. 52.9 4.3 , P = 0.0002 ) .


Apgar scores at 5 minutes ( 9.3 0.6 vs. 9.4 0.6 , p = 0.5 ) and duration of delivery 3rd stage ( 10.2 3.7 min vs. 8.9 5 min , P = 0.2 ) did not differ between early and late cord clamping groups respectively .


Late cord clamping leads to a significant increase in the hematocrit of the neonate but it does not have effects on Apgar score and duration of the 3rd stage of labor .


Unintentional injury is a leading cause of infant mortality .


To examine the role of caregiver health literacy in infant injury prevention behaviors .


A cross-sectional analysis of data collected in 2010-2012 from a randomized trial at four pediatric clinics was performed in 2012-2013 .


Caregiver health literacy was assessed with the Short Test of Functional Health Literacy in Adults .


Caregiver-reported adherence to American Academy of Pediatrics-recommended injury prevention behaviors was assessed across seven domains : ( 1 ) car seat position ; ( 2 ) car seat use ; ( 3 ) sleeping safety ; ( 4 ) fire safety ; ( 5 ) hot water safety ; ( 6 ) fall prevention ; and ( 7 ) firearm safety .


Data were analyzed from 844 English - and Spanish-speaking caregivers of 2-month-old children .


Many caregivers were non-adherent with injury prevention guidelines , regardless of health literacy .


Notably , 42.6 % inappropriately placed their children in the prone position to sleep , and 88.6 % did not have their hot water heater set < 120F .


Eleven percent of caregivers were categorized as having low health literacy .


Low caregiver health literacy , compared to adequate health literacy , was significantly associated with increased odds of caregiver non-adherence with recommended behaviors for car seat position ( AOR = 3.4 , 95 % CI = 1.6 , 7.1 ) and fire safety ( AOR = 2.0 , 95 % CI = 1.02 , 4.1 ) recommendations .


Caregivers with low health literacy were less likely to be non-adherent to fall prevention recommendations ( AOR = 0.5 , 95 % CI = 0.2 , 0.9 ) .


Non-adherence to injury prevention guidelines was common .


Low caregiver health literacy was significantly associated with some injury prevention behaviors .


Future interventions should consider the role of health literacy in promoting injury prevention .


During primary percutaneous coronary intervention ( PCI ) , manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion .


Small trials have suggested that thrombectomy improves surrogate and clinical outcomes , but a larger trial has reported conflicting results .


We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction ( STEMI ) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone .


The primary outcome was a composite of death from cardiovascular causes , recurrent myocardial infarction , cardiogenic shock , or New York Heart Association ( NYHA ) class IV heart failure within 180 days .


The key safety outcome was stroke within 30 days .


The primary outcome occurred in 347 of 5033 patients ( 6.9 % ) in the thrombectomy group versus 351 of 5030 patients ( 7.0 % ) in the PCI-alone group ( hazard ratio in the thrombectomy group , 0.99 ; 95 % confidence interval [ CI ] , 0.85 to 1.15 ; P = 0.86 ) .


The rates of cardiovascular death ( 3.1 % with thrombectomy vs. 3.5 % with PCI alone ; hazard ratio , 0.90 ; 95 % CI , 0.73 to 1.12 ; P = 0.34 ) and the primary outcome plus stent thrombosis or target-vessel revascularization ( 9.9 % vs. 9.8 % ; hazard ratio , 1.00 ; 95 % CI , 0.89 to 1.14 ; P = 0.95 ) were also similar .


Stroke within 30 days occurred in 33 patients ( 0.7 % ) in the thrombectomy group versus 16 patients ( 0.3 % ) in the PCI-alone group ( hazard ratio , 2.06 ; 95 % CI , 1.13 to 3.75 ; P = 0.02 ) .


In patients with STEMI who were undergoing primary PCI , routine manual thrombectomy , as compared with PCI alone , did not reduce the risk of cardiovascular death , recurrent myocardial infarction , cardiogenic shock , or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days .


( Funded by Medtronic and the Canadian Institutes of Health Research ; TOTAL ClinicalTrials.gov number , NCT01149044 . )


Expert consensus guidelines recommend low-density lipoprotein cholesterol as the primary serum lipid target for recurrent stroke risk reduction .


However , mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk .


Little is known about the effects of nontraditional lipid variables on recurrent stroke risk .


We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent ( < 120 days ) noncardioembolic stroke patients followed up for 2 years .


Independent associations of baseline serum lipid variables with recurrent ischemic stroke ( primary outcome ) and the composite end point of ischemic stroke/coronary heart disease/vascular death ( secondary outcomes ) were assessed .


Of all variables evaluated , only triglycerides/high-density lipoprotein cholesterol ( HDL-C ) ratio was consistently and independently related to both outcomes : compared with the lowest quintile , the highest triglycerides/HDL-C ratio quintile was associated with stroke ( adjusted hazard ratio , 1.56 ; 95 % confidence interval , 1.05-2 .32 ) and stroke/coronary heart disease/vascular death ( 1.39 ; 1.05-1 .83 ) , including adjustment for lipid modifier use .


Compared with the lowest quintile , the highest total cholesterol/HDL-C ratio quintile was associated with stroke/coronary heart disease/vascular death ( 1.45 ; 1.03-2 .03 ) .


Low-density lipoprotein cholesterol/HDL-C ratio , non-HDL-C , elevated triglycerides alone , and low HDL-C alone were not independently linked to either outcome .


Of various nontraditional lipid variables , elevated baseline triglycerides/HDL-C and total cholesterol/HDL-C ratios predict future vascular risk after a stroke , but only elevated triglycerides/HDL-C ratio is related to risk of recurrent stroke .


Future studies should assess the role of triglycerides/HDL-C as a potential therapeutic target for global vascular risk reduction after stroke .


There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances ( SD ) in patients with Alzheimer disease ( AD ) .


We tested the efficacy and safety of trazodone to treat SD in patients with AD .


We conducted a double-blind , randomized and controlled trial during periods of 7-9 days at baseline and 2 weeks of treatment .


Geriatric medical center of the university 's general hospital .


Individuals with probable AD and SD .


The complete analysis comprised 30 patients assigned to either the active treatment group ( N = 15 ) or the placebo group ( N = 15 ) .


Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks .


Patients were evaluated using actigraphy and structured scales before and after intervention .


Compared with the placebo group , trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment .


Neither trazodone nor placebo induced significant daytime sleepiness or naps .


The treatments with trazodone or placebo did not show any effects either on cognition ( Mini-Mental State Examination , forward/backward digit span task , letter-number sequencing , arithmetic , digit symbol-coding , and symbol search ) or functionality ( Katz index ) .


There were no differences in frequency or severity rating of adverse events between the groups .


This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD .


Despite rising international rates of obesity , men remain reluctant to participate in weight loss research .


There is a lack of evidence to guide the development of effective weight loss interventions that engage men .


The objective of this study was to provide a comprehensive process evaluation of the SHED-IT ( Self-Help , Exercise and Diet using Information Technology ) weight loss program for men , as delivered in the SHED-IT community weight loss trial , and to identify key components associated with success .


In an assessor-blinded randomised controlled trial , 159 overweight and obese men ( BMI 25.0-40 .0 kg/m2 ) were randomised to one of two gender-tailored weight loss interventions with no face-to-face contact , or a control group .


The interventions were informed by Bandura 's Social Cognitive Theory ( SCT ) with men encouraged to complete a Support Book containing SCT-based tasks including goal setting , reward setting , creation of social support strategies and self-monitoring of : i ) weight , ii ) physical activity , and iii ) diet .


At post-test , compliance with SCT tasks was examined and men also completed a process evaluation questionnaire .


Both SHED-IT intervention groups demonstrated greater weight loss during the intervention compared to the control , with no difference between intervention groups .


Most men engaged with the SCT tasks although compliance declined over time and utilisation of social support networks and reward selection was poor .


In a multiple regression model , the number of goals set ( [ 95 % CI ] = -0.3 [ -0.6 , -0.1 ] , p = 0.01 ) and the number of weight records documented ( [ 95 % CI ] = -0.2 [ -0.4 , -0.0 ] , p = 0.03 ) independently predicted weight loss .


The process evaluation indicated that men found the programs to be supportive , enjoyable and beneficial .


This process evaluation provides valuable information to inform the development of obesity treatment strategies that engage men .


Future studies with men should include a strong focus on self-monitoring and goal setting to enhance behaviour change and improve treatment effects .


Australian New Zealand Clinical Trials Registry ACTRN12610000699066 .


Hepatocellular carcinoma ( HCC ) risk-scores may predict HCC in Asian entecavir ( ETV ) - treated patients .


We aimed to study risk factors and performance of risk scores during ETV treatment in an ethnically diverse Western population .


We studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network .


A total of 744 patients were included ; 42 % Caucasian , 29 % Asian , 19 % other , 10 % unknown .


At baseline , 164 patients ( 22 % ) had cirrhosis .


During a median follow-up of 167 ( IQR 82-212 ) weeks , 14 patients developed HCC of whom nine ( 64 % ) had cirrhosis at baseline .


The 5-year cumulative incidence rate of HCC was 2.1 % for non-cirrhotic and 10.9 % for cirrhotic patients ( p < 0.001 ) .


HCC incidence was higher in older patients ( p < 0.001 ) and patients with lower baseline platelet counts ( p = 0.02 ) .


Twelve patients who developed HCC achieved virologic response ( HBV DNA < 80IU/mL ) before HCC .


At baseline , higher CU-HCC and GAG-HCC , but not REACH-B scores were associated with development of HCC .


Discriminatory performance of HCC risk scores was low , with sensitivity ranging from 18 % to 73 % , and c-statistics from 0.71 to 0.85 .


Performance was further reduced in Caucasians with c-statistics from 0.54 to 0.74 .


Predicted risk of HCC based on risk-scores declined during ETV therapy ( all p < 0.001 ) , but predictive performances after 1year were comparable to those at baseline .


Cumulative incidence of HCC is low in patients treated with ETV , but ETV does not eliminate the risk of HCC .


Discriminatory performance of HCC risk scores was limited , particularly in Caucasians , at baseline and during therapy .


To measure the effects of an HIV-Care-Program , focusing on nutrition and lifestyle , which can be provided at scale to HIV-infected patients , on clinical and anthropometrical parameters , and health status .


A cluster-randomized trial , including 5 health facilities randomized to intervention n = 100 ( HIV-Care-Program ) or control n = 101 ( Usual-Care ) .


The HIV-Care-Program consisted of counseling lessons for 6 months , on : nutrition , hygiene , coping with stigma and discrimination , embedded in practical activities .


Outcome variables were CD4 count after 6 months and time to antiretroviral therapy ( ARV ) initiation , using analysis of covariance and Kaplan-Meier method , respectively .


After 6 months , CD4 count dropped by 46.3 cells ( 7.7 % ) ( intervention ) and 129 ( 23 % ) ( control ) ( p = 0.003 ) .


Mean time to ARV ; 5.9 months 95 % CI ( 5.9 , 6.0 ) ( intervention ) ; 4.9 months 95 % CI ( 4.7 , 5.2 ) ( control ) ( p < 0.004 ) .


There was a partial correlation between CD4 count and initial viral load ( r = -0.190 , p = 0.017 ) .


The intervention provides a low-cost alternative improving health status , slowing down CD4 cell decline , delaying initiation of ARV and thus freeing local ARV capacities for patients in urgent need .


To test the association between docosahexaenoic acid ( DHA ) supplementation and perceived stress and cortisol response to a stressor during pregnancy in a sample of African American women living in low-income environments .


Sixty-four African American women were enrolled at 16-21 weeks of gestation .


Power calculations were computed using published standard deviations for the Perceived Stress Scale and the Trier Social Stress Test .


Participants were randomized to either 450 mg per day of DHA ( n = 43 ) or placebo ( n = 21 ) .


At baseline and at 24 and 30 weeks of gestation , perceived stress was assessed by self-report .


Cortisol response to a controlled stressor , the Trier Social Stress Test was measured from saliva samples collected upon arrival to the laboratory and after the completion of the Trier Social Stress Test .


Women in the DHA supplementation group reported lower levels of perceived stress at 30 weeks of gestation , controlling for depression and negative life events ( mean 27.4 compared with 29.5 , F [ 3 , 47 ] 5.06 , P = .029 , Cohen 's d = 0.65 ) .


Women in the DHA supplementation had lower cortisol output in response to arriving to the laboratory and a more modulated response to the stressor ( F [ 1.78 , 83.85 ] 6.24 , P = .004 , Cohen 's d = 0.76 ) .


Pregnant women living in urban low-income environments who received DHA reported reduced perceived stress and lower levels of stress hormones in the third trimester .


Docosahexaenoic acid supplementation may be a method for attenuating the effects of maternal stress during late pregnancy and improving the uterine environment with regard to fetal exposure to glucocorticoids .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT01158976 .


The objective of this study was to evaluate the performance of digital subtraction angiography ( DSA ) - like bone subtraction with 2 different registration methods for the identification of bone marrow edema pattern ( BMEP ) in patients with lytic bone lesions , using magnetic resonance imaging as the criterion standard .


Fifty-five patients with a lytic bone lesion were included in this prospective study with approval from the ethics committee .


All patients underwent magnetic resonance imaging and low-dose computed tomographic ( CT ) perfusion after signing an informed consent .


Two CT volumes were used for bone subtraction , which was performed with 2 different algorithms ( rigid and nonrigid ) .


Enhancement at the nonlytic bone marrow was considered as a sign of BMEP .


Two readers evaluated the images blindly .


The presence of BMEP on bone-subtracted CT images was evaluated subjectively and quantitatively .


Image quality was assessed .


Magnetic resonance imaging was used as the criterion standard .


Using a rigid registration method , the sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of CT with DSA-like bone subtraction BMEP was 77 % , 100 % , 100 % , 68 % , and 85 % , respectively .


The interobserver agreement was good ( , 0.782 ) .


Image quality was better using a nonrigid registration .


With this algorithm , artifacts interfered with image interpretation in only 5 % of cases .


However , there was a noticeable drop in sensitivity and negative predictive value when a nonrigid algorithm was used : 56 % and 52 % , respectively .


The interobserver agreement was average with a nonrigid subtraction algorithm .


Computed tomography with DSA-like bone subtraction is sensitive and highly specific for the identification of BMEP associated with lytic bone lesions .


Rigid registering should be preferred , but nonrigid algorithms can be used as a second option when artifacts interfere with image interpretation .


Tadalafil is used to treat erectile dysfunction after prostate cancer treatment , but its role as a preventive agent is undefined .


To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer , and secondarily to determine whether participant - or partner-reported overall sexual function and sexual and marital satisfaction were affected .


Stratified , placebo-controlled , double-blind , parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada .


Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013 .


One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy ( 63 % ) or brachytherapy ( 37 % ) .


Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4 , between weeks 20 and 24 , between weeks 28 and 30 , and 1 year thereafter .


Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy , between weeks 20 and 24 and weeks 28 and 30 , and at 1 year .


Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started .


Secondary end points were spontaneous erection at 1 year ; overall sexual function and satisfaction ; marital adjustment ; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year , predictors of tadalafil response ; and adverse events .


Among 221 evaluable participants , 80 ( 79 % ; 95 % CI , 70 % -88 % ) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 ( 74 % ; 95 % CI , 63 % -85 % ) assigned to receive placebo ( P = .49 ) ; an absolute difference of 5 % ( 95 % CI , -9 % to 19 % ) .


A significant difference was also not observed at 1 year ( 72 % ; 95 % CI , 60 % -84 % vs 71 % ; 95 % CI , 59 % -84 % ; P = .93 ) .


Tadalafil was not associated with significantly improved overall sexual function or satisfaction ; a significant difference was not observed in any domain subscale .


Partners of men assigned tadalafil noted no significant effect on sexual satisfaction , and marital adjustment was not significantly improved in participants or partners .


Among men undergoing radiotherapy for prostate cancer , daily use of tadalafil compared with placebo did not result in improved erectile function .


These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients .


clinicaltrials.gov Identifier : NCT00931528 .


This study investigated the effect of a re-wetting agent on the microtensile bond strengths ( mTBS ) of primary and permanent dentin after acid or laser etching .


Twelve permanent and 12 primary molar teeth were ground to expose an occlusal dentin surface .


Each group teeth were randomly divided into groups ; I-II : 37 % phosphoric acid etching with/without re-wetting agent , III-IV : Erbium : Yttrium aluminium garnet laser etching with/without re-wetting agent .


An etch-and-rinse adhesive was used , and vertical sticks were obtained for the microtensile test .


mTBS of permanent teeth was higher than that of primary teeth ( P < 0.05 ) .


Re-wetting agent groups were similar with control groups in both etching groups in the permanent teeth ( P > 0.05 ) .


Re-wetting agent group was similar with the control group in acid etch group ( P > 0.05 ) and lower than the control group in laser etch group in primary teeth ( P < 0.05 ) .


Acid etching in permanent teeth ; laser etching in primary teeth was found more successful .


The use of re-wetting agent did not provide an advance on bond strength of the adhesive in both primary and permanent teeth after acid-etch or laser-etch .


Evidence based practice ( EBP ) requires that health professionals are competent in integrating the best evidence in their decision making .


Being ` evidence-based ' requires skills and knowledge in epidemiology , biostatistics and information literacy .


EBP is commonly taught in medical and health sciences degrees , yet there is little evidence to guide educators as to the best teaching modality to increase learner competency in EBP .


This study is mixed methods in design .


A randomised controlled trial will examine the effectiveness of blended learning versus didactic approach of teaching EBP to medical students .


The primary outcome of the RCT is EBP competency as assessed by the Berlin tool .


Focus groups will be conducted to explore student perceptions and attitudes towards implementing a blended learning approach in teaching EBP .


A concurrent triangulation design will be implemented , permitting quantitative data to inform the effectiveness of the intervention and qualitative data to contextualise the results .


This study will provide novel evidence on the effectiveness of blended learning in teaching EBP to a cohort of undergraduate and graduate-entry medical students .


There is currently little evidence regarding the selection of patients for clinical trials in Parkinson 's Disease ( PD ) , especially those involving experimental therapies delivered using invasive techniques .


Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of results , as well as provoking discussion regarding future improvements in the enrolment process .


TRANSEURO is an open label multi-centre surgical transplant trial which seeks to investigate the feasibility and efficacy of grafts of human foetal ventral mesencephalic tissue in patients with PD .


The Cambridge based cohort of TRANSEURO participants ( n = 26 ) was compared with a population representative sample of patients with PD eligible for , but not enrolled in , TRANSEURO ( n = 33 ) .


Measurements were available in both populations for demographics , neuropsychological tests , tests of motor and non-motor function and quality of life .


Patients enrolled in TRANSEURO were younger and had significantly more years of education with higher scores on the revised Addenbrooke 's Cognitive Examination .


This difference was accounted for by memory , fluency and visuospatial subscores .


There were significant differences in the Movement Disorder Society Unified PD Rating Scale scores with better motor function but more motor complications in the enrolled group .


Those enrolled were also more likely to be under the care of the principal investigator of the study .


In this trial our population was younger and more educated with higher cognitive scores and better motor function than eligible PD patients not enrolled .


This raises interesting questions about the parity of access to clinical trials of this nature amongst patients with PD .


Little is known about the type of care older people of different ages receive at the end of life .


The goal of treatment is an important parameter of the quality of end-of-life care .


This study aims to provide an evaluation of the main goal of treatment in the last week of life of people aged 86 and older compared with those between 75 and 85 and to examine how treatment goals are associated with age .


Population - based cross sectional survey in Flanders , Belgium .


A stratified random sample of death certificates was drawn of people who died between 1 June and 30 November 2007 .


The effective study sample included 3,623 deaths ( response rate : 58.4 % ) .


Non-sudden deaths of patients aged 75 years and older were selected ( N = 1681 ) .


Main outcome was the main goal of treatment in the last week of life ( palliative care or life-prolonging/curative treatment ) .


In patients older than 75 , the main goal of treatment in the last week was in the majority of cases palliative care ( 77.9 % ) .


Patients between 75 and 85 more often received life-prolonging/curative treatment than older patients ( 26.6 % vs. 15.8 % ) .


Most patient and health care characteristics are similarly related to the main goal of treatment in both age groups .


The patient 's age was independently related to having comfort care as the main goal of treatment .


The main goal of treatment was also independently associated with the patient 's sex , cause and place of death and the time already in treatment .


Age is independently related to the main goal of treatment in the last week of life with people over 85 being more likely to receive palliative care and less likely to receive curative/life-prolonging treatment compared with those aged 75-85 .


This difference could be due to the patient 's wishes but could also be the result of the attitudes of care givers towards the treatment of older people .


To investigate baricitinib ( LY3009104 , formerly INCB028050 ) , a novel , oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis ( RA ) despite treatment with methotrexate .


In this phase IIb study , 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1 , 2 , 4 or 8mg baricitinib for 12weeks .


Patients assigned to 2 , 4 and 8 mg baricitinib continued blinded treatment for an additional 12weeks .


Patients assigned to placebo or 1 mg baricitinib were reassigned to 2 mg twice daily or 4 mg once daily baricitinib between weeks 12-24 .


The primary endpoint was the proportion of patients in the combined 4 and 8 mg groups achieving an American College of Rheumatology 20 % ( ACR20 ) response versus placebo at week 12 .


Significantly more patients in the combined baricitinib 4 and 8 mg groups compared with placebo achieved an ACR20 response at week 12 ( 76 % vs 41 % , p < 0.001 ) .


At week 12 , significant differences versus placebo were also observed in patients achieving ACR50 , ACR70 and remission as measured by Disease Activity Score for 28-joint counts , Clinical Disease Activity Index and Simplified Disease Activity Index .


Patients receiving 2 , 4 , or 8mg baricitinib maintained or improved in all measures through 24weeks .


Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups .


Serious infections developed in three patients receiving baricitinib .


No cases of tuberculosis , herpes zoster , opportunistic infections or deaths were reported .


Dose-dependent decreases in haemoglobin were observed with baricitinib .


Baricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease .


Baricitinib was well tolerated with no unexpected safety findings through week 24 .


NCT01185353 .


Modern immunosuppressant regimens have significantly decreased acute rejection rates , but may have increased the risk of graft loss driven by adverse drug reactions ( ADRs ) and medication errors ( MEs ) .


The objectives of this study were to determine the incidence and risk factors for MEs and ADRs and determine the association between transplant outcomes and these events .


This was a post hoc analysis of a prospective , randomized trial that included patients aged > 18 years that received a solitary renal transplant at an academic medical center recruited between March 2009 and July 2011 .


Patients were divided into groups based on developing a clinical significant ME ( CSME ) , defined as a significant ME that contributed to a hospital admission .


The mean study follow-up was 2.5 0.7 years .


There were a total of 233 MEs and 327 ADRs in the 200 patients included in the analysis , with 64 % of the cohort experiencing at least one ME and 87 % experiencing an ADR ; 23 patients ( 12 % ) experienced a CSME .


Patients that experienced CSMEs had a trend toward more post-transplant readmissions ( median 1 [ interquartile range ( IQR ) , 0-5 ] versus 0 [ 0-2 ] ; P = 0.06 ) , higher costs for readmissions ( median $ 18,091 [ IQR , $ 3023 - $ 56,268 ] versus $ 0 [ $ 0 - $ 15,991 ] ; P < 0.01 ) , and overall length of stay ( median 5.0 days [ IQR , 2.0-14 .0 ] versus 0.0 days [ IQR , 0.0-5 .5 ] ; P < 0.01 ) after the CSME event .


CSME patients were also more likely to experience graft failure ( 22 % versus 10 % ; P = 0.05 ) .


Significant MEs commonly occur in renal transplant recipients and are associated with an increased risk of deleterious clinical outcomes , including subsequent hospital days , costs , and graft loss .


In order to improve lung cancer survival in the UK , a greater proportion of resectable cancers must be diagnosed .


It is likely that resectability rates would be increased by more timely diagnosis .


Aside from screening , the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers .


Currently , lung cancers are mainly diagnosed by general practitioners ( GPs ) using the National Institute for Health and Clinical Excellence ( NICE ) guidelines for urgent referral for chest X-ray , which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than 3 weeks .


We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients .


We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates .


This trial would have to be large ( and consequently resource-intensive ) because most of these patients will not have lung cancer , making optimal design crucial .


We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial .


This trial will assess the feasibility and inform the design of a large , UK-wide , clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer .


It utilizes a combination of workshop , health economic , quality of life , qualitative , and quantitative methods in order to fully assess feasibility .


Clinicaltrials.gov NCT01344005 .


Sildenafil citrate is indicated for the treatment of erectile dysfunction .


An orally disintegrating tablet ( ODT ) of sildenafil citrate has been developed for the benefit of patients who have difficulty swallowing solid dosage forms .


The main goal of this study was to evaluate the bioequivalence of sildenafil ODT with and without water versus marketed sildenafil oral film-coated tablets .


A secondary objective was to evaluate the effects of a high-fat meal on the pharmacokinetics of sildenafil ODT .


The bioequivalence study of sildenafil ODT given with and without water versus marketed sildenafil citrate film-coated oral tablets was conducted in 36 subjects .


In a food-effect study , the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT was evaluated in 12 subjects .


Both studies were randomized , open-label , crossover , single-dose ( 50 mg ) studies in healthy men aged 45 years .


Plasma samples were collected for 14 hours postdose , and pharmacokinetics were determined by using noncompartmental analyses .


All subjects in both studies were Asian males between the ages of 45 and 69 years .


Sildenafil ODT without water was bioequivalent to the marketed sildenafil film-coated oral tablet as the 90 % CI for the ratio of geometric means of Cmax , AUC0 - , and AUC0-last were contained within equivalence limits ( 80 % -125 % ) .


When sildenafil ODTs were given with water , the 90 % CIs for sildenafil AUC0 - and AUC0-last were contained within the range of 80 % to 125 % ; however , the 90 % CI for sildenafil Cmax was not ( 79.76-92 .78 ) .


This difference in Cmax is unlikely to have any clinically meaningful impact .


High-fat meals reduced the rate but not the extent of absorption of sildenafil .


Mean Cmax was reduced by 59 % , and median Tmax was delayed from 0.625 hour ( fasting ) to 4 hours ( high-fat meal ) .


However , AUC values were comparable between fed and fasted treatments .


Sildenafil ODT , given with or without water , provides equivalent systemic exposure compared with marketed sildenafil film-coated oral tablets , thus offering a convenient alternative method of administration .


Considering the results of the food-effect study , sildenafil ODT should be taken on an empty stomach .


ClinicalTrials.gov identifiers : NCT01254383 ( bioequivalence ) and NCT01254396 ( food effect ) .


Facial responses to pain are believed to be an act of communication and , as such , are likely to be affected by the relationship between sender and receiver .


To investigate this effect by examining the impact that variations in communicative relations ( from being alone to being with an intimate other ) have on the elements of the facial language used to communicate pain ( types of facial responses ) , and on the degree of facial expressiveness .


Facial responses of 126 healthy participants to phasic heat pain were assessed in three different social situations : alone , but aware of video recording ; in the presence of an experimenter ; and in the presence of an intimate other .


Furthermore , pain catastrophizing and sex ( of participant and experimenter ) were considered as additional influences .


Whereas similar types of facial responses were elicited independent of the relationship between sender and observer , the degree of facial expressiveness varied significantly , with increased expressiveness occurring in the presence of the partner .


Interestingly , being with an experimenter decreased facial expressiveness only in women .


Pain catastrophizing and the sex of the experimenter exhibited no substantial influence on facial responses .


Variations in communicative relations had no effect on the elements of the facial pain language .


The degree of facial expressiveness , however , was adapted to the relationship between sender and observer .


Individuals suppressed their facial communication of pain toward unfamiliar persons , whereas they overtly displayed it in the presence of an intimate other .


Furthermore , when confronted with an unfamiliar person , different situational demands appeared to apply for both sexes .


To assess the incidence and progression of macular atrophy and other key anatomic outcomes over 7 to 8 years in an early cohort of ranibizumab-treated exudative age-related macular degeneration patients .


Follow-up analysis of long-term outcomes in a multicenter treatment cohort .


Fourteen study sites enrolled 65 previous subjects from the ranibizumab treatment arms of the ANCHOR , MARINA , and HORIZON trials .


In a single update visit , clinical assessment and retinal imaging studies were performed , with comparison with each subject 's prior results from the previous trials .


Early Treatment Diabetic Retinopathy Study visual acuity was the primary outcome .


Secondary outcomes , including area of macular atrophy and selected anatomic factors , were analyzed for associations with long-term vision outcomes .


At a mean 7.3 years after ANCHOR or MARINA enrollment , mean visual acuity was 54 letters , study eyes having received a mean 1.6 injections per year since the HORIZON study .


Macular atrophy was present in 98 % of study eyes , the mean area increasing from 0.83 0.96 mm ( 2 ) at the ANCHOR or MARINA year 2 exit to 2.22 1.6 mm ( 2 ) at the SEVEN-UP visit , a growth rate of 0.28 mm ( 2 ) / year .


Progression of macular atrophy was associated significantly with visual decline over this 5-year period ( P < .001 ) , and final macular atrophy lesion size was related significantly to final vision ( P < .001 ) .


Other key anatomic outcomes ( macular thickening , thinning , or fluid and submacular fibrosis ) did not have significant effects on vision outcomes .


Seven years after initiation of intensive ranibizumab therapy for exudative age-related macular degeneration , macular atrophy progression and severity were the primary anatomic determinants of visual outcomes .


Poisoning with organophosphorus ( OP ) compounds constitutes a global public health problem .


Standard treatment of OP poisoning involves use of atropine and pralidoxime .


While efficacy of atropine is well-established , clinical experience with pralidoxime in management of OP poisoning is controversial .


To explore the efficacy of add-on pralidoxime with atropine over atropine alone in the management of OP poisoning .


An open-label , parallel-group , randomized clinical trial was conducted in a tertiary care district hospital in West Bengal .


Patients presenting with features of OP poisoning were randomly allocated to receive atropine or atropine-plus-pralidoxime .


Efficacy was assessed by analyzing mortality , requirement for ventilator support and the duration of stay in hospital .


Chi-square test was done to compare the efficacy parameters between the two groups .


A two-tailed P-value < 0.05 was considered as statistically significant .


During the study period , 150 patients were screened following which 120 patients were randomized to either of the treatment arms .


Add-on pralidoxime therapy did not offer any appreciable benefit over atropine alone in terms of reducing mortality ( 18.33 % ( 11/60 ) versus 13.33 % ( 8/60 ) ) and ventilator requirement ( 5 % ( 3/60 ) versus 8.33 % ( 5/60 ) ) .


However , patients randomized in the add-on pralidoxime arm experienced longer duration of hospital stay ( 7.02 1.12 days ) than those receiving atropine-alone therapy ( 5.68 1.87 days ) ( P < 0.001 ) .


The present study suggested that add-on pralidoxime with atropine therapy did not offer any appreciable benefit over atropine alone in management of OP poisoning .


However , further trials are needed to explore different dosing regimens of pralidoxime in order to determine its efficacy in OP poisoning .


Inflammatory markers show significant associations with cardiovascular events and all-cause mortality after kidney transplantation .


Neopterin , reflecting interferon -- release , may better reflect the proinflammatory state of recipients than less specific markers .


Kidney transplant recipients in the Assessment of LEscol in Renal Transplant ( ALERT ) trial were examined and investigated for an association between serum neopterin and subsequent clinical events : graft loss , major cardiovascular events ( MACE ) and all-cause mortality .


After adjustment for established and emerging risk factors neopterin expressed as neopterin-to-creatinine ratio was significantly associated with MACE ( p = 0.009 ) and all-cause mortality ( p = 0.002 ) .


Endpoints were more frequent with increasing quartiles of neopterin-to-creatinine ratio .


The incidence rates of MACE and all-cause mortality were significantly increased in the upper quartiles compared with the first .


This long-term prospective analysis in stable kidney allograft recipients suggests that neopterin is associated with long-term risk of cardiovascular events and all-cause mortality , but not renal outcomes .


Acute pain can lead to immune dysfunction , which can be partly ameliorated by successful pain management .


Opioids , which are widely used for analgesia , can result in the deterioration of immune function .


This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery .


60 patients undergoing gastric cancer surgery were equally randomized into two groups .


They received post-operative patient-controlled intravenous ( IV ) analgesia using morphine either with or without flurbiprofen .


Visual analogue scale ( VAS ) scores , Bruggemann comfort scale ( BCS ) scores , morphine consumption , time of first flatus , incidence of nausea/vomiting , and T-lymphocyte subsets ( CD3 , CD4 , and CD8 ) and natural killer cells ( CD3CD16CD56 ) were evaluated .


No significant difference was observed in the VAS scores , BCS scores , and nausea/vomiting incidence between groups .


Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone .


The expression of CD3 , CD4 , CD4/CD8 , and CD3CD16CD56 decreased at 2 hours after incision and , except for CD3CD16CD56 , returned to baseline at 120 hours after surgery .


Moreover , the expression of CD3CD16CD56 at 2 hours after incision and the expression of CD3 , CD4 , CD4/CD8 , and CD3CD16CD56 at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone .


The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery .


Vitamin C has important physical and mental health benefits and plasma concentrations reflect recent intakes .


Inflammation associated with any acute illness can lead to poor appetite and low food intake in older people .


The aims of this report were to assess the prevalence and clinical significance of vitamin C deficiency among hospitalized acutely-ill older patients .


Three hundred and twenty two patients ( 152 [ 47 % ] female ) , aged 65 yrs .


and over who took part in a randomized , double blind , placebo-controlled trial had their nutritional status assessed from anthropometric , hematological and biochemical data at baseline , and after 6 weeks and 6 months .


Vitamin C was measured using a fluorimetric technique and logistic regression analysis was performed to determine the influence of a number of clinical indicators , including tissue inflammation measured using C-reactive protein on vitamin C concentrations .


Clinical outcome measures including symptoms of depression were also compared between patients with vitamin C deficiency and those with normal levels .


At baseline , 116 ( 36 % ) patients had a vitamin C concentration below 11 mol/L indicating biochemical depletion .


The figures at 6 weeks and 6 months were 28 ( 22 % ) and 44 ( 28 % ) patients , respectively .


Older age , male gender , smoking , increased dependency and tissue inflammation were associated with lower vitamin C concentrations .


Patients with vitamin C biochemical depletion had significantly increased symptoms of depression compared with those with higher concentrations at baseline ( p = 0.035 ) and at 6 weeks ( p = 0.028 ) .


A high proportion of older patients had sub-optimal vitamin C status and this was associated with increased symptoms of depression .


There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women .


The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women .


For the analyses in this paper , we included a total of 4,680 Hispanic women who participated in the Women 's Health Initiative ( WHI ) , a randomized clinical trial and observational study , at baseline ( 1994-1998 ) and at third-year follow-up and for whom blood pressure was measured at year 3 ( n = 3,848 ) .


Multivariable logistic regression models were used to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) of hypertension status , defined as systolic blood pressure 140 mm Hg and/or diastolic blood pressure 90 mm Hg , to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models .