Effects of stellate ganglionic block on hemodynamic changes and intrapulmonary shunt in perioperative patients with esophageal cancer . OBJECTIVE The aim of this study was to observe the effects of stellate ganglion block ( SGB ) on hemodynamic changes and intrapulmonary shunt during one-lung ventilation ( OLV ) . PATIENTS AND METHODS Thirty ASA class I-II patients undergoing elective esophageal surgery were randomly divided into two groups : general anesthesia group ( group N , n=15 ) and general anesthesia combined SGB group ( group S , n=15 ) , patients in group S were received left SGB before induction . Radial artery was cannulated for arterial blood pressure ( ABP ) monitoring and blood sampling and Swan-Ganz catheter was position in the pulmonary artery via right internal jugular vein under local anesthesia . ECG , MAP , HR , CVP , continuous cardiac output ( CCO ) index and BIS were continuously monitored during anesthesia . General anesthesia was induced with propofol 1.5-2.0 mg/kg , sufentanil 0.4 μg/kg , and Rocuronium 0.6-0.9 mg/kg . Endobronchial occluder was placed blindly after tracheal indubation and the correct position was verified by auscultation and fiberoptic bronchoscopy . The patients were mechanically ventilated . The ventilation conditions were Fio2=100 % , VT = 8-10 ml/kg , I : E = 1:2 and respiratory rate was adjusted to maintained PETCO2 at 35-45 mmHg during both two-lung ventilation ( TLV ) and OLV . Anesthesia was maintained with continuous infusion of propofol 4-10 mg/kg·h , sufentanil 0.2 μg/kg·h , vecuronium o.1 mg/kg·h , BIS was maintained at 45-55 . Blood samples were taken from radial artery and S-G catheter for blood gas analysis at following intervals : during spontaneous breathing when the patient was awake ( T0 ) , 1 min after tracheal indubation ( T1 ) , 1 min after patient was placed in lateral position ( T2 ) and 15 min after it ( T3 ) , 1 min after ribs was braced ( T4 ) , 30 , 60 , 120 min during the course of OLV ( T5 , T6 , T7 ) , the two lungs were ventilated again for 30 min ( T8 ) and Qs/Qt was calculated . RESULTS SVRI , MAP , HR in group N increased significantly at T1 , T2 , T4 compared with group S ( p < 0.05 ) . Qs/Qt was significantly increased after patient was placed in lateral position and increased further during OLV ; the calculated Qs/Qt values were highest at T5· PaO2 was significantly lower after OLV was started and reached the lowest level at T6 then was gradually increasing . There was no significant difference in Qs/Qt and PaO2 at all time points between two groups . CONCLUSIONS SGB before induction effectively suppress the stress response work as stable blood dynamics and does not affect Qs/Qt and arterial oxygenation during OLV , SGB is a safe technique of anesthesia for general thoracic surgery .

stellate ganglionic block

hemodynamic changes

intrapulmonary shunt

hemodynamic changes

intrapulmonary shunt

METHODS


Aloe vera gel and cesarean wound healing ; a randomized controlled clinical trial . BACKGROUND Failure in complete healing of the wound is one of the probable complications of cesarean . The present study aimed to determine the effectiveness of dressing with aloe vera gel in healing of cesarean wound . METHODS This prospective randomized double-blind clinical trial was conducted on 90 women who had undergone cesarean operation in Amir-al-Momenin hospital ( Gerash , Iran ) . The participants were randomly divided into two groups each containing 45 patients . In one group , the wound was dressed with aloe vera gel , while simple dressing was used in the control group . Wound healing was assessed 24 hours and 8 days after the cesarean operation using REEDA scale . The data were analyzed through Chi-square and t-test . RESULTS The participants ' mean age was 27.56±4.20 in the aloe vera group and 26.62±4.88 in the control group , but the difference was not statistically significant . However , a significant difference was found between the two groups concerning body mass index , heart rate , and systolic blood pressure ( P < 0.05 ) . Also , a significant difference was observed between the two groups with respect to the wound healing score 24 hours after the operation ( P=0.003 ) . After 8 days , however , the difference in the wound healing score was not significant ( P=0.283 ) . Overall , 45 participants in the aloe vera group and 35 ones in the control group had obtained a zero score 24 hours after the operation . These measures were respectively obtained as 42 and 41eight days after the operation . CONCLUSION According to the findings of this study , the women are recommended to be informed regarding the positive effects of dressing with aloe vera gel .

Aloe vera gel

aloe vera gel

dressed with aloe vera gel

simple dressing

healing

healing of cesarean wound

Wound healing

REEDA scale

concerning body mass index

heart rate

systolic blood pressure

the wound healing score

positive effects

women

undergone cesarean operation

45 patients

women


Does watching a video on third molar surgery increase patients ' anxiety level ? OBJECTIVE To identify the effects of watching live taping of third molar removal on patients ' anxiety levels before and after extraction . STUDY DESIGN This study was based on a prospective , cross-sectional , observational investigation of the different patient education techniques about the effect of third molar removal on patients ' anxiety level . A total of 333 patients were randomized into three groups : two study groups ( for group 1 , basic information was given verbally ; for group 2 , which was the study group , basic information was given verbally and through a movie on third molar extraction ) ; and a control group ( basic information was given verbally ; it did not include information on operative procedures and recovery ) . Anxiety levels were assessed by using the Dental Anxiety Scale ( DAS ) and the Spielberger State-Trait Anxiety Inventory ( STAI ) . Pain was assessed with a visual analog scale . Statistical analysis was performed with SPSS 16.0 . RESULTS Group 2 patients were significantly more anxious before the surgical procedure , and the most significant decreases in DAS and STAI scores were observed in that group . The age , surgery time , and education level were not correlated with anxiety or pain levels ; however , female patients had high levels of anxiety ( P < .05 ) . CONCLUSION Preoperative multimedia information increases the anxiety of patients undergoing third molar surgery .

third molar surgery

basic information was given verbally ;

Preoperative multimedia information

patients ' anxiety level

patients ' anxiety levels

patients ' anxiety level

333 patients

patients undergoing third molar surgery


Hepatectomy Versus Hepatectomy With Lymphadenectomy in Hepatocellular Carcinoma : A Prospective , Randomized Controlled Clinical Trial . GOALS AND BACKGROUND The role of preventive lymphadenectomy has not yet been determined for hepatocellular carcinoma ( HCC ) patients . We designed a study to evaluate the effect of hepatectomy combined with preventive lymphadenectomy on HCC patients . STUDY Patients were randomly divided into group A ( treated with hepatectomy alone ) and group B ( underwent hepatectomy combined with lymphadenectomy ) . The postoperative complications and oncologic prognoses were analyzed . RESULTS Of the 85 patients enrolled into this study , 79 cases ( 38 in group A and 41 in group B ) were pathologically confirmed to have HCC and received curative resection . One hundred and sixteen lymph nodes were dissected and evaluated as negative by the pathologist . The 12- , 36- , and 60-month disease-free survival rates of group A were 81.6 % , 68.4 % , and 63.2 % , respectively , whereas they were 78.0 % , 65.9 % , and 63.4 % , respectively , for group B . The 12- , 36- , and 60-month overall survival rates in group A were 94.7 % , 78.9 % , and 65.8 % , respectively , whereas they were 87.8 % , 78.0 % , and 70.7 % , respectively , in group B . The differences in the disease-free survival and overall survival between the 2 groups were not statistically significant according to the log-rank test ( P=0.811 and P=0.881 , respectively ) . The difference in the surgical complication rate between groups A and B was not statistically significant ( 47.4 % vs. 36.6 % , P=0.332 ) . CONCLUSIONS Although hepatectomy combined with regional lymphadenectomy is a safe procedure , preventive lymphadenectomy may not decrease the rate of tumor recurrence nor improve the prognosis in early-stage HCC patients .

( treated with hepatectomy alone )

oncologic prognoses

disease-free survival rates

overall survival rates

disease-free survival

overall survival

surgical complication rate

recurrence

prognosis

HCC

HCC

early-stage HCC patients .


Continual feeding of two types of microalgal biomass affected protein digestion and metabolism in laying hens . A 14-wk study was conducted to determine the nutritional efficacy and ssmetabolic impact of 2 types of microalgal biomass as alternative protein sources in laying hen diets . Shaver hens ( total = 150 and 26 wk old ) were fed 1 of 5 diets : a control or a defatted green microalgal biomass ( DG ; Desmodesmus spp . ) at 25 % and a full-fatted diatom biomass ( FD ; Staurosira spp . ) at 11.7 % inclusion with or without protease . This experiment consisted of 5 replicates per treatment and each replicate contained 6 hens individually reared in cages ( 1 hen for biochemical data/replicate ) . Despite decreased ADFI ( P = 0.03 ) , hens fed DG or FD had final BW , overall hen-day egg production , and egg quality similar to the controls . Feeding DG or FD did not alter plasma concentrations of insulin , glutamine , and uric acid or alkaline phosphatase activity at wk 8 or 14 but decreased plasma 3-methyhistine concentrations ( P = 0.03 ) and tartrate-resistant acid phosphatase ( TRAP ) activities ( P < 0.001 ) at wk 14 and improved ( P = 0.002 ) ileal total AA digestibility . Although DG or FD exhibited moderate effects on intestinal brush border protease activities and mRNA levels of duodenal transporters Pept1 , Lat1 , and Cat1 , both substantially enhanced ( P < 0.05 ) phosphorylation of hepatic protein synthesis key regulator S6 ribosomal protein ( S6 ) and the ratio of phospho-S6 to S6 in the liver of hens . However , DG and FD manifested with different impacts on weights of egg and egg albumen , proteolytic activity of jejunal digesta , plasma TRAP activity , ileal total AA digestibility , and several intestinal genes and hepatic proteins . Supplemental protease in the DG and FD diets produced mixed effects on a number of measures . In conclusion , our findings revealed the feasibility of including greater levels of microalgal biomass as a source of feed protein for laying hens and a novel potential of the biomass in improving dietary protein digestion and body protein metabolism than previously perceived .

Continual feeding

microalgal biomass

microalgal biomass

control

defatted green microalgal biomass ( DG

full-fatted diatom biomass

microalgal biomass

efficacy and ssmetabolic impact

plasma 3-methyhistine concentrations

mixed effects

number of measures .

laying hen

total = 150

26 wk old


Inclusion of anti-phospholipase A2 antibody to backgrounding diets on performance , feed efficiency , in vitro fermentation , and the acute-phase response of growing beef calves . In Exp . 1 , individual performance and daily DMI was measured on 70 crossbred weaned calves during a 70-d period using a GrowSafe system ( GrowSafe Systems Ltd. , Airdrie , AB , Canada ) at the University of Florida North Florida Research and Education Center Feed Efficiency Facility ( FEF ) . Calves were fed a low-concentrate ( LC ) growing diet , blocked by weight and sex , and then randomly assigned to pens to receive either no additional supplement ( CON ; n = 35 ) or receive a supplement of anti-phospholipase A2 antibody ( aPLA2 ) at an inclusion rate of 0.6 % of the diet DM ( n = 35 ) . After the 70-d feed efficiency ( FE ) trial ( Phase 1 ) , calves were loaded into a commercial livestock trailer and were driven for approximately 1,600 km during 24 h. Upon return to the FEF ( Phase 2 ) , calves were relocated to the same pens and groups and received the same diets and treatments for 28 d. Blood samples from each calf were collected on d 0 , 1 , 3 , 5 , 7 , 14 , 21 , and 28 relative to initiation of transportation and were analyzed for determination of concentrations of plasma ceruloplasmin and haptoglobin . In Phase 1 , initial BW ( 242.0 ± 3.7 kg ; P = 0.92 ) , BW at d 70 ( 313.0 ± 4.1 kg ; P = 0.79 ) , and ADG ( 1.01 ± 0.02 kg ; P = 0.95 ) were similar between treatments . However , daily DMI was greater ( P = 0.01 ) for CON ( 9.18 ± 0.15 kg ) than aPLA2 ( 8.53 ± 0.15 kg ) . In addition , residual feed intake was greater ( P = 0.002 ) for CON ( 0.389 ± 0.110 kg/d ) than aPLA2 calves ( -0.272 ± 0.110 kg/d ) . In Phase 2 , after transportation , there were no differences between treatments on BW loss due to transportation shrink ( 26.0 ± 0.6 kg ; P = 0.86 ) , BW at d 28 ( 339.0 ± 4.1 kg ; P = 0.72 ) , ADG ( 1.28 ± 0.03 kg/d ; P = 0.72 ) , G : F ( 0.164 ± 0.004 ; P = 0.83 ) , and concentrations of plasma haptoglobin ( 0.08 ± 0.02 mg/mL ; P = 0.41 ) . However , concentrations of plasma ceruloplasmin were greater ( P < 0.001 ) for CON calves ( 14.3 ± 0.3 mg/dL ) compared to aPLA2 calves ( 13.0 ± 0.3 mg/dL ) . In Exp . 2 , the effects of aPLA2 inclusion on LC and high-concentrate ( HC ) substrates on in vitro fermentation parameters were assessed . Addition of aPLA2 had no effects on in vitro fermentation parameters of LC and HC substrates . In conclusion , supplementation of aPLA2 improved FE of growing beef calves when fed LC diets in Phase 1 and addition of aPLA2 had no effect on fermentation parameters of LC and HC substrates . In addition , calves supplemented with aPLA2 had reduced concentrations of plasma ceruloplasmin after 24 h of transportation .

anti-phospholipase A2 antibody

low-concentrate ( LC ) growing diet

either no additional supplement

BW

anti-phospholipase A2 antibody

growing

calves


Efficacy of a tobacco quitline among adult cancer survivors . OBJECTIVE The purpose of the study ( conducted 2010-2013 ) was to determine the efficacy of two common types of tobacco quitlines in adult cancer survivors who regularly smoked cigarettes . METHOD Adult onset cancer survivors in Memphis , Tennessee ( n=427 , 67 % female , 60 % Caucasian ) were randomized either to a Proactive ( i.e. , counselor-initiated calls ) or Reactive ( i.e. , participant-initiated calls ) quitline . Both conditions also received nicotine replacement therapy . The primary outcome was biochemically-verified ( i.e. , salivary cotinine ) smoking cessation . RESULTS While 12-month self-reported abstinence was consistent with other published studies of smoking cessation ( 22 % and 26 % point prevalence abstinence for Proactive and Reactive conditions , respectively ) , 48 % of participants who were tested for cotinine failed biochemical verification , indicating a considerable falsification of self-reported cessation . Adjusted cessation rates were less than 5 % in both intervention conditions . CONCLUSION Our results are consistent with other studies indicating that traditional smoking cessation interventions are ineffective among cancer survivors . Moreover , self-reports of cessation were unreliable in cancer survivors participating in a quitline intervention , indicating that future studies should include biochemical verification . Given the importance of smoking cessation among cancer survivors and low cessation rates in the current study , it may be necessary to design alternative interventions for this population . ClinicalTrials.gov identifier : NCT00827866 .

tobacco quitline

tobacco quitlines

counselor-initiated calls

participant-initiated calls

nicotine replacement therapy

quitline intervention

Efficacy

smoking cessation .

smoking cessation

self-reports of cessation

cessation rates

adult

cancer survivors

adult

cancer

cancer

female

cancer


The development and feasibility of a composite score of echocardiographic indices that may stratify outcome in patients with diabetes mellitus . BACKGROUND Early detection of changes in cardiac structure and function associated with type 2 diabetes ( T2DM ) is important . However when multiple abnormalities are present , combining individual measurements can be subjective . This study sought to create a simple echo score that summarises measurements that may detect early and prognostically important changes in cardiac function . METHODS Standard echocardiography was performed on 849 people with T2DM ( median age 65years , 40 % female , median duration of diabetes 5.5years ) . Principal components analysis was performed on measurements of LV mass , LA volume , E : e ' , and s ' , to create an objective summary score . The score was included in two Cox proportional hazard models adjusted for CV risk factors : one estimated the development of heart failure ( HF ) and the second estimated any CV event . RESULTS The first two principal components represented 75 % of the variation between the four echo measurements . A continuous score that represents the residual difference between these two components was derived that only requires measurement of medial E : e ' and s ' . The score was significantly associated with the development of HF within four years ( hazard ratio 1.34 ; 95 % CI 1.15 , 1.56 ) . CONCLUSIONS We have developed a simple , objective score that enhances the use of echocardiography in the detection of sub-clinical cardiac disease in people with T2DM . Initial findings suggest that it may help identify those at increased risk of developing HF within four years .

Standard echocardiography

echocardiography

echo score

LV mass

LA volume , E : e '

s

objective summary score

heart failure ( HF )

any CV event

development of HF

score

patients with diabetes mellitus

type 2 diabetes ( T2DM )

median age 65years

female

diabetes


The effects of a single dose of oxytocin on working memory in schizophrenia .

single dose of oxytocin

working memory

schizophrenia .


N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism : a randomized , double-blind , placebo-controlled clinical trial of efficacy and safety . OBJECTIVES According to the proposed interference of N-acetylcysteine ( NAC ) with pathophysiologic processes of autistic disorders ( ADs ) , we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized , double-blind , clinical trial . METHODS The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community ( ABC-C ) Irritability subscale score . The participants were randomized into 2 groups . One group received risperidone plus NAC , and the other group received risperidone plus placebo . The dose of risperidone was titrated between 1 and 2.0 mg/d , and the dose of NAC was 600 to 900 mg/d . The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks . Changes in other subscales were considered as secondary outcome measures . RESULTS Forty patients completed the 10-week trial . Baseline characteristics including age , sex and body weight , as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups . Repeated-measures analysis showed significant effect for time × treatment interaction in irritability ( P = 0.01 ) and hyperactivity/noncompliance ( P = 0.02 ) subscales . By week 10 , the NAC group showed significantly more reduction in irritability ( P = 0.02 ) and hyperactivity/noncompliance ( P = 0.01 ) subscales scores . CONCLUSIONS N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes .

N-acetylcysteine

risperidone

N-acetylcysteine ( NAC )

NAC

risperidone

risperidone plus NAC

risperidone plus placebo

risperidone

NAC

the effectiveness and safety

Changes in other subscales

baseline scores

subscales

effect

in autism

the diagnosis of ADs

Forty


Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma ( LUX-Lung 3 and LUX-Lung 6 ) : analysis of overall survival data from two randomised , phase 3 trials . BACKGROUND We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label , randomised , phase 3 trials . METHODS Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 ( n=345 ) and LUX-Lung 6 ( n=364 ) . These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy ( pemetrexed-cisplatin [ LUX-Lung 3 ] or gemcitabine-cisplatin [ LUX-Lung 6 ] ) , stratified by EGFR mutation ( exon 19 deletion [ del19 ] , Leu858Arg , or other ) and ethnic origin ( LUX-Lung 3 only ) . We planned analyses of mature overall survival data in the intention-to-treat population after 209 ( LUX-Lung 3 ) and 237 ( LUX-Lung 6 ) deaths . These ongoing studies are registered with ClinicalTrials.gov , numbers NCT00949650 and NCT01121393 . FINDINGS Median follow-up in LUX-Lung 3 was 41 months ( IQR 35-44 ) ; 213 ( 62 % ) of 345 patients had died . Median follow-up in LUX-Lung 6 was 33 months ( IQR 31-37 ) ; 246 ( 68 % ) of 364 patients had died . In LUX-Lung 3 , median overall survival was 28.2 months ( 95 % CI 24.6-33.6 ) in the afatinib group and 28.2 months ( 20.7-33.2 ) in the pemetrexed-cisplatin group ( HR 0.88 , 95 % CI 0.66-1.17 , p=0.39 ) . In LUX-Lung 6 , median overall survival was 23.1 months ( 95 % CI 20.4-27.3 ) in the afatinib group and 23.5 months ( 18.0-25.6 ) in the gemcitabine-cisplatin group ( HR 0.93 , 95 % CI 0.72-1.22 , p=0.61 ) . However , in preplanned analyses , overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials : in LUX-Lung 3 , median overall survival was 33.3 months ( 95 % CI 26.8-41.5 ) in the afatinib group versus 21.1 months ( 16.3-30.7 ) in the chemotherapy group ( HR 0.54 , 95 % CI 0.36-0.79 , p=0.0015 ) ; in LUX-Lung 6 , it was 31.4 months ( 95 % CI 24.2-35.3 ) versus 18.4 months ( 14.6-25.6 ) , respectively ( HR 0.64 , 95 % CI 0.44-0.94 , p=0.023 ) . By contrast , there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial : in LUX-Lung 3 , median overall survival was 27.6 months ( 19.8-41.7 ) in the afatinib group versus 40.3 months ( 24.3-not estimable ) in the chemotherapy group ( HR 1.30 , 95 % CI 0.80-2.11 , p=0.29 ) ; in LUX-Lung 6 , it was 19.6 months ( 95 % CI 17.0-22.1 ) versus 24.3 months ( 19.0-27.0 ) , respectively ( HR 1.22 , 95 % CI 0.81-1.83 , p=0.34 ) . In both trials , the most common afatinib-related grade 3-4 adverse events were rash or acne ( 37 [ 16 % ] of 229 patients in LUX-Lung 3 and 35 [ 15 % ] of 239 patients in LUX-Lung 6 ) , diarrhoea ( 33 [ 14 % ] and 13 [ 5 % ] ) , paronychia ( 26 [ 11 % ] in LUX-Lung 3 only ) , and stomatitis or mucositis ( 13 [ 5 % ] in LUX-Lung 6 only ) . In LUX-Lung 3 , neutropenia ( 20 [ 18 % ] of 111 patients ) , fatigue ( 14 [ 13 % ] ) and leucopenia ( nine [ 8 % ] ) were the most common chemotherapy-related grade 3-4 adverse events , while in LUX-Lung 6 , the most common chemotherapy-related grade 3-4 adverse events were neutropenia ( 30 [ 27 % ] of 113 patients ) , vomiting ( 22 [ 19 % ] ) , and leucopenia ( 17 [ 15 % ] ) . INTERPRETATION Although afatinib did not improve overall survival in the whole population of either trial , overall survival was improved with the drug for patients with del19 EGFR mutations . The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials . FUNDING Boehringer Ingelheim .

Afatinib

cisplatin-based chemotherapy

afatinib

LUX-Lung

LUX-Lung 6

afatinib

gemcitabine-cisplatin [ LUX-Lung 6 ] )

overall survival

overall survival

overall survival

overall survival

overall survival

overall survival

overall survival

grade 3-4 adverse events

rash or acne

diarrhoea

paronychia

stomatitis or mucositis

neutropenia

fatigue

leucopenia

grade 3-4 adverse events

neutropenia

vomiting

leucopenia

LUX-Lung 6

adenocarcinoma

patients with EGFR

229 patients

239 patients

patients with del19 EGFR mutations

patients with Leu858Arg EGFR mutations


Exploring the role of tanezumab as a novel treatment for the relief of neuropathic pain . OBJECTIVE Evaluate efficacy and safety of tanezumab , a humanized monoclonal antibody against nerve growth factor , in neuropathic pain . DESIGN Two randomized controlled trials . SUBJECTS Patients with pain due to diabetic peripheral neuropathy ( DPN ) or postherpetic neuralgia ( PHN ) . METHODS In the DPN study , patients received subcutaneous tanezumab 20 mg or placebo on Day 1 and Week 8 . Evaluations included change from baseline in average DPN pain ( primary endpoint ) , Patient 's Global Assessment of DPN , and safety ( including neuropathy assessments ) . Due to a partial clinical hold limiting enrollment and treatment duration , the prespecified landmark analysis was modified post hoc from Week 16 to Week 8 . In the PHN study , patients received intravenous tanezumab 50 μg/kg , tanezumab 200 μg/kg , or placebo on Day 1 . Evaluations included change from baseline in average daily pain ( primary endpoint ) , Brief Pain Inventory-short form , Patient 's Global Assessment of pain from PHN , and safety . RESULTS Mean DPN pain reduction from baseline to Week 8 was greater with tanezumab vs placebo ( P = 0.009 ) ; differences in Patient 's Global Assessment of DPN were not significant ( P > 0.05 ) . Neither tanezumab dose resulted in significant differences vs placebo in efficacy in PHN ( P > 0.05 ) , although tanezumab 200 μg/kg provided some benefit . Neuropathy assessments showed no meaningful changes . CONCLUSIONS Tanezumab provided effective pain reduction in DPN . In PHN , only the highest tanezumab dose reduced pain ; treatment differences were not significant . No new safety concerns were observed despite preexisting neuropathy .

tanezumab

tanezumab

tanezumab

placebo

tanezumab

Mean DPN pain reduction

efficacy

neuropathic pain .

neuropathic pain .

diabetic peripheral neuropathy ( DPN

despite preexisting neuropathy


Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch : single dose administration in healthy volunteers . AIMS Transdermal fentanyl is a well established treatment for cancer pain . The aim of the present study is to assess the relative bioavailability of fentanyl from two different transdermal systems by evaluating plasma drug concentrations after single administration of Fentalgon® ( test ) , a novel bilayer matrix type patch , and Durogesic SMAT ( reference ) , a monolayer matrix type patch . In the Fentalgon patch the upper 6 % fentanyl reservoir layer maintains a stable concentration gradient between the lower 4 % donor layer and the skin . The system provides a constant drug delivery over 72 h. METHODS This was an open label , single centre , randomized , single dose , two period crossover clinical trial , that included 36 healthy male volunteers . The patches were applied to non-irritated and non-irradiated skin on the intraclavicular pectoral area . Blood samples were collected at different time points ( from baseline to 120 h post-removal of the devices ) and fentanyl concentrations were determined using a validated LC/MS/MS method . Bioequivalence was to be claimed if the 90 % confidence interval of AUC ( 0 , t ) and C ( max ) ratios ( test : reference ) were within the acceptance range of 80-125 % and 75-133 % , respectively . RESULTS The 90 % confidence intervals of the AUC ( 0 , t ) ratio ( 116.3 % [ 109.6 , 123.4 % ] ) and C ( max ) ratio ( 114.4 % [ 105.8 , 123.8 % ] were well included in the acceptance range and the C ( max ) ratio also met the narrower bounds of 80-125 % . There was no relevant difference in overall safety profiles of the two preparations investigated , which were adequately tolerated , as expected for opioid-naïve subjects . CONCLUSIONS The new bilayer matrix type patch , Fentalgon® , is bioequivalent to the monolayer matrix type Durogesic SMAT fentanyl patch with respect to the rate and extent of exposure of fentanyl ( Eudra/CT no . 2005-000046-36 ) .

Transdermal fentanyl

fentanyl

AUC ( 0 , t ) ratio

acceptance range

C ( max ) ratio

tolerated

male volunteers


Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion : a randomized clinical trial . BACKGROUND Ischemic preconditioning ( IPC ) and anesthetic preconditioning ( APC ) have been reported to attenuate ischemia-reperfusion ( IR ) injury after liver resection under continuous inflow occlusion . This study evaluates whether these strategies enhance hepatic protection of remnant liver against IR after liver resection with intermittent clamping ( INT ) . METHODS A total of 106 patients without underlying liver disease and submitted to liver resection using INT were randomized into 3 groups : IPC ( 10 minutes of inflow occlusion followed by 10 minutes of reperfusion before liver transection ) , APC ( sevoflurane administration for 20 minutes before liver transection ) , and INT ( no preconditioning ) . Patients were also stratified according to the extent of the hepatectomy . Cytoprotection was evaluated by comparing hepatocyte and endothelial dysfunction markers , apoptosis , histologic lesions , and postoperative outcome . RESULTS No differences were observed in preoperative chemotherapy and steatosis , total warm ischemia time , operative time , or blood loss . Kinetics of transaminases ( aspartate aminotransferase , P = .137 ; alanine aminotransferase , P = .616 ) , bilirubin ( P = .980 ) , and hyaluronic acid increase ( P = .514 ) revealed no differences . Significant apoptosis was present in 40 % of patients , mild-to-moderate leukocyte infiltration and steatosis in 45 % and 55 % , respectively , and mild sinusoidal congestion in 65 % , with a similar distribution in the 3 groups . When patients were stratified by major versus minor resections , no differences were observed in any of the variables studied . Postoperative clinical outcomes were also similar . CONCLUSION These results suggest that these protocols of IPC and APC used in this study do not provide better cytoprotection from IR when INT is used .

ischemic

anesthetic preconditioning

Ischemic preconditioning ( IPC )

anesthetic preconditioning ( APC )

intermittent clamping ( INT )

INT ( no preconditioning )

IPC

APC

INT

Cytoprotection

Kinetics of transaminases

bilirubin

hyaluronic acid

Significant apoptosis

mild sinusoidal congestion

106 patients

liver disease


Effect of self-collection of HPV DNA offered by community health workers at home visits on uptake of screening for cervical cancer ( the EMA study ) : a population-based cluster-randomised trial . BACKGROUND Control of cervical cancer in developing countries has been hampered by a failure to achieve high screening uptake . HPV DNA self-collection could increase screening coverage , but implementation of this technology is difficult in countries of middle and low income . We investigated whether offering HPV DNA self-collection during routine home visits by community health workers could increase cervical screening . METHODS We did a population-based cluster-randomised trial in the province of Jujuy , Argentina , between July 1 , 2012 , and Dec 31 , 2012 . Community health workers were eligible for the study if they scored highly on a performance score , and women aged 30 years or older were eligible for enrolment by the community health worker . 200 community health workers were randomly allocated in a 1:1 ratio to either the intervention group ( offered women the chance to self-collect a sample for cervical screening during a home visit ) or the control group ( advised women to attend a health clinic for cervical screening ) . The primary outcome was screening uptake , measured as the proportion of women having any HPV screening test within 6 months of the community health worker visit . Analysis was by intention to treat . This trial is registered with ClinicalTrials.gov , number NCT02095561 . FINDINGS 100 community health workers were randomly allocated to the intervention group and 100 were assigned to the control group ; nine did not take part . 191 participating community health workers ( 94 in the intervention group and 97 in the control group ) initially contacted 7650 women ; of 3632 women contacted by community health workers in the intervention group , 3049 agreed to participate ; of 4018 women contacted by community health workers in the control group , 2964 agreed to participate . 2618 ( 86 % ) of 3049 women in the intervention group had any HPV test within 6 months of the community health worker visit , compared with 599 ( 20 % ) of 2964 in the control group ( risk ratio 4·02 , 95 % CI 3·44-4·71 ) . INTERPRETATION Offering self-collection of samples for HPV testing by community health workers during home visits resulted in a four-fold increase in screening uptake , showing that this strategy is effective to improve cervical screening coverage . This intervention reduces women 's barriers to screening and results in a substantial and rapid increase in coverage . Our findings suggest that HPV testing could be extended throughout Argentina and in other countries to increase cervical screening coverage . FUNDING Instituto Nacional del Cáncer ( Argentina ) .

self-collection of HPV DNA

HPV DNA self-collection

HPV DNA self-collection

uptake of screening for cervical cancer

screening uptake .

screening coverage

cervical screening .

screening uptake

HPV screening test

HPV test

screening uptake

cervical screening coverage

reduces women 's barriers to screening

and rapid increase in coverage

increase cervical screening coverage

countries of middle and low income

province of Jujuy , Argentina

women

aged 30 years or older

women

women


Three-Arm Randomized Phase III Trial : Quality Aloe and Placebo Cream Versus Powder as Skin Treatment During Breast Cancer Radiation Therapy . BACKGROUND The efficacy of aloe extract in reducing radiation-induced skin injury is controversial . The purpose of the present 3-arm randomized trial was to test the efficacy of quality-tested aloe extract in reducing the severity of radiation-induced skin injury and , secondarily , to examine the effect of a moist cream versus a dry powder skin care regimen . MATERIALS AND METHODS A total of 248 patients with breast cancer were randomized to powder , aloe cream , or placebo cream . Acute skin toxicity was scored weekly and after treatment at weeks 1 , 2 , and 4 using a modified 10-point Catterall scale . The patients scored their symptom severity using a 6-point Likert scale and kept an acute phase diary . RESULTS The aloe formulation did not reduce acute skin toxicity or symptom severity . Patients with a greater body mass index were more likely to develop acute skin toxicity . A similar pattern of increased skin reaction toxicity occurred with both study creams compared with the dry powder regimen . CONCLUSION No evidence was found to support prophylactic application of quality aloe extract or cream to improve the symptoms or reduce the skin reaction severity . Our results support a dry skin care regimen of powder during radiation therapy .

Aloe and Placebo

Powder

aloe extract

moist cream

dry powder skin care regimen .

powder , aloe cream

placebo cream .

aloe extract

Breast Cancer

breast cancer


Using behavioral economics to predict opioid use during prescription opioid dependence treatment . BACKGROUND Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing , but these principles have not been examined in prescription opioid addiction , which is currently a major public health problem . This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction . METHODS Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial ( N=353 ) . Baseline measures assessed opioid source and indices of drug reinforcement value , including the total amount and proportion of income spent on drugs . Weekly urine drug screens measured opioid use . RESULTS Obtaining opioids from doctors was associated with lower pre-treatment drug spending , while obtaining opioids from dealers/patients was associated with greater spending . Controlling for demographics , opioid use history , and opioid source frequency , patients who spent a greater total amount ( OR=1.30 , p < .001 ) and a greater proportion of their income on drugs ( OR=1.31 , p < .001 ) were more likely to use opioids during treatment . CONCLUSIONS Individual differences in drug reinforcement value , as indicated by pre-treatment allocation of economic resources to drugs , reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction . Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population .

buprenorphine-naloxone

counseling

opioid use

indices of drug reinforcement value

Weekly urine drug screens

disrupted decision-making

reward-processing


The effects of stimulation of the autonomic nervous system via perioperative nutrition on postoperative ileus and anastomotic leakage following colorectal surgery ( SANICS II trial ) : a study protocol for a double-blind randomized controlled trial . BACKGROUND Postoperative ileus and anastomotic leakage are important complications following colorectal surgery associated with short-term morbidity and mortality . Previous experimental and preclinical studies have shown that a short intervention with enriched enteral nutrition dampens inflammation via stimulation of the autonomic nervous system and thereby reduces postoperative ileus . Furthermore , early administration of enteral nutrition reduced anastomotic leakage . This study will investigate the effect of nutritional stimulation of the autonomic nervous system just before , during and early after colorectal surgery on inflammation , postoperative ileus and anastomotic leakage . METHODS/DESIGN This multicenter , prospective , double-blind , randomized controlled trial will include 280 patients undergoing colorectal surgery . All patients will receive a selfmigrating nasojejunal tube that will be connected to a specially designed blinded tubing system . Patients will be allocated either to the intervention group , receiving perioperative nutrition , or to the control group , receiving no nutrition . The primary endpoint is postoperative ileus . Secondary endpoints include anastomotic leakage , local and systemic inflammation , ( aspiration ) pneumonia , surgical complications classified according to Clavien-Dindo , quality of life , gut barrier integrity and time until functional recovery . Furthermore , a cost-effectiveness analysis will be performed . DISCUSSION Activation of the autonomic nervous system via perioperative enteral feeding is expected to dampen the local and systemic inflammatory response . Consequently , postoperative ileus will be reduced as well as anastomotic leakage . The present study is the first to investigate the effects of enriched nutrition given shortly before , during and after surgery in a clinical setting . TRIAL REGISTRATION ClinicalTrials.gov : NCT02175979 - date of registration : 25 June 2014 . Dutch Trial Registry : NTR4670 - date of registration : 1 August 2014 .

perioperative nutrition

selfmigrating nasojejunal tube

receiving perioperative nutrition

receiving no nutrition

postoperative ileus

anastomotic leakage

anastomotic leakage

postoperative ileus

anastomotic leakage

local and systemic inflammation

( aspiration ) pneumonia

Clavien-Dindo

quality of life

postoperative ileus

anastomotic leakage

280 patients

colorectal surgery


The effect of power asymmetries on cooperation and punishment in a prisoner 's dilemma game . Recent work has suggested that punishment is detrimental because punishment provokes retaliation , not cooperation , resulting in lower overall payoffs . These findings may stem from the unrealistic assumption that all players are equal : in reality individuals are expected to vary in the power with which they can punish defectors . Here , we allowed strong players to interact with weak players in an iterated prisoner 's dilemma game with punishment . Defecting players were most likely to switch to cooperation if the partner cooperated : adding punishment yielded no additional benefit and , under some circumstances , increased the chance that the partner would both defect and retaliate against the punisher . Our findings show that , in a two-player game , cooperation begets cooperation and that punishment does not seem to yield any additional benefits . Further work should explore whether strong punishers might prevail in multi-player games .

cooperation and punishment

prisoner 's dilemma game

punishment

punishment

two-player game

cooperation

power asymmetries

iterated prisoner 's dilemma game


Reducing cancer screening disparities in medicare beneficiaries through cancer patient navigation . Significant racial disparities in cancer mortality are seen between Medicare beneficiaries . A randomized controlled trial tested the use of lay navigators ( care managers ) to increase cancer screening of Asian and Pacific Islander Medicare beneficiaries . The study setting was Moloka'i General Hospital on the island of Moloka'i , Hawai'i , which was one of six sites participating in the Cancer Prevention and Treatment Demonstration sponsored by the Centers for Medicare and Medicaid Services . Between 2006 and 2009 , 488 Medicare beneficiaries ( 45 % Hawaiian , 35 % Filipino , 11 % Japanese , 8 % other ) were randomized to have a navigator help them access cancer screening services ( experimental condition , n = 242 ) or cancer education ( control condition , n = 246 ) . Self-reported data on screening participation were collected at baseline and exit from the study , and differences were tested using chi-square . Groups were similar in demographic characteristics and baseline screening prevalence of breast , cervical , prostate , and colorectal cancers . At study exit , 57.0 % of women in the experimental arm and 36.4 % of controls had had a Papanicolaou test in the past 24 months ( P = .001 ) , 61.7 % of women in the experimental arm and 42.4 % of controls had had a mammogram in the past 12 months ( P = .003 ) , 54.4 % of men in the experimental arm and 36.0 % of controls had had a prostate-specific antigen test in the past 12 months ( P = .008 ) , and 43.0 % of both sexes in the experimental arm and 27.2 % of controls had had a flexible sigmoidoscopy or colonoscopy in the past 5 years ( P < .001 ) . Findings suggest that navigation services can increase cancer screening in Medicare beneficiaries in groups with significant disparities .

cancer patient navigation

cancer education

baseline

navigation services

cancer screening

cancer mortality

cancer screening

Papanicolaou test

mammogram

cancer screening

cancer patient navigation

488 Medicare beneficiaries

45 % Hawaiian

35 % Filipino

11 % Japanese

8 % other


Randomized Controlled Trial of Mind Reading and In Vivo Rehearsal for High-Functioning Children with ASD . This randomized controlled trial evaluated the efficacy of a computer software ( i.e. , Mind Reading ) and in vivo rehearsal treatment on the emotion decoding and encoding skills , autism symptoms , and social skills of 43 children , ages 7-12 years with high-functioning autism spectrum disorder ( HFASD ) . Children in treatment ( n = 22 ) received the manualized protocol over 12 weeks . Primary analyses indicated significantly better posttest performance for the treatment group ( compared to controls ) on 3 of the 4 measures of emotion decoding and encoding and these were maintained at 5-week follow-up . Analyses of secondary measures favored the treatment group for 1 of the 2 measures ; specifically , ASD symptoms were significantly lower at posttest and follow-up .

Mind Reading

In Vivo Rehearsal

computer software

vivo rehearsal treatment

High-Functioning

Children

ASD

children

ages 7-12 years


Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients . UNLABELLED Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis , end-stage liver disease , and hepatocellular carcinoma . Patients in whom interferon ( IFN ) /ribavirin ( RBV ) therapy has failed remain at risk as effective therapeutic options are limited . This phase 2 , randomized , open-label study evaluated an IFN- and RBV-free regimen of once-daily ombitasvir ( ABT-267 ) , an NS5A inhibitor , plus paritaprevir ( ABT-450 ) , an NS3/4A protease inhibitor dosed with ritonavir ( paritaprevir/ritonavir ) , in pegylated IFN/RBV treatment-experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection . Patients without cirrhosis ( aged 18-75 years ) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks ; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks . Sustained virologic response ( SVR ) at posttreatment week 24 ( SVR24 ) was the primary endpoint . Adverse events were collected throughout the study . One hundred ten patients received ≥1 dose of study medication . In the subtype 1b cohort , SVR24 rates were high ( 88.9 % -100 % ) regardless of paritaprevir dose or treatment duration . In the genotype 2 cohort , SVR24 rates were 57.9 % and 72.2 % with 100 mg and 150 mg of paritaprevir , respectively . The SVR24 rate was higher in patients with subtype 2a ( 90 % ) than 2b ( 27 % ) . Concordance between SVR12 and SVR24 was 100 % . The most common adverse events overall were nasopharyngitis ( 29 % ) and headache ( 14 % ) . CONCLUSION In this difficult-to-treat population of patients in whom prior pegylated IFN/RBV had failed , ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection .

interferon-

interferon ( IFN

/ribavirin ( RBV )

IFN- and RBV-free

ombitasvir ( ABT-267 )

NS5A inhibitor

paritaprevir ( ABT-450 )

NS3/4A protease inhibitor

ritonavir ( paritaprevir/ritonavir )

IFN/RBV

Sustained virologic response ( SVR )

cohort , SVR24 rates

cohort , SVR24 rates

between SVR12 and SVR24

were nasopharyngitis

and headache

patients with genotype 2 infection

One hundred ten patients


A feasibility study for a randomised controlled trial of treatment withdrawal in psoriatic arthritis ( REmoval of treatment for patients in REmission in psoriatic ArThritis ( RETREAT ( F ) ) . TNF therapy is effective for all aspects of psoriatic disease , but these drugs are costly and the long-term effects are unknown . Further , methotrexate causes concern with long-term adverse events . The purpose of this pilot study was to test the feasibility of drug withdrawal from patients with psoriatic arthritis , in stable low disease state . We examined the availability of patients , their willingness to participate , study procedures , and the proportion of patients in the withdrawal arm who relapsed during the study . Low disease state was defined by minimal disease activity criteria ( MDA ) , and relapse by failure to achieve these criteria . Patients in the withdrawal group underwent a phased withdrawal of medication where the last treatment added was the first withdrawn . Assessments were monthly for 3 months before study exit . Seventy-two patients were invited to participate , of which 57 were found to be eligible . Twenty-six ( 36.1 % ) subsequently attended the screening visit but 9 failed eligibility criteria so that 17 patients ( 29.8 % of the 57 eligible patients , 95 % confidence interval ( CI ) 18.4 , 43.4 % ) were randomised at a ratio of 2:1 in favour of the withdrawal arm ( 11 withdrawals , 6 standard care ) . Six patients experienced a flare , all of whom were in the withdrawal arm ( relapse rate 54.6 % , 95 % CI 23.4 , 83.3 % ) . Four of the flares were apparent from visit 3 ( 8 weeks after starting withdrawal ) . Given the high relapse rate , an alternative trial design of partial treatment withdrawal , possibly including a patient preference arm , is recommended .

drug withdrawal

withdrawal arm

phased withdrawal of medication

withdrawn

withdrawal arm

withdrawal arm

withdrawal )

test the feasibility

availability of patients

their willingness to participate

study procedures

Assessments

flare

relapse rate

psoriatic arthritis

Seventy-two


Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter . The effects of esmolol , an ultrashort-acting beta blocker , and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter , in a randomized , parallel , open-label study . Patients with either new onset ( less than 48 hours , n = 31 ) or old onset ( greater than 48 hours , n = 14 ) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol ( n = 21 ) or verapamil ( n = 24 ) . Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm . The heart rate declined with esmolol from 139 to 100 beats/min ( p less than 0.001 ) and with verapamil from 142 to 97 beats/min ( p less than 0.001 ) . Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm , whereas only 12 % of those who received verapamil converted ( p less than 0.03 ) . Mild hypotension was observed in both treatment groups . Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter . Moreover , conversion to sinus rhythm is significantly more likely with esmolol .

Esmolol

verapamil

esmolol

verapamil

esmolol

verapamil

esmolol

verapamil

esmolol-treated

verapamil

Esmolol

verapamil

esmolol

ventricular response

Drug efficacy

ventricular rate reduction

conversion to sinus rhythm .

heart rate

converted to sinus rhythm

Mild hypotension

efficacy and safety

acutely decreasing ventricular response

conversion to sinus rhythm

atrial fibrillation


Baseline distribution of participants with depression and impaired quality of life in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial . BACKGROUND Previous studies have demonstrated the psychosocial effect of heart failure in patients with reduced ejection fraction . However , the effects on patients with preserved ejection fraction have not yet been elucidated . This study aimed to determine the baseline characteristics of participants with heart failure with preserved ejection fraction as it relates to impaired quality of life ( QOL ) and depression , identify predictors of poor QOL and depression , and determine the correlation between QOL and depression . METHODS AND RESULTS Among patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial ( TOPCAT ) , 3400 patients completed the Kansas City Cardiomyopathy Questionnaire , 3395 patients completed European QOL 5D Visual Analog Scale , and 1431 patients in United States and Canada completed the Patient Health Questionnaire-9 . The mean summary score on the Kansas City Cardiomyopathy Questionnaire was 54.8 , and on European QOL 5D Visual Analog Scale , it was 60.3 ; 27 % of patients had moderate to severe depression . Factors associated with better Kansas City Cardiomyopathy Questionnaire and European QOL 5D Visual Analog Scale via multiple logistic regression analysis were American region , older age , no history of angina pectoris or asthma , no use of hypoglycemic agent , more activity level , and lower New York Heart Association class . Factors associated with depression via multiple logistic regression analysis included younger age , female sex , comorbid angina , chronic obstructive pulmonary disease , use of a hypoglycemic agent , lower activity level , higher New York Heart Association class , and selective serotonin reuptake inhibitor use . There were significant correlations between each of the QOL scores and depression . CONCLUSIONS Patients with heart failure with preserved ejection fraction , who were younger had higher New York Heart Association class or comorbid angina pectoris , had lower activity levels , lived in Eastern Europe or were taking hypoglycemic agents , were more likely to have impaired QOL and depression . CLINICAL TRIAL REGISTRATION URL : http : //www.clinicaltrials.gov . Unique identifier : NCT00094302 .

Aldosterone Antagonist Trial ( TOPCAT )

European QOL 5D Visual Analog Scale

European QOL 5D Visual Analog Scale

Patient Health Questionnaire-9 .

European QOL 5D Visual Analog Scale

European QOL 5D Visual Analog Scale

QOL scores

depression

depression

impaired quality of life

heart failure

preserved ejection fraction

3400 patients

heart failure

younger

impaired QOL and depression


A randomized controlled trial of guided self-help for improving the experience of caring for carers of clients with depression . AIM To evaluate the effectiveness of a cognitive behaviour therapy guided self-help manual for enhancing the experience of caregiving of family carers of individuals with depression . BACKGROUND The prevalence of depression is increasing markedly in Thailand . While primary carers give most of the support for individuals with depression , they receive little support from mental health services in this critical role . DESIGN A randomized controlled trial . METHOD Carers were randomized to guided self-help ( n = 27 ) , while the control group received standard information and support ( n = 27 ) . Both groups also received a short weekly telephone call . Participants were assessed at three time points ; the outcome measure was the Experience of Caregiving Inventory . A doubly multivariate analysis of variance ( anova ) procedure , including between-group and within-group factors , was implemented . Fieldwork was from October 2007-May 2008 . RESULTS Fifty-four carers completed the study and intent-to-treat analyses were undertaken . The findings showed there was a significant reduction in the total negative experience of caring , from baseline to post-treatment , in the intervention group recipients of the manual compared with the control group and treatment effects were maintained at one-month follow-up . Similarly , a significant improvement in the total positive experience of caring occurred , from baseline to post-treatment , in the intervention group in contrast with the control group and these outcomes were sustained at one-month follow-up . CONCLUSION Guided self-help strengthen carers ' positive and reduces their negative , experience of caring . The study contributes to the limited evidence base about this approach in a developing country such as Thailand .

guided self-help

guided self-help

short weekly telephone call

Caregiving Inventory

Guided self-help

experience of caring for carers

total negative experience of caring

total positive experience of caring

experience of caring

n = 27

( n = 27

Fifty-four carers


Reducing blood loss in simultaneous bilateral total knee arthroplasty : combined intravenous-intra-articular tranexamic acid administration . A prospective randomized controlled trial . BACKGROUND We asked whether tranexamic acid ( TXA ) administration could reduce blood loss and blood transfusion requirements after simultaneous bilateral total knee arthroplasty ( TKA ) . This study examined the role of a novel method of TXA administration in TKA . METHODS TXA was administered as a bolus dose of 15 mg/kg 10 min before the inflation of the tourniquet on the first side . This was followed by intra-articular administration of 3 grams at 10 min before the deflation of the tourniquet . IV infusion of 10 mg/kg/h was continued for 3h following completion on the second side . We measured volume of drained blood 48 h postoperatively , decrease in hemoglobin levels 12h postoperatively , amount of blood transfused ( BT ) , and number of patients requiring allogenic BT . RESULTS Median postoperative volume of drained blood was lower in the group receiving TXA ( 500.00 mL ) than in control subjects ( 900.00 mL ) ( p < 0.05 ) [ 95 % CI ( -525.00 ) to ( -300.00 ) ] . The median hemoglobin decrease 12 h postoperatively was lower in patients receiving TXA ( 2.10 g/dL ) than in control subjects ( 3.10 g/dL ) ( p < 0.05 ) [ 95 % CI ( -1.60 ) to ( -0.60 ) ] . The amount of BT and number of patients requiring BT were lower in patients receiving TXA than in control subjects . Nevertheless , the number of allogeneic units of packed red blood cells transfused in the postoperative period was not significantly higher in the control group than in the TXA group ( p=0.109 ) [ 95 % CI ( 0.101 ) to ( 0.117 ) ] . CONCLUSIONS This prospective randomized study showed that during simultaneous bilateral TKA , TXA reduced blood loss with negligible side effects .

tranexamic acid

tranexamic acid ( TXA )

TXA was administered as a bolus dose

intra-articular administration

IV infusion

TXA

TXA

blood loss

volume of drained blood

packed red blood cells transfused

blood loss

side effects .


Effects of adjunctive zonisamide treatment on weight and body mass index in children with partial epilepsy . BACKGROUND Zonisamide has been associated with weight loss in children and adults . AIMS OF THE STUDY To assess the effects of adjunctive zonisamide on weight and body mass index ( BMI ) in children with partial epilepsy . METHODS A subanalysis was conducted of a Phase III trial and extension study , in which children with partial epilepsy received adjunctive zonisamide ( target dose 8 mg/kg/day ; maximum 500 mg/day ) . Changes in weight were correlated with skeletal development and sexual maturation . RESULTS Overall , 179 children ( 93 male , 86 female ; age 6-18 years ) received zonisamide ( mean duration 370.6 days ) . Weight loss ≥ 5 % was reported for 64 of 179 ( 35.8 % ) zonisamide-treated children . Of these , 46.9 % were overweight/obese at study entry , compared with 23.4 % at study end ( P = 0.0007 ) ; 48.4 % had normal weight at study entry , compared with 65.6 % at study end ( P = 0.03 ) . Three patients were underweight at study entry , and four more became underweight by study end . No consistent correlations between weight loss and skeletal development or sexual maturation were observed . CONCLUSIONS Approximately one-third of children treated with zonisamide experienced ≥ 5 % weight loss . Weight loss was most apparent in children with high baseline BMI values and did not appear to be associated with any consistent effects on growth and development .

zonisamide

Zonisamide

zonisamide

adjunctive zonisamide

zonisamide

weight and body mass index

weight

weight and body mass index ( BMI )

weight

Weight loss ≥ 5 %

were overweight/obese

normal weight

were underweight

became underweight

experienced ≥ 5 % weight loss

Weight

children

partial epilepsy

weight loss

children

children

children

children

male

female

age 6-18 years )


Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches : an open-label , pragmatic , randomised controlled trial . BACKGROUND The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis . We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer . METHODS In this open-label , multicentre , pragmatic , randomised controlled trial , we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer , from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) or conventional diagnosis and staging ( CDS ) , for further investigation and staging . If a target node could not be accessed by EBUS-TBNA , then endoscopic ultrasound-guided fine needle aspiration ( EUS-FNA ) was allowed as an alternative procedure . Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre . We used a telephone randomisation method with permuted blocks of four generated by a computer . Because of the nature of the intervention , masking of participants and consenting investigators was not possible . The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose . This trial is registered with ClinicalTrials.gov , number NCT00652769 . FINDINGS Between June 10 , 2008 , and July 4 , 2011 , we randomly allocated 133 patients to treatment : 66 to EBUS-TBNA and 67 to CDS ( one later withdrew consent ) . Two patients from the EBUS-TBNA group underwent EUS-FNA . The median time to treatment decision was shorter with EBUS-TBNA ( 14 days ; 95 % CI 14-15 ) than with CDS ( 29 days ; 23-35 ) resulting in a hazard ratio of 1·98 , ( 1·39-2·82 , p < 0·0001 ) . One patient in each group had a pneumothorax from a CT-guided biopsy sample ; the patient from the CDS group needed intercostal drainage and was admitted to hospital . INTERPRETATION Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer , because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques . FUNDING UK Medical Research Council .

conventional diagnosis and staging

time-to-treatment decision

median time to treatment decision

pneumothorax

Lung cancer diagnosis

patients with suspected lung cancer .

lung cancer

133 patients

for patients with suspected lung cancer


Oxytocin increases eye contact during a real-time , naturalistic social interaction in males with and without autism . Autism spectrum conditions ( autism ) affect ~1 % of the population and are characterized by deficits in social communication . Oxytocin has been widely reported to affect social-communicative function and its neural underpinnings . Here we report the first evidence that intranasal oxytocin administration improves a core problem that individuals with autism have in using eye contact appropriately in real-world social settings . A randomized double-blind , placebo-controlled , within-subjects design is used to examine how intranasal administration of 24 IU of oxytocin affects gaze behavior for 32 adult males with autism and 34 controls in a real-time interaction with a researcher . This interactive paradigm bypasses many of the limitations encountered with conventional static or computer-based stimuli . Eye movements are recorded using eye tracking , providing an objective measurement of looking patterns . The measure is shown to be sensitive to the reduced eye contact commonly reported in autism , with the autism group spending less time looking to the eye region of the face than controls . Oxytocin administration selectively enhanced gaze to the eyes in both the autism and control groups ( transformed mean eye-fixation difference per second=0.082 ; 95 % CI:0.025-0.14 , P=0.006 ) . Within the autism group , oxytocin has the most effect on fixation duration in individuals with impaired levels of eye contact at baseline ( Cohen 's d=0.86 ) . These findings demonstrate that the potential benefits of oxytocin in autism extend to a real-time interaction , providing evidence of a therapeutic effect in a key aspect of social communication .

Oxytocin

Oxytocin

intranasal oxytocin

placebo-controlled

males

with and without autism

Autism spectrum conditions ( autism )

individuals with autism

males

autism


Real-Time Assessment of the Effect of Biofeedback Therapy with Migraine : A Pilot Study . BACKGROUND Biofeedback therapy has been reported to be effective in the treatment of migraine . However , previous studies have assessed its effectiveness using paper-and-pencil diaries , which are not very reliable . PURPOSE The objective of the present pilot study was to investigate the feasibility of using computerized ecological momentary assessment ( EMA ) for evaluating the efficacy of BF treatment for migraine in a randomized controlled trial . METHOD The subjects comprised one male and 26 female patients with migraine . They were randomly assigned to either biofeedback or wait-list control groups . Patients were asked to carry a palmtop-type computer to record momentary symptoms for 4 weeks before and after biofeedback treatment . The primary outcome measure was headache intensity . The secondary outcome measures included psychological stress , anxiety , irritation , headache-related disability and the frequency ( number of days per month ) of migraine attack and of headache of at least moderate intensity ( pain rating ≥50 ) . RESULTS Headache intensity showed significant main effects of period ( before vs. after therapy , p = 0.02 ) and group ( biofeedback vs. control groups , p = 0.42 ) and a significant period × group interaction ( p < 0.001 ) . Biofeedback reduced the duration of headaches by 1.9 days , and the frequency of days when headache intensity was ≥50 by 2.4 times . In addition , headache-related disability , psychological stress , depression , anxiety , and irritation were significantly improved . CONCLUSION The present study used computerized EMA to show that biofeedback could improve the symptoms of migraine , including psychological stress and headache-related disability .

Biofeedback Therapy

Biofeedback therapy

BF treatment

biofeedback

wait-list control groups .

biofeedback treatment

Effect of Biofeedback Therapy

evaluating the efficacy of BF treatment

headache intensity .

psychological stress

anxiety

, irritation

headache-related disability

headache of at least moderate intensity

RESULTS Headache intensity

duration

frequency of days when headache

headache-related disability

psychological stress

depression , anxiety

psychological stress

one

male

female

migraine


Hyperfractionated accelerated radiation therapy ( HART ) of 70.6 Gy with concurrent 5-FU/Mitomycin C is superior to HART of 77.6 Gy alone in locally advanced head and neck cancer : long-term results of the ARO 95-06 randomized phase III trial . PURPOSE To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil ( C-HART ) with hyperfractionated accelerated radiation therapy ( HART ) alone in locally advanced head and neck cancer . PATIENTS AND METHODS The primary endpoint was locoregional control ( LRC ) . Three hundred eighty-four patients with stage III ( 6 % ) and IV ( 94 % ) oropharyngeal ( 59.4 % ) , hypopharyngeal ( 32.3 % ) , and oral cavity ( 8.3 % ) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU ( C-HART ) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone ( HART ) . Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses . RESULTS The median follow-up time was 8.7 years ( 95 % confidence interval [ CI ] : 7.8-9.7 years ) . At 10 years , the LRC rates were 38.0 % ( C-HART ) versus 26.0 % ( HART , P=.002 ) . The cancer-specific survival and overall survival rates were 39 % and 10 % ( C-HART ) versus 30.0 % and 9 % ( HART , P=.042 and P=.049 ) , respectively . According to multivariate Cox regression analysis , the combined treatment was associated with improved LRC ( hazard ratio [ HR ] : 0.6 [ 95 % CI : 0.5-0.8 ; P=.002 ] ) . The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer ( P=.003 ) as compared with hypopharyngeal or oral cavity cancer ( P=.264 ) . CONCLUSIONS C-HART remains superior to HART in terms of LRC . However , this effect may be limited to oropharyngeal cancer patients .

5-FU/Mitomycin C

HART

mitomycin C/5-fluorouracil ( C-HART )

RESULTS The median follow-up

10 years , the

associated with improved

and increased

in terms

locally advanced head and neck cancer

locally advanced head and neck cancer

limited to oropharyngeal cancer


Effects of sodium and potassium supplementation on blood pressure and arterial stiffness : a fully controlled dietary intervention study . We performed a randomised , placebo-controlled , crossover study to examine the effects of sodium and potassium supplementation on blood pressure ( BP ) and arterial stiffness in untreated ( pre ) hypertensive individuals . During the study , subjects were on a fully controlled diet that was relatively low in sodium and potassium . After a 1-week run-in period , subjects received capsules with supplemental sodium ( 3 g d ( -1 ) , equals 7.6 g d ( -1 ) of salt ) , supplemental potassium ( 3 g d ( -1 ) ) or placebo , for 4 weeks each , in random order . Fasting office BP , 24-h ambulatory BP and measures of arterial stiffness were assessed at baseline and every 4 weeks . Of 37 randomized subjects , 36 completed the study . They had a mean pre-treatment BP of 145/81 mm Hg and 69 % had systolic BP ⩾140 mm Hg . Sodium excretion was increased by 98 mmol per 24 h and potassium excretion by 63 mmol per 24 h during active interventions , compared with placebo . During sodium supplementation , office BP was significantly increased by 7.5/3.3 mm Hg , 24-h BP by 7.5/2.7 mm Hg and central BP by 8.5/3.6 mm Hg . During potassium supplementation , 24-h BP was significantly reduced by 3.9/1.6 mm Hg and central pulse pressure by 2.9 mm Hg . Pulse wave velocity and augmentation index were not significantly affected by sodium or potassium supplementation . In conclusion , increasing the intake of sodium caused a substantial increase in BP in subjects with untreated elevated BP . Increased potassium intake , on top of a relatively low-sodium diet , had a beneficial effect on BP . Arterial stiffness did not materially change during 4-week interventions with sodium or potassium .

sodium and potassium supplementation

sodium and potassium supplementation

sodium

supplemental potassium

placebo

blood pressure and arterial stiffness :

measures of arterial

pre-treatment

increased

intake

blood pressure

arterial stiffness :

blood pressure ( BP )

arterial stiffness

sodium caused a substantial increase


A randomized , double-blind controlled trial of lumbar interlaminar epidural injections in central spinal stenosis : 2-year follow-up . BACKGROUND While low back pain is the number one cause of disability in the United States , lumbar spinal stenosis along with intervertebral disc herniation and degenerative spondylolisthesis is one of the 3 most common diagnosis of low back and leg pain for which surgery is performed . Numerous modalities of treatments including drug therapy and complex surgical fusions have been recommended for treatment of central spinal stenosis . Epidural injections are one of the commonly performed nonsurgical interventions in managing central spinal stenosis ; however , there has been paucity of literature in reference to efficacy of epidural injections in managing central spinal stenosis with lumbar interlaminar epidural injections . STUDY DESIGN A randomized , double-blind , active controlled trial . SETTING Private interventional pain management practice and specialty referral center in the United States . OBJECTIVE To assess the effectiveness of lumbar interlaminar epidural injections with or without steroids in providing effective and long-lasting pain relief with improvement in functional status for the management of chronic low back and lower extremity pain related to lumbar central spinal stenosis . METHODS A randomized , double-blind , active-control trial was designed with the inclusion of 120 patients assigned to 2 groups . Group I patients received lumbar interlaminar epidural injections of local anesthetic ( lidocaine 0.5 % ) 6 mL , whereas Group II received lumbar interlaminar epidural injections with local anesthetic ( lidocaine 0.5 % ) 5 mL mixed with 1 mL of steroids and 6 mg of betamethasone . OUTCOMES ASSESSMENT Outcomes were assessed utilizing the numeric pain rating scale ( NRS ) and Oswestry Disability Index ( ODI ) at 3 , 6 , 12 , 18 , and 24 months post treatment . The primary outcome measure was significant improvement , defined as 50 % improvement in pain and disability scores . RESULTS Significant relief and functional status improvement was seen in 72 % and 73 % of patients in Groups I and II at the end of 2 years considering all participants ; however , this was 84 % and 85 % in the successful group . Overall significant improvement was achieved for 65.7 ± 37.3 weeks in Group 1 and 68.9 ± 37.7 weeks in Group II at the end of 2 years when all participants were considered ; whereas , this was 77 ± 27.8 weeks and 77.9 ± 30.2 weeks when they were separated into successful categories . The average number of procedures per patient was 5 to 6 in both groups . LIMITATIONS Limitations of this trial include lack of placebo control group and treatment of patients with multiple procedures over a period of 2 years . CONCLUSION Lumbar interlaminar epidural injections of local anesthetic with or without steroids provide relief in a significant proportion of patients with lumbar central spinal stenosis . CLINICAL TRIAL NCT00681447 .

Epidural injections

epidural injections

lumbar interlaminar epidural injections

numeric pain rating scale ( NRS

Oswestry Disability Index ( ODI )

50 % improvement in pain

disability scores

lumbar spinal stenosis

lumbar central spinal stenosis


Assessment of paravalvular aortic regurgitation after transcatheter aortic valve replacement : intra-core laboratory variability . BACKGROUND There is significant disparity in the reported incidence of moderate and severe paravalvular aortic regurgitation ( PAR ) between the Placement of Aortic Transcatheter Valves ( PARTNER ) I and PARTNER II trials , which may be related to the echocardiographic methodologies used by separate core laboratories . To further explore the variability in echocardiographic interpretation of PAR , agreement between the grading of PAR by the core laboratory of PARTNER IIB was compared with that by a consortium of echocardiography core laboratory directors . METHODS The PARTNER IIB core laboratory reevaluated patients using primarily the circumferential extent of the regurgitant jet for PAR . A consortium of echocardiography core laboratory directors was formed to evaluate the echocardiographic images and to grade PAR and central and total aortic regurgitation in a randomly chosen subset of the randomized patients in the PARTNER IIB trial using a multiwindow , multiparametric approach . Both a four-class scale ( none or trace , mild , moderate , and severe ) and a seven-class ( none , trace , mild , mild to moderate , moderate , moderate to severe , and severe ) scale were used . Levels of grading agreement between the consortium and original core laboratory in both scales were determined using weighted κ statistics . RESULTS Only 87 patients assessed for PAR by the consortium could be paired with readings by the PARTNER IIB core laboratory . Using the four-class grading scheme the weighted κ statistic for PAR was 0.481 ( 95 % confidence limits , 0.367 , 0.595 ) . Using the seven-class scale , the weighted κ statistic for PAR was 0.517 ( 95 % confidence limits , 0.431 , 0.607 ) . For either grading scheme , 15.9 % of patients graded by the PARTNER IIB core laboratory as having moderate PAR would have been graded as having mild PAR using the multiparametric approach . Similar results were seen for central and total aortic regurgitation assessments . CONCLUSIONS Using primarily the circumferential extent criteria , the PARTNER IIB core laboratory overestimated the severity of PAR compared to the consortium using a multi-parametric approach . Although a more granular classification scheme for PAR may slightly improve concordance between core laboratories , differences in the incidence of moderate or severe PAR are likely related to differences in grading methodology . A multiparametric approach is advocated , and other echocardiographic methods for assessing PAR deserve further study .

transcatheter aortic valve replacement

echocardiographic images

PAR .

PAR

for PAR

the weighted κ statistic for PAR

the weighted κ statistic for PAR

moderate PAR

mild PAR

of PAR

severe PAR

PAR


The clinical effectiveness and cost-effectiveness of telephone triage for managing same-day consultation requests in general practice : a cluster randomised controlled trial comparing general practitioner-led and nurse-led management systems with usual care ( the ESTEEM trial ) . BACKGROUND Telephone triage is proposed as a method of managing increasing demand for primary care . Previous studies have involved small samples in limited settings , and focused on nurse roles . Evidence is limited regarding the impact on primary care workload , costs , and patient safety and experience when triage is used to manage patients requesting same-day consultations in general practice . OBJECTIVES In comparison with usual care ( UC ) , to assess the impact of GP-led telephone triage ( GPT ) and nurse-led computer-supported telephone triage ( NT ) on primary care workload and cost , patient experience of care , and patient safety and health status for patients requesting same-day consultations in general practice . DESIGN Pragmatic cluster randomised controlled trial , incorporating economic evaluation and qualitative process evaluation . SETTING General practices ( n = 42 ) in four regions of England , UK ( Devon , Bristol/Somerset , Warwickshire/Coventry , Norfolk/Suffolk ) . PARTICIPANTS Patients requesting same-day consultations . INTERVENTIONS Practices were randomised to GPT , NT or UC . Data collection was not blinded ; however , analysis was conducted by a statistician blinded to practice allocation . MAIN OUTCOME MEASURES Primary - primary care contacts [ general practice , out-of-hours primary care , accident and emergency ( A & E ) and walk-in centre attendances ] in the 28 days following the index consultation request . Secondary - resource use and costs , patient safety ( deaths and emergency hospital admissions within 7 days of index request , and A & E attendance within 28 days ) , health status and experience of care . RESULTS Of 20,990 eligible randomised patients ( UC n = 7283 ; GPT n = 6695 ; NT n = 7012 ) , primary outcome data were analysed for 16,211 patients ( UC n = 5572 ; GPT n = 5171 ; NT n = 5468 ) . Compared with UC , GPT and NT increased primary outcome contacts ( over 28-day follow-up ) by 33 % [ rate ratio ( RR ) 1.33 , 95 % confidence interval ( CI ) 1.30 to 1.36 ] and 48 % ( RR 1.48 , 95 % CI 1.44 to 1.52 ) , respectively . Compared with GPT , NT was associated with a marginal increase in primary outcome contacts by 4 % ( RR 1.04 , 95 % CI 1.01 to 1.08 ) . Triage was associated with a redistribution of primary care contacts . Although GPT , compared with UC , increased the rate of overall GP contacts ( face to face and telephone ) over the 28 days by 38 % ( RR 1.38 , 95 % CI 1.28 to 1.50 ) , GP face-to-face contacts were reduced by 39 % ( RR 0.61 , 95 % CI 0.54 to 0.69 ) . NT reduced the rate of overall GP contacts by 16 % ( RR 0.84 , 95 % CI 0.78 to 0.91 ) and GP face-to-face contacts by 20 % ( RR 0.80 , 95 % CI 0.71 to 0.90 ) , whereas nurse contacts increased . The increased rate of primary care contacts in triage arms is largely attributable to increased telephone contacts . Estimated overall patient-clinician contact time on the index day increased in triage ( GPT = 10.3 minutes ; NT = 14.8 minutes ; UC = 9.6 minutes ) , although patterns of clinician use varied between arms . Taking account of both the pattern and duration of primary outcome contacts , overall costs over the 28-day follow-up were similar in all three arms ( approximately £75 per patient ) . Triage appeared safe , and no differences in patient health status were observed . NT was somewhat less acceptable to patients than GPT or UC . The process evaluation identified the complexity associated with introducing triage but found no consistency across practices about what works and what does not work when implementing it . CONCLUSIONS Introducing GPT or NT was associated with a redistribution of primary care workload for patients requesting same-day consultations , and at similar cost to UC . Although triage seemed to be safe , investigation of the circumstances of a larger number of deaths or admissions after triage might be warranted , and monitoring of these events is necessary as triage is implemented . TRIAL REGISTRATION Current Controlled Trials ISRCTN20687662 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 19 , No . 13 . See the NIHR Journals Library website for further project information .

telephone triage

Telephone triage

triage

usual care ( UC )

GP-led telephone triage ( GPT )

GP-led telephone triage ( GPT )

n = 7012


Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer . PURPOSE We have previously reported that radiotherapy ( RT ) added to androgen-deprivation therapy ( ADT ) improves survival in men with locally advanced prostate cancer . Here , we report the prespecified final analysis of this randomized trial . PATIENTS AND METHODS NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer . Patients with T3-4 , N0/Nx , M0 prostate cancer or T1-2 disease with either prostate-specific antigen ( PSA ) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT . The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone . Overall survival was compared using a log-rank test stratified for prespecified variables . RESULTS One thousand two hundred five patients were randomly assigned between 1995 and 2005 , 602 to ADT alone and 603 to ADT+RT . At a median follow-up time of 8 years , 465 patients had died , including 199 patients from prostate cancer . Overall survival was significantly improved in the patients allocated to ADT+RT ( hazard ratio [ HR ] , 0.70 ; 95 % CI , 0.57 to 0.85 ; P < .001 ) . Deaths from prostate cancer were significantly reduced by the addition of RT to ADT ( HR , 0.46 ; 95 % CI , 0.34 to 0.61 ; P < .001 ) . Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity , but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT . CONCLUSION This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer .

Androgen-Deprivation Therapy Alone

radiotherapy ( RT )

androgen-deprivation therapy ( ADT )

Overall survival

Overall survival

higher frequency of adverse events

bowel toxicity

diarrhea

men

locally advanced prostate cancer

advanced prostate cancer

One thousand two hundred five patients

men

locally advanced prostate cancer


Computer-Assisted Face Processing Instruction Improves Emotion Recognition , Mentalizing , and Social Skills in Students with ASD . This study examined the extent to which a computer-based social skills intervention called FaceSay was associated with improvements in affect recognition , mentalizing , and social skills of school-aged children with Autism Spectrum Disorder ( ASD ) . FaceSay offers students simulated practice with eye gaze , joint attention , and facial recognition skills . This randomized control trial included school-aged children meeting educational criteria for autism ( N = 31 ) . Results demonstrated that participants who received the intervention improved their affect recognition and mentalizing skills , as well as their social skills . These findings suggest that , by targeting face-processing skills , computer-based interventions may produce changes in broader cognitive and social-skills domains in a cost- and time-efficient manner .

FaceSay

Emotion Recognition

Mentalizing

Social Skills

cost- and time-efficient manner

Students with ASD .

school-aged children

Autism Spectrum Disorder ( ASD ) .

school-aged children

autism


The nature of placebo response in clinical studies of major depressive disorder . OBJECTIVE To review factors influencing placebo response and clinical trial outcome in depression , and suggest ways to optimize trial success in mood disorders . DATA SOURCES PubMed searches were conducted by cross-referencing the terms depression , depressive with placebo , clinical trial , and clinical trials for studies published in English between 1970 and September 2013 . STUDY SELECTION Relevant abstracts were identified in PubMed , including clinical trials , quantitative studies , and qualitative research . We obtained and reviewed relevant articles and utilized their information to synthesize the present review . DATA EXTRACTION Included articles were grouped in the following areas of relevance : ( 1 ) biological validity of illness , ( 2 ) baseline severity of illness , ( 3 ) chronicity of the index episode of depression , ( 4 ) age of participants , ( 5 ) medical and psychiatric comorbidity , ( 6 ) probability of receiving placebo , ( 7 ) use of prospective treatment phases ( lead-in ) ( 8 ) dosing schedule , ( 9 ) trial duration , ( 10 ) frequency of follow-up assessments , and ( 11 ) study outcome measure . RESULTS Several key elements emerge as critical to the ultimate success of a clinical trial , including the probability of receiving placebo , study duration , dosing schedule , visit frequency , the use of blinded lead-in phases , the use of centralized raters , illness severity and duration , and comorbid anxiety . CONCLUSIONS Our increasing understanding of the placebo response in clinical trials of major depressive disorder lends to a , gradually , more predictable phenomenon and , hopefully , to one that becomes lesser in magnitude and variability . Several elements have emerged that seem to play a critical role in trial success , gradually reshaping the design of clinical , translational , as well as mechanistic studies in depression .

placebo

placebo

placebo

receiving placebo

placebo

placebo

probability of receiving placebo

study duration

dosing schedule

visit frequency

the use of blinded lead-in phases

the use of centralized raters

illness severity and duration

comorbid anxiety


Long-term functional outcomes and predictors of shunt-dependent hydrocephalus after treatment of ruptured intracranial aneurysms in the BRAT trial : revisiting the clip vs coil debate . BACKGROUND Acute hydrocephalus is a well-known sequela of aneurysmal subarachnoid hemorrhage ( SAH ) . Controversy exists about whether open microsurgical methods serve to reduce shunt dependency compared with endovascular techniques . OBJECTIVE To determine predictors of shunt-dependent hydrocephalus and functional outcomes after aneurysmal SAH . METHODS A total of 471 patients who were part of a prospective , randomized , controlled trial from 2003 to 2007 were retrospectively reviewed . All variables including demographic data , medical history , treatment , imaging , and functional outcomes were included as part of the trial . No additional variables were retrospectively collected . RESULTS Ultimately , 147 patients ( 31.2 % ) required a ventriculoperitoneal shunt ( VPS ) in our series . Age , dissecting aneurysm type , ruptured vertebrobasilar aneurysm , Fisher grade , Hunt and Hess grade , admission intraventricular hemorrhage , admission intraparenchymal hemorrhage , blood in the fourth ventricle on admission , perioperative ventriculostomy , and hemicraniectomy were significant risk factors ( P < .05 ) associated with shunt-dependent hydrocephalus on univariate analysis . On multivariate analysis , intraventricular hemorrhage and intraparenchymal hemorrhage were independent risk factors for shunt dependency ( P < .05 ) . Clipping vs coiling treatment was not statistically associated with VPS after SAH on both univariate and multivariate analyses . Patients who did not receive a VPS at discharge had higher Glasgow Outcome Scale and Barthel Index scores and were more likely to be functionally independent and to return to work 72 months after surgery ( P < .05 ) . CONCLUSION There is no difference in shunt dependency after SAH among patients treated by endovascular or microsurgical means . Patients in whom shunt-dependent hydrocephalus does not develop after SAH tend to have improved long-term functional outcomes .

Clipping

coiling

shunt-dependent hydrocephalus

shunt dependency

shunt-dependent hydrocephalus

functional outcomes

functional outcomes

shunt-dependent hydrocephalus

intraventricular hemorrhage

intraparenchymal hemorrhage

shunt dependency

Glasgow Outcome Scale

Barthel Index

shunt dependency

shunt-dependent hydrocephalus

Acute hydrocephalus

471 patients

shunt-dependent hydrocephalus


Mask ventilation with two different face masks in the delivery room for preterm infants : a randomized controlled trial . BACKGROUND If an infant fails to initiate spontaneous breathing after birth , international guidelines recommend a positive pressure ventilation ( PPV ) . However , PPV by face mask is frequently inadequate because of leak between the face and mask . Despite a variety of available face masks , none have been prospectively compared in a randomized fashion . We aimed to evaluate and compare leak between two commercially available round face masks ( Fisher & Paykel ( F & P ) and Laerdal ) in preterm infants < 33 weeks gestational age in the delivery room . METHODS Infants born at the Royal Alexandra Hospital from April to September 2013 at < 33 weeks gestational age who received mask PPV in the delivery room routinely had a flow sensor placed between the mask and T-piece resuscitator . Infants were randomly assigned to receive PPV with either a F & P or Laerdal face mask . All resuscitators were trained in the use of both face masks . We compared mask leak , airway pressures , tidal volume and ventilation rate between the two groups . RESULTS Fifty-six preterm infants ( n=28 in each group ) were enrolled ; mean±s.d . gestational age 28±3 weeks ; birth weight 1210±448 g ; and 30 ( 52 % ) were male . Apgar scores at 1 and 5 min were 5±3 and 7±2 , respectively . Infants randomized to the F & P face mask and Laerdal face mask had similar mask leak ( 30 ( 25-38 ) versus 35 ( 24-46 ) % , median ( interquartile range ) , respectively , P=0.40 ) and tidal volume ( 7.1 ( 4.9-8.9 ) versus 6.6 ( 5.2-8.9 ) ml kg ( -1 ) , P=0.69 ) during PPV . There were no significant differences in ventilation rate , inflation time or airway pressures between groups . CONCLUSION The use of either face mask during PPV in the delivery room yields similar mask leak in preterm infants < 33 weeks gestational age .

Mask ventilation

face mask

round face masks

Fisher & Paykel ( F & P )

Laerdal

PPV with either a F & P

Laerdal face mask

mask leak

airway pressures

tidal volume

ventilation rate

mask

tidal

ventilation rate

inflation time

airway

preterm infants :

Fifty-six

( 52 % ) were male


A randomized , multicenter , multivendor study of myocardial perfusion imaging with regadenoson CT perfusion vs single photon emission CT. BACKGROUND Myocardial CT perfusion ( CTP ) is a promising tool for the detection of myocardial ischemia . We hypothesize that regadenoson CTP is noninferior to regadenoson single photon emission CT ( SPECT ) for detecting or excluding myocardial ischemia . METHODS Patients ( men ≥ 45 years ; women ≥ 50 years ) with known or suspected coronary artery disease ( n = 124 ) were randomized to 1 of 2 diagnostic sequences : rest and regadenoson SPECT on day 1 , then regadenoson CTP and rest CTP ( and coronary CT angiography [ CTA ] ) ( CTA ; same acquisition ) on day 2 or regadenoson CTP and rest CTP ( and CTA ) on Day 1 , then rest and regadenoson SPECT on day 2 . Scanning platforms included 64- , 128- , 256- , and 320-slice systems . The primary analysis examined the agreement rate between CTP and SPECT for detecting or excluding reversible ischemia in ≥ 2 myocardial segments as assessed by independent , blinded readers . RESULTS Complete and interpretable CTP and SPECT scans were obtained for 110 patients . Regadenoson CTP was noninferior to SPECT for detecting or excluding reversible ischemia with an agreement rate of 0.87 ( 95 % confidence interval [ CI ] , 0.77-0.97 ) and sensitivity and specificity of 0.90 ( 95 % CI , 0.71-1.00 ) and 0.84 ( 95 % CI , 0.77-0.91 ) , respectively . The agreement rate for detecting or excluding ≥ 1 fixed defects by regadenoson CTP and SPECT was 0.86 ( 95 % CI , 0.74-0.98 ) . With SPECT as the reference standard , the diagnostic accuracies for detecting or excluding ischemia by regadenoson CTP and CTA alone were 0.85 ( 95 % CI , 0.78-0.91 ) and 0.69 ( 95 % CI , 0.60-0.77 ) , respectively . CONCLUSIONS This study establishes the noninferiority of regadenoson CTP to SPECT for detecting or excluding myocardial ischemia .

regadenoson CT perfusion

single photon emission CT.

respectively

The agreement

excluding ≥ 1 fixed

myocardial ischemia

myocardial ischemia

men

45 years

women

50 years

coronary artery disease

myocardial ischemia


Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial : differential effect on high- and low-grade disease . OBJECTIVE To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione ( androstenedione ) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial . METHODS We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls , nested in the Prostate Cancer Prevention Trial , a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk . Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme . RESULTS We observed a 22 % increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years . This significant increase did not vary by case-control status . Adjusted odds ratio and 95 % confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 ( 95 % confidence interval , 0.19-0.94 ) for low-grade ( Gleason score < 7 ) cases . Similar results were observed when analyzed using percent change . There were no significant associations between serum androstenedione levels and the risk of high-grade disease . CONCLUSION The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone ( DHT ) and of androstenedione to 5α-androstanedione-3,17-dione , which also leads to the reduction of DHT formation . This decrease in DHT may help reduce the risk of low-grade prostate cancer in men . Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression .

finasteride

finasteride

placebo-controlled

finasteride

Prostate Cancer