Functional outcome following intramedullary nailing of the femur : a prospective randomized comparison of piriformis fossa and greater trochanteric entry portals . BACKGROUND The purpose of the study was to prospectively compare the functional outcome of intramedullary nailing of the femur performed with use of a trochanteric and a piriformis fossa entry portal . METHODS One hundred and ten patients with a femoral shaft fracture were enrolled in a prospective , randomized study . Fifty-four patients were randomized to Group A ( piriformis fossa portal ) and fifty-six to Group B ( trochanteric portal ) . Outcome measures included the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index hip function score , pain , and blinded functional evaluation by a physical therapist . RESULTS Most measures of hip function did not differ between the two groups . The WOMAC score at three , six , and twelve months did not differ significantly between the piriformis fossa and trochanteric nailing groups . Functional tests included the chair stand test and the timed up and go test . Patients in Group B had significantly better scores on the chair stand test ( 13.3 compared with 11.1 in Group A , p = 0.04 ) at six months postoperatively , but there was no difference at twelve months ( 14.0 compared with 13.6 ) . The two groups did not differ significantly on the timed up and go test at either six or twelve months . The two groups also did not differ on the muscle strength testing . Intraoperative parameters differed significantly between the groups with respect to operative time , fluoroscopy time , and incision length , with the difference favoring Group B for each parameter . Analog pain scale values were similar in Group A ( 2.49 ) and Group B ( 2.15 ) at twelve months postoperatively . CONCLUSIONS Patients in our prospective randomized study who were treated with trochanteric nailing did not differ in hip function at one year postoperatively compared with patients treated with intramedullary nailing through the piriformis fossa . The values of several intraoperative parameters were significantly better in the trochanteric nailing group . Our data indicate that the functional hip outcome of femoral intramedullary nailing performed through the greater trochanter is equal to that of intramedullary nailing performed through the piriformis fossa .

intramedullary nailing of the femur :

( piriformis fossa portal )

( trochanteric portal )

intramedullary nailing

WOMAC score

chair stand test

muscle strength testing

respect to operative time

fluoroscopy time

incision length

hip function

One hundred and ten patients

femoral shaft fracture

Fifty-four

fifty-six


Social skills training for young adults with high-functioning autism spectrum disorders : a randomized controlled pilot study . Despite the psychosocial difficulties common among young adults with autism spectrum disorders ( ASD ) , little to no evidence-based social skills interventions exist for this population . Using a randomized controlled trial ( RCT ) design , the current study tested the effectiveness of an evidence-based , caregiver-assisted social skills intervention known as PEERS for Young Adults with high-functioning young adults with ASD ( ages 18-23 ) using self- and caregiver-report measures . Results revealed that treated young adults reported significantly less loneliness and improved social skills knowledge , while caregivers reported significant improvements in young adults ' overall social skills , social responsiveness , empathy , and frequency of get-togethers . Results support the effectiveness of using this caregiver-assisted , manualized intervention for young adults with ASD .

Social skills training

social skills interventions

an evidence-based

caregiver-assisted

manualized intervention

self- and caregiver-report measures

loneliness

improved social skills knowledge

overall social skills

social responsiveness

empathy

frequency of get-togethers


Enhancing the application and evaluation of a discrete trial intervention package for eliciting first words in preverbal preschoolers with ASD . This study evaluates the effectiveness of an intervention package including a discrete trial program ( Rapid Motor Imitation Antecedent Training ( Tsiouri and Greer , J Behav Educat 12:185-206 , 2003 ) combined with parent education for eliciting first words in children with ASD who had little or no spoken language . Evaluation of the approach includes specific intervention targets and functional spoken language outcomes ( Tager-Flusberg et al. , J Speech Lang Hear Res 52:643-652 , 2009 ) . Results suggest that RMIA , with parent training , catalyzes development of verbal imitation and production for some children . Three of five participants acquired word production within the DTT framework and achieved milestones of early functional spoken language use ( Tager-Flusberg et al. , J Speech Lang Hear Res 52:643-652 , 2009 ) . The implications of these findings for understanding the role of discrete trial approaches to language intervention are discussed .

discrete trial intervention package

combined with parent education for

verbal imitation and production

word production

early functional spoken language use

preverbal preschoolers

ASD

children

ASD

little or no spoken language

Three of five


[ The equipotency of ropivacaine , bupivacaine and etidocaine ] . Ropivacaine , congenerate to bupivacaine and mepivacaine has been widely studied in laboratory animals , but there have been few investigations of its efficacy in human epidural anesthesia and peripheral nerve blocks . The aim of this study was to compare the three long-acting local anesthetics ( bupivacaine 0.75 % , ropivacaine 1 % and etidocaine 1 % ) and to try , with reference to previous studies , to make some statement about the equipotency of ropivacaine relative to bupivacaine and etidocaine . METHODS . In a double blind randomized study , epidural anesthesia was carried out with 20 ml bupivacaine 0.75 % ( n = 24 ) and ropivacaine 1 % ( n = 21 ) . Following this study epidural anesthesia was carried out with 20 ml etidocaine 1 % ( n = 20 ) in an open study . Patients with ASA I or II were enrolled in the study . All patients were scheduled for varicose vein stripping . Male and female patients aged 18-70 years and weighing 50-100 kg were included in the study . Patients were all placed in a sitting position , after which the epidural space was identified by the " loss of resistance " technique and a midline approach , at the L-3/4 interspace . Injections of 3 ml of the local anesthetic were given , followed by the remainder of the local anesthetic at 10 ml/min 1 min later . Following injection patients were immediately positioned supine . Analgesia was determined by the pin-prick method and motor blockade was assessed according to the Bromage scale . Heart rate and blood pressure were monitored until 3 h after injection . RESULTS . The latency of analgesia for the first blocked segment ( T 12 for bupivacaine and ropivacaine and L-1 for etidocaine ) was 6.0 min for bupivacaine 0.75 , 5.5 min for ropivacaine 1 % , and 5.2 min for etidocaine 1 % , and the highest thoracic dermatome ( T 5 for bupivacaine , T 4 for ropivacaine and T 7 for etidocaine ) was reached after 24 +/- 10 , 26 +/- 9 , and 30 +/- 18 min for bupivacaine , ropivacaine , and etidocaine , respectively . The duration of sensory anesthesia at the T 10 dermatomal level was 257 +/- 102 , 278 +/- 67 , and 191 +/- 86 min for bupivacaine , ropivacaine , and etidocaine , respectively . The two-segment regression time was 199 +/- 80 min for bupivacaine , 201 +/- 52 min for ropivacaine , and 174 +/- 81 min for etidocaine . The total duration of sensory block was 340 +/- 103 min for bupivacaine , 428 +/- 65 min for ropivacaine and 223 +/- 62 min for etidocaine , respectively . In the ropivacaine and bupivacaine groups sensory anesthesia was considered adequate for surgery in all cases but one in each group ; in the etidocaine group , however 60 % of the patients showed inadequate analgesia and all these patients ( 12/20 ) required additional analgesics . Bupivacaine achieved an average of motor block 2.1 , ropivacaine 2.3 , and etidocaine 2.4 . CONCLUSION . The results of this study indicate that ropivacaine is an effective local anesthetic agent . Its potency is about equal to that of bupivacaine and much higher than that of etidocaine ...

ropivacaine

bupivacaine

etidocaine

Ropivacaine

bupivacaine

ropivacaine

etidocaine

ropivacaine

bupivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

bupivacaine

ropivacaine

etidocaine

ropivacaine

bupivacaine

etidocaine

Bupivacaine

ropivacaine

etidocaine

ropivacaine

bupivacaine

etidocaine

pin-prick method

latency of analgesia

duration of sensory anesthesia

two-segment regression time

total duration of sensory block

inadequate analgesia

ASA I or II

Male

female


[ Cisapride for the treatment of irritable stomach -- results of 2 multicenter studies ] .

Cisapride

stomach -- results

Cisapride

irritable stomach


Comparison of two artificial tear formulations for dry eye through high-resolution optical coherence tomography . PURPOSE The aim was to determine the efficacy of two artificial eye-drop formulations by analysing the lower tear film meniscus volume through a commercial high-resolution spectral-domain optical coherence tomographer . METHODS Twenty dry eye patients ( 12 men , eight women , aged 57.5 ± 8.4 years ) with refractive errors from -2.50 to +0.75 D ( mean -1.34 ± 1.02 D ) and cylinders lower than 1.00 D were examined . Tear meniscus volume was measured before , immediately after and 10 , 30 and 60 minutes after instillation using the Copernicus high-resolution spectral-domain optical coherence tomographer ( Optopol Tech SA , Zawiercie , Poland ) . Volume was calculated from the local area obtained from tomograms considering a regular distribution of the tear meniscus across the eyelid . Ten subjects were randomly assigned to first receive either polyethylene glycol ( Blink Intensive , Abbot Medical Optics Inc , CA , USA ) or hypromellose ( Artific , Farma-Lepori SA , Barcelona , Spain ) three times daily in both eyes for one month . Measures were then repeated and after a one-week wash-out period they were switched to the other eye-drop for another month . RESULTS Mean baseline volume was 0.38 ± 0.10 µL , while mean baseline volume after the wash-out period was slightly higher , 0.39 ± 0.10 µL ( p = 0.638 ) . Analysis of variance showed significant differences in meniscus volume with time after instillation with both formulations ( p < 0.001 ) , mean volume decreasing with time . At 30 and 60 minutes following instillation , values decreased to almost baseline ( average difference 0.02 ± 0.03 µL at t ( 30 ) , p = 0.016 and 0.01 ± 0.01 µL at t ( 60 ) , p = 0.098 ) . CONCLUSION An increase in tear film meniscus volume in dry eyes from the use of eye-drops has been shown . High resolution imaging of lower tear film meniscus with clinical optical coherence tomography systems provides useful measures of tear volume . Both formulations assessed in the present study are efficient in increasing tear meniscus volume and reducing dry eye signs and symptoms , although results in terms of increase in meniscus volume were higher with the polyethylene glycol formulation .

artificial tear formulations

two artificial eye-drop formulations

Tear meniscus volume


Side branch occlusion with everolimus-eluting and paclitaxel-eluting stents : three-year results from the SPIRIT III randomised trial . AIMS AND METHODS The rates of side branch occlusion and subsequent periprocedural MI during everolimus-eluting stent ( EES ) and paclitaxel-eluting stent ( PES ) placement were examined in the randomised SPIRIT III trial . Periprocedural myocardial infarction ( MI ) following drug-eluting stent placement is associated with long-term adverse outcomes . Occlusion of side branches may be an important factor contributing to periprocedural MIs . Consecutive procedural angiograms of patients randomly assigned to EES ( n=669 ) or PES ( n=333 ) were analysed by an independent angiographic core laboratory . Side branch occlusion was defined as Thrombolysis In Myocardial Infarction ( TIMI ) flow grade 0 or 1 . Clinical outcomes through three years were compared by stent type and presence of side branch occlusion . CONCLUSIONS A total of 2,048 side branches were evaluated ( EES N=1,345 side branches in 688 stented lesions , PES N=703 side branches in 346 stented lesions ) . Patients with compared to those without transient or final side branch occlusion had significantly higher non-Q-wave MI ( NQMI ) rates in-hospital ( 9.0 % vs. 0.5 % , p < 0.0001 ) . By multivariable analysis side branch occlusion was an independent predictor of NQMI ( OR 4.45 ; 95 % CI [ 1.82 , 10.85 ] ) . Transient or final side branch occlusion occurred less frequently in patients receiving EES compared to PES ( 2.8 % vs. 5.2 % , p=0.009 ) , contributing to the numerically lower rates of in-hospital NQMI with EES arm compared to PES ( 0.7 % vs. 2.3 % , p=0.05 ) . Patients treated with EES rather than PES were less likely to develop side branch occlusion during stent placement , contributing to lower rates of periprocedural MI with EES compared to PES .

everolimus-eluting

and

paclitaxel-eluting stents

everolimus-eluting stent ( EES )

paclitaxel-eluting stent ( PES )

Consecutive procedural angiograms

EES

PES

EES

PES

EES

PES

non-Q-wave MI ( NQMI ) rates

NQMI

rates of in-hospital NQMI

side branch occlusion


Locomoting-to-reach : information variables and control strategies for nested actions . Locomoting-to-reach is a basic perception/action behavior that requires visual information for the control of both locomotion and reaching components . We investigated the visual information and the control strategies used to guide both the head and the hand on approach to a target in a locomotion-to-reach task . In this study , participants were required to locomote in the dark to a lit target in three different conditions : monocular vision/target with image size , binocular vision/target with image size , and binocular vision/point-light target ( without image size ) . In task one , participants brought their eyes to the target . In task two , participants brought their outstretched hand to the target . Movement trajectories for both tasks were analyzed . Results show that participants were significantly more accurate when binocular information was present . In both tasks , participants were found to use a proportional rate control strategy rather than a constant τ strategy . In the walk-to-reach task , they used monocular and/or binocular τ information to guide the head and then switched to using relative disparity τ to guide the hand to final target acquisition , switching when the hand centric τ became less than the head centric τ. Dynamical models of the information and control strategies were used to perform simulations that were found to fit the data well . The conclusion is that proportional rate control is used sequentially with head centric , then hand-centric τ-based information , using at each moment the τ with the smallest value .

Locomoting-to-reach

Locomoting-to-reach

locomotion-to-reach task

Movement trajectories


Effect of intravenous dezocine on fentanyl-induced cough during general anesthesia induction : a double-blinded , prospective , randomized , controlled trial . PURPOSE To evaluate the suppressive effect of intravenous dezocine on fentanyl-induced cough during the induction of general anesthesia . METHODS A total of 120 patients , American Society of Anesthesiologists ( ASA ) physical status I-II , were randomized into two equally sized groups ( n = 60 ) . These two groups were given either intravenous dezocine 0.1 mg/kg or a matching placebo ( equal volume of 0.9 % saline ) 10 min before the induction of general anesthesia . Patients were induced with midazolam 0.1 mg/kg , fentanyl 5 μg/kg , propofol 1-1.5 mg/kg , and suxamethonium 1.5 mg/kg . The injection time of fentanyl was less than 2 s in all patients . The occurrence of cough was recorded 2 min after fentanyl bolus . RESULTS No patient in the dezocine group had cough , and 42 patients in the control group had cough . This difference was statistically different between these two groups ( P = 0.000 ) . CONCLUSION These results demonstrate that intravenous dezocine 0.1 mg/kg 10 min prior to induction was effective in suppressing fentanyl-induced cough in our patients .

dezocine

dezocine

intravenous dezocine

matching placebo

fentanyl

suxamethonium

cough

cough


The effects of therapeutic instrumental music performance on endurance level , self-perceived fatigue level , and self-perceived exertion of inpatients in physical rehabilitation . The present study investigated the effects of a Neurologic Music Therapy ( NMT ) sensory-motor rehabilitation technique , Therapeutic Instrumental Music Performance ( TIMP ) as compared to Traditional Occupational Therapy ( TOT ) , on endurance , self-perceived fatigue , and self-perceived exertion of 35 hospitalized patients in physical rehabilitation . The present study attempted to examine whether an active musical experience such as TIMP with musical cueing ( i.e. , rhythmic auditory cueing ) during physical exercises influences one 's perception of pain , fatigue , and exertion . All participants were diagnosed with a neurologic disorder or had recently undergone orthopedic surgery . Investigators measured the effects of TOT and TIMP during upper extremity exercise of the less affected or stronger upper extremity . Results showed no significant difference on endurance measures between the 2 treatment conditions ( TIMP and TOT ) . Statistically significant differences were found between TIMP and TOT when measuring their effects on perceived exertion and perceived fatigue . TIMP resulted in significantly less perception of fatigue and exertion levels than TOT . TIMP can be used foran effective sensory-motor rehabilitation technique to decrease perceived exertion and fatigue level of inpatients in physical rehabilitation .

TIMP

TOT

TOT

TOT

TOT

exertion and fatigue level

inpatients in physical rehabilitation .

physical rehabilitation

neurologic disorder

orthopedic surgery

physical rehabilitation


[ Impact of heparin on coagulation index during the therapy of molecular adsorbent recirculating system in patients with liver failure ] . OBJECTIVE To investigate the impact of coagulative parameters on different anticoagulation systems in molecular adsorbent recirculating system ( MARS ) in subjects with liver failure , and to evaluate the safety of different anticoagulation methods . METHODS A prospective experimental observation was designed . According to anticoagulation Methods , 174 MARS treatment sessions for 146 patients with liver failure and prothrombin time activity percentage ( PTA ) ≤ 40 % were randomly divided into 2 groups : 92 MARS treatment sessions in the heparin-free group and 82 in the low-dose heparin group . Time points of 0 , 0.5 , 1 , 2 , 3 , 4 , 5 and 6 h were selected to observe the coagulation changes of prothrombin time ( PT ) , PTA , thrombin time ( TT ) , activated partial thromboplastin time ( APTT ) and international normalized ratio ( INR ) dynamically . Adverse events such as line / filter coagulation , rupture and bleeding were also investigated and compared due to frequency and severity between the 2 groups . RESULTS There was no difference in PT , PTA , INR between the 2 groups , but significant differences were observed in APTT and TT and fibrinogen ( Fbg ) . APTT and TT levels in the low-dose heparin group was increased rapidly after the first given dose of anticoagulant heparin and reached the peak within 30 min.The levels at each time point was statistically different between the 2 groups ( P < 0.05 ) . A significant difference in the Fbg level was obtained between the 2 groups . In the low-dose heparin group it was stabilized and increased slightly at the end of the treatment . While in the heparin-free group it was decreased gradually and reached a ravine at the end of the treatment . A curve was observed after 2.5 h treatment between the 2 groups ( P=0.001 ) . There were 2 cases of severe bleeding after MARS was finished in the heparin group , and 1 was terminated because of degree III clotting in the heparin-free group . CONCLUSION Fibrinogen should be adsorbed while the blood touches the MARS circuit path and anticoagulants can prevent it . Comprehensive analysis of blood platelet count ( BPC ) , fibrin degradation products ( FDP ) , D-dimer and clinical symptoms is critical and required to determine the coagulation status to select an anticoagulation system before MARS . The use of low dose heparin in MARS improves the disorder of hypercoagulable state during the high coaguation period , while heparin-free during low coagulation period can effectively prevent the occurrence of bleeding and improve the mechanism of blood coagulation by reducing heparin-like substance in the blood .

heparin

MARS

coagulation index

different anticoagulation systems

anticoagulation

liver failure ]

liver failure


Learning through interaction in children with autism : preliminary data from asocial-communication-based intervention . The study evaluates a social-communication-based approach to autism intervention aimed at improving the social interaction skills of children with autism spectrum disorder . We report preliminary results from an ongoing randomized controlled trial of 51 children aged 2 years 0 months to 4 years 11 months . Participants were assigned to either a target treatment or community treatment group . Families in the target treatment group were given 2 hours of therapy and coaching each week in an intervention emphasizing social-interaction and the parent-child relationship . Children in the community treatment group received a variety of services averaging 3.9 hours per week . After 12 months , outcomes were measured to determine changes in the groups in social interaction and communication . In addition , a regression analysis was conducted to determine whether changes in social interaction skills were associated with language development . Results suggest that children in the treatment group made significantly greater gains in social interaction skills in comparison to the community treatment group , but no between-group differences were found for standard language assessments . Initiation of joint attention , involvement , and severity of language delay were found to be significantly associated with improvement of language skills in children with autism . Finally caregiver skills targeted by the intervention were found to be significantly associated with changes in children 's interaction skills .

social-communication-based approach

therapy and coaching

community treatment

social interaction skills

gains in social interaction skills

standard language assessments

language skills

children 's interaction skills

children

autism

children

autism spectrum disorder

children

autism

children 's


A controlled crossover trial of fenfluramine in autism . We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism . On active drug most of the children lost weight and blood serotonin levels fell by an average of 60 % . There was a fall in urinary dopamine ( DA ) and noradrenaline ( NA ) levels and increased excretion of homovanillic acid ( HVA ) . Some of the children showed improvement in tests of cognitive and language function , although the results did not achieve overall statistical significance . Event-related brain potentials ( ERPs ) were obtained in seven subjects on an auditory choice reaction time task . Side effects of the drug included irritability and lethargy . Fenfluramine may have a limited place in the management of some patients with autistic disorder .

fenfluramine

fenfluramine

lost weight

blood serotonin levels

urinary dopamine ( DA )

noradrenaline ( NA ) levels

Event-related brain potentials ( ERPs )

Side effects

irritability and lethargy

autism

children

autism

children

children

autistic


Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation . BACKGROUND AND PURPOSE Prolonged wakefulness impairs sustained vigilant attention , measured with the psychomotor vigilance task ( PVT ) , and induces a compensatory increase in sleep intensity in recovery sleep , quantified by slow-wave activity ( SWA ) in the sleep electroencephalogram ( EEG ) . These effects of sleep deprivation are counteracted by the adenosine receptor antagonist caffeine , implying involvement of the adenosine neuromodulator/receptor system . To examine a role for adenosine A ( 2A ) receptors , we investigated whether variation of the A ( 2A ) receptor gene ( ADORA2A ) modified effects of caffeine on PVT and SWA after sleep deprivation . EXPERIMENTAL APPROACH A haplotype analysis of eight single-nucleotide polymorphisms of ADORA2A was performed in 82 volunteers . In 45 young men carrying five different allele combinations , we investigated the effects of prolonged waking and 2 × 200 mg caffeine or 2 × 100 mg modafinil on psychomotor vigilance , sleepiness , and the waking and sleep EEG . KEY RESULTS Throughout extended wakefulness , the carriers of haplotype HT4 performed faster on the PVT than carriers of non-HT4 haplotype alleles . In haplotype HT4 , caffeine failed to counteract the waking-induced impairment of PVT performance and the rebound of SWA in recovery sleep . However , caffeine was effective in non-HT4 allele carriers , and modafinil reduced the consequences of prolonged waking , independently of ADORA2A haplotype . CONCLUSIONS AND IMPLICATIONS Common genetic variation of ADORA2A is an important determinant of psychomotor vigilance in rested and sleep-deprived state . It also modulates individual responses to caffeine after sleep deprivation . These findings demonstrate a role for adenosine A ( 2A ) receptors in the effects of prolonged wakefulness on vigilant attention and the sleep EEG .

caffeine

sleep deprivation

vigilant attention

psychomotor vigilance task ( PVT )

slow-wave activity ( SWA )

sleep electroencephalogram ( EEG )

PVT

SWA

young

men

five different allele combinations


[ Methodologic comparison of the polyfrequency oscillation method , transcutaneous oxygen pressure measurement and body plethysmography in bronchial provocation with methacholine ] . A bronchial provocation challenge test was conducted with 30 subjects using metacholin . In randomised sequence lung function analysis tests were carried out with the bodyplethysmograph ( Raw , FEV1 ) and the polyfrequent oscillation method ( resistance , reactance between 2 and 52 Hz ) , whereas the transcutaneous oxygen pressure ( tc-PO2 ) was measured continuously . Correlations between the various parameters , the change of the values at PD60 sGaw in relation to the initial values , the interindividual variability and the reactivity were determined . Medium correlations were found for the oscillatory parameters and Raw , whereas for tc-PO2 and Raw the correlation was markedly lower . In terms of percentage the greatest change was found in reactance , in relation to the initial value , followed by Raw and FEV1 . The interindividual variability resulted in the highest values for the reactance , followed by Raw and FEV1 . Interindividual variability showed the highest values for the reactance before oscillatory resistance and Raw . In respect of reactivity , reactance also had the highest values . Overall evaluation showed that bodyplethysmography and the polyfrequent oscillation method ( reactance or resonance frequency ) are comparably sensitive .

polyfrequency oscillation method

methacholine

metacholin

bodyplethysmograph

transcutaneous oxygen pressure

bodyplethysmography

polyfrequent oscillation method

oscillatory parameters and Raw

tc-PO2 and Raw

greatest change

Raw and FEV1 .

highest values

Raw

FEV1 .

variability

oscillatory resistance and Raw .

reactance

subjects


Naltrexone in autistic children : a double-blind and placebo-controlled study . A double-blind , placebo-controlled study was designed to assess critically the effects of naltrexone on behavioral symptoms and learning in autistic children , and its safety . This is a preliminary report on 18 children , ages 3.08 to 7.99 years , who completed this ongoing study . Subjects were randomly assigned to naltrexone or placebo and received daily doses over a period of 21 days . Naltrexone was superior to placebo according to blind Clinical Global Consensus Ratings ( unpublished scale ) . However , other behavioral rating measures did not confirm this result . There was only a suggestion that naltrexone reduced fidgety and hyperactive behavior and tended to alleviate overall symptomatology in older children . Naltrexone did not appear to affect discrimination learning . Results are preliminary and , owing to the small sample size , can be considered only suggestive until this study is completed or replication is obtained from independent research .

Naltrexone

naltrexone

naltrexone

placebo

Naltrexone

placebo

naltrexone

Naltrexone

behavioral symptoms

learning

Clinical Global Consensus Ratings

fidgety and hyperactive behavior

overall symptomatology

discrimination learning

autistic

children

autistic

children

older children


The effectiveness and cost of passive warming in adult ambulatory surgery patients . Hypothermia is a common problem for surgical patients and can result in many complications . Because few studies compare methods of passive warming , we used an unblinded , prospective , experimental , randomized design to compare the effectiveness of two passive methods of normothermia management in the postanesthesia care unit ( PACU ) . We assigned a total of 578 adult ambulatory surgery patients to either a control group that was given two folded , warmed cotton blankets or a treatment group that was given a warmed , unfolded cotton sheet and cotton blanket . We recorded patients ' temperatures on their arrival in the PACU and at 30 minutes after arrival . The treatment group had temperatures that were significantly higher than those of the control group 30 minutes after arrival in the PACU , and the treatment group experienced a greater change in temperature from baseline measurements to those taken at 30 minutes . The treatment group also used fewer warmed blankets , resulting in cost savings for the PACU .

control group

two folded , warmed cotton blankets

effectiveness

cost

passive warming

effectiveness

temperatures

change in temperature

adult

ambulatory surgery patients

surgical patients

adult

ambulatory surgery patients


Design and implementation of the TRACIA : intracoronary autologous transplant of bone marrow-derived stem cells for acute ST elevation myocardial infarction . OBJECTIVE To describe the design of a protocol of intracoronary autologous transplant of bone marrow-derived stem cells for acute ST-elevation myocardial infarction ( STEMI ) and to report the safety of the procedure in the first patients included . METHODS The TRACIA study was implemented following predetermined inclusion and exclusion criteria . The protocol includes procedures such as randomization , bone marrow retrieval , stem cells processing , intracoronary infusion of stem cells in the infarct-related artery , preand- post MRI , pre-and-post SPECT with radioisotope ventriculography , and clinical follow-up at 6 months . RESULTS Eight patients with a diagnosis of acute STEMI and duration of symptoms of ? 24 hours that were perfused successfully through primary percutaneous coronary intervention ( PPCI ) with a LVEF of ? 45 % were assigned randomly to two groups ( n = 4 each ) . One group treated with stem cells and the other corresponded to the control group . Neither death , re-infarction , no need for revascularization or thrombosis of the stent were observed at follow-up . CONCLUSIONS The initial experience at the Instituto Nacional de Cardiología Ignacio Chávez in the treatment of acute STEMI by means of autologous transplantation of bone marrow-derived stem cells is encouraging . Implementation was possible in the first eight patients with no complications .

stem cells

control group .

acute STEMI and duration of symptoms

death

Eight patients

acute STEMI


Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis . This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis . Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine ( LS ) bone mineral density ( BMD ) in both prevention and treatment of glucocorticoid-induced osteoporosis . Introduction In patients on glucocorticoids , a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate . We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids . Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate ( 5 mg/day ) and stratified based on glucocorticoids duration [ treatment ( > 3 months ) and prevention ( ≤ 3 months ) subpopulations ] were subgrouped by age ; gender ; menopausal status in women ; dose and duration of prednisone during the trial ; and baseline serum 25-OH vitamin D , LS BMD T-score , creatinine clearance , and concomitant medication use . Results At month 12 , zoledronic acid significantly increased LS BMD versus risedronate in patients ≤ 74 years ( P < 0.05 ) in the treatment and 65-74 years ( P = 0.0008 ) in the prevention subpopulation . At month 12 , zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender ( all P < 0.05 ) , cumulative prednisone dose ( all P < 0.01 ) , and postmenopausal status ( all P < 0.05 ) . In premenopausal women , in both subpopulations , zoledronic acid significantly increased total hip BMD ( all P < 0.05 ) versus risedronate at month 12 but not LS BMD . Osteoporotic patients in the prevention ( P=0.0189 ) and osteopenic patients in the treatment subpopulation ( P=0.0305 ) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12 . Conclusions This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients .

zoledronic acid

risedronate

zoledronic acid

Zoledronic acid

risedronate

glucocorticoids

zoledronic acid

risedronate

zoledronic acid

risedronate

zoledronic acid

risedronate

lumbar spine bone mineral density

BMD

LS BMD

patients on glucocorticoids


Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer . OBJECTIVE The safety and efficacy of gemcitabine plus carboplatin ( GC ) or paclitaxel plus carboplatin ( TC ) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer ( OC ) . METHODS Patients with stage IC-IV OC were randomized to either GC ( gemcitabine 1,000 mg/m ( 2 ) , days 1 and 8 , plus carboplatin area under the curve [ AUC ] 5 , day 1 ) or TC ( paclitaxel 175 mg/m ( 2 ) plus carboplatin AUC 6 , day 1 ) every 21 days for up to six cycles . Patients with complete response ( CR ) were allowed optional consolidation with paclitaxel 135 mg/m ( 2 ) every 28 days for ≤ 12 months . Patients without CR received single-agent crossover therapy at induction doses/schedules until CR , disease progression ( PD ) , or unacceptable toxicity . PD or death in 636 patients was required to compare induction arms with 80 % statistical power for progression-free survival ( PFS ) , the primary endpoint . RESULTS Randomized induction therapy was received by 820 of 919 patients enrolled ; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy . PFS was similar for GC and TC ( median , 20.0 and 22.2 months , respectively ; P=.199 ) . Despite high censoring rates ( > 52 % ) , overall survival was longer for TC ( median , 57.3 versus 43.8 months for GC ; P=.013 ) . Controlling for patient characteristics including performance status , residual tumor size , and tumor stage , there was no statistical difference in a multivariate analysis ( HR=1.22 ; 95 % CI=0.99-1.52 ; P=.067 ) . CONCLUSIONS GC does not improve PFS over TC as first-line induction chemotherapy in OC . Although favoring TC , overall survival analyses were limited by the study design and high censoring rates .

induction gemcitabine

GC ( gemcitabine

plus carboplatin

TC ( paclitaxel

plus carboplatin AUC 6

paclitaxel

complete response ( CR )

ovarian cancer

ovarian cancer ( OC ) .

Patients with stage IC-IV OC

Patients with complete response ( CR )

toxicity


Estrogen therapy for severe persistent depressions in women . Positive results are reported from a double-blind study of estrogen therapy administered to severely depressed , inpatient women who had failed to respond to various conventional treatments of depression . Large doses of oral conjugated estrogen were administered for a three-month period to 23 premenopausal and postmenopausal inpatient women . Placebos were administered for a comparable period to 17 similar patients . The posttreatment Hamilton ratings of depression were significantly reduced in the estrogen-treated group , but not in the placebo group . Possible physiological mechanisms are discussed . The risk-benefit ratio for estrogen therapy of depression in these patients was judged to be favorable . However , periodic endometrial biopsies are required to monitor the endometrial response of women receiving high doses of estrogens .

Estrogen therapy

estrogen therapy

oral conjugated estrogen

Placebos

estrogen-treated

placebo

estrogen therapy

estrogens

reduced

risk-benefit ratio

depression

favorable

persistent depressions

women

severely depressed

women

depression

women


[ Comparative effects of nebivolol and valsartan on atrial electromechanical coupling in newly diagnosed stage 1 hypertensive patients ] . OBJECTIVES Hypertension is an important cardiovascular risk factor for the development of atrial fibrillation ( AF ) . Increased atrial electromechanical coupling time interval measured by tissue Doppler is accepted as an important factor for prediction of AF development in hypertensive patients . The aim of this study was to compare the effects of valsartan , an angiotensin receptor blocker , and nebivolol , a beta-blocker , on atrial electromechanical coupling in newly diagnosed stage 1 hypertensive patients . STUDY DESIGN The study included 60 newly diagnosed stage 1 hypertensive patients with no other systemic disease . The patients were randomized to receive nebivolol 5 mg ( 30 patients ; 21 women , 9 men ; mean age 48.4 ± 11.4 years ) and valsartan 160 mg ( 30 patients ; 21 women , 9 men ; mean age 49.8 ± 11.3 years ) . All the patients underwent tissue Doppler echocardiographic examination before and three months after treatment to compare the effects of the two drugs on atrial electromechanical coupling . RESULTS Baseline blood pressures , electrocardiographic and echocardiographic findings , and atrial electromechanical coupling were similar in both groups ( p > 0.05 ) . Both drugs significantly reduced blood pressure after treatment , with similar efficacy ( p > 0.05 ) . Atrial electromechanical coupling time intervals showed significant decreases in both groups . CONCLUSION Prolonged interatrial electromechanical time intervals in hypertensives are improved with antihypertensive treatment .

nebivolol

valsartan

valsartan

nebivolol

nebivolol 5 mg

atrial electromechanical coupling

atrial fibrillation ( AF ) .

AF development


Oral bioavailability of moxifloxacin after Roux-en-Y gastric bypass surgery . OBJECTIVES Roux-en-Y gastric bypass surgery is the most commonly performed procedure for the treatment of morbid obesity . This anatomical alteration may affect the absorption and consequently the bioavailability of oral drugs . This study aims to investigate the oral bioavailability of moxifloxacin in 12 healthy volunteers who underwent gastric bypass surgery . PATIENTS AND METHODS In this randomized crossover study , each subject received two single standard doses of 400 mg of moxifloxacin orally or intravenously administered on two occasions separated by a washout period of 1 week . Serial venous blood samples were drawn up to 72 h after dosing and moxifloxacin plasma levels were measured by a validated HPLC method with fluorescence detection . [ clinicaltrials.gov database ( identifier : NCT01130922 ) . ] RESULTS After oral dosing , moxifloxacin plasma concentrations reached a maximum ( C ( max ) ) of 3.38 ± 1.41 mg/L after 1.75 h ( 0.75-4.00 ) . After intravenous dosing , C ( max ) and T ( max ) were 4.53 ± 1.43 mg/L and 1.03 h ( 0.75-2.50 ) , respectively . The mean areas under the plasma concentration time curve extrapolated to infinity ( AUC ( ∞ ) ) were 46.2 ± 1.4 mg · h/L after oral dosing and 52.3 ± 1.3 mg · h/L after intravenous dosing , resulting in a mean oral bioavailability of 88.32 % [ 90 % confidence interval ( CI ) 85.64 % -91.08 % ] . CONCLUSIONS This study confirms that exposure to moxifloxacin is equivalent for oral and intravenous administration of 400 mg dosages in healthy volunteers who underwent gastric bypass surgery . But these exposures were more than 50 % higher than those described for subjects without gastric bypass . This may suggest a higher enterohepatic recirculation of moxifloxacin after gastric bypass .

moxifloxacin

Roux-en-Y gastric bypass surgery

Roux-en-Y gastric bypass surgery

moxifloxacin

gastric bypass surgery

moxifloxacin

moxifloxacin

moxifloxacin plasma levels

moxifloxacin plasma concentrations


A randomized study comparing levofloxacin , omeprazole , nitazoxanide , and doxycycline versus triple therapy for the eradication of Helicobacter pylori . OBJECTIVES Resistance to standard Helicobacter pylori ( HP ) treatment regimens has led to unsatisfactory cure rates in HP-infected patients . This study was designed to evaluate a novel four-drug regimen ( three antibiotics and a proton pump inhibitor ( PPI ) ) for eradication of HP infection in treatment-naive patients . METHODS Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study . All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage . Patients were then randomized to either levofloxacin , omeprazole , nitazoxanide , and doxycycline ( LOAD ) therapy for 7 days ( LOAD-7 ) or 10 days ( LOAD-10 ) , including levofloxacin 250 mg with breakfast , omeprazole 40 mg before breakfast , nitazoxanide ( Alina ) 500 mg twice daily with meals and doxycycline 100 mg at dinner , or lansoprozole , amoxicillin , and clarithromycin ( LAC ) therapy for 10 days , which included lansoprozole 30 mg , amoxicillin 1 g with breakfast and dinner , and clarithromycin 500 mg with breakfast and dinner . HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy . RESULTS Intention-to-treat analysis revealed significant differences ( P < 0.05 ) in the respective eradication rates of the LOAD therapies ( 88.9 % ( 80/90 ) LOAD-10 , 90 % ( 81/90 ) LOAD-7 , 89.4 % ( 161/180 ) for combined LOAD ) compared with those receiving LAC , 73.3 % ( 66/90 ) . There were no differences in adverse effects between the groups . CONCLUSIONS This open-label , prospective trial demonstrates that LOAD is a highly active regimen for the treatment of HP in treatment-naive patients . A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen .

doxycycline

triple therapy

four-drug regimen

doxycycline 100 mg

LOAD

Helicobacter pylori

stool antigen testing

Intention-to-treat analysis

eradication rates

adverse effects

HP-infected patients .


Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer . Inhibitors of COX indicate that upregulation of inflammatory eicosanoids produced by COX , and in particular prostaglandin E ( 2 ) ( PGE ( 2 ) ) , are early events in the development of colorectal cancer ( CRC ) . Ginger has shown downregulation of COX in vitro and decreased incidence/multiplicity of adenomas in rats . This study was conducted to determine if 2.0 g/d of ginger could decrease the levels of PGE ( 2 ) , 13-hydroxy-octadecadienoic acids , and 5- , 12- , and 15-hydroxyeicosatetraenoic acid ( 5- , 12- , and 15-HETE ) , in the colon mucosa of healthy volunteers . To investigate this aim , we randomized 30 subjects to 2.0 g/d ginger or placebo for 28 days . Flexible sigmoidoscopy at baseline and day 28 was used to obtain colon biopsies . A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies , and levels were expressed per protein or per free arachidonic acid . There were no significant differences in mean percent change between baseline and day 28 for any of the eicosanoids , when normalized to protein . There was a significant decrease in mean percent change in PGE ( 2 ) ( P = 0.05 ) and 5-HETE ( P = 0.04 ) , and a trend toward significant decreases in 12-HETE ( P = 0.09 ) and 15-HETE ( P = 0.06 ) normalized to free arachidonic acid . There was no difference between the groups in terms of total adverse events P = 0.55 ) . On the basis of these results , it seems that ginger has the potential to decrease eicosanoid levels , perhaps by inhibiting their synthesis from arachidonic acid . Ginger also seemed to be tolerable and safe . Further investigation in people at high risk for CRC seems warranted .

ginger root extract

ginger

2.0 g/d ginger or

placebo

Flexible sigmoidoscopy

Ginger

Flexible sigmoidoscopy

eicosanoid levels

mean percent change

eicosanoids

mean percent change in PGE ( 2 )

free arachidonic acid .

total adverse events

tolerable and safe .

normal risk for colorectal cancer

healthy


[ Treatment of primary osteoporosis with calcium and salmon calcitonin ] . Fifty-nine consecutive patients ( 19 men , 40 women , mean age 60.8 [ 27-80 ] years ) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin . All the patients were given 1 g calcium by mouth every morning . Group 1 ( n = 20 ) received no other specific medication while group 2 ( n = 19 ) were given 100 I.U . calcitonin subcutaneously every second evening and group 3 ( n = 20 ) received the same dose every evening . The pain reported by the patients was subdivided into four severity grades , and analgesic consumption was recorded . In group 1 there was a nonsignificant decrease in pain , but in groups 2 and 3 there was a highly significant diminution in pain ( P less than 0.005 ) and in analgesic intake ( P less than 0.01 ) . Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5 % increase in the distal radius in group 2 ( P = 0.0001 ) and a 7.1 % increase in group 3 ( P = 0.0001 ) , while in group 1 mineral content had decreased by 4.3 % ( nonsignificant ) . These results show that a significant gain in bone mass can be achieved by administration of calcitonin , either daily or on alternate days . The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1 .

calcium

salmon calcitonin

salmon calcitonin

calcium

calcitonin

pain

analgesic consumption

pain

pain

analgesic intake

bone density

distal radius

bone mass


Residual platelet reactivity , bleedings , and adherence to treatment in patients having coronary stent implantation treated with prasugrel . Recent guidelines have recommended the use of aspirin and prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention . However , prasugrel use has been evaluated only in randomized trials . This study sought to evaluate bleeding rates and adherence to treatment in " real-world " patients treated with prasugrel . In total 298 consecutive patients 68 ± 10 years old ( 31 % > 75 years old ) underwent stent implantation and received prasugrel therapy . Indications to prasugrel therapy were ( 1 ) ST-elevation acute myocardial infarction ( 41 % ) , ( 2 ) drug-eluting stent implantation in diabetics ( 24 % ) , ( 3 ) stent thrombosis ( 3 % ) , ( 4 ) left main coronary artery drug-eluting stent implantation ( 6 % ) , and ( 5 ) percutaneous coronary intervention in patients with high residual platelet reactivity on clopidogrel therapy ( 26 % ) . All patients received a loading of prasugrel 60 mg . Patients ≥75 years old and with body weight ≤60 kg received a maintenance dose of 5 mg/day ( 10 mg/day for all the other patients ) . Follow-up data including adherence to prasugrel therapy were collected by telephone interviews or outpatient visits . Minimal follow-up length was 6 months ( mean 9 ± 3 ) . Major , minor , and minimal bleedings ( Thrombolysis In Myocardial Infarction criteria ) occurred in 2.7 % , 4.7 % , and 15.1 % of enrolled patients . Low residual platelet reactivity ( p = 0.001 ) and female gender ( p = 0.29 ) were independent predictors of bleeding events . The most frequent minimal bleeding event was epistaxis . Only 8 patients ( 2.7 % ) permanently discontinued prasugrel therapy because of bleeding events ( n = 4 ) , possible side effects ( n = 2 ) , or medical decisions not associated with bleeding or side effects ( n = 2 ) . Fourteen patients ( 4.7 % ) temporarily discontinued prasugrel ( average 6.5 days ) mainly because of surgical procedures . No definite or probable stent thrombosis occurred , although 3 patients develop de novo myocardial infarction and 1 an ischemic stroke . There were 11 deaths because of heart failure or refractory cardiogenic shock in 9 , pulmonary embolism in 1 , and cancer in 1 . In conclusion , in clinical practice , major and minor bleeding event rates associated with prasugrel therapy are comparable to those reported in controlled randomized trials . The minimal bleeding event rate is higher than reported but does not seem to affect adherence to treatment .

prasugrel

prasugrel

prasugrel

prasugrel

prasugrel

bleeding rates


Epicutaneous allergen-specific immunotherapy ameliorates grass pollen-induced rhinoconjunctivitis : A double-blind , placebo-controlled dose escalation study . BACKGROUND Epicutaneous allergen administration using a patch may be an alternative to subcutaneous or sublingual immunotherapy . OBJECTIVE To optimize treatment dose and to demonstrate the efficacy and safety of epicutaneous immunotherapy . METHODS This monocentric , placebo-controlled , double-blind trial included 132 patients with grass pollen-induced rhinoconjunctivitis . In February 2008 , patients were randomly allocated to receive placebo or 3 different doses of allergen . Before and during the pollen season 2008 , patients received 6 weekly patches . Efficacy was assessed 4 to 5 months later ( n = 110 ) and during the pollen season of the treatment-free follow-up year in 2009 ( n = 93 ) . The primary outcome was patient-reported changes in hay fever symptoms assessed by a visual analog scale . Secondary outcome measures were weekly visual analog scale symptom scores during pollen season , use of rescue medication , changes in conjunctival and skin reactivity , as well as safety . RESULTS Hay fever symptoms during the pollen season were reduced by more than 30 % in 2008 and by 24 % in 2009 in the high-dose group as compared with that in the placebo group , and the alleviation of symptoms in the follow-up year was dependent on the treatment dose . Higher allergen doses were associated with drug-related adverse events ( AEs ) , predominantly manifested by pruritus , erythema , wheal , or eczema . Eleven systemic AEs of grades 1 to 2 required treatment and led to study exclusion . The dropout rate due to AEs was 8.3 % . No drug-related serious AE was recorded . CONCLUSION Epicutaneous immunotherapy is safe and efficacious in a dose-dependent manner after 6 patches only .

allergen-specific immunotherapy

safety

Hay fever symptoms

drug-related adverse events ( AEs )

systemic AEs

dropout rate

serious AE


Hemiarthroplasty compared to internal fixation with percutaneous cannulated screws as treatment of displaced femoral neck fractures in the elderly : cost-utility analysis performed alongside a randomized , controlled trial . UNLABELLED We estimated the cost-effectiveness of hemiarthroplasty compared to internal fixation for elderly patients with displaced femoral neck fractures . Over 2 years , patients treated with hemiarthroplasty gained more quality-adjusted life years than patients treated with internal fixation . In addition , costs for hemiarthroplasty were lower . Hemiarthroplasty was thus cost effective . INTRODUCTION Estimating the cost utility of hemiarthroplasty compared to internal fixation in the treatment of displaced femoral neck fractures in the elderly . METHODS A cost-utility analysis ( CUA ) was conducted alongside a clinical randomized controlled trial at a university hospital in Norway ; 166 patients , 124 ( 75 % ) women with a mean age of 82 years were randomized to either internal fixation ( n = 86 ) or hemiarthroplasty ( n = 80 ) . Patients were followed up at 4 , 12 , and 24 months . Health-related quality of life was assessed with the EQ-5D , and in combination with time used to calculate patients ' quality-adjusted life years ( QALYs ) . Resource use was identified , quantified , and valued for direct and indirect hospital costs and for societal costs . Results were expressed in incremental cost-effectiveness ratios . RESULTS Over the 2-year period , patients treated with hemiarthroplasty gained 0.15-0.20 more QALYs than patients treated with internal fixation . For the hemiarthroplasty group , the direct hospital costs , total hospital costs , and total costs were non-significantly less costly compared with the internal fixation group , with an incremental cost of €2,731 ( p = 0.81 ) , €2,474 ( p = 0.80 ) , and €14,160 ( p = 0.07 ) , respectively . Thus , hemiarthroplasty was the dominant treatment . Sensitivity analyses by bootstrapping supported these findings . CONCLUSION Hemiarthroplasty was a cost-effective treatment . Trial registration , NCT00464230 .

Hemiarthroplasty

hemiarthroplasty

internal fixation .

hemiarthroplasty

Hemiarthroplasty

hemiarthroplasty

internal fixation

cost-effectiveness

quality-adjusted life years


Changes in H reflex and V wave following short-term endurance and strength training . This study examined the effects of 3 wk of either endurance or strength training on plasticity of the neural mechanisms involved in the soleus H reflex and V wave . Twenty-five sedentary healthy subjects were randomized into an endurance group ( n = 13 ) or strength group ( n = 12 ) . Evoked V-wave , H-reflex , and M-wave recruitment curves , maximal voluntary contraction ( MVC ) , and time-to-task-failure ( isometric contraction at 40 % MVC ) of the plantar flexors were recorded before and after training . Following strength training , MVC of the plantar flexors increased by 14.4 ± 5.2 % in the strength group ( P < 0.001 ) , whereas time-to-task-failure was prolonged in the endurance group ( 22.7 ± 17.1 % ; P < 0.05 ) . The V wave-to-maximal M wave ( V/M ( max ) ) ratio increased significantly ( 55.1 ± 28.3 % ; P < 0.001 ) following strength training , but the maximal H wave-to-maximal M wave ( H ( max ) /M ( max ) ) ratio remained unchanged . Conversely , in the endurance group the V/M ( max ) ratio was not altered , whereas the H ( max ) /M ( max ) ratio increased by 30.8 ± 21.7 % ( P < 0.05 ) . The endurance training group also displayed a reduction in the H-reflex excitability threshold while the H-reflex amplitude on the ascending limb of the recruitment curve increased . Strength training only elicited a significant decrease in H-reflex excitability threshold , while H-reflex amplitudes over the ascending limb remained unchanged . These observations indicate that the H-reflex pathway is strongly involved in the enhanced endurance resistance that occurs following endurance training . On the contrary , the improvements in MVC following strength training are likely attributed to increased descending drive and/or modulation in afferents other than Ia afferents .

endurance or strength training

endurance group

strength group

strength training

endurance training

MVC of the plantar flexors

the V/M ( max ) ratio

the H ( max ) /M ( max ) ratio

the H-reflex excitability threshold

H-reflex excitability threshold

ascending limb

enhanced endurance resistance

improvements in

Twenty-five


Predictors of recruited melanoma families into a behavioral intervention project . BACKGROUND Examination of families represents an important priority in health research . In this paper we report on individual and family-level factors associated with enrollment in a cancer prevention research project . We approached families affected by melanoma for possible participation in a randomized controlled trial of a web-based communication and support intervention . METHODS We recruited three family members per family for assessment - the melanoma case , a first-degree relative ( FDR ) , and a relative who is a parent of a child age 18 or younger . Recruitment involved three steps : requesting the physician 's consent to approach the melanoma case , approaching the case to request their participation and family contact information , and they approaching the FDRs and parents . RESULTS Of the 1380 families approached , 313 were enrolled , 263 were excluded because we could not find or contact a family member ( FDR or parent ) , 331 did not have eligible family members , and 473 refused . The most frequently noted reason for refusal was being too busy or having no time . The primary predictors of participation for cases ( OR=1.6 ; CI=1.01-2.51 ) and FDRs ( OR=2.15 ; CI=1.11-4.13 ) included higher educational attainment . FDRs were more likely to enroll if they were female ( OR=1.77 ; CI=1.1-.85 ) and parents were more likely to enroll if the case had been diagnosed more recently ( OR=3.3 ; CI=1.9-5.93 ) , if the parent was partnered ( OR=4.37 ; CI=1.86-10.26 ) , and if the parent lived in the same city as the case ( OR=2.88 ; CI=1.08-7.68 ) . CONCLUSIONS The results can provide information on potential directions for future family recruitment .

behavioral intervention project

report

individual and family-level factors

refusal

participation

higher educational attainment .

diagnosed more recently

parent was partnered

melanoma

melanoma

three family members per family

18 or younger


Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia . Tipifarnib ( T ) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia ( AML ) . Based on preclinical synergy , a phase 1 trial of T plus etoposide ( E ) yielded 25 % complete remission ( CR ) . We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults ( age range , 70-90 years ; median , 76 years ) who were not candidates for conventional chemotherapy . Arm A ( T 600 mg twice a day × 14 days , E 100 mg days 1-3 and 8-10 ) and arm B ( T 400 mg twice a day × 14 days , E 200 mg days 1-3 and 8-10 ) yielded similar CR , but arm B had greater toxicity . Total CR was 25 % , day 30 death rate 7 % . A 2-gene signature of high RASGRP1 and low aprataxin ( APTX ) expression previously predicted for T response . Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78 % CR rate and negative predictive value 87 % . This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies . The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively . This study is registered at www.clinicaltrials.gov as # NCT00602771 .

tipifarnib plus etoposide

elderly adults

acute myelogenous leukemia

elderly adults

AML

adults

70-90 years

median , 76 years


A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib ( CP-690,550 ) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone . OBJECTIVE To compare the efficacy , safety , and tolerability of 6 dosages of oral tofacitinib ( CP-690,550 ) with placebo for the treatment of active rheumatoid arthritis ( RA ) in patients receiving a stable background regimen of methotrexate ( MTX ) who have an inadequate response to MTX monotherapy . METHODS In this 24-week , double-blind , phase IIb study , patients with active RA ( n = 507 ) were randomized to receive placebo or tofacitinib ( 20 mg/day , 1 mg twice daily , 3 mg twice daily , 5 mg twice daily , 10 mg twice daily , or 15 mg twice daily ) . All patients continued to receive a stable dosage of MTX . The primary end point was the American College of Rheumatology 20 % improvement criteria ( ACR20 ) response rate at week 12 . RESULTS At week 12 , ACR20 response rates for patients receiving all tofacitinib dosages ≥3 mg twice daily ( 52.9 % for 3 mg twice daily , 50.7 % for 5 mg twice daily , 58.1 % for 10 mg twice daily , 56.0 % for 15 mg twice daily , and 53.8 % for 20 mg/day ) were significantly ( P ≤ 0.05 ) greater than those for placebo ( 33.3 % ) . Improvements were sustained at week 24 for the ACR20 , ACR50 , and ACR70 responses , scores for the Health Assessment Questionnaire disability index , the 3-variable Disease Activity Score in 28 joints using the C-reactive protein level ( DAS28-CRP ) , and a 3-variable DAS28-CRP of < 2.6 . The most common treatment-emergent adverse events occurring in > 10 % of patients in any tofacitinib group were diarrhea , upper respiratory tract infection , and headache ; 21 patients ( 4.1 % ) experienced serious adverse events . Sporadic increases in transaminase levels , increases in cholesterol and serum creatinine levels , and decreases in neutrophil and hemoglobin levels were observed . CONCLUSION In patients with active RA in whom the response to MTX has been inadequate , the addition of tofacitinib at a dosage ≥3 mg twice daily showed sustained efficacy and a manageable safety profile over 24 weeks .

placebo

background methotrexate

methotrexate alone

oral tofacitinib ( CP-690,550 )

placebo

methotrexate ( MTX )

MTX monotherapy

placebo

tofacitinib

MTX

tofacitinib

efficacy , safety , and tolerability


Effects of body orientation on maximum voluntary arm torques . INTRODUCTION Increased reliance on bulbospinal motor systems has been implicated in individuals with chronic stroke during maximum voluntary arm joint torque generation . METHODS Maximum isometric single-joint and multi-joint arm strength was observed in two body orientations ( sitting and supine ) while maintaining identical head/neck/trunk/extremity joint configurations in order to identify bulbospinal contributions to maximum joint torque generation in 11 individuals with stroke and 10 individuals without stroke . RESULTS During sitting , shoulder flexion was greater for both groups , whereas shoulder extension and elbow flexion , part of the " flexion synergy , " were greater only in individuals with stroke . CONCLUSIONS Body orientation influenced isometric arm strength , notably the constituents of flexion synergy in individuals with stroke , suggesting bulbospinal motor pathway involvement . From a practical perspective , clinical evaluation of single joint strength in the supine position may underestimate strength available during activities of daily living that are performed in an upright orientation .

body orientation

bulbospinal motor systems

sitting

Body orientation

supine position

upright orientation .

shoulder flexion

shoulder extension and elbow flexion

isometric arm strength

flexion synergy

single joint strength

chronic stroke

stroke

10 individuals

without stroke


Use of an Internet portal to improve community-based pediatric ADHD care : a cluster randomized trial . OBJECTIVE To determine the effectiveness of a quality improvement program to improve pediatricians ' adherence to existing , evidence-based , attention-deficit/hyperactivity disorder ( ADHD ) practice guidelines . METHODS Forty-nine community-based pediatricians at 8 practices participated in a cluster-randomized trial . Practices were matched according to the numbers of pediatricians and the proportions of patients receiving Medicaid . The medical charts for a random sample of patients with ADHD for each of the participating pediatricians were examined at baseline and 6 months . All practices participated in 4 sessions of training , including didactic lectures and office flow modification workshops . Practices were then given access to an ADHD Internet portal that allowed parents , teachers , and pediatricians to input information ( eg , rating scales ) about patients , after which information was scored , interpreted , and formatted in a report style that was helpful for assessment and treatment of patients with ADHD . Physicians evaluated their practice behaviors quarterly and addressed underperforming areas . RESULTS Pediatricians in the intervention group , compared with those in the control group , demonstrated significantly higher rates of many American Academy of Pediatrics-recommended ADHD care practices , including collection of parent ( Cohen 's d = 0.69 ) and teacher ( d = 0.68 ) rating scales for assessment of children with ADHD , use of Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria ( d = 0.85 ) , and use of teacher rating scales to monitor treatment responses ( d = 1.01 ) . CONCLUSION A quality improvement intervention that can be widely disseminated by using Internet-based information technology significantly improved the quality of ADHD care in community-based pediatric settings .

Use of an Internet portal

quality improvement program

ADHD Internet portal

control

A quality improvement intervention

Internet-based information technology

practice behaviors

underperforming areas .

collection of parent

teacher

rating scales

Statistical Manual of Mental Disorders

teacher rating scales

pediatric

ADHD

Forty-nine


Effect of ischemic postconditioning in correction of tetralogy of Fallot . Inappropriate myocardial protection is considered one of the main causes of mortality and morbidity in the correction of tetralogy of Fallot ( TOF ) . Results of previous reports about the effects of ischemic postconditioning on myocardial protection in animals and humans are very encouraging . This randomized and controlled trial aimed to assess the effect of ischemic postconditioning on protection against myocardial ischemia reperfusion injury in TOF patients receiving cardioplegia . From January 2008 to June 2010 , 80 consecutive children undergoing correction of TOF were enrolled and randomly assigned to either a postconditioning group ( three cycles of 30 seconds of ischemia and 30 seconds of reperfusion using re-clamping and de-clamping starting 30 seconds after the initial de-clamping of the aorta , n = 41 ) or a control group ( n = 39 ) . Cardiac troponin I ( cTnI ) was assayed preoperatively , and then 4 hours , 8 hours , 12 hours , 20 hours , and 48 hours after persistent reperfusion . The pre- , intra- and postoperative relevant data of all selected patients were analyzed . As a result , ischemic postconditioning reduced postoperative peak release by 45 % for cTnI compared with the control group ( 0.43 ± 0.18 ng/mL versus 0.78 ± 0.15 ng/mL , P < 0.0001 ) . Ischemic postconditioned patients had a lower peak inotropic score during the first postoperative 24 hours ( 5.6 ± 2.2 µg/kg/minute versus 8.6 ± 3.6 µg/kg/minute , P < 0.0001 ) , extubation time ( 21.5 ± 7.3 hours versus 30.2 ± 12.4 hours , P = 0.0002 ) and length of ICU stay ( 43.4 ± 12.6 hours versus 56.3 ± 17.8 hours , P = 0.0003 ) , while they had a higher cardiac output on the first postoperative day ( 1.41 ± 0.26 L/minute versus 1.28 ± 0.25 L/minute , P = 0.0255 ) as compared to the control group . In conclusion , ischemic postconditioning may to some extent provide myocardial protection in children undergoing correction of tetralogy of Fallot .

control group

ischemic postconditioning

myocardial protection

ischemic postconditioning

protection against myocardial ischemia

Cardiac troponin I

postoperative peak release

tetralogy of Fallot ( TOF ) .


Skin improvement with two different oestroprogestins in patients affected by acne and polycystic ovary syndrome : clinical and instrumental evaluation . BACKGROUND Despite it is accepted that acne is mostly caused by an hyper-responsiveness of the pilo-sebaceous unit to normal circulating androgen hormones , in a few patients , especially women , acneic lesions can be associated with increased serum androgen levels ( hyperandrogenism ) , of which polycystic ovary syndrome ( PCOS ) is the most common cause . In women with acne and proven PCOS therapy with estroprogestins ( EPs ) can be an excellent option . OBJECTIVE The aim of the study was to assess the effects of two estroprogestins ( EPs ) , ethinyl-estradiol ( EE ) 30 mcg/drospirenone ( DRSP ) 3 mg , and ethinyl-estradiol ( EE ) 30 mcg/chlormadinone acetate ( CMA ) 2 mg , both on increased serum androgen levels and on several skin parameters in women affected by mild to severe acne and polycystic ovary syndrome ( PCOS ) . METHODS Fifty-nine women were randomized to receive EE/DRSP ( n = 32 ) or EE/CMA ( n = 27 ) for six months . Evaluation of serum androgen levels , grading of acne and hirsutism ( respectively with Pillsbury and Ferriman-Gallwey score ) and non-invasive assessment of skin hydration , transepidermal water loss ( TEWL ) and skin homogeneity were performed at baseline , at 3 and 6 months ( end of treatment ) . RESULTS Both treatments were well tolerated and showed a significant improvement of skin and hormonal parameters , although EE/DRSP showed a more potent effect on acne and seborrhea . CONCLUSIONS Estroprogestins represent an effective and safe treatment in women with acne and polycystic ovary syndrome ( PCOS ) . Nevertheless , the combination EE 30 mcg/DRSP 3 mg appears to be a more potent therapeutic option .

oestroprogestins

estroprogestins ( EPs )

estroprogestins ( EPs )

EE/DRSP

EE/CMA

EE/DRSP

Estroprogestins

EE 30 mcg/DRSP 3 mg

Skin improvement

serum androgen levels

serum androgen levels

skin parameters

skin and hormonal parameters

acne and seborrhea .

effective and safe treatment

potent therapeutic option

acne

polycystic ovary syndrome :

women

women

acne

women

mild to severe acne

polycystic ovary syndrome ( PCOS )

Fifty-nine

women

women

acne


Midlife women online : evaluation of an internet-based program to prevent unintended pregnancy & STIs . BACKGROUND Midlife women are an underserved population in the areas of unintended pregnancy and STI prevention yet remain at risk for both health conditions . METHODS A randomized controlled trial of an Internet-based multimedia program to reduce risk of unintended pregnancy and STIs among midlife women was conducted with 164 women ages 40-55 years of age . RESULTS Women in the treatment condition compared to the control condition reported significant gains in attitudes , self-efficacy , and behavioral intentions at posttest . CONCLUSION Interventions specifically targeted to midlife women can impact constructs known to reduce risk . Implications for future research and intervention development are presented .

Internet-based multimedia program

unintended pregnancy and STI


The competition between enamel and dentin adhesion within a cavity : an in vitro evaluation of class V restorations . To gain more insight into the consequences of curing contraction within the tooth cavity , we assessed the margin behavior of 12 contemporary restorative systems in class V restorations with margins located on enamel and dentin after mechanical loading and water storage . Mixed class V cavities were prepared on extracted human molars and restored using five etch and rinse and seven self-etch adhesive systems with their corresponding composites . Marginal adaptation was evaluated by using a computer-assisted quantitative marginal analysis in a scanning electron microscope ( SEM ) on epoxy replicas before , after thermal and mechanical stressing and after 1 year of water storage . The interactions of " testing conditions " , " adhesive-composite combination " and " tooth substrate " with " marginal adaptation " were evaluated by two-way ANOVA . Fatigue , stress and storage conditions had significant effects on the marginal adaptation . Only two groups ( Optibond FL and G Bond ) presented equal percentages of marginal adaptation on enamel and dentin ; in the other groups , the rate of degradation was product dependent . All materials tested showed a distinct behavior on enamel and dentin . In addition to mechanical resistance and long-term stability , differences within materials also exist in their ability to simultaneously bond to enamel and dentin .

five etch and rinse

seven self-etch adhesive systems

scanning electron microscope

Fatigue , stress and storage conditions

marginal adaptation .

marginal adaptation on enamel

and

dentin

rate of degradation

enamel

dentin


Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults . A number of recent studies have assessed the impact of dietary omega-3 polyunsaturated fatty acids ( n-3 PUFAs ) on behavioral outcomes ; however , very little attention has been given to their impact upon brain function in physiological terms . Sixty-five healthy adults aged 18-29yrs took part in this double-blind , placebo-controlled study assessing the effects of 12 weeks daily dietary supplementation with docosahexaenoic acid-rich fish oil ( 1g , 2g ) or placebo ( olive oil ) . Relative changes in the concentration of oxyhemoglobin and deoxyhemoglobin were assessed in the prefrontal cortex using near-infrared spectroscopy during performance of nine computerized cognitive tasks . Supplementation with both doses of fish oil , in comparison with placebo , resulted in significantly increased concentrations of oxyhemoglobin and total levels of hemoglobin , indicative of increased cerebral blood flow , during the cognitive tasks . Changes in hemodynamic response to tasks were not accompanied by consistent changes in cognitive performance .

Docosahexaenoic acid-rich fish oil

placebo-controlled

docosahexaenoic acid-rich fish oil

or placebo ( olive oil ) .

cerebral hemodynamic response

cerebral blood flow

hemodynamic

cognitive performance

healthy

young adults

Sixty-five

healthy

adults aged 18-29yrs


Early intervention for autism with a parent-delivered Qigong massage program : a randomized controlled trial . A recent randomized controlled trial ( RCT ) of a dual parent and trainer-delivered qigong massage intervention for young children with autism resulted in improvement of measures of autism as well as improvement of abnormal sensory responses and self-regulation . The RCT evaluated the effects of the parent-delivered component of the intervention . Forty-seven children were randomly assigned to treatment and wait-list control groups . Treatment group children received the parent-delivered program for 4 mo . Trained therapists provided parent training and support . Improvement was evaluated in two settings -- preschool and home -- by teachers ( blind to group ) and parents . Results showed that the parent-delivered program was effective in improving measures of autism ( medium effect size ) and sensory and self-regulatory responses ( large effect size ) . Teacher data on measures of autism were confirmed by parent data . Results indicate that the parent-delivered component of the program provided effective early intervention for autism that was suitable for delivery at home .

parent-delivered Qigong massage program

parent-delivered program for 4 mo

parent training and support

parent-delivered component

autism

abnormal sensory responses

self-regulation .

sensory and self-regulatory responses

young children

autism

Forty-seven

children


Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy . OBJECTIVE To compare efficacy between double-dose methotrexate and single-dose methotrexate for treatment of tubal ectopic pregnancy ( EP ) . METHODS Between March 2008 and February 2011,157 patients who had tubal EP diagnosed by a non-laparoscopic approach and were hemodynamically stable were enrolled in a prospective study in Qassim , Saudi Arabia . The participants were randomized to receive either double-dose ( 50mg/m ( 2 ) intramuscularly on days 0 and 4 ; group 1 ) or single-dose ( 50mg/m ( 2 ) intramuscularly on day 0 ; group 2 ) methotrexate . Serum human chorionic gonadotropin ( β-hCG ) levels were followed until negative . RESULTS The overall success rate was comparable between groups 1 and 2 ( 88.6 % versus 82.0 % , P=0.1 ) . The duration of follow up until negative β-hCG was shorter in group 1 ( P=0.001 ) . Receiver operative characteristics showed that higher cut-off levels of β-hCG and gestational mass diameter were associated with successful outcome in group 1 . Among participants with initial β-hCG of 3600-5500 mIU/mL , the success rate was higher in group 1 ( P=0.03 ) . There was no significant difference between groups in adverse effects . CONCLUSION For treatment of EP , double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate ; it had better success among patients with moderately high β-hCG and led to a shorter follow up .

methotrexate

methotrexate

methotrexate

methotrexate

overall success rate

adverse effects

tubal EP


Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas : long-term results of a Japanese multicenter randomized controlled trial . BACKGROUND The value of pancreatoduodenectomy ( PD ) with extended lymphadenectomy for pancreatic cancer has been evaluated by many retrospective studies and 3 randomized controlled trials ( RCT ) . However , the protocols used and the results found in the 3 RCTs were diverse . Therefore , a multicenter RCT was proposed in 1998 to evaluate the primary end point of long-term survival and the secondary end points of morbidity , mortality and quality of life of patients undergoing standard versus extended lymphadenectomy in radical PD for pancreatic cancer . METHODS From March 2000 to May 2003 , 112 patients with potentially curable pancreatic head cancer were enrolled and intraoperatively randomized to a standard or extended lymphadenectomy group . No resected patients received any adjuvant treatments . RESULTS A hundred and one eligible patients were analyzed . Demographic and histopathological characteristics of the two groups were similar . The mean operating time , intraoperative blood loss and number of retrieved lymph nodes were greater in the extended group , but the other operative results were comparable . CONCLUSIONS Although this multicenter RCT was conducted in a strict setting , extended lymphadenectomy in radical PD did not benefit long-term survival in patients with resectable pancreatic head cancer and led to levels of morbidity , mortality and quality of life comparable to those found after standard lymphadenectomy .

extended lymphadenectomy

extended lymphadenectomy

standard or extended lymphadenectomy

extended lymphadenectomy

standard lymphadenectomy .

mean operating time

intraoperative blood loss

number of retrieved lymph nodes

radical PD

pancreatic cancer

pancreatic head cancer

A hundred and one

resectable pancreatic head cancer


[ Prophylactic intraaortic balloon pumping in high-risk cardiac surgery patients ] . BACKGROUND We examined the impact of prophylactic IABP insertion in EuroSCORE-stratified high-risk cardiac surgery patients with a score ≥8 . MATERIAL AND METHODS A randomized trial with 104 patients either without prophylactic IABP insertion ( group A , n=52 ) or with IABP ( group B , n=52 ) was conducted . The primary endpoint was 30-day mortality . RESULTS The median age of the patients was 74 years and 43 % of participants were females . The 30-day mortality did not differ between group A ( 17.3 % ) and group B ( 13.4 % ; p=0.78 ) . The median hospital stay was 14 days in both groups . Intra- and postoperative IABP support was required by 13 patients ( 21 % ) in group A . The median ventilation time ( 14 hours versus 13 hours ) , median catecholamine dose , frequency of dialysis-dependent acute renal failure ( 28 % versus 18 % ) , cardiac indices , and frequency of a low cardiac output syndrome ( 26 % versus 25 % ) did not significantly differ between groups . CONCLUSION Prophylactic preoperative IABP insertion in EuroSCORE-stratified high-risk patients is not associated with decreased 30-day mortality .

prophylactic IABP insertion

30-day mortality

median hospital

median ventilation

median catecholamine dose

high-risk cardiac surgery patients


Armodafinil and modafinil in patients with excessive sleepiness associated with shift work disorder : a pharmacokinetic/pharmacodynamic model for predicting and comparing their concentration-effect relationships . Armodafinil , the longer lasting R-isomer of racemic modafinil , improves wakefulness in patients with excessive sleepiness associated with shift work disorder ( SWD ) . Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses . Pooled Multiple Sleep Latency Test ( MSLT ) data from 2 randomized , double-blind , placebo-controlled trials in 463 patients with SWD , 1 with armodafinil 150 mg/d and 1 with modafinil 200 mg/d ( both administered around 2200 h before night shifts ) , were used to build a pharmacokinetic/pharmacodynamic model . Predicted plasma drug concentrations were obtained by developing and applying a population pharmacokinetic model using nonlinear mixed-effects modeling . Armodafinil 200 mg produced a plasma concentration above the EC ( 50 ) ( 4.6 µg/mL ) for 9 hours , whereas modafinil 200 mg did not exceed the EC ( 50 ) . Consequently , armodafinil produced greater increases in predicted placebo-subtracted MSLT times of 0.5-1 minute ( up to 10 hours after dosing ) compared with modafinil . On a milligram-to-milligram basis , armodafinil 200 mg consistently increased wakefulness more than modafinil 200 mg , including times late in the 8-hour shift .

Armodafinil and modafinil

Armodafinil

armodafinil

placebo-controlled

armodafinil 150 mg/d

1 with modafinil 200 mg/d

pharmacokinetic/pharmacodynamic

wakefulness

excessive sleepiness

shift work disorder ( SWD )

plasma concentrations

pharmacokinetic/pharmacodynamic

plasma drug concentrations

pharmacokinetic model

plasma concentration

excessive sleepiness

excessive sleepiness

shift work disorder

SWD


Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD . BACKGROUND Combining maintenance medications with different mechanisms of action may improve outcomes in COPD . In this study we evaluated the efficacy and safety of fluticasone/salmeterol ( FSC ) ( 250/50 mcg twice daily ) when added to tiotropium ( 18 mcg once daily ) ( TIO ) in subjects with symptomatic moderate to severe COPD . METHODS This was a 24-week , randomized , double-blind , parallel group , multi-center study . Subjects 40 years or older with cigarette smoking history ≥10 pack-years and with the diagnosis of COPD and post-bronchodilator FEV ( 1 ) ≥40 to ≤ 80 % of predicted normal and FEV ( 1 ) /FVC of ≤0.70 were enrolled . Following a 4-week treatment with open-label TIO 18 mcg once daily , subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo . The primary efficacy endpoint was AM pre-dose FEV ( 1 ) and secondary endpoints included other measures of lung function , rescue albuterol use , health status and exacerbations . RESULTS The addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV ( 1 ) , 2 h post-dose FEV ( 1 ) , AM pre-dose FVC , 2 h post-dose FVC and AM pre-dose IC compared with TIO alone . Furthermore , this combination was superior to TIO alone in reducing rescue albuterol use . However , there were no significant differences between the treatment groups in health status or COPD exacerbations . The incidence of adverse events was similar in both groups . CONCLUSIONS The addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events . NCT00784550 .

fluticasone propionate/salmeterol

tiotropium

fluticasone/salmeterol ( FSC )

tiotropium

efficacy and safety

moderate to severe COPD


A simplified score for transfer of patients requiring mechanical ventilation to a long-term care hospital . BACKGROUND Long-term care hospitals are Medicare providers of postacute care that have a mean length of stay of 25 days or more . Early identification and timely transfer of patients requiring mechanical ventilation to such hospitals may improve the efficiency of inpatient care . OBJECTIVES To develop a predictive model and a simplified score for use on day 7 of hospitalization to assess whether a patient receiving mechanical ventilation is likely to require an additional 25 days of hospitalization ( ie , would qualify for transfer to a long-term care hospital ) . METHODS A retrospective , cross-sectional study using hospital discharge and billing data from the 2005 Nationwide Inpatient Sample for 54 686 Medicare beneficiaries admitted to US community hospitals who met the study 's eligibility criteria . The outcome was overall length of stay ( ≥32 vs < 32 days ) . Split-sample validation was used . Multivariable survey-logistic regression analyses were performed to assess predictors and probability of the outcome . A simplified score was derived from the final predictive model . RESULTS The discriminatory power of the predictive model was 0.75 and that of the simplified score was 0.72 . The model calibrated well . All predictors were significantly ( P < .01 ) associated with a hospitalization of 32 days or longer ; having a tracheostomy was the strongest predictor ( odds ratio , 4.74 ) . The simplified scores ranged from -5 to 110 points and were categorized into 3 classes of risk . CONCLUSIONS Efforts to aid discharge decision making and optimize hospital resource planning could take advantage of our predictive model and the simplified scoring tool .

mechanical ventilation

predictive model

mechanical ventilation

efficiency

overall length of stay

postacute care


Single negative colposcopy : is it enough to rule out high-grade disease ? It has been proposed that women who have a negative colposcopic examination or who have no cervical intraepithelial neoplasia ( CIN ) on colposcopic biopsy can be safely returned to routine screening with the next visit being three or five years later . We present data regarding 551 women who had colposcopy in Wales for a low-grade cytological abnormality and who were followed through Cervical Screening Wales for subsequent CIN . Of 436 women declared CIN free initially , 26 ( 6.0 % ) had high-grade CIN diagnosed on follow-up . We suggest that additional screening at an interval of less than three years should be offered to women with a negative colposcopy or a biopsy without CIN .

Single negative colposcopy

colposcopic biopsy

colposcopy

CIN free

high-grade CIN

women

women

low-grade cytological abnormality

subsequent CIN

women


Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy . A randomized double-blind casein-controlled trial . The Italian Multicenter Study Group . In a double blind randomized study , branched-chain amino acids and placebo ( casein ) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis . After a 15-day run-in period with controlled diet ( 45-65 g protein ) , the patients were administered , in addition to their diet , branched-chain amino acids ( 0.24 g/kg , 30 patients ) or an equinitrogenous amount of casein ( 34 patients ) . One patient on branched-chain amino acids and two on casein were lost to the study . After 3 months , the index of portal-systemic encephalopathy significantly improved in patients on active treatment ( from 40 [ S.D . 14 ] % to 21 [ 17 ] ) , but was not in subjects receiving casein ( from 37 [ 13 ] % to 36 [ 12 ] ) . Two or more parameters of the index improved in 24 patients treated with amino acids ( 80 % ; confidence limits , 61-92 % ) , and only in 12 receiving casein ( 35 % ; confidence limits , 20-54 % ; p less than 0.001 ) . Patients who did not improve were given an alternative treatment for 3 more months . Casein-treated patients given branched-chain amino acids rapidly improved . The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance , which became consistently positive in amino acid-treated subjects ; there was also a mild improvement in nutritional parameters and in liver function tests . The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy .

oral branched-chain amino acid

branched-chain amino acids

placebo ( casein )

branched-chain amino acids

equinitrogenous amount of casein

active treatment

casein

amino acids

casein

alternative treatment

amino acids

amino acid-treated

oral branched-chain amino acids

casein

improved .

chronic hepatic encephalopathy

chronic hepatic encephalopathy

cirrhosis

cirrhotic patients

chronic encephalopathy


Arthroscopic rotator cuff repair with and without acromioplasty in the treatment of full-thickness rotator cuff tears : a multicenter , randomized controlled trial . BACKGROUND The primary objective of this prospective randomized controlled trial was to compare functional and quality-of-life indices and rates of revision surgery in arthroscopic rotator cuff repair with and without acromioplasty . METHODS Eighty-six patients consented and were randomly assigned intraoperatively to one of two study groups , and sixty-eight of them completed the study . The primary outcome was the Western Ontario Rotator Cuff ( WORC ) index . Secondary outcome measures included the American Shoulder and Elbow Surgeons ( ASES ) shoulder assessment form and a count of revisions required in each group . Outcome measures were completed preoperatively and at three , six , twelve , eighteen , and twenty-four months after surgery . RESULTS WORC and ASES scores improved significantly in each group over time ( p < 0.001 ) . There were no differences in WORC or ASES scores between the groups that had arthroscopic cuff repair with or without acromioplasty at any time point . There were no differences in scores on the basis of acromion type , nor were any interaction effects identified between group and acromion type . Four participants ( 9 % ) in the group that had arthroscopic cuff repair alone , one with a Type-2 and three with a Type-3 acromion , required additional surgery by the twenty-four-month time point . The number of patients who required additional surgery was greater ( p = 0.05 ) in the group that had arthroscopic cuff repair alone than in the group that had arthroscopic cuff repair and acromioplasty . CONCLUSIONS Our findings are consistent with previous research reports in which there was no difference in functional and quality-of-life indices for patients who had rotator cuff repair with or without acromioplasty . The higher reoperation rate was found in the group without acromioplasty . Further study that includes follow-up imaging and patient-reported outcomes over a greater follow-up period is needed .

Arthroscopic rotator cuff repair with

without acromioplasty

arthroscopic rotator cuff repair with

without acromioplasty

arthroscopic cuff repair with

without acromioplasty

arthroscopic cuff repair

functional and quality-of-life indices

rates of revision surgery

and a

count of revisions

WORC

ASES scores

WORC

ASES scores

repair

additional surgery

functional and quality-of-life indices

higher reoperation rate

full-thickness rotator cuff tears

Eighty-six

sixty-eight


Once-daily topical brimonidine tartrate gel 0·5 % is a novel treatment for moderate to severe facial erythema of rosacea : results of two multicentre , randomized and vehicle-controlled studies . BACKGROUND Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity . Brimonidine tartrate ( BT ) is a highly selective α ( 2 ) -adrenergic receptor agonist with vasoconstrictive activity . OBJECTIVE To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety . METHODS In study A , 122 subjects were randomized to receive a single application of BT 0·07 % , 0·18 % , 0·5 % or vehicle . In study B ( 4-week treatment and 4-week follow-up ) , 269 subjects were randomized to receive BT 0·5 % once daily , BT 0·18 % once daily , vehicle once daily , BT 0·18 % twice daily or vehicle twice daily . Evaluations included Clinician 's Erythema Assessment ( CEA ) , Patient 's Self-Assessment ( PSA ) , Chroma Meter measurements and adverse events . RESULTS In study A , a single application of topical BT gel reduced facial erythema in a dose-dependent fashion . A significant difference between BT 0·5 % and vehicle in Chroma Meter redness value was observed from 30min to 12h after application . In study B , BT 0·5 % once daily had a statistically superior success profile ( defined as a two-grade improvement on both CEA and PSA over 12h ) compared with vehicle once daily on days 1 , 15 and 29 ( all P < 0·001 ) . No tachyphylaxis , rebound of erythema or aggravation of other disease signs ( telangiectasia , inflammatory lesions ) was observed . All regimens were safe and well tolerated with similarly low incidence of adverse events . CONCLUSIONS Once-daily BT gel 0·5 % is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea .

topical brimonidine tartrate gel

of erythema of rosacea

its efficacy and safety

Patient 's Self-Assessment ( PSA

Chroma Meter measurements

adverse

topical BT gel reduced facial erythema

vehicle in Chroma Meter redness

statistically superior success

two-grade improvement on both CEA

regimens were safe and well

incidence of adverse

significantly greater

Erythema of rosacea

122 subjects

269 subjects


Rapid injection of propofol reduces vascular pain and facilitates Laryngeal Mask Airway insertion . STUDY OBJECTIVE To compare the clinical efficacy of a rapid injection of propofol in regard to pain and ability to facilitate Laryngeal Mask Airway ( LMA ) insertion . DESIGN Randomized , single-blinded , placebo-controlled study . SETTING University hospital . PATIENTS 120 ASA physical status 1 and 2 patients undergoing elective orthopedic surgeries . INTERVENTIONS Patients were randomly allocated to one of 4 groups . Group A patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 3.3 mg/sec . Group B patients were pretreated with lidocaine 0.5 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec . In Group C , patients were pretreated with lidocaine 1.0 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec . In Group D , patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 50 mg/sec . MEASUREMENTS Pain on injection was measured using a 4-point scale . Scale and success rate of smooth LMA insertion also were recorded . MAIN RESULTS Rapid injection was less painful than after pretreatment with lidocaine 0.5 mg/kg , but was similar to slow injection after pretreatment with lidocaine 1.0 mg/kg . Rapid injection facilitated LMA insertion , unlike slow injection with lidocaine 0.5 mg/kg pretreatment , and was similarly successful to slow injection after pretreatment with lidocaine 1.0 mg/kg . CONCLUSIONS The rapid administration of propofol reduces pain and facilitates LMA insertion versus slow administration of propofol .

propofol

propofol

placebo-controlled

Rapid injection

lidocaine

slow injection

pretreatment with lidocaine

Rapid injection

slow injection

lidocaine

slow injection

after pretreatment with lidocaine

rapid administration

propofol

slow administration

propofol

painful

LMA insertion

Laryngeal Mask Airway insertion

LMA

orthopedic surgeries