A neuropsychological rehabilitation program for patients with Multiple Sclerosis based on the model of the ICF . BACKGROUND Forty to sixty percent of MS patients suffer from cognitive impairments . Cognitive deficits are a great burden for patients affected . In particular they may lead to a reduced quality of life , loss of work and problems with the social environment . OBJECTIVE The aim of this study was to evaluate a specific neuropsychological rehabilitation program for MS patients according to the ICF to be able to meet more properly individual requirements on the therapy level of function as well as of activities and participation . METHODS Forty patients with MS were randomised in an intervention ( IG ) - and a control group ( CG ) . The outcome measure of the IG , who started an intensive computer based home training of attention and attended psychological counselling was compared to the untrained CG . RESULTS In specific domains of attention ( simple and cued alertness and divided attention ) significant group differences between CG and IG could be found . The IG reported an improvement of mental fatigue and retardation . CONCLUSION These findings support the idea that a neuropsychological rehabilitation program , which based on the model of ICF , could improve cognitive impairment and could also have a positive influence of activities and participation .

intervention ( IG )

control group

( CG )

psychological counselling

untrained CG

IG

cognitive impairments

Cognitive deficits

quality of life

function

activities and participation .

outcome measure

mental fatigue and retardation .

cognitive impairment

activities and participation .

MS

Forty


[ The comparation of the efficacy of surgical treatment for lung cancer by minimally invasive thoracoscopic and by traditional thoracotomy ] . OBJECTIVE To observe the clinical effects of lung cancer , 75 patients with lung cancer were randomly divided into two groups , observation group underwent minimally invasive thoracic surgery 38 cases and the control group underwent conventional thoracotomy 37 cases . RESULTS Observation group was significantly reduced compared with the control group in blood loss , postoperative pleural fluid drainage , postoperative hospital stay , the difference was statistically significant . While there was no statistically significant in the number of lymph node dissection , operative time and postoperative chest tube drainage time .

minimally invasive thoracoscopic

traditional thoracotomy

invasive thoracic surgery

conventional thoracotomy

postoperative hospital stay

lymph node dissection

operative time

postoperative chest tube drainage time

lung cancer

lung cancer


Fluticasone or montelukast in preschool wheeze : a randomized controlled trial . INTRODUCTION Approximately 30 % of children younger than 3 years experience at least 1 episode of wheezing . Antiasthmatic medication is routinely prescribed , but its effectiveness remains unclear . Our study was aimed to evaluate the effect of anti-inflammatory treatment on frequency and severity of preschool wheeze episodes ( PWEs ) . METHODS Children aged 6 to 36 months with the first up to the third PWE were randomly assigned to receive montelukast , fluticasone , or no treatment for 12 weeks . The outcome measures were the number of PWEs , the number of hospitalizations due to PWE , and the severity of respiratory symptoms . results : There were no significant differences in outcome measures between the groups . However , tobacco-exposed children treated with fluticasone had significantly fewer PWEs ( P = .01 ) . CONCLUSION Neither montelukast nor fluticasone has proven effective in the prevention of PWE recurrence . Children of smoking parents may benefit from fluticasone treatment after PWE . This observation requires confirmation in larger studies .

Fluticasone

montelukast

Antiasthmatic medication

anti-inflammatory treatment

montelukast

fluticasone

no treatment

fluticasone

montelukast

fluticasone

fluticasone

preschool wheeze episodes ( PWEs )

the severity of respiratory symptoms

PWEs

PWE recurrence

preschool wheeze :

children younger than 3 years

preschool wheeze episodes ( PWEs ) .

Children of smoking parents


Efficacy of artemisinin-based combination treatments of uncomplicated falciparum malaria in under-five-year-old Nigerian children . The efficacy of 3-day regimens of artemether-lumefantrine and artesunate-amodiaquine were evaluated in 747 children < 5 years of age with uncomplicated malaria from six geographical areas of Nigeria . Fever clearance was significantly faster ( P = 0.006 ) and the proportion of children with parasitemia 1 day after treatment began was significantly lower ( P = 0.016 ) in artesunate-amodiaquine-compared with artemether-lumefantrine-treated children . Parasite clearance times were similar with both treatments . Overall efficacy was 96.3 % ( 95 % confidence interval [ CI ] 94.5-97.6 % ) , and was similar for both regimens . Polymerase chain reaction-corrected parasitologic cure rates on Day 28 were 96.9 % ( 95 % CI 93.9-98.2 % ) and 98.3 % ( 95 % CI 96.1-99.3 % ) for artemether-lumefantrine and artesunate-amodiaquine , respectively . Gametocyte carriage post treatment was significantly lower than pretreatment ( P < 0.0001 ) . In anemic children , mean time to recovery from anemia was 10 days ( 95 % CI 9.04-10.9 ) and was similar for both regimens . Both treatments were well tolerated and are safe and efficacious treatments of uncomplicated falciparum malaria in young Nigerian children .

artemether-lumefantrine

artesunate-amodiaquine

artemether-lumefantrine-treated

artemether-lumefantrine

artesunate-amodiaquine

clearance

Parasite clearance

parasitologic cure rates

Gametocyte carriage post treatment

mean time to recovery from anemia

under-five-year-old

747 children

< 5 years of age

uncomplicated malaria

anemic

children

young

children


The REFLO-STEMI trial comparing intracoronary adenosine , sodium nitroprusside and standard therapy for the attenuation of infarct size and microvascular obstruction during primary percutaneous coronary intervention : study protocol for a randomised controlled trial . BACKGROUND Microvascular obstruction ( MVO ) secondary to ischaemic-reperfusion injury is an important but underappreciated determinant of short- and longer-term outcome following percutaneous coronary intervention ( PCI ) treatment of ST-elevation myocardial infarction ( STEMI ) . Several small studies have demonstrated a reduction in the degree of MVO utilising a variety of vasoactive agents , with adenosine and sodium nitroprusside ( SNP ) being most evaluated . However , the evidence base remains weak as the trials have had variable endpoints , differing drug doses and delivery . As such , the results regarding benefit are conflicting . METHODS The REperfusion Facilitated by LOcal adjunctive therapy in STEMI ( REFLO-STEMI ) trial is a multicentre , prospective , randomised , controlled , open label , study with blinded endpoint analysis : Patients presenting within 6 h of onset of STEMI and undergoing planned primary PCI ( P-PCI ) with TIMI 0/1 flow in the infarct-related artery ( IRA ) and no significant bystander coronary artery disease on angiography , are randomised into one of three groups : PCI with adjunctive pharmacotherapy ( intracoronary adenosine or SNP ) or control ( standard PCI ) . All receive Bivalirudin anticoagulation and thrombus aspiration . The primary outcome is infarct size ( IS ) ( determined as a percentage of total left ventricular mass ) measured by cardiac magnetic resonance imaging ( CMRI ) undertaken at 48 to 72 h post P-PCI . Secondary outcome measures include MVO ( hypoenhancement within infarct core ) on CMRI , angiographic markers of microvascular perfusion and MACE during 1-month follow-up . The study aims to recruit 240 patients ( powered at 80 % to detect a 5 % absolute reduction in IS ) . DISCUSSION The REFLO-STEMI study has been designed to address the weaknesses of previous trials , which have collectively failed to demonstrate whether adjunctive pharmacotherapy with adenosine and/or SNP can reduce measures of myocardial injury ( infarct size and MVO ) and improve clinical outcome , despite good basic evidence that they have the potential to attenuate this process . The REFLO-STEMI study will be the most scientifically robust trial to date evaluating whether adjunctive therapy ( intracoronary adenosine or SNP following thrombus aspiration ) reduces CMRI measured IS and MVO in patients undergoing P-PCI within 6 h of onset of STEMI . TRIAL REGISTRATION Trial registered 20th November 2012 : ClinicalTrials.gov Identifier NCT01747174 .

intracoronary adenosine

sodium nitroprusside

standard therapy

vasoactive agents

adenosine

sodium nitroprusside ( SNP )

angiography

Bivalirudin anticoagulation

thrombus aspiration

adjunctive pharmacotherapy

Bivalirudin anticoagulation

thrombus aspiration

240 patients


Effect of dietary zinc oxide on jejunal morphological and immunological characteristics in weaned piglets . The aim of this study was to evaluate age-related changes and the effect of dietary Zn concentration on morphological and immunological characteristics in the gastrointestinal tract of piglets . A total of 96 purebred Landrace piglets were weaned at the age of 26 ± 1 d , and randomly allocated into 3 treatment groups fed with low ( 57 mg Zn/kg ) , medium ( 164 mg Zn/kg ) , and high ( 2425 mg Zn/kg ) dietary Zn ( ZnO ) . Piglets ( 4 males and 4 females per treatment group ) were killed at 33 ± 1 , 40 ± 1 , 47 ± 1 , and 54 ± 1 d of age . In the jejunum , villus height , crypt depth , and the number of goblet cells producing neutral , acidic , sulfated , and sialylated mucins were measured . Intraepithelial lymphocytes were characterized by flow cytometry and the gene expression of mucin 2 ( MUC2 ) , mucin 20 ( MUC20 ) , β-defensin 3 , and trefoil factor 3 ( TFF3 ) was determined by reverse transcription quantitative PCR . Villus height and crypt depth in the jejunum showed age related differences ( P < 0.01 ) , whereas the dietary concentrations of Zn had no effect . The mucin types were modified mainly by age , and dietary Zn had no effect in the proximal jejunum . In the distal jejunum , age and Zn had effects on the mucin types . The abundance of sulfomucins decreased ( P < 0.001 ) and sialomucins increased with age ( P < 0.001 ) , while high dietary ZnO reduced the sulfomucins ( P < 0.001 ) and increased the sialomucins ( P < 0.05 ) in the crypts . The phenotypes of lymphocytes in the epithelium of the proximal jejunum showed relatively constant percentages of T-cells , as well as natural killer cells . High dietary Zn treatment led to a reduced abundance of CD8 ( + ) γδ T-cells ( P < 0.05 ) . The apportionment of different cytotoxic T-cell was age dependent . Although the percentage of CD4 ( - ) CD8β ( + ) increased ( P < 0.01 ) , the relative amount of CD4 ( + ) CD8β ( + ) decreased with age ( P < 0.05 ) . The expression of MUC2 and MUC20 was not influenced by age or dietary Zn concentration . High Zn intakes resulted in a reduced gene expression of β-defensin 3 ( P < 0.05 ) , but did not affect the expression of TFF3 . It is concluded that Zn in the form of ZnO appears to have specific effects on the innate and adaptive gut associated immune system of piglets . These might contribute to the positive effects of Zn on the prevention of postweaning diarrhea .

dietary zinc oxide

abundance of sulfomucins

0.001 ) and sialomucins

constant percentages of T-cells

cells

High dietary Zn treatment

abundance of CD8 ( + ) γδ

different cytotoxic

percentage of CD4 ( - ) CD8β ( + )

expression of β-defensin

weaned piglets .

age of 26 ± 1 d

males

females


Working memory and cognitive flexibility-training for children with an autism spectrum disorder : a randomized controlled trial . BACKGROUND People with autism spectrum disorders ( ASDs ) experience executive function ( EF ) deficits . There is an urgent need for effective interventions , but in spite of the increasing research focus on computerized cognitive training , this has not been studied in ASD . Hence , we investigated two EF training conditions in children with ASD . METHODS In a randomized controlled trial , children with ASD ( n = 121 , 8-12 years , IQ > 80 ) were randomly assigned to an adaptive working memory ( WM ) training , an adaptive cognitive flexibility-training , or a non-adaptive control training ( mock-training ) . Braingame Brian , a computerized EF-training with game-elements , was used . Outcome measures ( pretraining , post-training , and 6-week-follow-up ) were near-transfer to trained EFs , far-transfer to other EFs ( sustained attention and inhibition ) , and parent 's ratings of daily life EFs , social behavior , attention deficit hyperactivity disorder ( ADHD ) -behavior , and quality of life . RESULTS Attrition-rate was 26 % . Children in all conditions who completed the training improved in WM , cognitive flexibility , attention , and on parent 's ratings , but not in inhibition . There were no significant differential intervention effects , although children in the WM condition showed a trend toward improvement on near-transfer WM and ADHD-behavior , and children in the cognitive flexibility condition showed a trend toward improvement on near-transfer flexibility . CONCLUSION Although children in the WM condition tended to improve more in WM and ADHD-behavior , the lack of differential improvement on most outcome measures , the absence of a clear effect of the adaptive training compared to the mock-training , and the high attrition rate suggest that the training in its present form is probably not suitable for children with ASD .

EF training conditions

Attrition-rate

near-transfer WM and ADHD-behavior

WM and ADHD-behavior

children

autism spectrum disorder

autism spectrum disorders ( ASDs )

children

ASD

children

ASD

8-12 years

ASD


Randomized controlled trial of parental responsiveness intervention for toddlers at high risk for autism . This study tested the effects of a parent-mediated intervention on parental responsiveness with their toddlers at high risk for an autism spectrum disorder ( ASD ) . Participants included caregivers and their 66 toddlers at high risk for ASD . Caregivers were randomized to 12 sessions of an individualized parent education intervention aimed at improving parental responsiveness or to a monitoring control group involving 4 sessions of behavioral support . Parental responsiveness and child outcomes were measured at three time points : at beginning and end of the 3-month treatment and at 12-months post-study entry . Parental responsiveness improved significantly in the treatment group but not the control group . However , parental responsiveness was not fully maintained at follow up . There were no treatment effects on child outcomes of joint attention or language . Children in both groups made significant developmental gains in cognition and language skills over one year . These results support parental responsiveness as an important intervention target given its general association with child outcomes in the extant literature ; however , additional supports are likely needed to fully maintain the treatment effect and to affect child outcomes .

parental responsiveness intervention

Parental responsiveness

Parental responsiveness

parental responsiveness

Parental responsiveness

parental responsiveness

child outcomes

joint attention or language

cognition and language skills

toddlers

high risk for autism

toddlers

66 toddlers

ASD


Feasibility study of the effects of art as a creative engagement intervention during stroke rehabilitation on improvement of psychosocial outcomes : study protocol for a single blind randomized controlled trial : the ACES study . BACKGROUND Benefits of art participation after stroke are becoming increasingly recognized . Qualitative studies suggest that participation in visual arts creative engagement interventions ( CEIs ) during rehabilitation after stroke may improve mood , self-esteem , hope and some aspects of physical recovery . This study examines the feasibility of undertaking a randomized controlled trial of a CEI delivered by artists within in-patient stroke rehabilitation to test effectiveness . METHODS/DESIGN This trial is a two arm , single-blind , randomized controlled feasibility trial within in-patient stroke rehabilitation . We will recruit 80 patients receiving stroke rehabilitation in two stroke units in a health board area of Scotland ( 40 patients in each arm ) . Intervention arm participants will receive a visual-arts based CEI facilitated by experienced artists . Artists will follow an intervention protocol with specific components that enable participants to set , achieve and review artistic goals . Participants will receive up to eight intervention sessions , four within a group and four one-to-one with the artist . Control group participants will receive usual care only.Data collection will occur at baseline , post-intervention and three-month follow-up . Stroke-related health status is the primary outcome ; mood , self-esteem , self-efficacy , perceived recovery control and hope are secondary outcomes . Semi-structured interviews will be conducted with purposively selected patients , artists and healthcare staff to elicit views and experiences of the intervention and feasibility and acceptability of trial processes . Recruitment rates , retention rates and patient preference for art participation will also be collected . Data will indicate , with confidence intervals , the proportion of patients choosing or refusing participation in the CEI and will allow calculation of recruitment rates for a future definitive trial . Summary data will indicate potential variability , magnitude and direction of difference between groups . Findings will inform sample size calculations for a definitive trial . Thematic analysis of qualitative data will be managed using the Framework Approach . Framework is an analytical approach for qualitative data , commonly used in policy and medical research . DISCUSSION If shown to demonstrate effects , this intervention has the potential to address aspects of stroke recovery previously . Not routinely addressed in rehabilitation . TRIAL REGISTRATION Registered with Clinical Trials.Gov : NCT02085226 on 6th March 2014 .

stroke rehabilitation

visual-arts based CEI

facilitated by experienced artists

effects

psychosocial outcomes :

mood , self-esteem , hope

Stroke-related health status

feasibility and acceptability

recruitment rates

80 patients

stroke


Comparison of intrathecal bupivacaine , levobupivacaine for cesarean section . BACKGROUND Some investigators found a greater incidence of hypotension in patients receiving intrathecal hyperbaric solution than in patients receiving plain solution for cesarean section . OBJECTIVE Compare the effects of intrathecal hyperbaric bupivacaine 10 mg with intrathecal bupivacaine 11 mg and intrathecal levobupivacaine 11 mg , all with 10 microg of fentanyl , for cesarean section . MATERIAL AND METHOD This prospective , randomized , double-blinded study was approved by the Ethics Committee . Ninety ASA I-II parturients undergoing elective cesarean section were enrolled . Group H received 10 mg of 0.5 % hyperbaric bupivacaine plus fentanyl 10 g , Group B received 11 mg of 0.5 % bupivacaine plus fentanyl 10 g , and Group L received 11 mg of 0.5 % levobupivacaine plus fentanyl 10 g. Spinal anesthesia ( SA ) was undertaken in right lateral position and spinal solutions were injected approximately 30 to 40 seconds . Sensory and motor block were assessed at 5-minute intervals . Side-effects such as hypotension , nausea , pruritus , shivering , and headache were recorded RESULTS Demographic data were similar in all groups . The level of an absence of cold sensation , the level of pinprick analgesia , and time to achieve sensory block to T4 level of Group H was significantly higher than Group B and Group L. The degree of motor block was comparable in all groups . The incidence of visceral pain was minimal , rated as mild pain and only found in Group B . The incidence of hypotension was comparable with Group H = 67 % , Group B = 56 % , and Group L = 50 % . Other side effects such as nausea , vomiting , pruritus , shivering , and headache were not statistically significant . Patient 's satisfaction rated as very good and was not different between the three groups . CONCLUSION The level of absence of cold sensation , level of pinprick analgesia , and time to achieve sensory block to T4 level were statistically higher in patients receiving hyperbaric bupivacaine than in patients receiving plain bupivacaine and plain levobupivacaine , while the differences were not statistically significant in all groups regarding effective surgical anesthesia , postoperative analgesia , and side effects . Therefore , Levobupivacaine can be an alternative to bupivacaine .

intrathecal bupivacaine

levobupivacaine

intrathecal hyperbaric solution

intrathecal hyperbaric bupivacaine

intrathecal bupivacaine

intrathecal levobupivacaine

fentanyl

0.5 % bupivacaine plus fentanyl 10 g

Spinal anesthesia ( SA )

hyperbaric bupivacaine

bupivacaine

levobupivacaine

Levobupivacaine

bupivacaine

hypotension

nausea

pruritus

shivering

headache

absence of cold sensation

level of pinprick analgesia

motor block

visceral pain

hypotension

nausea

vomiting

pruritus

shivering

headache

satisfaction

The level of absence of cold sensation

level of pinprick analgesia

effective surgical anesthesia

postoperative analgesia

side effects

alternative

Ninety


Femoral nerve block using 0.25 % or 0.5 % bupivacaine for analgesia after arthroscopic anterior cruciate ligament reconstruction . BACKGROUND Femoral nerve block ( FNB ) with varying concentrations of bupivacaine is often used for postoperative analgesia after anterior cruciate ligament ( ACL ) reconstruction . OBJECTIVE To determine whether FNB using 0.25 % or 0.5 % bupivacaine provided better analgesia with less effect on quadriceps strengths after ACL reconstruction . MATERIAL AND METHOD One hundred patients were randomized to receive FNB with 20 mL of 0.25 % or 0.5 % bupivacaine . Data regarding demographic , effectiveness of FNB , time to first pain , time to first analgesic , pain scores , morphine use , and recovery of sensory and motor function were recorded . RESULTS Median time to first morphine requirement was 12 hours in 0.5 % bupivacaine group and 10 hours in 0.25 % bupivacaine group ( p = 0.048 ) . Pain score at 18 hours was lower in 0.5 % bupivacaine group compared with 0.25 % bupivacaine group ( p = 0.001 ) . When specify to the patellar tendon graft subgroup , the patients requiring morphine were 70 % in 0.5 % bupivacaine group and 90 % in 0.25 % bupivacaine group ( p = 0.03 ) . No differences were found in demographic data , effectiveness of FNB , time to first pain , morphine consumption , and recovery of sensorimotor function . CONCLUSION FNB with 0.5 % bupivacaine provided longer time to first analgesic and lower narcotic requirements after patellar tendon graft ACL reconstruction when compared to 0.25 % bupivacaine . Both concentrations showed similar effect on quadriceps strengths .

Femoral nerve block ( FNB )

bupivacaine

FNB using 0.25 % or 0.5 % bupivacaine

FNB

20 mL of 0.25 % or 0.5 % bupivacaine .

FNB

bupivacaine

bupivacaine

0.5 % bupivacaine

0.25 % bupivacaine

morphine

0.5 % bupivacaine

0.25 % bupivacaine

FNB

FNB with 0.5 % bupivacaine

0.25 % bupivacaine .

One hundred


The influence of prostaglandin inhibition by indomethacin on blood pressure and renal function in hypertensive patients treated with cilazapril . 1 . In a placebo-controlled double-blind cross-over study lasting 6 weeks , twenty patients with essential hypertension were treated with placebo for 2 weeks followed by oral cilazapril 2.5 mg once a day or oral indomethacin 50 mg twice daily for 2 weeks . Afterwards they received the combination of both drugs for a further 2 weeks . 2 . Cilazapril significantly lowered systolic and diastolic blood pressure for a period of 24 h post administration . 3 . Indomethacin significantly attenuated the antihypertensive activity of cilazapril . This was more pronounced in those patients who were treated for the initial 2 weeks with indomethacin plus placebo ( and subsequently with cilazapril in addition ) than in the subjects who first received cilazapril plus placebo and then the combination . 4 . Correspondingly the decrease of plasma renin activity ( PRA ) and urinary prostaglandin excretion ( PGE2 ) was more pronounced in those patients treated initially with indomethacin . 5 . The effect of indomethacin on the antihypertensive effect of cilazapril appears to depend upon the sequence of drug administration .

indomethacin

cilazapril

placebo-controlled

placebo

oral cilazapril

oral indomethacin

Cilazapril

Indomethacin

cilazapril

indomethacin plus placebo

cilazapril

cilazapril plus placebo

indomethacin

indomethacin

cilazapril

blood pressure

renal function

systolic and diastolic blood pressure

antihypertensive activity

plasma renin activity ( PRA )

hypertensive

twenty

essential hypertension


Dental prophylaxis decreases the risk of esophageal cancer in males ; a nationwide population-based study in Taiwan . BACKGROUND Periodontal disease ( PD ) is one of the most common chronic inflammatory diseases . Esophageal cancer ( EC ) is also a common cause of death due to cancer among males . Systemic inflammatory processes have been shown to increase the risk of cancer . We conducted a retrospective cohort study to investigate the association between PD and EC . METHODS A total of 718,409 subjects were recruited from the Taiwan National Health Insurance Research Database ( NHIRD ) and followed from January 1 , 2000 to December 31 , 2010 . Of these , 519,831 subjects were diagnosed with PD and were grouped according to the most advanced treatment they received : dental prophylaxis , intensive treatment , or no treatment . The IRs of EC were compared among groups . RESULTS A total of 682 patients developed EC , resulting in an overall IR of 0.11 case-number per 1000 person-years ( ‰/y ) . The dental prophylaxis group had a significantly lower IR of EC ( 0.06‰/y ) than other groups ( p < 0.001 ) . Multivariable Cox regression analysis further revealed that male subjects [ hazard ratio ( HR ) = 10.04 , 95 % confidence interval ( CI ) = 7.58-13.30 ] , as well as a history of esophageal ulcers ( HR = 7.10 , 95 % CI = 5.03-10.01 ) , alcohol abuse ( HR = 5.46 , 95 % CI = 2.26-13.18 ) , or esophageal reflux ( HR = 1.86 , 95 % CI = 1.02-3.52 ) , were factors associated with a higher risk of EC . And the dental prophylaxis group showed a significantly lower risk for EC ( HR = 0.53 , 95 % CI = 0.44-0.65 ) . Further subgroup analysis showed that the dental prophylaxis group among males had a significant lower risk ( HR = 0.54 , 95 % CI = 0.44-0.66 ) for EC , while that of the females did not has statistically significant difference . CONCLUSION For this cohort , subjects received dental prophylaxis reduced the risk of EC compared to all PD and no PD groups among males .

Dental prophylaxis

dental prophylaxis

no treatment

esophageal cancer

Esophageal cancer ( EC )

cancer .

PD

EC

IRs of EC

EC

overall IR

Dental prophylaxis decreases

esophageal cancer

males

Esophageal cancer ( EC )

cancer

males

male


Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia ( TESLA Part B ) : a randomised , double-blind , placebo-controlled trial . BACKGROUND Homozygous familial hypercholesterolaemia is a rare , serious disorder caused by very low or absent plasma clearance of LDL , substantially raised LDL cholesterol , and accelerated development of cardiovascular disease . Conventional lipid-lowering treatments are modestly effective . Evolocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , reduced LDL cholesterol by 16 % in a pilot study . We now report results with evolocumab in a randomised , double-blind , placebo-controlled phase 3 trial . METHODS This randomised , double-blind , placebo-controlled phase 3 trial was undertaken at 17 sites in ten countries in North America , Europe , the Middle East , and South Africa . 50 eligible patients ( aged ≥12 years ) with homozygous familial hypercholesterolaemia , on stable lipid-regulating therapy for at least 4 weeks , and not receiving lipoprotein apheresis , were randomly allocated by a computer-generated randomisation sequence in a 2:1 ratio to receive subcutaneous evolocumab 420 mg or placebo every 4 weeks for 12 weeks . Randomisation was stratified by LDL cholesterol at screening ( < 11 mmol/L or ≥11 mmol/L ) and implemented by a computerised interactive voice-response system . Patients , study personnel , and the funder were masked to treatment and to the efficacy results by the central laboratory not returning LDL cholesterol or any lipid results to the clinical sites after the baseline visit . The primary endpoint was percentage change in ultracentrifugation LDL cholesterol from baseline at week 12 compared with placebo , analysed by intention-to-treat . This trial is registered with ClinicalTrials.gov , number NCT01588496 . FINDINGS Of the 50 eligible patients randomly assigned to the two treatment groups , 49 actually received the study drug and completed the study ( 16 in the placebo group and 33 in the evolocumab group ) . Compared with placebo , evolocumab significantly reduced ultracentrifugation LDL cholesterol at 12 weeks by 30·9 % ( 95 % CI -43·9 % to -18·0 % ; p < 0·0001 ) . Treatment-emergent adverse events occurred in ten ( 63 % ) of 16 patients in the placebo group and 12 ( 36 % ) of 33 in the evolocumab group . No serious clinical or laboratory adverse events occurred , and no anti-evolocumab antibody development was detected during the study . INTERPRETATION In patients with homozygous familial hypercholesterolaemia receiving stable background lipid-lowering treatment and not on apheresis , evolocumab 420 mg administered every 4 weeks was well tolerated and significantly reduced LDL cholesterol compared with placebo . FUNDING Amgen Inc .

evolocumab

placebo-controlled

Evolocumab

monoclonal antibody

evolocumab

placebo-controlled

placebo-controlled

placebo

evolocumab

evolocumab

LDL cholesterol

( aged ≥12 years )

hypercholesterolaemia


Pharmacodynamic analysis of intravenous recombinant urate oxidase using an indirect pharmacological response model in healthy subjects . AIM Pharmacodynamic analysis of intravenous recombinant urate oxidase produced by Escherichia coli was performed in healthy subjects using a pharmacokinetic/pharmacodynamic ( PK/PD ) model . METHODS A randomized , single-blind , placebo-controlled study was performed in 40 healthy Chinese subjects ( 4 groups of 10 subjects each , placebo 4:1 ratio ) who received infusions of uricase ( single doses of 0.1 , 0.2 , and 0.3 mg/kg ; multiple doses of 0.2 mg·kg ( -1 ) ·d ( -1 ) for 7 d ) . PK profiles were determined through plasma uricase activity , and PD profiles were established using uric acid levels in plasma and urine . The plasma PD parameter was estimated as changes in plasma uric acid levels as the effect in the indirect response model . Adverse events were also monitored . RESULTS A two-compartment PK model with constant iv input and first-order output was used to describe the kinetic process of plasma uricase . The low value ( 2.8 U/L ) of drug concentration that achieved 50 % of maximum effect ( EC50 ) indicated that low plasma uricase concentrations were sufficient to produce pharmacological effects . A strong relationship ( r ( 2 ) =0.9991 ) between the mean uric acid concentration in blood and the mean uric acid excretion rate in urine in the range of 11 to 30 h after single dosing was found . Infusions of uricase were well tolerated in all subjects . CONCLUSION The PK/PD model predicted the effective dose to be 0.1 mg/kg in healthy subjects . The excretion rate of uric acid in urine may be used as a new index for pharmacological effects in further clinical trials .

intravenous recombinant urate oxidase

intravenous recombinant urate oxidase

placebo-controlled

uricase

healthy

pharmacokinetic/pharmacodynamic

healthy


Selenium Treatment and Chagasic Cardiopathy ( STCC ) : study protocol for a double-blind randomized controlled trial . BACKGROUND Heart disease progression occurs in 30 % of patients with chronic Trypanosoma cruzi infection . Supplementation with selenium ( Se ) in animal model of T. cruzi infection produced promising results . There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease . The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy . METHODS The Selenium Treatment and Chagasic Cardiopathy trial is a superiority , double-blind , placebo-controlled , randomized clinical trial . The eligibility criteria are as follows : ( 1 ) a Chagas disease diagnosis confirmed by serology ; ( 2 ) segmental , mild or moderate global left ventricular systolic dysfunction ; and ( 3 ) age between 18 and 65 years . The exclusion criteria are as follows : ( 1 ) pregnancy , ( 2 ) diabetes mellitus , ( 3 ) tobacco use , ( 4 ) alcohol abuse , ( 5 ) evidence of nonchagasic heart disease , ( 6 ) depression , ( 7 ) dysphagia with evidence of food residues in the esophagus , ( 8 ) dysphagia with weight loss higher than 15 % of usual weight in the last four months and/or ( 9 ) conditions that may result in low protocol adherence . The intervention will be 100 μg of sodium selenite once daily for 365 consecutive days compared to placebo . The following are the primary outcomes to be measured : ( 1 ) the trajectories of the left ventricular ejection fraction in the follow-up period ; ( 2 ) reduction of heart disease progression rates , with progression defined as a 10 % decrease in left ventricular ejection fraction ; and ( 3 ) rate of hospital admissions attributable to dysrhythmia , heart failure or stroke due to Chagas disease . One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1 . The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes . Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up . DISCUSSION If Se treatment reduces the progression of Chagas cardiopathy , the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost . TRIAL REGISTRATION Clinical Trials.gov ID : NCT00875173 ( registered 20 October 20 2008 ) .

Selenium Treatment

Chagasic Cardiopathy ( STCC )

Se treatment

progression of Chagas cardiopathy

patients with Chagas heart disease

patients with chagasic cardiopathy

age between 18 and 65 years

diabetes mellitus ,

tobacco use ,

alcohol abuse

evidence of nonchagasic heart disease

depression

dysphagia


[ A clinical trial of ultrasound-guided facet joint block in the lumbar spine to treat facet joint related low back pain ] . OBJECTIVE To determine the feasibility and clinical efficacy of ultrasound-guided facet joint injection and nerve block in lumbar facet joint for the treatment of facet-joint related low back pain . METHODS 20 patients with facet-joint pain were randomized into two groups received block blindly ( B group ) or guided by ultrasound ( US group ) respectively . The location of needle tip was confirmed by CT in both groups , and the accuracy was computed afterwards . VAS score , puncture time and one-time puncture success rate ( % ) were recorded . VAS scores and pain remission rates in both groups were recorded at 30 min , 1 d , 2 d , 6 weeks after the block . RESULTS The VAS scores were 3.3 +/- 0.4 in US group and 1.2 +/- 0.3 in B group ( P < 0.05 ) . The puncture time was ( 206 +/- 27 ) s in US group while ( 397 +/- 31 ) s in B group ( P < 0.05 ) . There were 37 facet joint blocks guided by ultrasound , in which 32 were correctly targeted with the first puncture . The success rate is 86.5 % . There were 35 facet joint blocks blindly , in which 11 were correctly targeted with the first puncture . The success rate is 31.4 % . The difference of one-time puncture success rate between the two groups was significant ( P < 0.05 ) . Differences of VAS and pain remission rate at half an hour after facet joint injection between B group and US group were significant ( P < 0.05 ) . There were 8 , 9 , 9 , and 9 patients in US group obtaining a reduction in VAS scores > or = 3 at 30 min , 1 d , 2 d and 6 weeks after the procedure respectively , while the numbers of such patients were 5 , 6 , 5 , 5 in B group ( P > 0.05 ) . After 6 weeks of follow-up , the overall remission rates were ( 72.3 +/- 14.0 ) % in US group , and ( 56.7 +/- 11.0 ) % in B group , there was no significant difference between the two groups ( P > 0.05 ) . CONCLUSION The ultrasound-guided lumbar facet joint injection technique had a high feasibility and accuracy , and had better clinical efficacy than block blindly .

ultrasound-guided facet joint block

ultrasound-guided facet joint injection

nerve block in lumbar facet joint

facet joint blocks guided by ultrasound

facet joint blocks blindly

block blindly

VAS score

VAS scores and pain remission rates

VAS scores

puncture time

success rate

success rate

one-time puncture success rate

VAS and pain remission rate

VAS scores

overall remission rates

facet joint related low back pain ]

facet-joint related low back pain

facet-joint pain


Detection and quantification of the solid component in pulmonary subsolid nodules by semiautomatic segmentation . OBJECTIVE To determine whether semiautomatic volumetric software can differentiate part-solid from nonsolid pulmonary nodules and aid quantification of the solid component . METHODS As per reference standard , 115 nodules were differentiated into nonsolid and part-solid by two radiologists ; disagreements were adjudicated by a third radiologist . The diameters of solid components were measured manually . Semiautomatic volumetric measurements were used to identify and quantify a possible solid component , using different Hounsfield unit ( HU ) thresholds . The measurements were compared with the reference standard and manual measurements . RESULTS The reference standard detected a solid component in 86 nodules . Diagnosis of a solid component by semiautomatic software depended on the threshold chosen . A threshold of -300 HU resulted in the detection of a solid component in 75 nodules with good sensitivity ( 90 % ) and specificity ( 88 % ) . At a threshold of -130 HU , semiautomatic measurements of the diameter of the solid component ( mean 2.4 mm , SD 2.7 mm ) were comparable to manual measurements at the mediastinal window setting ( mean 2.3 mm , SD 2.5 mm [ p = 0.63 ] ) . CONCLUSION Semiautomatic segmentation of subsolid nodules could diagnose part-solid nodules and quantify the solid component similar to human observers . Performance depends on the attenuation segmentation thresholds . This method may prove useful in managing subsolid nodules . KEY POINTS • Semiautomatic segmentation can accurately differentiate nonsolid from part-solid pulmonary nodules • Semiautomatic segmentation can quantify the solid component similar to manual measurements • Semiautomatic segmentation may aid management of subsolid nodules following Fleischner Society recommendations • Performance for the segmentation of subsolid nodules depends on the chosen attenuation thresholds .

semiautomatic segmentation .

semiautomatic volumetric software

detection of a solid component

solid component


Disorder-dissociated effects of fluoxetine on brain function of working memory in attention deficit hyperactivity disorder and autism spectrum disorder . BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) and autism spectrum disorder ( ASD ) are often co-morbid and share performance and brain dysfunctions during working memory ( WM ) . Serotonin agonists modulate WM and there is evidence of positive behavioural effects in both disorders . We therefore used functional magnetic resonance imaging ( fMRI ) to investigate shared and disorder-specific brain dysfunctions of WM in these disorders , and the effects of a single dose of the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine . METHOD Age-matched boys with ADHD ( n = 17 ) , ASD ( n = 17 ) and controls ( n = 22 ) were compared using fMRI during an N-back WM task . Patients were scanned twice , under either an acute dose of fluoxetine or placebo in a double-blind , placebo-controlled randomized design . Repeated-measures analyses within patients assessed drug effects on performance and brain function . To test for normalization effects of brain dysfunctions , patients under each drug condition were compared to controls . RESULTS Under placebo , relative to controls , both ADHD and ASD boys shared underactivation in the right dorsolateral prefrontal cortex ( DLPFC ) . Fluoxetine significantly normalized the DLPFC underactivation in ASD relative to controls whereas it increased posterior cingulate cortex ( PCC ) deactivation in ADHD relative to control boys . Within-patient analyses showed inverse effects of fluoxetine on PCC deactivation , which it enhanced in ADHD and decreased in ASD . CONCLUSIONS The findings show that fluoxetine modulates brain activation during WM in a disorder-specific manner by normalizing task-positive DLPFC dysfunction in ASD boys and enhancing task-negative default mode network ( DMN ) deactivation in ADHD .

fluoxetine

dose of fluoxetine

autism spectrum disorder .

Age-matched

boys

ASD


Effect of orlistat on weight loss , hormonal and metabolic profiles in women with polycystic ovarian syndrome : a randomized double-blind placebo-controlled trial .

orlistat

women

polycystic ovarian syndrome


Comparing antipsychotic treatments for schizophrenia : a health state approach . The overall impact of first and second generation antipsychotics on quality of life and symptoms of people with schizophrenia remains controversial . We applied health state modeling to data from the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) Schizophrenia study , a randomized trial of antipsychotic medications , and evaluated the likelihood of patients moving to more favorable health states over time . We applied K-means clustering to the data to create discrete groupings of patients with symptom and side effect characteristics that were then validated using quality of life measures . We compared cluster distributions across medications at baseline and 6 months after randomization . 1,049 patients were included in the initial cluster analysis . Five health states were identified : ( 1 ) low symptoms and low side effects ( LS + LSE ) ( 2 ) low symptoms and obesity ( LS + Ob ) ( 3 ) high symptoms and low side effects ( HS + LSE ) ( 4 ) high symptoms with depression and akathisia ( HS + Dp + Ak ) and ( 5 ) moderate symptoms and high side effects ( MS + HSE ) . Six-month outcomes among patients randomly assigned to perphenazine , olanzapine , risperidone and quetiapine were compared . At baseline , almost 20 % of patients were in the worst health state ( HS + Dp + Ak ) , with greater decreases at 6 months in this health state for perphenazine ( 9.2 % decrease ) and olanzapine ( 11.1 % ) groups compared to risperidone ( 4.7 % ) and quetiapine ( 6.7 % ) . This study demonstrated that health state analysis can provide insight into the overall clinical state of patients beyond the mere comparison of average scores and largely confirmed original CATIE findings .

antipsychotics

antipsychotic medications

perphenazine , olanzapine , risperidone

quetiapine

perphenazine

olanzapine

risperidone

quality of life

symptoms

schizophrenia

more favorable health states

symptom

side effect characteristics

quality of life measures

depression

akathisia

worst health state

schizophrenia :

people with schizophrenia

1,049 patients


Nicardipine is superior to esmolol for the management of postcraniotomy emergence hypertension : a randomized open-label study . BACKGROUND Emergence hypertension after craniotomy is a well-documented phenomenon for which natural history is poorly understood . Most clinicians attribute this phenomenon to an acute and transient increase in catecholamine release , but other mechanisms such as neurogenic hypertension or activation of the renin-angiotensin-aldosterone system have also been proposed . In this open-label study , we compared the monotherapeutic antihypertensive efficacy of the 2 most titratable drugs used to treat postcraniotomy emergence hypertension : nicardipine and esmolol . We also investigated the effect of preoperative hypertension on postcraniotomy hypertension and the natural history of postcraniotomy hypertension in the early postoperative period . METHODS Fifty-two subjects were prospectively randomized to receive either nicardipine or esmolol as the sole drug for treatment of emergence hypertension at the conclusion of brain tumor resection ( 40 subjects finally analyzed ) . After a uniform anesthetic , standardized protocols of these antihypertensive medications were administered for the treatment of systolic blood pressure ( SBP ) > 130 , with the goal of maintaining SBP < 140 throughout the first postoperative day . In the event of study medication " failure , " a " rescue " antihypertensive ( labetalol or hydralazine ) was used . The O'Brien-Fleming Spending Function was used to calculate the appropriate α value for each interim analysis of the primary outcome ; univariate analysis was performed otherwise , with a 2-sided P < 0.05 considered statistically significant . RESULTS The incidence of nicardipine failure ( 5 % , 95 % confidence interval [ CI ] 0.1 % -24.9 % ) was significantly less than that of esmolol ( 55 % , 95 % CI 31.5 % -76.9 % ) as a sole drug in controlling SBP after brain tumor resection ( difference 99 % CI 13.8 % -75.7 % , P = 0.0012 ) . The presence of preoperative hypertension or the approach to surgery ( open craniotomy versus endonasal transsphenoidal ) had no significant effect on the incidence of failure of the antihypertensive regimen used . We did not observe a difference in the need for opioid therapy for postcraniotomy pain between drug groups ( 99 % CI difference -39.2 % -30.2 % ) . Failure of the study drug predicted the need for rescue drug therapy in the initial 12 hours after discharge from the recovery room ( difference success versus failure = -41.7 % , 99 % CI difference -72.3 % to -1.8 % , P = 0.0336 ) but not during the period 12 to 24 hours after discharge from the recovery room ( difference success versus failure = -27.4 % , 99 % CI difference -63.8 % -9.2 % , P = 0.143 ) . However , in those patients carrying a preoperative diagnosis of hypertension , the need for rescue medication was only different during the period 12 to 24 hours after discharge from the recovery room ( difference normotensive versus hypertensive = -35.4 % , 99 % CI difference -66.9 % to -0.3 % , P = 0.0254 ) . CONCLUSIONS Nicardipine is superior to esmolol for the treatment of postcraniotomy emergence hypertension . This type of hypertension is thought to be a transient phenomenon not solely related to sympathetic activation and catecholamine surge but also possibly encompassing other physiologic factors . For treating postcraniotomy emergence hypertension , nicardipine is a relatively effective sole drug , whereas if esmolol is used , rescue antihypertensive medications should be readily available .

Nicardipine

esmolol

nicardipine and esmolol

nicardipine or esmolol

( labetalol or hydralazine

hypertension

systolic blood pressure ( SBP )

SBP

The incidence of nicardipine failure

of preoperative hypertension

the need for rescue drug therapy

the need for rescue medication

emergence hypertension

hypertension

Fifty-two subjects

hypertension


Effects of aerobic exercise on cognition and hippocampal volume in Alzheimer 's disease : study protocol of a randomized controlled trial ( The FIT-AD trial ) . BACKGROUND Alzheimer 's disease , a global public health issue , accounts for 60 to 80 % of all dementias . Alzheimer 's disease primarily causes cognitive impairment and drugs have only modest short-term effects , highlighting a pressing need to develop effective interventions . Aerobic exercise holds promise for treating cognitive impairment in Alzheimer 's disease through biologically sound mechanisms . Nonetheless , aerobic exercise studies in Alzheimer 's disease are limited with mixed findings . METHODS/DESIGN This pilot randomized controlled trial will investigate the effects of a 6-month , individualized , moderate-intensity cycling intervention ( 20 to 50 minutes per session , 3 times a week ) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer 's disease . The specific aims are to : 1 ) determine the immediate effect of the cycling intervention on cognition in Alzheimer 's disease ; 2 ) examine if the cycling intervention slows cognitive decline in Alzheimer 's disease from baseline to 12 months ; and 3 ) assess the effect of aerobic exercise on hippocampal volume over 12 months . Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control ( low-intensity stretching ) and followed for another 6 months . Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data . Cognition will be measured by the Alzheimer 's disease Assessment Scale-Cognition at baseline before randomization and at 3 , 6 , 9 , and 12 months . Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months . The sample size of 90 will give 80 % power to detect a 2.5-point difference in within-group changes in the Alzheimer 's disease Assessment Scale-Cognition at 6 months for the cycling group . DISCUSSION Findings from this study will address the critical gap of exercise efficacy in Alzheimer 's disease and use of magnetic resonance imaging as an outcome measure in clinical trials . This study will provide a potential treatment that may increase physical function and quality of life and curb the prohibitive costs for the growing dementia population . TRIAL REGISTRATION Primary registration : ( NCT01954550 ; date of registration : 20 September 2013 ) . Secondary registration : ( NCT01954550 ; date of registration : 1 October 2013 ) .

aerobic exercise

Aerobic exercise

aerobic exercise

moderate-intensity cycling intervention

aerobic exercise

cycling

low-intensity stretching

cognition

cognitive decline

Hippocampal volume

exercise efficacy

physical function and quality of life

prohibitive costs

Alzheimer 's disease

Alzheimer 's disease

Alzheimer 's disease

older adults

mild-to-moderate Alzheimer 's disease

Ninety


Secondary analysis of RTOG 9508 , a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases ; poststratified by the graded prognostic assessment ( GPA ) . PURPOSE Radiation Therapy Oncology Group ( RTOG ) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis ( BM ) treated with whole-brain radiation therapy ( WBRT ) and stereotactic radiosurgery ( SRS ) versus WBRT alone . An improved prognostic index , the graded prognostic assessment ( GPA ) has been developed . Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA , the conclusions may vary . METHODS AND MATERIALS In this analysis , 252 of the 331 patients were evaluable by GPA . Of those , 211 had lung cancer . Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database . Multiple Cox regression was used to compare survival between treatment groups , adjusting for GPA . Treatment comparisons within subgroups were performed with the log-rank test . A free online tool ( brainmetgpa.com ) simplified GPA use . RESULTS The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases ; however , there was a benefit for the subset of patients with GPA 3.5 to 4.0 ( median survival time [ MST ] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months , P=.05 ) regardless of the number of metastases . Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS , the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months , respectively . CONCLUSIONS This secondary analysis of predominantly lung cancer patients , consistent with the original analysis , shows no survival advantage for the group overall when treated with WBRT and SRS ; however , in patients with high GPA ( 3.5-4 ) , there is a survival advantage regardless of whether they have 1 , 2 , or 3 BM . This benefit did not extend to patients with lower GPA . Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted .

whole-brain radiation therapy

WBRT plus stereotactic radiosurgery

whole-brain radiation therapy ( WBRT )

stereotactic radiosurgery ( SRS

WBRT alone

RTOG 9508

WBRT

SRS

WBRT

SRS

WBRT

SRS

survival benefit

MST

survival advantage

1-3 brain metastases

252 of the 331 patients

lung cancer

Breast cancer

lung cancer


Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer : results of a randomized phase II neoadjuvant study . PURPOSE Cure rates for localized high-risk prostate cancers ( PCa ) and some intermediate-risk PCa are frequently suboptimal with local therapy . Outcomes are improved by concomitant androgen-deprivation therapy ( ADT ) with radiation therapy , but not by concomitant ADT with surgery . Luteinizing hormone-releasing hormone agonist ( LHRHa ; leuprolide acetate ) does not reduce serum androgens as effectively as abiraterone acetate ( AA ) , a prodrug of abiraterone , a CYP17 inhibitor that lowers serum testosterone ( < 1 ng/dL ) and improves survival in metastatic PCa . The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression . PATIENTS AND METHODS A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa ( N = 58 ) . For the first 12 weeks , patients were randomly assigned to LHRHa versus LHRHa plus AA . After a research prostate biopsy , all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy . RESULTS The levels of intraprostatic androgens from 12-week prostate biopsies , including the primary end point ( dihydrotestosterone/testosterone ) , were significantly lower ( dehydroepiandrosterone , Δ ( 4 ) -androstene-3,17-dione , dihydrotestosterone , all P < .001 ; testosterone , P < .05 ) with LHRHa plus AA compared with LHRHa alone . Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease , with residual T3- or lymph node-positive disease in the majority . CONCLUSION LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone . Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden .

LHRHa with AA

LHRHa

LHRHa plus AA

LHRHa plus AA followed by prostatectomy

serum androgens

levels of intraprostatic androgens

localized high-risk prostate cancer

localized high-risk PCa ( N = 58 )


Sulforaphane treatment of autism spectrum disorder ( ASD ) . Autism spectrum disorder ( ASD ) , characterized by both impaired communication and social interaction , and by stereotypic behavior , affects about 1 in 68 , predominantly males . The medico-economic burdens of ASD are enormous , and no recognized treatment targets the core features of ASD . In a placebo-controlled , double-blind , randomized trial , young men ( aged 13-27 ) with moderate to severe ASD received the phytochemical sulforaphane ( n = 29 ) -- derived from broccoli sprout extracts -- or indistinguishable placebo ( n = 15 ) . The effects on behavior of daily oral doses of sulforaphane ( 50-150 µmol ) for 18 wk , followed by 4 wk without treatment , were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians : the Aberrant Behavior Checklist ( ABC ) , Social Responsiveness Scale ( SRS ) , and Clinical Global Impression Improvement Scale ( CGI-I ) . Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane . After 18 wk , participants receiving placebo experienced minimal change ( < 3.3 % ) , whereas those receiving sulforaphane showed substantial declines ( improvement of behavior ) : 34 % for ABC ( P < 0.001 , comparing treatments ) and 17 % for SRS scores ( P = 0.017 ) . On CGI-I , a significantly greater number of participants receiving sulforaphane had improvement in social interaction , abnormal behavior , and verbal communication ( P = 0.015-0.007 ) . Upon discontinuation of sulforaphane , total scores on all scales rose toward pretreatment levels . Dietary sulforaphane , of recognized low toxicity , was selected for its capacity to reverse abnormalities that have been associated with ASD , including oxidative stress and lower antioxidant capacity , depressed glutathione synthesis , reduced mitochondrial function and oxidative phosphorylation , increased lipid peroxidation , and neuroinflammmation .

Sulforaphane

phytochemical sulforaphane

broccoli sprout extracts

indistinguishable placebo

sulforaphane

Social Responsiveness Scale ( SRS )

Initial scores for ABC and SRS

for SRS

in social interaction

abnormal behavior

verbal communication

depressed glutathione synthesis

predominantly males

young

men

( aged 13-27

moderate to severe ASD

participants receiving sulforaphane


α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer : results from the CONKO-001 study . BACKGROUND Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin ( α-SMA ) expression and stromal density in the peritumoural stroma . The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients . METHODS CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation . Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome . RESULTS High α-SMA expression in tumour stroma was associated with worse patient outcome ( DFS : P=0.05 , OS : P=0.047 ) . A dense stroma reaction was associated with improved disease-free survival ( DFS ) and overall survival ( OS ) in the overall study population ( DFS : P=0.001 , OS : P=0.001 ) . This positive prognostic impact was restricted to patients with no adjuvant treatment ( DFS : P < 0.001 , OS : P < 0.001 ) . In multivariable analysis , α-SMA and stromal density expression were independently predictive factors for survival . CONCLUSIONS Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection . In contrast to former investigations , we found a positive prognostic impact for a dense stroma . This significant influence was restricted to patients who received no adjuvant therapy .

associated with worse patient outcome

A dense stroma reaction

improved disease-free survival ( DFS )

overall survival

positive prognostic impact

factors for survival

negative prognostic

positive prognostic

in pancreatic cancer

162 patients

pancreatic cancer patients


Benefits of an oxygen reservoir cannula versus a conventional nasal cannula during exercise in hypoxemic COPD patients : a crossover trial . BACKGROUND The Oxymizer® is a special nasal cannula that provides a higher luminal diameter in combination with an incorporated oxygen ( O2 ) reservoir . It is assumed that a higher O2 concentration can be delivered breath by breath in order to increase oxygenation . OBJECTIVE We aimed to investigate the effects of the Oxymizer on endurance time in comparison to a conventional nasal cannula ( CNC ) . METHODS Forty-three patients with severe chronic obstructive pulmonary disease ( COPD , age 60 ± 9 years , FEV1 37 ± 16 % pred . ) and indications for LTOT were recruited during pulmonary rehabilitation for this cross-over study . After an initial maximal incremental cycle test , all patients performed 4 cycling endurance time tests at 70 % of their peak work rate ( twice with the Oxymizer and twice with a CNC , in reverse order ) . RESULTS The endurance time was significantly higher when patients cycled while using the Oxymizer in comparison to while using the CNC [ 858 ± 754 vs. 766 ± 652 s ; between-group difference 92 s ( 95 % confidence interval 32-152 ) , p < 0.001 ] . In addition to a longer cycling duration , O2 saturation at isotime was significantly higher with the Oxymizer ( 93.5 ± 5.4 vs. 90.4 ± 5.3 % ; p = 0.027 ) . Furthermore , there was a positive correlation ( r = 0.427 , p = 0.002 ) between the O2 flow rate and improvements in the constant work rate test , showing greater improvements in favor of the Oxymizer in patients with a higher demand for O2 ( ≥ 4 liters/min ) . CONCLUSION We show that O2 delivery via the Oxymizer is superior to a CNC with regard to endurance capacity and oxygenation during exercise in patients with severe COPD . It seems that patients with a higher demand for O2 ( ≥ 4 liters/min ) , in particular , may benefit more from the use of the Oxymizer .

oxygen reservoir cannula

conventional nasal cannula

endurance time

longer cycling duration

hypoxemic COPD patients :

Forty-three patients

chronic obstructive pulmonary disease

age 60 ± 9 years


Administration of subcutaneous buffered lidocaine prior to breast lymphoscintigraphy reduces pain without decreasing lymph node visualization . UNLABELLED Breast lymphoscintigraphy using ( 99m ) Tc-sulfur colloid ( ( 99m ) Tc-SC ) is well established in clinical practice for staging patients with breast carcinoma . Nearly all patients report having pain during the procedure . However , techniques used to minimize pain during breast lymphoscintigraphy are highly variable across institutions . Our study was to determine whether anesthetizing the skin with sodium bicarbonatehether-buffered lidocaine before performing breast lymphoscintigraphy reduced the pain experienced by the patients . The second objective of this study was to evaluate whether anesthetizing the skin with buffered lidocaine changed visualization of lymph nodes . METHODS This prospective , patient-masked and randomized study involved performing breast lymphoscintigraphy in a control group and experimental group of female breast cancer patients . The control group did not receive skin anesthetic before ( 99m ) Tc-SC injections , whereas the experimental group first underwent skin anesthesia with an injection of 2 % sodium bicarbonate-buffered lidocaine . All patients were asked to rate their pain levels , using the National Institutes of Health pain scale , before the procedure and immediately after the injections . The change in pain from baseline was compared between the 2 groups . After the injections , scintigraphic imaging of the axilla was performed , and the number of axillary lymph nodes visualized was recorded . RESULTS No significant difference was found in preprocedural baseline pain from the control group , compared with the experimental group . There was a statistically significant difference in the increase in pain experienced during the procedure between the control group and the experimental group ( P = 0.009 ) . There was no significant difference in the detection of lymph nodes between the control and experimental groups ( P = 0.56 ) . CONCLUSION The results from our study indicate that injecting subcutaneous buffered lidocaine before intradermal injection of ( 99m ) Tc-SC for breast lymphoscintigraphy significantly decreases patient pain without interfering with lymph node visualization .

lidocaine

lymphoscintigraphy

breast lymphoscintigraphy

lidocaine

pain

pain

pain

pain

visualization of lymph nodes .

change in pain from baseline

baseline pain

increase in pain

detection of lymph nodes

patient pain

lymph node visualization .

breast lymphoscintigraphy

breast carcinoma

breast lymphoscintigraphy

breast lymphoscintigraphy

female

breast cancer


Dexmedetomidine pretreatment alleviates propofol injection pain . OBJECTIVE The incidence of propofol injection pain during induction of general anesthesia varies from 28 % to 90 % . This prospective , randomized , double-blind , placebo-controlled study evaluated the effect of dexmedetomidine ( DEX ) for reducing the incidence and severity of propofol injection pain . METHODS Patients undergoing elective surgical procedures were randomly allocated into seven groups of 30 patients each . Experimental treatments were intravenously administered over 10 min ( total volume 10 mL ) prior to intravenous propofol injection , as follows : group I , the control group , was given isotonic saline . Patients in groups II , III , and IV received DEX 0.25 µg/kg , 0.5 µg/kg , or 1.0 µg/kg , respectively , mixed with isotonic saline immediately before propofol injection . Patients in groups V , VI , and VII received DEX as above , but 5 minutes before propofol injection . Propofol consisted of 1 % long-chain triglyceride propofol ( 2.5 mg/kg ) injected at 1 mL/s . RESULTS Median propofol injection pain score was 0.00 ( IQR 0.00-3.00 ) in patients who received 1.0 µg/kg DEX 5 min before the propofol injection ( group VII ) , and only 1 patient ( of 30 ) in this group received a pain score > 2 . The median pain score and number of patients with pain scores > 2 in group VII were both significantly less than in the control ( group I ; p = 0.000 , both ) . There were no differences in either mean arterial pressure or heart rate at any time point after DEX injection among the groups . CONCLUSIONS Pretreatment with intravenous DEX 1 µg/kg 5 min prior to injection of long-chain triglyceride propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection .

Dexmedetomidine

propofol

dexmedetomidine ( DEX )

propofol

isotonic saline .

propofol

propofol injection pain score

arterial pressure

heart rate

propofol injection pain .


Safety and possible effects of low-intensity resistance training associated with partial blood flow restriction in polymyositis and dermatomyositis . INTRODUCTION Our aim was to evaluate the safety and efficacy of a low-intensity resistance training program combined with partial blow flow restriction ( BFR training ) in a cohort of patients with polymyositis ( PM ) and dermatomyositis ( DM ) . METHODS In total , 13 patients with PM and DM completed a 12-week twice a week low-intensity ( that is , 30 % one-repetition-maximum ( 1RM ) ) resistance exercise training program combined with partial blood flow restriction ( BFR ) . Assessments of muscle strength , physical function , quadriceps cross sectional ( CSA ) area , health-related quality of life , and clinical and laboratory parameters were assessed at baseline and after the intervention . RESULTS The BFR training program was effective in increasing the maximal dynamic strength in both the leg-press ( 19.6 % , P < 0.001 ) and knee-extension exercises ( 25.2 % P < 0.001 ) , as well as in the timed-stands ( 15.1 % , P < 0.001 ) and timed-up-and-go test ( -4.5 % , P =0.002 ) . Quadriceps CSA was also significantly increased after the intervention ( 4.57 % , P =0.01 ) . Similarly , all of the components of the Short Form-36 Health Survey , the Health Assessment Questionnaire scores , and the patient- and physician reported Visual Analogue Scale were significantly improved after training ( P < 0.05 ) . Importantly , no clinical evidence or any other self-reported adverse event were found . Laboratory parameters ( creatine kinase and aldolase ) were also unchanged ( P > 0.05 ) after the intervention . CONCLUSIONS We demonstrated that a 12-week supervised low-intensity resistance training program associated with partial blood flow restriction may be safe and effective in improving muscle strength and function as well as muscle mass and health-related quality of life in patients with PM and DM . TRIAL REGISTRATION Clinicaltrials.gov NCT01501019 . Registered November 29 , 2011 .

low-intensity resistance training

partial blood flow restriction ( BFR )

BFR

leg-press

knee-extension exercises

maximal dynamic strength

knee-extension exercises

timed-stands

timed-up-and-go test

Quadriceps CSA

self-reported adverse

polymyositis and dermatomyositis .

with PM and DM completed


A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism . BACKGROUND With rates of autism diagnosis continuing to rise , there is an urgent need for effective and efficient service delivery models . Pivotal Response Treatment ( PRT ) is considered an established treatment for autism spectrum disorder ( ASD ) ; however , there have been few well-controlled studies with adequate sample size . The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group ( PRTG ) for targeting language deficits in young children with ASD . METHODS Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG ( N = 27 ) or psychoeducation group ( PEG ; N = 26 ) for 12 weeks . The PRTG taught parents behavioral techniques to facilitate language development . The PEG taught general information about ASD ( clinical trial NCT01881750 ; http : //www.clinicaltrials.gov ) . RESULTS Analysis of child utterances during the structured laboratory observation ( primary outcome ) indicated that , compared with children in the PEG , children in the PRTG demonstrated greater improvement in frequency of utterances ( F ( 2 , 43 ) = 3.53 , p = .038 , d = 0.42 ) . Results indicated that parents were able to learn PRT in a group format , as the majority of parents in the PRTG ( 84 % ) met fidelity of implementation criteria after 12 weeks . Children also demonstrated greater improvement in adaptive communication skills ( Vineland-II ) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG . CONCLUSIONS This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date . The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children , especially in functional and adaptive communication skills . Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms .

Pivotal Response Treatment Group

Pivotal Response Treatment ( PRT

PRT parent training group ( PRTG )

parents of children with autism

young children

ASD

Fifty-three

children

autism

between 2 and 6 years old


A 5-year randomized trial to compare 1 or 2 implants for implant overdentures . The hypothesis of this 5-y randomized clinical trial was that there would be no significant difference in the satisfaction of edentulous participants with removable complete overdentures attached to 1 or 2 mandibular implants . Secondary aims were to test changes in satisfaction between and within the groups from baseline to 5 y and differences between the groups in implant survival and prosthodontic maintenance over 5 y . Each of the 86 participants ( mean age , 67 y ) was randomly allocated to receive either 1 implant in the midline ( group 1 ) or 2 implants in the canine areas ( group 2 ) attached to a mandibular overdenture opposing a maxillary complete denture . Satisfaction was self-assessed by participants on a visual analog scale at baseline prior to implants , as well as at 2 mo and 1 , 3 , and 5 y with implant overdentures , whereas implant survival and prosthodontic maintenance were assessed by clinical examination . After 5 y , 29 participants in group 1 and 33 in group 2 were available , with most dropouts due to death . Satisfaction with the implant denture after 5 y was significantly ( P < 0.001 ) higher than at baseline in both groups and remained with no significant difference ( P = 0.32 ) between the groups . No implants failed in group 1 but 5 failed before loading in 4 participants in group 2 . Most participants required maintenance or occasionally denture replacement , and although differences between the groups were not statistically significant , group 1 experienced almost twice as many fractured dentures usually adjacent to the implant attachment . We conclude that there were no significant differences after 5 y in satisfaction or survival of implants with mandibular overdentures retained by 1 implant or 2 implants . Additional research is required to confirm long-term treatment effectiveness of single-implant dentures and the implications of prosthetic maintenance with implant overdentures ( ClinicalTrials.gov : NCT02117856 ) .

implants

mandibular implants

1 implant in the midline

2 implants in the canine areas

satisfaction

satisfaction

implant survival

Satisfaction was self-assessed

visual analog scale

death .

Satisfaction

failed

maintenance

denture replacement

fractured dentures

satisfaction or survival of implants

effectiveness

implant overdentures

( mean age , 67 y )


The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients . BACKGROUND Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro-esophageal reflux disease ( GERD ) patients as reflected by an increase in baseline impedance . The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor ( PPI ) PPI therapy on baseline impedance and heartburn severity in GERD patients . METHODS Forty-seven GERD patients randomized to endoscopic fundoplication ( n = 32 ) or PPI therapy ( n = 15 ) , and 29 healthy controls were included . Before randomization and 6 months after treatment , baseline impedance was obtained during 24-h pH-impedance monitoring . Heartburn severity was evaluated using the GERD-HRQL questionnaire . KEY RESULTS Before treatment , baseline impedance in GERD patients was lower than in healthy controls ( p < 0.001 ) . Antireflux therapy increased baseline impedance ( from 1498 [ IQR 951-2472 ] to 2393 [ IQR 1353-3027 ] Ω , p = 0.001 ) , however it only led to a partial recovery when compared to healthy controls ( 2393 [ IQR 1353-3027 ] vs 2983 [ 2335-3810 ] Ω , p < 0.01 ) . The effect of both treatment options was not significantly different ( p = 0.13 ) despite the increased number of non-acid reflux events in the PPI group . No correlation was found between baseline impedance and GERD symptoms before or after treatment . CONCLUSIONS & INFERENCES Reduction in acid reflux by endoscopic fundoplication or PPI therapy leads to an increase in baseline impedance in GERD patients , likely to reflect recovery of mucosal integrity . The impact of non-acid reflux events on esophageal mucosal integrity may be limited as no difference in the increase in baseline impedance was observed after both treatment options . The lack of association between impedance baseline and heartburn severity indicates that other factors may contribute to heartburn perception in GERD .

endoscopic fundoplication

proton pump inhibitors

endoscopic fundoplication

endoscopic fundoplication

PPI therapy

baseline impedance and

severity

increase in baseline impedance .

GERD

GERD patients

baseline impedance in


Intratunnel versus extratunnel autologous hamstring double-bundle graft for anterior cruciate ligament reconstruction : a comparison of 2 femoral fixation procedures . BACKGROUND Anatomic double-bundle anterior cruciate ligament ( ACL ) reconstruction provides excellent results for restoring normal kinematics to the knee . Nevertheless , strong evidence supporting an ideal method for fixation of the ACL graft is lacking . HYPOTHESIS Intratunnel femoral fixation of the ACL graft via a cross-pin fixation technique would provide better clinical and objective results than the extratunnel femoral fixation with cortical buttons . STUDY DESIGN Randomized clinical trial ; Level of evidence , 2 . METHODS Seventy patients with a unilateral ACL-deficient knee were randomly assigned to 1 of 2 femoral fixation groups . Group A ( 35 patients ) was fixed with 2 bioabsorbable Rigidfix pins , 1 cross-pin per bundle , while group B ( 35 patients ) was secured with 1 EndoButton cortical button per bundle . All femoral tunnels were created via an anteromedial portal , and a bioabsorbable Biointrafix interference screw was used for tibial fixation for both groups . The evaluation of the patients was performed by history details , clinical examination findings , measurement of the joint laxity by KT-1000 arthrometer , and use of validated patient outcome questionnaires . Statistical analysis was carried out with Fisher exact and Mann-Whitney U tests , with P < .05 considered the cutoff level of significance . RESULTS At a mean follow-up of 30 months , 34 and 32 patients of group A and B , respectively , were available for evaluation . There were no statistically significant differences between the treatment groups regarding the subjective and objective outcomes , except for KT-1000 arthrometer values . The median KT-1000 value of patients in the cross-pin fixation group was 1.30 mm , while the median value in the cortical button fixation group was 1.95 mm ( P < .001 ) . Four patients with ACL grafts that were fixed with cortical buttons demonstrated failure of stability via the instrumented knee laxity testing , while patients from the other group had no failures . CONCLUSION Intratunnel femoral fixation of the double-bundle ACL graft from the cross-pin fixation technique provided better instrumented knee laxity results than did the extratunnel femoral fixation with cortical buttons . Future larger studies comparing these 2 techniques should be conducted to ensure the availability of stronger evidence supporting the findings of this study .

KT-1000 arthrometer

cortical button fixation

cortical buttons

restoring normal kinematics to the knee

median KT-1000 value

knee laxity


Matching doses of distraction with child risk for distress during a medical procedure : a randomized clinical trial . BACKGROUND Parents often want to provide support to their children during medical procedures , but not all parents are effective in providing distraction after brief training . OBJECTIVE The aim of this study was to investigate the effects of three doses of distraction intervention for children at high and medium risk for procedure-related distress . METHODS Children undergoing scheduled intravenous insertions for diagnostic or treatment purposes and their parents participated . A computerized application , Children , Parents and Distraction , was used to predict distress risk . Doses of intervention were basic ( parents trained on providing distraction ) , enhanced ( basic training plus tailored instructions , environmental modifications , and support and guidance from the research assistant ) , and professional ( a trained research assistant provided distraction ) . Outcome measures were Observational Scale of Behavioral Distress-Revised for behavioral distress , Oucher for self-reported pain , parent report of child distress , and salivary cortisol for physiological distress . RESULTS A total of 574 children , ages 4-10 , and their parents participated . The Children , Parents and Distraction predicted that the risk for distress was high for 156 children , medium for 372 , and low for 46 . Children predicted to have higher risk for distress displayed more behavioral distress ( p < .01 ) . Children in the medium-risk group who had the professional intervention displayed significantly less behavioral distress ( p < .001 ) . Children in the high-risk group tended to have less behavioral distress when receiving the professional intervention ( p = .07 ) . There were no significant group differences for self-report of pain , parent report of distress , or cortisol levels . DISCUSSION Some parents may need additional training in providing distraction to their children during procedures , and some children at medium and high risk for distress may need professional support . Parents should be asked about their preferences in acting as the distraction coach and , if willing , be provided as much training and support as possible in the clinical situation .

doses of distraction intervention

risk for distress

behavioral distress

behavioral distress

self-report of pain ,

parent report of distress

cortisol levels

child

risk for distress

children

children

ages 4-10


Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes . AIM To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes ( T2DM ) . METHODS This randomized , multinational , open-label trial included subjects treated for T2DM with metformin ± sulphonylurea , who had glycated haemoglobin ( HbA1c ) levels of 7.5-12 % . Subjects were assigned to 24 weeks of insulin glargine , titrated to target fasting plasma glucose of 4.0-5.5 mmol/L or liraglutide , escalated to the highest approved clinical dose of 1.8 mg daily . The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c < 7 % . RESULTS The mean [ standard deviation ( s.d . ) ] age of the participants was 57 ( 9 ) years , the duration of diabetes was 9 ( 6 ) years , body mass index was 31.9 ( 4.2 ) kg/m ( 2 ) and HbA1c level was 9.0 ( 1.1 ) % . Equal numbers ( n = 489 ) were allocated to glargine and liraglutide . Similar numbers of subjects in both groups attained an HbA1c level of < 7 % ( 48.4 vs. 45.9 % ) ; therefore , superiority of glargine over liraglutide was not observed ( p = 0.44 ) . Subjects treated with glargine had greater reductions of HbA1c [ -1.94 % ( 0.05 ) and -1.79 % ( 0.05 ) ; p = 0.019 ] and fasting plasma glucose [ 6.2 ( 1.6 ) and 7.9 ( 2.2 ) mmol/L ; p < 0.001 ] than those receiving liraglutide . The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events ( p < 0.001 ) . The mean ( s.d . ) weight change was +2.0 ( 4.0 ) kg for glargine and -3.0 ( 3.6 ) kg for liraglutide ( p < 0.001 ) . Symptomatic hypoglycaemia was more common with glargine ( p < 0.001 ) . A greater number of subjects in the liraglutide arm withdrew as a result of adverse events ( p < 0.001 ) . CONCLUSION Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially , with nearly half of subjects reaching target levels of 7 % .

insulin glargine

liraglutide

insulin glargine

liraglutide

insulin glargine

liraglutide

glargine

liraglutide


Topiramate impairs cognitive function in methadone-maintained individuals with concurrent cocaine dependence . Topiramate is being investigated as a potential pharmacotherapy for the treatment of addictive disorders . However , its cognitive side effects raise concerns about its use , especially in populations with cognitive impairment , such as persons with chronic substance use disorders . This study investigated topiramate 's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind , randomized , controlled trial of topiramate for cocaine dependence treatment . After 5 weeks of stabilization on daily oral methadone ( M = 96 mg ) , participants were randomized to topiramate ( n = 18 ) or placebo ( n = 22 ) . Cognitive testing took place at 2 time points : study weeks 4 through 5 to assess baseline performance and 10 to 13 weeks later to assess performance during stable dosing ( 300 mg topiramate or placebo ) . All participants were maintained on methadone at both testing times , and testing occurred 2 hours after the daily methadone plus topiramate/placebo administration . The topiramate and placebo groups did not differ on sex , level of education , premorbid intelligence , methadone dose , or illicit drug use . Topiramate slowed psychomotor and information processing speed , worsened divided attention , reduced n-back working memory accuracy , and increased the false alarm rate in recognition memory . Topiramate had no effects on visual processing , other measures of psychomotor function , risk-taking , self-control , Sternberg working memory , free recall , and metamemory . These findings indicate that topiramate may cause cognitive impairment in this population . This effect may limit its acceptability and use as a treatment in individuals with chronic opioid and cocaine use disorders , among whom preexisting cognitive impairments are common . ( PsycINFO Database Record

Topiramate

Topiramate

pharmacotherapy

topiramate 's

topiramate

methadone

topiramate

placebo

topiramate

placebo

topiramate/placebo

topiramate

placebo

Topiramate

Topiramate

cognitive impairment

may limit its acceptability

concurrent cocaine dependence

chronic substance use disorders

dually dependent on cocaine and opioids

18 )


Parent-implemented social intervention for toddlers with autism : an RCT . OBJECTIVES To compare the effects of two 9-month parent-implemented interventions within the Early Social Interaction ( ESI ) Project . Both individual-ESI , offered 2 or 3 times per week at home or in the community , and group-ESI , offered once per week in a clinic , taught parents how to embed strategies to support social communication throughout everyday activities . METHODS Participants in the randomized controlled trial included 82 children diagnosed with autism spectrum disorder at 16 to 20 months . Children were matched on pretreatment nonverbal developmental level and pairs were randomly assigned to treatment condition . Child outcomes included measures of social communication , autism symptoms , adaptive behavior , and developmental level . Child outcomes are reported from baseline to the end of the 9-month interventions . RESULTS Children in individual-ESI showed differential change on a standardized examiner-administered observational measure of social communication , as they improved at a faster rate than children in group-ESI . Individual-ESI also showed differential efficacy on a parent report measure of communication , daily living , and social skills , as they showed improvement or stability , whereas group-ESI led to worsening or no significant change on these skills . Finally , individual-ESI showed differential change on examiner-administered measures of receptive language skills , as children in individual-ESI improved significantly , whereas group-ESI showed no change . CONCLUSIONS These findings support the efficacy of individual-ESI compared with group-ESI on child outcomes , suggesting the importance of individualized parent coaching in natural environments . The efficacy of a parent-implemented intervention using little professional time has potential for community viability , which is particularly important in light of the lack of main effects on child outcomes of most other parent-implemented interventions .

Parent-implemented social intervention

parent-implemented interventions

individual-ESI

group-ESI

individual-ESI

group-ESI

Individual-ESI

group-ESI

individual-ESI

group-ESI

individual-ESI

group-ESI

individualized parent coaching

parent-implemented intervention

parent-implemented interventions

receptive language skills

toddlers

autism

children

autism spectrum disorder

16 to 20 months


Effect of fermented milk containing Lactobacillus casei strain Shirota on constipation-related symptoms and haemorrhoids in women during puerperium . Constipation and haemorrhoids are common complaints after childbirth . The objective of this pilot study was to evaluate impact of fermented milk containing Lactobacillus casei strain Shirota ( LcS ) on stool consistency and frequency , constipation-related symptoms and quality of life , and incidence of haemorrhoids in women during puerperium . Forty women who had natural childbirth were randomised to group consuming either one bottle/day of fermented milk containing at least 6.5×109 cfu of LcS , or placebo , for 6 weeks after childbirth . Subjects filled in a diary on their bowel habits including number of bowel movement , stool consistency and incidence of haemorrhoids , and answered questionnaires on constipation-related symptoms ( PAC-SYM ) and quality of life ( PAC-QOL ) during the study period . The probiotic group showed the better scores on overall PAC-SYM ( P=0.013 ) , PAC-SYM subscales of abdominal symptoms ( P=0.043 ) and rectal symptoms ( P=0.031 ) , and PAC-QOL satisfaction subscale ( P=0.037 ) in comparison with the placebo group . In the probiotic group , two to four subjects experienced haemorrhoids during the first 3 weeks of treatment . The number decreased in week 4 and no one had haemorrhoids on most days in week 5-6 . In the placebo group , on average four subjects had haemorrhoids from the beginning , and no obvious change was observed until week 6 . No statistically significant effect was observed on stool consistency and frequency . The study products did not cause any adverse event in the subjects . Results of this study indicate that continuous consumption of fermented milk containing LcS might alleviate constipation-related symptoms , provide satisfactory bowel habit and result in earlier recovery from haemorrhoids in women during puerperium . Nonetheless , there are several limitations in interpretation of the results attributed to the study design , including lack of baseline data . Further study is required in order to confirm the efficacy .

Constipation and haemorrhoids

stool consistency and frequency

constipation-related symptoms

quality of life

incidence of haemorrhoids

women during puerperium .

constipation-related symptoms

natural childbirth

placebo

during puerperium


Prospective randomized comparison between transperitoneal laparoscopic pyeloplasty and retroperitoneoscopic pyeloplasty for primary ureteropelvic junction obstruction . BACKGROUND AND OBJECTIVES To compare laparoscopic transperitoneal versus retroperitoneoscopic pyeloplasty for primary ureteropelvic junction obstruction in a prospective randomized manner and assess overall results with long-term follow-up . METHODS In this prospective study , from 2008 to 2012 , 112 cases of primary ureteropelvic junction obstruction were randomized in a 1:1 ratio into 2 groups . Group I included patients who underwent transperitoneal laparoscopic pyeloplasty , and group II consisted of patients who underwent retroperitoneoscopic laparoscopic pyeloplasty . Demographic and clinical characteristics and postoperative and operative data were collected and analyzed . The statistical analysis was performed with the Fisher exact test , χ2 test , and Mann-Whitney U test for independent groups , and P < .05 was considered statistically significant . RESULTS The total operative time and intracorporeal suturing time were significantly higher in group II than in group I ( P < .001 ) . The visual analog scale score for pain on postoperative day 1 and the requirement for tramadol were significantly higher in group I than in group II ( P=.004 ) . The hospital stay and the rate of temporary ileus were significantly greater ( P < .036 and P < .02 , respectively ) in group I than in group II . The success rate of transperitoneal laparoscopic pyeloplasty versus retroperitoneoscopic laparoscopic pyeloplasty was 96.4 % versus 96.6 % with a mean follow-up period of 30.75±4.85 months versus 30.99±5.59 months ( P < .88 ) . CONCLUSION Transperitoneal laparoscopic pyeloplasty is associated with significantly greater postoperative pain , a higher tramadol dose , a higher rate of ileus , and a longer hospital stay in comparison with retroperitoneoscopic laparoscopic pyeloplasty . Although the operative time for retroperitoneoscopic laparoscopic pyeloplasty is significantly longer , the success rate remains the same for both procedures .

retroperitoneoscopic pyeloplasty

laparoscopic transperitoneal

retroperitoneoscopic pyeloplasty

The total operative time

intracorporeal suturing time

The visual analog scale score for pain

hospital stay

rate of temporary ileus

The success rate


Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer : final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12 . BACKGROUND Zoledronic acid ( ZOL ) plus adjuvant endocrine therapy significantly improved disease-free survival ( DFS ) at 48- and 62-month follow-up in the ABCSG-12 trial . We present efficacy results of a final additional analysis after 94.4 months . PATIENTS AND METHODS Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with < 10 positive lymph nodes , and were scheduled for standard goserelin therapy . All 1803 patients received goserelin ( 3.6 mg every 28 days ) and were randomized to tamoxifen ( 20 mg/days ) or anastrozole ( 1 mg/days ) , both with or without ZOL ( 4 mg every 6 months ) for 3 years . The primary end point was DFS ; recurrence-free survival and overall survival ( OS ) were secondary end points . RESULTS After 94.4-month median follow-up ( range , 0-114 months ) , relative risks of disease progression [ hazard ratio ( HR ) = 0.77 ; 95 % confidence interval ( CI ) 0.60-0.99 ; P = 0.042 ] and of death ( HR = 0.66 ; 95 % CI 0.43-1.02 ; P = 0.064 ) are still reduced by ZOL although no longer significant at the predefined significance level . Overall , 251 DFS events and 86 deaths were reported . Absolute risk reductions with ZOL were 3.4 % for DFS and 2.2 % for OS . There was no DFS difference between tamoxifen alone versus anastrozole alone , but there was a pronounced higher risk of death for anastrozole-treated patients ( HR = 1.63 ; 95 % CI 1.05-1.45 ; P = 0.030 ) . Treatments were generally well tolerated , with no reports of renal failure or osteonecrosis of the jaw . CONCLUSION These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment , and this benefit is maintained long-term . CLINICALTRIALSGOV NCT00295646 ( http : //www.clinicaltrials.gov/ct2/results ? term=00295646 ) .

Zoledronic acid

tamoxifen

Zoledronic acid ( ZOL )

plus adjuvant endocrine therapy

goserelin ( 3.6 mg every 28 days )

anastrozole ( 1 mg/days )

ZOL

premenopausal early breast cancer :

Austrian Breast and Colorectal Cancer

women


Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control . BACKGROUND Mass drug administration ( MDA ) with azithromycin , carried out for the control of blinding trachoma , has been linked to reduced mortality in children . While the mechanism behind this reduction is unclear , it may be due , in part , to improved nutritional status via a potential reduction in the community burden of infectious disease . To determine whether MDA with azithromycin improves anthropometric indices at the community level , we measured the heights and weights of children aged 1 to 4 years in communities where one ( single MDA arm ) or three annual rounds ( annual MDA arm ) of azithromycin had been distributed . METHODS Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm . Mean height-for-age , weight-for-age and weight-for-height z scores were compared between treatment arms . RESULTS No significant differences in mean height-for-age , weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms , nor was there a significant reduction in prevalence of stunting , wasting or underweight between arms . CONCLUSIONS Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia . This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status .

mass drug administration

azithromycin

azithromycin

MDA with azithromycin

azithromycin

MDA with azithromycin

azithromycin MDA

heights and weights

Mean height-for-age

weight-for-age

weight-for-height z scores

significant differences

mean height-for-age

weight-for-age

weight-for-height z scores

significant reduction

anthropometric outcomes

children

trachoma

children

children aged 1 to 4 years

azithromycin

children