Can simvastatin improve erectile function and health-related quality of life in men aged ≥40 years with erectile dysfunction ? Results of the Erectile Dysfunction and Statins Trial [ ISRCTN66772971 ] . OBJECTIVE To evaluate the effectiveness and cost-effectiveness of simvastatin on erectile function and health-related quality of life in men aged ≥40 years with erectile dysfunction ( ED ) . PATIENTS AND METHODS ED is common in men aged ≥40 years and impacts upon their overall health-related quality of life and that of their partners . Men aged ≥40 years who were not receiving lipid lowering or anti-hypertensive medication and not at high cardiovascular risk were recruited from 10 general practices in the East of England . In total , 173 eligible men with untreated ED were randomized to double-blind treatment with 40 mg of simvastatin or placebo once daily for 6 months . Data were collected at three points over 30 weeks . The main outcome was erectile function ( International Index of Erectile Function-5 score ) . Secondary outcomes included male ED-specific quality of life ( MED-QoL ) , quality-adjusted life years ( QALYs ) using the generic Euroqol measure ( EQ-5D ) , endothelial function , cardiovascular risk , cholesterol and health service costs . RESULTS There was no significant difference in erectile function between the simvastatin and placebo groups ( mean change , 1.28 vs 0.07 , z = 1.1 , p = 0.27 ) , although a significant improvement in MED-QoL was observed ( 5 % vs 2 % , z = 2.09 , p = 0.04 ) . Both 10-year cardiovascular risk and low-density lipoprotein were reduced ( cardiovascular risk , z = -3.67 , p < 0.001 ; low-density lipoprotein , z = -5.46 , p < 0.001 ) , with no consistent change in endothelial function . The frequency of sexual encounters is correlated with improved erectile function . The joint distribution of costs and QALY benefits indicates that the probability of simvastatin being cost-effective for willingness-to-pay thresholds of £20,000 and £30,000 is 86 % and 83 % , respectively . CONCLUSIONS Identifying men with ED provides an opportunity to modify future cardiovascular risk and to improve MED-QoL by treating them with 40 mg of simvastatin . The joint analysis of costs and QALY benefits suggests that there is high probability that simvastatin is a cost-effective strategy in men with ED . The findings could influence urological and primary care practice by including questions on ED during routine consultations and relevant clinical protocols . This provides an opportunity to impart lifestyle advice .

simvastatin

endothelial function

cardiovascular risk

cholesterol

health service

erectile function

10-year cardiovascular risk

low-density lipoprotein

endothelial function

frequency of sexual encounters

joint distribution of costs

QALY benefits

cost-effective

Men

≥40 years

anti-hypertensive

men

untreated ED


Effectiveness of web-based tailored smoking cessation advice reports ( iQuit ) : a randomized trial . AIMS To determine whether web-based tailored cessation advice , based on social cognitive theory and the perspectives on change model , was more effective in aiding a quit attempt than broadly similar web-based advice that was not tailored . DESIGN Participants were allocated randomly to one of two groups , to receive either a cessation advice report and progress report that were tailored to individual-level characteristics or a cessation advice report that presented standardized ( non-tailored ) content . Tailoring was based on smoking-related beliefs , personal characteristics and smoking patterns , self-efficacy and outcome expectations . SETTING Participant enrolment and baseline assessments were conducted remotely online via the study website , with the advice reports presented by the same website . PARTICIPANTS Participants ( n = 1758 ) were visitors to the QUIT website who were based in the United Kingdom , aged 18 years or over and who smoked cigarettes or hand-rolled tobacco . MEASUREMENTS Follow-up assessments were made at 6 months by telephone interview . The primary outcome measure was self-reported 3 months prolonged abstinence , and secondary outcomes were 1 month prolonged abstinence , 7-day and 24-hour point prevalence abstinence . FINDINGS The intervention group did not differ from the control group on the primary outcome ( 9.1 % versus 9.3 % ; odds ratio = 1.02 95 % confidence interval 0.73-1.42 ) or on any of the secondary outcomes . Intervention participants gave more positive evaluations of the materials than control participants . CONCLUSIONS A web-based intervention that tailored content according to smoking-related beliefs , personal characteristics and smoking patterns , self-efficacy and outcome expectations , was not more effective than web-based materials presenting broadly similar non-tailored information .

web-based tailored smoking cessation

baseline assessments

smoking cessation


Pilot randomized controlled dosing study of cranberry capsules for reduction of bacteriuria plus pyuria in female nursing home residents .

cranberry capsules

bacteriuria plus pyuria

female


The acute effects of fluid intake on urine specific gravity and fluid retention in a mildly dehydrated state . Many athletes arrive at training sessions and competitions in a mildly hypohydrated ( HYPO ) state and are instructed to drink fluids before exercise to reach a euhydrated ( HYD ) state . Ten recreational athletes ( 6 women , 4 men ; 71.9 ± 4.6 kg , 25.2 ± 0.9 years ) participated in the studies to examine ( a ) the day-to-day variability of morning urine specific gravity ( USG ) , ( b ) the effects of consuming 600 ml of water on the hydration status of HYD and HYPO ( USG > 1.020 ) subjects , and ( c ) the effects of consuming water ( W ) , salt-water ( SW , 40 mM Na ) , a carbohydrate-electrolyte solution with 3 % or light carbohydrate ( CES-L , 20 mM Na ) or a CES with 6 % carbohydrate ( CES , 20 mM Na ) on the hydration status of HYPO subjects . The hydration status was assessed with USG and body mass measures and urine volume collections . The day-to-day variability in morning USG ( coefficient of variation = 0.2 ± 0.1 % ) was low and the responses to 600 ml of W ingestion were repeatable . Pretrial USG was 1.022 ± 0.001 in the HYPO trial and decreased < 1.020 by 45 minutes ( 1.013 ± 0.003 ) . In the CES study , HYPO subjects reached HYD status at 45 minutes in all conditions ( W 1.013 ± 0.003 , SW 1.013 ± 0.003 , CES-L 1.011 ± 0.003 , CES 1.017 ± 0.004 ) because salt or CES ingestion did not affect fluid retention ( W 68 % , SW 72 % , CES-L 68 % , CES 76 % ) . This study demonstrated that mildly HYPO subjects could reach euhydration within 45 minutes of the ingestion of 600 ml of W or a combination of salt and CES solutions . Following this practice will minimize the incidence of starting a practice or competition hypohydrated .

600 ml of water

water ( W )

salt-water

CES with 6 % carbohydrate

salt

mildly dehydrated state

HYPO

Ten

6 women , 4 men

25.2 ± 0.9 years


The effects of different intensities and durations of the general warm-up on leg press 1RM . The precision of maximum strength assessments ( 1 repetition maximum ; 1RM ) is important to evaluate the functional capacity and to prescribe and monitor the training load . Several factors can affect the precision of 1RM tests , including the warm-up procedure . General and specific warm-up routines are recommended to enhance performance . The effects of a specific warm-up have already been acknowledged in improving performance . However , the effects of a general warm-up ( GWU ) are unclear but seem to depend on its ability to increase muscle temperature while avoiding fatigue . Furthermore , temperature elevation is dependent on both the duration and the intensity of the activity , which may eventually affect 1RM performance . The objective of this study was to investigate the effect of different intensities and durations of GWU on 1RM performance . Sixteen strength-trained men were tested for 1RM leg press after 4 GWU conditions after specific warm-up : short duration and low intensity ( SDLI ; i.e. , 5 minutes at 40 % V [ Combining Dot Above ] O2max ) , long duration and low intensity ( LDLI ; i.e. , 15 minutes at 40 % V [ Combining Dot Above ] O2max ) , short duration and moderate intensity ( SDMI ; i.e. , 5 minutes at 70 % V [ Combining Dot Above ] O2max ) , long duration and moderate intensity ( LDMI ; i.e. , 15 minutes at 70 % V [ Combining Dot Above ] O2max ) , and the control ( CTRL ) no-GWU condition . Leg press 1RM values were higher ( on average 3 % ) when subjects performed LDLI ( 367.8 ± 70.1 kg ; p = 0.01 ) , compared with the other 4 conditions . After the LDMI condition , 1RM values were lower ( on average -4 % ) than in the other 4 conditions ( 345.6 ± 70.5 kg ; p = 0.01 ) . There were no differences between SDMI , SDLI , and CTRL ( 359.4 ± 69.2 kg , 359.1 ± 69.3 kg , and 359.4 ± 70.4 kg , respectively ; p = 0.99 ) . According to our results , long-duration low-intensity general warm-up seems be appropriately to improve 1RM performance in strength-trained individuals .

general warm-up on leg press 1RM

general warm-up ( GWU )

effects

on leg press 1RM .

effect

1RM leg press

Leg press 1RM values

Sixteen

strength-trained

men


The effects of orthotic heel lifts on Achilles tendon force and strain during running . This study assessed the effects of orthotic heel lifts on Achilles tendon ( AT ) force and strain during running . Ten females ran barefoot over a force plate in three conditions : no heel lifts ( NHL ) , with 12 mm heel lifts ( 12HL ) and with 18 mm heel lifts ( 18HL ) . Kinematics for the right lower limb were collected ( 200 Hz ) . AT force was calculated from inverse dynamics . AT strain was determined from kinematics and ultrasound images of medial gastrocnemius ( 50 Hz ) . Peak AT strain was less for 18HL ( 5.5 ± 4.4 % ) than for NHL ( 7.4 ± 4.2 % ) ( p = .029 , effect size [ ES ] = 0.44 ) but not for 12HL ( 5.8 ± 4.8 % ) versus NHL ( ES = 0.35 ) . Peak AT force was significantly ( p = .024 , ES = 0.42 ) less for 18HL ( 2382 ± 717 N ) than for NHL ( 2710 ± 830 N ) but not for 12HL ( 2538 ± 823 N , ES = 0.21 ) . The 18HL reduced ankle dorsiflexion but not flexion-extension ankle moments and increased the AT moment arm compared with NHL . Thus , 18HL reduced force and strain on the AT during running via a reduction in dorsiflexion , which lengthened the AT moment arm . Therefore , heel lifts could be used to reduce AT loading and strain during the rehabilitation of AT injuries .

orthotic heel lifts

orthotic heel lifts

no heel lifts

12 mm heel lifts

18 mm heel lifts

Achilles tendon force and strain

Achilles tendon ( AT ) force and strain

Kinematics for the right lower limb

AT strain

Peak AT strain

Ten

females


The effect of magnesium added to levobupivacaine for femoral nerve block on postoperative analgesia in patients undergoing ACL reconstruction . PURPOSE The aim of this prospective randomised double-blind study is to investigate the effect of magnesium added to local anaesthetics on postoperative VAS scores , total opioid consumption , time to first mobilisation , patient satisfaction and rescue analgesic requirements in arthroscopic ACL reconstruction surgery . METHODS A total of 107 American Society of Anaesthesiologists physical status grade I and II patients between 18 and 65 years of age who were scheduled to undergo elective anterior crucial ligament ( ACL ) reconstruction with hamstring autografts were enrolled in the study . The patients were randomly allocated to Groups L ( n = 51 ) and LM ( n = 56 ) using the closed-envelope method . Group LM was administered 19 ml of 0.25 % levobupivacaine and 1 ml of 15 % magnesium sulphate , while Group L was administered 20 ml of 0.25 % levobupivacaine for femoral blockade . General anaesthesia was administered using laryngeal airway masks following neural blockade in both groups . The patients were evaluated for heart rate and mean arterial pressure , oxygen saturation , visual analogue score ( VAS ) , verbal rating scale ( VRS ) , rescue analgesic requirements , total opioid consumption , side effects and time to first mobilisation at the 1st , 2nd , 4th , 6th , 12th and 24th hours postoperatively . RESULTS There was no statistically significant difference in terms of demographic data , mean arterial pressure , heart rate or oxygen saturation between groups . The area under the curve VAS and VRS scores were lower at 4 , 6 , 12 and 24 h in Group LM ( p = 0.001 , p = 0.016 , respectively ) . The rescue analgesic requirement and the total opioid consumption were significantly lower in Group LM ( p = 0.015 , p = 0.019 , respectively ) . The time to first mobilisation and the Likert score ( completely comfortable ; quite comfortable ; slight discomfort ; painful ; very painful ) were higher , and the block onset time was lower in Group LM ( p = 0.014 and p = 0.012 , respectively ) . There was no difference in terms of side effects . CONCLUSIONS The addition of magnesium to levobupivacaine prolongs the sensory and motor block duration without increasing side effects , enhances the quality of postoperative analgesia and increases patient satisfaction ; however , the addition of magnesium delays the time to first mobilisation and decreases rescue analgesic requirements .

magnesium

levobupivacaine

magnesium

levobupivacaine

magnesium sulphate

0.25 % levobupivacaine

magnesium

heart rate and mean arterial pressure

oxygen saturation

rescue analgesic requirements

total opioid consumption

area under the curve VAS and VRS scores

block onset time

ACL reconstruction

between 18 and 65 years of age


Effect of whole body vibration on stereotypy of young children with autism . The objective of this case was report on the effects of acute whole body vibration exposure on stereotyped behaviour of young children with autism . Four young boys ( ages 4-5 years ) diagnosed with autism participated . The children were participants in an early intensive behavioural intervention clinic and during downtimes stood on a whole body vibration platform with the machine turned off ( control condition ) and on ( treatment condition ) for three to four , 30 s periods ( frequency=28 Hz ; amplitude 0.97 mm ) . The outcome measure was frequency of stereotypic behaviour , which was evaluated for 5 min before and after standing on the vibration platform . The results revealed that whole body vibration was not able to uniformly decrease the rates of all types of stereotypy ; that is , some stereotypy decreased while others were unchanged . Subjectively , the children enjoyed whole body vibration which was easy to integrate into the behavioural programme .

whole body vibration

whole body vibration

control condition

stereotypy

effects

stereotyped behaviour

frequency of stereotypic behaviour

rates of all types of stereotypy ;

stereotypy

easy

young children with autism .


Comparing microvascular alterations during minimal extracorporeal circulation and conventional cardiopulmonary bypass in coronary artery bypass graft surgery : a prospective , randomized study . OBJECTIVES Minimal extracorporeal circulation ( MECC ) has been introduced in coronary artery bypass graft ( CABG ) surgery , offering clinical benefits owing to reduced hemodilution and no blood-air interface . Yet , the effects of MECC on the intraoperative microvascular perfusion in comparison with conventional extracorporeal circulation ( CECC ) have not been studied so far . METHODS The current study aimed to analyze alterations in microvascular perfusion at 4 predefined time points ( T1-T4 ) during on-pump CABG using orthogonal polarization spectral imaging . Forty patients were randomized for being operated on with either MECC or CECC . Changes in functional capillary density ( FCD ) , blood flow velocity , and vessel diameter were analyzed by a blinded investigator . RESULTS After start of extracorporeal circulation ( ECC ) and aortic crossclamping ( T2 ) , both groups showed a significant drop of FCD , with a significantly higher FCD in the MECC group ( 206.8 ± 33.6 cm/cm² in CECC group versus 217.8 ± 35.3 cm/cm² in MECC group ; P = .034 ) . In the late phase of the ECC ( T3 ) , FCD in the MECC group was already recovered , whereas FCD in the CECC group was still significantly depressed ( 223.1 ± 35.6 cm/cm² in MECC group ; P = .100 vs T1 ; 211.1 ± 36.9 cm/cm² in CECC group ; P = .017 vs T1 ) . After termination of ECC ( T4 ) , FCD recovered in both groups to baseline . Blood flow velocity tended to be higher in the MECC group , with a significant intergroup difference after aortic crossclamping ( T2 ) . CONCLUSIONS Orthogonal polarization spectral imaging data reveal an impairment of microvascular perfusion during on-pump CABG . Changes in FCD indicate a faster recovery of the microvascular perfusion in MECC during the reperfusion period . Beneficial recovery of microvascular organ perfusion could partly explain the perioperative advantages reported for MECC .

extracorporeal circulation

cardiopulmonary bypass

coronary artery bypass graft surgery

MECC

MECC

CECC

microvascular alterations

alterations in microvascular perfusion

functional capillary density ( FCD )

blood flow velocity

vessel diameter

FCD

FCD

coronary artery bypass

Forty


Rationale and study design of the increase of vagal tone in heart failure study : INOVATE-HF . BACKGROUND Imbalance between the parasympathetic and sympathetic nervous systems is a recognized contributor to progression of chronic heart failure . Current therapy with beta adrenergic antagonists is designed to moderate the up-regulation of norepinephrine and sympathetic effects ; however , to date , there are no therapies that specifically address the withdrawal of parasympathetic influences on cardiac function and structure . METHODS/RESULTS In order to evaluate the impact of vagus nerve stimulation , an international multi-center randomized clinical trial ( INOVATE-HF ) has been designed to assess safety and efficacy of vagus nerve stimulation in symptomatic patients with heart failure on optimal medical therapy using the CardioFit System ( BioControl Medical , Yehud , Israel ) . Up to 650 patients from 80 sites will be recruited and randomized in a 3:2 ratio to receive active treatment or standard optimal medical therapy . Inclusion criteria include left ventricular systolic dysfunction , the presence of New York Heart Association Class III symptoms , sinus rhythm , and QRS width less than 120 milliseconds . The study is powered to detect differences in the primary efficacy end point of all-cause mortality and heart failure hospitalization and 2 safety end points . CONCLUSION Vagal nerve stimulation with CardioFit as a treatment for symptomatic heart failure is under active investigation as a novel approach to restore balance between the sympathetic and parasympathetic nervous systems . If shown to be safe and effective in decreasing heart failure events and mortality , this novel approach will impact the treatment paradigm for heart failure .

CardioFit System

standard optimal medical therapy .

CardioFit

safety and efficacy

all-cause mortality

heart failure hospitalization

heart failure events

mortality


Dietary patterns differ between urban and rural older , long-term survivors of breast , prostate , and colorectal cancer and are associated with body mass index . BACKGROUND Older adult cancer survivors are at greater risk of cancer recurrence and other comorbidities that can be prevented through improved diet and weight management . The tertiary prevention needs of rural-dwelling survivors can be even greater , yet little is known about rural and urban differences in lifestyle factors among this high-risk population . OBJECTIVES To compare dietary patterns of urban and rural cancer survivors and to examine associations of dietary patterns with body mass index ( BMI ) . DESIGN A secondary analysis was performed of baseline data from the Reach Out to Enhance Wellness ( RENEW ) trial , a diet and exercise intervention among overweight , long-term ( ≥5 years ) , older survivors of colorectal , breast , and prostate cancer . Survivors in the present analysis ( n=729 ) underwent two 45- to 60-minute telephone surveys , which included two 24-hour dietary recalls . Principal components analysis and multivariable general linear models were used to derive dietary patterns and to evaluate associations between dietary patterns and BMI , respectively . RESULTS Principal components analysis identified three primary dietary patterns among rural dwellers ( high sweets and starches , high reduced-fat dairy , cereal , nuts , and fruits , and mixed ) and three among urban dwellers ( high fruits and vegetables , high meat and refined grains , and high sugar-sweetened beverages ) . Among rural survivors , greater adherence to the high reduced-fat dairy , cereal , nuts , and fruits pattern was positively associated with lower BMI ( P trend < 0.05 ) , whereas higher scores on the mixed pattern was associated with greater BMI ( P trend < 0.05 ) . Greater adherence to the high fruits and vegetables pattern among urban survivors was inversely associated with BMI ( P trend < 0.05 ) . CONCLUSIONS Urban and rural differences in dietary intake behavior should be considered in designing public health interventions among the increasing population of older cancer survivors . In addition , targeting overall dietary patterns might be one approach to help reduce the burden of obesity among this population .

compare

dietary patterns

diet and exercise intervention

cancer recurrence

comorbidities

dietary patterns

body mass index ( BMI ) .

Reach Out to Enhance Wellness

Older adult


[ Medical safety and staff mental health ] . Improvement in patient safety is a high-priority issue of great social import . Several studies have reported that most adverse events are due to errors of hospital staff , and emphasized the necessity of promoting countermeasures against medical errors . Root cause analysis ( RCA ) has been implemented to prevent such errors . However , the retrospective and qualitative nature of RCA is a limitation in scientific analyses examining causal relationships . We showed that prospective design path analysis using structural equation modeling ( SEM ) model for both direct and indirect effects enabled statistical exploration of root causes and estimation of their impact on the outcome . Our findings suggested such analysis to be useful in devising countermeasures against medical errors . The SEM model constructed in this study suggested that one of the potential root causes was sleep disturbance . We conducted a randomized crossover study whether or not brief bright light ( BL ) exposure on workday mornings can improve health , performance and safety in nurses with rapidly rotating shifts . Significant improvements were noted in the BL periods compared with the non-BL periods for self-assessed sleepiness at 10 : 00 on day-shift days , self-assessment of night sleep for day-shift days and for fatigue . Mean response time evaluated using the psychomotor vigilance task test ( PVT ) showed significant improvement in the BL periods compared with the non-BL periods . The frequency of perceived adverse events and near misses was also lower in the BL than in the non-BL periods , but not significantly so , possibly indicating that the one-month observation period was too short to achieve any significant success . Despite our study 's limitations , we have effectively demonstrated the potential for preventing medical error risk among night-shift workers .

structural equation modeling ( SEM )

BL

sleep disturbance

self-assessed sleepiness

Mean response time

Medical safety

nurses with rapidly rotating shifts

night-shift workers


Investigations into the potential effects of multiple dose ketorolac on the pharmacokinetics and pharmacodynamics of racemic warfarin . 1 . The potential interaction between racemic warfarin given as a 25 mg single oral dose and chronically administered ketorolac was studied in 12 young healthy male volunteers . 2 . Ketorolac produced no major change in the pharmacokinetics of ( R ) - or ( S ) -warfarin . 3 . Ketorolac did not alter the pharmacodynamic profile of racemic warfarin . 4 . Ketorolac increased template bleeding time by a factor of 1.35 as compared with placebo . 5 . The results suggest that the ketorolac-warfarin interaction is unlikely to be of major clinical significance ; however , combined use of ketorolac and warfarin in patients should be undertaken with due caution and appropriate monitoring .

racemic warfarin

racemic warfarin

Ketorolac

Ketorolac

Ketorolac

ketorolac

warfarin

increased template bleeding time

young

healthy

male


A randomized double-blind study of atomoxetine versus placebo for attention-deficit/hyperactivity disorder symptoms in children with autism spectrum disorder . OBJECTIVE The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder ( ADHD ) in patients with autism spectrum disorder ( ASD ) has not been established . METHOD In this study , 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks . The primary endpoint was the ADHD Rating Scale ( ADHD-RS ) score ; secondary endpoints were the Clinical Global Impression of ADHD-Improvement ( CGI-I ) and the Conners Teacher Rating Scale-Revised : Short Form ( CTRS-R : S ) score . RESULTS Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6 ; after 8 weeks , mixed-effect model repeated-measure means were 31.6 ( 95 % confidence interval 29.2-33.9 ) and 38.3 ( 36.0-40.6 ) , respectively , with a difference in least square means of -6.7 ( -10.0 to -3.4 ; p < .001 ) . The CTRS-R : S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo , but not the other CTRS-R : S subscores . However , there were not significantly more patients on atomoxetine ( 20.9 % ) who improved much , or very much according to the CGI-I , than on placebo ( 8.7 % ; p = 0.14 ) . Adverse events ( mostly nausea , decrease in appetite , fatigue , and early morning awakening ) were reported in 81.3 % of atomoxetine patients and 65.3 % of placebo patients ( p > .1 ) . There were no serious adverse events . CONCLUSIONS Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated . Adverse events in this study were similar to those in other studies with ADHD patients without ASD . Clinical trial registration information-A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD ; www.clinicaltrials.gov ; NCT00380692 .

atomoxetine

placebo

atomoxetine

atomoxetine

placebo

atomoxetine

placebo

atomoxetine

placebo

atomoxetine

placebo

atomoxetine

Atomoxetine

Atomoxetine

ADHD Rating Scale ( ADHD-RS ) score

ADHD-RS

CTRS-R : S

CTRS-R : S

nausea

adverse events


Effect of chelation therapy on progressive diabetic nephropathy in patients with type 2 diabetes and high-normal body lead burdens . BACKGROUND A previous study in type 2 diabetic patients with high-normal body lead burdens showed that EDTA chelation therapy for 3 months slows progressive diabetic nephropathy during a 12-month follow-up . The effect of a longer course of therapy on kidney function decrease over a longer follow-up is not known . STUDY DESIGN A 12-month run-in phase , then a randomized single-blind study with a 27-month intervention . SETTING & PARTICIPANTS University medical center ; 50 patients ( serum creatinine , 1.5-3.9 mg/dL ) with high-normal body lead burden ( ≥80- < 600 μg ) were randomly assigned to the treatment and control groups . INTERVENTION The treatment group received weekly chelation therapy for 3 months to reduce their body lead burden to < 60 μg and then as needed for 24 months to maintain this level . The control group received placebo for 3 months and then weekly for 5 weeks at 6-month intervals for 24 months . OUTCOMES The primary end point was change in estimated glomerular filtration rate ( eGFR ) over time . A secondary end point was a 2-fold increase in baseline serum creatinine level or the requirement for renal replacement therapy . MEASUREMENTS Body lead burdens were assessed by EDTA mobilization tests and eGFR was calculated using the equation for Chinese patients with type 2 diabetes . RESULTS Mean baseline eGFRs in the treatment and control groups were similar . After 3 months of chelation therapy , the change in eGFR in the treatment group ( +1.0 ± 4.8 mL/min/1.73 m ( 2 ) ) differed significantly from that in the control group ( -1.5 ± 4.8 mL/min/1.73 m ( 2 ) ; P = 0.04 ) . In the subsequent 24-month intervention , the yearly rate of decrease in eGFR ( 5.6 ± 5.0 mL/min/1.73 m ( 2 ) per year ) in the treatment group was slower than that ( 9.2 ± 3.6 mL/min/1.73 m ( 2 ) per year ; P = 0.04 ) in the control group . 17 ( 68 % ) control-group patients and 9 ( 36 % ) treatment-group patients achieved the secondary end point . LIMITATIONS Small sample size , not double blind . CONCLUSIONS A 27-month course of EDTA chelation therapy retards the progression of diabetic nephropathy in type 2 diabetic patients with high-normal body lead burdens .

chelation therapy

EDTA chelation therapy

type 2 diabetes

high-normal body lead burdens

type 2 diabetic


The in vitro effects of verbascoside on human platelet aggregation . Preliminary in vitro and animal studies have shown that verbascoside , a phenolic compound , may have several favourable biological activities , including an influence on endothelial function and on platelet aggregation . We sought to evaluate the effects of verbascoside , biotechnologically produced from plant cell cultures , on human platelet aggregation ( PA ) . The blood from 40 aspirin-naïve volunteers with at least one cardiovascular risk factor was preincubated in vitro with verbascoside ( 1 and 2 mg/dL ) and aspirin ( 100 μM ) . The blood from 20 patients with a prior diagnosis of coronary heart disease who were chronically assuming aspirin was preincubated in vitro with verbascoside ( 1 and 2 mg/dL ) . PA is measured with a light transmission aggregometry and multiplate analyzer . As compared to reference , preincubation with verbascoside resulted in a significant inhibition of adenosine diphosphate ( ADP ) and arachidonic acid ( AA ) -induced PA ( p < 0.01 for both ) . Verbascoside 2 mg/dL did not show a stronger effect as compared to verbascoside 1 mg/dL ( p = 0.4 ) . As expected , the in vitro addition of aspirin reduced AA induced PA ( p < 0.01 ) , but not that induced by ADP ( p = 0.5 ) . The addition of verbascoside to the blood of aspirin-treated patients did not improve the values of PA after AA stimulus ( p = 0.8 ) , whereas it ensured a stronger inhibition after ADP stimulus ( p < 0.01 ) . Verbascoside in vitro affects PA by mildly inhibiting aggregation , triggered both by ADP and AA . These preliminary data , while intriguing , require confirmation in subjects receiving verbascoside orally in order to determine whether these findings are clinically relevant .

verbascoside

verbascoside

verbascoside

values of PA

human platelet aggregation .


Rosiglitazone and cognitive function in clozapine-treated patients with schizophrenia : a pilot study . Studies have shown that insulin resistance is associated with cognitive impairment . Peroxisome proliferator-activated receptor-γ ( PPAR-γ ) agonists improve insulin sensitivity . The purpose of this study was to evaluate the effect of rosiglitazone , a PPAR-γ agonist , on cognition in clozapine-treated patients with schizophrenia . In an eight-week double-blind , placebo-controlled pilot trial , clozapine-treated patients with schizophrenia were randomized to receive rosiglitazone ( 4mg/day ) or placebo . A neuropsychological battery including the Digit Span subtest from the Wechsler Adult Intelligence Scale-III ( WAIS-III ) , the verbal fluency test , the Hopkins Verbal Learning Test ( HVLT ) , the Trail-Making Test ( TMT ) and the Wisconsin Card Sorting Test ( WCST ) was administered at baseline and week eight . Nineteen patients completed the study . There were no significant differences on any demographic or general clinical variables between the rosiglitazone group ( n=9 ) and the placebo group ( n=10 ) . When baseline scores were controlled , there were no significant differences in change scores of cognitive performance over eight weeks between the two groups . In this pilot study , rosiglitazone had no cognitive benefit in clozapine-treated patients with schizophrenia . Future studies with longer treatment duration and larger sample size are needed to further explore the potential role of rosiglitazone in improving cognitive function in patients with schizophrenia .

Rosiglitazone

clozapine-treated

cognitive performance

cognitive benefit

schizophrenia


Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer : final analysis of overall survival . BACKGROUND A randomized phase II study in first-line MBC demonstrated superior efficacy and safety of weekly nab-paclitaxel compared with docetaxel . Final survival analyses and updated safety results are reported . PATIENTS AND METHODS Three hundred two patients with no previous chemotherapy for MBC were randomized to receive nab-paclitaxel 300 mg/m ( 2 ) q3w , nab-paclitaxel 100 mg/m ( 2 ) or 150 mg/m ( 2 ) the first 3 of 4 weeks ( qw 3/4 ) , or docetaxel 100 mg/m ( 2 ) q3w . The trial was powered for analyses of antitumor activity and safety . RESULTS Treatment with nab-paclitaxel 150 mg/m ( 2 ) qw 3/4 resulted in a median overall survival ( OS ) of 33.8 months compared with 22.2 , 27.7 , and 26.6 months for nab-paclitaxel 100 mg/m ( 2 ) qw 3/4 , nab-paclitaxel 300 mg/m ( 2 ) q3w , and docetaxel , respectively ( overall P = .047 ) . Patients receiving 150 mg/m ( 2 ) nab-paclitaxel had prolonged median OS compared with those in the 100 mg/m ( 2 ) nab-paclitaxel arm ( hazard ratio , 0.575 ; P = .008 ) . A trend toward a longer OS was noted in the 150 mg/m ( 2 ) nab-paclitaxel arm versus docetaxel arm ( hazard ratio , 0.688 ) . Grade 3 or 4 fatigue , neutropenia , and febrile neutropenia were less frequent in all nab-paclitaxel arms compared with docetaxel . CONCLUSIONS Consistent with previously published efficacy results , these data suggest that 150 mg/m ( 2 ) qw 3/4 may represent the most clinically efficacious nab-paclitaxel dosing regimen for patients with no previous chemotherapy for MBC . A phase III trial confirming these results would be necessary and prudent before widespread adoption of the 150 mg/m ( 2 ) dose in clinical practice .

docetaxel

docetaxel

nab-paclitaxel 300 mg/m ( 2 )

nab-paclitaxel 100 mg/m ( 2 )

150 mg/m ( 2 )

docetaxel 100 mg/m ( 2 )

docetaxel

docetaxel

efficacy

safety

survival

safety

antitumor activity

safety

survival

median OS

OS

Grade 3 or 4 fatigue

neutropenia ,

febrile neutropenia

metastatic breast cancer

Three hundred two

with no previous chemotherapy

MBC


Nutritional orientation , knowledge and quality of diet in heart failure : randomized clinical trial . BACKGROUND Non-pharmacological measures are recommended for heart failure patients . However , most studies evaluate low sodium diet , while little is known about the effects of interventions to improve adherence and knowledge of patients about diet content . OBJECTIVE To evaluate if a global nutritional orientation could affect nutritional knowledge , adherence to food guidelines , anthropometrics and quality of life in heart failure patients . METHODS Forty six patients were randomized to intervention or control group . Both groups received usual care with medical and nursing staff ; the intervention group received additional nutritional guidance about diet and its relationship with disease , sources of nutrients , and reduction of dietary sodium and fats . Enforcement of the nutritional guidance was performed after 4 weeks . Both groups were evaluated at baseline , and after 6 weeks and 6 months . Evaluations included anthropometric parameters , sodium excretion in 24-hour urine , dietary recall , nutrition knowledge and quality of life questionnaires . RESULTS Mean age of included patients was 58 ± 10 years and 70 % were male . After 6 months of follow-up , the nutritional knowledge of intervention group increased compared to control ( p < 0.05 ) . Caloric , fat and sodium intake decreased in the intervention group compared to control ( p < 0.05 ) . No significant differences were seen in quality of life or anthropometric parameters . CONCLUSIONS Nutritional orientation was effective to modify 1 ) knowledge about food and nutrition , and 2 ) quality of diet in outpatients with heart failure . Further studies are necessary to evaluate the benefits on quality of life and prognosis .

usual care

with medical and nursing staff

anthropometrics

and quality of life

anthropometric parameters

sodium excretion in 24-hour urine

dietary recall , nutrition knowledge

quality of life questionnaires

the nutritional knowledge

Caloric , fat and sodium intake

1 ) knowledge about food and nutrition

2 ) quality of diet

on quality of life and prognosis

heart failure

heart failure patients

heart failure patients .

Forty six patients

male

outpatients with heart failure


Lactobacillus plantarum CECT7315 and CECT7316 stimulate immunoglobulin production after influenza vaccination in elderly . OBJECTIVE The effectiveness of influenza vaccination in preventing illness is lower in the elderly ; this is why the ability of Lactobacillus plantarum CECT 7315/7316 to stimulate the response to influenza vaccination in elderly was evaluated . RESEARCH METHODS AND PROCEDURES A randomized , double-blind , placebo-controlled human trial including 60 institutionalized volunteers aged 65-85 years was performed . All the volunteers were vaccinated with a trivalent influenza vaccine ( A/Wisconsin/67/2005 NYMC X-161B ( H3N2 ) , A/Solomon Islands/3/2006 ( H1N1 ) and B/Malaysia/2506/2004 ) for the Spanish vaccine campaign 2006/2007 . The consumption of the probiotic began between three and four months after the vaccination . Volunteers were randomly assigned to one of three following groups : group A ( receiving 5*10 ( 9 ) cfu/day of L. plantarum CECT 7315/7316 in 20 g powdered skim milk ) , group B ( receiving 5*10 ( 8 ) cfu/day of L. plantarum CECT 7315/7316 in 20 g powdered skim milk ) and group C or placebo ( 20 g powered skim milk ) . The participants consumed the probiotic during 3 months . RESULTS The consumption of L. plantarum CECT 7315/7316 during 3 months after influenza vaccination increased the levels of influenza-specific IgA and IgG antibodies . Moreover , a trend towards an increase in influenza-specific IgM antibodies was also observed . CONCLUSION L. plantarum CECT7315/7316 has an immunostimulating effect and could be used to improve the response to influenza vaccination in elderly .

Lactobacillus plantarum CECT7315

influenza vaccination

influenza vaccination

Lactobacillus plantarum CECT 7315/7316

influenza vaccination

placebo-controlled

A/Solomon Islands/3/2006 ( H1N1 )

B/Malaysia/2506/2004 )

plantarum CECT 7315/7316

plantarum CECT 7315/7316

placebo

powered skim milk

plantarum CECT 7315/7316

influenza vaccination

plantarum CECT7315/7316

influenza vaccination

immunoglobulin production

influenza-specific IgM antibodies

influenza vaccination

elderly

influenza vaccination

elderly

institutionalized volunteers

aged 65-85 years


Randomized controlled trial : Multimodal Anxiety and Social Skill Intervention for adolescents with autism spectrum disorder . Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted .

Multimodal Anxiety and

Social Skill Intervention

Multimodal Anxiety and

MASSI

feasibility

preliminary outcomes

subject adherence

therapist fidelity

ASD social impairment

anxiety symptoms

feasible

adolescents

autism spectrum disorder

ASD

adolescents

ASD and anxiety symptoms


Pentraxin-3 in chronic heart failure : the CORONA and GISSI-HF trials . AIMS Pentraxin-3 ( PTX3 ) is a component of the humoral arm of innate immunity which can regulate inflammatory processes . Since the role of inflammation in the progression of chronic heart failure ( HF ) is debated , we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF . METHODS AND RESULTS Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF ( CORONA ) and 1233 patients enrolled in the GISSI-Heart Failure trial ( GISSI-HF ) . The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors , high sensitivity C-reactive protein ( hsCRP ) , and N-terminal pro brain natriuretic peptide ( NT-proBNP ) . PTX3 concentration [ median ( Q1-Q3 ) = 5.34 ( 3.55-7.64 ) ng/mL , n = 2690 ] was higher in females , in older patients , and those with lower body mass index . Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [ 759 events , hazard ratio ( HR ) for 1 SD increase 1.20 , 95 % confidence interval ( CI ) 1.12-1.30 , P < 0.0001 ] , cardiovascular mortality ( 587 events , HR 1.27 , 95 % CI 1.17-1.38 , P < 0.0001 ) , or hospitalization for worsening HF ( 720 events , HR 1.21 , 95 % CI 1.12-1.30 , P < 0.0001 ) , and marginally improved discrimination . Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP . Rosuvastatin lowered hsCRP levels but significantly raised PTX3 . CONCLUSION In two independent clinical trials that enrolled patients with chronic HF , PTX3 was consistently associated with outcomes . The opposite effects of a statin on hsCRP and PTX3 call for further investigation . TRIAL REGISTRATION NCT00336336 ( GISSI-HF ) , NCT00206310 ( CORONA ) .

Pentraxin-3 ( PTX3 )

statin

baseline PTX3 levels

Baseline elevated PTX3

statin

PTX3 concentration

risk of all-cause mortality

cardiovascular mortality

hospitalization for worsening HF

fatal events

hsCRP levels

PTX3 .

chronic heart failure :

1457 patients

1233 patients

patients with chronic HF


Early versus late hCG administration to trigger ovulation in mild stimulated IUI cycles : a randomized clinical trial . OBJECTIVES To verify non-inferiority of the clinical pregnancy rate of Early hCG administration ( leading follicle sizes within 16.0-16.9 mm in diameter ) compared to Late hCG administration ( leading follicle sizes within 18.0-18.9 mm in diameter ) . STUDY DESIGN Prospective randomized trial . Six hundred and twelve infertile women candidates for intrauterine insemination ( IUI ) received HP-hMG 75 IU/day SC from cycle days 4 to 8 and then as per ovarian response . Ovulation was randomly triggered ( hCG 5000 IU , IM ) when the leading follicle diameter ranged between either 16.0 and 16.9 mm ( Early hCG group , n=227 ) or 18.0 and 18.9 mm ( Late hCG group , n=207 ) and IUI was performed approximately 36 h later . RESULTS Whereas population and sperm characteristics were comparable in both groups , the number of follicles ≥ 14 mm in diameter ( P < 0.007 ) and serum estradiol levels ( P < 0.001 ) on the day of hCG were lower in the Early versus the Late hCG groups . Clinical ( 11.9 % versus 12.1 % ) and ongoing ( 11.0 % versus 8.6 % ) pregnancy rates per randomized women were similar in the two groups and statistical non-inferiority of clinical and ongoing pregnancy rates was demonstrated . CONCLUSION These results suggest that hCG administered when the largest follicle size reaches 16.0-16.9 mm leads to similar clinical and ongoing pregnancy rates as when it reaches 18.0-18.9 mm in IUI cycles .

hCG administration

Early hCG administration

Late hCG administration

HP-hMG

hCG

population and sperm characteristics

number of follicles

serum estradiol levels

pregnancy rates


Modified constraint-induced movement therapy improved upper limb function in subacute poststroke patients : a small-scale clinical trial . BACKGROUND Constraint-induced movement therapy ( CIMT ) has been advocated as a means of facilitating motor function in poststroke patients ; however , the evidence for its efficacy is controversial . OBJECTIVE To evaluate the effect of modified CIMT on improving paretic arm function in poststroke patients during a subacute rehabilitation period . METHODS A single-blinded randomized controlled trial was conducted at the Loewenstein Rehabilitation Hospital , Israel . Twenty-eight subacute stroke patients with arm paresis after a first ischemic stroke in the middle cerebral artery area were randomized into a modified CIMT or control group by a 1:2 ratio . The modified CIMT group received 1-hour daily physical rehabilitation sessions for 2 weeks . The unaffected arm was restrained during the sessions . Subjects were encouraged to wear a restrictive mitten up to 4 hours a day . The control group received similar intensive regular rehabilitation . Three upper limb function tests , developed for this study , were used as outcome measures . The subjects were asked to perform the following tasks , with the affected hand for 30 seconds : ( 1 ) transfer pegs from a saucer to a pegboard ; ( 2 ) grasp , carry , and release a hard rubber ball ; and ( 3 ) " eating , " using a spoon to remove the jelly from the plate , bring it towards the mouth , and then place it on another plate . The number of repetitions in each test was recorded as an outcome . RESULTS The modified CIMT group showed significantly higher changes in all 3 tests compared to the standard rehabilitation group . CONCLUSION Our study provides additional support for the use of modified CIMT during a subacute rehabilitation period of poststroke patients . CIMT may facilitate functional improvement of a plegic hand .

CIMT

modified CIMT

control

CIMT

physical rehabilitation

restrictive mitten

CIMT

modified CIMT

CIMT

The number of repetitions in each test

subacute poststroke

poststroke

Twenty-eight

subacute stroke

ischemic stroke


Effectiveness and safety of donepezil in boys with fragile x syndrome : a double-blind , randomized , controlled pilot study . The present study was designed as a 12-week , randomized , double-blind , placebo-controlled pilot study to evaluate the effectiveness and safety of donepezil in boys with fragile X syndrome . Twenty boys with fragile X syndrome were randomized to receive 12 weeks of treatment with either placebo or donepezil ( 2.5 mg daily for initial 4 weeks followed by 5 mg daily for next 8 weeks ) . The outcome measures included change in intelligence quotient scores on Stanford-Binet Intelligence Scale ( Hindi adaptation by Kulshrestha ) , change in behavioral scores by Conners 3 Parent Rating Scale ( Short ) and Childhood Autism Rating Scale , safety , and tolerability of donepezil . The study failed to show significant difference in intelligence quotient and behavioral scales with donepezil therapy over 12 weeks . However , donepezil appeared to be safe and well tolerated .

donepezil

donepezil

placebo

donepezil

donepezil

donepezil

effectiveness and safety

Childhood Autism Rating Scale

safety , and tolerability

intelligence quotient

behavioral scales

boys

fragile x syndrome

boys

fragile X syndrome .

Twenty

boys

fragile X syndrome


Chloroprocaine and lidocaine decrease hospital stay and admission rate after outpatient epidural anesthesia . Lumbar epidural anesthesia with 20 ml of either 3 % 2-chloroprocaine ( C ) , 1.5 % lidocaine ( L ) , or 1.5 % mepivacaine ( M ) with epinephrine was studied in 84 outpatients undergoing surgery ( extracorporeal shock wave lithotripsy ( ESWL ] . The average duration of the procedure was 31.9 minutes . The total duration of sensory anesthesia was 133 +/- 28 minutes ( C ) , 182 +/- 38 ( L ) , and 247 +/- 42 ( M ) ( p less than 0.05 ) . Times to discharge were 269 +/- 62 minutes ( C ) , 284 +/- 62 ( L ) , and 357 +/- 71 ( M ) . The time to discharge with M , almost six hours , was significantly longer than with C or L. There was a trend to an increasing rate of unplanned overnight hospital admission with increasing duration of the local anesthetic drug employed . Continuous epidural anesthesia with C , L or M appears safe and effective for outpatient surgical procedures such as ESWL . In contrast to previous understanding , mepivacaine produces significantly longer anesthesia and recovery times and may not be optimal for outpatient epidural use .

Chloroprocaine and lidocaine

3 % 2-chloroprocaine ( C )

1.5 % lidocaine ( L )

average duration of the procedure

total duration of sensory anesthesia

Times to discharge

time to discharge

unplanned overnight hospital admission


Effects of telephone call interventions on patients ' well-being in a radiation therapy department . This study examined the effects of telephone call interventions by a collaborative team on patients ' well-being . Fifty-five subjects undergoing radiation therapy for cure and who were able to communicate by telephone comprised the sample . Subjects were randomly assigned to a control group , who received the usual care or to an experimental group , who received a weekly telephone call intervention in addition to the usual care . Speilberger 's State Trait Inventory , the Side Effects Profile , and the Coping Strategies Profile were used along with a telephone survey to collect data . Analysis of the data showed no significant differences between groups in anxiety , severity of side effects , helpfulness of self-care strategies , and coping strategies . However , the survey indicated that the telephone calls were clinically significant and provided a mechanism for demonstrating that the health care professionals cared about their patients and provided an opportunity for patients to talk about their concerns . The investigators believe that collaboration , caring , and communication are the essence of exemplary health care .

telephone call interventions

telephone call interventions

Speilberger 's State Trait Inventory

the Side Effects Profile

Coping Strategies Profile

anxiety

severity of side effects

helpfulness of self-care strategies

coping strategies

clinically significant

patients ' well-being .


Reaching out , inviting back : using Interactive voice response ( IVR ) technology to recycle relapsed smokers back to Quitline treatment -- a randomized controlled trial . BACKGROUND Tobacco dependence is a chronic , relapsing condition that typically requires multiple quit attempts and extended treatment . When offered the opportunity , relapsed smokers are interested in recycling back into treatment for a new , assisted quit attempt . This manuscript presents the results of a randomized controlled trial testing the efficacy of interactive voice response ( IVR ) in recycling low income smokers who had previously used quitline ( QL ) support back to QL support for a new quit attempt . METHODS A sample of 2985 previous QL callers were randomized to either receive IVR screening for current smoking ( control group ) or IVR screening plus an IVR intervention . The IVR intervention consists of automated questions to identify and address barriers to re-cycling in QL support , followed by an offer to be transferred to the QL and reinitiate treatment . Re-enrollment in QL services for both groups was documented . RESULTS The IVR system successfully reached 715 ( 23.9 % ) former QL participants . Of those , 27 % ( 194/715 ) reported to the IVR system that they had quit smoking and were therefore excluded from the study and analysis . The trial 's final sample was composed of 521 current smokers . The re-enrollment rate was 3.3 % for the control group and 28.2 % for the intervention group ( p < .001 ) . Logistic regression results indicated an 11.2 times higher odds for re-enrollment of the intervention group than the control group ( p < .001 ) . Results did not vary by gender , race , ethnicity , or level of education , however recycled smokers were older ( Mean = 45.2 ; SD = 11.7 ) than smokers who declined a new treatment cycle ( Mean = 41.8 ; SD = 13.2 ) ; ( p = 0.013 ) . The main barriers reported for not engaging in a new treatment cycle were low self-efficacy and lack of interest in quitting . After delivering IVR messages targeting these reported barriers , 32 % of the smokers reporting low self-efficacy and 4.8 % of those reporting lack of interest in quitting re-engaged in a new QL treatment cycle . CONCLUSION Proactive IVR outreach is a promising tool to engage low income , relapsed smokers back into a new cycle of treatment . Integration of IVR intervention for recycling smokers with previous QL treatment has the potential to decrease tobacco-related disparities . TRIAL REGISTRATION ClinicalTrials.gov Identifier : NCT01260597 .

interactive voice response ( IVR )

IVR intervention

IVR system

IVR system

IVR messages

Proactive IVR outreach

IVR

successfully reached

quit smoking

re-enrollment rate

recycled

smokers

were older

self-efficacy

lack of interest

low self-efficacy

relapsed smokers

low income smokers

previously used quitline ( QL ) support

QL callers

smokers


Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines : a randomized , double-blind study . The purpose of this study was to evaluate the effectiveness of lactobacilli on vaginal health and proinflammatory cytokines . Sixty-seven patients with bacterial vaginosis ( BV ) , 50 with intermediate flora and 42 with normal vaginal flora were enrolled in this double-blind study . The subjects were randomized to receive probiotic lactobacilli vaginal tablets ( L. brevis CD2 , L. salivarius subsp . salicinius , L. plantarum ) or the vaginal pH tablet ( active comparator ) . Cervico-vaginal lavage was collected to measure the concentrations of IL-1β , TNFα and IL-6 by ELISA . Neutral sphingomyelinase activity was also quantified in both arms before and after treatment . The probiotic vaginal tablet was well tolerated and no side effects were reported . The study demonstrated a cure rate of nearly 80 % ; i.e. , 32 % of the women could restore normal vaginal flora and 47 % had improved Nugent score , whereas 20 % of the subjects did not clear BV in the first follow-up ( after 8 days treatment ) . The pH tablet containing pH lowering compounds induced resolution of BV and restoration of normal vaginal flora in 74 % and 26 % , respectively . The lactobacilli tablet was found to be better than the pH tablet in preventing BV in healthy subjects . A significant reduction in IL-1β and IL-6 vaginal cytokines was observed after treatment with lactobacilli , while the active comparator did not have any effect on local proinflammatory cytokines . Vaginal neutral sphingomyelinase activity was not modified in either group . Vaginal tablets containing lactobacilli can cure BV and reduce vaginal inflammatory response .

vaginal tablets

lactobacilli

pH tablets

lactobacilli

cure

preventing

IL-1β and IL-6 vaginal cytokines

Vaginal neutral sphingomyelinase

cure BV

vaginal inflammatory

Sixty-seven

bacterial vaginosis ( BV

vaginal flora


Celecoxib as adjunctive treatment to risperidone in children with autistic disorder : a randomized , double-blind , placebo-controlled trial . RATIONAL Autism is associated with activation of the inflammatory response system . OBJECTIVE This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor , celecoxib , as adjunctive therapy in the treatment of autism METHODS In a 10-week randomized double-blind placebo-controlled study , 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders , fourth edition , text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone . The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day , respectively . Patients were assessed at baseline and after 2 , 4 , 6 , and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community ( ABC-C ) Rating Scale . Primary outcome measure was the change in irritability subscale of ABC-C . RESULTS Significant time × treatment interaction was observed for Irritability ( F ( 1.658 , 63.021 ) = 13.580 , P < 0.001 ) , Lethargy/Social Withdrawal ( F ( 1.948 , 74.032 ) = 16.811 , P < 0.001 ) , and Stereotypic Behavior ( F ( 1.742 , 66.198 ) = 12.104 , P < 0.001 ) , but not for Hyperactivity/Noncompliance ( F ( 2.564 , 97.424 ) = 1.469 , P = 0.232 ) , and Inappropriate Speech subscales ( F ( 1.607 , 61.075 ) = 0.173 , P = 0.794 ) . By week 10 , patients in the celecoxib group showed significantly greater improvement in the Irritability ( P < 0.001 ) , Lethargy/Social Withdrawal ( P < 0.001 ) , and Stereotypic Behavior ( P < 0.00 ) but not in Hyperactivity/Noncompliance ( P = 0.202 ) and Inappropriate Speech ( P = 0.802 ) subscales than the placebo group . Complete response was achieved by four ( 20 % ) patients in the placebo group and 11 ( 55 % ) patients in the celecoxib group ( χ ( 2 ) ( 1 ) = 5.227 , P = 0.022 ) . Frequency of side effects was similar between the two groups . CONCLUSIONS Combination of risperidone and celecoxib was superior to risperidone alone in treating irritability , social withdrawal , and stereotypy of children with autism . ( Registration , www.irct.ir ; IRCT138711091556N2 ) .

Celecoxib

risperidone

cyclooxygenase-2 inhibitor , celecoxib

celecoxib plus risperidone

placebo plus risperidone

risperidone

celecoxib

efficacy

children with autistic disorder :

40 outpatient children

risperidone alone in treating


The impact of patient and physician computer mediated communication skill training on reported communication and patient satisfaction . OBJECTIVE The objective was to evaluate parallel patient and physician computer-mediated communication skill training on participants ' report of skill use and patient satisfaction . METHODS Separate patient and clinician web-tools comprised of over 500 , 10-s video clips demonstrating patient-centered skills in various ways . Four clinician members of the American Academy of Family Physicians National Research Network participated by enrolling 194 patients into a randomized patient trial and 29 physicians into a non-randomized clinician trial of respective interventions . All participants completed baseline and follow-up self-report measures of visit communication and satisfaction . RESULTS Intervention patients reported using more skills than controls in five of six skill areas , including identification of problems/concerns , information exchange , treatment adherence , shared decision-making and interpersonal rapport ( all p < .05 ) ; post intervention , physicians reported using more skills in the same 5 areas ( all p < .01 ) . Intervention group patients reported higher levels of satisfaction than controls in five of six domains ( all p < .05 ) . CONCLUSION Communication skill training delivered in a computer mediated format had a positive and parallel impact on both patient and clinician reported use of patient-centered communication and in patient satisfaction . PRACTICE IMPLICATIONS Computer-mediated interventions are cost and time effective thereby increasing patient and clinician willingness to undertake training .

patient and clinician web-tools

500 , 10-s

Communication skill training

patient-centered skills

communication

satisfaction

skills

treatment adherence

satisfaction

positive and parallel impact

patient-centered communication

patient satisfaction

cost

time effective

194 patients


Selected polymorphisms of GSTP1 and TERT were associated with glioma risk in Han Chinese . BACKGROUND Current evidence suggests that a majority of the inherited risks play a major role in glioma susceptibility , and glioma is due to the co-inheritance of multiple low-risk variants . These variants can be identified through association studies including such as genome-wide association studies ( GWAS ) , which has led the glioma epidemiology researchers to focus on identifying potential disease-causing factors . METHODS We evaluated and validated 10 tag single nucleotide polymorphisms ( tSNPs ) in seven genes associated with glioma susceptibility in a Han Chinese population , including 301 glioma cases and 302 controls , using a multiplexed single nucleotide polymorphism ( SNP ) MassEXTEND assay . We ascertained the genotypic frequencies for each tSNP in control subjects were within Hardy-Weinberg equilibrium ( HWE ) using an exact test , and then compared the genotype and allele frequencies of glioma patients and control subjects using the χ2 test . We then applied three genetic models ( dominant , recessive , and additive ) using PLINK software to assess the association of each tSNP with glioma risk . RESULTS We identified two tSNPs to be associated with glioma susceptibility ( rs1695 , GSTP1 , P = 0.019 ; rs2853676 , TERT , P = 0.039 ) , which we confirmed using dominant and additive model analyses . The genotype & ldquo ; GA & rdquo ; for rs1695 was recognized to be a protective genotype for glioma ( OR , 0.67 ; 95 % CI , 0.47-0.96 ; P = 0.027 ) , while the genotype & ldquo ; AG & rdquo ; for rs2853676 was shown to be a risk genotype for glioma ( OR , 1.50 ; 95 % CI , 1.05-2.15 ; P = 0.025 ) . CONCLUSION Our results , and those from previous studies , suggest potential genetic contributes for GSTP1 and TERT in glioma development .

glioma risk

glioma


A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers : methodological issues in a feasibility study . BACKGROUND Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown . METHODS Attrition ( dropouts ) and compliance with treatment were assessed in a 25-week randomized , placebo controlled , crossover , feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers . Each treatment lasted 4 weeks with 2 weeks of washout in between . Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions . The interventions consisted of packets of green tea , black tea , caffeinated water , or placebo . Participants were assigned to each treatment for four weeks , and were instructed to drink five packets per day while on the treatment . Dropout from the trial and compliance ( consumption of ≥85 % of the prescribed treatment packets ) are the main outcome measures reported . RESULTS There was a high rate of dropout ( 51 % ) from the study , and the rates were significantly higher among smokers ( 64 % ) than non-smokers ( 36 % ) . Among participants who completed the study the rate of compliance was 72 % . The highest rates of dropouts occurred between the first and second treatment visits in both smokers ( 38 % dropout ) and non-smokers ( 18 % dropout ) . Throughout the study smokers were more likely to dropout than non-smokers . Black tea treatment was associated with the highest rates of dropout among smokers ( 37 % ) , but was associated with the lowest rate of dropout among non-smokers ( 4 % ) . CONCLUSIONS In a study conducted to test the feasibility of a four-treatment crossover tea trial , a high rate of dropout among smokers and non-smokers was observed . Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials . TRIAL REGISTRATION NUMBER ISRCTN70410203 .

tea

four tea treatments

Dropout

compliance

high rate of

highest

rates of dropouts

rates of

smokers

non-smokers

32 smokers and 33 non-smokers

premalignant oral lesions


Promoting physical activity in patients with colon adenomas : a randomized pilot intervention trial . BACKGROUND Physical activity decreases risk of colon polyps and colon cancer and might reduce risk of colon cancer recurrence . Focusing on recent calls for translation of epidemiologic evidence into clinical care , our pilot study delivered an evidence-based physical activity intervention in adults with polyps , who are thus at elevated risk of developing colon cancer . The objective was to evaluate change in physical activity , measured by steps per day and minutes of moderate/vigorous physical activity . METHODS Sixteen adults with adenomas detected and removed at screening colonoscopy were recruited to a 12-week physical activity intervention . Participants were randomized to receive a standard ( 30 minutes/day ) or high ( 60 minutes/day ) walking program . Physical activity was measured via blinded pedometer and accelerometer at baseline and follow-up . Intervention messages focused on self-monitoring using pedometers and overcoming barriers to engaging in physical activity . RESULTS Participants in both arms significantly increased objectively measured minutes of moderate/vigorous physical activity over the course of the intervention . Both arms exceeded the intervention goal , but there was not a significant difference between arms at follow-up . Results were similar for pedometer measured physical activity , with a significant overall increase in steps/day from baseline to follow-up , but no between arm difference in change . CONCLUSION Simple interventions of minimal contact time focusing on walking can significantly increase physical activity in individuals at increased risk of developing colon cancer . TRIAL REGISTRATION ClinicalTrials.gov NCT01476631 .

screening colonoscopy

physical activity intervention

Physical activity

moderate/vigorous

pedometer measured physical activity

increase in steps/day

patients with colon adenomas

adults

Sixteen

adults


Margarines fortified with α-linolenic acid , eicosapentaenoic acid , or docosahexaenoic acid alter the fatty acid composition of erythrocytes but do not affect the antioxidant status of healthy adults . We aimed to investigate the effects of increased intake of α-linolenic acid ( ALA ) , EPA , or DHA incorporated into a food matrix on the fatty acid composition of erythrocytes and on biomarkers of oxidant/antioxidant status . To this end , a controlled dietary study was conducted in 74 healthy men and women . The participants were randomly assigned to 1 of 3 interventions in which margarines fortified with either 10 weight percent ALA , EPA , or DHA ethyl esters replaced their normal spread for 6 wk . The total intakes of ALA , EPA , and DHA were 4.4 , 2.2 , and 2.3 g/d , respectively . Consuming EPA increased the erythrocyte proportion of EPA ( 394 % ) and the omega-3 index ( sum of EPA and DHA , 38 % ) . Consumption of DHA increased erythrocyte DHA ( 91 % ) , the omega-3 index ( 98 % ) , and EPA ( 137 % ) . The omega-3 index increased to a significantly greater extent in the DHA group than in the EPA group . ALA did not increase erythrocyte EPA or the omega-3 index . We found no change in plasma uric acid or antioxidant capacity in any of the groups . Plasma malondialdehyde ( MDA ) increased with the EPA and DHA interventions . All 3 interventions decreased erythrocyte linoleic acid hydroperoxides but did not affect their MDA concentrations . In conclusion , the intake of both isolated EPA and DHA incorporated into margarine resulted in an enhanced incorporation of EPA and DHA into erythrocytes . Our findings indicate that DHA is quantitatively superior to EPA in view of the EPA+DHA tissue incorporation and also that 4 g/d ALA is not sufficient to increase the omega-3 index over a 6-wk period .

α-linolenic acid

eicosapentaenoic acid

docosahexaenoic acid

DHA ethyl esters

erythrocyte proportion of EPA

omega-3 index

erythrocyte DHA

EPA

omega-3 index

erythrocyte EPA

omega-3 index

healthy

men and women


[ Localised prostate cancer : the PREFERE trial ] . Prostate cancer is the most common carcinoma of the elderly man and holds the third place in the ranking of cancer-specific mortality . However , mortality rates of 3 % are low , and half of the patients will die from intercurrent disease . Due to the significantly improved diagnostic methods and the increasing use of PSA screening , there has been a stage migration towards early tumour stages that are prognostically heterogeneous and require differentiated treatment . Based on the discussions of the Joint Federal Committee ( G-BA ) and the conceptual work of the MDS , the Competence Centre Oncology of the MDK , the IQWIG and the National Association of Statutory Health Insurance Funds ( GKV-Spitzenverband ) , a prospective randomised multicentre trial was developed comparing the four treatments actually recommended by the German and European guidelines for localised prostate cancer ( radical prostatectomy , percutaneous radiotherapy and permanent seed implantation and active surveillance ) allowing a rejection of one or two treatment options . The trial is expected to start at the beginning of next year .

radical prostatectomy

percutaneous radiotherapy

permanent seed implantation

active surveillance

cancer-specific mortality

mortality rates

radical prostatectomy

percutaneous radiotherapy

permanent seed implantation

active surveillance

[ Localised prostate cancer :

carcinoma


Different cardiac biomarkers to detect peri-procedural myocardial infarction in contemporary coronary stent trials : impact on outcome reporting . OBJECTIVE To assess the differential implications of cardiac biomarker type on peri-procedural myocardial infarction ( PMI ) reporting . SETTING The Resolute 'All-Comers ' stent trial . INTERVENTIONS Blood samples for creatine kinase ( CK ) , CK-myoband ( CK-MB ) mass or cardiac troponin ( cTn ) ( optional ) were collected before and at 6 , 12 and 18 h after the assigned percutaneous coronary intervention or at discharge . PMIs were adjudicated using either the 2007 universal definition of MI ( type-4a ) or the extended historical definition of MI . PATIENTS 2121/2292 patients ( 92.5 % ) had an analysable dataset for either biomarker . 890/2121 patients ( 42 % ) presented with an acute coronary syndrome ( ACS ) . 267/890 patients ( 30 % ) were within 24 h of an ST-segment elevation MI . MAIN OUTCOME MEASURES Type-4a MI was diagnosed in 208/2121 patients ( 9.8 % ) when cTn was used ( CK-MB mass if cTn not available ) , and in 93/2121 of patients ( 4.4 % ) when CK-MB mass was used ( cTn if CK-MB mass not available ) . With the extended historical CK-based definition of MI , PMI was diagnosed in 65/2121 patients ( 3.1 % ) . Adjudication of type-4a MI in patients with an ACS was problematic with < 10 % of the potential type-4a MI being confirmed as an event , as compared with approximately 95 % in stable patients undergoing elective PCI . Type-4a MI was not associated with the subsequent hazard for cardiac mortality ( p=0.6 ) . CONCLUSIONS The percentage of adjudicated PMI events is driven by the MI-definition criteria and biomarker type . Type-4a MI may not be a reliable component of the primary composite end point in coronary stent investigations which recruit patients with ACS . TRIAL REGISTRATION NUMBER http : //www.ClinicalTrials.gov ; Unique identifier : NCT00617084 .

percutaneous coronary intervention

Type-4a MI

PMI

type-4a MI

cardiac mortality

PMI events

contemporary coronary stent trials :

267/890 patients


A parent-mediated intervention to increase responsive parental behaviors and child communication in children with ASD : a randomized clinical trial . Longitudinal research has demonstrated that responsive parental behaviors reliably predict subsequent language gains in children with autism spectrum disorder . To investigate the underlying causal mechanisms , we conducted a randomized clinical trial of an experimental intervention ( Focused Playtime Intervention , FPI ) that aims to enhance responsive parental communication ( N = 70 ) . Results showed a significant treatment effect of FPI on responsive parental behaviors . Findings also revealed a conditional effect of FPI on children 's expressive language outcomes at 12-month follow up , suggesting that children with baseline language skills below 12 months ( n = 24 ) are most likely to benefit from FPI . Parents of children with more advanced language skills may require intervention strategies that go beyond FPI 's focus on responsive communication .

parent-mediated intervention

Focused Playtime Intervention , FPI )

FPI

FPI

FPI

responsive parental behaviors

child communication

responsive parental behaviors

language gains

responsive parental communication

responsive parental behaviors

language skills

responsive communication

children with ASD :


Direct renin inhibition improves parasympathetic function in diabetes . AIM The renin-angiotensin-aldosterone system ( RAAS ) and autonomic nervous system regulate the cardiovascular system . Blockade of the RAAS may slow the progression of end-organ damage . Direct renin inhibition offers a means for blocking the RAAS . The objective of this study was to examine the effect of direct renin inhibition on cardiovascular autonomic function . METHODS In this double-blind , placebo-controlled trial , 60 individuals with diabetes were randomly assigned to 300 mg of aliskiren or placebo once daily for 6 weeks . The primary end point was a change in tests of cardiovascular autonomic function . Autonomic function was assessed by power spectral analysis and RR-variation during deep breathing [ i.e . mean circular resultant ( MCR ) , expiration/inspiration ( E/I ) ratio ] . The MCR and E/I ratio assess parasympathetic function . Secondary measures included change in biochemical parameters [ e.g . plasma renin activity , leptin and interleukin-6 ] . Change in cardiovascular autonomic function and blood analytes were analysed by a mixed effects model for repeated measures . RESULTS Baseline characteristics were similar between treatment groups . In response to aliskiren compared with placebo , blood pressure was reduced as well as plasma renin activity [ from 2.4 ± 3.8 ( mean ± standard deviation ) to 0.5 ± 0.4 µg/l/h , p < 0.001 ] . There was a significant interaction ( aliskiren × visit ) for MCR ( p = 0.003 ) and E/I ratio ( p = 0.003 ) indicating improvement in MCR and E/I ratio for those on aliskiren . MCR means , baseline vs. follow-up , were 41.8 ± 19.7 vs. 50.8 ± 26.1 ( aliskiren ) and 38.2 ± 23.6 vs. 37.5 ± 24.1 ( placebo ) . CONCLUSIONS Parasympathetic function ( i.e . MCR and E/I ratio ) was enhanced by downregulation of the RAAS .

placebo-controlled

aliskiren

placebo

aliskiren

placebo

Autonomic function

change in biochemical parameters

blood pressure

diabetes

diabetes


In vitro biocompatibility tests of glass ionomer cements impregnated with collagen or bioactive glass to fibroblasts . AIM AND DESIGN To evaluate the biocompatibility of glass ionomer cement ( GIC ) impregnated with collagen or bioactive glass to BHK-21 fibroblasts in vitro . Mineral Trioxide Aggregate was used as the standard for comparison . Human maxillary central incisors ( n = 70 ) were instrumented with a rotary NiTi system and filled . Following resection of the apical 3mm , root end cavities were prepared and restored with conventional GIC ( group 1 ) or GIC with 0.01 % , 0.1 % or 1 % collagen ( groups 2 , 3 , 4 respectively ) or , 10 % , 30 % or 50 % bioactive glass ( groups 5 , 6 , 7 respectively ) , or Mineral Trioxide Aggregate ( group 8 ) . The root slices were incubated in tissue culture plates with BHK-21 fibroblast cell line . Phase contrast and scanning electron microscopes were used to score cell quantity , morphology and cell attachment . The data were statistically analyzed by one way ANOVA with Post Hoc Tukey HSD test ( p = 0.05 ) . RESULTS AND CONCLUSIONS Group 5 showed the highest scores which was significantly higher than all other groups ( p < 0.05 ) except group 8 , with which there was no significant difference ( p > 0.05 ) . Glass ionomer cement with 10 % bioactive glass showed better adhesion and spreading of cells than glass ionomer cement with 0.01 % collagen . The biocompatibility of collagen and bioactive glass was concentration dependent . The addition of bioactive glass improved the biocompatibility of glass ionomer cement to fibroblasts better than addition of collagen .

score cell quantity

morphology

cell attachment

ANOVA with Post Hoc Tukey HSD test

better adhesion

spreading of cells

Human maxillary central incisors


Adjunctive perampanel for refractory partial-onset seizures : randomized phase III study 304 . OBJECTIVE To assess efficacy and safety of once-daily 8 or 12 mg perampanel , a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid ( AMPA ) receptor antagonist , when added to concomitant antiepileptic drugs ( AEDs ) in the treatment of drug-resistant partial-onset seizures . METHODS This was a multicenter , double-blind , placebo-controlled trial ( ClinicalTrials.gov identifier : NCT00699972 ) . Patients ( ≥12 years , with ongoing seizures despite 1-3 AEDs ) were randomized ( 1:1:1 ) to once-daily perampanel 8 mg , 12 mg , or placebo . Following baseline ( 6 weeks ) , patients entered a 19-week double-blind phase : 6-week titration ( 2 mg/week increments to target dose ) followed by a 13-week maintenance period . Percent change in seizure frequency was the primary endpoint ; 50 % responder rate was the primary endpoint for EU registration . RESULTS Of 388 patients randomized and treated , 387 provided seizure frequency data . Using this intent-to-treat population over the double-blind phase , the median percent change in seizure frequency was -21.0 % , -26.3 % , and -34.5 % for placebo and perampanel 8 and 12 mg , respectively ( p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo , respectively ) . Fifty percent responder rates during the maintenance period were 26.4 % , 37.6 % , and 36.1 % , respectively , for placebo , perampanel 8 mg , and perampanel 12 mg ; these differences were not statistically significant for 8 mg ( p = 0.0760 ) or 12 mg ( p = 0.0914 ) . Sixty-eight ( 17.5 % ) patients discontinued , including 40 ( 10.3 % ) for adverse events . Most frequent treatment-emergent adverse events were dizziness , somnolence , irritability , headache , fall , and ataxia . CONCLUSIONS This trial demonstrated that once-daily , adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures . Doses of perampanel 8 and 12 mg were safe , and tolerability was acceptable . CLASSIFICATION OF EVIDENCE This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures .

perampanel

perampanel

improved seizure control


Development , awareness and inductive selectivity . Two studies examined whether adults and children could learn to make context-dependent inferences about novel stimuli and the role of awareness of context cues in such learning . Participants were trained to match probes to targets on the basis of shape or color with the relevant dimension shifting according to item context . A selective induction test then examined context-dependent responding in a more complex matching task . Awareness of the role of context was assessed using a behavioral task and explicit questions . Experiment 1 showed that after training with the procedure described by Sloutsky and Fisher ( 2008 ) , only a minority of adults showed evidence of context-dependent responding in the selective induction test . Experiment 2 used a modified training protocol that promoted attention to context cues . This led to reliable selective induction in a majority of adults and a sizeable proportion of 4- to 6-year-olds . Crucially , in both age groups , selective induction was dependent on awareness of context . Hence , children as young as 4 can learn to make selective inferences about novel stimuli , but only when they are aware of the relevant context cues . These results challenge previous claims that selective induction in children is the product of implicit learning .

trained to match probes to targets

induction test

behavioral task

explicit questions

training

modified training protocol

selective induction

selective induction

adults

children

4- to 6-year-olds


Assessing the bioequivalence of topical retinoid products by pharmacodynamic assay . PURPOSE To develop a simple pharmacodynamic ( PD ) assay for the evaluation of the bioequivalence of topically applied retinoid products . METHODS Daily applications of products containing tretinoin or adapalene were made to the forearms of human subjects for up to 21 days . Percutaneous absorption was enhanced through the use of polyethylene film occlusion ( 5 h ) . Pharmacologic activity was assessed through the daily measurement of three cutaneous responses intimately linked to retinoid-induced changes in epidermal differentiation : ( 1 ) erythema ; ( 2 ) exfoliation ( scaling/peeling ) , and ( 3 ) increased transepidermal water loss . RESULTS The PD model exhibited the sensitivity and specificity required to function as a bioequivalence surrogate . It was possible to differentiate between : ( 1 ) three concentrations of tretinoin in a commercial cream product line ; ( 2 ) two concentrations of tretinoin in a commercial gel product line ; ( 3 ) different vehicles ( gel vs. cream ) containing the same concentration of tretinoin , and ( 4 ) tretinoin and adapalene at the same concentration . The applicability of this model for bioequivalence testing was established by showing that it had sufficient power to determine that three test tretinoin cream products and two approved generic tretinoin gel products were equivalent to their corresponding reference products . CONCLUSIONS A surrogate PD model to assess retinoid bioequivalence has been developed .

retinoid products .

polyethylene film occlusion

erythema ;

exfoliation ( scaling/peeling )

transepidermal water loss .

sensitivity and specificity

retinoid bioequivalence

pharmacodynamic ( PD ) assay

forearms of human subjects


Errors during the preparation of drug infusions : a randomized controlled trial . BACKGROUND We investigated the extent and frequency of dose errors and treatment delays made as a consequence of preparing drug infusions at the bedside , rather than using pre-filled syringes . METHODS Forty-eight nurses with critical care experience volunteered to take part in this randomized , blinded , controlled study conducted in the simulation centre of an urban hospital . They assisted in the management of a simulated patient with septic shock . Vasopressor infusions were prepared either by diluting concentrated drugs from ampoules or were provided in syringes pre-filled beforehand by an intensive care unit resident . RESULTS The time taken for the infusion to be started and the final concentration of the drugs were measured . We also measured the concentration of infusions prepared by a pharmacist and a pharmaceutical company . Nurses took 156 s to start infusions when using pre-filled syringes compared with 276 s when preparing them de novo , a mean delay of 106 s [ 95 % confidence interval ( CI ) 73-140 s , P < 0.0001 ] . One infusion prepared from ampoules contained one-fifth of the expected concentration of epinephrine ; another contained none at all . Medication errors were 17.0 times less likely when pre-filled syringes were used ( 95 % CI 5.2-55.5 ) , and infusions prepared by pharmacy and industry were significantly more likely to contain the expected concentration ( P < 0.001 for norepinephrine and P=0.001 for epinephrine ) . CONCLUSIONS Providing drug infusions in syringes pre-filled by pharmacists or pharmaceutical companies would reduce medication errors and treatment delays , and improve patient safety . However , this approach would have substantial financial implications for healthcare providers , especially in less developed countries .

drug infusions at the bedside

pre-filled syringes

Vasopressor infusions

syringes pre-filled

pre-filled syringes

epinephrine

pre-filled syringes

infusions

norepinephrine

epinephrine

drug infusions

pre-filled

final concentration of the drugs

concentration of infusions

Medication errors

medication errors

treatment delays

patient safety

Forty-eight

septic shock


[ Photoplethysmographic evaluation of the effect of a vascular tonic drug ] .

vascular tonic drug ]

[ Photoplethysmographic evaluation

vascular tonic drug ]


Virtual patients design and its effect on clinical reasoning and student experience : a protocol for a randomised factorial multi-centre study . BACKGROUND Virtual Patients ( VPs ) are web-based representations of realistic clinical cases . They are proposed as being an optimal method for teaching clinical reasoning skills . International standards exist which define precisely what constitutes a VP . There are multiple design possibilities for VPs , however there is little formal evidence to support individual design features . The purpose of this trial is to explore the effect of two different potentially important design features on clinical reasoning skills and the student experience . These are the branching case pathways ( present or absent ) and structured clinical reasoning feedback ( present or absent ) . METHODS/DESIGN This is a multi-centre randomised 2 x 2 factorial design study evaluating two independent variables of VP design , branching ( present or absent ) , and structured clinical reasoning feedback ( present or absent ) .The study will be carried out in medical student volunteers in one year group from three university medical schools in the United Kingdom , Warwick , Keele and Birmingham . There are four core musculoskeletal topics . Each case can be designed in four different ways , equating to 16 VPs required for the research . Students will be randomised to four groups , completing the four VP topics in the same order , but with each group exposed to a different VP design sequentially . All students will be exposed to the four designs . Primary outcomes are performance for each case design in a standardized fifteen item clinical reasoning assessment , integrated into each VP , which is identical for each topic . Additionally a 15-item self-reported evaluation is completed for each VP , based on a widely used EViP tool . Student patterns of use of the VPs will be recorded.In one centre , formative clinical and examination performance will be recorded , along with a self reported pre and post-intervention reasoning score , the DTI . Our power calculations indicate a sample size of 112 is required for both primary outcomes . DISCUSSION This trial will provide robust evidence to support the effectiveness of different designs of virtual patients , based on student performance and evaluation . The cases and all learning materials will be open access and available on a Creative Commons Attribution-Share-Alike license .

Virtual patients design

Virtual Patients ( VPs )

VP

VP

VP

VP

clinical reasoning

student experience :

clinical reasoning skills

student experience

15-item self-reported evaluation

student performance

evaluation


[ Does urapidil attenuate the hypertensive response to tracheal intubation at the time of general anesthesia ? ] .

urapidil

tracheal intubation

anesthesia


A comparative study of ofloxacin and amoxycillin/clavulanate in hospitalized patients with lower respiratory tract infections . We conducted an open randomized trial to compare the efficacy of parenteral and oral ofloxacin with that of amoxycillin/clavulanate . A total of 121 patients was studied ; 92 were clinically evaluable . Of these , 59 patients were treated with ofloxacin and 33 with the comparator drug . Patients were given the drugs intravenously for a minimum of three days followed by oral preparations for the next seven to ten days . Ofloxacin was usually administered as a 200 mg dose bd . In the ofloxacin treated group all patients showed clinical improvement . In the comparator group 94 % improved clinically ( either a complete or partial response ) , while 6 % were clinical failures . Of the bacteriologically evaluable patients 19 of 20 showed a satisfactory bacteriological response in the ofloxacin treated group , while in the comparator group the bacteriological response was judged satisfactory in 14 of 17 patients . A small proportion of patients ( 7 % ) treated with ofloxacin suffered mild adverse effects ( nausea , vomiting , headache , hypotension and rash ) . On the whole , ofloxacin was well tolerated by our patients . The two deaths that occurred were in the comparator group . We conclude that ofloxacin in both oral and parenteral forms is an effective and safe drug in the treatment of lower respiratory tract infections .

ofloxacin

amoxycillin/clavulanate

ofloxacin

amoxycillin/clavulanate

ofloxacin

Ofloxacin

ofloxacin

ofloxacin

ofloxacin

lower respiratory tract infections .

clinical improvement .

satisfactory bacteriological response

tolerated


Who is at low risk for cardiovascular disease ? An assessment of different definitions . BACKGROUND There is little information regarding the determinants and trends of the prevalence of low cardiovascular risk factor ( RF ) profile in the general population . The aim of this study was to assess the prevalence and trends of low RF profile in the Swiss population according to different definitions . METHODS Population-based cross-sectional studies conducted in 1984-1986 ( N=3300 ) , 1988-1989 ( N=3331 ) , 1992-1993 ( N=3133 ) and 2003-2006 ( N=6170 ) and restricted to age group 35-75 years . Seven different definitions of low RF profile were used to assess determinants , while two definitions were used to assess trends . RESULTS Prevalence of low RF profile varied between 6.5 % ( 95 % confidence interval : 5.9-7.1 ) and 9.7 % ( 9.0-10.5 ) depending on the definition used . This prevalence was higher than in other countries . Irrespective of the definition used , the prevalence of low RF profile was higher in women and in physically active participants , and decreased with increasing age or in the presence of a family history of cardiovascular disease . Using one definition , the prevalence of low RF profile increased from 3.8 % ( 3.1-4.5 ) in 1984-1986 to 6.7 % ( 6.1-7.3 ) in 2003-2006 ; using another definition , the results were 5.9 % ( 5.1-6.8 ) and 9.7 % ( 9.0-10.5 ) , respectively . CONCLUSION Switzerland is characterized by a high and increasing prevalence of low RF profile within the age group 35 to 75 , irrespective of the criteria used . This high prevalence might partly explain the low and decreasing trend in cardiovascular mortality rates .

low cardiovascular risk factor

prevalence and trends of low RF profile

low RF profile

low RF profile

RF profile

1988-1989 (

1992-1993 (

2003-2006 (

age group 35-75 years

age group 35 to 75


Effect of antipsychotic drugs on cortical thickness . A randomized controlled one-year follow-up study of haloperidol , risperidone and olanzapine . BACKGROUND Imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time . The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis . We aimed to investigate the effects of low doses of haloperidol , risperidone and olanzapine on cortical thickness . METHOD We investigated the effects of risperidone ( N=16 ) , olanzapine ( N=18 ) and low doses of haloperidol ( N=18 ) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients . The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed . A group of 45 healthy volunteers was also longitudinally evaluated . Magnetic resonance imaging brain scans ( 1.5T ) were obtained and images were analyzed by using BRAINS2 . RESULTS There were no significant effects of time ( F ( 1,47 ) < 1.66 ; P > 0.204 ) , treatment group ( F ( 2,47 ) < 1.47 ; P > 0.242 ) or group-by-time interaction ( F ( 2,47 ) < 1.82 ; P > 0.174 ) for any of the cortical thickness variables . When the group of healthy controls was included in the analyses , it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level ( F ( 3,81 ) =2.686 ; P=0.052 ) . After the Bonferroni adjustment for multiple comparisons , there were no significant associations between changes in cortical thickness and clinical and cognitive outcome . CONCLUSIONS Low doses of haloperidol , risperidone , and olanzapine seem to equally affect gray matter cortical thickness , overall and lobes , at the medium-term ( 1 year ) . The clinical effectiveness of treatments was not significantly related to changes in cortical thickness .

antipsychotic drugs

haloperidol

risperidone

olanzapine

antipsychotic medication

haloperidol

risperidone

olanzapine

risperidone

olanzapine

haloperidol

haloperidol

risperidone

olanzapine

cortical thickness .

effects of antipsychotic medication

cortical thickness

cortical thickness changes

clinical

cortical thickness variables .

changes in cortical thickness

cortical thickness

risperidone

olanzapine

haloperidol

schizophrenia spectrum

healthy


Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease . OBJECTIVE To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin . METHODS Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin ( n = 78 ) or double-dose statin ( n = 72 ) for 52 weeks . RESULTS Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin , while LDL-C levels re-increased after 12 weeks in double-dose statin . Although lathosterol/TC increased , campesterol/TC decreased more in ezetimibe-plus-statin . In contrast , lathosterol/TC unchanged and campesterol/TC increased , increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin . Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks , but similar at 52 weeks . CONCLUSION Although the difference in PCSK9 between 2 groups was transient , that in both campesterol and lathosterol persisted until 52 weeks . These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels .

ezetimibe-plus-statin

double-dose statin therapy

ezetimibe-plus-statin

patients with coronary artery disease .


Is EEG-biofeedback an effective treatment in autism spectrum disorders ? A randomized controlled trial . EEG-biofeedback has been reported to reduce symptoms of autism spectrum disorders ( ASD ) in several studies . However , these studies did not control for nonspecific effects of EEG-biofeedback and did not distinguish between participants who succeeded in influencing their own EEG activity and participants who did not . To overcome these methodological shortcomings , this study evaluated the effects of EEG-biofeedback in ASD in a randomized pretest-posttest control group design with blinded active comparator and six months follow-up . Thirty-eight participants were randomly allocated to the EEG-biofeedback , skin conductance ( SC ) -biofeedback or waiting list group . EEG- and SC-biofeedback sessions were similar and participants were blinded to the type of feedback they received . Assessments pre-treatment , post-treatment , and after 6 months included parent ratings of symptoms of ASD , executive function tasks , and 19-channel EEG recordings . Fifty-four percent of the participants significantly reduced delta and/or theta power during EEG-biofeedback sessions and were identified as EEG-regulators . In these EEG-regulators , no statistically significant reductions of symptoms of ASD were observed , but they showed significant improvement in cognitive flexibility as compared to participants who managed to regulate SC . EEG-biofeedback seems to be an applicable tool to regulate EEG activity and has specific effects on cognitive flexibility , but it did not result in significant reductions in symptoms of ASD . An important finding was that no nonspecific effects of EEG-biofeedback were demonstrated .

EEG-biofeedback

EEG-biofeedback

EEG-biofeedback

EEG-biofeedback

skin conductance ( SC ) -biofeedback

EEG-

SC-biofeedback

EEG-biofeedback sessions

EEG-biofeedback

19-channel EEG recordings

delta and/or theta power

symptoms of ASD

cognitive flexibility

cognitive flexibility

symptoms of ASD .