Comparative bioavailability study with two pantoprazole delayed-released tablet formulations administered with and without food in healthy subjects . OBJECTIVE To assess the comparative bioavailability of two formulations ( 40 mg delayed-released [ DR ] tablet ; test and reference ) of pantoprazole ( CAS 102625-70-7 ) in healthy volunteers of both sexes , with and without food . METHODS The study was conducted using an open , randomized , two-period crossover design with a 1-week washout interval , in two groups , with and without food . Plasma samples were obtained for up to 24 h post dose . Plasma pantoprazole concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry ( LC-MS-MS ) with positive ion electrospray ionization using multiple reactions monitoring ( MRM ) . From the pantoprazole plasma concentration vs. time curves , the pharmacokinetic parameters AUC ( last ) and C ( max ) were obtained , with and without food . RESULTS The limit of quantification was 5 ng/mL for plasma pantoprazole analysis . The geometric mean and 90 % confidence interval CI of test/reference percent ratios were , without and with food , respectively : 104.6540 % ( 90.8616 % -120.5401 % ) and 99.9708 % ( 90.9987 % -109.8275 % ) for C ( max ) , 95.6634 % ( 85.2675 % -107.3267 % ) and 89.3500 % ( 83.6630 % -95.4237 % ) for AUC ( last ) . CONCLUSION Since the 90 % CI for AUC ( last ) and C ( max ) ratios were within the 80-125 % interval proposed by the US FDA , it was concluded that pantoprazole 40 mg DR tablet ( test formulation ) with and without food was bioequivalent to the reference 40 mg DR tablet for both the rate and extent of absorption .

pantoprazole

pantoprazole

pantoprazole

pantoprazole

comparative bioavailability

limit of quantification

C ( max )

AUC ( last )

C ( max ) ratios


Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation . Dietary supplementation of glutamine prevents intestinal dysfunction and atrophy in weanling piglets , but the underlying mechanism ( s ) are largely unknown . This study was conducted to test the hypothesis that weaning or glutamine may modulate expression of genes that are crucial for intestinal metabolism and function . In Expt . 1 , we obtained small intestine from 28-d-old pigs weaned at 21 d of age and from age-matched suckling piglets . In Expt . 2 , piglets were weaned at 21 d of age and then had free access to diets supplemented with 1 % L-glutamine ( wt : wt ) or isonitrogenous L-alanine ( control ) . At d 28 , we collected small intestine for biochemical and morphological measurements and microarray analysis of gene expression using the Operon Porcine Genome Oligo set . Early weaning resulted in increased ( 52-346 % ) expression of genes related to oxidative stress and immune activation but decreased ( 35-77 % ) expression of genes related to macronutrient metabolism and cell proliferation in the gut . Dietary glutamine supplementation increased intestinal expression ( 120-124 % ) of genes that are necessary for cell growth and removal of oxidants , while reducing ( 34-75 % ) expression of genes that promote oxidative stress and immune activation . Functionally , the glutamine treatment enhanced intestinal oxidative-defense capacity ( indicated by a 29 % increase in glutathione concentration ) , prevented jejunal atrophy , and promoted small intestine growth ( +12 % ) and body weight gain ( +19 % ) in weaned piglets . These findings reveal coordinate alterations of gene expression in response to weaning and aid in providing molecular mechanisms for the beneficial effect of dietary glutamine supplementation to improve nutrition status in young mammals .

dietary glutamine supplementation

Dietary supplementation of glutamine

L-glutamine

isonitrogenous L-alanine

Dietary glutamine supplementation

glutamine treatment

glutamine supplementation

gene expression

cell proliferation in the gut .

jejunal atrophy

21 d


Symptomatic treatment versus combination chemotherapy for patients with extensive non-small cell lung cancer . In a randomized clinical trial , 87 patients with inoperable , extensive non-small cell lung cancer ( NSCLC ) were randomized to receive either combination chemotherapy ( cisplatin at 70 mg/m2 intravenously [ i.v . ] on day 1 and etoposide at 100 mg/m2 i.v . on day 1 and 200 mg/m2 orally on days 2 and 3 ) or symptomatic treatment . No statistically significant differences in survival time were found between the two treatment techniques . A major problem in the interpretation of the results was the use of semicurative radiation therapy ( 3000 to 4200 cGy ) to the primary tumor and mediastinum , which was given with symptomatic intent . Three long-term survivors were seen in the latter group .

Symptomatic treatment

combination chemotherapy

combination chemotherapy ( cisplatin

etoposide

symptomatic treatment

survival time

Three long-term survivors


Penetration and accumulation of moxifloxacin in uterine tissue . OBJECTIVE To determine whether moxifloxacin penetrates the uterine tissue and accumulates at levels sufficient to eradicate the major pathogens causing pelvic inflammatory disease ( PID ) . METHOD In a prospective , multicenter , open-label , parallel-group study we determined the concentration of moxifloxacin in plasma and uterine tissue after a single , 400-mg intravenous dose of moxifloxacin . Study participants were randomized for time of tissue sampling , which was performed 1 , 2 , 4 , 7 , or 24 hours following the moxifloxacin infusion . RESULTS Of 43 participants , 40 were randomized to tissue sampling . Moxifloxacin accumulated in uterine tissue and concentrations were highest 1 hour after infusion in both plasma and tissue . Tissue to plasma ratios remained between 1.7 and 2.1 for 24 hours . Moxifloxacin was found to be safe and well tolerated . CONCLUSION Based on known minimum inhibitory concentration data , the uterine tissue concentrations of moxifloxacin achieved over 24 hours would be sufficient to eradicate the range of bacterial pathogens responsible for PID .

moxifloxacin

moxifloxacin

400-mg intravenous dose of moxifloxacin

moxifloxacin

Penetration and accumulation

eradicate the major pathogens

Tissue to plasma ratios

safe and well tolerated

uterine tissue concentrations

pelvic inflammatory disease ( PID )

PID


Effect of adhesive system type and tooth region on the bond strength to dentin . PURPOSE This study evaluated the bond strength of two etch-and-rinse adhesive systems ( two- and three-step ) and a self-etching system to coronal and root canal dentin . MATERIALS AND METHODS The root canals of 30 human incisors and canines were instrumented and prepared with burs . The posts used for luting were duplicated with dual resin cement ( Duo-link ) inside Aestheti Plus # 2 molds . Thus , three groups were formed ( n = 10 ) according to the adhesive system employed : All-Bond 2 ( TE3 ) + resin cement post ( rcp ) + Duo-link ( Dl ) ; One-Step Plus ( TE2 ) + rcp + Dl ; Tyrian/One-Step Plus ( SE ) + rcp + Dl . Afterwards , 8 transverse sections ( 1.5 mm ) were cut from 4 mm above the CEJ up to 4 mm short of the root canal apex , comprising coronal and root canal dentin . The sections were submitted to push-out testing in a universal testing machine EMIC ( 1 mm/min ) . Bond strength data were analyzed with two-way repeated measures ANOVA and Tukey 's test ( p < 0.05 ) . RESULTS The relationship between the adhesives was not the same in the different regions ( p < 0.05 ) . Comparison of the means achieved with the adhesives in each region ( Tukey ; p < 0.05 ) revealed that TE3 ( mean +/- standard deviation : 5.22 +/- 1.70 ) was higher than TE2 ( 2.60 +/- 1.74 ) and SE ( 1.68 +/- 1.85 ) . CONCLUSION Under the experimental conditions , better bonding to dentin was achieved using the three-step etch-and-rinse system , especially in the coronal region . Therefore , the traditional etch-and-rinse three-step adhesive system seems to be the best choice for teeth needing adhesive endodontic restorations .

etch-and-rinse adhesive systems

and a self-etching system

coronal and root canal dentin

Bond strength data

relationship between the adhesives

root canals


[ Radiotherapy of malignant brain gliomas using teniposide ] . Efficacy of radiochemotherapy of malignantly-converted brain gliomas using teniposide was evaluated in a randomized prospective study . Combined use of cytostatics and irradiation appeared safe , tolerable and significantly more effective than radiotherapy alone as assessed by local control of tumor and survival .

Radiotherapy

teniposide

radiochemotherapy

teniposide

cytostatics

irradiation

radiotherapy alone

Efficacy

local control of tumor and

survival

malignant brain gliomas

malignantly-converted brain gliomas


Heart rate variability characteristics in sedentary postmenopausal women following six months of exercise training : the DREW study . BACKGROUND Decreased heart rate variability ( HRV ) is associated with a higher risk of mortality . Overall , postmenopausal women have lower levels of HRV than premenopausal women , which may be additionally complicated by lifestyle related behaviors such as physical inactivity and obesity . Though cardiorespiratory exercise training increases HRV , little is known regarding the exercise dose necessary to promote this improvement . METHODOLOGY/PRINCIPAL FINDINGS Our primary aim was to measure HRV in post-menopausal women following 6-months of exercise training . We examined supine resting HRV in 373 post-menopausal women ( 45-75 y ) after 6-months of randomly assigned and double-blinded administered exercise training exercise training at 50 % , 100 % and 150 % of the NIH Consensus Development Panel 's recommended minimal physical activity level . This corresponded to 4 , 8 , or 12 kcal/kg per week ( KKW ) of energy expenditure . At baseline , we observed no significant differences in HRV or hormone replacement use between treatment groups . However , we did observe that Caucasian women and those taking antidepressant medications had lower levels of baseline HRV . After 6-months of exercise intervention , we observed a dose dependent increase in all parasympathetically derived time and frequency domain measurements across exercise groups after adjustment for age , ethnicity , antidepressants , and baseline rMSSD ( all , P < 0.001 ) . For example , the parasympathetic index rMSSD was greater than control ( 23.19+/-1.0 ) for the 4-KKW ( 25.98+/-0.8 ; P = 0.14 ) , 8-KKW ( 27.66+/-1.0 ; P < 0.05 ) , and 12-KKW ( 27.40+/-0.0 ; P < 0.05 ) groups at follow-up . CONCLUSIONS/SIGNIFICANCE Moderate intensity exercise training exercise is sufficient to improve HRV in previously sedentary postmenopausal women in a dose-dependent manner , as 4-KKW is insufficient to improve parasympathetic indices of HRV , while 12-KKW conferred no greater improvement than 8-KKW . TRIAL REGISTRATION Clinicaltrials.gov NCT 00011193 .

exercise training

cardiorespiratory exercise training

exercise training

exercise training exercise training

exercise intervention

HRV

hormone

baseline HRV

antidepressants

parasympathetic index rMSSD

postmenopausal women


Effects of 20 mg rosuvastatin on VLDL1- , VLDL2- , IDL- and LDL-ApoB kinetics in type 2 diabetes . AIMS/HYPOTHESIS In addition to its efficacy in reducing LDL-cholesterol , rosuvastatin has been shown to significantly decrease plasma triacylglycerol . The use of rosuvastatin may be beneficial in patients with type 2 diabetes , who usually have increased triacylglycerol levels . However , its effects on the metabolism of triacylglycerol-rich lipoproteins in type 2 diabetic patients remains unknown . METHODS We performed a randomised double-blind crossover trial of 6-week treatment with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes who were being treated with oral glucose-lowering agents . In each patient , an in vivo kinetic study of apolipoprotein B ( ApoB ) -containing lipoproteins with [ 13C ] leucine was performed at the end of each treatment period . A central randomisation centre used computer-generated tables to allocate treatments . Participants , caregivers and those assessing the outcomes were blinded to group assignment . RESULTS Rosuvastatin 20 mg significantly reduced plasma LDL-cholesterol , triacylglycerol and total ApoB . It also significantly reduced ApoB pool sizes of larger triacylglycerol-rich VLDL particles ( VLDL1 ; p = 0.011 ) , smaller VLDL particles ( VLDL2 ; p = 0.011 ) , intermediate density lipoprotein ( IDL ; p = 0.011 ) and LDL ( p = 0.011 ) . This reduction was associated with a significant increase in the total fractional catabolic rate of VLDL1-ApoB ( 6.70 +/- 3.24 vs 4.52 +/- 2.34 pool/day , p = 0.049 ) , VLDL2-ApoB ( 8.72 +/- 3.37 vs 5.36 +/- 2.64 , p = 0.011 ) , IDL-ApoB ( 7.06 +/- 1.68 vs 4.21 +/- 1.51 , p = 0.011 ) and LDL-ApoB ( 1.02 +/- 0.27 vs 0.59 +/- 0.13 , p = 0.011 ) . Rosuvastatin did not change the production rates of VLDL2- , IDL- or LDL- , but did reduce VLDL1-ApoB production rate ( 12.4 +/- 4.5 vs 19.5 +/- 8.4 mg kg ( -1 ) day ( -1 ) , p = 0.035 ) . No side effects of rosuvastatin were observed during the study . CONCLUSIONS/INTERPRETATION In type 2 diabetic patients rosuvastatin 20 mg not only induces a significant increase of LDL-ApoB catabolism ( 73 % ) , but also has favourable effects on the catabolism of triacylglycerol-rich lipoproteins , e.g . a significant increase in the catabolism of VLDL1-ApoB ( 48 % ) , VLDL2-ApoB ( 63 % ) and IDL-ApoB ( 68 % ) , and a reduction in the production rate of VLDL1-ApoB ( -36 % ) . The effects of rosuvastatin on the metabolism of triacylglycerol-rich lipoproteins may be beneficial for prevention of atherosclerosis in type 2 diabetic patients .

rosuvastatin

rosuvastatin

rosuvastatin

placebo

rosuvastatin 20 mg

Rosuvastatin

Rosuvastatin

rosuvastatin

rosuvastatin

LDL-cholesterol

plasma triacylglycerol

triacylglycerol levels .

smaller VLDL particles

intermediate density lipoprotein

production rates of VLDL2-

IDL-

LDL-

VLDL1-ApoB production rate

side effects

LDL-ApoB catabolism

catabolism of VLDL1-ApoB

IDL-ApoB

type 2 diabetes

type 2 diabetes

type 2 diabetic

eight

type 2 diabetes

type 2 diabetic

atherosclerosis

type 2 diabetic


A comparison of single-dose versus conventional-dose antibiotic treatment of bacteriuria in elderly women . The efficacy of single-dose antibiotic therapy for the treatment of bacteriuria in a group of non-catheterized elderly women was compared with that of conventional 7-10 day courses of antibiotic therapy . Thirty-one women received single-dose treatment and 22 conventional-dose treatment . The cure rates at 1 and 6 weeks for the single-dose treatments were 52 % and 38 % , respectively , and the cure rates for the conventional-dose treatments at 1 and 6 weeks were 59 % and 52 % , respectively . It is concluded that there may be a place for the use of single-dose antibiotic therapy for the treatment of selected elderly women with bacteriuria , but larger studies are needed .

single-dose

conventional-dose antibiotic treatment

single-dose antibiotic therapy

single-dose treatment

conventional-dose treatment

single-dose antibiotic therapy

cure rates

cure rates


Use of topical selamectin for the treatment of Syphacia muris infection in laboratory rats . Efficacy of selamectin was studied in naturally acquired S. muris infections in rats . Fourty-eight S. muris-positive rats were divided into six treated and two control groups . Selamectin ( 6 mg/kg ) was applied topically to the skin in a single spot at the base of the neck in the treatment group . The rats of treated and control groups were necropsied on the 24th day after the treatment . Topical selamectin was found to be 40.7-63.3 % effective ( based on egg per gram method ) in eliminating S. muris infection in rats . The efficacy of the treatment against S. muris ( based on adult worm counts ) in male and female rats was 35.14-58.88 % , respectively ( mean 48.39 % ) .

selamectin

selamectin

Selamectin

selamectin

Efficacy

muris infection

efficacy of the treatment

Fourty-eight

S. muris-positive rats

male and female rats


Multiple sclerosis risk after optic neuritis : final optic neuritis treatment trial follow-up . OBJECTIVE To assess the risk of developing multiple sclerosis ( MS ) after optic neuritis and the factors predictive of high and low risk . DESIGN Subjects in the Optic Neuritis Treatment Trial , who were enrolled between July 1 , 1988 , and June 30 , 1991 , were followed up prospectively for 15 years , with the final examination in 2006 . SETTING Neurologic and ophthalmologic examinations at 13 clinical sites . PARTICIPANTS Three hundred eighty-nine subjects with acute optic neuritis . MAIN OUTCOME MEASURES Development of MS and neurologic disability assessment . RESULTS The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50 % ( 95 % confidence interval , 44 % -56 % ) and strongly related to presence of lesions on a baseline non-contrast-enhanced magnetic resonance imaging ( MRI ) of the brain . Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72 % of patients with 1 or more lesions . After 10 years , the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions . Among patients without lesions on MRI , baseline factors associated with a substantially lower risk for MS included male sex , optic disc swelling , and certain atypical features of optic neuritis . CONCLUSIONS The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS . In the absence of MRI-detected lesions , male sex , optic disc swelling , and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS . This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis .

Optic Neuritis Treatment

brain MRI

Multiple sclerosis risk

Development of MS

neurologic disability assessment

MS

risk of developing MS

risk for MS

the 15-year risk of MS

developing MS

MS

optic neuritis

optic neuritis

Three hundred eighty-nine

acute optic neuritis


The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia . Sequential methotrexate ( Mtx ) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia ( ALL ) to determine whether serum drug concentration , clearance and dosage affect event free survival ( EFS ) . Higher serum concentration and area under the plasma concentration curve ( AUC ) were not associated with an improved EFS . Methotrexate clearance was not found to be of prognostic significance . Patients who tolerated only low 6-mercaptopurine ( 6-MP ) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy . This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL .

serum methotrexate

methotrexate

Methotrexate

6-mercaptopurine ( 6-MP )

event free survival

Methotrexate clearance

rate of leukaemia relapse

survival

childhood

acute lymphoblastic leukaemia

children

childhood

ALL


The effect of intravenous lidocaine on QT changes during tracheal intubation . Laryngoscopy and tracheal intubation may provoke changes of cardiac repolarisation . The aim of this study was to assess the effect of intravenous lidocaine on the ECG changes induced by laryngoscopy and tracheal intubation . Forty-three female patients were randomly allocated to receive lidocaine ( 1.5 mg.kg ( -1 ) ) or placebo immediately after induction of anaesthesia and changes in the ECG and arterial blood pressure were recorded . Correction of QT interval was calculated using Bazett 's formula ( QTcb ) , Fridericia 's correction ( QTcf ) , and Framingham formula ( QTcF ) . Transmural dispersion of repolarisation ( TDR ) was determined as Tpeak-Tend time . There were no changes in the QTc value in the lidocaine group . In the placebo group , significant increases in QTcb , QTcf and QTcF values were observed after intubation compared to either control measurements or to comparative measurements in the lidocaine group . There were no significant differences in TDR either between or within the groups . Lidocaine diminishes prolongation of QTc , induced by tracheal intubation but there is no effect of intubation on TDR .

lidocaine

lidocaine

lidocaine

placebo

lidocaine

placebo

lidocaine

Lidocaine

QT changes

cardiac repolarisation

ECG changes

ECG and arterial blood pressure

QT interval

QTc value

QTcb , QTcf and QTcF values

TDR

QTc

TDR

tracheal intubation

laryngoscopy

tracheal intubation

Forty-three

female


Anxiety sensitivity as an incremental predictor of later anxiety symptoms and syndromes . Although anxiety sensitivity ( AS ) has been shown to predict anxiety symptoms and panic , this literature is limited in regard to evaluating AS as an incremental predictor of anxiety psychopathology relative to other established risk factors including sex and negative affect . The present report prospectively evaluated whether AS was predictive of later changes in anxiety symptoms after controlling for potential confounding factors . Consistent with hypothesis , AS was found to be a significant , incremental predictor of anxiety symptoms over time , even after controlling for sex and negative affectivity . These data provide novel evidence for the unique association between AS of the development of anxiety symptoms .

anxiety psychopathology

anxiety symptoms

anxiety symptoms

Anxiety sensitivity

later anxiety symptoms and syndromes

anxiety sensitivity

anxiety symptoms and panic

anxiety psychopathology

anxiety symptoms .


A randomized controlled trial for reducing risks for sexually transmitted infections through enhanced patient-based partner notification . OBJECTIVES We sought to assess the effectiveness of approaches targeting improved sexually transmitted infection ( STI ) sexual partner notification through patient referral . METHODS From January 2002 through December 2004 , 600 patients with Neisseria gonorrhoeae or Chlamydia trachomatis were recruited from STI clinics and randomly assigned to either a standard-of-care group or a group that was counseled at the time of diagnosis and given additional follow-up contact . Participants completed an interview at baseline , 1 month , and 6 months and were checked at 6 months for gonorrhea or chlamydial infection via nucleic acid amplification testing of urine . RESULTS Program participants were more likely to report sexual partner notification at 1 month ( 86 % control , 92 % intervention ; adjusted odds ratio [ AOR ] = 1.8 ; 95 % confidence interval [ CI ] = 1.02 , 3.0 ) and were more likely to report no unprotected sexual intercourse at 6 months ( 38 % control , 48 % intervention ; AOR = 1.5 ; 95 % CI = 1.1 , 2.1 ) . Gonorrhea or chlamydial infection was detected in 6 % of intervention and 11 % of control participants at follow-up ( AOR = 2.2 ; 95 % CI = 1.1 , 4.1 ) , with greatest benefits seen among men ( for gender interaction , P = .03 ) . CONCLUSIONS This patient-based sexual partner notification program can help reduce risks for subsequent STIs among urban , minority patients presenting for care at STI clinics .

standard-of-care group

unprotected sexual intercourse

Gonorrhea or chlamydial infection

sexually transmitted infections


A sensory integration therapy program on sensory problems for children with autism . The study was planned to investigate the effect of a sensory integration therapy program on sensory problems of children with autism . This study was conducted at the Trakya University Training and Research Center for Mentally and Physically Handicapped Children in Turkey . The children were separated into two groups , each comprising 15 children between 7 and 11 years of age with autism , according to DSM-IV criteria . The children in each group were assessed initially on a checklist , Sensory Evaluation Form for Children with Autism , developed to evaluate sensory characteristics of children with autism , and at the end of the study , participants were assessed again on the checklist . Statistically significant differences between groups indicated that the sensory integration therapy program positively affected treated children .

sensory integration therapy program

sensory integration therapy program

sensory integration therapy program

sensory problems

sensory characteristics

sensory problems

autism

autism

Children

children between 7 and 11 years

autism


Onset of action of ciclesonide once daily in the treatment of seasonal allergic rhinitis . Ciclesonide is an intranasal corticosteroid approved for the treatment of allergic rhinitis . We conducted a randomized , double-blind , parallel-group , placebo-controlled study to evaluate the time to onset of action of ciclesonide 200 microg once daily in 502 adults with seasonal allergic rhinitis of at least 2 years ' duration . To trigger immunologic priming , patients underwent between one and five priming sessions with exposure to 3,500 grains/m ( 3 ) ( +/-500 ) of ragweed pollen in an environmental exposure chamber . The criteria for a successful priming session were a patient-assessed instantaneous total nasal symptom score of at least 6 ( of a possible 12 ) and a nasal congestion or rhinorrhea score of at least 2 ( of a possible 3 ) 90 minutes after allergen exposure during at least two consecutive priming sessions . Patients were then randomly assigned to receive either a single dose of ciclesonide 200 microg ( n = 251 ) or placebo ( n = 251 ) administered intranasally . The difference in the change from baseline total nasal symptom scores in the two groups was assessed hourly for 12 hours after administration . Onset of action was determined to have taken place the first time that the effects of ciclesonide , as reflected in the total nasal symptom score , were significantly greater than those of placebo at a particular hourly assessment , provided that the subsequent hourly assessment also showed a statistically significant difference . The onset of action of ciclesonide occurred within 1 hour of administration ( p = 0.01 vs. placebo ) , and the significant difference in total nasal symptom scores between ciclesonide and placebo was maintained through post-treatment hour 12 ( p = 0.018 ) .

ciclesonide

Ciclesonide

ciclesonide

ciclesonide

placebo

ciclesonide

placebo

ciclesonide

ciclesonide

placebo

Onset of action

total nasal symptom score

nasal congestion or rhinorrhea score

baseline total nasal symptom scores

Onset of action

total nasal symptom score

onset of action of ciclesonide

total nasal symptom scores

seasonal allergic rhinitis


Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle . A prospective randomized trial with long-term follow-up . OBJECTIVE The goal of this study has been to determine whether hyaluronic acid ( HA ) or exercise therapy can improve functional parameters in patients with osteoarthritis ( OA ) of the ankle . METHODS In a prospective clinical trial , 43 ankles ( 30 patients ) with radiographic Kellgren Lawrence grade III OA were randomized to receive three intra-articular HA injections , with one-week interval of or exercise therapy for six weeks . Patients were evaluated by the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Scale and followed-up after 12 months . RESULTS Total AOFAS Ankle-Hindfoot score of OA patients has improved in both groups , varying from 61.6+/-16.8 to 90.1+/-9.7 with HA treatment and from 72.1+/-16.6 to 87.5+/-17.5 using exercise therapy at the end of the trial ( p < 0.01 ) . There were no statistically significant differences between the groups . CONCLUSION This prospective randomized trial confirmed that , both HA injections and exercise therapy provide functional improvement . However , larger trials with longer follow-up are necessary for more definite conclusions .

hyaluronic acid

exercise therapy

hyaluronic acid ( HA )

exercise therapy

three intra-articular HA injections

exercise therapy

HA

exercise therapy

HA

exercise therapy

osteoarthritis of the ankle

osteoarthritis

OA


Best evidence in critical care medicine . Steroids to prevent post-extubation airway obstruction in adult critically ill patients .

Steroids

post-extubation airway obstruction

adult

critically ill


LEGO therapy and the social use of language programme : an evaluation of two social skills interventions for children with high functioning autism and Asperger Syndrome . LEGO therapy and the Social Use of Language Programme ( SULP ) were evaluated as social skills interventions for 6-11 year olds with high functioning autism and Asperger Syndrome . Children were matched on CA , IQ , and autistic symptoms before being randomly assigned to LEGO or SULP . Therapy occurred for 1 h/week over 18 weeks . A no-intervention control group was also assessed . Results showed that the LEGO therapy group improved more than the other groups on autism-specific social interaction scores ( Gilliam Autism Rating Scale ) . Maladaptive behaviour decreased significantly more in the LEGO and SULP groups compared to the control group . There was a non-significant trend for SULP and LEGO groups to improve more than the no-intervention group in communication and socialisation skills .

LEGO therapy

social use of language programme

LEGO therapy

social skills interventions

LEGO

SULP

no-intervention control group

LEGO

LEGO

SULP

SULP

LEGO

no-intervention

social skills

Maladaptive behaviour

communication and socialisation skills

children

high functioning autism

Asperger Syndrome

high functioning autism

Asperger Syndrome


Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis : a multicentre , randomised , double-blind , placebo-controlled phase IIb study . BACKGROUND A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions . We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind , placebo-controlled phase IIb study . METHODS The study was done in 51 centres in nine countries . Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing ( GdE ) lesion on screening MRI . Of 720 patients screened , 306 eligible patients were enrolled . Patients , aged 18-50 years , were randomly assigned to placebo ( n=102 ) , laquinimod 0.3 mg a day ( n=98 ) , or 0.6 mg a day ( n=106 ) . Brain MRI scans and clinical assessments were done at week -4 , baseline , and monthly from week 12 to week 36 . The primary outcome was the cumulative number of GdE lesions at weeks 24 , 28 , 32 , and 36 . The principal analysis of the primary endpoint was done on the intention-to-treat cohort . This study is registered with ClinicalTrials.gov , number NCT00349193 . FINDINGS Compared with placebo , treatment with laquinimod 0.6 mg per day showed a 40.4 % reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans ( simple means 4.2 [ SD 9.2 ] vs 2.6 [ 5.3 ] , p=0.0048 ) ; treatment with 0.3 mg per day showed no significant effects ( 3.9 [ 5.5 ] vs placebo , p=0.6740 ) . Both doses of laquinimod were well tolerated , with some transient and dose-dependent increases in liver enzymes . A case of Budd-Chiari syndrome-ie , a thrombotic venous outflow obstruction of the liver-occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0.6 mg laquinimod . Anticoagulant treatment resulted in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation . INTERPRETATION In patients with relapsing-remitting multiple sclerosis , 0.6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated .

laquinimod

laquinimod

laquinimod

placebo

laquinimod

MRI-monitored disease activity

active lesions

MRI-monitored disease

gadolinium enhancing ( GdE ) lesion

cumulative number of GdE lesions

liver enzymes

Budd-Chiari syndrome-ie

liver enzymes

hepatic decompensation

MRI-measured disease activity

relapsing-remitting multiple sclerosis

multicentre

51 centres in nine countries .


The effect of cyclosporin administered during a third-party blood transfusion protocol on humoral immune responses . Antigen pre-treatment in animals undoubtedly prolongs graft survival . In man , however , routine pre-transplantation blood transfusions have recently become controversial , principally because of the adverse effect of transfusion-induced sensitisation on graft survival rates . We have monitored the effect of cyclosporin administered during a planned programme of third-party blood transfusions on the development of both cytotoxic and anti-idiotypic antibodies . A total of 24 patients were recruited to the study ; ten received cyclosporin with blood transfusions ( BT ) ( group 1 ) , 14 received BT alone ( group 2 ) . Anti-HLA antibodies developed in 3 of 9 patients in group 1 and 8 of 12 patients in group 2 ( P less than 0.05 ) . Anti-idiotypic antibody activity was detectable in 9 of 9 patients in group 1 and 7 of 12 patients in group 2 ( P less than 0.006 ) . The mechanism by which cyclosporin can prevent an anti-HLA antibody response and promote an anti-idiotypic response is unclear .

cyclosporin

Antigen pre-treatment

cyclosporin

BT alone

graft survival

graft survival rates

Anti-HLA antibodies

Anti-idiotypic antibody activity

anti-HLA antibody response

anti-idiotypic response

third-party blood transfusion protocol

Antigen pre-treatment in animals


Influence of infusion time on the acute toxicity of amphotericin B : results of a randomized double-blind study .

amphotericin B

acute toxicity of amphotericin B :

infusion time

acute toxicity of amphotericin B


Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer . PURPOSE Postoperative radiotherapy for breast cancer has a number of associated complications . This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy . PATIENTS AND METHODS Forty women were randomized before radiotherapy after various operations for breast cancer . Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks . Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise . The World Health Organization Quality of Life-BREF ( WHOQOL-BREF ) , brief fatigue inventory ( BFI ) , range of motion ( ROM ) of the shoulder , and pain score were assessed before and after radiotherapy . RESULTS There were no significant differences noted at baseline between groups . In the exercise group , there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy . On the other hand , patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy . There were statistically significant differences in the changes in the WHOQOL , BFI , shoulder ROM , and pain score between the groups . CONCLUSION Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy .

supervised exercise therapy

radiotherapy

radiotherapy

moderate-intensity exercise

radiotherapy

radiotherapy

exercise group

control group

radiotherapy

radiotherapy

control

radiotherapy

radiotherapy

brief fatigue inventory ( BFI )

range of motion ( ROM ) of the shoulder

pain score

WHOQOL-BREF and shoulder ROM

decrease in BFI and pain score

WHOQOL-BREF

shoulder ROM

increase in BFI and pain score

WHOQOL

BFI

shoulder ROM

pain score

Twenty-three patients

control group

patients


Cognitive effects of risperidone in children with autism and irritable behavior . OBJECTIVE The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior . METHOD Thirty-eight children , ages 5-17 years with autism and severe behavioral disturbance , were randomly assigned to risperidone ( 0.5 to 3.5 mg/day ) or placebo for 8 weeks . This sample of 38 was a subset of 101 subjects who participated in the clinical trial ; 63 were unable to perform the cognitive tasks . A double-blind placebo-controlled parallel groups design was used . Dependent measures included tests of sustained attention , verbal learning , hand-eye coordination , and spatial memory assessed before , during , and after the 8-week treatment . Changes in performance were compared by repeated measures ANOVA . RESULTS Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age > or=18 months completed the cognitive part of the study . No decline in performance occurred with risperidone . Performance on a cancellation task ( number of correct detections ) and a verbal learning task ( word recognition ) was better on risperidone than on placebo ( without correction for multiplicity ) . Equivocal improvement also occurred on a spatial memory task . There were no significant differences between treatment conditions on the Purdue Pegboard ( hand-eye coordination ) task or the Analog Classroom Task ( timed math test ) . CONCLUSION Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance .

risperidone

risperidone

risperidone

placebo

risperidone

placebo

Risperidone

cognitive processes

verbal learning

hand-eye coordination

spatial memory assessed before

ANOVA

spatial memory task

Analog Classroom Task ( timed math test

cognitive performance


A comparison between the effect of oxytocin only and oxytocin plus propranolol on the labor ( a double blind randomized trial ) . OBJECTIVE The comparison between the effect of oxytocin alone or in combination with propranolol on labor . METHODS A double blind randomized controlled trial was performed on 150 nulliparas with a gestational age of 39-41 weeks of pregnancy and a Bishop score of < or =5 . In the first group ( oxytocin group = 75 ) , oxytocin alone was used for induction of labor . In the second group ( propranolol group = 75 cases ) , before the beginning of oxytocin , 2 mg propranolol was slowly injected intravenously then the oxytocin was initiated . RESULTS The number of patients who delivered in the first day showed no difference between the two groups . The mean duration for obtaining good contractions was shorter in the propranolol group in both the first and second day of induction The mean interval between the beginning of induction until the beginning of active phase at the first day of induction was shorter in the propranolol group . The mean interval between the beginning of induction until delivery at the first day of induction was shorter in the propranolol group . The amount of necessary oxytocin for the first day of induction was less in the propranolol group . CONCLUSION Propranolol may shorten the induction duration and labor and reduce the amount of necessary oxytocin .

oxytocin only

oxytocin plus propranolol

oxytocin alone

in combination with propranolol

oxytocin

oxytocin alone

( propranolol

oxytocin

propranolol

oxytocin

propranolol

propranolol

propranolol

oxytocin

propranolol

Propranolol

oxytocin

labor

labor .

induction of labor .

amount of necessary oxytocin

induction duration and labor

nulliparas

pregnancy

Bishop score of < or =5


Effect of preoperative skull block on pediatric moyamoya disease . OBJECT Stable hemodynamics , normocapnia , and adequate pain relief are considered important factors in the reduction of neurological complications in pediatric patients undergoing encephaloduroarteriomyosynangiosis ( EDAMS ) operations for the treatment of moyamoya disease . A preoperative skull block may reduce hemodynamic fluctuations and hypo- or hyperventilation due to emergence delirium or oversedation and provide adequate pain relief , thereby reducing postoperative morbidity . METHODS Pediatric patients ( age 3-13 years ) undergoing EDAMS surgery for moyamoya disease were randomly divided into a nerve block ( NB ) group ( 18 cases ) or control group ( 21 cases ) . The treatment group patients received a preoperative NB ( 0.25 % 5-8 ml bupivacaine mixed with 20-40 mg methylprednisolone ) targeting the supraorbital , supratrochlear , auriculotemporal , and posterior auricular nerves . Patients in the control group did not receive NB . General anesthesia with sevoflurane was induced in both groups . RESULTS In the NB group , stable hemodynamic parameters were obtained with a lower sevoflurane concentration than in the control group . For delirious awakening , the odds ratio in the control group was 4.9 compared with the NB group . Pain and analgesic requirement were higher in the control patients than in the NB-treated patients during the postanesthesia care unit stay . However , the arterial CO ( 2 ) tension in the postanesthesia care unit did not differ between the 2 groups . The odds ratio in the control group for the rate of morbidity ( cerebral infarction and reversible ischemic neurological deficits ) during the first 24 hours following the operation was 3.2 compared with the NB group . CONCLUSIONS The use of skull block during EDAMS surgery provided easy hemodynamic control , calm awakening , and better pain relief and may be related to the reduced postoperative morbidity .

EDAMS surgery

NB

bupivacaine

methylprednisolone

sevoflurane

postoperative morbidity .

stable hemodynamic parameters

delirious awakening

Pain

analgesic requirement

hemodynamic control , calm awakening

pain relief

postoperative morbidity

moyamoya disease

pediatric

moyamoya disease

Pediatric

age 3-13 years

EDAMS surgery

moyamoya disease


The effects of improvisational music therapy on joint attention behaviors in autistic children : a randomized controlled study . The purpose of this study was to investigate the effects of improvisational music therapy on joint attention behaviors in pre-school children with autism . It was a randomized controlled study employing a single subject comparison design in two different conditions , improvisational music therapy and play sessions with toys , and using standardized tools and DVD analysis of sessions to evaluate behavioral changes in children with autism . The overall results indicated that improvisational music therapy was more effective at facilitating joint attention behaviors and non-verbal social communication skills in children than play . Session analysis showed significantly more and lengthier events of eye contact and turn-taking in improvisational music therapy than play sessions . The implications of these findings are discussed further .

improvisational music therapy

improvisational music therapy

effects

facilitating joint attention behaviors

non-verbal social communication skills

autistic

children

pre-school children

autism

children

autism


Cardiopulmonary exercise variables in diastolic versus systolic heart failure . The response to cardiopulmonary exercise ( CPX ) in patients with heart failure ( HF ) with normal left ventricular ( LV ) ejection fractions ( EFs ) is not well characterized . To determine if CPX testing could distinguish between patients with HF with normal EFs ( > 50 % ; i.e. , diastolic HF ) and those with decreased EFs ( > or =50 % ; i.e. , systolic HF ) , CPX responses were compared between 185 patients with systolic HF ( 79 % men , mean age 62.6 +/- 10.9 years ) and 43 with diastolic HF ( 54 % men , mean age 67.4 +/- 9.8 years ) enrolled in a phase II multicenter clinical trial . All patients were evaluated with echocardiography and a standardized CPX test as part of the trial . CPX variables , including oxygen uptake at peak exercise ( peak VO ( 2 ) ) and the slope of the ventilation/carbon dioxide production ratio ( VE/VCO ( 2 ) ) , were determined and analyzed by core laboratory personnel . Echocardiographic measurements included the LV EF , the E/A ratio , filling time , cavity volumes , right ventricular function , and mitral regurgitation . Patients in the diastolic HF group tended to be older ( p < 0.08 ) , with more women ( p < 0.006 ) and with greater body mass indexes ( p < 0.02 ) , than those in the systolic HF group . There was no significant difference in the use of beta blockers or the incidence of coronary artery disease . Patients with diastolic HF had decreased E/A ratios ( 0.9 +/- 0.4 vs 1.4 +/- 1.1 , p < 0.02 , diastolic HF vs systolic HF ) and increased filling times ( 30.4 +/- 3.2 vs 26.5 +/- 4.7 ms , p < 0.01 , diastolic HF vs systolic HF ) . No significant differences in peak VO ( 2 ) ( 14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min , p = 0.06 , diastolic HF vs systolic HF ) were observed . The VE/VCO ( 2 ) ratios for the 2 groups were abnormal and comparable ( 32 2 +/- 7.5 vs 34.0 +/- 8.3 , p = 0.3 , diastolic HF vs systolic HF ) . In conclusion , the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO ( 2 ) and ventilation despite marked differences in the LV EF .

Cardiopulmonary exercise

cardiopulmonary exercise ( CPX )

CPX

CPX

echocardiography

standardized CPX test

CPX

CPX

LV EF

the E/A ratio

filling time

cavity volumes

right ventricular function

mitral regurgitation

use of beta blockers

incidence of coronary artery disease

E/A ratios

filling times

peak VO ( 2 )

VE/VCO ( 2 )

peak VO ( 2 ) and ventilation


Effect of ranitidine on the disposition of orally and intravenously administered triazolam . The effect of orally administered ranitidine on the pharmacokinetic properties of orally and intravenously administered triazolam was determined . Twelve healthy males with a mean age of 35 years were enrolled in this four-way , randomized , crossover study . Each subject received a total of four treatments , each separated by one week . The treatments consisted of ( 1 ) one orally administered 0.25-mg triazolam tablet after treatment with ranitidine ; ( 2 ) one orally administered 0.25-mg triazolam tablet , with no ranitidine pretreatment ; ( 3 ) a 0.25-mg intravenous dose of triazolam after treatment with ranitidine ; and ( 4 ) a 0.25-mg intravenous dose of triazolam , with no ranitidine pretreatment . Ranitidine pretreatment consisted of five 150-mg oral doses ( as the hydrochloride salt ) given every 12 hours ; the last dose was given two hours before triazolam was administered . Blood samples were taken at intervals up to 12 hours after triazolam treatment . Serum triazolam concentrations were measured by modified high-performance liquid chromatography , and pharmacokinetic values were calculated . Pretreatment with ranitidine had no effect on the disposition of intravenously administered triazolam but significantly increased the area under the serum drug concentration-time curve of oral triazolam . Ranitidine pretreatment had no effect on triazolam 's terminal elimination rate constant or on the time to reach maximum serum triazolam concentration . Ranitidine pretreatment increased the systemic availability of triazolam by increasing its absorption .

ranitidine

ranitidine

triazolam

Ranitidine

triazolam

triazolam

ranitidine

Ranitidine

triazolam 's

Ranitidine

triazolam

disposition

pharmacokinetic properties

Serum triazolam concentrations

pharmacokinetic values

systemic availability of triazolam

absorption .


Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa . OBJECTIVES To compare the efficacy and safety of polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU/dexamethasone phosphate 0.1 % ( PN+Dx ) otic solution with polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU ( PN-Dx ) in patients with acute bacterial otitis externa ( AOE ) , in order to determine the possible benefit of the addition of dexamethasone . RESEARCH DESIGN AND METHODS Active controlled , double-blind , randomized , parallel group , multi-center clinical trial in ear , nose , and throat ( ENT ) specialist practices with a planned interim analysis for sample size adaptation . In total , 338 patients aged 18-76 who had a previous episode of otitis externa within the last year were randomized to receive 10 +/- 2 days of treatment with two drops , three times daily , of either PN+Dx or PN-Dx . MAIN OUTCOME MEASURES Change in the clinical symptom score ( consisting of the subscores redness , swelling , pain , and secretion ) and of the visual analogue scale ( VAS ) rating for pain from Visit 1 ( Day 1 ) to Visit 2 ( Day 4 +/- 1 ) , patient 's assessment of efficacy at Visit 3 ( Day 10 +/- 2 ) , and the frequency and type of adverse events . RESULTS There was a significantly greater reduction of swelling from Visit 1 to Visit 2 with PN+Dx , and more patients rated the efficacy of PN+Dx as 'very good ' or 'good ' at Visit 3 ( p = 0.03 ) . There was also a significantly greater decrease in the clinical symptom score from Visit 1 to Visit 2 in the PN+Dx group in patients who had at least a moderately severe symptom score with more than seven points at Visit 1 ( p = 0.01 ) and in patients suffering from their current episode of otitis externa for more than 2 days ( p = 0.02 ) . In total , 14 adverse events were reported during the study period with no related adverse drug reactions for PN+Dx . CONCLUSIONS The addition of dexamethasone phosphate to polymyxin B/neomycin significantly reduces swelling in patients with AOE and leads to significantly higher patient 's ratings of treatment efficacy . It especially leads to an overall reduction of symptoms in cases of moderately or more severe otitis externa and cases lasting for more than 2 days .

Dexamethasone phosphate

antibiotic ear drops

PN+Dx

PN-Dx

dexamethasone phosphate

polymyxin B/neomycin

visual analogue scale ( VAS )

rating for pain

patient 's assessment of efficacy

frequency and type of adverse events

swelling

efficacy

clinical symptom score

severe symptom score

adverse drug reactions

acute bacterial otitis externa

aged 18-76

episode of otitis externa

patients with AOE


Complementary feeding with fortified spread and incidence of severe stunting in 6- to 18-month-old rural Malawians . OBJECTIVE To compare growth and incidence of malnutrition in infants receiving long-term dietary supplementation with ready-to-use fortified spread ( FS ) or micronutrient-fortified maize-soy flour ( likuni phala [ LP ] ) . DESIGN Randomized , controlled , single-blind trial . SETTING Rural Malawi . PARTICIPANTS A total of 182 six-month-old infants . INTERVENTION Participants were randomized to receive 1 year of daily supplementation with 71 g of LP ( 282 kcal ) , 50 g of FS ( FS50 ) ( 256 kcal ) , or 25 g of FS ( FS25 ) ( 130 [ corrected ] kcal ) . OUTCOME MEASURES Weight and length gains and the incidences of severe stunting , underweight , and wasting . RESULTS Mean weight and length gains in the LP , FS50 , and FS25 groups were 2.37 , 2.47 , and 2.37 kg ( P = .66 ) and 12.7 , 13.5 , and 13.2 cm ( P = .23 ) , respectively . In the same groups , the cumulative 12-month incidence of severe stunting was 13.3 % , 0.0 % , and 3.5 % ( P = .01 ) , of severe underweight was 15.0 % , 22.5 % , and 16.9 % ( P = .71 ) , and of severe wasting was 1.8 % , 1.9 % , and 1.8 % ( P > .99 ) . Compared with LP-supplemented infants , those given FS50 gained a mean of 100 g more weight and 0.8 cm more length . There was a significant interaction between baseline length and intervention ( P = .04 ) ; in children with below-median length at enrollment , those given FS50 gained a mean of 1.9 cm more than individuals receiving LP . CONCLUSION One-year-long complementary feeding with FS does not have a significantly larger effect than LP on mean weight gain in all infants , but it is likely to boost linear growth in the most disadvantaged individuals and , hence , decrease the incidence of severe stunting .

fortified spread ( FS )

LP

FS

FS ( FS25 )

LP

LP-supplemented

LP .

FS

LP

severe stunting

growth

malnutrition

Weight and length gains

incidences of severe stunting

underweight

wasting

Mean weight and length gains

severe stunting

underweight

severe wasting

weight

length

mean weight gain

linear growth

incidence of severe stunting


Central neuronal mechanisms of gastric electrical stimulation in diabetic gastroparesis . OBJECTIVE The mechanisms underlying symptom improvement in gastric electrical stimulation ( GES ) are not fully understood . Modulation of the central nervous system excitability may be involved . The objective of the study was to investigate the central effects of GES , including the possible modulation of the visceral sensory nervous system . MATERIAL AND METHODS A gastric electrical stimulator was implanted in seven diabetic patients with medically refractory gastroparesis . A double-blinded protocol was used to investigate the patients at baseline and one month after recovery with the stimulator turned on and off ( 1-month periods ) . The following assessments were carried out : mechanical , thermal and electrical stimulations with sensory recordings in the esophagus and duodenum , and standardized , self-administered , daily symptom questionnaires . RESULTS No difference was found between baseline and the on- and off periods in overall gut pain thresholds across all stimulus modalities in the esophagus ( p=0.63 ) , duodenum ( p=0.19 ) or esophagus and duodenum combined ( p=0.76 ) . No difference in the sensory response to mechanical stimulation was found in the esophagus before ( all p > 0.31 ) and after ( all p > 0.43 ) smooth muscle relaxation with butylscopolamine . Similar findings were observed in the duodenum . No differences were found in thermal sensitivity ( esophagus ( p=0.67 ) and duodenum ( p=0.17 ) ) , sensory response to electrical stimulation ( esophagus ( p=0.57 ) and duodenum ( p=0.52 ) ) or induced somatic referred pain areas ( esophagus ( p=0.75 ) and duodenum ( p=0.51 ) ) . No difference was seen in the induced somatic referred pain areas or self-reported symptoms . CONCLUSIONS No evidence was found for GES-induced modulation of the visceral sensory system and central excitability . However , GES has been proven to modulate the central nervous system in animal studies , necessitating further human experiments in order unambiguously to establish the possible central effects of GES .

gastric electrical stimulation

gastric electrical stimulation ( GES )

GES

gastric electrical stimulator

butylscopolamine

GES-induced

GES

GES

overall gut pain

thermal sensitivity

induced somatic referred pain areas

somatic referred pain areas

self-reported symptoms

diabetic gastroparesis

seven

diabetic

medically refractory gastroparesis


Randomized trial of a decision aid for individuals considering genetic testing for hereditary nonpolyposis colorectal cancer risk . BACKGROUND Despite the potential benefits of genetic testing for hereditary nonpolyposis colorectal cancer ( HNPCC ) risk , individuals can find the genetic testing decision-making process complicated and challenging . The goal of the current study was to measure the effectiveness of a tailored decision aid designed specifically to assist individuals to make informed decisions regarding genetic testing for HNPCC risk . METHODS In all , 153 individuals were randomized to receive the decision aid or a control pamphlet at the end of their first genetic counseling consultation . Of these , 109 ( 71.2 % ) completed the first questionnaire 1 week after consultation , whereas 95 ( 62.1 % ) completed the 6-month follow-up questionnaire . RESULTS Although the decision aid had no significant effect on postdecisional regret or actual genetic testing decision , the trial results demonstrated that participants who received the decision aid had significantly lower levels of decisional conflict ( ie , uncertainty ) regarding genetic testing ( chi-square ( 1 ) = 8.97 ; P = .003 ) and were more likely to be classified as having made an informed choice concerning genetic testing ( chi-square ( 1 ) = 4.37 ; P = .037 ) than participants who received a control pamphlet . Also , men who received the decision aid had significantly higher knowledge levels regarding genetic testing compared with men who received the control pamphlet , whereas no such differences were found for women ( chi-square ( 2 ) = 6.76 ; P = .034 ) . CONCLUSIONS A decision aid for individuals considering genetic testing for HNPCC is an effective intervention to reduce uncertainty and assist individuals to make an informed choice regarding genetic testing for HNPCC after genetic counseling .

decision aid

control pamphlet

decision aid

control pamphlet

decision aid

questionnaire

follow-up questionnaire .

genetic testing

informed choice

higher knowledge levels


Engagement with electronic screen media among students with autism spectrum disorders . This study investigated the relative engagement potential of four types of electronic screen media ( ESM ) : animated video , video of self , video of a familiar person engaged with an immersive virtual reality ( VR ) game , and immersion of self in the VR game . Forty-two students with autism , varying in age and expressive communication ability , were randomly assigned to the experimental conditions . Gaze duration and vocalization served as dependent measures of engagement . The results reveal differential responding across ESM , with some variation related to the engagement metric employed . Preferences for seeing themselves on the screen , as well as for viewing the VR scenarios , emerged from the data . While the study did not yield definitive data about the relative engagement potential of ESM alternatives , it does provide a foundation for future research , including guidance related to participant profiles , stimulus characteristics , and data coding challenges .

Engagement with electronic screen media

ESM

VR

ESM

Gaze duration

vocalization


Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence . We conducted a single-blind , random assignment , placebo-controlled , 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence . Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment . Subjects treated with fixed doses of 200 mg/day desipramine ( N = 17 ) , 400 mg/day amantadine-placebo ( N = 16 ) , and placebo ( N = 21 ) did not differ for lifetime cocaine use , lifetime histories of psychopathology , admission scores on psychometric assessments , and sociodemographics . All treatment groups demonstrated dramatic and persistent decreases in cocaine use , craving for cocaine , and psychiatric symptoms consequent to treatment . Although there was a trend for more dropouts by subjects taking desipramine , there were no significant differences among treatment groups regarding retention in treatment , craving for cocaine , and decreased cocaine use confirmed by urine toxicology . There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence . Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression , thus the dosage of desipramine may have been subtherapeutic .

amantadine

desipramine

psychotherapy

placebo-controlled

desipramine hydrochloride

amantadine hydrochloride

desipramine

amantadine-placebo

placebo

desipramine

desipramine

desipramine

desipramine

dramatic and persistent decreases

cocaine use

craving for cocaine

psychiatric symptoms

dropouts

retention in treatment

craving for cocaine

decreased cocaine use

urine toxicology

cocaine abstinence

cocaine dependence


Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals . UNLABELLED In 242 community-dwelling seniors , supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27 % at month 12 and 39 % at month 20 . Additionally , parameters of muscle function improved significantly . INTRODUCTION The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially . Randomized controlled trials using falls as primary outcome are needed . We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men . METHODS Our study population consisted of 242 individuals recruited by advertisements and mailing lists ( mean [ +/- SD ] age , 77 +/- 4 years ) . All serum 25-hydroxyvitamin D ( 25 [ OH ] D ) levels were below 78 nmol/l . Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months , which was followed by a treatment-free but still blinded observation period of 8 months . Falls were documented using diaries . The study took place in Bad Pyrmont , Germany ( latitude 52 degrees ) and Graz , Austria ( latitude 46 degrees ) . RESULTS Compared to calcium mono , supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27 % at month 12 ( RR = 0.73 ; CI = 0.54-0.96 ) and 39 % at month 20 ( RR = 0.61 ; CI = 0.34-0.76 ) . Concerning secondary endpoints , we observed significant improvements in quadriceps strength of 8 % , a decrease in body sway of 28 % , and a decrease in time needed to perform the TUG test of 11 % . DISCUSSION Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals .

vitamin D

calcium supplementation

calcium

calcium plus vitamin D

vitamin D

calcium

calcium

vitamin D

calcium

calcium

vitamin D

vitamin D

calcium

vitamin D

falls and parameters of muscle function

muscle function

risk of falling

falls and parameters of muscle function

Falls

subjects with first falls

improvements in quadriceps strength

body sway

time needed to perform the TUG test

number of falls

muscle function

community-dwelling

older individuals

seniors

women

men

mean [ +/- SD ] age , 77 +/- 4 years


Which socio-demographic factors are associated with participation in oral cancer screening in the developing world ? Results from a population-based screening project in India . BACKGROUND This study examines socio-demographic determinants of participation in a population-based randomized controlled trial that proved that oral visual inspection was effective in reducing oral cancer mortality in high-risk individuals in India . METHODS Multivariate logistic regression was used to establish socio-demographic characteristics of participants versus non-participants in the intervention arm . Compliance with referral was analysed according to the socio-demographic characteristics of screen-positives . RESULTS Of 96,517 eligible subjects , 87,655 were screened , 8688 individuals never received the invitation and 174 refused screening . Compared to the non-screened , a higher proportion of screened individuals were women ( OR=4.51 ; CI : 4.28-4.75 ) , lived in better housing ( OR=1.35 ; CI : 1.25-1.41 ) , had television/radio ( OR=1.50 ; CI : 1.43-1.58 ) and were tobacco and alcohol users ( OR=2.75 ; CI : 2.57-2.95 ) . Being 65 and older decreased the chances of screening ( OR=0.39 ; CI : 0.37-0.42 ) , as well as living in high-size households ( OR=0.73 ; CI : 0.68-0.78 ) . Sixty-three percent of 5143 screen-positives complied with referral . Controlling for all other factors , individuals older than 44 , and those with more advanced lesions were more likely to comply with referral ( p < 0.001 ) . Individuals living in better housing were less likely to comply with referral ( OR=0.79 ; CI : 0.65-0.95 ) . CONCLUSIONS In summary , adequate coverage can be obtained in population-based oral screening in developing countries . The study underscores the important role of patient-provider communication in assuring high compliance with referral .

socio-demographic factors

participation in oral cancer screening

population-based screening

oral visual inspection

intervention

referral

screened

screening

screened

screening

referral

population-based oral screening

patient-provider communication

oral cancer mortality

Compliance with referral

screened

chances of screening

living in high-size households


The effect of acupressure at the extra 1 point on subjective and autonomic responses to needle insertion . BACKGROUND Premedication with sedatives can decrease the discomfort associated with invasive anesthetic procedures . Some researchers have shown that acupressure on the acupuncture extra 1 point is effective for sedation . We investigated whether acupressure on the extra 1 point could alleviate the pain of needle insertion . METHODS We investigated the effect of acupressure at the extra 1 point or a sham point on needle insertion using verbal rating scale ( VRS ) pain scores and heart rate variability ( HRV ) . Twenty-two healthy female volunteers were randomly allocated to two groups : the extra 1 group received acupressure at the extra 1 point , and the sham group received acupressure at a sham point . After starting the electrocardiogram record , a 27-gauge needle was inserted into the skin of a forearm . Thereafter , another needle was inserted into the skin of the other forearm during acupressure . RESULTS Acupressure at the extra 1 point significantly reduced the VRS , but acupressure at the sham increased the VRS . Acupressure at the extra 1 significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion . CONCLUSIONS Acupressure at the extra 1 point significantly reduced needle insertion pain compared with acupressure at the sham point . Also , acupressure at the extra 1 point significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion , which implies a reduction in sympathetic nervous system activity .

acupressure

acupressure at the extra 1 point

acupressure at a sham point

Acupressure

acupressure

Acupressure

Acupressure

acupressure

acupressure

autonomic responses

discomfort

pain

verbal rating scale ( VRS ) pain scores

heart rate variability ( HRV ) .

VRS

VRS

needle insertion pain

sympathetic nervous system activity .

Twenty-two

healthy

female


Placebo-controlled trial evaluating safety with 12-months continuous use of 6 % hydrogen peroxide whitening strips . OBJECTIVE To assess the safety and tolerability of 6 % hydrogen peroxide whitening strips over 12 months . METHODS 80 adults were randomly assigned equally to one of two treatments : 6 % hydrogen peroxide strips or placebo strips . Strips were worn 5 min daily for 12 months . Safety and tolerability were assessed via oral status interviews and oral examinations at baseline and after 1 , 2 , 3 , 6 , 9 , and 12 months of use . RESULTS Tooth sensitivity and oral irritation were the two most common adverse events . After 12 months use , tooth sensitivity was reported by 10 % of subjects in the 6 % strip group with a 95 % confidence interval ( CI ) of ( 2.8 % , 23.7 % ) and 5 % of subjects in the placebo group with a 95 % CI of ( 0.6 % , 16.9 % ) . The occurrence of reported oral irritation was 0 % in the 6 % strip group with a 95 % CI of ( 0 % , 8.8 % ) and 2.5 % in the placebo strip group with a 95 % CI of ( 0.1 % , 13.2 % ) . The occurrence of observed oral irritation was also similar between groups . The groups did not differ significantly ( p > 0.67 ) for the percent of subjects with each type of adverse event . In the 6 % strip group , two subjects discontinued product use due to an adverse event ( tooth sensitivity ) compared to no subjects in the placebo group . Groups did not differ significantly ( p > 0.49 ) with respect to this outcome . CONCLUSION Use of 6 % hydrogen peroxide whitening strips over 12 months resulted in a safety profile similar to that seen with placebo strips .

Placebo-controlled

6 % hydrogen peroxide whitening strips

6 % hydrogen peroxide whitening strips

6 % hydrogen peroxide strips

placebo strips

6 % strip

placebo

6 % strip

placebo strip

6 % strip

placebo

6 % hydrogen peroxide whitening strips

placebo strips

adults


Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications . BACKGROUND Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease ( CHD ) risk . AIM OF THE STUDY The aim of this pilot study was to examine the effects of fatty fish and lean ( white ) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition . METHODS The study was an 8-week controlled , parallel intervention . Inclusion criteria were myocardial infarction or unstable ischemic attack , age under 70 years , use of betablockers and presence of sinus rhythm . The subjects were randomized to one of the following groups : 4 meals/week fatty fish ( n = 11 ) , 4 meals/week lean fish ( n = 12 ) and control diet including lean meat ( n = 10 ) . RESULTS The mean ( +/-SD ) of reported fish meals per week was 4.3 +/- 0.4 , 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups , respectively . The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only ( P < 0.05 ) . Systolic and diastolic blood pressure levels decreased in the lean fish group ( 0 vs. 8 week : 3.5 +/- 3.2 and 4.6 +/- 3.6 % , respectively , P < 0.05 ) . Serum total triglyceride concentration did not significantly change . HDL cholesterol concentration change differed among groups but without significant post hoc differences . Apolipoprotein A-1 concentration decreased in the control group ( 0 vs. 8 week , P < 0.05 ) . Coagulation factors , 25-hydroxy vitamin D , and heart rate variability ( 24 h Holter ) did not change among the groups . CONCLUSIONS Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients .

fatty and lean fish intake

fatty fish

lean ( white ) fish

4 meals/week

fatty fish

( n = 11 ) , 4 meals/week

lean fish

( n = 12 ) and

control diet

including lean meat ( n = 10 ) .

lean fish

blood pressure

fatty acid composition of serum lipids

cardiovascular risk factors

Systolic and diastolic blood pressure

Serum total triglyceride concentration

HDL cholesterol concentration

Apolipoprotein A-1 concentration

coronary heart disease ( CHD )

unstable ischemic attack

age under 70 years

CHD patients


[ No effect of spironolactone on bulimia nervosa symptoms ] . Some case reports mention that Spironolactone , a mineral corticoid antagonist and aldosterone antagonist , reduces binging in patients with bulimia nervosa . Therefore , we decided to study these findings by using a randomized , double-blind , placebo controlled study design . In one study arm , patients with bulimia nervosa were treated with 150 mg Spironolactone per day ; in the other arm , patients received a placebo for a total of 8 weeks . The target variables were the number of binges and the bulimia scale of the Eating Disorder Inventory . The study included 93 patients . The results show that the number of binges and the scores on the bulimia scale decreased somewhat , but this occurred in both groups . We were not able to show any significant statistical differences between the Spironolactone group and the placebo group . Additional evaluations , executed with data from the Symptom-Check-List ( SCL-90R ) and with other scales from the EDI-2 also showed no effect of Spironolactone . Therefore , a treatment with Spironolactone seems to have no effect on bulimia nervosa symptoms .

spironolactone

Spironolactone

mineral corticoid antagonist

aldosterone antagonist

placebo

150 mg Spironolactone per day

placebo

Spironolactone

Spironolactone

Spironolactone

No effect

binging

number of binges

significant statistical differences

Symptom-Check-List ( SCL-90R )

no effect

bulimia nervosa

bulimia nervosa


Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients : a double-blind , randomized cross-over study . PURPOSE Breast cancer patients with treatment-induced menopause experience frequent and severe hot flashes ( HF ) . We compared venlafaxine and clonidine for the treatment of HF with regard to side effects , efficacy , quality of life and sexual functioning . METHODS In a double-blind , cross-over study , 60 breast cancer patients experiencing HF were randomized to 8 weeks venlafaxine followed by 2 weeks wash-out , and 8 weeks clonidine or vice versa . HF frequency and severity , side effects , quality of life and sexuality were assessed . RESULTS Thirty patients started with venlafaxine and 30 with clonidine . Premature discontinuation for toxicity occurred in 14/59 during venlafaxine and 5/53 during clonidine ( P = .038 ) . Venlafaxine induced more side effects . Median reduction in HF score was 49 % for venlafaxine and 55 % for clonidine ( ns ) . CONCLUSION Venlafaxine and clonidine are equally , but moderately effective in HF reduction . Side effects are the main reason for drug discontinuation , occurring more often with venlafaxine .

Venlafaxine

clonidine

venlafaxine

clonidine

venlafaxine

clonidine

venlafaxine

clonidine

venlafaxine

clonidine

Venlafaxine

venlafaxine

clonidine

Venlafaxine

clonidine

venlafaxine

hot flashes

severe hot flashes ( HF )

side effects

efficacy

quality of life

sexual functioning

HF frequency and severity

, side effects ,

quality of life

and

sexuality

toxicity

side effects

Median reduction in HF score

HF reduction

Side effects

Breast cancer

menopause

severe hot flashes ( HF )

breast cancer patients

HF

Thirty patients


Less tachycardia in adults when using atropine 0.9 mg compared with 1.2 mg plus neostigmine 2.5 mg . OBJECTIVE Compare the increase in heart rate in adults after 0.9 vs. 1.2 mg of atropine plus neostigmine 2.5 mg as the non-depolarizing muscle relaxant reversal agent . MATERIAL AND METHOD A randomized , double blind , controlled trial on 46 adults ASA I-II , undergoing elective gynecological or general surgery with balanced general anesthesia was performed . The subjects were randomized into two groups , After surgery , the study group received 0.9 mg of atropine , while the control group received 1.2 mg of atropine . Both groups received 2.5 mg of neostigmine simultaneously . RESULTS The heart rate and blood pressure were taken at 0 , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 15 , 20 , 25 , and 30 min after the injection . The increase in heart rate and blood pressure between the two groups were compared . The heart rate ( at 3 , 4 , 5 , and 6 min ) of patients in the study group increased significantly less than that of patients in the control group . There was no significant difference in blood pressure between groups and no side effects occurred . CONCLUSION The authors conclude that 0.9 mg of atropine with 2.5 mg neostigmine can be safely used as the reversal agent for a non-depolarizing muscle relaxant , particularly in patients for whom any increase in heart rate would be harmful .

atropine

neostigmine

atropine

plus

neostigmine

0.9 mg of atropine

control

1.2 mg of atropine

2.5 mg of neostigmine

atropine

neostigmine

tachycardia

heart rate

heart rate

blood pressure

heart rate

blood pressure

heart rate

blood pressure

heart rate


Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer . PURPOSE The combination of vaccines and chemotherapy holds promise for cancer therapy , but the effect of cytotoxic chemotherapy on vaccine-induced antitumor immunity is unknown . This study was conducted to assess the effects of systemic chemotherapy on ALVAC-CEA/B7.1-induced T-cell immunity in patients with metastatic colorectal cancer . EXPERIMENTAL DESIGN Patients with metastatic colorectal cancer were treated with fluorouracil , leucovorin , and irinotecan and were also given ALVAC-CEA/B7.1 vaccine with or without tetanus toxoid adjuvant . Eligible patients were randomized to ALVAC followed by chemotherapy and booster vaccination ( group 1 ) , ALVAC and tetanus toxoid followed by chemotherapy ( group 2 ) , or chemotherapy alone followed by ALVAC in patients without disease progression ( group 3 ) . Humoral immune responses were measured by standard ELISA assay , and carcinoembryonic antigen ( CEA ) -specific T-cell responses were measured by IFN-gamma enzyme-linked immunospot assay . RESULTS One hundred eighteen patients were randomized to receive either ALVAC before and concomitantly with chemotherapy ( n = 39 ) , ALVAC with tetanus adjuvant before and concomitantly with chemotherapy ( n = 40 ) , or chemotherapy followed by ALVAC ( n = 39 ) . Serious adverse events were largely gastrointestinal ( n = 30 ) and hematologic ( n = 24 ) . Overall , 42 patients ( 40.4 % ) showed objective clinical responses . All patients developed antibody responses against ALVAC , but increased anti-CEA antibody titers were detected in only three patients . Increases in CEA-specific T cells were detected in 50 % , 37 % , and 30 % of patients in groups 1 , 2 , and 3 , respectively . There were no differences in clinical or immune responses between the treatment groups . CONCLUSION The combination of ALVAC-CEA/B7.1 vaccine and systemic chemotherapy has an acceptable safety profile in patients with metastatic colorectal cancer . Systemic chemotherapy did not affect the generation of CEA-specific T-cell responses following vaccination .

Combination chemotherapy

ALVAC-CEA/B7.1 vaccine

vaccines

chemotherapy

fluorouracil

leucovorin

irinotecan

ALVAC-CEA/B7.1 vaccine

tetanus toxoid adjuvant

ALVAC

chemotherapy

booster vaccination

ALVAC

tetanus toxoid

chemotherapy

chemotherapy

ALVAC

ELISA assay

ALVAC

chemotherapy

ALVAC

tetanus adjuvant

chemotherapy

chemotherapy

ALVAC

ALVAC-CEA/B7.1 vaccine

chemotherapy

Serious adverse events

gastrointestinal

hematologic

antibody responses against ALVAC

anti-CEA antibody titers

CEA-specific T cells

CEA-specific T-cell responses

metastatic colorectal cancer

One hundred eighteen


Local delivery of a recombinant adenoassociated vector containing a tumour necrosis factor alpha antagonist gene in inflammatory arthritis : a phase 1 dose-escalation safety and tolerability study . OBJECTIVE To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR : Fc , an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor-immunoglobulin Fc fusion gene ( tgAAC94 ) , in subjects with inflammatory arthritis . METHODS In a double-blind , placebo-controlled , phase 1 , dose-escalation study , 15 subjects with inflammatory arthritis ( 14 with rheumatoid arthritis and 1 with ankylosing spondylitis ) not receiving tumour necrosis factor alpha ( TNFalpha ) inhibitors with persistent moderate ( grade 2 ) or severe ( grade 3 ) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR : Fc at 1 x 10 ( 10 ) ( n = 5 ) or 1 x 10 ( 11 ) ( n = 6 ) DNase resistant particles per ml joint volume or placebo ( n = 4 ) into a knee ( n = 14 ) or ankle ( n = 1 ) . Safety was assessed through adverse event monitoring . As a secondary objective , changes in injected joint tenderness and swelling scores , each measured on a four-point scale , were evaluated . RESULTS Intra-articular injections of rAAV2-TNFR : Fc were well tolerated with no major safety issues . One event , mild knee pruritus , was considered probably related . Synovial fluid TNFR : Fc protein was not detected ( nor expected ) at the doses used . At 12 weeks after injection , a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR : Fc and placebo , respectively . CONCLUSION A single dose of intra-articular rAAV2-TNFR : Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFalpha antagonist use . It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR : Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis .

placebo-controlled

rAAV2-TNFR : Fc

or placebo

safety and tolerability

safety and tolerability

Safety

Synovial fluid TNFR : Fc protein

decrease in swelling

safety and efficacy


Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes : North American Breast Cancer Intergroup Trial E 2197 . PURPOSE The combination of doxorubicin and cyclophosphamide ( AC ) is a standard adjuvant regimen . Doxorubicin and docetaxel ( AT ) is one of the most active cytotoxic regimens for metastatic breast cancer . The purpose of this trial was to determine whether adjuvant AT improved disease-free survival compared with AC in operable breast cancer . PATIENTS AND METHODS Women with invasive breast cancer were eligible if there were one to three positive lymph nodes or if the node-negative tumor was greater than 1 cm . Patients were randomly assigned after surgery to receive doxorubicin ( 60 mg/m ( 2 ) ) plus either cyclophosphamide ( 600 mg/m ( 2 ) ; AC ) or docetaxel ( 60 mg/m ( 2 ) ; AT ) given every 3 weeks for four cycles , followed by hormone therapy for patients with estrogen receptor ( ER ) and/or progesterone receptor ( PR ) -positive tumors . RESULTS There were 2,882 eligible patients enrolled . After a median follow-up of 79.5 months , there was no significant difference in disease-free survival ( DFS ; 85 % in both arms ) or overall survival ( 91 % v 92 % ) at 5 years . The hazard ratio for AC versus AT was 1.02 ( 95 % CI for DFS , 0.86 to 1.22 ; P = .78 ) . In an exploratory analysis of prespecified stratification factors by ER and PR expression there were trends toward improved DFS for AT in ER/PR-negative disease . Grade 3 neutropenia associated with fever or infection occurred more often with AT ( 26 % v 10 % ; P < .05 ) . CONCLUSION AT did not improve DFS or overall survival in this population , and was associated with more toxicity .

Concurrent doxorubicin plus docetaxel

doxorubicin and cyclophosphamide ( AC )

Doxorubicin and docetaxel ( AT )

doxorubicin

plus either cyclophosphamide

or docetaxel

AC

AT

metastatic breast cancer .

disease-free survival

breast cancer

operable breast cancer

Women

invasive breast cancer


Genetic testing for BRCA1 : effects of a randomised study of knowledge provision on interest in testing and long term test uptake ; implications for the NICE guidelines . INTRODUCTION Interest in searching for mutations in BRCA1 and BRCA2 is high . Knowledge regarding these genes and the advantages and limitations of genetic testing is limited . It is unknown whether increasing knowledge about breast cancer genetic testing alters interest in testing . METHODS Three hundred and seventy nine women ( 260 with a family history of breast cancer ; 119 with breast cancer ) from The Royal Marsden NHS Foundation Trust were randomised to receive or not receive written educational information on cancer genetics . A questionnaire was completed assessing interest in BRCA1 testing and knowledge on breast cancer genetics and screening . Actual uptake of BRCA1 testing is reported with a six year follow-up . RESULTS Eighty nine percent of women at risk of breast cancer and 76 % of women with breast cancer were interested in BRCA1 testing ( P < 0.0001 ) . Provision of educational information did not affect level of interest . Knowledge about breast cancer susceptibility genes was poor . According to the NICE guidelines regarding eligibility for BRCA1 and BRCA2 testing , the families of 66 % of the at risk group and 13 % of the women with breast cancer would be eligible for testing ( probability of BRCA1 mutation > or=20 % ) . Within six years of randomisation , genetic testing was actually undertaken on 12 women , only 10 of whom would now be eligible , on the NICE guidelines . CONCLUSIONS There is strong interest in BRCA1 testing . Despite considerable ignorance of factors affecting the inheritance of breast cancer , education neither reduced nor increased interest to undergo testing . The NICE guidelines successfully triage those with a high breast cancer risk to be managed in cancer genetics clinics .

Genetic testing for

receive or

not receive

written educational information

questionnaire

testing

interest in

testing

testing

testing

level of interest

genetic testing

interest to undergo testing


[ Intra-uterine insemination with controlled ovarian hyperstimulation compared to an expectant management in couples with unexplained subfertility and an intermediate prognosis : a randomised study ] . OBJECTIVE Intrauterine insemination ( IUI ) with controlled ovarian hyperstimulation ( COH ) is commonly used as treatment of first choice in couples with unexplained subfertility . This treatment should only be applied when there is a realistic increase in chance of pregnancy , particularly because it carries the increased risk of multiple pregnancies . We evaluated the effectiveness of IUI with COH relative to expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy . DESIGN Multicentre randomised clinical study . METHOD 253 couples with unexplained subfertility and a probability of a spontaneous ongoing pregnancy of 30 % to 40 % within 12 months , were randomly assigned to IUI with COH for 6 months or expectant management for 6 months . The primary endpoint of our study was ongoing pregnancy within 6 months . Analysis was carried out according to the intention to treat principle . This study was registered with the Dutch Trial Register and has the International Standard Randomised Clinical Trial number ISRCTN72675518 . RESULTS Of the 253 couples included , 127 couples were allocated to IUI with COH and 126 to expectant management . In the intervention group , 42 women ( 33 % ) conceived , of which 29 pregnancies were ongoing ( 23 % ) . In the expectant management group , 40 women ( 32 % ) conceived , of which 34 pregnancies were ongoing ( 27 % ) ( relative risk : 0.85 ; 95 % CI : 0.63-1.1 ) . In the expectant management group one twin pregnancy occurred and in the intervention group one woman conceived twins and one a triplet . CONCLUSION A substantial beneficial effect of IUI with COH in couples with unexplained subfertility and an intermediate prognosis can be excluded . Expectant management for a period of 6 months therefore appears justified in these couples .

controlled ovarian hyperstimulation

Intrauterine insemination ( IUI )

ovarian hyperstimulation ( COH )

IUI with COH

expectant management

IUI with COH

IUI

expectant management

expectant management

IUI with COH

Intrauterine insemination ( IUI )

increase in chance of pregnancy

spontaneous ongoing pregnancy

ongoing pregnancy within 6 months

conceived

ongoing

twin pregnancy

twins and one a triplet

Expectant management

unexplained subfertility

unexplained subfertility

253 couples


A pilot study of a low-tilt biphasic waveform for transvenous cardioversion of atrial fibrillation : improved efficacy compared with conventional capacitor-based waveforms in patients . BACKGROUND The optimal waveform tilt for defibrillation is not known . Most modern defibrillators used for the cardioversion of atrial fibrillation ( AF ) employ high-tilt , capacitor-based biphasic waveforms . METHODS We have developed a low-tilt biphasic waveform for defibrillation . This low-tilt waveform was compared with a conventional waveform of equivalent duration and voltage in patients with AF . Patients with persistent AF or AF induced during a routine electrophysiology study ( EPS ) were randomized to receive either the low-tilt waveform or a conventional waveform . Defibrillation electrodes were positioned in the right atrial appendage and distal coronary sinus . Phase 1 peak voltage was increased in a stepwise progression from 50 V to 300V . Shock success was defined as return of sinus rhythm for > /=30 seconds . RESULTS The low-tilt waveform produced successful termination of persistent AF at a mean voltage of 223 V ( 8.2 J ) versus 270 V ( 6.7 J ) with the conventional waveform ( P = 0.002 for voltage , P = ns for energy ) . In patients with induced AF the mean voltage for the low-tilt waveform was 91V ( 1.6 J ) and for the conventional waveform was 158 V ( 2.0 J ) ( P = 0.005 for voltage , P = ns for energy ) . The waveform was much more successful at very low voltages ( less than or equal to 100 V ) compared with the conventional waveform ( Novel : 82 % vs Conventional 22 % , P = 0.008 ) . CONCLUSION The low-tilt biphasic waveform was more successful for the internal cardioversion of both persistent and induced AF in patients ( in terms of leading edge voltage ) .

low-tilt biphasic waveform

low-tilt waveform

conventional waveform

low-tilt waveform

conventional waveform

low-tilt waveform

conventional waveform

low-tilt biphasic waveform

efficacy

return of sinus rhythm

termination of persistent AF

mean voltage

atrial fibrillation


Smoking cessation with smokeless tobacco and group therapy : an open , randomized , controlled trial . Smokeless tobacco might be effective as an adjunct for smoking cessation . We evaluated the efficacy of smokeless tobacco and group support for smoking cessation in an open , randomized study that compared smokeless tobacco plus group support versus group support only . The study enrolled 263 healthy smokers ( M ( age ) = 49 years ) who smoked a mean of 24 cigarettes/day , with a mean of 31 pack-years . Smokeless tobacco was provided for 7 weeks ( or up to 12 ) , combined with eight group support visits provided by nurses . The control group received group support only . Smoking cessation rates were statistically significantly better in the smokeless tobacco group than in the control group during the first 7 weeks . Point-prevalence abstinence rates at 7 weeks were 36.4 % versus 20.8 % ( OR = 2.52 , p = .001 ) , respectively ; and continuous abstinence rates from weeks 4 to 7 were 31.5 % versus 19.2 % ( OR = 1.94 , p = .023 ) , respectively . The primary outcomes ( i.e. , 6-month point prevalence ) were 23.1 % versus 20.8 % , respectively ( OR = 1.31 , ns ) . Smokeless tobacco was relatively well tolerated , although 15 subjects ( 11.2 % ) stopped use due to adverse events . A total of 25 subjects ( 17.5 % ) were still using smokeless tobacco after 6 months . This trial demonstrated short-term efficacy of smokeless tobacco in combination with group support for smoking cessation but no long-term efficacy .

smokeless tobacco

group therapy

Smokeless tobacco

smokeless tobacco

group support

smokeless tobacco

group support

group support only

Smokeless tobacco

control

group support only

Smokeless tobacco

smokeless tobacco

Smoking cessation

smoking cessation

smoking cessation

Smoking cessation rates

Point-prevalence abstinence rates

continuous abstinence rates

6-month point prevalence

tolerated

adverse events .

long-term efficacy .

healthy smokers


Beneficial effects of a diabetes specific formula on insulin sensitivity and free fatty acid in patients with type 2 diabetes mellitus . BACKGROUND This prospective , randomized , controlled study was designed to investigate the effects of a diabetes specific formula ( Diason low energy : 313.8 kJ/100 ml ) , compared with a standard formula , on insulin sensitivity , serum C peptide , serum lipids and free fatty acid ( FFA ) in type 2 diabetics . METHODS In total of 71 type 2 diabetics completed the study . Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days . Venous blood samples ( 0.5 , 1 , 2 , 3 hours ) were collected at day-7 after a 75 g oral glucose tolerance test ( OGTT ) , day 1 after a standard test meal ( 1673.6 kJ ) and after 6 days of either the test diabetes specific formula or a standard formula . Plasma glucose , serum insulin , C peptide and lipids were measured . RESULTS After the intervention period , the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour ( P < 0.05 ) and 1 hour ( P < 0.01 ) ; significantly lower peak height of plasma glucose ( P = 0.05 ) ; significantly lower plasma insulin concentrations at 0.5 hour ( P < 0.01 ) , 1 hour ( P < 0.01 ) and 2 hours ( P < 0.01 ) ; and a significantly lower plasma insulin peak compared to controls ; both OGTT and a standard test meal ( P < 0.05 ) . The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower . The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT , but not different from the standard mixed meal . Both formulas were well tolerated . CONCLUSIONS In summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control . On top of this , the insulin sensitivity ( HOMA-IS ) was significantly improved and may therefore directly improve the impact on long term complications . The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need of nutritional support .

diabetes specific formula

diabetes specific formula

Diason low energy

: 313.8 kJ/100 ml )

standard formula

Enteral formulas

diabetes specific formula

standard formula

diabetes specific formula

diabetes specific formula

standard formula

nutrition formulas

standard mixed meal

diabetes specific formula

disease specific formula

Beneficial effects

insulin sensitivity

free fatty acid

insulin sensitivity

serum C peptide

serum lipids

free fatty acid ( FFA )

Plasma glucose

serum insulin

C peptide

lipids

peak height of plasma glucose

plasma insulin peak

glucose and insulin

C peptide level

glycemic control

insulin sensitivity ( HOMA-IS )

type 2 diabetics .


Long pediatric colonoscope versus intermediate length adult colonoscope for colonoscopy . BACKGROUND Controversy exists on how the length and diameter of colonoscopes affect the quality of colonoscopy . The aim of this study was to compare a long pediatric colonoscope with an intermediate length adult colonoscope with regards to completion rate and cecal intubation time . Whether either scope may be more efficient in any subgroups was also investigated . METHODS Asymptomatic patients admitted to the physical check-up department of Buddhist Dalin Tzu Chi General Hospital were included . A single endoscopist performed all of the colonoscopic examinations under sedation . Consecutive patients were randomized to undergo colonoscopy with either intermediate length adult colonoscope ( CF-240I ) or long pediatric colonoscope ( PCF-240L ) . The success rate and time required to reach cecum were compared between the two groups . RESULTS Between April 2005 and February 2006 , a total of 918 patients were enrolled . Incomplete colonoscopy occurred in 21 ( 2.3 % ) cases ( 14 in the CF-240I group and seven in the PCF-240L group , P > 0.1 ) . The overall cecal mean insertion time was 6.00 +/- 3.66 min . There was no significant difference between the CF-240I and PCF 240L groups with regard to the cecal intubation rate ( 96.9 % vs 98.5 % , P = 0.18 ) , the need for abdominal pressure ( 71.7 % vs 73.4 % , P = 0.55 ) and change of position ( 13.5 % vs 11.5 % , P = 0.37 ) . However , the cecal intubation time was shorter in the CF-240I group ( 5.75 +/- 3.18 vs 6.26 +/- 3.30 min , P = 0.02 ) . Subgroup analysis by sex , age , and body mass index showed comparable outcomes between the two groups except that the cecal intubation times were significantly shorter in the CF-240I group when only men ( 4.78 +/- 2.57 vs 5.50 +/- 2.93 min , P < 0.01 ) or those younger than 50 years ( 5.50 +/- 2.90 vs 6.25 +/- 3.68 min , P = 0.02 ) were considered . CONCLUSION Cecal intubation time is shorter in patients examined with an intermediate length adult colonoscope , mainly in the subgroups of men and those younger than 50 years of age .

Long pediatric colonoscope

intermediate length adult colonoscope

long pediatric colonoscope

intermediate length adult colonoscope

colonoscopic examinations

PCF 240L

intermediate length adult colonoscope

quality of colonoscopy .

efficient

Incomplete colonoscopy

overall cecal mean insertion time

regard to the cecal intubation rate

change of position

cecal intubation time

comparable outcomes

cecal intubation times

Cecal intubation time

Asymptomatic patients