Results of a phase III , 8-week , multicenter , prospective , randomized , double-blind , parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension . BACKGROUND Amlodipine besylate has been used in Korea for the treatment of hypertension for > 17 years , with well-established efficacy and tolerability . Amlodipine camsylate is a newer formulation developed for generic use . It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials . However , to date , no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension . OBJECTIVE This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension . METHODS This Phase III , 8-week , prospective , randomized , double-blind , parallel-group study was conducted in 13 cardiology centers across the Republic of Korea . Male and female Korean patients aged 18 to 75 years having uncomplicated , mild to moderate , essential hypertension ( sitting diastolic blood pressure [ SiDBP ] 90- < 110 mm Hg ) and receiving no antihypertensives in the 2 weeks before randomization were eligible . Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate . For the first 4 weeks , patients received amlodipine 5 mg QD ( morning ) . After 4 weeks , if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline , the dose of amlodipine was increased to 10 mg QD for 4 weeks . Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit ( baseline [ week 0 ] and weeks 4 and 8 of treatment ) ; mean values were calculated and recorded . At weeks 4 and 8 , tolerability was assessed using history taking and laboratory analysis , and compliance was assessed using pill counts . The primary end point was change from baseline in SiDBP at week 8 . Secondary end points were change from baseline in sitting systolic blood pressure ( SiSBP ) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not . RESULTS A total of 189 patients were enrolled ( mean age , 53 years ; 105 women , 84 men ; mean body weight , 65.8 kg ) . One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment ( this patient did not use any study medication ) and was excluded from the modified intent-to-treat ( ITT ) analysis . Thus , 188 patients were treated and included in the ITT analysis ( 94 patients per treatment group ; ITT analysis ) ; 161 patients were included in the perprotocol ( PP ) analysis ( n = 80 for amlodipine camsylate , n = 81 for amlodipine besylate ) ( 14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation ) . Mean ( SD ) SiSBP and SiDBP were significantly decreased from baseline in both groups ( amlodipine camsylate , from 146.7 [ 12.3 ] /96.6 [ 5.4 ] to 127.9 [ 14.8 ] /83.4 [ 7.7 ] mm Hg [ both , P < 0.001 ] ; amlodipine besylate , from 146.8 [ 12.8 ] /96.7 [ 5.1 ] to 128.0 [ 10.1 ] /83.8 [ 7.5 ] mm Hg [ both , P < 0.001 ] ) . The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant . The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar ( 56/69 [ 81.2 % ] and 83/92 [ 90.2 % ] , respectively ) . The prevalences of clinical adverse events ( AEs ) were not significantly different between the 2 treatment groups ( amlodipine camsylate , 27.3 % ; amlodipine besylate , 28.7 % ) . The most common AEs were dizziness and dyspnea ( both in 3/94 [ 3.2 % ] and 1/94 [ 1.1 % ] patients who received amlodipine camsylate and amlodipine besylate , respectively ) . CONCLUSION The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension .

amlodipine camsylate

amlodipine besylate

Amlodipine besylate

Amlodipine camsylate

amlodipine camsylate

amlodipine besylate

amlodipine camsylate

amlodipine besylate

amlodipine camsylate

amlodipine besylate

amlodipine 5 mg QD ( morning )

dose of amlodipine

amlodipine camsylate

amlodipine besylate )

amlodipine camsylate

amlodipine besylate

amlodipine camsylate

amlodipine besylate

effectiveness and tolerability

blood pressure

Trough blood pressure and heart rate

tolerability

SiDBP

sitting systolic blood pressure

Mean ( SD ) SiSBP

SiDBP

SiSBP/SiDBP

SiDBP response rates

clinical adverse events

dizziness and dyspnea

adults

hypertension

mild to moderate hypertension

Male

female

aged 18 to 75

hypertension

mean age , 53 years

women

men

adults

mild to moderate hypertension


Intensive insulin therapy improves endothelial function and microvascular reactivity in young people with type 1 diabetes . AIMS/HYPOTHESIS Macrovascular disease is an important cause of the increased morbidity and mortality rates associated with type 1 diabetes , and this vascular impairment begins in childhood . The aim of this study was to determine whether introducing intensive diabetes management [ intensive insulin therapy ( IIT ) and 'Sweet Talk ' text-messaging support ] produces measurable improvements in endothelial function . METHODS One hundred and twenty-six patients fulfilled the eligibility criteria ( type 1 diabetes for > 1 year ; on conventional insulin therapy ( CIT ) ; aged between 8 and 18 years ) , of whom 92 enrolled . Patients were randomised to group 1 , CIT only ( n=28 ) ; group 2 , CIT and Sweet Talk ( n=33 ) ; or group 3 , IIT and Sweet Talk ( n=31 ) . Vascular assessments ( including measures of endothelial damage , activation , dysfunction and oxidative stress ) and HbA1c were performed at baseline and repeated after 12 months of the study . RESULTS Glycaemic control deteriorated in patients on CIT , but improved significantly in patients allocated to IIT ( p=0.007 ) . IIT was associated with significantly greater improvements in E-selectin ( p < 0.0001 ) than CIT ( group 1 , p=0.026 and group 2 , p=0.053 ) . Vascular responses to acetylcholine improved in patients on IIT ( p=0.017 ) , but not in patients receiving CIT . These changes were all independent of HbA1c level . CONCLUSIONS/INTERPRETATION IIT appears to be associated with improvements in vascular markers , independently of changes in HbA1c , suggesting that IIT may confer vascular protection in addition to improving glycaemic control .

Intensive insulin therapy

'Sweet Talk ' text-messaging support ]

conventional insulin therapy ( CIT )

CIT

only ( n=28 ) ; group 2 ,

CIT and Sweet

endothelial function

endothelial function

Glycaemic control

E-selectin

Vascular responses

vascular markers

glycaemic control

young people

type 1 diabetes

One hundred and twenty-six patients

aged between 8 and 18 years


Effect of a ferrule and increased clinical crown length on the in vitro fracture resistance of premolars restored using two dowel-and-core systems . This study investigated the effect of a crown-lengthening ferrule on the fracture resistance of endodontically-treated teeth restored with two dowel-core systems . Thirty-two extracted mandibular first premolars were sectioned perpendicular to the long axis at a point 1.0 mm occlusal to the buccal cementoenamel junction . Following endodontic treatment , the teeth were randomly assigned to four groups : cast Ni-Cr alloy dowel-core with no ferrule ( Group A1 ) , cast Ni-Cr alloy dowel-core with 2.0 mm ferrule ( Group A2 ) , prefabricated carbon fiber-reinforced dowel-resin core with no ferrule ( Group B1 ) and carbon fiber-reinforced dowel-resin core with 2.0 mm ferrule ( Group B2 ) . Each specimen was embedded in a self-cured acrylic resin block from 2.0 mm apical to the margins of a cast Ni-Cr alloy crown , then loaded at 150 degrees from the long axis in a universal testing machine at a crosshead speed of 1.0 mm/minute until fracture . The data were recorded and analyzed using ANOVA and Fisher 's exact tests , with alpha = 0.05 . Mean failure loads ( kN ) for the A1 , A2 , B1 and B2 Groups were : 1.46 ( S.D . 0.45 ) , 1.07 ( 0.21 ) , 1.13 ( 0.30 ) and 1.02 ( 0.27 ) . The teeth restored with cast Ni-Cr dowel-cores and 2.0 mm ferrules demonstrated significantly lower fracture strengths , p = 0.04 . There were significant differences in the root fracture patterns between the two dowel systems , with the carbon fiber-reinforced dowel-resin core system , being the less severe p < 0.05 . Crown lengthening with a 2.0 mm apical extended ferrule resulted in reduced fracture strengths for endodontically-treated teeth restored using two dowel-core systems and cast metal crowns . The carbon fiber-reinforced dowel-resin core system reduced the severity of the root fractures .

ferrule

crown-lengthening ferrule

2.0 mm apical extended ferrule

ANOVA and Fisher 's exact tests

Mean failure loads

fracture strengths

root fracture patterns

fracture strengths

Thirty-two

root fractures


Effectiveness of cetrorelix for the prevention of premature luteinizing hormone surge during controlled ovarian stimulation using letrozole and gonadotropins : a randomized trial . OBJECTIVE To evaluate the effectiveness of a GnRH antagonist in preventing premature LH surge under a letrozole and gonadotropin protocol . DESIGN Prospective , randomized clinical trial . SETTING A teaching hospital and tertiary medical center . PATIENT ( S ) Sixty-one patients were randomly assigned into two letrozole and gonadotropin-treated groups . These were distinguished by the absence ( group I ) or presence ( group II ) of supplementation with 0.25 mg of cetrorelix . INTERVENTION ( S ) Controlled ovarian stimulation with letrozole and gonadotropins , cetrorelix and intrauterine insemination . MAIN OUTCOME MEASURE ( S ) Rate of premature LH surge . RESULT ( S ) Compared with group I , the rate of premature LH surge was statistically significantly lower for group II ( 43.4 % [ 13/30 ] vs. 19.4 % [ 6/31 ] ) , but the amount of gonadotropins used was statistically significantly higher ( 817.5 +/- 28.5 vs. 907.5 +/- 27.3 IU ) . Patients with premature LH surge had a statistically significantly lower pregnancy rate ( 21.4 % [ 9/42 ] vs. 0 [ 0/18 ] ) relative to their unaffected counterparts . CONCLUSION ( S ) A flexible protocol of 0.25 mg of cetrorelix for IUI cycles appears to suppress the rate of premature LH surge during ovarian stimulation with letrozole and gonadotropins . However , the incidence of premature LH surge remains too high , and modification will be necessary before the application of cetrorelix to IVF treatment .

cetrorelix

two letrozole and gonadotropin-treated

cetrorelix

premature luteinizing hormone surge

premature LH surge

Rate of premature LH surge .

rate of premature LH surge

amount of gonadotropins

premature LH surge

pregnancy rate

premature LH surge

premature LH surge

Sixty-one


Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle . We recently showed that resistance exercise and ingestion of essential amino acids with carbohydrate ( EAA+CHO ) can independently stimulate mammalian target of rapamycin ( mTOR ) signaling and muscle protein synthesis in humans . Providing an EAA+CHO solution postexercise can further increase muscle protein synthesis . Therefore , we hypothesized that enhanced mTOR signaling might be responsible for the greater muscle protein synthesis when leucine-enriched EAA+CHOs are ingested during postexercise recovery . Sixteen male subjects were randomized to one of two groups ( control or EAA+CHO ) . The EAA+CHO group ingested the nutrient solution 1 h after resistance exercise . mTOR signaling was assessed by immunoblotting from repeated muscle biopsy samples . Mixed muscle fractional synthetic rate ( FSR ) was measured using stable isotope techniques . Muscle protein synthesis and 4E-BP1 phosphorylation during exercise were significantly reduced ( P < 0.05 ) . Postexercise FSR was elevated above baseline in both groups at 1 h but was even further elevated in the EAA+CHO group at 2 h postexercise ( P < 0.05 ) . Increased FSR was associated with enhanced phosphorylation of mTOR and S6K1 ( P < 0.05 ) . Akt phosphorylation was elevated at 1 h and returned to baseline by 2 h in the control group , but it remained elevated in the EAA+CHO group ( P < 0.05 ) . 4E-BP1 phosphorylation returned to baseline during recovery in control but became elevated when EAA+CHO was ingested ( P < 0.05 ) . eEF2 phosphorylation decreased at 1 and 2 h postexercise to a similar extent in both groups ( P < 0.05 ) . Our data suggest that enhanced activation of the mTOR signaling pathway is playing a role in the greater synthesis of muscle proteins when resistance exercise is followed by EAA+CHO ingestion .

control

EAA+CHO

EAA+CHO group

nutrient solution

resistance exercise

mTOR signaling

Postexercise FSR

Increased FSR

Akt phosphorylation

4E-BP1 phosphorylation

eEF2 phosphorylation

Sixteen

male


Comparison of two sedation techniques in patients undergoing surgical procedures under regional anaesthesia . OBJECTIVE Intraoperative comfort and patient satisfaction during surgical procedures under regional anaesthesia can be improved with the use of supplemental intravenous sedation . The authors conducted a study to compare two sedation techniques for surgical procedures performed under regional anaesthesia , i.e. , midazolam and pethidine combination compared with midazolam and tramadol combination . METHODS Forty adult American Society of Anaesthesiologists ( ASA ) grade 1-111 patients , aged between 40-65 years undergoing surgery under regional anaesthesia ( sub-arachnoid block ) were included . The patients were randomly divided into two groups . All patients received standardized premedication , intraoperative monitoring and oxygen therapy . Group A patients received midazolam 0.03 mg/kg followed by pethidine 20 mg intravenously , and group B patients received midazolam 0.03 mg/kg followed by tramadol 20 mg intravenously after the institution of regional anaesthesia . Monitoring included ECG , blood pressure , respiratory rate , oxygen saturation and sedation score . Complications , if any , were recorded . Monitoring was continued during the recovery room stay . All patients were interviewed in the evening and time of ambulation and rating of OR experience was noted . RESULTS Data analysis showed no significant difference between pethidine and tramadol for all the haemodynamic variables ( p = > 0.05 ) . There was also no significant difference in patient 's and surgeon 's assessment of their experience . Complications and recovery characteristics also did not show any significant difference . CONCLUSION Midazolam-tramadol combination may be used as an alternative to midazolam-pethidine combination for sedation during surgical procedures performed under regional anaesthesia .

sedation techniques

midazolam

pethidine combination

midazolam

tramadol combination

pethidine

tramadol

Midazolam-tramadol combination

midazolam-pethidine combination

patient satisfaction

ECG

blood pressure

respiratory rate

oxygen saturation

sedation score

haemodynamic variables

Forty

40-65 years


Enhancing attitudes and intentions in prospective blood donors : evaluation of a new donor recruitment brochure . BACKGROUND Although little empiric evidence has been published concerning the efficacy of blood donor recruitment materials , research suggests that simple attempts to enhance knowledge may not be sufficient to motivate donation . In contrast , recent donor motivation studies highlight the importance of anxiety , attitudes , and perceived ability to cope with donation ( i.e. , self-efficacy ) as crucial determinants of donation intention . Therefore , recruitment materials that specifically address these constructs have the potential to outperform traditional educational brochures . STUDY DESIGN AND METHODS Participants were randomly assigned to read one of three brochures : 1 ) a new brochure addressing common donor concerns and suggesting specific coping strategies , 2 ) a standard blood center brochure , or 3 ) a control brochure on healthy eating and exercise . Standardized questionnaires were completed before and after the brochures to assess change in blood donation anxiety , attitude , self-efficacy , and intention . RESULTS Although no significant changes were noted for the control brochure , after reading the new brochure participants reported significant improvements in attitude , anxiety , self-efficacy , and donation intention . The standard donation brochure had an intermediate effect . CONCLUSION Efforts to address common donor fears and to provide useful coping suggestions may improve the effectiveness of blood donation recruitment materials .

donor recruitment brochure

blood donor recruitment materials

brochures

brochure

standard blood center brochure

a

attitudes

intentions

motivate donation

anxiety , attitudes

perceived ability to cope with donation

blood donation recruitment materials

prospective blood donors


Transthoracic versus transesophageal cardioversion of atrial fibrillation under light sedation : a prospective randomized trial . BACKGROUND Electrical cardioversion ( ECV ) of atrial fibrillation ( AF ) is limited by a 5-10 % failure rate and by the expense arising from a perceived need for general anesthesia . A transesophageal approach using light sedation has been proposed as a means of augmenting the success rate and avoiding the need for general anesthesia . We hypothesized that the high rate of success and the lower energy requirement associated with biphasic cardioversion might eliminate any advantage of the transesophageal approach . METHODS We randomly assigned 60 patients attending for ECV of persistent AF to a transesophageal or a transthoracic approach . Sedation of moderate depth was achieved with intravenous midazolam . The dose of midazolam was titrated in the same manner in both groups . RESULTS Sinus rhythm was restored in 29/30 patients ( 97 % ) in each group using a similar number of shocks for both groups ( 1.3 +/- 0.6 transesophageal vs 1.4 +/- 0.7 transthoracic , P = NS ) with a similar procedure duration ( 14.1 +/- 8.2 minutes vs 13.8 +/- 7.5 minutes , P = NS ) . Both groups received similar doses of midazolam ( 4.2 +/- 2.7 mg vs 4.4 +/- 2.8 mg , P = NS ) and both reported a similar discomfort score in ( 0.9 +/- 1.3 vs 1.1 +/- 1.8 , P = NS ) . No complication occurred in either group . CONCLUSION AF may be cardioverted safely and effectively by either a transthoracic or a transesophageal approach . The use of sedation of moderate depth renders cardioversion by either approach acceptable . As transesophageal ECV shows no clear advantage , transthoracic cardioversion should remain the approach of first choice .

Transthoracic

transesophageal cardioversion

transesophageal

transthoracic approach

intravenous midazolam

Sinus rhythm

discomfort score

complication

safely and effectively


Short-term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole-body insulin sensitivity through gains in peripheral , not hepatic insulin sensitivity . CONTEXT Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus ; however , the contributions of peripheral and hepatic tissues to these improvements are not known . OBJECTIVE Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions . DESIGN Subjects were randomly assigned to one of two groups . The energy balance group consumed an isocaloric diet consisting of 50 % carbohydrate , 30 % fat , and 20 % protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70 % of maximum oxygen consumption maximum during the second 7 d of the 15-d study period . Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study . SETTING The study was performed at Ohio State University 's General Clinical Research Center . PARTICIPANTS There were 18 obese , mildly diabetic humans included in the study . INTERVENTION Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES Whole-body , peripheral , and hepatic insulin sensitivity were measured . RESULTS Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin . Likewise , it did not alter endogenous glucose production during high-dose insulin . However , 1-wk of exercise training increased both whole-body ( P < 0.05 ) and peripheral insulin sensitivity ( P < 0.0001 ) during high-dose insulin . CONCLUSION Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral , not heptic insulin sensitivity .

Short-term aerobic exercise training

Short-term aerobic exercise training

aerobic exercise

energy balance

energy balance plus exercise

isoglycemic/hyperinsulinemic clamp

Aerobic exercise training

Exercise training

exercise training

short-term aerobic exercise

whole-body insulin sensitivity

endogenous glucose production


Mechanical efficiency and propulsion technique after 7 weeks of low-intensity wheelchair training . BACKGROUND To evaluate the effect of a 7-week low-intensity hand rim wheelchair training on the submaximal metabolic cost , mechanical efficiency and propulsion technique in able-bodied participants . METHODS Participants were randomly divided over an experimental group ( n=14 ) and a control group ( n=7 ) . The experimental group received 7 weeks wheelchair training ( 3 week ( -1 ) , 70 min ) at a low intensity ( 30 % of the heart rate reserve ) , whereas the control group did not receive training . During pre- and post-tests , submaximal exercise was performed on a stationary wheelchair ergometer at fixed levels of power output . Mechanical efficiency , oxygen uptake , heart rate , timing parameters and stroke angles were measured . Video recordings were made to determine the stroke pattern . FINDINGS Mechanical efficiency increased and metabolic cost decreased significantly in the experimental group compared to the control group . Push time increased and cycle frequency decreased as a result of training . The stroke angle increased in the experimental group during the training period . The experimental group preferred double-looping over propulsion , while the control group mainly used single-looping over propulsion patterns during the post-test . INTERPRETATION A low-intensity , 7-week training protocol has a beneficial effect on the mechanical efficiency and metabolic cost of wheelchair propulsion in able-bodied participants . The improved mechanical efficiency seems to be the result of changes in propulsion technique that were found .

wheelchair training

low intensity

control

did not receive training

mechanical efficiency

Mechanical efficiency ,

oxygen uptake

heart rate

, timing parameters and

stroke angles

stroke pattern

Mechanical efficiency increased and

metabolic cost

decreased

Push time

cycle frequency

stroke angle

single-looping over propulsion


A randomized , placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities . The purpose of this study was to determine the efficacy of controlled-release ( CR ) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders . A randomized double-blind , placebo-controlled crossover trial of CR melatonin ( 5 mg ) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects . Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs . Clinician rating of severity of the sleep disorder and improvement from baseline , along with caregiver ratings of global functioning and family stress were also obtained . Fifty-one children ( age range 2-18 years ) who did not respond to sleep hygiene intervention were enrolled . Fifty patients completed the crossover trial and 47 completed the open-label phase . Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min . Similarly , significant improvement was observed in clinician and parent ratings . There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase . Overall , the therapy improved the sleep of 47 children and was effective in reducing family stress . Children with neurodevelopmental disabilities , who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance , showed improvement in melatonin therapy .

placebo-controlled

melatonin treatment

melatonin

placebo-controlled

CR melatonin

melatonin therapy .

efficacy

Sleep characteristics

Clinician rating

caregiver ratings

total night-time sleep

sleep latency

clinician and parent ratings .

open-label somnolog measures

sleep efficiency

the longest sleep episode

improved the sleep

effective in reducing family stress

impaired sleep maintenance

delayed sleep phase syndrome

impaired sleep maintenance

children

neurodevelopmental disabilities

delayed sleep phase syndrome

impaired sleep maintenance

children

neurodevelopmental disabilities

autistic spectrum disorders

Fifty-one

children ( age range 2-18 years )

Children

neurodevelopmental disabilities


Risperidone versus haloperidol in children and adolescents with AD : a randomized , controlled , double-blind trial . OBJECTIVE The aim of the study was to compare safety , efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder ( AD ) . METHOD This study was designed as a double-blind , prospective , for a 12-week period . A total of 30 subjects , between the ages of 8 and 18 with AD based on DSM IV criteria , were included in the study . Behavioral Rating Scales were performed by the investigators and the parents . Safety assessment included vital signs , electrocardiogram , electroencephalogram , adverse events , laboratory tests , extrapyramidal symptoms and the side effects . Both treatments were applied in a once daily dosage regimen of 0.01-0.08 mg/kg/day . RESULTS The reduction from baseline in Ritvo-Freeman Real Life Rating Scale ( RF-RLRS ) , sensory motor ( subscale I ) and language ( subscale V ) scores were significant in risperidone group ( P < 0.05 ) . Compared to haloperidol , risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist ( ABC ) and Turgay DSM-IV Pervasive Developmental Disorder ( PDD ) scale scores ( P < 0.05 and P < 0.01 ) . There was a greater increase of prolactin in the risperidone group , while alanine amino transferase ( ALT ) had further increased in the haloperidol group . Sensory motor behaviors ( subscale I ) and language at the end of the 12th week , RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group ( P < 0.05 ) . CONCLUSIONS Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms , impulsivity , language skills , and impaired social relations in children with AD . These results demonstrated that both drugs were safe and well tolerated in the treatment of AD .

Risperidone

haloperidol

risperidone

haloperidol

electrocardiogram

electroencephalogram

safety , efficacy and tolerability

Behavioral Rating Scales

Safety assessment

prolactin

alanine amino transferase ( ALT

Sensory motor behaviors ( subscale I )

language

impaired social relations


Comparison with computed tomography of two ultrasound devices for diagnosis of abdominal aortic aneurysm . Screening for abdominal aortic aneurysms ( AAAs ) in patients at risk will become more cost effective if a simple , inexpensive , and reliable ultrasound device is available . The aim of this study was to compare a 2-dimensional , handheld ultrasound device and a newly developed ultrasound volume scanner ( based on bladder scan technology ) with computed tomography ( CT ) for diagnosing AAA . A total of 146 patients ( mean age 69 +/- 10 years ; 127 men ) were screened for the presence of AAAs ( diameter > 3 cm ) using CT. All patients were examined with the handheld ultrasound device and the volume scanner . Maximal diameters and volumes were used for the analyses . AAAs were diagnosed by CT in 116 patients ( 80 % ) . The absolute difference of aortic diameter between ultrasound and CT was < 5 mm in 88 % of patients . Limits of agreement between ultrasound and CT ( -6.6 to 9.4 mm ) exceeded the limits of clinical acceptability ( +/-5 mm ) . An excellent correlation between ultrasound and CT was observed ( r = 0.98 ) . The correlation coefficient between the volume scanner and CT was 0.86 , with agreement of 90 % and kappa value of 0.73 . Using an optimal cut-off value of > 56 ml , defined by receiver-operating characteristic curve analysis , sensitivity , specificity , and the positive and negative predictive values of the volume scanner for detecting AAA were 90 % , 90 % , 97 % , and 71 % , respectively . In conclusion , this study shows that a 2-dimensional , handheld ultrasound device and a newly developed ultrasound volume scanner can effectively identify patients with AAAs confirmed by CT .

computed tomography

handheld ultrasound device

ultrasound volume scanner

computed tomography ( CT )

CT

ultrasound

CT

CT

ultrasound

CT

CT

Maximal diameters and volumes

absolute difference of aortic diameter

abdominal aortic aneurysm .


Can analysis of the bispectral index prove helpful when monitoring titration of doses of midazolam and ketamine for sedation during paediatric cardiac catheterization . OBJECTIVE We investigated the use of the bispectral index for monitoring sedation during cardiac catheterization . The scores for the bispectral index may not reflect correct values in children , but may be helpful during titration of sedatives such as midazolam and ketamine . METHODS We conducted a prospective randomized clinical trial in 126 patients scheduled for cardiac catheterization in a teaching hospital . They ranged in age from 4 months to 15 years . In 66 patients , sedation was performed without use of the bispectral index , while the index was used in the other 60 patients . The data collected included heart rate , mean arterial pressure , respiratory rate , saturation of oxygen , amount of sedatives , awakening time and adverse effects . We subdivided the patients into age-related groups for each parameter . RESULTS The demographic data were not statistically different . Monitoring with the bispectral index in those aged from 1 to 3 years revealed use of lower doses of midazolam , at 2.09 mg per kg per hr , with standard deviation of 0.36 , and similarly lowers doses of ketamine , at 2.07 mg per kg per hr , with standard deviation of 0.22 , the values in those not monitored being 2.93 , with standard deviation of 0.45 , and 2.96 with standard deviation of 0.51 respectively , these difference being statistically significant ( p = 0.001 and p = 0.04 , respectively ) . In those aged from 3 to 6 years of age , dosage of midazolam was 2.09 , with deviation of 0.36 , and of ketamine 1.78 , with deviation of 0.27 , following use of the bispectral index , compared to 2.89 with deviation of 0.28 , and 2.62 with deviation of 0.69 respectively , when the bispectral index was not used , these again being significant differences ( p = 0.033 and p = 0.04 ) . The requirements for respiratory support and adverse effects were also significantly lower when using the bispectral index ( p less than 0.05 ) . No significant difference was found regarding dosages at the ages of 4 months to 1 year , and 6 to 15 years . The awakening time , however , was shorter with use of the index in those aged from 1 to 6 years . CONCLUSIONS When using the bispectral index for monitoring sedation during catheterization in children , we noted decreased need for doses of midazolam and ketamine , a lower need for respiratory support and less adverse effects .

midazolam

ketamine

bispectral index

midazolam and ketamine

bispectral index

paediatric cardiac catheterization

cardiac catheterization

adverse effects

awakening time

midazolam

ketamine

respiratory support

adverse effects

paediatric cardiac catheterization

126 patients

aged from 3 to 6 years of age

children


The effect of oral sodium acetate administration on plasma acetate concentration and acid-base state in horses . AIM Sodium acetate ( NaAcetate ) has received some attention as an alkalinizing agent and possible alternative energy source for the horse , however the effects of oral administration remain largely unknown . The present study used the physicochemical approach to characterize the changes in acid-base status occurring after oral NaAcetate/acetic acid ( NAA ) administration in horses . METHODS Jugular venous blood was sampled from 9 exercise-conditioned horses on 2 separate occasions , at rest and for 24 h following a competition exercise test ( CET ) designed to simulate the speed and endurance test of 3-day event . Immediately after the CETs horses were allowed water ad libitum and either : 1 ) 8 L of a hypertonic NaAcetate/acetic acid solution via nasogastric tube followed by a typical hay/grain meal ( NAA trial ) ; or 2 ) a hay/grain meal alone ( Control trial ) . RESULTS Oral NAA resulted in a profound plasma alkalosis marked by decreased plasma [ H+ ] and increased plasma [ TCO2 ] and [ HCO3- ] compared to Control . The primary contributor to the plasma alkalosis was an increased [ SID ] , as a result of increased plasma [ Na+ ] and decreased plasma [ Cl- ] . An increased [ Atot ] , due to increased [ PP ] and a sustained increase in plasma [ acetate ] , contributed a minor acidifying effect . CONCLUSION It is concluded that oral NaAcetate could be used as both an alkalinizing agent and an alternative energy source in the horse .

sodium acetate

Sodium acetate ( NaAcetate )

competition exercise test

typical hay/grain meal

hay/grain meal alone

effect

plasma acetate concentration

acid-base state

acid-base status

Jugular venous blood

profound plasma alkalosis

plasma [ H+ ]

plasma [ TCO2 ] and [ HCO3- ]

plasma alkalosis

SID

[ Atot ]

[ PP ]

plasma [ acetate

acidifying effect


Pharmacokinetics and relative bioavailability of prajmalium bitartrate after single oral dosing . Pharmacokinetics and relative bioavailability of the marketed prajmalium bitartrate tablet ( Neo-Gilurytmal , CAS 2589-47-1 ) compared to an oral solution were investigated in an open , randomized , single-dose two-fold crossover study in 20 healthy male volunteers . One subject was identified to be a poor metabolizer . In the study population with normal metabolic status the two oral formulations proved to be bioequivalent with regard to the pharmacokinetic parameters Cmax , AUC ( 0-Tlast ) , AUC ( 0-infinity ) and Ae ( 24h ) . tmax was prolonged after administration of the tablets . The relative bioavailability of prajmalium bitartrate from the tablet amounted to 112 % . The poor metabolizer demonstrated in both oral formulations high plasma concentrations , increased AUCs and prolonged terminal half-lives as well as increased renal excretion of prajmalium bitartrate .

prajmalium bitartrate

prajmalium bitartrate tablet

Neo-Gilurytmal , CAS 2589-47-1

oral solution

Pharmacokinetics

relative bioavailability

poor metabolizer .

pharmacokinetic parameters Cmax

AUC ( 0-Tlast )

AUC ( 0-infinity )

Ae ( 24h )

tmax

relative bioavailability

high plasma concentrations

healthy

male

One

poor metabolizer


Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas . The recurrence of hepatocellular carcinoma ( HCC ) after minimally invasive therapy is frequent . Adoptive immunotherapy is thought to be an effective method to lower recurrence and metastasis rates of malignant tumors . Therefore , 85 HCC patients after transcatheter arterial chemoembolization and radiofrequency ablation therapy were randomized to immunotherapy group and no adjuvant therapy group . Autologous cytokine-induced killer ( CIK ) cells were transfused via hepatic artery to the patients . The alteration of levels of lymphocyte subsets in peripheral blood of patients was examined by flow cytometry . All patients were screened by computed tomography every 2 months to observe the tumor recurrent conditions . After CIK cell infusions , the percentages of CD3+ , CD4+ , CD56+ , CD3+CD56+ cells , and CD4+/CD8+ ratio increased from 68.6+/-11.0 % , 31.1+/-9.0 % , 15.6+/-7.9 % , 5.2+/-3.1 % , and 1.1+/-0.5 to 70.7+/-10.1 % , 33.5+/-8.0 % , 18.4+/-9.4 % , 5.9+/-2.8 % , and 1.3+/-0.7 , respectively ( P < 0.05 ) ; whereas the percentage of CD8 cells decreased from 31.1+/-7.8 % to 28.6+/-8.3 % ( P < 0.05 ) . The 1-year and 18-month recurrence rates of the study group were 8.9 % and 15.6 % , compared with 30.0 % and 40.0 % of the control group ( both P value < 0.05 ) . The data suggest that CIK cell transfusion is an effective treatment . It can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC .

cytokine-induced killer cells

Adoptive immunotherapy

radiofrequency ablation therapy

immunotherapy

no adjuvant therapy

CIK cell

CIK cell transfusion

percentage of CD8 cells

hepatocellular carcinomas

tumor recurrent conditions

HCC


Improving the transition from residential to outpatient addiction treatment : gender differences in response to supportive telephone calls . Substance use relapse rates are often high in the first months after discharge from inpatient substance abuse treatment , and patient adherence to aftercare plans is often low . Four residential addiction treatment centers participated in a feasibility study designed to estimate the efficacy of a post-discharge telephone intervention intended to encourage compliance with aftercare . A total of 282 participants ( 100 women , 182 men ) with substance use disorders were included in this secondary analysis . The findings revealed that women were more likely than men to attend aftercare . This " gender effect " persisted after adjustment for a number of potential mediators .

inpatient substance abuse treatment

patient adherence to aftercare

efficacy

attend aftercare

residential to outpatient addiction

women

men


Effect of upper arm brachial basilic and prosthetic forearm arteriovenous fistula on left ventricular hypertrophy . BACKGROUND Creation of an arteriovenous fistula ( AVF ) may increase left ventricular hypertrophy in the hemodialysis population . Aim of this study was to compare the effects of a brachial-basilic ( BB ) AVF and the prosthetic brachial-antecubital forearm loop access ( PTFE ) on cardiac performance . METHODS Patients were randomized to receive BB-AVF or prosthetic brachial-antecubital forearm loop access . Before and three months after AVF creation patients underwent an echocardiographic examination . Mann-Whitney U-test was used to compare relative increase between the measured cardiac parameters for the two groups . RESULTS Twenty-seven patients participated in the study . The relative increase in left ventricular parameters was not significantly different between the two groups . Only left ventricular end-diastolic diameter tended to be of significance . Mean blood flow through the brachial artery was 1680+/-156 and 1450+/-221 mL/min three months after surgery for the PTFE and the BB-AVF group , respectively . CONCLUSION After three months of follow-up , changes in cardiac structure were comparable between patients with BB and PTFE AVFs . Also access flow was comparable at this time . In general , the effects of creation of a fistula on LV structure were limited . Longer follow up time may be needed to explore the long term effects of different vascular accesses on cardiac function .

brachial-basilic ( BB ) AVF

BB-AVF

left ventricular hypertrophy

left ventricular hypertrophy

cardiac performance .

Mann-Whitney U-test

measured cardiac parameters

left ventricular parameters

left ventricular end-diastolic diameter

Mean blood flow

changes in cardiac structure

access flow

cardiac function .

hemodialysis population .

AVF creation patients

patients with BB and PTFE AVFs .


The effect of coenzyme Q10 on microcirculatory endothelial function of subjects with type 2 diabetes mellitus .

coenzyme Q10

microcirculatory endothelial function

type 2 diabetes mellitus


The cost-effectiveness of parasitologic diagnosis for malaria-suspected patients in an era of combination therapy . The introduction of artemisinin-based combination therapy in sub-Saharan Africa has prompted calls for increased use of parasitologic diagnosis for malaria . We evaluated the cost-effectiveness of rapid diagnostic tests ( RDTs ) in comparison to microscopy in guiding treatment of non-severe febrile illness at varying levels of malaria endemicity using data on test accuracy and costs collected as part of a Tanzanian trial . If prescribers complied with current guidelines , microscopy would give rise to lower average costs per patient correctly treated than RDTs in areas of both high and low transmission . RDT introduction would result in an additional 2.3 % and 9.4 % of patients correctly treated , at an incremental cost of $ 25 and $ 7 in the low and high transmission settings , respectively . Cost-effectiveness would be worse if prescribers do not comply with test results . The cost of this additional benefit may be higher than many countries can afford without external assistance or lower RDT prices .

artemisinin-based combination therapy

rapid diagnostic tests ( RDTs )

microscopy

cost-effectiveness

cost-effectiveness

costs

costs

patients correctly treated

incremental cost

Cost-effectiveness


Impact of a 16-community trial to promote judicious antibiotic use in Massachusetts . OBJECTIVES Reducing unnecessary antibiotic use , particularly among children , continues to be a public health priority . Previous intervention studies have been limited by size or design and have shown mixed results . The objective of this study was to determine the impact of a multifaceted , community-wide intervention on overall antibiotic use for young children and on use of broad-spectrum agents . In addition , we sought to compare the intervention 's impact on commercially and Medicaid-insured children . METHODS We conducted a controlled , community-level , cluster-randomized trial in 16 nonoverlapping Massachusetts communities , studied from 1998 to 2003 . During 3 years , we implemented a physician behavior-change strategy that included guideline dissemination , small-group education , frequent updates and educational materials , and prescribing feedback . Parents received educational materials by mail and in primary care practices , pharmacies , and child care settings . Using health-plan data , we measured changes in antibiotics dispensed per person-year of observation among children who were aged 3 to < 72 months , resided in study communities , and were insured by a participating commercial health plan or Medicaid . RESULTS The data include 223,135 person-years of observation . Antibiotic-use rates at baseline were 2.8 , 1.7 , and 1.4 antibiotics per person-year among those aged 3 to < 24 , 24 to < 48 , and 48 to < 72 months , respectively . We observed a substantial downward trend in antibiotic prescribing , even in the absence of intervention . The intervention had no additional effect among children aged 3 to < 24 months but was responsible for a 4.2 % decrease among those aged 24 to < 48 months and a 6.7 % decrease among those aged 48 to < 72 months . The intervention effect was greater among Medicaid-insured children and for broad-spectrum agents . CONCLUSIONS A sustained , multifaceted , community-level intervention was only modestly successful at decreasing overall antibiotic use beyond substantial secular trends . The more robust impact among Medicaid-insured children and for specific medication classes provides an argument for specific targeting of resources for patient and physician behavior change .

Antibiotic-use rates

antibiotic prescribing

overall antibiotic use

children who were aged 3 to < 72 months


Impact of a controlled heated breathing tube humidifier on sleep quality during CPAP therapy in a cool sleeping environment . There are conflicting data on the effect of adding a heated humidifier to nasal continuous positive airway pressure ( CPAP ) therapy for patients with obstructive sleep apnoea syndrome ( OSAS ) . The effects of heated humidification on sleep quality and treatment side-effects for patients who prefer a cold bedroom environment have not been studied . A randomised , controlled crossover trial involving 19 patients with a first-ever diagnosis of OSAS measured the effect of conventional heated humidification added to CPAP compared with a controlled heated breathing tube humidifier ( ThermoSmart ( R ) ; Fisher and Paykel Healthcare , Auckland , New Zealand ) on sleep quality . During the night in the sleep laboratory at a mean room temperature of 14 degrees C , less condensation formed with the controlled heated breathing tube humidifier ( 1.9 mL versus 35.3 mL ) in the delivery system . In addition , the total sleep time , time spent in sleep stages 3 and 4 , and rapid eye movement sleep phases were significantly longer and the overall side-effect score was lower than with conventional heated humidification . Patients on nasal continuous positive airway pressure desiring a cool bedroom temperature could benefit from controlled heated breathing tube humidification technology ( with inputs from ambient temperature , set pressure and flow ) .

CPAP therapy

heated humidifier

sleep quality

sleep quality

treatment side-effects

sleep quality

condensation

total sleep time

time spent in sleep stages 3 and 4

rapid eye movement sleep phases

overall side-effect score


A randomised double-blind trial of cyclosporin and azathioprine in refractory rheumatoid arthritis . Fifty-two patients with severe rheumatoid arthritis ( RA ) from four Australian centres were randomised to receive cyclosporin A ( CSA ) ( n = 25 ) or azathioprine ( AZA ) ( n = 27 ) for six months . Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively . The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg . Assessments of side-effects and outcomes of benefit were made monthly by independent , blinded observers . Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values . However , there were no statistically significant differences in these parameters between the two groups . There was a mean increase in serum creatinine concentration associated with CSA ; no persons were withdrawn from the study for this reason . Seven CSA recipients ( three gastrointestinal symptoms , two neurological symptoms , two other ) and 12 AZA recipients ( six gastrointestinal symptoms , four inefficacy , two other ) withdrew from treatment prematurely . Seven CSA recipients became hypertensive and four required anti-hypertensive therapy . Adverse events not requiring cessation of therapy were more commonly seen among CSA patients . In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies . CSA toxicities were predictable and manageable but required close monitoring .

cyclosporin

azathioprine

cyclosporin A ( CSA )

azathioprine ( AZA )

CSA

AZA

CSA

AZA

CSA

AZA

CSA

CSA

cyclosporin

azathioprine

CSA

serum creatinine concentration

six gastrointestinal symptoms

four inefficacy

two other

hypertensive

anti-hypertensive therapy

CSA toxicities

refractory rheumatoid arthritis

Fifty-two


Response of patients to enalapril , felodipine and their combination .

patients to enalapril , felodipine


Randomized , comparative study of the efficacy and safety of artesunate plus amodiaquine , administered as a single daily intake versus two daily intakes in the treatment of uncomplicated falciparum malaria . BACKGROUND Artesunate plus amodiaquine is a coblistered ACT , given as a single daily intake . It has been suggested that , in view of the number of tablets to be taken ( particularly in adults ) , it may be possible to improve compliance by allowing patients to divide the daily dose . The objectives of this randomized , comparative , open-label , multicentre study , conducted in Senegal and in Cameroon in 2005 , was to demonstrate the non-inferiority and to compare the safety of artesunate plus amodiaquine , as a single daily intake versus two daily intakes . METHODS A three-day treatment period and 14-day follow-up period was performed in any subject weighting more than 10 kg , presenting with a malaria paroxysm confirmed by parasitaemia > or = 1,000/microl , after informed consent . Patients were randomly allocated into one of the two regimens , with dosage according to bodyweight range . All products were administered by an authorized person , blinded to both the investigating physician and the biologist . The primary endpoint was an adequate response to treatment on D14 ( WHO definition ) . The two-sided 90 % confidence interval of the difference was calculated on intent to treat ( ITT ) population ; the acceptance limit for non-inferiority was 3 % . The safety was evaluated by incidence of adverse events . RESULTS Three-hundred and sixteen patients were included in the study . The two patient groups were strictly comparable on D0 . The adequate responses to treatment were similar for the two treatment regimens on D14 , PCR-corrected ( 99,4 % in the one-daily intake group versus 99,3 % in the comparative group ) . The statistical analyses demonstrated the non-inferiority of administering artesunate/amodiaquine as two intakes . The drug was well tolerated . The main adverse events were gastrointestinal disorders ( 2.5 % ) and pruritus ( 2.5 % ) ; safety profiles were similar in the two groups . CONCLUSION This pilot study confirms the efficacy and good tolerability of artesunate plus amodiaquine , administrated either in one or in two daily intakes .

artesunate plus amodiaquine

amodiaquine

efficacy

safety

compliance

non-inferiority

safety of artesunate plus amodiaquine

adequate response to treatment on D14

incidence of adverse events

adequate responses to treatment

non-inferiority

well tolerated

gastrointestinal disorders

uncomplicated falciparum malaria .

Three-hundred and sixteen


Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment . OBJECTIVE To evaluate the therapeutic efficacy and safety of epoetin zeta , compared with epoetin alfa , in maintaining target haemoglobin ( Hb ) concentrations in patients with anaemia and chronic kidney disease ( CKD ) maintained on haemodialysis . METHODS Patients received epoetin zeta or epoetin alfa intravenously , 1-3 times/week for 12 weeks , then the alternative treatment for 12 weeks , in this double-blind , crossover , phase III trial . Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis . Patients had received epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable epoetin dose . MAIN OUTCOME MEASURES Primary efficacy endpoints were intra-individual differences ( test-reference ) in mean Hb levels and mean weekly dose/kg of body weight . Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies , tolerability , and adverse events ( AEs ) . RESULTS In total , 313 patients were randomized to receive epoetin zeta ( n = 155 ) or epoetin alfa ( n = 158 ) ; 146 and 145 patients ( respectively ) switched treatment after 12 weeks . Mean ( range ) Hb levels were 11.35 ( 8.96-14.22 ) g/dL and 11.54 ( 8.74-13.84 ) g/dL for patients receiving epoetin zeta and epoetin alfa , respectively ( 95 % confidence interval [ CI ] [ test-reference ] : 0.09-0.28 g/dL , within the predefined equivalence range of +/-0.6 g/dL ) . Mean ( range ) weekly doses were 92.68 ( 12.74-398.41 ) IU/kg/wk and 92.58 ( 10.53-393.07 ) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa , respectively ( 95 % CI [ test-reference ] : -4.67 and 4.29 IU/kg/wk , within the equivalence range of +/-45.00 IU/kg/wk ) . Patients underwent minor nominal dose adjustments during treatment crossover . AE profile was similar for both products ; the most commonly reported AEs were infections and infestations ( in 26.5 % of patients receiving epoetin zeta and 23.6 % receiving epoetin alfa ) . No patients developed neutralizing anti-erythropoietin antibodies . CONCLUSIONS Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia . No unexpected AEs were seen .

epoetin zeta

epoetin alfa

epoetin zeta

epoetin alfa

epoetin zeta

epoetin alfa

epoetin

epoetin

epoetin zeta

epoetin alfa

epoetin zeta

epoetin alfa

Epoetin zeta

tolerability

adverse events ( AEs )

Mean ( range ) Hb levels

Mean ( range ) weekly doses

infections and infestations

renal anaemia

18-75 years old

CKD stage 5

313 patients

renal anaemia


Association of efavirenz hypersusceptibility with virologic response in ACTG 368 , a randomized trial of abacavir ( ABC ) in combination with efavirenz ( EFV ) and indinavir ( IDV ) in HIV-infected subjects with prior nucleoside analog experience . PURPOSE To evaluate the association of efavirenz hypersusceptibility ( EFV-HS ) with clinical outcome in a double-blind , placebo-controlled , randomized trial of EFV plus indinavir ( EFV+IDV ) vs. EFV+IDV plus abacavir ( ABC ) in 283 nucleoside-experienced HIV-infected patients . METHOD AND RESULTS Rates of virologic failure were similar in the 2 arms at week 16 ( p = .509 ) . Treatment discontinuations were more common in the ABC arm ( p = .001 ) . Using logistic regression , there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score . Using 3 different genotypic scoring systems , EFV-HS was significantly associated with reduced virologic failure at week 16 , independent of treatment assignment . In some patients on the nucleoside-sparing arm , the nucleoside-resistance mutation L74V was selected for in combination with the uncommonly occurring EFV-resistance mutations K103N+L100I ; L74V was not detected as a minority variant , using clonal sequence analysis , when the nucleoside-sparing regimen was initiated . CONCLUSION Premature treatment discontinuations in the ABC arm and the presence of EFV-HS HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV . In addition , L74V , when combined with K103N+L100I , may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance .

efavirenz

ACTG 368

abacavir ( ABC )

efavirenz ( EFV )

indinavir ( IDV

placebo-controlled

EFV-HS

EFV-HS HIV

EFV+IDV

Rates of virologic failure

Treatment discontinuations

virologic failure

either

baseline ABC resistance

or regimen sensitivity score

treatment discontinuations

adding ABC to EFV+IDV

effects on nucleoside resistance

HIV-infected

HIV-infected


[ Optimization of the postoperative period in children after adenotonsillectomy ] .

Optimization

adenotonsillectomy

[ Optimization

children

adenotonsillectomy


Osteosarcoma : the addition of muramyl tripeptide to chemotherapy improves overall survival -- a report from the Children 's Oncology Group . PURPOSE To compare three-drug chemotherapy with cisplatin , doxorubicin , and methotrexate with four-drug chemotherapy with cisplatin , doxorubicin , methotrexate , and ifosfamide for the treatment of osteosarcoma . To determine whether the addition of muramyl tripeptide ( MTP ) to chemotherapy enhances event-free survival ( EFS ) and overall survival in newly diagnosed patients with osteosarcoma . PATIENTS AND METHODS Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments . All patients received identical cumulative doses of cisplatin , doxorubicin , and methotrexate and underwent definitive surgical resection of primary tumor . Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design . The primary end points for analysis were EFS and overall survival . RESULTS In the current analysis , there was no evidence of interaction , and we were able to examine each intervention separately . The chemotherapy regimens resulted in similar EFS and overall survival . There was a trend toward better EFS with the addition of MTP ( P = .08 ) . The addition of MTP to chemotherapy improved 6-year overall survival from 70 % to 78 % ( P = .03 ) . The hazard ratio for overall survival with the addition of MTP was 0.71 ( 95 % CI , 0.52 to 0.96 ) . CONCLUSION The addition of ifosfamide to cisplatin , doxorubicin , and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma . The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS .

muramyl tripeptide

muramyl tripeptide ( MTP )

receive ifosfamide and/or MTP

overall survival -- a

EFS and overall survival

EFS and overall survival

EFS

6-year overall survival

hazard ratio for overall survival

EFS

overall survival

overall survival

EFS

Children 's

Six hundred sixty-two

osteosarcoma


Reduced albuminuria with sarpogrelate is accompanied by a decrease in monocyte chemoattractant protein-1 levels in type 2 diabetes . BACKGROUND AND OBJECTIVES Sarpogrelate has been shown to reduce albuminuria in diabetic nephropathy . For examination of whether this is based on the same mechanisms as angiotensin II receptor blockers or thiazolidinedione , effects of sarpogrelate on atherosclerotic inflammatory molecules and their relations to albuminuria in patients who had diabetes and had already been treated with angiotensin II receptor blockers and with or without thiazolidinedione were examined . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Forty patients who had diabetes with nephropathy and arteriosclerosis obliterans and had already been treated with angiotensin II receptor blocker ( n = 40 ) were randomly assigned to sarpogrelate ( 300 mg/d ; n = 20 ) or aspirin group ( 100 mg/d ; n = 20 ) . Plasma monocyte chemoattractant protein-1 and urinary albumin-to-creatinine ratio and monocyte chemoattractant protein-1 were measured at baseline and 16 wk after administration . RESULTS Only the sarpogrelate group showed increases in plasma adiponectin and decreases in both plasma and urinary monocyte chemoattractant protein-1 and albumin-to-creatinine ratio levels . Moreover , percentage change of monocyte chemoattractant protein-1 level correlated positively to that of albumin-to-creatinine ratio . Even when the sarpogrelate group was further divided into two groups with ( n = 9 ) or without thiazolidinedione ( n = 11 ) , changes in monocyte chemoattractant protein-1 or albumin-to-creatinine ratio did not differ . CONCLUSIONS Sarpogrelate can reduce albuminuria and plasma and urinary monocyte chemoattractant protein-1 levels while increasing plasma adiponectin in diabetic nephropathy . These effects seem to be mediated via mechanisms that are different from those of angiotensin II receptor blocker or thiazolidinedione .

sarpogrelate

Sarpogrelate

thiazolidinedione

sarpogrelate

angiotensin II receptor blockers

thiazolidinedione

angiotensin II receptor blocker

sarpogrelate

aspirin group

sarpogrelate

sarpogrelate

thiazolidinedione

Sarpogrelate

angiotensin II receptor blocker

thiazolidinedione

plasma adiponectin

type 2 diabetes

diabetes

Forty

diabetes


Effect of a nutrition intervention during early childhood on economic productivity in Guatemalan adults . BACKGROUND Substantial , but indirect , evidence suggests that improving nutrition in early childhood in developing countries is a long-term economic investment . We investigated the direct effect of a nutrition intervention in early childhood on adult economic productivity . METHODS We obtained economic data from 1424 Guatemalan individuals ( aged 25-42 years ) between 2002 and 2004 . They accounted for 60 % of the 2392 children ( aged 0-7 years ) who had been enrolled in a nutrition intervention study during 1969-77 . In this initial study , two villages were randomly assigned a nutritious supplement ( atole ) for all children and two villages a less nutritious one ( fresco ) . We estimated annual income , hours worked , and average hourly wages from all economic activities . We used linear regression models , adjusting for potentially confounding factors , to assess the relation between economic variables and exposure to atole or fresco at specific ages between birth and 7 years . FINDINGS Exposure to atole before , but not after , age 3 years was associated with higher hourly wages , but only for men . For exposure to atole from 0 to 2 years , the increase was US $ 0.67 per hour ( 95 % CI 0.16-1.17 ) , which meant a 46 % increase in average wages . There was a non-significant tendency for hours worked to be reduced and for annual incomes to be greater for those exposed to atole from 0 to 2 years . INTERPRETATION Improving nutrition in early childhood led to substantial increases in wage rates for men , which suggests that investments in early childhood nutrition can be long-term drivers of economic growth .

nutrition intervention

nutrition intervention

nutrition intervention

atole

fresco

atole

atole

economic productivity

hourly wages

tendency for hours worked

annual incomes

substantial increases in wage rates

Guatemalan adults .


A field trial of production and financial consequences of helminthosis control in sheep production in Ethiopia . We used a partial-budget analysis to evaluate profitability of different management strategies of three genotypes of sheep in a 2 x 2 x 3 factorial experiment conducted at Debre Berhan research station in the central highlands of Ethiopia . This involved two anthelmintic-treatment levels ( treated vs. non-treated ) , two supplementary nutrition levels ( protein-energy supplementation yes/no ) and three genotypes : indigenous Menz ( n=40 ) , 50 % Awassi x 50 % Menz crosses ( n=38 ) and 75 % Awassi x 25 % Menz crosses ( n=31 ) . All sheep were exposed to natural sub-clinical helminthosis challenge . Supplemented sheep were offered a concentrate mix daily on an individual basis . Anthelmintic-treated sheep were drenched with fenbendazole against nematodes and with triclabendazole against trematodes . Data were collected during the experimental period ( for 10 months from approximately 1 year of age ) on feed intake , live weight , eggs per gram ( EPG ) of faeces , packed-cell volume ( PCV ) , wool weight , and adult-worm burden . Actual market input and output prices were recorded . Supplemented sheep had significantly higher marginal profit ( MP ) per sheep than non-supplemented sheep ( ETB 33 vs. 4 ) . Likewise , anthelmintic treated sheep performed significantly better than their non-treated contemporaries ( MP=ETB 28 vs. 8 ) . The 75 % Awassi crosses were least profitable .

concentrate mix daily

profitability

feed intake

live weight

eggs per gram ( EPG ) of faeces

packed-cell volume ( PCV )

wool weight

adult-worm burden

market input and output prices

marginal profit ( MP )

performed

profitable

sheep production in Ethiopia .

central highlands of Ethiopia


Cryotherapy does not affect peroneal reaction following sudden inversion . CONTEXT If ankle joint cryotherapy impairs the ability of the ankle musculature to counteract potentially injurious forces , the ankle is left vulnerable to injury . OBJECTIVE To compare peroneal reaction to sudden inversion following ankle joint cryotherapy . DESIGN Repeated measures design with independent variables , treatment ( cryotherapy and control ) , and time ( baseline , immediately post treatment , 15 minutes post treatment , and 30 minutes post treatment ) . SETTING University research laboratory . PATIENTS OR OTHER PARTICIPANTS Twenty-seven healthy volunteers . INTERVENTION ( S ) An ice bag was secured to the lateral ankle joint for 20 minutes . MAIN OUTCOME MEASURES The onset and average root mean square amplitude of EMG activity in the peroneal muscles was calculated following the release of a trap door mechanism causing inversion . RESULTS There was no statistically significant change from baseline for peroneal reaction time or average peroneal muscle activity at any post treatment time . CONCLUSIONS Cryotherapy does not affect peroneal muscle reaction following sudden inversion perturbation .

cryotherapy

control

Twenty-seven

healthy


The impact of fasting and treatment omission on susceptibility to hypoglycaemia in children and adolescents with GH and cortisol insufficiency . OBJECTIVE Hypoglycaemia may be a frequent occurrence in young GH deficient patients and so we studied the response to fasting in children and adolescents with GH and/or cortisol deficiency . METHODS A total of 20 patients ( 2-18 years ) fasted for 14 h ( 22.00-12.00 h ) on two occasions as part of a randomized cross-over study . Fourteen had pituitary hormone deficiency ( PHD ) including GH deficiency ( GHD ) . Of the 14 patients , seven were ACTH sufficient ( PHDC+ ) and seven ACTH deficient ( PHDC- ) . Six had primary adrenal failure ( PAF ) . Subjects administered or omitted their normal dose of evening GH and/or morning hydrocortisone . Glucose , insulin , GH , cortisol , ketones and catecholamines were measured at 04.00 h and regularly from 07.00 to 12.00 h. Insulin sensitivity was assessed by HOMA and hypoglycaemia defined as a blood glucose ( BG ) < /= 3.3 mmol/l . RESULTS BG was related to age and body mass index on treatment but no subject became hypoglycaemic on or off therapy prior to 07.00 h. Five children ( aged 3 , 4 , 7 , 8 and 11 years ) were hypoglycaemic between 07.00 and 12.00 h off treatment . There was a positive relationship between GH AUC and minimum BG in patients with PHD on treatment ( r ( 2 ) = 0.45 , P = 0.012 ) with increased insulin sensitivity off treatment . Increased cortisol levels were seen in PHDC+ patients off GH ( P < 0.001 ) . A negative relationship was observed between minimum BG and adrenaline ( r ( 2 ) = 0.37 , P = 0.01 ) , ketone bodies ( r ( 2 ) = -0.20 , P = 0.05 ) and NEFA ( r ( 2 ) = -0.35 , P = 0.02 ) . Noradrenaline levels were reduced in patients with PHDC- . Low BMI ( on treatment ) and young age ( off treatment ) were determinants of low BG levels in a multiple regression model . CONCLUSIONS Unrecognized overnight hypoglycaemia in children and adolescents on pituitary hormone replacement is uncommon but BG levels quickly become abnormal when treatment and meals are omitted . The insulin antagonistic actions of GH are important in preventing hypoglycaemia . Patients with PHD have altered sympathetic nerve activity .

fasting

treatment omission

fasted

evening GH

morning hydrocortisone

susceptibility to hypoglycaemia

Glucose

insulin

GH

cortisol

ketones

catecholamines

Insulin sensitivity

HOMA

hypoglycaemia

blood glucose

age and body mass index

hypoglycaemic

GH AUC

minimum BG

insulin sensitivity

Increased cortisol levels

BG

adrenaline

ketone bodies

Noradrenaline levels

BMI

low BG levels

BG levels

insulin antagonistic actions of GH

sympathetic nerve activity

children

adolescents

GH and cortisol insufficiency

young

GH deficient

children

adolescents

GH and/or cortisol deficiency

20 patients

( 2-18 years

Fourteen

pituitary hormone deficiency ( PHD )

GH deficiency ( GHD )

seven

seven

ACTH deficient ( PHDC- )

Six

primary adrenal failure ( PAF )

PHDC-

children

adolescents

PHD


Evaluation of the effects of human leukocyte IFN-alpha on the immune response to the HBV vaccine in healthy unvaccinated individuals . HBV vaccine needs 3 injections over 6 months to induce immunity . Thus , the use of adjuvants capable of inducing earlier immune protection would be highly desirable . Most adjuvants may act by inducing cytokines , and among them , type I interferons ( IFNs ) , deserve a special attention in view of the potent immunomostimulatory activity observed in mouse models and on dendritic cell functions . The aim of the present trial was to evaluate the effects of IFN-alpha administered as an adjuvant of HBV vaccine in healthy unvaccinated individuals . No significant enhancing effect on the antibody response was observed , in spite of an early and transient upregulation of costimulatory molecule expression on peripheral blood mononuclear cells , which may be suggestive of an IFN-mediated activation of antigen presenting cells . We conclude that , under the conditions used in this trial , natural IFN-alpha does not act as an adjuvant of the HBV vaccine in healthy unvaccinated individuals .

leukocyte IFN-alpha

HBV vaccine

HBV vaccine

IFN-alpha

adjuvant of HBV vaccine

IFN-alpha

immune response to the HBV vaccine

antibody response

peripheral blood mononuclear cells

healthy unvaccinated individuals .


Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma . BACKGROUND/AIMS Vitamin K2 ( VK2 ) appears to have a potent inhibitory activity for cell growth including HCC cells . We investigated whether VK2 could reduce incidence of tumor recurrence after treatment of HCC . Forty-five patients with cured or possibly cured HCC were randomly selected , assigning patients to treatment ( n=21 ) or control group ( n=24 ) with randomization list . METHODOLOGY For the treatment group , forty-five mg of Glakay was given orally every day after therapy for HCC . No patients complained of adverse effects . Abdominal ultrasonography and dynamic CT were performed at 3-month intervals . Recurrence was confirmed by abdominal angiography . RESULTS Recurrence of HCC occurred in 7 cases ( 33.3 % ) for the treatment group and 12 cases ( 50.0 % ) for the control group during mean observation periods of 19.5 and 16.5 months , respectively . Administration of VK2 was not an independent variable for the recurrence on univariate analysis . Cumulative incidence of HCC recurrence did not differ between the two groups , and the cumulative survival rate tended to be high in treatment group ( p =0.054 ) . Cox regression analysis revealed that serum albumin concentration alone was an independent factor affecting the recurrence . CONCLUSIONS These findings suggest that VK2 does not appear to prevent recurrence of HCC after curative treatment . Our study is preliminary and large-scale trials are needed to determine whether VK2 is of benefit to decrease the recurrence of HCC .

vitamin K2

Vitamin K2 ( VK2 )

control

Glakay

dynamic CT

abdominal angiography

recurrence

adverse effects

Recurrence

Recurrence of HCC

recurrence

Cumulative incidence of HCC recurrence

cumulative survival rate

serum albumin concentration

recurrence of HCC

recurrence of HCC

hepatocellular carcinoma

Forty-five patients

HCC


Effects of losartan and enalapril on high-sensitivity C-reactive protein and total antioxidant in renal transplant recipients with Renin-Angiotensin system polymorphisms . BACKGROUND As renin-angiotensin system ( RAS ) activity may affect the severity of oxidative stress and inflammatory markers , we assessed the effects of enalapril ( E ) and/or losartan ( L ) on these markers in renal transplant recipients with RAS polymorphisms . PATIENTS AND METHODS After determination by PCR of RAS genotypes , consisting of the angiotensin-converting enzymes ( ACE I/D ) , angiotensinogens ( AGT M235T ) and angiotensin II type 1 receptors ( ATR1 A1166C ) , 76 recipients were recruited randomly and assigned 4 groups . The first ( n = 17 ) and second ( n = 24 ) groups were treated with E ( E ( + ) : 10 mg/d ) and L ( L ( + ) : 50 mg/d ) alone , respectively . The third positive control group ( n = 17 ) received E + L ( E ( + ) L ( + ) : 10 mg/d + 50 mg/d ) and the fourth negative control group ( n = 18 ) received no medication ( E ( - ) : L ( - ) ) . High-sensitivity C-reactive protein ( hs-CRP ) and total antioxidant ( TA ) inflammatory and antioxidative markers were measured after 2 months . After a 2-week washout period , the E ( + ) group was changed to L ( + ) and vice versa in a crossover design . They were followed for another 8 weeks before retesting hs-CRP and TA . A value of P < or = .05 was considered significant . RESULTS After 2 and 4 months of treatment with the drug regimen , hs-CRP and TA levels were significantly decreased and consequently increased among the E ( + ) L ( + ) , L ( + ) and E ( + ) groups ( P < .05 ) . On analyzing the relationship between RAS polymorphisms and baseline hs-CRP or TA levels , CC genotype of ATR1 showed lower hs-CRP levels ( P = .04 ) . However , none of the RAS polymorphisms predicted the antioxidant and anti-inflammatory response rates to the drugs ( P > .05 ) . CONCLUSION Although hs-CRP was lower in the CC genotype patients of ATR1 polymorphisms E and/or L reduced hs-CRP and increased TA regardless of the RAS genotype .

losartan and enalapril

enalapril ( E ) and/or losartan

E

L

E + L

E ( + ) L ( + ) , L ( + )

E ( + )

hs-CRP

TA levels

hs-CRP levels

hs-CRP

renal transplant

Renin-Angiotensin system polymorphisms

renal transplant

RAS polymorphisms .


The effects of candesartan on diabetes glomerulopathy : a double-blind , placebo-controlled trial . Our objective was to study the effects of candesartan on diabetic glomerulopathy in young normoalbuminuric and normotensive patients with type 1 diabetes in a double-blind , placebo-controlled trial . In 13 patients aged 24 years at baseline , we evaluated blood pressure , kidney biopsies and kidney function tests at baseline and after 5 years of treatment . Kidney biopsies were examined with light and electron microscopy , glomerular filtration rate and effective renal plasma flow determined with inulin and para-aminohippuric acid clearances . Two patients in the placebo group needed antihypertensive treatment because they developed microalbuminuria and/or hypertension , but no patient in the candesartan group did . A significant reduction in mesangial matrix volume and mesangial volume occurred in the candesartan group , although changes in morphological parameters were similar between groups . Office blood pressure was significantly lower in the candesartan group at follow-up than in the placebo group . Deterioration in morphological parameters observed in earlier studies of our patients did not become worse during treatment with candesartan or placebo . The effects of candesartan , with reduction in morphological parameters and lowering of blood pressure , might influence future treatment of glomerulopathy in type 1 diabetes patients .

candesartan

placebo-controlled

candesartan

placebo-controlled

placebo

candesartan

candesartan

placebo

candesartan

placebo

candesartan

diabetes glomerulopathy :

diabetic glomerulopathy

microalbuminuria and/or hypertension

morphological parameters

Office blood pressure

morphological parameters

morphological parameters

lowering of blood pressure


[ Effects of early acupuncture on motor function of the limb in the severe head injury patients ] . UNLABELLED OBJECTIVE ; To observe the effects of early acupuncture on motor function of the limb in the severe head injury patients . METHODS Ninety-six patients were randomly divided into an observation group and a control group , 48 cases in each group . The patient in the control group were treated by routine treatment of neurosurgical operation and drug treatment ( Mannitol , Citioline Sodium , Cefeazidime , etc. ) . While the patient in the observation group were treated by the routine treatment and acupuncture treatment 48 h ( -1 ) week after operation in different stages with different acupoints selected when the situation was stable . The selected main points were Neiguan ( PC 6 ) , Qu-chi ( LI 11 ) , Waiguan ( TE 5 ) , Hegu ( LI 4 ) , Binao ( LI 14 ) , Jianyu ( LI 15 ) , Fengshi ( GB 31 ) , Xuehai ( SP 10 ) , Yinlingquan ( SP 9 ) , Sanyinjiao ( SP 6 ) , Taichong ( LR 3 ) , etc.. The limb motor function was evaluated with Fugl-Meyer Assessment ( FMA ) scale before treatment and after 10-week treatment . RESULTS There was a significant improvement in the FMA score in the two groups after the treatment ( P < 0.01 ) . The comparison between the two groups after the treatment showed that the improvement of FMA score in the observation group was significantly better than the control group ( P < 0.05 or P < 0.01 ) . CONCLUSION Early acupuncture can improve the limb motor function in the severe head injury patients .

acupuncture

early acupuncture

Mannitol

Citioline Sodium

Cefeazidime , etc.

routine treatment

acupuncture treatment

acupuncture

limb motor function

Fugl-Meyer Assessment ( FMA ) scale

FMA score

improvement of FMA score

head injury

Ninety-six


Controversies in the management of Hodgkin 's disease .

management

Hodgkin 's disease .


Prospective randomized controlled trial to evaluate " fast-track " elective open infrarenal aneurysm repair . BACKGROUND AND AIMS Fast-track programs have been introduced in many surgical fields to minimize postoperative morbidity and mortality . Morbidity after elective open infrarenal aneurysm repair is as high as 30 % ; mortality ranges up to 10 % . In terms of open infrarenal aneurysm repair , no randomized controlled trials exist to introduce and evaluate such patient care programs . MATERIALS AND METHODS This study involved prospective randomization of 82 patients in a " traditional " and a " fast-track " treatment arm . Main differences consisted in preoperative bowel washout ( none vs. 3 l cleaning solution ) and analgesia ( patient controlled analgesia vs. patient controlled epidural analgesia ) . Study endpoints were morbidity and mortality , need for postoperative mechanical ventilation , and length of stay ( LOS ) on intensive care unit ( ICU ) . RESULTS The need for assisted postoperative ventilation was significantly higher in the traditional group ( 33.3 % vs. 5.4 % ; p = 0.011 ) . Median LOS on ICU was shorter in the fast-track group , 41 vs. 20 h. The rate of postoperative medical complications was significantly lower in the fast-track group , 16.2 % vs. 35.7 % ( p = 0.045 ) . CONCLUSION We introduced and evaluated an optimized patient care program for patients undergoing open infrarenal aortic aneurysm repair which showed a significant advantage for " fast-track " patients in terms of postoperative morbidity .

fast-track

preoperative bowel washout

patient care program

postoperative morbidity

mortality

Morbidity

mortality

morbidity

mortality

assisted postoperative ventilation

Median LOS on ICU

postoperative morbidity


Chronology of panic and avoidance , age of onset in panic disorder , and prediction of treatment response . A report from the Cross-National Collaborative Panic Study . The relevance of the chronology between panic disorder and avoidance behavior and of an early , medium or late onset of panic disorder was tested . Groups from the sample of the cross-national collaborative panic study ( CNCPS ) were compared for differences in basic characteristics and for the ability to predict treatment response . Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment . Patients with an early onset of panic disorder suffered more often from agoraphobia . The treatment response was similar in the groups with early , medium or late onset of panic disorder . Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or imipramine .

treatment

treatment

short-term treatment with alprazolam

imipramine

avoidance behavior

panic disorder

agoraphobia

early onset of panic disorder

agoraphobia

treatment response

similar

panic disorder and avoidance behavior

age of onset of panic disorder

panic disorder

full syndrome

panic disorder


Microtensile bond strength of a repair composite to leucite-reinforced feldspathic ceramic . The purpose of this study was to evaluate the microtensile bond strength of a repair composite resin to a leucite-reinforced feldspathic ceramic ( Omega 900 , VITA ) submitted to two surface conditionings methods : 1 ) etching with hydrofluoric acid + silane application or 2 ) tribochemical silica coating . The null hypothesis is that both surface treatments can generate similar bond strengths . Ten ceramic blocks ( 6x6x6 mm ) were fabricated and randomly assigned to 2 groups ( n=5 ) , according to the conditioning method : G1- 10 % hydrofluoric acid application for 2 min plus rinsing and drying , followed by silane application for 30 s ; G2- airborne particle abrasion with 30 microm silica oxide particles ( CoJet-Sand ) for 20 s using a chairside air-abrasion device ( CoJet System ) , followed by silane application for 5 min . Single Bond adhesive system was applied to the surfaces and light cured ( 40 s ) . Z-250 composite resin was placed incrementally on the treated ceramic surface to build a 6x6x6 mm block . Bar specimens with an adhesive area of approximately 1 +/- 0.1 mm ( 2 ) were obtained from the composite-ceramic blocks ( 6 per block and 30 per group ) for microtensile testing . No statistically significant difference was observed between G1 ( 10.19 +/- 3.1 MPa ) and G2 ( 10.17 +/- 3.1 MPa ) ( p=0.982 ) ( Student 's t test ; á = 0.05 ) . The null hypothesis was , therefore , accepted . In conclusion , both surface conditioning methods provided similar microtensile bond strengths between the repair composite resin and the ceramic . Further studies using long-term aging procedures should be conducted .

tribochemical silica coating

hydrofluoric acid

silane

bond strengths

microtensile testing


[ How to treat the relapse of NSCLC after surgery and chemotherapy ? IFTC 0702 randomized phase III study ] . BACKGROUND As chemotherapy gains wider acceptance for the treatment of earlier stages of NSCLC , particularly in the adjuvant and neoadjuvant setting , physicians face a growing population of high performance status patients who have relapsed after their first-line chemotherapy . The type of second-line chemotherapy after initial adjuvant or neoadjuvant treatment with a platinum-based regimen remains largely undefined . The current study has been designed to compare the classical mono chemotherapy docetaxel with a docetaxel cisplatin doublet . METHODS Patients will be randomized in 2 arms . Arm : docetaxel cisplatin ( cycles repeated every 21 days ) , 4 cycles followed by 2 cycles of docetaxel alone in case of objective response or stabilisation . Arm B : docetaxel alone ( cycles repeated every 21 days ) , 4 cycles followed by 2 cycles of docetaxel alone in case of objective response or stabilisation . EXPECTED RESULTS 300 patients will be randomized with a statistical hypothesis of a progression free survival of 3 months in the control arm and of 4.5 months in the experimental arm .

second-line chemotherapy

platinum-based regimen

mono chemotherapy docetaxel

docetaxel cisplatin doublet

docetaxel cisplatin

docetaxel alone

relapse of NSCLC

progression free survival


Effect of erythromycin and gentamicin on abomasal emptying rate in suckling calves . BACKGROUND Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying . HYPOTHESIS Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying . ANIMALS Five male Holstein-Friesian calves ( 8-15 days of age ) . METHODS Calves received each of the following 4 IM treatments in random order : control , 2 mL of 0.9 % NaCl ; erythromycin , 8.8 mg/kg ; low-dose gentamicin , 4.4 mg/kg ; high-dose gentamicin , 6.6 mg/kg . Abomasal emptying rate was assessed by acetaminophen and glucose absorption . Calves were fed 2 L of cow 's milk containing acetaminophen ( 50 mg/kg body weight ) 30 minutes after each treatment was administered , and jugular venous blood samples were obtained periodically after suckling . The maximum observed plasma acetaminophen concentration ( actual C ( max ) ) and time of actual C ( max ) ( actual T ( max ) ) were determined , and pharmacokinetic modeling was used to calculate model C ( max ) and model T ( max ) . RESULTS Erythromycin increased abomasal emptying rate , as indicated by a shorter time to actual T ( max ) and model T ( max ) ( P < .05 ) . Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control . Administration of high-dose gentamicin resulted in a longer time to actual T ( max ) ( P= .021 ) but did not change model T ( max ) ( P= .62 ) . CONCLUSIONS AND CLINICAL RELEVANCE IM injection of erythromycin increased abomasal emptying rate in dairy calves , whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption . The clinical relevance of these findings remains to be determined .

erythromycin

gentamicin

erythromycin

control

erythromycin

low-dose gentamicin

high-dose gentamicin

acetaminophen

abomasal emptying rate

gastric emptying

abomasal emptying

Abomasal emptying

acetaminophen and glucose absorption

plasma acetaminophen concentration

abomasal emptying rate

Abomasal emptying rate

time to actual T ( max )

model T ( max )

abomasal emptying rate

rate of abomasal emptying


[ 4 years ' experience with a balloon-expandable endoprosthesis . Experimental and clinical application ] . During a 4-year period of clinical application of the balloon-expandable Palmaz stent , a randomized trial comparing stent implantation and traditional balloon angioplasty of iliac arteries in arterial occlusive disease was started . The first long-term results , recorded after 2 years , indicate statistically significant differences in the complication rate ( after stenting 2/62 and after angioplasty 5/69 ) and patency ( greater than or equal to 70 % of original lumen size upon stent implantation or balloon inflation : 95 % after stenting and 72 % after angioplasty ) . Clinical improvement after 2 years was 89 % after stenting and 70 % after angioplasty . Parallel to the clinical trials , experimental canine artery stenting was performed to evaluate differences in the long-term patency of stents exposed to restricted flow . Significant differences in neointimal healing were found between normally perfused stents and stents with artificially reduced flow : during the total observation period of 6 months the neointimal height was up to 200 % higher in flow-restricted stents , while the histological composition of the neointima was the same as with normally perfused stents .

balloon-expandable endoprosthesis .

balloon-expandable Palmaz stent

complication rate

patency

Clinical improvement

neointimal healing

neointimal height

stenting 2/62

angioplasty 5/69 )

clinical trials


Effect of food on the antiviral activity of didanosine enteric-coated capsules : a pilot comparative study . OBJECTIVES To determine the effect of food on the antiviral activity of enteric-coated ( EC ) capsules of didanosine ( ddI ) . METHODS We conducted a pilot , randomized , open-label study of 28-day ddI-EC capsules monotherapy-administered in a fasted state ( group 1 , n=11 ) or with food ( group 2 , n=10 ) to treatment-naïve chronically HIV-1-infected individuals . To assess the antiviral efficacy , HIV-1 RNA was determined at baseline , day 3 , day 7 and weekly thereafter . The area under the HIV-1 RNA curve minus baseline weighted by time ( AUCMB/day ) was calculated . RESULTS Mean baseline HIV-1 RNA was 4.2 log ( 10 ) copies/mL in group 1 and 3.8 log ( 10 ) copies/mL in group 2 . After 28 days , the mean HIV-1 RNA reduction was 0.99 log ( 10 ) copies/mL [ 95 % confidence interval ( CI ) 0.45-1.53 ] for group 1 and 0.89 log ( 10 ) copies/mL ( 95 % CI 0.38-1.40 ) for group 2 . AUCMB/day values were 0.775 log ( 10 ) copies/mL ( 95 % CI 0.33-1.22 ) and 0.774 log ( 10 ) copies/mL ( 95 % CI 0.48-1.07 ) , respectively , showing no difference in the rate of decrease of HIV-1 RNA ( P=0.995 ) . Mean ddI plasma levels at day 28 were 0.0234 mg/L for group 1 and 0.0227 mg/L for group 2 ( P=0.96 ) . CONCLUSIONS In this pilot study , the administration of food did not have any significant effect on the antiviral activity of ddI-EC capsules .

food

didanosine enteric-coated capsules

food

fasted state

with food

antiviral activity


Safety and tolerability of cold-adapted influenza vaccine , trivalent , in infants younger than 6 months of age . OBJECTIVE Young children are at high risk for influenza-related complications . Vaccination of close household contacts is recommended to provide indirect protection to children < 6 months of age . Studies have shown that live , cold-adapted influenza vaccine , trivalent , is efficacious in children . To assess the risks associated with inadvertent exposure of infants to vaccine viruses from vaccinated contacts , this study was designed to evaluate the safety and tolerability of cold-adapted influenza vaccine , trivalent , administered intranasally to healthy children 6 to < 24 weeks of age . METHODS Healthy infants aged 6 to < 16 weeks and 16 to < 24 weeks , respectively , were randomly assigned to receive 2 doses of influenza vaccine , or placebo intranasally 35 +/- 7 days apart . Reactogenicity events were monitored for 11 days after each dose . Other adverse events were monitored through 28 to 35 days after dose 2 . RESULTS Of the infants aged 6 to < 16 weeks , 31 received influenza vaccine and 28 received placebo , and of those aged 16 to < 24 weeks , 30 received influenza vaccine and 31 received placebo . In the 6- to < 16-week cohort , more influenza vaccine , recipients experienced irritability ( 66.7 % vs 35.7 % ) and runny nose or nasal congestion ( 63.3 % vs 33.3 % ) after dose 1 but not dose 2 . There were no significant increases in any other reactogenicity events or adverse events in the vaccine recipients compared with the placebo group . CONCLUSIONS Although there was an increase in mild reactogenicity events in children 6 to < 16 weeks of age , cold-adapted influenza vaccine , trivalent , was generally well tolerated in infants 6 to < 24 weeks of age . These findings support further evaluation of cold-adapted influenza vaccine , trivalent , in infants < 6 months of age .

influenza vaccine , trivalent

influenza vaccine

influenza vaccine

2 doses of influenza vaccine

placebo

influenza vaccine

placebo

influenza vaccine

placebo .

placebo

influenza vaccine

influenza vaccine

Safety and tolerability

safety and tolerability

irritability

runny nose or nasal congestion

reactogenicity events or adverse events

mild reactogenicity events

infants younger than 6 months of age

Young children

children < 6 months of age

healthy

children 6 to < 24 weeks of age

Healthy

6 to < 16 weeks

16 to < 24 weeks

6 to < 16 weeks

6 to < 24 weeks

6 months


Prognosis of advanced hepatocellular carcinoma : comparison of three staging systems in two French clinical trials . OBJECTIVE The objective of this study was to assess the performance of three staging systems [ Okuda , Cancer of the Liver Italian Program ( CLIP ) and Barcelona Clinic Liver Cancer group ( BCLC ) ] , for predicting survival in patients with hepatocellular carcinoma ( HCC ) and to explore how to improve prognostic classification among French patients with HCC whose main etiology is alcoholic cirrhosis . METHODS We have pooled two randomized clinical trials in palliative condition from the Fédération Francophone de Cancerologie Digestive . They had included 416 and 122 patients . Performances of Okuda , CLIP and BCLC scores have been compared using Akaike information criterion , discriminatory ability ( Harrell 's C and the Royston 's D statistics ) , monotonicity of gradients and predictive accuracy ( Schemper statistics Vs ) . To explore how to improve classifications , univariate and multivariate Cox model analyses were carried out . RESULTS The pooled database included 538 patients . The median survival was 5.3 months ( 95 % confidence interval 4.6-6.2 ) . For all statistics CLIP staging system had a better prognostic ability . Performances of all staging systems were rather disappointing . World Health Organization performance status ( WHO PS ) for CLIP or alpha-fetoprotein for BCLC allowed a significant improvement of prognostic information . CONCLUSION Our results indicate that CLIP staging seems to be most adapted to palliative setting and that it could be better by associating WHO PS .

survival

advanced hepatocellular carcinoma :

416 and 122 patients

included 538 patients


Closure of the femoral artery after cardiac catheterization : a comparison of Angio-Seal , StarClose , and manual compression . OBJECTIVES To compare Angio-Seal ( AS ) and StarClose ( SC ) and manual compression ( MC ) on efficacy of hemostasis , complication rate , safety of early mobilization , and patient comfort . BACKGROUND Closure of the femoral artery after cardiac catheterization can be obtained through different methods . Today , physicians can choose from a number of different devices to achieve arterial closure . METHODS In a prospective trial 450 patients were randomized to AS , SC , or MC . Patients were mobilized 1 to 2 hr after device placement , and 6 hr after MC . Data were collected during hospital admission and by telephone at one month after hospital discharge . RESULTS Devices were used in 138/150 allocated to AS and 124/150 allocated to SC patients ( 92 % vs. 83 % , P = 0.015 ) Patients with MC experienced more pain during sheath removal than patients receiving a device , and rated their period of bed rest as less comfortable . Oozing and need for pressure bandage at the puncture site were observed in 37 AS patients and 57 SC patients ( 25 % vs. 38 % , P = 0.002 ) . Hematoma occurred in 15 AS patients , in 17 SC patients , and in 14 MC patients ( 11 vs. 14 vs. 9 % , ns ) . CONCLUSION There is no difference in safety between the three methods of arterial closure . SC was more often not used or successfully deployed . SC patients more often had continuing oozing . On patient comfort , closure devices performed better than MC . Early ambulation in patients with a closure device is safe . AS is the preferred method of arterial closure after cardiac catheterization .

Angio-Seal ( AS )

StarClose ( SC )

manual compression ( MC )

AS

SC

MC

MC

efficacy of hemostasis

complication rate

safety of early mobilization

patient comfort

pain during sheath removal

period of bed rest

Hematoma

safety

oozing

patient comfort