Asthma and the home environment of low-income urban children : preliminary findings from the Seattle-King County healthy homes project . OBJECTIVES Childhood asthma is a growing public health concern in low-income urban communities . Indoor exposure to asthma triggers has emerged as an important cause of asthma exacerbations . We describe indoor environmental conditions related to asthma triggers among a low-income urban population in Seattle/King County , Washington , as well as caregiver knowledge and resources related to control of these triggers . METHODS Data are obtained from in-person , structured , closed-end interviews with the caretakers of children aged 4-12 years with persistent asthma living in households with incomes less than 200 % of poverty . Additional information is collected during a home inspection . The children and their caregivers are participants in the ongoing Seattle-King County Healthy Homes Project , a randomized controlled trial of an intervention to empower low-income families to reduce exposure to indoor asthma triggers . We report findings on the conditions of the homes prior to this intervention among the first 112 enrolled households . RESULTS A smoker was present in 37.5 % of homes . Mold was visible in 26.8 % of homes , water damage was present in 18.6 % of homes , and damp conditions occurred in 64.8 % of households , while 39.6 % of caregivers were aware that excessive moisture can increase exposures to allergens . Dust-trapping reservoirs were common ; 76.8 % of children 's bedrooms had carpeting . Cockroach infestation in the past 3 months was reported by 23.4 % of caregivers , while 57.1 % were unaware of the association of roaches and asthma . Only 19.8 % of the children had allergy-control mattress covers . CONCLUSIONS Many low-income urban children with asthma in King County live in indoor environments that place them at substantial risk of ongoing exposure to asthma triggers . Substandard housing and lack of resources often underlie these exposures . Initiatives involving health educators , outreach workers , medical providers , health care insurers , housing agencies , and elected officials are needed to reduce these exposures .

intervention

Mold was visible

water damage

damp conditions

Dust-trapping reservoirs

association of roaches and asthma

allergy-control mattress covers .

children

children

asthma

children

asthma

children

asthma


Impact of an encounter-based prompting system on resident vaccine administration performance and immunization knowledge . OBJECTIVES To evaluate an encounter-based immunization prompting system on resident performance in administering vaccines and knowledge of immunization guidelines . DESIGN/METHODS Prospective randomized , controlled trial . Subjects were first- and second-year pediatric residents in a hospital-based continuity clinic . The intervention group received manual prompts of immunizations due . Postclinic chart review compared immunizations due with those administered . Acceptable and unacceptable reasons for not administering vaccines were assigned . Resident knowledge was measured by a 70-item examination . RESULTS The intervention group had significantly less missed opportunities/vaccine administration errors ( 11.4 % vs 21.6 % ) . The most common reason for unacceptable errors in the intervention group : vaccine was given too early ; in the control group : vaccine was postponed to next visit . Pre- and postintervention knowledge scores were similar : intervention group ( 75.5 % vs 80.7 % , control group ; 76.5 % vs 81.3 % ) . CONCLUSION An immunization prompting system in a hospital-based pediatric resident continuity clinic reduced missed opportunities/vaccine administration errors without significantly impacting resident knowledge of immunization guidelines.immunization schedule , vaccination , immunization , prompting systems , resident education .

encounter-based prompting system

manual prompts of immunizations due

Resident knowledge

postintervention knowledge scores


The GH response to low-dose bolus growth hormone-releasing hormone ( GHRH ( 1-29 ) NH2 ) is attenuated in patients with longstanding post-irradiation GH insufficiency . OBJECTIVE Previous studies have suggested that post-irradiation GH insufficiency results from a loss of GHRH secretion , since many patients were able to release GH following exogenous GHRH stimulation . However , supramaximal doses of GHRH were used and the response may decline with time after radiotherapy . We re-evaluated the GHRH dose-response curve in patients post cranial irradiation and in controls . DESIGN Randomized controlled study . METHODS Five adult male long-term survivors of childhood brain tumours ( median age 21.8 years ( 18.4-26.7 ) ; 13.7 years ( 11.4-15.7 ) post-radiotherapy , > 30Gy ) and five matched controls were studied . An intravenous bolus of GHRH ( 1-29 ) NH ( 2 ) was administered in doses at the lower ( 0.05 microg/kg ) and upper ( 0.15 microg/kg ) range of the dose-response curves for young males , as well as the standard supramaximal dose ( 1 . 0 microg/kg ) . GH was measured before stimulation , every 2min for the first hour and every 5min for the second hour . All studies were conducted in a random fashion . RESULTS Significantly lower peak and area under the curve ( AUC ) GH concentrations occurred in the irradiated group using 0.15 microg/kg ( median peak Irradiated , 4 . 5mU/l vs median Controls , 37.4mU/l ; P < 0.01 ) and 1.0 microg/kg ( median peak Irradiated , 4.8mU/l vs median Controls , 15.2mU/l ; P < 0 . 05 ) GHRH ( 1-29 ) NH ( 2 ) . In irradiated subjects there was an incremental rise in GH output with increasing doses of GHRH ( 1-29 ) NH ( 2 ) ( median AUC : 122mU/l.min vs 179mU/l.min vs 268mU/l.min ; P=0.007 ) reflecting altered pituitary sensitivity and reduced responsiveness . CONCLUSION The GH response to bolus GHRH ( 1-29 ) NH ( 2 ) is attenuated in adult long-term survivors of childhood brain tumours . This may reflect direct pituitary damage and/or the loss of the tropic effects of chronic GHRH deficiency .

supramaximal doses of GHRH

radiotherapy

GHRH

GHRH ( 1-29 ) NH ( 2 )

GHRH ( 1-29 ) NH ( 2 )

GHRH ( 1-29 ) NH ( 2 )

GH

rise in GH output

patients post cranial irradiation

controls

Five

adult

male

childhood brain tumours

five

young

adult

childhood brain tumours


Auditory integration training for children with autism : no behavioral benefits detected . Auditory integration training and a control treatment were provided for 16 children with autism in a crossover experimental design . Measures , blind to treatment order , included parent and teacher ratings of behavior , direct observational recordings , IQ , language , and social/adaptive tests . Significant differences tended to show that the control condition was superior on parent-rated measures of hyperactivity and on direct observational measures of ear-occlusion . No differences were detected on teacher-rated measures . Children 's IQs and language comprehension did not increase , but adaptive/social behavior scores and expressive language quotients decreased . The majority of parents ( 56 % ) were unable to report in retrospect when their child had received auditory integration training . No individual child was identified as benefiting clinically or educationally from the treatment .

Auditory integration training

Auditory integration training

control treatment

auditory integration training

autism

autism

parent and teacher ratings of behavior

direct observational recordings

IQ

language

social/adaptive tests

Significant differences

No differences

teacher-rated measures

did not increase

adaptive/social behavior scores

and

expressive language quotients decreased

unable to report in retrospect

benefiting clinically or educationally

children with autism :

16 children

autism


Antisaccade and smooth pursuit eye movements in healthy subjects receiving sertraline and lorazepam . Patients suffering from some psychiatric and neurological disorders demonstrate abnormally high levels of saccadic distractibility when carrying out the antisaccade task . This has been particularly thoroughly demonstrated in patients with schizophrenia . A large body of evidence has been accumulated from studies of patients which suggests that such eye movement abnormalities may arise from frontal lobe dysfunction . The psychopharmacology of saccadic distractibility is less well understood , but is relevant both to interpreting patient studies and to establishing the neurological basis of their findings . Twenty healthy subjects received lorazepam 0.5 mg , 1 mg and 2 mg , sertraline 50 mg and placebo in a balanced , repeated measures study design . Antisaccade , no-saccade , visually guided saccade and smooth pursuit tasks were carried out and the effects of practice and drugs measured . Lorazepam increased direction errors in the antisaccade and no-saccade tasks in a dose-dependent manner . Sertraline had no effect on these measures . Correlation showed a statistically significant , but rather weak , association between direction errors and smooth pursuit measures . Practice was shown to have a powerful effect on antisaccade direction errors . This study supports our previous work by confirming that lorazepam reliably worsens saccadic distractibility , in contrast to other psychotropic drugs such as sertraline and chlorpromazine . Our results also suggest that other studies in this field , particularly those using parallel groups design , should take account of practice effects .

sertraline

lorazepam

lorazepam 0.5 mg , 1 mg and 2 mg

sertraline 50 mg

placebo

Lorazepam

Sertraline

lorazepam

sertraline

no effect

these measures

antisaccade direction errors

saccadic distractibility


Ropivacaine-clonidine combination for caudal blockade in children . BACKGROUND Adding clonidine to weak ropivacaine solutions ( < 0.2 % ) could potentially enhance analgesia as well as further reduce the risk for unwanted motor blockade . The aim of the present study was to compare the postoperative pain-relieving quality of a ropivacaine 0.1 % -clonidine mixture to that of plain ropivacaine 0.2 % following caudal administration in children . METHODS In a prospective , observer-blinded fashion , 40 ASA 1 paediatric patients undergoing subumbilical surgery were randomly allocated to receive a caudal injection of either plain ropivacaine 0.2 % ( 1 ml/kg ) ( R0.2 ) or a mixture of ropivacaine 0.1 % with clonidine 2 microg/kg ( 1 ml/kg ) ( R0.1C ) . Objective pain scale score and need for supplemental analgesia were used to evaluate analgesia during the first 24 h postoperatively . Residual postoperative sedation was also assessed . RESULTS A significantly higher number of patients in the R0.1C group ( 18/20 ) could be managed without supplemental analgesia during the first 24 h postoperatively compared to the R0.2 group ( 11/20 ) ( P=0.034 ) . Both the degree and the duration of postoperative sedation was similar in both groups . No signs of postoperative motor blockade were observed . CONCLUSIONS The combination of clonidine ( 2 microg/kg ) and ropivacaine 0.1 % is associated with an improved quality of postoperative analgesia compared to plain 0.2 % ropivacaine . The improved analgesic quality of the clonidine-ropivacaine mixture is achieved without causing any significant degree of postoperative sedation .

Ropivacaine-clonidine combination

clonidine

weak ropivacaine solutions

ropivacaine 0.1 % -clonidine mixture

plain ropivacaine

plain ropivacaine 0.2 % ( 1 ml/kg )

ropivacaine 0.1 %

clonidine 2 microg/kg ( 1 ml/kg )

Objective pain scale score

plain 0.2 % ropivacaine

enhance analgesia

pain-relieving quality

Residual postoperative sedation

supplemental analgesia

postoperative motor blockade

improved analgesic quality

caudal blockade

children

paediatric patients

subumbilical surgery


American College of Cardiology/European Society of Cardiology International Study of Angiographic Data Compression Phase I : The effect of lossy data compression on recognition of diagnostic features in digital coronary angiography . OBJECTIVES This study intended to determine the effect of varying degrees of lossy Joint Photographic Experts Group ( JPEG ) compression on detection of coronary angiographic features . BACKGROUND Compression of digital coronary angiograms facilitates playback of images and decreases cost . There are little data on the effect of compression on the accuracy of coronary angiography . METHODS At six centers , 71 angiographers each reviewed a set of 100 angiographic sequences . The 100 sequences were divided into four , 25-sequence subsets . Each subset of 25 was displayed either as original images or at one of three compression ratios ( CRs ) ( 6:1 , 10:1 or 16:1 ) . The effect of lossy compression on the sensitivity and specificity for detection of diagnostic features was determined . The effect of compression on subjective measures of image quality graded by the angiographers was also examined . RESULTS Lossy compression at a ratio of 16:1 decreased the sensitivity for the detection of diagnostic features ( 76 % vs. 80 % p = 0.004 ) . The largest effect was in the detection of calcification ( 52 % vs. 63 % at 16:1 compression vs. original images , p < 0.001 ) . Subjective indicators of image quality indicated a reduction in confidence in interpretation at CRs of 10:1 and 16:1 . CONCLUSIONS With increased ratios of lossy compression , a degradation of digital coronary angiograms occurs that results in decreased diagnostic accuracy . The sensitivity for detection of common diagnostic features was decreased , and subjective assessment of image quality was impaired . Caution is warranted in the interpretation of coronary angiograms that have been subjected to lossy JPEG compression beyond a ratio of 6:1 .

data compression

digital coronary angiography

coronary angiograms

JPEG compression

Photographic

Lossy compression

detection of calcification

confidence in interpretation

decreased diagnostic accuracy

digital coronary angiography


Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers . BACKGROUND Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease . The interaction of antimicrobial therapy and acid suppression is not yet well elucidated . AIMS To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volunteers . METHODS In two crossover studies omeprazole 20 mg b.d. , lansoprazole 30 mg b.d. , roxithromycin 300 mg b.d. , and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days . Blood plasma levels of the drugs were measured . In addition , roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy . RESULTS The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other . When compared to roxithromycin administered alone , its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice ( 3.0-5.0 microg/mL vs. 0.3-0.4 microg/mL ) and gastric tissue ( antrum : 3.8-4.0 vs. 2.8 microg/g , fundus : 5.9-7.4 vs. 4.2-4.4 microg/g ) . CONCLUSIONS Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other . However , proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori .

proton pump inhibitors

roxithromycin

proton pump inhibitors

roxithromycin

omeprazole 20 mg b.d.

lansoprazole 30 mg b.d.

roxithromycin 300 mg b.d.

roxithromycin

omeprazole or lansoprazole

proton pump inhibitors

roxithromycin

roxithromycin

Proton pump inhibitors

roxithromycin

proton pump inhibitors

Blood plasma levels

roxithromycin concentrations

blood plasma pharmacokinetics

gastric tissue

concentration of roxithromycin

volunteers

healthy


Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts : randomised double-blind trial . BACKGROUND Photodynamic therapy ( PDT ) with topical 5-aminolaevulinic acid ( ALA ) followed by irradiation with incoherent light ( ALA-PDT ) for recalcitrant warts have had beneficial results . Therefore , we undertook a randomised , parallel , double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant foot and hand warts . METHODS Recalcitrant foot and hand warts were randomly assigned to six repetitive ALA-PDT or placebo-PDT interventions combined with standard treatment encompassing paring followed by a keratolytic ( Verucid ) . Standardised photographs of each wart were taken before , during ( week 7 ) and after treatment ( weeks 14 and 18 ) . The area of each wart compared with entry area was the primary outcome variable , measured from photographs by an evaluator unaware of treatment allocation for intervention . Pain intensity immediately and 24 h after each intervention was assessed by a five-point scale . FINDINGS A total of 232 foot and hand warts in 45 patients were entered into the trial : 117 warts were allocated to ALA-PDT and 115 warts to placebo-PDT . In week 14 , the median relative reduction in wart area was 98 % in the ALA-PDT group ( interquartile range 100 % , 55 % ) versus 52 % ( 100 % , 0 ) in the placebo group ( p=0.0006 ) . In week 18 , the median relative reduction in wart area was 100 % in the ALA-PDT group ( 100 % , 57 % ) versus 71 % ( 100 % , 0 ) in the placebo-PDT arm ( p=0.008 ) . Both the number of vanishing warts and the difference in relative wart area of persisting warts at week 14 and 18 were significant ( p < 0.05 ) in favour of ALA-PDT . Significantly more ALA-PDT warts were graded at a higher pain intensity after treatment than placebo-PDT warts . INTERPRETATION ALA-PDT is superior to placebo-PDT when both wart area and number of vanishing warts are considered .

Photodynamic therapy

5-aminolaevulinic acid

placebo

ALA-PDT

placebo-PDT

ALA-PDT

placebo-PDT

ALA-PDT

ALA-PDT

placebo-PDT

ALA-PDT

placebo-PDT

placebo-PDT

foot and hand warts :

Pain intensity

median relative reduction in wart area

median relative reduction in wart area

number of vanishing warts

higher pain intensity

area and number of vanishing warts

recalcitrant foot and hand warts

Recalcitrant

warts


Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation : a double-blind randomised study . HAEST Study Group . Heparin in Acute Embolic Stroke Trial . BACKGROUND Patients with acute ischaemic stroke and atrial fibrillation have an increased risk of early stroke recurrence , and anticoagulant treatment with heparins has been widely advocated , despite missing data on the balance of risk and benefit . METHODS Heparin in Acute Embolic Stroke Trial ( HAEST ) was a multicentre , randomised , double-blind , and double-dummy trial on the effect of low-molecular-weight heparin ( LMWH , dalteparin 100 IU/kg subcutaneously twice a day ) or aspirin ( 160 mg every day ) for the treatment of 449 patients with acute ischaemic stroke and atrial fibrillation . The primary aim was to test whether treatment with LMWH , started within 30 h of stroke onset , is superior to aspirin for the prevention of recurrent stroke during the first 14 days . FINDINGS The frequency of recurrent ischaemic stroke during the first 14 days was 19/244 ( 8.5 % ) in dalteparin-allocated patients versus 17/225 ( 7.5 % ) in aspirin-allocated patients ( odds ratio=1.13 , 95 % CI 0.57-2.24 ) . The secondary events during the first 14 days also revealed no benefit of dalteparin compared with aspirin : symptomatic cerebral haemorrhage 6/224 versus 4/225 ; symptomatic and asymptomatic cerebral haemorrhage 26/224 versus 32/225 ; progression of symptoms within the first 48 hours 24/224 versus 17/225 ; and death 21/224 versus 16/225 . There were no significant differences in functional outcome or death at 14 days or 3 months . INTERPRETATION The present data do not provide any evidence that LMWH is superior to aspirin for the treatment of acute ischaemic stroke in patients with atrial fibrillation . However , the study could not exclude the possibility of smaller , but still worthwhile , effects of either of the trial drugs .

Low molecular-weight heparin

aspirin

heparins

Heparin

low-molecular-weight heparin ( LMWH

dalteparin

aspirin

LMWH

aspirin

dalteparin

aspirin :

LMWH

early stroke recurrence

recurrent stroke

frequency of recurrent ischaemic stroke

symptomatic cerebral haemorrhage

functional outcome or death

acute ischaemic stroke

atrial fibrillation

acute ischaemic stroke

atrial fibrillation


Lack of effect of a low-fat , high-fiber diet on the recurrence of colorectal adenomas . Polyp Prevention Trial Study Group . BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a standard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after randomization . RESULTS A total of 1905 of the randomized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( +/-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas .

low-fat , high-fiber diet

diet that was low in fat

fruits and vegetables

recurrence of colorectal adenomas

one recurrent adenoma

unadjusted risk ratio

number of such lesions

recurrence of large adenomas

advanced adenomas

risk of recurrence

men

women

colorectal adenomas


Human motor responses to simultaneous aversive stimulation and failure on a valued task . The effects of presentation of an aversive stimulus and simultaneous failure on a bogus intelligence test upon a subject 's aggressive reactions were studied . The subject 's fist clenching was used as an indicator of aggression . Four conditions , generated by the combinations of two kinds of stimulus delivered to the subjects ( aversive or nonaversive ) and two outcomes of the task ( failure or success ) , were investigated . 20 female and 20 male students ( ages : 17-34 years ) were instructed , upon the reception of an aversive or nonaversive acoustic signal , to press with the right hand a device that displayed a slide . Each slide presented an item from an intelligence test , to which the subjects were either allowed to answer successfully ( success ) or not ( failure ) . Failure increased the subject 's autonomic arousal , as measured by photoplethysmographic sensors , in all stimulation conditions , but only the condition with aversive stimulation increased the speed of clenching . This was interpreted as indicating subject 's tendencies to aggression . These results are discussed in relation to the effects of frustration .

aversive stimulation and failure

aversive or nonaversive

aversive or nonaversive acoustic signal

aggressive reactions

fist clenching

indicator of aggression

autonomic arousal ,

speed of clenching

tendencies to aggression

subject 's fist clenching


Immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine compared with a group A+C meningococcal polysaccharide vaccine in adolescents in a randomised observer-blind controlled trial . This study evaluated the immunogenicity and reactogenicity of a group C meningococcal conjugate vaccine ( MenC ) compared with a group A+C meningococcal polysaccharide vaccine ( MenPS ) in healthy adolescents . Subjects were randomised to receive one dose of either MenC ( n=92 ) or MenPS ( n=90 ) . Group C meningococcal IgG antibody concentrations and bactericidal titres were higher in the MenC group than the MenPS group at 1 month ( 22.8 U/ml vs 4.0 U/ml , p < 0.001 , and 87 vs 20 , p < 0.001 , respectively ) and 12 months ( 6.1 U/ml vs 3.0 U/ml , p < 0.001 , and 81.3 vs 20.2 , p < 0.001 , respectively ) . No differences in post immunisation reaction rates were noted between the two vaccinated groups . This study demonstrated the safety and enhanced immunogenicity of the candidate meningococcal conjugate vaccine as compared with the licensed polysaccharide vaccine in adolescents .

MenC

MenPS

Immunogenicity

reactogenicity

immunogenicity

reactogenicity

post immunisation reaction rates

immunogenicity

adolescents


Language , speech sound production , and cognition in three-year-old children in relation to otitis media in their first three years of life . OBJECTIVE As part of a prospective study of possible effects of early-life otitis media on speech , language , cognitive , and psychosocial development , we tested relationships between children 's cumulative duration of middle ear effusion ( MEE ) in their first 3 years of life and their scores on measures of language , speech sound production , and cognition at 3 years of age . METHODS We enrolled 6350 healthy infants by 2 months of age who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small town/rural and 4 suburban private pediatric practices . We intensively monitored the children 's middle ear status by pneumatic otoscopy , supplemented by tympanometry , throughout their first 3 years of life ; we monitored the validity of the otoscopic observations on an ongoing basis ; and we treated children for otitis media according to specified guidelines . Children who met specified minimum criteria regarding the persistence of MEE became eligible for a clinical trial in which they were assigned randomly to undergo tympanostomy tube placement either promptly or after a defined extended period if MEE remained present . From among those remaining , we selected randomly , within sociodemographic strata , a sample of 241 children who represented a spectrum of MEE experience from having no MEE to having MEE whose cumulative duration fell just short of meeting randomization criteria . In subjects so selected , the estimated duration of MEE ranged from none to 65.6 % of the first year of life and 44.8 % of the first 3 years of life . In these 241 children we assessed language development , speech sound production , and cognition at 3 years of age , using both formal tests and conversational samples . RESULTS We found weak to moderate , statistically significant negative correlations between children 's cumulative durations of MEE in their first year of life or in age periods that included their first year of life , and their scores on formal tests of receptive vocabulary and verbal aspects of cognition at 3 years of age . However , the percent of variance in these scores explained by time with MEE in the first year of life beyond that explained by sociodemographic variables ranged only from 1.2 % to 2.9 % , and the negative correlations were concentrated in the subgroup of children whose families had private health insurance ( rather than Medicaid ) . We found no significant correlations in the study population as a whole or in any subgroup between time with MEE during antecedent periods and children 's scores on measures of spontaneous expressive language , speech sound production , or other measured aspects of cognition . In contrast , by wide margins , scores on all measures were consistently highest among the most socioeconomically advantaged children and lowest among the most socioeconomically disadvantaged children . CONCLUSIONS Our findings suggest either that persistent early-life MEE actually causes later small , circumscribed impairments of receptive language and verbal aspects of cognition in certain groups of children or that unidentified , confounding factors predispose children both to early-life otitis media and to certain types of developmental impairment . Findings in the randomized clinical trial component of the larger study should help distinguish between causality and confounding as explanations for our findings.language , speech , cognition , development , otitis media , middle ear effusion .

pneumatic otoscopy

supplemented by tympanometry

otitis media

tympanostomy tube placement

scores on all measures

developmental impairment

findings.language , speech , cognition


Randomised , double blind , placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease : the ISOLDE trial . OBJECTIVES To determine the effect of long term inhaled corticosteroids on lung function , exacerbations , and health status in patients with moderate to severe chronic obstructive pulmonary disease . DESIGN Double blind , placebo controlled study . SETTING Eighteen UK hospitals . PARTICIPANTS 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second ( FEV ( 1 ) ) 50 % of predicted normal . INTERVENTIONS Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo . MAIN OUTCOME MEASURES Efficacy measures : rate of decline in FEV ( 1 ) after the bronchodilator and in health status , frequency of exacerbations , respiratory withdrawals . Safety measures : morning serum cortisol concentration , incidence of adverse events . RESULTS There was no significant difference in the annual rate of decline in FEV ( 1 ) ( P=0.16 ) . Mean FEV ( 1 ) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo ( P < 0.001 ) . Median exacerbation rate was reduced by 25 % from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate ( P=0.026 ) . Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate ( P=0.0043 ) . Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group ( 25 % v 19 % , P=0.034 ) . CONCLUSIONS Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV ( 1 ) but did produce a small increase in FEV ( 1 ) . Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status . These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease .

placebo

fluticasone propionate

corticosteroids

placebo

Efficacy

respiratory withdrawals

morning serum cortisol concentration

incidence of adverse events

annual rate of decline in FEV ( 1 )

Mean FEV ( 1 )

significantly higher

Median exacerbation rate

Health status deteriorated

Withdrawals

rate of decline in FEV ( 1 )

produce a small increase in FEV ( 1 ) .

exacerbations

slower decline in health status

men

women

aged between 40 and 75 years


Increased growth hormone response to sumatriptan challenge in adult autistic disorders . Serotonergic ( 5-HT ) abnormalities have been documented in autism . To assess sensitivity of the 5-HT1d receptor , growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls . In this study , 11 adult patients with autism or Asperger 's disorder were compared with nine matched controls . All subjects were randomized to single dose sumatriptan ( 6 mg SQ ) and placebo challenges , separated by a 1-week interval , and growth hormone was measured before and during the challenges . The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline . This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls , independent of placebo effects . Therefore , abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism .

sumatriptan

5-HT1d receptor agonist sumatriptan

single dose sumatriptan ( 6 mg SQ )

placebo challenges

sumatriptan

Increased growth hormone

growth hormone response

growth hormone

diagnosisxdrugxtime interaction

growth hormone response

adult

autistic disorders


Outcome of CNS disease at diagnosis in disseminated small noncleaved-cell lymphoma and B-cell leukemia : a Children 's Cancer Group study . PURPOSE To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children 's Cancer Group trials . PATIENTS AND METHODS Of 462 patients with disseminated disease , 49 ( 10.6 % ) had CNS disease at diagnosis ( CNS+ ) . CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies ( CSF+/Mass ; CNPs ) in 36 patients and isolated CNPs in 13 . Of the CNS+ patients , 28 had M2 ( 5 % to 25 % blasts ) or M3 ( > 25 % blasts ) bone marrow involvement . All patients received protocol-based systemic and intrathecal chemotherapy . Thirty-six patients also received CNS irradiation . RESULTS Relapses occurred in 21 ( 43 % ) of 49 patients , predominantly in the CNS ( 71 % ) and bone marrow ( 52 % ) . The 3-year event-free survival +/- SE for all patients with CNS+ disease was 45 % +/- 7 % . Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase ( LDH ) diagnosis , with a relative failure rate ( RFR ) of 1.52 ( 95 % confidence interval [ CI ] , 0.88 to 2.6 ; P =.15 ) . In comparison , the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 ( 95 % CI , 0.96 to 2.0 ; P =.029 ) and 2.2 ( 95 % CI , 1.5 to 3.0 ; P < .001 ) , respectively . The RFR for patients with isolated CNPs was 0.87 ( 95 % CI , 0.36 to 2.1 ; P =.76 ) . CONCLUSION We conclude that , with the treatments used during the period covered by these studies , the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level , but the effect was not statistically significant .

Children 's Cancer Group trials

CNS irradiation

Relapses

3-year event-free survival

higher treatment failure rate

relative failure rate ( RFR )

RFRs

CNS disease

nominally worse outcome

B-cell leukemia

Children 's

Cancer

B-cell leukemia

Children 's

Cancer

disseminated disease

CNS

CNS+

CNS+

All


Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery . Children are sensitive to the inflammatory side effects of cardiopulmonary bypass ( CPB ) . Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children . In 20 operations , 19 children were randomized to heparin-coated ( group HC , n = 10 ) or standard ( group C , n = 10 ) bypass circuits . Plasma levels of acute phase reactants , interleukins , granulocytic proteins and complement factors were measured . All were significantly elevated after CPB . Levels of complement factor C3a ( 851 ( 791-959 ) ng/ml [ median with quartiles ] in group C , 497 ( 476-573 ) ng/ml in group HC , p < 0.001 ) , Terminal Complement Complex ( 114 ( 71-130 ) AU/ml in group C , 35.5 ( 28.9-51.4 ) AU/ml in group HC , p < 0.001 ) , and interleukin-6 ( 570 ( 203-743 ) pg/ml in group C , 168 ( 111-206 ) pg/ml in group HC , p = 0.005 ) , were significantly reduced in group HC . Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population , as reflected by significantly reduced levels of circulating complement factors and interleukin-6 .

heparin-coated CPB circuits

heparin-coated

standard

Heparin-coated CPB circuits

Plasma levels of acute phase reactants

interleukins

granulocytic proteins

complement factors

Levels of complement factor C3a

Terminal Complement Complex


Does waiting matter ? A randomized controlled trial of new non-urgent rheumatology out-patient referrals . OBJECTIVE To examine the effect of waiting times on the health status of patients referred for a non-urgent rheumatology opinion . METHODS The study was a randomized controlled clinical study evaluating a 'fast track ' appointment with a 6-week target waiting time against an 'ordinary ' appointment in the main city out-patient clinic of the rheumatology service for the Lothian and Borders region ( population approximately 1 million ) . Health status was measured using the SF12 physical and mental summary component T-scores and pain was measured with a 100 mm visual analogue pain scale . Secondary outcomes were health utility and perceived health both measured with the EuroQol instrument , mental health measured with the Hospital Anxiety and Depression scale , disability with the modified Health Assessment Questionnaire and economic costs measured from a societal perspective . RESULTS Mean waiting times were 43 days ( sigma = +/-16 ) and 105 days ( sigma = +/-51 ) for 'fast track ' and 'ordinary ' appointments , respectively . Both groups showed significant improvements in mean [ 95 % confidence interval ( CI ) ] scores for pain : 11 ( 7 , 16 ) ( P < 0.001 ) ; physical health status : 4 ( 2 , 5 ) ( P < 0.001 ) ; mental health status : 2 ( 0.1 , 4 ) ( P < 0.02 ) ; and health utility : 0.11 ( 0.07 , 0.16 ) ( P < 0.001 ) by the end of the 15-month period of the study , but there was no significant difference between either arm of the study . CONCLUSIONS Rationing by delay was not detrimental to either mental or physical health and patients in both arms of the study showed significant and similar improvement in health by 15 months . Expenditure of resources on waiting times without regard to clinical outcomes is likely to be wasteful and additional resources should be directed at achieving the greatest clinical benefit . More research into effective methods of controlling demand and better identification of those who would benefit from access to specialist care is needed .

'ordinary ' appointment

pain

health utility

Anxiety and Depression scale

Mean waiting times

pain

physical health status

mental health status

health utility


Identifying the indications for laparoscopically assisted vaginal hysterectomy : a prospective , randomised comparison with abdominal hysterectomy in patients with symptomatic uterine fibroids . OBJECTIVE To compare laparoscopically assisted vaginal hysterectomy ( LAVH ) and total abdominal hysterectomy ( TAH ) in patients with uterine fibroids . DESIGN A prospective randomised study . SETTING The San Paolo Hospital , Milan . POPULATION Sixty-two patients , who were not suitable for a vaginal hysterectomy , requiring treatment for uterine fibroids . METHODS Randomisation between LAVH and TAH . Comparison of outcomes on the whole series , patients with uteri < or = 500 g ( Group 1 ) and patients with uteri > 500 g ( Group 2 ) . MAIN OUTCOME MEASURES To establish operating time , blood loss , complications , febrile morbidity , analgesics administration and hospital stay for both treatment approaches . RESULTS Median uterine weight was 400 g in both LAVH and TAH group . Median operating time was longer for LAVH ( 135 min compared with 120 min for TAH ; P = 0.001 ) , but patients undergoing LAVH had less analgesics administration ( 23 % compared with 77 % , P < 0.001 ) and a shorter median hospital stay ( 3.8 compared with 5.8 days ; P < 0.001 ) . LAVH , when compared with TAH in the two weight subgroups , required a significantly longer operating time only in Group 2 , significantly reduced analgesics administration only in Group 1 , and significantly reduced hospital stay in both groups . Conversions of LAVH to laparotomy were significantly more frequent in Group 2 ( 3/11 ) than in Group 1 ( 0/20 ) ( P = 0.04 ) . CONCLUSIONS Compared with TAH , LAVH has advantages in removing uteri weighing < or = 500 g , with comparable operating time , less post-operative pain and shorter recovery . Among uteri weighing > 500 g LAVH showed a shorter recovery , but longer operating time than TAH and a 27 % rate of conversion to laparotomy .

abdominal hysterectomy

total abdominal hysterectomy ( TAH )

LAVH

TAH

LAVH

TAH

LAVH

TAH

LAVH

LAVH

TAH

TAH

LAVH

LAVH

TAH

laparotomy

operating time

blood loss

complications

febrile morbidity

analgesics administration

hospital stay

Median uterine weight

Median operating time

analgesics administration

median hospital stay

operating time

analgesics administration

hospital stay

advantages

operating time

post-operative pain

recovery

conversion to laparotomy

symptomatic uterine fibroids

uterine fibroids

Sixty-two

uterine fibroids


Secretin and autism : a two-part clinical investigation . Recent anecdotal reports have touted the gastrointestinal ( GI ) hormone secretin as a treatment modality for autism , though there is little clinical evidence or literature to support its viability . We undertook a two-part clinical trial to investigate these claims . Fifty-six patients ( 49 boys , 7 girls , mean age = 6.4 years , SD = 2.7 ) enrolled in an open-label trial of secretin , during which they received one injection of the hormone ( 2 IU/kg ) . All subjects were evaluated by their parents at baseline and follow-up visits ( 3-6 weeks later , M = 3.7 , SD = 1.4 weeks ) with Childhood Autism Rating Scales ( CARS ) . Thirty-four patients were labeled with Pervasive Developmental Disorder Not Otherwise Specified , and 22 met diagnostic criteria for Autistic Disorder . Forty-five patients were concurrently on other drug treatments . At follow-up , some reported minimal but potentially significant improvements including changes in GI symptoms , expressive and/or receptive language function , and improved awareness and social interactions . No adverse effects were reported or observed . Subsequently , 17 of the most responsive patients from Study 1 began a double-blind trial that also included 8 newly enrolled patients . Patients in this second study were alternatively entered into one of two groups and received injections of secretin or placebo with crossover at 4 weeks . Patients from Study 1 entered into Study 2 at an average of 6.5 ( SD = 0.8 ) weeks after beginning Study 1 . Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children , overall it produced few clinically meaningful changes when compared to children given placebo injections .

secretin

secretin

secretin

placebo

secretin

placebo

Childhood Autism Rating Scales ( CARS )

changes in GI symptoms

adverse effects

Fifty-six

boys

girls

mean age = 6.4 years , SD = 2.7

Thirty-four

Pervasive Developmental Disorder

Autistic Disorder

Forty-five

drug treatments


Comments on " Secretin and autism : a two-part clinical investigation " by M.G . Chez et al .

Secretin

Secretin

autism

autism :


Assessment in multisite randomized clinical trials of patients with autistic disorder : the Autism RUPP Network . Research Units on Pediatric Psychopharmacology . Assessment of autistic disorder ( autism ) symptoms , primary and secondary , poses more challenging problems than ordinarily found in multisite randomized clinical trial ( RCT ) assessments . For example , subjects may be uncommunicative and extremely heterogeneous in problem presentation , and current pharmacological treatments are not likely to alter most core features of autism . The Autism Research Units on Pediatric Psychopharmacology ( RUPP Autism Network ) resolved some of these problems during the design of a risperidone RCT in children/adolescents . The inappropriateness of the usual anchors for a Clinical Global Impression of Severity ( CGI-S ) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3 , mildly ill . The communication problems , compromising use of the patient as an informant , were addressed by several strategies , including careful questioning of care providers , rating scales , laboratory tests , and physical exams . The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects . The problems of neuropsychologically testing nonverbal , lower functioning , sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques . The problems of assessing low-end IQs , neglected by most standardized test developers , was resolved by an algorithm of test hierarchy . Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new , specially adapted battery . Reliability on the Autism Diagnostic Interview ( currently the most valid diagnostic instrument ) and other clinician instruments required extensive cross-site training ( in-person , videotape , and teleconference sessions ) . Definition of a treatment responder required focus on individually relevant target symptoms , synthesis of possible modest improvements in many domains , and acceptance of attainable though imperfect goals . The assessment strategy developed is implemented in a RCT of risperidone ( McDougle et al. , 2000 ) for which the design and other methodological challenges are described elsewhere ( Scahill et al. , 2000 ) . Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders .

risperidone RCT

risperidone

autistic disorder

communication problems

careful questioning of care providers

rating scales

laboratory tests

physical exams

response

side effects .

low-end IQs

Autism Diagnostic Interview

autistic disorder

children/adolescents

autism


Comparison of a 5 day regimen of cefdinir with a 10 day regimen of cefprozil for treatment of acute exacerbations of chronic bronchitis . Patients with acute exacerbations of chronic bronchitis were treated with cefdinir 300 mg bd for 5 days or cefprozil 500 mg bd for 10 days in a prospective , randomized , double-blind , multicentre study . Of the 548 patients enrolled , 281 ( 51 % ) were evaluable . The clinical cure rates at the test-of-cure visit were 80 % ( 114/142 ) and 72 % ( 100/139 ) for the evaluable patients treated with cefdinir and cefprozil , respectively . Respiratory tract pathogens were isolated from 409 ( 75 % ) of 548 admission sputum specimens , with the predominant pathogens being Haemophilus parainfluenzae , Haemophilus influenzae , Staphylococcus aureus and Moraxella catarrhalis . The microbiological eradication rates at the test-of-cure visit were 81 % ( 157 of 193 pathogens ) and 84 % ( 166 of 198 pathogens ) for the evaluable patients treated with cefdinir and cefprozil , respectively . Adverse event rates while on treatment were equivalent between the two treatment groups . The incidence of diarrhoea during therapy was higher for patients treated with cefdinir ( 17 % ) than for patients treated with cefprozil ( 6 % ) ( P < 0.01 ) , but most cases were mild and did not lead to discontinuation of treatment . These results indicate that a 5 day regimen of cefdinir is as effective and safe in the treatment of patients with acute exacerbations of chronic bronchitis as a 10 day regimen of cefprozil .

cefdinir

cefprozil

cefdinir

cefprozil

cefdinir

cefprozil

cefdinir

cefprozil

cefdinir

cefprozil

cefdinir

cefprozil

clinical cure rates

Respiratory tract pathogens

microbiological eradication rates

Adverse event rates

incidence of diarrhoea

effective and safe

cefdinir and cefprozil

cefdinir


The effectiveness of omeprazole , clarithromycin and tinidazole in eradicating Helicobacter pylori in a community screen and treat programme . Leeds Help Study Group . INTRODUCTION Helicobacter pylori screening and treatment has been proposed as a cost-effective method of preventing gastric cancer . AIM To assess , in a randomized controlled trial , the efficacy of therapy in eradicating H. pylori as part of a screening programme , and to report the adverse events associated with this strategy . METHODS Subjects between the ages of 40-49 years were randomly selected from the lists of 36 primary care centres . Participants attended their local practice and H. pylori status was determined by 13C-urea breath test . Infected subjects were randomized to receive omeprazole 20 mg b.d. , clarithromycin 250 mg b.d . and tinidazole 500 mg b.d . for 7 days ( OCT ) or identical placebos . Eradication was determined by a 13C-urea breath test 6 months and 2 years after the first visit . Successful eradication was defined as two negative 13C-urea breath tests or one negative and one missing test . Adverse events and compliance were assessed at the 6-month visit . RESULTS A total of 32 929 subjects were invited to attend , 8407 were evaluable , and 2329 ( 28 % ) of these were H. pylori-positive . A total of 1161 subjects were randomized to OCT and 1163 to placebo ; over 80 % returned for a repeat 13C-urea breath test on at least one occasion . The eradication rates in those allocated to OCT were as follows : intention-to-treat , 710 out of 1161 ( 61 % ; 95 % confidence interval : 58-64 % ) ; evaluable 710 out of 967 ( 73 % ; 95 % CI : 71-76 % ) ; took all medication 645 out of 769 ( 84 % ; 95 % CI : 81-87 % ) . Adverse events occurred in 45 % of the treatment group and in 18 % of the placebo group ( relative risk 2.5 ; 95 % CI : 2.1-2.9 ) . Compliance , male gender , no antibiotic prescription in the subsequent 2 years and experiencing a bitter taste with the medication were independently associated with treatment success . CONCLUSIONS The OCT regimen has an eradication rate of 61 % in intention-to-treat analysis and is therefore less successful in treating H. pylori as part of a screening programme compared with hospital studies in dyspeptic patients .

omeprazole

clarithromycin

tinidazole

omeprazole 20 mg b.d.

clarithromycin 250 mg b.d

and tinidazole 500 mg b.d .

placebos

eradicating Helicobacter pylori

Eradication

Successful eradication

negative 13C-urea breath tests

one negative and one missing test

Adverse events

compliance

pylori-positive

eradication rates

Adverse events

experiencing a bitter taste

eradication rate

between the ages of 40-49 years

32 929

H. pylori-positive

dyspeptic


Reduction of oral mucositis by filgrastim ( r-metHuG-CSF ) in patients receiving chemotherapy . Mucositis , the inflammation and necrosis of mucosal membranes , is a serious and debilitating consequence of many cancer therapies . We were interested in the potential role of filgrastim ( recombinant methionyl human granulocyte colony-stimulating factor , r-metHuG-CSF ) in the reduction of mucositis . Patients with newly diagnosed small-cell lung cancer ( SCLC ) were treated with CAE chemotherapy ( cyclophosphamide , doxorubicin , and etoposide ) and placebo or filgrastim . If patients had an episode of febrile neutropenia , they received unblinded filgrastim in subsequent CAE cycles . Oral mucositis was considered to have occurred if a patient reported any clinical sign or symptom of oral mucositis with or without oral candidiasis . Oral mucositis was analyzed using the unadjusted chi-square test , and time to first episode of mucositis was analyzed using the stratified log-rank test as well as the Cox proportional hazards regression model . During cycle 1 , placebo-treated patients had more episodes of mucositis ( 47 % ) compared with those patients randomized to filgrastim ( 28 % ) . Across all cycles of treatment , 70 % of placebo-treated patients experienced mucositis , compared with 53 % of patients randomized to filgrastim . A significant reduction in the incidence of chemotherapy-related oral mucositis occurred across multiple cycles of treatment in patients treated with filgrastim .

filgrastim

r-metHuG-CSF

chemotherapy

filgrastim

r-metHuG-CSF

CAE chemotherapy

cyclophosphamide

doxorubicin

etoposide

placebo

Reduction of oral mucositis

Mucositis

reduction of mucositis

Oral mucositis

Oral mucositis

time to first episode of mucositis

mucositis

mucositis

oral mucositis

patients receiving chemotherapy


A laser-powered hydrokinetic system for caries removal and cavity preparation . BACKGROUND Laser systems have been developed for the cutting of dental hard tissues . The erbium , chromium : yttrium-scandium-gallium-garnet , or Er , Cr : YSGG , laser system used in conjunction with an air-water spray has been shown to be efficacious in vitro for cavity preparation . METHODS The authors randomly selected subjects for cavity preparation with conventional air turbine/bur dental surgery or an Er , Cr : YSGG laser-powered system using a split-mouth design . They prepared Class I , III and V cavities , placed resin restorations and evaluated subjects on the day of the procedure and 30 days and six months postoperatively for pulp vitality , recurrent caries , pain and discomfort , and restoration retention . Sixty-seven subjects completed the study . RESULTS There were no statistical differences between the two treatment groups for the parameters measured with one exception ; there was a statistically significant decrease in discomfort levels for the laser system at the time of cavity preparation for subjects who declined to receive local anesthetic . CONCLUSIONS The Er , Cr : YSGG laser system is effective for preparation of Class I , III and V cavities and resin restorations are retained by lased tooth surfaces . CLINICAL IMPLICATIONS Hard-tissue cutting lasers are being introduced for use in operative dentistry . In this study , an Er , Cr : YSGG laser has been shown to be effective for cavity preparation and restoration replacement .

Laser systems

Er , Cr : YSGG , laser system

Er , Cr : YSGG laser-powered system

resin restorations

Er , Cr : YSGG laser system

Er , Cr : YSGG laser

pulp vitality

recurrent caries

pain and discomfort

restoration retention

discomfort levels for the laser system

randomly selected subjects

cavity preparation

Sixty-seven


Response of pre-core mutant chronic hepatitis B infection to lamivudine . The proportion of chronic liver disease associated with the pre-core mutant of hepatitis B virus ( HBV ) infection is increasing , particularly in Mediterranean Europe and in Asia . The pre-core mutant HBV is unable to produce hepatitis B e antigen ( HBeAg ) , so that patients with this variant do not present with HBV characterised by HBeAg in the serum . Pre-core mutant chronic hepatitis B infection usually proceeds to serious liver disease . Wild-type HBV infection may be mild and respond relatively well to interferon ( IFN ) alpha therapy , but IFN alpha is not an effective therapeutic option in pre-core mutant hepatitis B infection and new therapeutic options are needed . Clinical data show that lamivudine is an effective treatment for patients with pre-core mutant hepatitis B . There is profound suppression of HBV replication and improvement in indicators of liver disease in most patients . In conclusion , lamivudine is suitable for treatment of a wide range of patients with chronic hepatitis B , including those with pre-core mutant HBV infection .

lamivudine

lamivudine

lamivudine

HBeAg in the serum .

effective

HBV replication

indicators of liver disease


Clinical pathway for fractured neck of femur : a prospective , controlled study . OBJECTIVE To assess outcomes of using a clinical pathway for managing patients with fractured neck of femur . DESIGN Prospective , pseudorandomised , controlled trial . SETTING St Vincent 's Hospital , Melbourne , Victoria ( a tertiary referral , university teaching hospital ) , 1 October 1997 to 30 November 1998 . PARTICIPANTS 111 patients ( 80 women and 31 men ; mean age , 81 years ) admitted via the emergency department with a primary diagnosis of fractured neck of femur . INTERVENTIONS Management guided by a clinical pathway ( 55 patients ) or established standard of care ( control group , 56 patients ) . MAIN OUTCOME MEASURES Timing of referrals and discharge planning ; total length of stay ; and complication and readmission rates within 28 days of discharge . RESULTS Patients managed according to the clinical pathway had a shorter total stay ( 6.6 versus 8.0 days ; P = 0.03 ) , even if assessment for placement by the Aged Care Assessment Service was required ( 9.5 versus 13.6 days ; P = 0.03 ) . There were no significant differences in complication and readmission rates between pathway and control patients ( complication rates , 24 % versus 36 % ; P = 0.40 ; readmission rates , 4 % versus 11 % ; P = 0.28 ) . CONCLUSION Coordinated multidisciplinary care of patients with fractured neck of femur reduces length of stay without increasing complications .

complication

fractured neck of femur :

fractured neck of femur

111 patients


Plasma antioxidant status after high-dose chemotherapy : a randomized trial of parenteral nutrition in bone marrow transplantation patients . BACKGROUND Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants . It is not known whether parenteral nutrition ( PN ) administered during bone marrow transplantation ( BMT ) supports systemic antioxidant status . OBJECTIVE The aims of the study were to determine 1 ) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2 ) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone . DESIGN Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose , amino acids , micronutrients , and lipid ( 120 kJ/d ) or a solution containing only micronutrients ( identical to those in standard PN ) and a small amount of lipid ( 12 kJ/d ) . Plasma antioxidant status was measured before conditioning therapy and serially at days 1 , 3 , 7 , 10 , and 14 after BMT . RESULTS Plasma glutathione ( GSH ) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy . Plasma cysteine concentrations were unchanged , whereas cystine concentrations increased . Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time . Plasma alpha-tocopherol concentrations were lower in patients given standard PN . There were no differences in other plasma antioxidants between groups . CONCLUSIONS A significant decline in GSH-glutathione disulfide , cysteine-cystine , and vitamin E status occurs after chemotherapy and BMT . Standard PN does not improve antioxidant status compared with administration of micronutrients alone . Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed .

high-dose chemotherapy

Chemotherapy and radiation therapy

parenteral nutrition ( PN )

bone marrow transplantation ( BMT )

high-dose chemotherapy

BMT

PN

PN

BMT

micronutrients

, and lipid

solution containing only micronutrients

chemotherapy

BMT

high-dose chemotherapy

BMT

Plasma antioxidant status

Plasma glutathione ( GSH )

GSH redox state

Plasma cysteine concentrations

GSH peroxidase activity

Plasma alpha-tocopherol concentrations

plasma antioxidants

GSH-glutathione disulfide

cysteine-cystine

vitamin E status

bone marrow transplantation

Twenty-four


Atrophy and intestinal metaplasia one year after cure of H. pylori infection : a prospective , randomized study . BACKGROUND & AIMS Helicobacter pylori-infected gastric mucosa evolves through stages of chronic gastritis , intestinal metaplasia ( IM ) , glandular atrophy ( GA ) , and dysplasia before carcinoma develops . We studied if H. pylori eradication would alter the course of premalignant histologic changes in the stomach . METHODS Volunteers from the Yantai County in China underwent upper endoscopy with biopsy specimens obtained from the antrum and corpus . H. pylori-infected subjects were randomized to receive either a 1-week course of omeprazole , amoxicillin , and clarithromycin ( OAC ) or placebo . At 1 year , endoscopies with biopsies were repeated . RESULTS A total of 587 H. pylori-infected subjects were randomized to OAC ( n = 295 ) and placebo ( n = 292 ) . At 1 year , H. pylori was eradicated in 226 subjects assigned to OAC . In the placebo group , 245 patients remained H. pylori infected . Analysis of paired samples obtained from the same patients showed that acute and chronic gastritis decreased in both the antrum and corpus after H. pylori eradication ( P < 0.001 ) and activity of IM decreased in antrum ( P = 0.014 ) . In the H. pylori-infected group , antral biopsy specimens had more pronounced acute gastritis ( P = 0.01 ) , whereas corpus specimens showed increased acute and chronic gastritis ( P < 0.001 ) and a marginal increase in GA ( P = 0.052 ) . When histologic changes were compared between the 2 groups , decrease in acute and chronic gastritis was more frequent after H. pylori eradication ( P < 0.001 ) but changes in IM were similar . In the H. pylori-infected group , increase in GA was seen in the corpus ( P = 0.01 ) . CONCLUSIONS At 1 year , H. pylori eradication is beneficial in preventing progression of pathologic changes of the gastric mucosa .

upper endoscopy with biopsy

placebo

OAC

OAC

placebo

acute and chronic gastritis

activity of IM

acute gastritis

acute and chronic gastritis

GA

acute and chronic gastritis

IM

GA

pathologic changes

intestinal metaplasia

H. pylori infection


The Finnish Diabetes Prevention Study . The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were randomized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aimed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme .

intensive diet-exercise programme

individual dietary advice

efficacy

type 2 diabetes

death .

weight reduction

weight reduction

greater reductions

cardiovascular risk factors

efficacy and feasibility

Diabetes

Diabetes

type 2 diabetes

impaired glucose tolerance ( IGT )

IGT


Transesophageal echocardiography in quantification of emboli during femoral nailing : reamed versus unreamed techniques . We quantified the embolic load to the lungs created with two different techniques of femoral nailing . Eleven patients with 12 traumatic femur fractures were randomized to reamed ( 7 fractures ) and unreamed ( 5 fractures ) groups . Intramedullary nailing was with the AO/ASIF* universal reamed or unreamed nail . Transesophageal echocardiography ( TEE ) was used to evaluate the quantity and quality of emboli generated by nailing . Data were analyzed using software that digitized the TEE images and quantified the area of embolic particles in each frame . The duration of each level of embolic phenomena ( zero , moderate , severe ) was used to determine total embolic load with various steps ( fracture manipulation , proximal portal opening , reaming , and nail passage ) . Manual grading of emboli correlated highly with software quantification . Our data confirm the presence and similarity of emboli generation with both methods of intramedullary nailing . Unreamed nails do not protect the patient from pulmonary embolization of marrow contents .

Transesophageal echocardiography

reamed

unreamed

femoral nailing

reamed

unreamed

reamed

unreamed nail

Transesophageal echocardiography ( TEE

emboli

Unreamed nails


[ Comparative study between 5 % prilocaine and 2 % mepivacaine by the subarachnoid route in transurethral resections ] . OBJECTIVE To compare the duration of spinal block with 5 % prilocaine and 2 % mepivacaine in short procedures for transurethral resection and to assess possible complications in the immediate postoperative period . MATERIAL AND METHODS Fifty-seven patients scheduled for transurethral resection of the prostate or a vesical tumor . Patients were ASA I-III , over 55 years of age and randomly assigned to two groups to receive 5 % prilocaine ( 1 mg/kg , n = 27 ) or 2 % mepivacaine ( 0.8 mg/kg , n = 30 ) . We collected data on anesthetic technique , levels of extension of motor and sensory blockades , duration of blockades and complications within the first 24 hours after surgery . RESULTS Demographic data , ASA classification and duration of surgery were similar in both groups . We found statistically significant differences ( p < 0.05 ) in duration of sensory blockade ( 120.92 +/- 36.21 min with prilocaine and 145.83 +/- 35.81 min with mepivacaine ) and in motor blockade ( 106.29 +/- 38.16 min with prilocaine and 133.16 +/- 42.21 min with mepivacaine ) . Five cases of hypotension and 4 of bradycardia occurred in each group and one patient in the mepivacaine group suffered slight postoperative cephalea . CONCLUSIONS Both local anesthetics offer good surgical conditions with hemodynamic stability and few complications . The duration of sensory and motor blockade is shorter with prilocaine than with mepivacaine , making prilocaine more appropriate for short interventions .

5 % prilocaine

2 % mepivacaine

5 % prilocaine

2 % mepivacaine

2 % mepivacaine ( 0.8 mg/kg , n = 30 )

prilocaine

mepivacaine

duration

assess possible complications

anesthetic technique

duration of blockades

complications within the first 24 hours

duration of sensory blockade

motor blockade

hypotension

bradycardia

surgical conditions

complications

sensory

motor blockade

Fifty-seven

vesical tumor


Comparison of high and low dose of the inhaled steroid , budesonide , as an initial treatment in newly detected asthma . The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies . It is not , however , clear whether the treatment should be started with a high or a low dose of the inhaled steroid . We have compared the effects of high and low dose inhaled steroid , budesonide , in patients with newly detected asthma . We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma . The patients were randomly allocated to two treatment groups : one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day . The drugs were given with a Turbuhaler dry powder inhaler . During the 3-month treatment period , no significant differences between the treatment groups were noted in morning or evening PEF values , in spirometric parameters , in asthmatic symptoms or in the use of rescue beta2-agonists . The decrease in bronchial hyperresponsiveness was , however , more marked in the high dose budesonide group , reaching a borderline significance ( P=0.10 high vs. low dose budesonide ) . In addition , in serum markers of asthmatic inflammation significant differences were shown between the treatment groups . The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group ( P=0.02 ; high vs. low dose budesonide ) . In serum ECP no change was observed in the low dose budesonide group , but a marked decrease in the high-dose budesonide group ( P=0.008 ; high vs. low dose budesonide ) . The change was even more marked with regard to serum EPX ( P=0.005 ; high vs. low dose budesonide ) . Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid . The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response .

inhaled steroid , budesonide

inhaled steroids

high and low dose inhaled steroid

budesonide

800 microg inhaled budesonide

200 microg inhaled budesonide

Turbuhaler dry powder inhaler

budesonide

budesonide

morning or evening PEF values

more marked

serum markers of asthmatic inflammation

more marked

serum ECP

marked

regard to serum EPX

asthma

asthma

101 adult patients

bronchial asthma

inhaled steroid

pharmacological treatment

asthma


Is a calculated total hip BMD of clinical use ? The diagnosis of osteoporosis is based on bone mass measurement . To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the standard measurement site . This information is not available for many early measurements . We have assessed whether it is possible to derive clinically useful information about total hip bone mineral density ( BMD ) from measurements at other hip sites . The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were reviewed . The total hip BMD as directly measured was compared with that obtained from the formula : Total hip BMD = 0.48 x Neck BMD + 0.62 x Trochanteric BMD + 0.03 . In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods . In the pretreatment state there was good agreement between the two measures ( r2 = 0.96 , SEE 0.012 g/cm2 ) . If the formula was used to compute a change in total hip BMD , the agreement between both methods remained good . However , the standard error of the estimate of the change represented 59 % of the observed change . This indicates that the error associated with this estimate is too great to allow clinically meaningful conclusions to be drawn from calculated total hip BMD . We conclude that , whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip , these estimates are too imprecise to allow conclusions about change in BMD to be made .

total hip BMD

Total hip BMD

Neck BMD

Trochanteric BMD

rate of change in hip BMD

agreement

change in total hip BMD

agreement

error associated with this estimate

calculated total hip BMD .

total hip BMD

change in BMD

osteoporosis


On the search for the neurophysiological manifestation of recollective experience . M.E . Smith ( 1993 ) obtained event-related brain potentials ( ERPs ) from subjects performing a recognition memory task using " remember " ( R ) and " know " ( K ) judgments , and reported observing in the ERP a " neurophysiological manifestation of recollective experience " as a difference between the positive waveforms elicited by stimuli that yielded R and K judgments . We replicated his experiment and examined the componential structure of the R > K effect in two ways . First , we found that correction for P300 latency jitter eliminated the effect reported by Smith . Second , the application of principal component analysis indicated that the positive waveform elicited by the words in the test list was a P300 . These analyses do not support the hypothesis that there is a new component ( the " memory-evoked shift " ) that is a specific manifestation of recollection .

recognition memory task

P300 latency jitter

positive waveform

" memory-evoked shift " )

event-related brain potentials ( ERPs )


5-fluorouracil plus folinic acid with or without ifosfamide in advanced colorectal cancer : a phase II randomized trial . AIM This phase II trial evaluated the biomodulation of 5-fluorouracil ( 5-FU ) plus folinic acid ( FA ) with or without ifosfamide ( IFO ) in chemotherapy-naive patients with colorectal cancer . PATIENTS AND METHODS Forty-eight patients were randomized to receive : FA ( 25 mg/m2 iv bolus days 1 to 3 ) , followed by 5-FU ( 750 mg/m2 iv bolus days 1 to 3 ) , arm A ; or FA ( 25 mg/m2 iv bolus days 1 to 3 ) , followed by 5-FU ( 750 mg/m2 iv bolus days 1 to 3 ) plus IFO ( 2,000 mg/m2 in 1000 mL 5 % dextrose in a 2-hr infusion , days 1 to 3 ) , arm B. Mesna was added during and after IFO to prevent hemorrhagic cystitis . Treatment was repeated every 21 days in both arms . RESULTS Forty-five patients were assessable for response : in arm A , 5 patients achieved a partial response ( overall response , 25 % ) , and in arm B , 2 patients achieved a complete and 1 a partial response ( overall response , 12 % ) . Time to failure was 3.5 months ( range , 1-38 ) in patients treated with 5-FU plus FA , and 3 months ( range , 1-21 ) in patients treated with the IFO combination . The median survival time was 13.5 months ( range , 1-49 months ) in arm A and 16 months ( range , 1-43 months ) in arm B . Diarrhea , stomatitis and vomiting were the most common nonhematologic toxicities in both arms . The most notable hematologic toxicity was leukopenia ; 15 % and 20 % of patients experienced grade 4 in arm A and arm B , respectively . CONCLUSIONS IFO does not increase the activity of the 5-FU plus FA combination in advanced colorectal cancer .

folinic acid

ifosfamide

5-fluorouracil ( 5-FU )

folinic acid ( FA

ifosfamide

FA

FA

IFO

partial response

complete

partial response

Time to failure

median

survival time

Diarrhea

stomatitis

vomiting

nonhematologic toxicities

hematologic toxicity

leukopenia

advanced colorectal cancer

colorectal cancer

Forty-eight

Forty-five


Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain . OBJECTIVE The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain . BACKGROUND Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen . METHODS In this randomized , parallel-group , double-blind , repeated-dose , active-comparator , 4-week , multicenter study , 469 patients were randomly assigned to receive a 1-tablet ( n = 156 ) or 2-tablet ( n = 153 ) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg ( HI1 and HI2 , respectively ) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg ( CA , n = 160 ) , the active comparator , every 6 to 8 hours as needed for pain . Efficacy was measured through pain relief scores , number of daily doses of study medication , number of daily doses of supplemental analgesics , number of patients who discontinued therapy due to an unsatisfactory analgesic response , and global assessment scores . RESULTS Of the 469 patients , 255 ( 54.4 % ) were female and 214 ( 45.6 % ) were male . The mean age was 51.1 years . Types of chronic pain included back ( 214 ; 45.6 % ) , arthritic ( 145 ; 30.9 % ) , other musculoskeletal ( 65 ; 13.9 % ) , cancer ( 6 ; 1.3 % ) , diabetic neuropathic ( 3 ; 0.6 % ) , postherpetic neuralgic ( 5 ; 1.1 % ) , other neurologic ( 21 ; 4.5 % ) , and other unclassified chronic pain ( 10 ; 2.1 % ) . During the 48 hours prior to the study , 351 ( 74.8 % ) patients had been treated with opioid or opioid-nonopioid combination analgesics . The overall mean daily pain relief score was significantly greater in the HI2 group ( 2.25+/-0.89 ) than in the HI1 group ( 1.98+/-0.87 ) ( P = 0.003 ) or the CA group ( 1.85+/-0.96 ) ( P < 0.001 ) . The overall mean number of daily doses of study medication was significantly less in the HI2 group ( 2.94+/-0.99 ) than in the HI1 group ( 3.23+/-0.76 ) ( P = 0.036 ) or the CA group ( 3.26+/-0.75 ) ( P = 0.014 ) . The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group ( 0.24+/-0.49 ) than in the HI1 group ( 0.34+/-0.58 ) ( P = 0.021 ) or CA group ( 0.49+/-0.85 ) ( P = 0.010 ) . The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group ( 2 ; 1.3 % ) than in the CA group ( 12 ; 7.5 % ) ( P = 0.008 ) . HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 ( P < 0.001 vs HI1 and CA ) , week 2 ( P < 0.001 vs HI1 and CA ) , and week 3 ( P = 0.008 vs HI1 and P < 0.001 vs CA ) ; daily doses of study medication for week 1 ( P = 0.019 vs HI1 and P = 0.011 vs CA ) ; daily doses of supplemental analgesics for week 1 ( P = 0.010 vs HI1 and CA ) ; and global assessment scores for week 1 ( P = 0.018 vs HI1 and P < 0.001 vs CA ) , week 2 ( P = 0.005 vs HI1 and P < 0.001 vs CA ) , and week 4 ( P = 0.013 vs HI1 and P = 0.023 vs CA ) . There were no significant differences between HI1 and CA in any efficacy variable . There were no significant differences in the number of patients experiencing adverse events in the HI2 ( 127 ; 83 % ) , HI1 ( 124 ; 79.5 % ) , and CA ( 129 ; 80.6 % ) groups . However , the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group ( 40 ; 26.1 % ) than in the HI1 group ( 23 ; 14.7 % ) ( P = 0.013 ) . CONCLUSIONS The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg . Moreover , 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg .

hydrocodone and ibuprofen

codeine and acetaminophen

hydrocodone

ibuprofen

codeine

acetaminophen

Hydrocodone

ibuprofen

codeine 30 mg and acetaminophen 300 mg

hydrocodone

ibuprofen

codeine

acetaminophen

codeine

acetaminophen

pain relief scores

overall mean daily pain relief score

pain relief scores

daily doses of study medication

daily doses of supplemental analgesics

efficacy

chronic pain

female

male

51.1 years

chronic pain

back

arthritic

other musculoskeletal

cancer

diabetic neuropathic

postherpetic neuralgic

other neurologic

unclassified chronic pain


The effect of halothane and isoflurane on plasma cytokine levels . The aim of this study was to investigate the effect of halothane vs. isoflurane on cytokine production during minor elective surgery . Forty adult patients , ASA I-II were randomly allocated to receive halothane or isoflurane . Venous samples for interleukin ( IL ) -1beta , IL-2 , IL-6 , tumour necrosis factor-alpha ( TNF-alpha ) and interferon-gamma ( IFN-gamma ) were taken before anaesthesia , before incision , at the end of anaesthesia and 24 h postoperatively . In both groups , IL-6 and TNF-alpha levels remained low throughout the study period . Before incision , in both groups IL-1beta and IFN-gamma showed a decrease ( p < 0.01 for IL-1beta in isoflurane group and p < 0.05 for the others ) compared with pre-induction . By the end of anaesthesia and surgery , IL-1beta had increased significantly ( p < 0.05 ) and IFN-gamma had decreased significantly ( p < 0.05 ) in both groups compared with pre-incisional levels . By 24 h postoperatively in both groups , IL-1beta had decreased significantly ( p < 0.05 ) , whereas IFN-gamma had increased significantly ( p < 0.05 ) compared with the end of anaesthesia and surgery level . Pre-incisionally , IL-2 increased in the halothane group ( p < 0.01 ) , whereas it decreased significantly in the isoflurane group ( p < 0.001 ) compared with the pre-induction level . By the end of anaesthesia and surgery and by 24 h postoperatively , IL-2 had decreased significantly in the halothane group ( p < 0.001 ) , whereas it increased significantly in the isoflurane group ( p < 0.001 ) compared with pre-incision and end of anaesthesia and surgery levels , respectively .

halothane

isoflurane

halothane

isoflurane

halothane

isoflurane

halothane

isoflurane

halothane

isoflurane

plasma cytokine levels

cytokine production

IL-6 and TNF-alpha levels

IL-1beta and IFN-gamma

IFN-gamma

IFN-gamma


A comparative efficacy and safety study of clarithromycin , roxithromycin and erythromycin stearate in mild pneumonia . The efficacy and safety of clarithromycin , roxithromycin and erythromycin stearate in mild pneumonia were compared in an open randomized trial . Eighty-six male patients , doing their obligatory military service , ranging between 19 and 24 years of age ( mean 20 ) , were randomly treated : 29 with clarithromycin 500 mg 12-hourly , 30 with roxithromycin 150 mg 12-hourly , and 27 with erythromycin stearate 500 mg 6-hourly , each course being administered for 10 days . Seventy-eight patients were able to be evaluated for efficacy , 28 receiving clarithromycin , 28 roxithromycin , and 22 erythromycin stearate . There were no significant differences among the groups in terms of clinical success rates ( clinical cure or improvement : 89 % for clarithromycin , 82 % for roxithromycin , and 73 % for erythromycin stearate , p = 0.32 ) . However , we found that there were significant differences among the groups in terms of clinical cure rates ( 75 % for clarithromycin , 64 % for roxithromycin , and 41 % for erythromycin stearate , p = 0.04 ) . Adverse events , mostly gastrointestinal , caused discontinuation of treatment in 3.4 % of the patients in the clarithromycin group , in 6.6 % of the patients in the roxithromycin group , and in 18.5 % of the patients in the erythromycin stearate group . The results indicate that there were no statistically significant differences among the three treatment groups in terms of clinical success rates , but that clarithromycin and roxithromycin were better tolerated .

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin 500 mg 12-hourly

roxithromycin

erythromycin

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin

roxithromycin

erythromycin stearate

clarithromycin

roxithromycin

efficacy and safety

efficacy and safety

efficacy

terms of clinical success rates

clinical cure rates

tolerated

pneumonia

Eighty-six

male

19 and 24 years

Seventy-eight


The anesthetic and recovery profile of two doses ( 60 and 80 mg ) of plain mepivacaine for ambulatory spinal anesthesia . UNLABELLED Reports of transient neurological symptoms with the use of subarachnoid lidocaine has generated interest in alternate local anesthetics of intermediate duration , such as mepivacaine . This prospective randomized , double-blinded , dose-response study examined the anesthetic and recovery profiles of 60- and 80-mg doses of preservative-free plain mepivacaine for ambulatory spinal anesthesia . Sixty patients undergoing ambulatory anterior cruciate ligament repair of the knee under spinal anesthesia were randomized into two groups ; Group 1 ( 29 patients ) received 4 mL of 1.5 % ( 60-mg dose ) and Group 2 ( 31 patients ) received 4 mL of 2 % ( 80-mg dose ) of plain mepivacaine . All patients received a combined spinal-epidural anesthetic technique . The epidural catheter was used only in the event the surgery outlasted the duration of surgical anesthesia with subarachnoid mepivacaine . Epidural supplementation was administered in three patients ( 12 % ) in Group 1 and one patient ( 3 % ) in Group 2 when the sensory block regressed to L-1 with surgery expected to last longer than 15 min . The cephalad dermatome level of the block and degree of motor block was comparable in the two groups . Times to two-segment and T-10 regression were comparable in the two groups ( 112 +/- 26 min in Group 1 versus 122 +/- 28 min in Group 2 ) . Time to L-1 regression was significantly longer in Group 2 ( 146 +/- 28 min in Group 1 versus 159 +/- 19 min in Group 2 ) . All of the ambulatory milestones were significantly faster in Group 1 . Side effects , such as hypotension and emesis were negligible , severe bradycardia and urinary retention did not occur , and none of the patients in the two groups reported transient neurological symptoms over 24 h. In conclusion , plain mepivacaine in a 60- or 80-mg dose is a suitable local anesthetic choice for ambulatory spinal anesthesia with respect to anesthetic , as well as recovery profiles . IMPLICATIONS We evaluated the anesthetic and recovery profiles of 60- and 80-mg doses of plain mepivacaine for ambulatory spinal anesthesia . Both doses produced comparable sensory and motor block . Sensory and motor regression and ambulatory milestones were 20-30 min longer with the 80-mg dose . Side effects were negligible and transient neurological symptoms were not reported during a 24-h follow-up .

plain mepivacaine

subarachnoid lidocaine

mepivacaine

preservative-free plain mepivacaine

plain mepivacaine

spinal-epidural anesthetic technique

subarachnoid mepivacaine

mepivacaine

cephalad dermatome level of the block

degree of motor block

Times to two-segment

T-10 regression

Time to L-1 regression

hypotension

and

emesis

bradycardia

urinary retention

transient neurological symptoms

Sensory and motor regression

Side effects

transient neurological symptoms

spinal anesthesia .

Sixty patients

spinal anesthesia


Epirubicin-based chemotherapy in metastatic breast cancer patients : role of dose-intensity and duration of treatment . PURPOSE To determine whether the duration and the dose of epirubicin modify the long-term outcome of patients with metastatic breast cancer ( MBC ) . PATIENTS AND METHODS Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens : arm A : 11 cycles of fluorouracil 500 mg/m ( 2 ) , epirubicin 75 mg/m ( 2 ) , and cyclophosphamide 500 mg/m ( 2 ) ( FEC 75 ) every 21 days ; arm B : four cycles of FEC 100 ( same regimen but with epirubicin 100 mg/m ( 2 ) ) then eight cycles of FEC 50 ( epirubicin 50 mg/m ( 2 ) ) ; and arm C : four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization . RESULTS Hematologic toxicity was similar . Nausea/vomiting and stomatitis were significantly less frequent in arm A as was left ventricular ejection fraction decrease in arm C ( A = six patients , B = five patients , and C = one patient ) . Six patients died of infections ( A = four patients and C = two patients ) . After four cycles , the objective response rate ( ORR ) was better with FEC 100 than with FEC 75 ( 49.2 % v 40 % , respectively ; P : =.07 ) . The ORR was better with the longer regimens ( arm A , 56.9 % ; B , 64 % ; and C , 47.6 % ; P : =.06 ) and was 41 % after second-line FEC 100 . After a median follow-up of 41 months , the response duration and time to progression ( TTP ) were significantly better with arm B , the longer regimen ( P : =.012 and P : < 10 ( -3 ) , respectively ) . The median survival times for arms A , B , and C were similar ( 17.9 , 18.9 , and 16 . 3 months , respectively ; P : =.49 ) . CONCLUSION In MBC , longer epirubicin-based regimens are better in terms of response duration and TTP . FEC 100 regimens improve the ORR . However , four initial cycles of FEC 100 and identical retreatment at disease progression yielded equivalent overall survival to longer regimens .

Epirubicin-based chemotherapy

epirubicin

fluorouracil

epirubicin

cyclophosphamide

FEC

FEC 100

epirubicin

FEC 50 ( epirubicin

FEC 100

FEC

FEC

FEC

FEC

FEC

Hematologic toxicity

Nausea/vomiting and stomatitis

left ventricular ejection fraction

died of infections

objective response rate ( ORR )

ORR

median survival times

response duration and TTP

ORR

overall survival

metastatic breast cancer

metastatic breast cancer ( MBC )

Four hundred seventeen

anthracycline-naive MBC


The effect of case management on the costs of health care for enrollees in Medicare Plus Choice plans : a randomized trial . OBJECTIVE To measure the effects of case management on an older population 's costs of health care . DESIGN A 1-year randomized controlled trial . SETTING Multiple sites of care in San Francisco , California . PARTICIPANTS Patients aged 65 or older of primary care physicians in a large provider organization bearing financial risk for their care ( n = 6409 ) . INTERVENTION Screening for high risk and provision of social work-based case management . OUTCOME MEASURES Volume and cost of hospital , physician , case management , and other health-related services . RESULTS The experimental group used more case management services than the control group ( 0.09 vs. 0.02 months per person , P < .001 ) . The experimental group 's average total payments for health care were slightly lower ( $ 3148 vs $ 3277 , P = .40 ) . CONCLUSIONS This study provides no statistically significant evidence that social work-oriented case management reduces the use or the cost of health care for high-risk older people . Other potentially favorable effects of this type of case management need to be evaluated , as do the effects of other types of case management .

case management

social work-based case management

costs of health care

costs of health care

case management services

total payments for health care

cost of health care

older population 's

aged 65 or older


Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers . BACKGROUND It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness . The authors investigated the effect of altering central cholinergic transmission , by physostigmine and scopolamine , on unconsciousness produced by propofol . METHODS Propofol was administered to American Society of Anesthesiologists physical status 1 ( n = 17 ) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted ( inability to respond to verbal commands , abolition of spontaneous movement ) . Central nervous system function was assessed by use of the Auditory Steady State Response ( ASSR ) and Bispectral Index ( BIS ) analysis of electrooculogram . During continuous administration of propofol , reversal of unconsciousness produced by physostigmine ( 28 microgram/kg ) and block of this reversal by scopolamine ( 8.6 microgram/kg ) were evaluated . RESULTS Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 ( +/- SD ) microgram/ml ( n = 17 ) . Unconsciousness was associated with reductions in ASSR ( 0.10 +/- 0.08 microV [ awake baseline 0.32 +/- 0.18 microV ] , P < 0.001 ) and BIS ( 55.7 +/- 8.8 [ awake baseline 92.4 +/- 3.9 ] , P < 0.001 ) . Physostigmine restored consciousness in 9 of 11 subjects , with concomitant increases in ASSR ( 0.38 +/- 0.17 microV , P < 0.01 ) and BIS ( 75.3 +/- 8.3 , P < 0.001 ) . In all subjects ( n = 6 ) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS ( ASSR and BIS during propofol-induced unconsciousness : 0.09 +/- 0.09 microV and 58.2 +/- 7.5 , respectively ; ASSR and BIS after physostigmine administration : 0.08 +/- 0.06 microV and 56.8 +/- 6.7 , respectively , NS ) . CONCLUSIONS These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission .

Physostigmine

physostigmine

scopolamine

Propofol

physostigmine

scopolamine

Central nervous system function

reversal of unconsciousness

block of this reversal

unconsciousness

plasma concentration

Unconsciousness

ASSR

BIS

restored consciousness

ASSR

BIS

ASSR and BIS


Influence of asimadoline , a new kappa-opioid receptor agonist , on tubular water absorption and vasopressin secretion in man . AIMS The purpose of the study was to investigate the effects of asimadoline , a new kappa-opioid agonist , on renal function and on hormones related to body fluid balance as well as its tolerability in healthy subjects . METHODS In a placebo-controlled , randomised , double-blind crossover design we studied the effects of single oral doses of 1 , 5 , and 10 mg of asimadoline , in 24 healthy volunteers . Two hour control urine collections were followed by 2 h postdose urine collections and subsequently 2.5 % saline was given i.v . at a rate of 0.3 ml min ( -1 ) kg ( -1 ) during another 2 h urine collection . Blood was obtained hourly . Arginine-vasopressin ( AVP ) , atrial natriuretic peptide ( alpha-hANP ) , endothelin ( ET-1 ) and cAMP were determined by r.i.a . or ELISA . RESULTS GC-MS measurements revealed Cmax values of asimadoline in plasma ranging from 18 ng ml ( -1 ) at the 1 mg dose , 91 ng ml ( -1 ) at the 5 mg dose , to 214 ng ml ( -1 ) at the 10 mg dose after an average of 1.1-1.4 h. Without effects on blood pressure , heart rate , GFR or urine electrolyte excretion , urine volume increased after 1-2 h after administration of 5 and 10 mg asimadoline from 3.3+/-1.3 to 5.6+/-1.4 ( P < 0.05 ) and from 3.2 +/-1.6 to 5.5+/-2.2 ml min ( -1 ) ( P < 0.01 ) , respectively . CH2O rose from 0.2+/-1.5 to 2.0+/-1.6 ( P < 0.05 ) and from 0.6+/-1.6 to 3.0+/-1.6 ml min ( -1 ) ( P < 0.01 ) . Urinary excretion of AVP was suppressed only with the 10 mg dose from 46+/-23 to 25+/-15 fmol min ( -1 ) ( P < 0.05 ) without and from 410+/-206 to 181+/-125 fmol min ( -1 ) ( P < 0.05 ) with stimulation by 2.5 % saline . Plasma AVP was suppressed only by the 10 mg dose of asimadoline in six of eight subjects during the 2.5 % saline infusion . Changes in the alpha-hANP or ET-1 systems were not affected by asimadoline . CONCLUSIONS Asimadoline is diuretic in man after single doses of 5 or 10 mg probably through a direct effect at the renal tubular level . Suppression of AVP secretion was observed only at the highest dose level of 10 mg of asimadoline .

asimadoline

asimadoline

placebo-controlled

1 , 5 , and 10 mg of asimadoline

2.5 % saline

effects

endothelin ( ET-1 )

cAMP

Cmax values of asimadoline in plasma

blood pressure

heart rate

GFR

urine electrolyte excretion

urine volume

Urinary excretion

Plasma AVP

vasopressin secretion in

man

healthy subjects


Uvulopalatopharyngoplasty versus laser assisted uvulopalatoplasty for the treatment of snoring : an objective randomised clinical trial . This study was designed to evaluate objectively the clinical effectiveness of surgery for snoring and to compare the results of conventional uvulopalatopharyngoplasty ( UPPP ) and laser assisted uvulopalatoplasty ( LAUP ) in the treatment of snoring . Patients who had been referred for investigation and treatment of their snoring were randomly allocated to receive either UPPP or LAUP . Forty-seven patients with confirmed palatal flutter had surgery and all of them had a preoperative and postoperative objective assessment of their snoring loudness and duration in the home . The recording device ( Snore Box ) is simple for the patient to operate , portable with a built in microphone , and able to produce objective results , which can be automatically analysed . Of the 38 patients , who had technically valid recordings , 22 underwent LAUP and 16 UPPP . Overall the mean postoperative Snore Index ( SI ) was less than the preoperative SI ( P < 0.0001 ) , the average difference being 78.2 snores/h . There was no significant difference between the LAUP and UPPP regarding the fall in the SI . This study is the first objective comparative study to demonstrate the effectiveness of snoring surgery .

Uvulopalatopharyngoplasty

laser assisted uvulopalatoplasty

UPPP

LAUP

LAUP

snoring loudness

duration in the home

mean postoperative Snore Index ( SI )

SI

SI

effectiveness of snoring surgery

snoring

Forty-seven