Utilization of health care services by patients with chronic obstructive pulmonary disease . In order to identify healthcare resource use patterns associated with chronic obstructive pulmonary disease ( COPD ) , resource utilization ( RU ) data collection was integrated into a randomized , double-blind placebo-controlled study of Viozan ( sibenadet HCl ) . This study enrolled patients with symptomatic , smoking-related COPD , randomized to receive sibenadet or placebo for a 52-week treatment period . A questionnaire establishing typical pre-trial , COPD-related RU was completed by each patient . Subsequent data were collected by means of an Interactive Voice Response System ( IVRS ) at 30-day intervals ( 14 time points ) during the study and in the follow-up period . The IVRS system facilitated data collection and minimized inconvenience to the patient . Compliance with the requirement to record details of the healthcare services during the year-long study was high . No overall trend for lower RU was associated with sibenadet therapy , which correlates with the lack of sustained clinical effect seen in studies conducted concurrently . These data do , however , provide valuable information on RU associated with COPD and insights into adjustments associated with changes in disease course . Physicians were seen to be the most common source of care for patients with COPD and more of the patients with severe COPD ( stage III ) than mild ( stage I ) were seen to utilize the most expensive resources ( e.g . inpatient hospital care ) . For those patients who experienced an exacerbation during the trial ( irrespective of treatment group ) , resource use was increased during the periods when an exacerbation was reported when compared with the periods before or after an exacerbation . The proportion of cases attending the physician doubled and with a trip to the Emergency Room ( ER ) increased approximately ninefold during the reporting period in which the exacerbation occurred compared with the previous month . This study has shown that use of an IVRS , even in elderly patients , is an effective means of gathering RU data over long periods . The study findings suggest that the advent of effective therapeutic interventions , particularly any with the ability to minimize exacerbations and limit disease progression , could impact on the health care services used and potentially reduce associated costs .

placebo-controlled

sibenadet

placebo

Interactive Voice Response System

healthcare resource use patterns

RU

inpatient hospital care

resource use

chronic obstructive pulmonary disease

chronic obstructive pulmonary disease

COPD

symptomatic , smoking-related COPD

severe COPD ( stage III )

mild ( stage I )

elderly


Topical imiquimod 5 % cream as an effective treatment for external genital and perianal warts in different patient populations . BACKGROUND Genital infection with human papillomavirus , the cause of genital warts , is one of the most common sexually transmitted diseases . GOAL The aim of this analysis was to determine whether patients ' demographic variables affect the efficacy of imiquimod 5 % cream versus vehicle cream for the treatment of external genital and perianal warts . STUDY DESIGN Male and female immunocompetent patients applied imiquimod 5 % cream topically to external genital warts 3 times a week until wart clearance or for up to 16 weeks . RESULTS As previously published , the intent-to-treat ( ITT ) clearance rate was 50 % ( 54/109 ) in the imiquimod-treated group and 11 % ( 11/100 ) in the vehicle-treated group ( P < 0.0001 ) . The ITT clearance rate in the imiquimod-treated group was higher in females ( 72 % ) than in males ( 33 % ) . We have examined the clearance rates for subgroups based on variables of gender , baseline wart area , duration of current outbreak of warts , previous wart treatment , and tobacco use . For each of these subgroups , imiquimod was statistically more effective than vehicle in eradicating external genital and perianal warts . CONCLUSION Imiquimod 5 % cream is an effective treatment for external genital and perianal warts and provides a significant benefit in comparison with vehicle cream , independent of gender , initial wart size , duration of current outbreak of warts , previous wart treatment , or tobacco use .

imiquimod 5 % cream

imiquimod 5 % cream

vehicle cream

imiquimod 5 % cream topically

imiquimod-treated

vehicle-treated

imiquimod-treated

imiquimod

vehicle

Imiquimod 5 % cream

vehicle

genital and perianal

intent-to-treat ( ITT ) clearance rate

ITT clearance rate

effective

external genital and perianal warts

wart treatment , or tobacco use

external genital and perianal warts

external genital and perianal warts

Male

female

immunocompetent

wart

warts

genital and perianal warts


Carbon dioxide versus normal saline as a uterine distension medium for diagnostic vaginoscopic hysteroscopy in infertile patients : a prospective , randomized , multicenter study . OBJECTIVE To evaluate the satisfaction rate , efficacy , and complication rate of carbon dioxide ( CO ( 2 ) ) versus normal saline as a uterine distension medium for outpatient diagnostic vaginoscopic hysteroscopy in infertile patients . DESIGN Prospective , randomized multicenter study . SETTING Hysteroscopy units in two university hospitals and in a private center . PATIENT ( S ) One hundred eighty-nine infertile women undergoing outpatient hysteroscopy . INTERVENTION ( S ) Outpatient hysteroscopy was performed with CO ( 2 ) ( group A ) or normal saline ( group B ) and with endometrial biopsy when indicated . MAIN OUTCOME MEASURE ( S ) Quality of the visualization of the uterine cavity , procedure time , complications , patient discomfort , and satisfaction rate . RESULT ( S ) Significantly lower abdominal and shoulder tip pain and a lower incidence of vasovagal reactions were observed in group B in comparison with group A . A higher satisfaction rate and a lower operative time were obtained in the normal saline group in comparison with the CO ( 2 ) group . Moreover , group A required significantly more analgesics after the procedure than group B . CONCLUSION ( S ) Uterine distension with normal saline seems to have less adverse effects and is better tolerated by patients . Moreover , it allows operative procedures to be performed with the new bipolar instruments .

Carbon dioxide

normal saline

carbon dioxide ( CO ( 2 ) )

normal saline

CO ( 2 ) ( group A )

normal saline ( group B )

endometrial biopsy

CO ( 2 )

satisfaction rate

efficacy

complication rate

procedure time

complications

patient discomfort

satisfaction rate

abdominal and shoulder tip pain

vasovagal reactions

higher satisfaction rate

lower operative time

infertile

One hundred eighty-nine

infertile

women


Liposome-entrapped D. pteronyssinus vaccination in mild asthma patients : effect of 1-year double-blind , placebo-controlled trial on inflammation , bronchial hyperresponsiveness and immediate and late bronchial responses to the allergen . BACKGROUND Allergen vaccination is effective in mite-allergic asthma . Liposomes are immunological adjuvants that can act as allergen carriers . OBJECTIVE To evaluate the immunological and functional effects of a liposome-entrapped D. pteronyssinus vaccine on mite monosensitive , mild asthma patients . METHODS A double-blind , placebo-controlled trial was conducted on 26 asthma patients who randomly received vaccination or placebo for 1 year . The levels of exposure to Der p 1 allergen were constant during the study . Allergen bronchial challenge was made at the beginning ( T0 ) and after 1 year of treatment ( T12 ) . The day before and 24 h after the allergen provocation , patients were challenged with methacholine ( Mth ) ( until FEV1 fell by 40 % ) and blood and sputum samples were obtained . Dose-response curves to Mth were evaluated in terms of Mth-PD20 ( dose of Mth that induced 20 % drop in FEV1 ) , slope ( Mth-DRS ) and level of plateau . Blood and sputum eosinophils and serum levels of eosinophil cationic protein ( ECP ) and intercellular adhesion molecule-1 ( ICAM-1 ) were measured . RESULTS Groups were comparable at the start of the trial . At TI2 , previous to the allergen challenge , the active group showed higher values of both FEV1 and Mth-PD20 and lower values of Mth-DRS . The number of patients presenting a level of plateau increased in the active group ( from two to four ) and decreased in the placebo group ( from two to one ) . At T12 , before the allergen challenge , serum ECP levels increased in the placebo group and blood eosinophils showed a trend towards lower numbers in the active one . The immediate response and the changes in Mth-DRS values , sputum eosinophils and serum ECP levels following the allergen challenge were attenuated in the active group . CONCLUSION Liposome-entrapped D. Pteronyssinus vaccination : ( i ) protects mild asthma patients from the worsening of asthma due to sustained mite exposure ; and ( ii ) reduces the functional and inflammatory changes induced by allergen bronchial provocation .

placebo-controlled

placebo

methacholine

FEV1 and Mth-PD20

Mth-DRS

serum ECP levels

mild asthma patients :

mild asthma patients


The results of a randomized study on the use of long-acting octreotide in hepatocellular carcinoma .

octreotide

hepatocellular carcinoma


Low-dose mifepristone for uterine leiomyomata . OBJECTIVE To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms , and to measure side effects . METHODS Forty premenopausal women with large , symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study . Uterine volume was measured at bimonthly intervals by sonography . Serum concentrations of hemoglobin levels , follicle-stimulating hormone , and liver enzymes were obtained , and endometrial samples , symptoms , and menstrual bleeding were also assessed . RESULTS Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study . Mean uterine volume shrank by 48 % ( P < .001 ) in the 5-mg group and 49 % ( P < .001 ) in the 10-mg group , a nonsignificant difference . Leiomyoma-related symptoms were comparably reduced in both groups . Amenorrhea occurred in 60-65 % of both groups . Hemoglobin levels increased by 2.5 g/dL in anemic subjects . The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group . Simple endometrial hyperplasia occurred in 28 % of all subjects , with no difference between groups . No atypical hyperplasia was noted . CONCLUSION Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression , improvement in symptoms , and few side effects . Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone .

mifepristone

mifepristone

Mifepristone

mifepristone

uterine leiomyoma size and symptoms

Mean uterine volume shrank

Leiomyoma-related symptoms

Amenorrhea

Hemoglobin levels

hot flashes

Simple endometrial hyperplasia

atypical hyperplasia

leiomyoma regression

improvement in symptoms

few side effects


Enteral nutrition with eicosapentaenoic acid , gamma-linolenic acid , and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome . OBJECTIVE Previously , we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants ( EPA+GLA ; Oxepa ) had significantly reduced pulmonary inflammation , increased oxygenation , and improved clinical outcomes . In a subset of acute respiratory distress syndrome patients from this trial , we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin ( IL ) -8 , IL-6 , tumor necrosis factor-alpha , and leukotriene B4 that are responsible , in part , for pulmonary inflammation . DESIGN Prospective , randomized , double-blind , controlled clinical trial . SETTING Intensive Care Unit of the Ohio State University Medical Center . PATIENTS A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome . INTERVENTIONS A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous , isocaloric standard diet that was tube fed at a minimum caloric delivery of 75 % of basal energy expenditure times 1.33 for at least 4 to 7 days . MEASUREMENTS AND MAIN RESULTS Bronchoalveolar lavage ( BAL ) was performed at baseline and study days 4 and 7 to obtain BAL fluid ( BALF ) for measurement of total protein , ceruloplasmin , and transferrin , total neutrophil count , IL-8 , IL-6 , tumor necrosis factor-alpha , and leukotriene B4 . Oxygenation , measured as Pao2/Fio2 , was assessed before BAL . Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet . BALF levels of total protein , neutrophils , and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients . BALF levels of IL-6 declined similarly during the study in both groups . A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients . Significant improvements in oxygenation ( Pao2/Fio2 ) occurred in EPA+GLA patients on study day 4 as compared with controls . Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability , IL-8 , and leukotriene B4 . CONCLUSIONS This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support , in part , the potential mechanisms underlying the previously described clinical improvements with this diet . Additional controlled studies are needed to confirm these findings .

antioxidants

eicosapentaenoic acid

gamma-linolenic acid

antioxidants

isonitrogenous

EPA+GLA

Bronchoalveolar lavage ( BAL )

total protein

ceruloplasmin

transferrin

total neutrophil count

IL-6 , tumor necrosis factor-alpha

leukotriene B4

Oxygenation

BALF ceruloplasmin

total protein

neutrophils

leukotriene B4

tumor necrosis factor-alpha

oxygenation

neutrophil

leukotriene


S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications . The F-box protein S-phase kinase-associated protein 2 ( Skp2 ) positively regulates the G1-S transition by controlling the stability of several G1 regulators , such as the cell cycle inhibitor p27kip1 . However , the clinical significance of Skp2 in patients with laryngeal squamous cell carcinoma ( LSCC ) remains unknown . In this study , a potential distribution of Skp2 in LSCC and its clinical implications was investigated by an immunohistochemical study . Overall , Skp2 overexpression was observed in 36.7 % ( 37 of 102 ) patients and was significantly associated with lymph node metastasis ( p=0.002 ) and was inversely associated with p27kip1 expression ( p=0.026 ) . Survival analysis using the Kaplan-Meier method showed that Skp2 overexpression was significantly associated with shorter disease-free and overall survival ( p=0.0051 and p=0.0002 , respectively ) . When Skp2 expression and p27kip1 expression were combined , patients with both Skp2 overexpression and reduced expression of p27kip1 revealed poorest disease-free and overall survival as compared to the other cases ( p=0.0017 and p < 0.0001 , respectively ) . Additionally , in early stage ( I , II ) cases , Skp2 expression was also revealed to possess a significant prognostic factor in overall survival ( p=0.0234 ) , but not in disease-free survival ( p=0.2055 ) . By multivariate analysis using the Cox proportional hazards model , tumor grade , tumor size , clinical stage and Skp2 expression were independent prognostic factors both in disease-free and overall survival . These findings indicated that Skp2 expression was closely associated with tumor progression and represented an independent marker for prognosis of LSCC .

S-phase kinase-associated protein

S-phase kinase-associated protein

immunohistochemical study

Skp2 overexpression

Survival analysis

disease-free and overall survival

Skp2 expression

p27kip1 expression

expression of p27kip1

poorest disease-free

overall survival

overall survival ( p=0.0234 )

disease-free survival

disease-free and overall survival .

Skp2 expression

laryngeal squamous cell carcinomas

LSCC


Double-blind , placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders . L-Carnosine , a dipeptide , can enhance frontal lobe function or be neuroprotective . It can also correlate with gamma-aminobutyric acid ( GABA ) -homocarnosine interaction , with possible anticonvulsive effects . We investigated 31 children with autistic spectrum disorders in an 8-week , double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo . Outcome measures were the Childhood Autism Rating Scale , the Gilliam Autism Rating Scale , the Expressive and Receptive One-Word Picture Vocabulary tests , and Clinical Global Impressions of Change . Children on placebo did not show statistically significant changes . After 8 weeks on L-carnosine , children showed statistically significant improvements on the Gilliam Autism Rating Scale ( total score and the Behavior , Socialization , and Communication subscales ) and the Receptive One-Word Picture Vocabulary test ( all P < .05 ) . Improved trends were noted on other outcome measures . Although the mechanism of action of L-carnosine is not well understood , it may enhance neurologic function , perhaps in the enterorhinal or temporal cortex .

placebo-controlled

L-carnosine supplementation

L-Carnosine

dipeptide

L-carnosine

placebo

placebo

L-carnosine

L-carnosine

Childhood Autism Rating Scale

children

autistic spectrum disorders


The development and evaluation of a computer-based program to test and to teach the recognition of facial affect . Autism is a chronic pervasive neurodevelopmental disorder characterized by the early onset of social and communicative impairments as well as restricted , ritualized , stereotypic behavior . The endophenotype of autism includes neuropsychological deficits , for instance a lack of " Theory of Mind " and problems recognizing facial affect . In this study , we report the development and evaluation of a computer-based program to teach and test the ability to identify basic facially expressed emotions . 10 adolescent or adult subjects with high-functioning autism or Asperger-syndrome were included in the investigation . A priori the facial affect recognition test had shown good psychometric properties in a normative sample ( internal consistency : rtt=.91-.95 ; retest reliability : rtt=.89-.92 ) . In a prepost design , one half of the sample was randomly assigned to receive computer treatment while the other half of the sample served as control group . The training was conducted for five weeks , consisting of two hours training a week . The trained individuals improved significantly on the affect recognition task , but not on any other measure . Results support the usefulness of the program to teach the detection of facial affect . However , the improvement found is limited to a circumscribed area of social-communicative function and generalization is not ensured .

computer-based program

computer-based program

computer treatment

facial affect .

basic facially expressed emotions

affect recognition task

teach the detection of facial affect

adolescent

adult


Fluvoxamine as effective as clomipramine against symptoms of severe depression : results from a multicentre , double-blind study . BACKGROUND Although selective serotonin reuptake inhibitors ( SSRIs ) are better tolerated than tricyclic antidepressants , their efficacy in severe depression remains to be further elucidated . METHOD A double-blind , multicentre study was conducted in 86 severely depressed inpatients ( > or= 25 on the 17-item Hamilton depression rating scale [ HAMD ] total score ) to compare the efficacy and safety of fluvoxamine with that of clomipramine . Following placebo run-in , 86 patients were randomised to receive fluvoxamine or clomipramine ( 100-250 mg/day ) for 8 weeks . RESULTS Fluvoxamine and clomipramine both resulted in marked improvements ; there were no statistically significant differences between them on the 17-item HAMD total score , the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale , at any visit . At the end of the study , 71 % in the fluvoxamine group and 69 % in the clomipramine group were responders ( > or= 50 % decrease in 17-item HAMD total score ) . However , fluvoxamine was better tolerated than clomipramine . Clomipramine was associated with a higher incidence of overall and treatment-related adverse events . In addition , the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine ( 24 % vs 11 % ) . CONCLUSION Fluvoxamine and clomipramine are equally effective in severe depression , but fluvoxamine has a better safety and tolerability profile .

Fluvoxamine

clomipramine

fluvoxamine

clomipramine .

placebo

fluvoxamine or clomipramine

severe depression

efficacy

efficacy

safety

improvements

17-item HAMD total score

17-item HAMD total score )

tolerated

adverse events

discontinued prematurely

adverse events

safety

tolerability

severe depression

depression


Bioavailability of omega-3 essential fatty acids from perilla seed oil . Increased dietary intake of fish oil omega-3 fatty acids , eicosapentanoic acid and docosohexanoic acid , and their precursor , alpha-linolenic acid ( ALA ) , is associated with various health benefits . Enteric-coating ( Entrox ) , which improves stability of omega-3 capsules , has been shown to facilitate fish oil absorption after chronic treatment . To assess the effect of Entrox coating on the short-term bioavailability of ALA administered in the form of ALA-rich Perilla seed oil , 12 healthy subjects ( 6 males and 6 females ) received in a random order Entrox-coated and non-coated ALA formulations , each as a single 6g dose separated by a 3-week washout period . Measurements of plasma ALA concentrations from 0 to 24h showed no difference in ALA pharmacokinetics between the two formulations . However , significantly greater increases in plasma ALA levels from baseline to 24h were observed after ingestion of Entrox vs. non-coated product , suggesting a possible benefit of Entrox with long-term treatment .

omega-3 essential fatty acids

perilla seed oil

fish oil omega-3 fatty acids

alpha-linolenic acid

ALA

Bioavailability

plasma ALA concentrations

plasma ALA levels


[ The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with diabetes mellitus in the LIFE-study ] . INTRODUCTION The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear . In a prespecified analysis of the LIFE-study we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients . MATERIAL AND METHODS A total of 1195 patients in the LIFE-study had diabetes at the time of the randomisation . The patients were randomised for double-blind treatment with losartan versus atenolol . The patients had ECG-verified left ventricular hypertrophy , mean age 67 years , blood pressure 177/96 mmHg after two weeks placebo run-in period . Patients were followed for at least four years ( mean 4.7 years ) . The primary composite endpoint was cardiovascular death , stroke or myocardial infarction . RESULTS Blood pressure was reduced to 146/79 and 148/79 in losartan-treated patients and atenolol-treated patients , respectively . The primary endpoint occurred in 103 patients assigned losartan ( n = 586 ) and 139 assigned atenolol ( n = 609 ) . Relative risk reduction 24 % ( p < 0.031 ) . Cardiovascular mortality was reduced by 37 % in favour of losartan ( p < 0.028 ) , and all cause mortality by 39 % ( p < 0.002 ) . DISCUSSION Losartan was very effective in reducing cardiovascular morbidity and mortality as compared to atenolol . These results will have a major impact on the choice of anti-hypertensive treatment for patients with hypertension and diabetes .

losartan

atenolol

losartan

atenolol

losartan

atenolol

placebo

losartan-treated

atenolol-treated

losartan

atenolol

losartan

Losartan

atenolol

cardiovascular morbidity

mortality

cardiovascular morbidity

mortality

cardiovascular death

, stroke or myocardial infarction

Blood pressure

Relative risk reduction

Cardiovascular mortality

mortality

cardiovascular morbidity

mortality

diabetes mellitus

hypertension


Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis . BACKGROUND Symptoms of allergic rhinitis are mediated in part by cysteinyl leukotrienes . OBJECTIVE To evaluate the clinical benefit of montelukast , a cysteinyl leukotriene receptor antagonist , administered once daily for treating seasonal allergic rhinitis . METHODS This multicenter , randomized , double-blind , placebo- and active-controlled study enrolled 1,214 healthy , nonsmoking outpatients aged 15 to 85 years with spring allergic rhinitis , positive skin test to a spring allergen , and predefined daytime nasal symptoms . After a 3- to 5-day placebo run-in period , patients were randomly assigned to treatment with montelukast 10 mg ( n = 522 ) , loratadine 10 mg ( n = 171 ) , or placebo ( n = 521 ) once daily at bedtime for 2 weeks . During the run-in and treatment periods , symptoms were evaluated in a daily diary using a 0 ( best ) to 3 ( worst ) scale . RESULTS Baseline characteristics of randomized patients were clinically similar in the three treatment groups . Montelukast was significantly more effective than placebo ( P = 0.003 ) in improving the daytime nasal symptoms score ( difference in least square means , -0.09 ; 95 % confidence interval , -0.16 , -0.03 ) averaged over 2 weeks of therapy . The treatment effect of montelukast was significantly greater ( P < 0.05 ) , relative to placebo , for all secondary endpoints , including nighttime symptoms and daytime eye symptoms , patient and physician global evaluations of allergic rhinitis , and rhinoconjunctivitis quality of life . Loratadine , which served as a positive control , was significantly more effective than placebo for most endpoints , validating the study results . Both montelukast and loratadine were well tolerated . CONCLUSION Therapy with montelukast significantly improves assessments of symptom severity as well as quality-of-life parameters for patients with seasonal allergic rhinitis .

montelukast

placebo-

placebo

montelukast

loratadine

placebo

Montelukast

placebo

montelukast

Loratadine

montelukast

loratadine

montelukast

spring seasonal allergic rhinitis

seasonal allergic rhinitis

symptoms

daytime nasal symptoms score

rhinoconjunctivitis quality of life

well tolerated

symptom severity

quality-of-life parameters


Effects of oral Lactobacillus GG on enteric microflora in low-birth-weight neonates . BACKGROUND Colonization patterns , especially by anaerobic flora , may play an important role in neonatal gut function . Probiotics could affect disease risk either directly through colonization or indirectly by promoting changes in gut microbial ecology . METHODS To study the ability of Lactobacillus GG ( LGG ) to colonize the neonatal gut and modify its microbial ecology , a prospective , randomized study was performed in 71 preterm infants of less than 2000 g birth weight . Infants less than 1500 g ( 24 treated , 15 control ) received 10 ( 9 ) LGG orally twice daily for 21 days . Those infants weighing 1500 to 1999 g ( 23 treated , 9 control ) were treated for 8 days . Stools were collected before treatment and on day 7 to 8 ( and day 14 and 21 , in the infants weighing less than 1500 g ) for quantitative aerobic and anaerobic cultures . RESULTS Colonization with LGG occurred in 5 of 24 ( 21 % ) infants who weighed less than 1500 g versus 11 of 23 ( 47 % ) in larger infants . Colonization was limited to infants who were not on antibiotics within 7 days of treatment with LGG . There was a paucity of bacterial species at baseline , although larger infants had more bacterial species ( 1.59 +/- 0.13 ( SEM ) vs 1.11 +/- 0.12 ; P < 0.03 ) and higher mean log colony forming units ( CFU ) ( 8.79 +/- 0.43 vs 7.22 +/- 0.63 ; P < 0.05 ) compared with infants weighing less than 1500 g LGG . Treatment in infants weighing less than 1500 g resulted in a significant increase in species number by day 7 , with further increases by day 21 . This increase was mainly the result of increased Gram ( + ) and anaerobic species . No difference in species number was noted in controls . Mean log CFU of Gram ( - ) bacteria did not change in treated infants weighing less than 1500 g. However , Gram ( + ) mean log CFU showed a significant increase on day 21 ( 6.1 +/- 0.9 ) compared with day 0 ( 3.5 +/- 0.9 ) ( P < 0.05 ) . No significant changes in species number or quantitative counts were noted after LGG treatment in the infants weighing 1500 to 1999 g LGG was well tolerated in all infants . CONCLUSION The neonatal response to a probiotic preparation is dependent on gestational and post-natal age and prior antibiotic exposure . Although LGG is a relatively poor colonizer in infants , especially those infants weighing less than 1500 g at birth , it does appear to affect neonatal intestinal colonization patterns .

oral Lactobacillus GG

Lactobacillus GG ( LGG )

LGG

antibiotics

enteric microflora

disease risk

Colonization with LGG occurred

Colonization

bacterial species

mean log colony forming units ( CFU )

species number

Mean log CFU of Gram ( - ) bacteria

Gram ( + ) mean log CFU

species number or quantitative counts

LGG was well tolerated

Infants less than 1500 g

infants weighing less than 1500 g


Gastrointestinal safety of NO-aspirin ( NCX-4016 ) in healthy human volunteers : a proof of concept endoscopic study . BACKGROUND AND AIMS NCX-4016 is a nitric oxide-releasing derivative of aspirin with antiplatelet activity . The aim of this study was to investigate the effect of NCX-4016 on gastrointestinal mucosa and platelet functions in healthy human volunteers . METHODS This was a parallel-group , double-blind , placebo-controlled study . Forty healthy subjects were randomly allocated to receive 7 days of treatment with NCX-4016 ( 400 and 800 mg twice daily ) , equimolar doses of aspirin ( 200 and 420 mg twice daily ) , or placebo . Upper endoscopies were performed before and at the end of the treatment period , and gastroduodenal lesions were graded using a predefined scoring system . Basal and posttreatment platelet aggregation in response to arachidonic acid ( AA ) and serum thromboxane ( TX ) B ( 2 ) and AA-stimulated platelet TXB ( 2 ) production were investigated . RESULTS Mucosal endoscopic injury score on day 7 was 0.63 +/- 0.16 in the placebo group and 11.0 +/- 3.0 and 16.1 +/- 1.6 in healthy volunteers treated with 200 and 420 mg aspirin twice daily ( P < 0.0001 vs. placebo ) . NCX-4016 was virtually devoid of gastric and duodenal toxicity , resulting in a total gastric and duodenal endoscopic score of 1.38 +/- 0.3 and 1.25 +/- 0.5 ( P < 0.0001 vs. aspirin , not significant vs. placebo ) . NCX-4016 inhibited AA-induced platelet aggregation as well as serum TXB ( 2 ) and platelet TXB ( 2 ) generation induced by AA to the same extent as aspirin ( not significant vs. aspirin ) . CONCLUSIONS In this study , we have proven the concept that addition of an NO-donating moiety to aspirin results in a new chemical entity that maintains cyclooxygenase-1 and platelet inhibitory activity while nearly avoiding gastrointestinal damage .

NO-aspirin ( NCX-4016 )

NCX-4016 ( 400 and 800 mg twice daily )

placebo

aspirin

Gastrointestinal safety

antiplatelet activity

platelet functions

gastroduodenal lesions

predefined scoring system

Mucosal endoscopic injury score

gastric and duodenal toxicity

AA-induced platelet aggregation

serum TXB ( 2 )

platelet TXB ( 2 ) generation

gastrointestinal damage

healthy human

healthy human

Forty

healthy


ACE inhibitors or AT-1 antagonists - which is OPTIMAAL after acute myocardial infarction ? OPTIMAAL ( Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan ) is the first major study to compare an angiotensin II Type 1 antagonist losartan ( Cozaar trade mark , Merck ) with an ACE inhibitor captonpril ( Capoten trade mark , Elan ) after myocardial infarction in patients with left ventricular dysfunction . Patients were assigned to a target dose of losartan 50 mg/day and captopril 50 mg t.i.d. , as tolerated . The primary end point was all-cause mortality and there were 499 ( 18 % ) and 447 ( 16 % ) deaths in the losartan and captopril group , respectively ( p = 0.07 ) . However , there were significantly more cardiovascular deaths with losartan ( 420 , 15 % ) than with captopril ( 363 , 13 % ; p = 0.03 ) . Losartan was better tolerated than captopril with fewer patients discontinuing medication ( 17 versus 23 % for losartan and captopril , respectively ) . In conclusion , if tolerated , captopril should remain the preferred treatment for patients after complicated acute myocardial infarction .

ACE inhibitors

AT-1 antagonists

captonpril

losartan

captopril

losartan

captopril

captopril

Losartan

captopril

losartan

captopril

captopril

all-cause mortality

deaths

cardiovascular deaths

tolerated

patients discontinuing medication

acute myocardial infarction

myocardial infarction

left ventricular dysfunction


Ambulatory phlebectomy versus compression sclerotherapy : results of a randomized controlled trial . BACKGROUND Although no randomized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy , both techniques are used to treat varicose veins worldwide . We performed a randomized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy . METHODS From September 1996 to October 1998 , we randomly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy . Our primary outcome parameters were as follows : recurrence rates at 1 and 2 years and complications related to therapy . Eighty-two patients were included , of whom 16 were included with both of their legs . The number of treated legs was therefore 98 , but two patients were lost to follow-up . RESULTS One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy ( P < 0.001 ) ; at 2 years , six additional recurrences were found , but then solely for compression sclerotherapy ( P < 0.001 ) . Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters , teleangiectatic matting , scar formation , and bruising from bandaging . CONCLUSION Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg . Recurrence rates are significantly lower than for compression sclerotherapy therapy . If varicose veins persist 4 weeks after compression sclerotherapy , it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option .

Ambulatory phlebectomy

compression sclerotherapy

compression sclerotherapy

ambulatory phlebectomy

compression sclerotherapy

ambulatory phlebectomy

compression sclerotherapy

ambulatory phlebectomy

phlebectomy

compression sclerotherapy

compression sclerotherapy

compression sclerotherapy

ambulatory phlebectomy

compression sclerotherapy therapy

compression sclerotherapy

ambulatory phlebectomy

One year recurrence

recurrences


The role of choice in health education intervention trials : a review and case study . Although the randomized , controlled trial ( RCT ) is considered the gold standard in research for determining the efficacy of health education interventions , such trials may be vulnerable to " preference effects " ; that is , differential outcomes depending on whether an individual is randomized to his or her preferred treatment . In this study , we review theoretical and empirical literature regarding designs that account for such effects in medical research , and consider the appropriateness of these designs to health education research . To illustrate the application of a preference design to health education research , we present analyses using process data from a mixed RCT/preference trial comparing two formats ( Group or Self-Directed ) of the " Women take PRIDE " heart disease management program . Results indicate that being able to choose one 's program format did not significantly affect the decision to participate in the study . However , women who chose the Group format were over 4 times as likely to attend at least one class and were twice as likely to attend a greater number of classes than those who were randomized to the Group format . Several predictors of format preference were also identified , with important implications for targeting disease-management education to this population .

Group

Self-Directed )

Group format

randomized to the Group format .

decision to participate

Women

heart disease

women


Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil . Treatment of Alzheimer 's disease sometimes uses combinations of drugs because dementia is frequently associated with behavioral symptoms . Risperidone and donepezil are both metabolized through cytochrome P450 2D6 and 3A4 , raising the possibility of drug interactions with combination therapy . The objective of this study was to determine whether significant drug interactions occur with concomitant administration of donepezil and risperidone . In an open-label , three-way crossover study , 24 healthy men were randomly assigned to receive 0.5 mg of risperidone twice daily , 5 mg of donepezil once daily , or both drugs for 14 consecutive days , followed by a 21-day washout period . The treatment ratios of AUC and associated 90 % confidence intervals ( CIs ) for risperidone active moiety , defined as risperidone plus 9-hydroxyrisperidone ( ratio = 110.2 % ; 90 % CI = 103.7-117.2 ) , and for donepezil ( ratio = 97.1 % ; 90 % CI = 90.0-103.6 ) were within the 80 % to 125 % of bioequivalence range . The treatment ratios of Cmax and associated 90 % CIs for risperidone active moiety ( ratio = 114.6 % ; 90 % CI = 107.0-122.8 ) and for donepezil ( ratio = 96.1 % ; 90 % CI = 90.0-102.6 ) were also within the bioequivalence range . Therefore , no significant pharmacokinetic differences occurred in either risperidone active moiety or donepezil when given alone or in combination . Adverse events ( predominantly headache , nervousness , and somnolence ) were minor and comparable for all treatment groups . The results indicate that no clinically meaningful drug interactions occurred between risperidone 1 mg daily and donepezil 5 mg daily at steady state , and therefore no dosage adjustment is required when both drugs are combined with the dosage regimen studied . Additional investigations are warranted to determine the potential for interactions in elderly patients with dementia who may eliminate risperidone and donepezil more slowly and thus be more vulnerable to clinical drug interactions than the young healthy subjects examined in this study .

risperidone

donepezil .

Risperidone

donepezil

donepezil

risperidone .

risperidone

donepezil

Pharmacokinetic and safety assessments

drug interactions

ratios of AUC

pharmacokinetic

clinically meaningful drug interactions

healthy

young

healthy


Optimal therapy for advanced chronic venous insufficiency . INTRODUCTION While definitive therapy awaits level I evidence , controversy persists regarding the optimal operation for treatment of advanced chronic venous insufficiency ( CVI ) . We propose a pragmatic approach to the correction or amelioration of venous hypertension resulting from hydrodynamic and hydrostatic venous reflux . We evaluated a strategy of balloon dissection , subfascial endoscopic perforating vein surgery ( SEPS ) with routine posterior deep compartment fasciotomy , including ligation and stripping of the superficial system , for use when reflux is documented at duplex ultrasound ( US ) scanning . METHODS This is a cooperative , multicenter , retrospective review of 832 patients stratified by CEAP classification . The series consisted of 300 patients with C4 CVI , 119 patients with C5 CVI , and 413 patients with C6 CVI . A subset of 92 patients with C4 disease were prospectively randomized , and ambulatory venous pressure ( AVP ) was determined preoperatively and postoperatively . All patients underwent duplex US scanning to document reflux in the deep , superficial , and perforating venous systems . Efficacy , safety , and durability were evaluated over follow-up of 1 to 9 years ( mean , 31/2 years ) . Uniformity was attempted by adoption of the senior author 's protocol and technique through on-site preceptorship in each surgeon 's operative theater . RESULTS This technique interrupted 3 to 14 ( mean , 7 ) incompetent perforating veins per patient . Of the 832 patients undergoing SEPS , 460 ( 55 % ) underwent saphenous vein ligation and stripping at the same operation . In 92 % ulcers healed or were significantly improved within 4 to 14 weeks . In 64 ( 8 % ) patients , ulcers failed to heal or there was no benefit from the operation . Thirty-two patients ( 4 % ) experienced recurrent ulceration or skin deterioration at 6 months-2 years ( mean , 15 mo ) . Repeat SEPS was successful in 25 of these 96 patients , and deep valve repair was successful in 4 patients . In the 92 randomized patients with C4 disease , 41 refused postoperative AVP , leaving 51 compliant patients . The SEPS group ( n = 25 ) had significantly reduced AVP ( P < .01 ) compared with the control group ( n = 26 ) . Complications in 825 patients were less than 3 % and consisted mostly of transient neurologic disorders ( eg , paradysthesia ) , but deep venous thrombosis occurred in 2 patients , with pulmonary embolus in 1 . No operative deaths occurred . Follow-up for 1 to 9 years ( mean , 31/2 years ) demonstrated durability . CONCLUSION The efficacy , safety , and durability of this operative protocol proved beneficial in our clinical experience with 832 patients during 9 years of follow-up . The SEPS subset of randomized patients with C4 disease experienced significant decrease in AVP , objectively supporting the effectiveness of reflux surgery in advanced CVI . Until definitive level I evidence is available , this operative technique is advocated as optimal therapy for CVI .

duplex US scanning

SEPS

saphenous vein ligation and stripping

Efficacy , safety , and durability

ulcers failed to heal

AVP

transient neurologic disorders

deep venous thrombosis

deaths

durability

92 patients with C4 disease


Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens . Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries , which GH dosage to use and which age to start puberty induction are issues of debate . This study shows final height ( FH ) in 60 girls with Turner syndrome treated in a randomized dose-response trial , combining GH treatment with low dose estrogens at a relatively young age . Girls were randomly assigned to group A ( 4 IU/m ( 2 ) .d ; approximately 0.045 mg/kg/d ) , group B ( first year , 4 IU/m ( 2 ) .d ; thereafter 6 IU/m ( 2 ) .d ) , or group C ( first year , 4 IU/m ( 2 ) .d ; second year , 6 IU/m ( 2 ) .d ; thereafter , 8 IU/m ( 2 ) .d ) . After a minimum of 4 yr of GH treatment , at a mean age of 12.7 +/- 0.7 yr , low dose micronized 17beta-estradiol was given orally . After a mean duration of GH treatment of 8.6 +/- 1.9 yr , FH was reached at a mean age of 15.8 +/- 0.9 yr. FH , expressed in centimeters or SD score , was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A , 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B , and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters , corrected for height SD score and age at start of treatment , was significant between groups A and B [ regression coefficient , 4.1 ; 95 % confidence interval ( CI ) , 1.4 , 6.9 ; P < 0.01 ] , and groups A and C ( coefficient , 5.0 ; 95 % CI , 2.3 , 7.7 ; P < 0.001 ) , but not between groups B and C ( coefficient , 0.9 ; 95 % CI , -1.8 , 3.6 ) . Fifty of the 60 girls ( 83 % ) had reached a normal FH ( FH SD score , more than -2 ) . After starting estrogen treatment , the decrease in height velocity ( HV ) changed significantly to a stable HV , without affecting bone maturation ( change in bone age/change in chronological age ) . The following variables contributed significantly to predicting FH SD score : GH dose , height SD score ( ref . normal girls ) , chronological age at start of treatment , and HV in the first year of GH treatment . GH treatment was well tolerated . In conclusion , GH treatment leads to a normalization of FH in most girls , even when puberty is induced at a normal pubertal age . The optimal GH dosage depends on height and age at the start of treatment and first year HV .

estrogens

GH treatment

GH treatment

micronized 17beta-estradiol

GH

estrogen

GH

GH

GH

Final height in girls

final height ( FH )

duration of GH treatment

FH

FH in centimeters

normal FH

bone maturation

FH SD score

GH dose

height SD score

HV

well tolerated

FH

girls

turner syndrome

girls

Turner syndrome

Girls

Fifty

girls


A preliminary study of the optimal anesthesia positioning for the morbidly obese patient . BACKGROUND Hypoxemia during the induction of general anesthesia for the morbidly obese patient is a major concern of anesthesiologists . The etiology of this pathophysiological problem is multifactorial , and patient positioning may be a contributing factor . The present study was designed to identify optimal patient positioning for the induction of general anesthesia that minimizes the risk of hypoxemia in these patients . METHODS 26 morbidly obese patients ( body mass index-BMI 56 +/- 3 ) were randomly assigned to one of three positions for induction of anesthesia : 1 ) 30 degrees Reverse Trendelenburg ; 2 ) Supine-Horizontal ; 3 ) 30 degrees Back Up Fowler . Mask ventilation , full neuromuscular paralysis and direct laryngoscopy were performed . Any airway difficulties were noted . After endotracheal tube placement , subjects were ventilated for 5 minutes with 1 % isoflurane in a mixture of 50 % oxygen/50 % air and then disconnected from the ventilation circuit . The time required for capillary oxygen saturation ( SaO2 ) , as measured by pulse oximeter , to decline from 100 % to 92 % was noted and identified as the safe apnea period ( SAP ) . Ventilation was then immediately re-established . The lowest SaO2 after resuming ventilation and the time from that nadir to an SaO2 of 97 % were also recorded . RESULTS BMI and hip-waist ratios of patients in groups 1 , 2 and 3 did not significantly differ . There were no differences in airway difficulties between the different groups . The SAP in groups 1 , 2 and 3 was 178 +/- 55 , 123 +/- 24 and 153 +/- 63 seconds , respectively . The SaO2 of patients in the reverse Trendelenburg position dropped the least and took the shortest time to recover to 97 % . CONCLUSIONS In morbidly obese patients , the 30 degrees Reverse Trendelenburg position provided the longest SAP when compared to the 30 degrees Back Up Fowler and Horizontal-Supine positions . Since on induction of general anesthesia morbidly obese patients may be difficult to mask ventilate and/or intubate , this extra time may preclude adverse sequelae resulting from hypoxemia . Therefore , Reverse Trendelenburg is recommended as the optimal position for induction .

anesthesia positioning

30 degrees Reverse Trendelenburg

Supine-Horizontal

30 degrees Back Up Fowler

Reverse Trendelenburg

Back Up Fowler

Horizontal-Supine

Reverse Trendelenburg

airway difficulties

safe apnea period ( SAP )

BMI and hip-waist ratios of patients

airway difficulties

SAP

position

time to recover

morbidly obese patient .


The effect of topical nasal fluticasone on objective sleep testing and the symptoms of rhinitis , sleep , and daytime somnolence in perennial allergic rhinitis . Recent data suggested that daytime somnolence in patients with allergic rhinitis was secondary to disrupted sleep caused by nasal congestion . Medications , which decreased congestion , would be expected to improve sleep and daytime somnolence . Previously , we showed that nasal steroids improved all three symptoms . Presently , we have not performed objective sleep testing to determine if there is a correlation between subjective improvement of congestion , sleep , and daytime somnolence . The objective of this 8-week , double-blind , placebo-controlled study was to determine if topical nasal fluticasone is effective at decreasing subjective congestion and daytime somnolence and improving sleep and if this improvement correlated with a change in overnight sleep testing ( polysomnography ) . We recruited 32 subjects with perennial allergic rhinitis and randomized them in a double-blinded , cross-over fashion , to receive placebo or fluticasone ( 50 micrograms a spray ) , 2 sprays each side everyday , using Balaam 's design . Questionnaires , quality of life instruments , daily diary , Epworth Sleepiness Scale , and an overnight sleep test with polysomnograms were used as tools . The last 2 weeks of each 4-week treatment period were summarized , scored , and compared by PROC MIXED in SAS . Correlations between arousals on sleep tests and subjective tests were performed . Fluticasone improved subjective sleep when compared with placebo ( p = 0.04 ) ; however , there was no difference in the apnea/hypopnea index in those that were treated . Daytime sleepiness and fatigue were decreased by > 10 % in the treated group ; however , this was not statistically significant . However , fluticasone used at approved doses improves subjective sleep in patients with perennial allergic rhinitis without a change in the apnea/hypopnea index .

fluticasone

placebo-controlled

fluticasone

placebo

fluticasone

objective sleep testing

disrupted sleep

sleep and daytime somnolence

subjective congestion

daytime somnolence

improving sleep

overnight sleep testing

( polysomnography

Questionnaires

sleep tests and subjective tests

subjective sleep

apnea/hypopnea index

Daytime sleepiness

fatigue

subjective sleep

perennial allergic rhinitis .

allergic rhinitis

perennial allergic rhinitis

perennial allergic rhinitis


The effects of peer counseling on smoking cessation and reduction . OBJECTIVE To evaluate a peer counseling intervention for pregnant smokers . METHODS One hundred forty-two pregnant , predominantly Hispanic women were assigned to a peer-led smoking cessation program or to usual care . RESULTS Compared with usual care , peer counseling reduced smoking ( -9.1 versus -4.5 cigarettes daily , P =.03 ) , but did not affect absolute quit rates ( 24 % versus 21 % ) at 36 weeks ' gestation . Infant birth weight negatively correlated with cigarettes smoked per day ( r = -0.29 , P < .01 ) and expired carbon monoxide ( r = -0.39 , ( P < .001 ) at delivery . Birth weight for infants born to women who quit smoking averaged 7.2 lb versus 6.8 and 6.3 lb for mothers smoking one to six and more than six cigarettes per day at delivery ( P < .01 ) . CONCLUSION Peer counseling reduced the number of cigarettes smoked daily but did not increase cigarette abstinence rates . Infant birth weight increases with both smoking cessation and smoking reduction , suggesting that peer counseling intervention programs may improve newborn health despite their failure to affect smoking cessation .

peer counseling

peer counseling intervention

usual care , peer counseling

Peer counseling

peer counseling intervention programs

cessation

quit rates

Infant birth weight

Peer counseling

number of cigarettes smoked daily

cigarette abstinence rates

Infant birth weight

newborn health

pregnant smokers

One hundred forty-two

pregnant

women


Continuous low-level heatwrap therapy for treating acute nonspecific low back pain . OBJECTIVE To evaluate the efficacy of 8 hours of continuous low-level heatwrap therapy for the treatment of acute nonspecific low back pain ( LBP ) . DESIGN Prospective , randomized , parallel , single-blind ( investigator ) , placebo-controlled , multicenter clinical trial . SETTING Five community-based research facilities . PARTICIPANTS Two-hundred nineteen subjects , aged 18 to 55 years , with acute nonspecific LBP . INTERVENTION Subjects were stratified by baseline pain intensity and gender and randomized to one of the following groups : evaluation of efficacy ( heatwrap , n=95 ; oral placebo , n=96 ) and blinding ( oral ibuprofen , n=12 ; unheated back , wrap n=16 ) . All treatments were administered for 3 consecutive days with 2 days of follow-up . MAIN OUTCOME MEASURES Primary : day 1 mean pain relief ( 0- to 5-point verbal response scale ) . Secondary : muscle stiffness ( 101-point numeric rating scale ) , lateral trunk flexibility ( fingertip-floor distance ) , and Roland-Morris Disability Questionnaire over 3 days of treatment and 2 days of follow-up . RESULTS Heatwrap therapy was shown to provide significant therapeutic benefits when compared with placebo during both the treatment and follow-up period . On day 1 , the heatwrap group had greater pain relief ( 1.76+/-.10 vs 1.05+/-.11 , P < .001 ) , less muscle stiffness ( 43.1+/-1.21 vs 47.6+/-1.21 , P=.008 ) , and increased flexibility ( 18.6+/-.44 cm vs 16.5+/-.45 cm , P=.001 ) compared with placebo . Disability was also reduced in the heatwrap group ( 5.3 vs 7.4 , P=.0002 ) . Adverse events were mild and infrequent . CONCLUSION Continuous low-level heatwrap therapy was shown to be effective for the treatment of acute , nonspecific LBP .

continuous low-level heatwrap therapy

placebo-controlled

heatwrap , n=95 ; oral placebo , n=96 )

Heatwrap therapy

placebo

heatwrap

placebo

heatwrap

heatwrap therapy

muscle stiffness

101-point numeric rating scale

Roland-Morris Disability Questionnaire

therapeutic benefits

pain relief

muscle stiffness

flexibility

Disability

Adverse events

acute nonspecific low back pain ( LBP )

Two-hundred nineteen

aged 18 to 55 years

acute nonspecific LBP


Evaluation of 25-gauge Quincke and 24-gauge Gertie Marx needles for spinal anaesthesia for caesarean section . OBJECTIVE To compare the insertion characteristics and rate of complications between 25-gauge Quincke and 24-gauge Gertie Marx needles . DESIGN Prospective , randomized study . SETTING University of Benin Teaching Hospital ; a university-affiliated tertiary centre . SUBJECTS Parturients ( ASA 1 and 2 ) scheduled for elective caesarean section . They were randomly assigned to receive spinal anaesthesia with either 25-gauge Quincke needle or 24-gauge Gertie Marx needle . The patients with abnormal spaces , coagulopathy , infection , pre-eclampsia/eclampsia or obesity were excluded . MAIN OUTCOME MEASURES The number of attempts at successful identification of the spinal space , intraoperative complications , incidence of postdural puncture headache ( PDPH ) , non-postdural puncture headache ( NPDPH ) and backache . RESULTS Sixty women were studied . The 24-gauge Gertie Marx needle resulted in more successful location of the spinal space on the second attempt ( P < 0.05 ) . Non-postdural puncture headache was seen in 43 % of the study population . PDPH was seen in 10 % of the Quincke group and none in the Gertie Marx group . There was no difference in the incidence of backache in both groups . CONCLUSION The ease of insertion and low incidence of PDPH with the Gertie Marx needle may encourage trainee anaesthetists to use this needle for caesarean section .

intraoperative complications

successful location of the spinal space

Non-postdural puncture headache

PDPH

backache

PDPH

abnormal spaces

coagulopathy

infection

pre-eclampsia/eclampsia

obesity

Sixty

women


Iontophoretic administration of dexamethasone sodium phosphate for acute epicondylitis . A randomized , double-blinded , placebo-controlled study . BACKGROUND A better treatment modality is needed to control the pain of medial or lateral epicondylitis ( tennis elbow ) . HYPOTHESIS Dermal iontophoretic administration of dexamethasone sodium phosphate will be significantly more effective in controlling pain than a placebo in patients with medial or lateral elbow epicondylitis . STUDY DESIGN Randomized , double-blinded , placebo-controlled study . METHODS On six occasions , 1 to 3 days apart within 15 days , 199 patients with elbow epicondylitis received 40 mA-minutes of either active or placebo treatment . RESULTS Dexamethasone produced a significant 23-mm improvement on the 100-mm patient visual analog scale ratings , compared with 14 mm for placebo at 2 days and 24 mm compared with 19 mm at 1 month . More patients treated with dexamethasone than those treated with placebo scored moderate or better on the investigator 's global improvement scale ( 52 % versus 33 % ) at 2 days , but the difference was not significant at 1 month ( 54 % versus 49 % ) . Investigator-rated pain and tenderness scores favored dexamethasone over placebo at 2 days . Patients completing six treatments in 10 days or less had better results than those treated over a longer period . CONCLUSIONS Iontophoresis treatment was well tolerated by most patients and was effective in reducing symptoms of epicondylitis at short-term follow-up .

Iontophoretic

dexamethasone sodium phosphate

placebo-controlled

iontophoretic

dexamethasone

placebo-controlled

placebo

Dexamethasone

placebo

dexamethasone

placebo

Iontophoresis

pain

pain

tolerated

symptoms of epicondylitis

acute epicondylitis

medial or lateral elbow epicondylitis

epicondylitis


Acute and subchronic effects of levocetirizine and diphenhydramine on memory functioning , psychomotor performance , and mood . BACKGROUND Central nervous system adverse effects , such as sedation , often accompany the use of first-generation antihistamines . These effects might interfere with memory functioning and psychomotor performance . Levocetirizine was recently introduced as a new antihistamine said to be free from sedative effects . OBJECTIVE We sought to investigate the effects of levocetirizine ( 5 mg ) , diphenhydramine ( 50 mg ) , and placebo on memory and psychomotor performance after acute ( day 1 ) and subchronic ( day 4 ) daily administration in 48 healthy volunteers ( 24 men and 24 women ) . METHODS This study was a double-blind , placebo-controlled , randomized clinical trial . Treatments were administrated on days 1 , 2 , 3 , and 4 , 3 hours before the start of the laboratory test battery ( performed on days 1 and 4 ) , comprising a word-learning test , the Sternberg Memory Scanning Test , a tracking test ( easy and hard version ) , and a divided attention test ( tracking and memory scanning simultaneously ) . Statistical analyses were performed separately for days 1 and 4 by using analysis of variance . RESULTS On day 1 , diphenhydramine significantly impaired tracking performance ( easy : F ( 1,90 ) = 25.9 , P < .0001 ; hard : F ( 1,90 ) = 20.5 , P < .0001 ) and divided attention ( tracking : F ( 1,90 ) = 23.8 , P < .0001 ; memory scanning : F ( 1,90 ) = 22.0 , P < .0001 ) . Results on word-learning tests and Sternberg Memory Scanning Tests were not significantly impaired . On day 4 , the effects of diphenhydramine did not reach significance . In contrast , on both days 1 and 4 , levocetirizine did not significantly impair laboratory test performance . CONCLUSION The results show that memory , attention , and tracking performance are unaffected after acute and subchronic administration of levocetirizine ( 5 mg ) , whereas diphenhydramine ( 50 mg ) significantly affected divided attention and tracking after acute administration .

levocetirizine

diphenhydramine

Levocetirizine

levocetirizine

diphenhydramine

and placebo

placebo-controlled

diphenhydramine

diphenhydramine

levocetirizine

levocetirizine

diphenhydramine

mood

memory and psychomotor performance

tracking performance

divided attention

memory scanning

word-learning tests

Sternberg Memory Scanning Tests

laboratory test performance

memory

attention

tracking performance

divided attention

tracking

48 healthy volunteers ( 24

men

and 24

women


Clonidine premedication improves metabolic control in type 2 diabetic patients during ophthalmic surgery . BACKGROUND In stressful conditions , increasing blood glucose concentrations are closely related to an increase in catecholamines and cortisol release . Clonidine , a centrally acting alpha ( 2 ) -adrenoceptor agonist , has neuroendocrine effects , including inhibition of sympathoadrenal activity . We therefore evaluated the effect of clonidine on blood glucose control and insulin requirements during ophthalmic surgery when given as premedication in type 2 diabetic patients . METHODS After randomization , patients were premedicated with clonidine or flunitrazepam ( control ) . Patients were given insulin by continuous i.v . infusion to maintain blood glucose in the range 5.5-11.1 mmol litre ( -1 ) . Blood glucose concentrations were measured every 15 min during surgery , and hourly for 6 h after surgery . Plasma C-peptide and counter-regulatory hormones were also measured . RESULTS Glycaemia was significantly lower in the clonidine group ( P < 0.01 ) and the median amount of insulin administered was significantly reduced : clonidine group 9.0 ( interquartile range 5.1 ) units ; control 18.6 ( 10.2 ) units ; P < 0.01 ) . Plasma catecholamine concentrations were lower in patients given clonidine ( P < 0.05 ) but there was no difference in cortisol concentrations . CONCLUSION Premedication of type 2 diabetic patients with clonidine 90 min before surgery improves blood glucose control and decreases insulin requirements during ophthalmic surgery .

Clonidine

clonidine

clonidine

flunitrazepam

insulin

clonidine

clonidine

blood glucose control

insulin requirements

Blood glucose concentrations

Glycaemia

median amount of insulin administered

Plasma catecholamine concentrations

cortisol concentrations .

blood glucose control

type 2 diabetic

ophthalmic

type 2 diabetic

type 2 diabetic


Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery . UNLABELLED Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting . We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass ( CPB ) in patients treated with aspirin until the day before surgery . The study was a prospective , randomized , double-blinded , placebo-controlled , parallel-group trial . Eighty patients were included and divided into two groups : one group received tranexamic acid 30 mg/kg , and one group received placebo ( 0.9 % NaCl ) as a bolus injection before CPB . Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay . Transfusions of packed red cells were given when the hematocrit value was less than 20 % during CPB and less than 25 % after surgery . The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group ( mean [ SD ] ) ( 475 [ 274 ] mL versus 713 [ 243 ] mL ; P < 0.001 ) . An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid . Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery . IMPLICATIONS Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding . The administration of a single dose of tranexamic acid ( 30 mg/kg ) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients .

tranexamic acid

coronary surgery

aspirin

Tranexamic acid

coronary artery bypass grafting

tranexamic acid

cardiopulmonary bypass ( CPB )

aspirin

placebo-controlled

tranexamic acid 30 mg/kg ,

placebo

Transfusions

tranexamic acid

placebo

tranexamic acid . Tranexamic acid

coronary artery bypass grafting

aspirin

coronary artery bypass grafting

tranexamic acid

postoperative bleeding

effects

Postoperative blood loss

Transfusions of blood products

hematocrit value

postoperative bleeding

inhibition of fibrinolysis

postoperative bleeding

postoperative bleeding .

postoperative bleeding

fibrinolysis

surgery

surgery

Eighty patients

the patients in the placebo group


Esmolol blunts the cerebral blood flow velocity increase during emergence from anesthesia in neurosurgical patients . UNLABELLED Cerebral hyperemia has been demonstrated during emergence from anesthesia in neurosurgical patients , but its mechanism is speculative . We performed this study to test the hypothesis that this could be attributed to sympathetic overactivity . Thirty neurosurgical patients were included in a prospective , randomized , double-blinded study comparing esmolol , a short-acting beta-blocker , and a placebo . Esmolol ( 0.3 mg. kg ( -1 ) . min ( -1 ) ) was infused from the end of anesthesia to 15 min after extubation . Cerebral blood flow velocity ( CBFV ) , mean arterial blood pressure , and heart rate were recorded before anesthesia , during anesthesia after surgery , at extubation , and 5-60 min after extubation . Cardiac output ( COe ) was estimated by using an esophageal Doppler from anesthesia to 60 min after extubation . CBFV , COe , and heart rate were significantly lower in the esmolol group . Mean arterial blood pressure was comparable between the groups . There was no correlation between CBFV and COe at any time point during the study . In conclusion , esmolol blunted the CBFV increase during emergence , confirming that sympathetic overactivity contributes to cerebral hyperemia during neurosurgical recovery . IMPLICATIONS Esmolol blunted the postoperative increase in cerebral blood flow velocity in neurosurgical patients . The origin of sympathetic hyperactivity and its potential deleterious consequences require further study .

Esmolol

esmolol

placebo .

Esmolol

anesthesia

extubation

cerebral blood flow velocity increase

Cerebral hyperemia

Cerebral blood flow velocity ( CBFV )

mean arterial blood pressure

heart rate

Cardiac output ( COe )

CBFV

COe

heart rate

Mean arterial blood pressure

CBFV

COe

CBFV increase

cerebral hyperemia

cerebral blood flow velocity

neurosurgical patients

neurosurgical patients

Thirty

neurosurgical patients

neurosurgical patients


Multiple risk factor intervention reduces cardiovascular risk in hypertensive patients with echolucent plaques in the carotid artery . OBJECTIVE In a previously published randomized 6-year study we observed that multiple risk factor intervention reduced cardiovascular risk in high-risk hypertensive men , and that this effect was confined to patients with carotid artery plaques . Hypothetically , the underlying mechanism might have been a stabilization of echolucent , instable , rupture-prone plaques . The aim of the present study was to examine plaque characteristics by B-mode ultrasound in the previous intervention study , and also to investigate the relationship between plaque characteristics at baseline and cardiovascular events during the 6-year follow-up in the two randomization groups . METHODS High resolution B-mode ultrasound was used to characterize plaque echogenicity in four subgroups - dominantly echolucent , substantially echolucent , dominantly echogenic , and uniformly echogenic . RESULTS In the usual care group 17 of 32 ( 53 % ) patients with echolucent plaques at baseline suffered from a combined end-point ( any death or nonfatal myocardial infarction or nonfatal stroke ) during follow-up compared with seven of 28 ( 25 % ) patients in the intervention group ( P = 0.036 ) . The corresponding numbers in patients with echogenic plaques were n = 4/13 ( 31 % ) and n = 4/17 ( 24 % ) , respectively ( NS ) . In the usual care group 11 of 33 ( 33 % ) patients with no plaques suffered from a combined end-point during follow-up compared with 11 of 30 ( 37 % ) in the intervention group . CONCLUSION Our data indicate that the beneficial effect of the multiple risk intervention programme was confined to those patients with echolucent plaques . The data have to be confirmed with a large-scale trial .

Multiple risk factor intervention

B-mode ultrasound

High resolution B-mode ultrasound

usual care group

usual care group

intervention group

multiple risk intervention programme

plaque characteristics

plaque characteristics

cardiovascular events

characterize plaque echogenicity

echolucent plaques

death

echogenic plaques

beneficial effect

high-risk hypertensive men


Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma . BACKGROUND AND AIM Adjuvant locoregional chemotherapy has been shown to be useful to prevent recurrence after curative resection of hepatocellular carcinoma ( HCC ) in some retrospective studies . Our aim was to compare the dose effect in the prevention of tumor recurrence . METHODS A prospective randomized controlled trial was conducted in patients with curative resection of HCC ; they were given either one intra-arterial dose of cisplatin/lipiodol , or received four doses , once every 3 months . The rates of recurrence , disease-free and overall survival were compared . RESULTS During a median follow up of 818 days , 21 patients received one dose and 19 received four doses , with 10 ( 47.6 % ) and eight ( 42.1 % ) recurrences , respectively . The 1-year , 2-year and 3-year disease-free survival rates were 71 % , 54 % and 44 % for the one-dose group and 74 % , 60 % and 40 % for the four-dose group ( P = 0.78 ) . The respective overall survival rates were 85 % , 74 % , 55 % and 84 % , 71 % , 40 % ( P = 0.64 ) . The only prognostic factor was presence of vascular permeation . The side-effects were mild and tolerable . CONCLUSIONS There is no significant difference in the survival rates between the two groups . Adjuvant chemotherapy may not be useful .

adjuvant chemotherapy

curative resection

Adjuvant locoregional chemotherapy

cisplatin/lipiodol

Adjuvant chemotherapy

rates of recurrence

disease-free

overall survival

overall survival rates

presence of vascular permeation

side-effects

survival rates

hepatocellular carcinoma .


Effect of postural supports on neuromotor function in very preterm infants to term equivalent age . OBJECTIVE To determine the effect of a postural support nappy and/or a postural support roll on neuromotor function in very preterm infants when nursed prone to term equivalent age . METHODS A randomized observer blind controlled trial of 123 very preterm infants was conducted in the neonatal intensive care unit of the sole tertiary referral centre in Western Australia . Infants were stratified by gestational age ( < 29 weeks or 29-30 weeks ) , then randomized into one of three intervention groups : postural support nappy , postural support nappy and postural support roll , or disposable nappy and postural support roll . Interventions started when infants were stable and ceased when routine side-lying commenced . Measurements of shoulder and hip posture were performed pre-intervention , 5 weeks post-intervention and term postmenstrual age . RESULTS Infants nursed with a postural support roll and a postural support nappy demonstrated improved hip posture to term equivalent age compared with infants nursed with either a postural support roll only , or a postural support nappy only . Infants nursed with a postural support roll either with or without a postural support nappy demonstrated improved shoulder posture to term equivalent age . CONCLUSIONS Combined use of a postural support roll and a postural support nappy while very preterm infants are nursed prone improves hip posture up to term postmenstrual age . Use of a postural support roll improves shoulder posture up to term equivalent age .

postural supports

postural support nappy

postural support roll

postural support nappy

postural support roll

postural support nappy

postural support roll

postural support nappy

postural support roll

neuromotor function

neuromotor function

shoulder and hip posture

hip posture

shoulder posture

hip posture

shoulder posture

very preterm

infants

neuromotor function

very preterm

infants

very preterm

infants

Infants

29 weeks or 29-30 weeks


Sustained ventricular arrhythmias and mortality among patients with acute myocardial infarction : results from the GUSTO-III trial . BACKGROUND In many patients , ventricular arrhythmias will develop early after acute myocardial infarction . We studied the incidence , timing , and outcomes of such arrhythmias in the international Global Utilization of Streptokinase and TPA ( alteplase ) for Occluded Coronary Arteries ( GUSTO ) -III trial . METHODS We identified independent predictors of inhospital ventricular fibrillation ( VF ) and ventricular tachycardia ( VT ) and compared 30-day and 1-year mortality rates of patients who did ( n = 1121 ) and did not ( n = 13,921 ) have these arrhythmias during the index hospitalization . RESULTS Significant independent predictors of inhospital VF were higher Killip class , lower baseline systolic pressure , intravenous preenrollment lidocaine use , shorter time to thrombolysis , and beta-blocker use < 2 weeks before enrollment ; independent predictors of inhospital VT were lower baseline systolic pressure , intravenous lidocaine use before enrollment , higher Killip class , faster baseline heart rate , and advanced age . The 30-day mortality rate was 31 % in patients with VF , 24 % in those with VT , 44 % in those with both , and 6 % in those with neither ( P =.001 ) . The corresponding 1-year mortality rates were 34 % , 29 % , 49 % , and 9 % ( P =.001 ) . The 30-day and 1-year mortality rates were higher for patients with late ( > 48 hours after enrollment ) versus early arrhythmias ( < or =48 hours after enrollment ) . CONCLUSIONS Despite thrombolysis , inhospital ventricular arrhythmias are associated with higher 30-day and 1-year mortality rates after acute myocardial infarction , particularly when occurring later during the initial hospitalization . Better therapies are needed to improve outcomes of these arrhythmias .

lidocaine use

Killip class

lower baseline systolic pressure

intravenous preenrollment lidocaine use

thrombolysis

baseline systolic pressure

intravenous lidocaine

baseline heart rate

30-day mortality rate

1-year mortality rates

30-day and 1-year mortality rates

mortality rates

acute myocardial infarction

acute myocardial infarction


Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome : a prospective , randomized , controlled study . Inhaled nitric oxide ( NO ) improves systemic oxygenation ( PaO2/FIO2 ) in adult patients with acute respiratory distress syndrome ( ARDS ) . However , individual response varies , and previous trials demonstrated no outcome benefit . This prospective , randomized study in 40 ARDS patients analyzed dose-response ( DR ) characteristics during long-term inhaled NO . Patients were randomized for conventional therapy ( control ) or continuous treatment with 10 parts per million ( ppm ) inhaled NO until weaning was initiated . We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals . Before treatment ( Day 0 ) , peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients . After 4 days , the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm . At higher doses ( 10 and 100 ppm ) , oxygenation deteriorated , and the response to inhaled NO disappeared in several patients . This effect was not observed in the control group . There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit . In conclusion , long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters . Hence , previous trials on therapy with inhaled NO in ARDS should be carefully interpreted , as they used constant NO concentrations , which may have become overdoses leading to deterioration of oxygenation after several days .

nitric oxide

nitric oxide ( NO )

NO

conventional therapy ( control )

NO

NO-treated

NO-treated

dose-response ( DR ) characteristics

DR curve of the NO-treated patients

oxygenation deteriorated

oxygenation

adult

ARDS


Comparative clinical and microbiological effects of subgingival metronidazole application in adult periodontitis ; 12-months results . The aim of the present study was to evaluate the clinical and microbiological effects of subgingival application of 25 % metronidazole dental gel as an adjunct to scaling and root planing ( SRP ) in the treatment of adult periodontitis . Eighty teeth in 18 patients were evaluated using a split mouth design . The test teeth received SRP and a 25 % metronidazole gel applied subgingivally on days 0 and 7 . The control teeth received SRP only . Clinical and microbiological examinations were carried out before treatment and on weeks 1 , 3 , 7 , 13 , 26 , 38 and 52 of the experimental period . Colony forming units of Porphyromonas gingivalis and Prevotella intermedia / Prevotella nigrescens were determined . Both treatments provided significant improvements in all the clinical and microbiological parameters ( P < 0.05 ) . However , none of the differences between the study groups were statistically significant ( P > 0.05 ) . As a conclusion , the present study does not provide evidence in favour of the routine use of adjunctive metronidazole dental gel in the treatment of adult periodontitis .

metronidazole

metronidazole dental gel

scaling and root planing ( SRP )

SRP

metronidazole gel

SRP only

clinical and microbiological parameters

adult periodontitis

Eighty teeth in 18 patients

adult periodontitis .


Pharmacokinetics and tolerance of single- and multiple-dose oral or intravenous linezolid , an oxazolidinone antibiotic , in healthy volunteers . AIMS To determine the pharmacokinetics and tolerance of oral and intravenous linezolid , an oxazolidinone antibiotic , in healthy volunteers following single- and multiple-dose administration . METHODS In two randomized , double-blind , placebo-controlled , dose-escalating trials , subjects were exposed either to oral ( 375 , 500 or 625 mg ) or intravenous ( 500 or 625 mg ) linezolid or placebo twice daily . Serial blood and urine samples were obtained after the first- and multiple-dose administrations for up to 18 days . Non-compartmental pharmacokinetic analyses were used to describe the disposition of linezolid . RESULTS Plasma linezolid concentrations and area under the concentration-time curves increased proportionally with dose irrespective of the route of administration . Plasma linezolid concentrations remained above the MIC90 for susceptible target pathogens ( 4.0 mg/L ) for the majority of the 12 h dosing interval . Mean clearance , half-life and volume of distribution were similar irrespective of dose for both the oral and intravenous routes . Linezolid was well tolerated and the frequency of drug-related adverse events was similar between the linezolid and placebo groups . CONCLUSIONS Oral and intravenous linezolid exhibit linear pharmacokinetics , with concentrations remaining above the target MIC90 for most of the dosing interval . These results support a twice-daily schedule for linezolid and demonstrate the feasibility of converting from intravenous to oral dosing without a dose adjustment .

linezolid

linezolid

placebo-controlled

linezolid

placebo

linezolid .

linezolid

linezolid

Linezolid

linezolid

linezolid

Pharmacokinetics

and

tolerance

tolerance

Serial blood and urine samples

pharmacokinetic analyses

Plasma linezolid concentrations

tolerated

linear pharmacokinetics

target MIC90


Enhanced pitch sensitivity in individuals with autism : a signal detection analysis . Past research has shown a superiority of participants with high-functioning autism over comparison groups in memorizing picture-pitch associations and in detecting pitch changes in melodies . A subset of individuals with autism , known as " musical savants , " is also known to possess absolute pitch . This superiority might be due to an abnormally high sensitivity to fine-grained pitch differences in sounds . To test this hypothesis , psychoacoustic tasks were devised so as to use a signal detection methodology . Participants were all musically untrained and were divided into a group of 12 high-functioning individuals with autism and a group of 12 normally developing individuals . Their task was to judge the pitch of pure tones in a " same-different " discrimination task and in a " high-low " categorization task . In both tasks , the obtained psychometric functions revealed higher pitch sensitivity for subjects with autism , with a more pronounced advantage over control participants in the categorization task . These findings confirm that pitch processing is enhanced in " high-functioning " autism . Superior performance in pitch discrimination and categorization extends previous findings of enhanced visual performance to the auditory domain . Thus , and as predicted by the enhanced perceptual functioning model for peaks of ability in autism ( Mottron & Burack , 2001 ) , autistic individuals outperform typically developing population in a variety of low-level perceptual tasks .

psychoacoustic tasks

pitch of pure tones

higher pitch sensitivity

categorization task .

pitch processing

pitch discrimination and categorization

visual performance

high-functioning autism


A single nasal allergen challenge increases induced sputum inflammatory markers in non-asthmatic subjects with seasonal allergic rhinitis : correlation with plasma interleukin-5 . BACKGROUND Seasonal allergic rhinitis ( SAR ) is a risk factor for asthma in affected individuals . Nasal allergic inflammation enhances bone-marrow eosinophil production , mainly via IL-5 , and rhinitis patients have increased airway inflammation during the pollen season . OBJECTIVE To assess the impact of nasal allergy on sputum inflammatory markers . METHODS In an open-labelled , randomized , placebo-controlled cross-over study with 16 non-asthmatic SAR patients ( median age 25 years , 56 % males ) , the effect of a single nasal allergen challenge performed out of season on induced sputum inflammatory parameters was evaluated . SAR patients were identified by history , skin-prick test and specific IgE . All patients had normal lung function/bronchial hyper-responsiveness out of season and a negative asthma/wheezing history . Sputum cells and supernatant levels of ECP , sICAM , IL-5 and IL-10 , and plasma levels of IL-5 and ECP , were measured before and 24 h after nasal allergen challenge . After a washout period of at least 4 weeks , the procedure was repeated with placebo challenge ( diluent ) . RESULTS Nasal allergen challenge led to an increase in sputum ECP ( pre = 60 +/- 12 , post = 212 +/- 63 micro g/L , P = 0.02 vs. placebo ) , and sICAM ( 4.8 +/- 2.7 to 6.5 +/- 2.9 ng/mL , P = 0.02 vs. placebo ) , whereas IL-10 decreased after provocation ( 44 +/- 11 to 29 +/- 6 pg/mL , P = 0.06 vs. placebo ) . Sputum IL-5 was undetectable in all patients . The absolute number of blood and sputum eosinophils did not change significantly after allergen or placebo challenge ( P > 0.07 , both comparisons ) . Plasma levels of IL-5 increased after allergen challenge ( 8.7 +/- 2.9 to 14.5 +/- 3.9 pg/mL , P = 0.001 ) , and the increase in plasma IL-5 was positively correlated with the rise in sputum ECP in a subgroup of 'responders ' ( n = 12 , r = 0.71 , P = 0.01 ) . CONCLUSIONS A single nasal allergen challenge in SAR patients increased markers of allergic inflammation in the lower respiratory tract , possibly via pronounced activation of inflammatory cells through circulating immediate-type reaction cytokines like IL-5 . These findings may provide additional explanatory data for the high susceptibility of SAR patients to incident asthma .

single nasal allergen challenge

placebo-controlled

single nasal allergen challenge

single nasal allergen challenge

sputum inflammatory markers

sputum inflammatory markers

sputum inflammatory

sICAM

IL-5 and IL-10

plasma levels of IL-5 and ECP

sputum ECP

sICAM

Sputum IL-5

blood and sputum eosinophils

Plasma levels of IL-5

sputum ECP

allergic inflammation

56 %


Validation of a novel satisfaction questionnaire for patients with rheumatoid arthritis receiving outpatient clinical nurse specialist care , inpatient care , or day patient team care . OBJECTIVES To develop and validate a questionnaire for measuring satisfaction with different forms of complex multidisciplinary care in patients with rheumatoid arthritis ( RA ) . METHODS The satisfaction questionnaire ( score range 0-100 ) comprised 28 items covering 11 domains . Together with a visual analog scale ( VAS , range 0-100 ) on overall satisfaction , the questionnaire was applied in 210 RA patients who participated in a randomized trial comparing 3 types of multidisciplinary care . RESULTS The questionnaire was returned by 174 patients ( 83 % ) . The questionnaire and VAS scores in the total group were 75 ( SD 12 ) and 83 ( SD 20 ) , respectively . Reliability analysis showed Cronbach 's alpha of the questionnaire was 0.91 . Spearman 's correlation coefficient between the satisfaction questionnaire score and VAS score was 0.58 ( P < 0.01 ) . Mean total satisfaction questionnaire scores were 72 ( SD 9 ) , 76 ( SD 14 ) , and 78 ( SD 11 ) , in the nurse specialist , inpatient and day patient groups , respectively ( nurse specialist versus day patient , P = 0.004 ) . Significant differences between nurse specialist and day patients were seen in the following domains : waiting time during the treatment , autonomy , coordination , non-financial access , and quality of general information ( all P < 0.05 ) . CONCLUSION Overall , patients were highly satisfied with the multidisciplinary care they received . Major differences regarding the organization of care were reflected in the results of the questionnaire scores . The satisfaction questionnaire appears to be a useful instrument for measuring satisfaction with complex multidisciplinary care in RA patients .

satisfaction questionnaire

satisfaction questionnaire

questionnaire

satisfaction

satisfaction questionnaire

overall satisfaction

questionnaire and VAS scores

the questionnaire

waiting time during the treatment

autonomy

coordination

non-financial access

quality of general information

satisfaction questionnaire

satisfaction

174 patients ( 83 % )


Effect of a high-protein , energy-restricted diet on weight loss and energy expenditure after weight stabilization in hyperinsulinemic subjects . OBJECTIVE To determine the effect of replacing some dietary carbohydrate with protein , during energy restriction , on weight loss , total energy expenditure ( TEE ) , resting energy expenditure ( REE ) , respiratory quotient ( RQ ) , and the thermic effect of feeding ( TEF ) in subjects with hyperinsulinemia . DESIGN Parallel , clinical intervention study of 12 weeks energy restriction ( 6.5 MJ/day ) and 4 weeks energy balance ( 8.2 MJ/day ) in two groups of subjects randomly assigned to either a high-protein ( HP ) diet ( 27 % of energy ( % E ) as protein , 45 % E as carbohydrate ) or a lower-protein ( LP ) diet ( 16 % E as protein , 57 % E as carbohydrate ) . SUBJECTS A total of 36 obese nondiabetic volunteers with hyperinsulinemia ( 10 males/26 females , aged 34-65 y , BMI 28-43 kg/m ( 2 ) , fasting insulin 12-45 mU/l ) . MEASUREMENTS Body weight and composition , TEE , REE , and RQ were measured at baseline and at week 16 . In addition , the TEF to an HP or LP meal was determined for 3 h , at baseline and at week 16 . RESULTS After 16 weeks , weight loss was similar in response to each diet ; the overall decrease was 7.9+/-0.6 kg ( P < 0.001 ) , of which 6.8+/-0.5 kg was fat ( P < 0.001 ) . REE fell similarly with each diet ; the overall decrease was 719+/-106 kJ/day ( P < 0.001 ) . The TEF was 2 % greater after the HP than after the LP meal at baseline ( P < 0.01 ) and 0.8 % greater at week 16 ( P=0.35 ) . After 16 weeks , the TEF was not reduced in either dietary group . There was no change in TEE after 16 weeks . CONCLUSION In subjects with hyperinsulinemia an energy-restrictive diet containing an increased protein-to-carbohydrate ratio does not enhance weight loss or significantly affect energy expenditure . Caloric restriction , rather than the macronutrient composition of the diet , is the most important determinant of weight loss .

high-protein , energy-restricted diet

energy restriction

energy balance

high-protein ( HP ) diet

lower-protein ( LP ) diet

HP

LP

weight loss and energy expenditure

weight loss

protein-to-carbohydrate ratio

hyperinsulinemic subjects .

hyperinsulinemia

obese

hyperinsulinemia

males/26 females

hyperinsulinemia


Comparison of the efficacy and safety of faropenem daloxate and cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in adults . In this multicentre , multinational , comparative , double-blind clinical trial , outpatients with both clinical signs and symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive for 7 days either a twice-daily oral regimen of faropenem daloxate ( 300 mg ) or a twice daily oral regimen of cefuroxime axetil ( 250 mg ) . Among 452 patients considered valid for clinical efficacy , faropenem daloxate treatment was found to be statistically equivalent to cefuroxime axetil ( 89.0 % vs. 88.4 % -95 % CI=-5.2 % ; +6.4 % ) at the 7-16 days post-therapy assessment . At 28-35 days post-therapy , the continued clinical cure rate in the faropenem daloxate group was 92.6 % and that for the cefuroxime axetil group was 94.9 % ( 95 % CI : -6.8 % ; +1.2 % ) . A total of 148 organisms was obtained in 136 microbiologically valid patients ( 30.1 % ) . The predominant causative organisms were Streptococcus pneumoniae ( 47.1 % ) , Haemophilus influenzae ( 30.1 % ) , Staphylococcus aureus ( 14.7 % ) and Moraxella catarrhalis ( 8.8 % ) . The bacteriological success rate at the 7-16 days post-therapy evaluation was similar in both treatment groups : 91.5 % and 90.8 % in the faropenem daloxate and cefuroxime axetil groups , respectively ( 95 % CI=-9.2 % ; +9.5 % ) . Eradication or presumed eradication was detected for 97.3 % and 96.3 % of S. pneumoniae , 85.0 % and 90.5 % of H. influenzae , 88.9 % and 90.9 % of S. aureus and 100.0 % and 83.3 % of M. catarrhalis in faropenem daloxate and cefuroxime axetil recipients , respectively . At least one drug-related event was reported by 9.5 % of the faropenem daloxate-treated patients and by 10.3 % of those who received cefuroxime axetil . The most frequently reported drug-related events were diarrhoea ( 2.2 % versus 2.9 % ) , nausea/vomiting ( 1.5 % vs. 0.7 % ) , abdominal pain ( 0.7 % vs 1.5 % ) and skin reactions ( 1.5 % vs. 1.1 % ) . Overall , faropenem daloxate was at least as effective clinically and bacteriologically as cefuroxime axetil and was well tolerated .

faropenem daloxate ( 300 mg )

cefuroxime axetil

faropenem daloxate treatment

cefuroxime axetil

faropenem daloxate group

cefuroxime axetil

faropenem daloxate

cefuroxime axetil

faropenem daloxate-treated

cefuroxime axetil

faropenem daloxate

cefuroxime axetil

efficacy and safety

acute bacterial maxillary sinusitis

clinical cure rate

bacteriological success rate

Eradication or presumed eradication

drug-related event

diarrhoea

nausea/vomiting

abdominal pain

skin reactions

clinically and bacteriologically

tolerated

acute bacterial maxillary sinusitis

adults .

acute sinusitis


Effects of ezetimibe , a new cholesterol absorption inhibitor , on plasma lipids in patients with primary hypercholesterolemia . AIMS This randomized , double-blind , placebo-controlled , parallel-group study evaluated the safety and efficacy of ezetimibe 10 mg/day in patients with primary hypercholesterolemia . METHODS AND RESULTS Following dietary stabilization , a 2-12-week washout period , and a 4-week , single-blind , placebo lead-in period , 827 patients with baseline low-density lipoprotein cholesterol ( LDL-C ) > or =3.36 mmol/l ( 130 mg/dl ) to < or =6.47 mmol/l ( 250 mg/dl ) and triglycerides < or =3.95 mmol/l ( 350 mg/dl ) were randomized 3:1 to receive ezetimibe 10 mg or placebo orally once daily in the morning for 12 weeks . The primary efficacy endpoint was percentage reduction in direct plasma LDL-C. Ezetimibe reduced direct LDL-C by a mean of 17.7 % from baseline to endpoint , compared with an increase of 0.8 % with placebo ( P < 0.01 ) . Response to ezetimibe was generally consistent across all subgroups analyzed . Ezetimibe also significantly improved levels of plasma total cholesterol , apolipoprotein B , high-density lipoprotein ( 2 ) -cholesterol and lipoprotein ( a ) , and elicited a trend toward lower triglyceride levels . Ezetimibe did not alter the serum concentrations of lipid-soluble vitamins or significantly affect baseline or stimulated cortisol production . Ezetimibe was well tolerated , with a safety profile similar to that of placebo . CONCLUSIONS Ezetimibe , which significantly reduces LDL-C and favorably affects other lipid variables , may provide a well tolerated and effective new option for lipid management in the future .

ezetimibe

placebo-controlled

ezetimibe

placebo

ezetimibe 10 mg or placebo

ezetimibe

Ezetimibe

Ezetimibe

Ezetimibe

Ezetimibe

plasma lipids

direct LDL-C

levels of plasma total cholesterol

apolipoprotein B

well tolerated

safety profile

LDL-C

lipid variables

well tolerated


A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer . BACKGROUND This randomized trial was conducted to compare the efficacy and side effects of intravesical mitoxantrone instillation with those of doxorubicin in superficial bladder cancer following transurethral resection . METHODS Sixty-three patients were randomized into mitoxantrone and doxorubicin groups . Most of the patients enrolled were elderly people ( mean age , 71 years ) . The instilled doses of doxorubicin and mitoxantrone were 30 and 14 mg , respectively . Disease recurrence and side effects were compared using Fisher 's exact test . The interval to recurrence was shown by Kaplan-Meier survivorship curves , and the log-rank test was used to compare the time to recurrence . RESULTS The median follow-up period was 36 months . Thirty-three patients received mitoxantrone , whereas 30 patients used doxorubicin . The recurrence rate in the doxorubicin group was 30 % ( 95 % CI : 19.8 % -38.8 % ) , while it was 27.3 % ( 95 % CI : 17.5 % -36.8 % ) in the mitoxantrone group . The median recurrence-free survival in the mitoxantrone group and in the doxorubicin group was 22 and 20 months , respectively ( p=0.580 ) . Higher recurrence rates were found for Grade III and multiple primary tumors . There was no significant difference in response rates ( p=0.784 ) . The incidence of side effects was 20 % in the doxorubicin group and 21.2 % in the mitoxantrone group . However , the difference was not significant ( p > 0.99 ) . CONCLUSIONS The results revealed that the efficacy and side effects of mitoxantrone were similar to those of doxorubicin . Especially for patients with pulmonary tuberculosis or aged patients with primary bladder tumors , mitoxantrone and doxorubicin may be the tolerable and effective intravesical agents .

mitoxantrone

doxorubicin

intravesical mitoxantrone instillation

doxorubicin

mitoxantrone

doxorubicin

doxorubicin

mitoxantrone

mitoxantrone

doxorubicin

doxorubicin

mitoxantrone

mitoxantrone

doxorubicin

doxorubicin

mitoxantrone

mitoxantrone

doxorubicin

mitoxantrone

doxorubicin

efficacy

side effects

Disease recurrence

side effects

interval to recurrence

time to recurrence

recurrence rate

median recurrence-free survival

recurrence rates

response rates

side effects

efficacy