The specific role of isoflavones on estrogen metabolism in premenopausal women . BACKGROUND There is increasing evidence that dietary factors may play a role in the production , metabolism , and bioavailability of sex hormones and their impact on target tissues . The specific objective of this study was to evaluate the effectiveness of supplementing a group of premenopausal women who were free of breast carcinoma with a dietary supplement of isoflavones ( 40 mg per day ) in producing a change in steroid hormones and menstrual cycle length . METHODS Sixty-eight consecutively recruited , premenopausal , omnivorous women of all races and ethnicities between the ages of 25 years and 55 years were admitted to the study and randomized to an experimental group supplemented with soy ( 40 mg genistein per day ) or to a control group that consumed a placebo for a 12-week period . Changes in their anthropometric , nutritional , and hormonal biomarkers from early follicular phase were analyzed at baseline and post-intervention . RESULTS Serum-free estradiol and estrone levels decreased moderately in the experimental group . Serum hormone-binding globulin levels increased in 41.4 % of women in the experimental group compared with 37.5 % of women in the placebo group . Free estradiol decreased in 53.85 % of women in the experimental group compared with 37.5 % of women in the placebo group . Estrone decreased in 55.56 % of women in the experimental group compared with 42.86 % in the placebo group . Those women in the experimental group who were consuming soy had their mean menstrual cycle length increased by 3.52 days compared with a mean decrease of 0.06 days for women in the placebo group ( P = 0.04 ) from baseline to the third menstrual cycle . In addition , women who were taking soy had their mean follicular phase increase by 1.46 days compared with a mean increase of 0.14 days for women who were taking the placebo ( P = 0.08 ) . CONCLUSIONS These data suggest that increased isoflavone intake affects estrogen metabolism by altering the steroid hormone concentrations and menstrual cycle length , thereby demonstrating a potential to reduce the risk for breast carcinoma .

isoflavones

isoflavones

soy ( 40

placebo

placebo

placebo

placebo

soy

placebo

soy

placebo

isoflavone

anthropometric

nutritional

hormonal biomarkers

Serum-free estradiol

estrone levels

Serum hormone-binding globulin levels

Free estradiol

mean menstrual cycle length

mean follicular phase increase

in premenopausal

women

carcinoma

Sixty-eight

25 years

55 years


Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status : a randomized , double-blind , placebo-controlled , phase IV study . Flavonoids , such as troxerutin , have been shown to be safe and effective agents for the treatment of chronic venous insufficiency . The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg ( Fleboside ampoules ) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids . The purpose of this randomized , double-blind , placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients . 30 patients were randomized to receive one of two treatments : troxerutin 150 mg and carbazochrome 1.5 mg , or placebo , i.m . 3 ml ampoules twice a day for five consecutive days after the surgical procedure , starting from the day of surgery . Efficacy parameters were assessed as follows : at baseline ( T1 ) , after the first administration ( T2 ; day of surgery ) , the second day after the surgical procedure ( T3 ) , and the fifth day after the surgical procedure ( T4 ) ; hemorrhoidal symptoms based on a visual analogue scale ( VAS ) : pain , discharge , bleeding , inflammation , and pruritus ; analgesic intake , if any ; time to restore a physiological defecation ; edema evaluation ( based on a four-point scale : 0 = absent ; 1 = mild ; 2 = moderate ; 3 = severe ) ; camera pictures taken at T1 and T4 ( in selected patients ) ; and blood coagulation tests . Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score ( p = 0.007 and p = 0.001 , respectively ) in favor of the active combination treatment . A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 ( p < 0.001 ) in favor of the active combination group . No adverse events were reported . Neither the active combination nor placebo affected blood coagulation tests . We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and carbazochrome 1.5 mg is effective , well tolerated and superior to placebo in improving hemorrhoidal and post-surgical symptoms during the five days following surgery .

troxerutin

troxerutin

carbazochrome

placebo

combination of troxerutin

carbazochrome

placebo

Efficacy

pain

discharge

bleeding

inflammation

pruritus

camera pictures taken at T1 and T4

blood coagulation tests

significant difference

total VAS score

bleeding

pruritus

inflammation

edema

No adverse events

blood coagulation

acute uncomplicated hemorrhoids

post-hemorrhoidectomy


Safety of intravitreous fomivirsen for treatment of cytomegalovirus retinitis in patients with AIDS . PURPOSE To report data regarding the safety of intravitreous fomivirsen for treatment of cytomegalovirus ( CMV ) retinitis in patients with acquired immunodeficiency syndrome ( AIDS ) . DESIGN Critical review of safety data from three randomized controlled clinical trials with supplemental information from an expanded drug access program . METHODS Adverse ocular events reported by clinician investigators were listed using terms modified from the COSTART dictionary . Data for two doses ( 165-microg/injection [ 35 eyes , 30 patients ] and 330-microg/injection [ 153 eyes , 120 patients ] ) and two 330-microg/injection dose schedules of different intensity were pooled to calculate incidence rates for each event . Rates were calculated as " events/patient-year " ( based on total cumulative reported events and duration of treatment ) for events that could recur during treatment . Rates were calculated as " patients with events/person-year " for the following events : retinal detachment , cataract , visual field disturbance , and retinal pigment epitheliopathy . To assess the ability to manage events , we reviewed treatments given for two events ( anterior chamber inflammation , increased intraocular pressure ) in one trial . We also report an analysis comparing the proportion of eyes that developed one or more key events to the cumulative number of injections . RESULTS Incidence rates were dose and schedule dependent ( 165 microg/injection , 4.06 events/patient-year ; 330 microg/injection , 6.58 events/patient-year [ less intense regimen ] and 8.35 events/patient-year [ more intense regimen ] ) . The most frequently reported events were anterior chamber inflammation and increased intraocular pressure . We found no evidence that the proportion of patients with events increased as the number of injections increased . CONCLUSIONS Intravitreous fomivirsen is well tolerated with an acceptable safety profile . Adverse ocular events associated with doses and schedules used clinically can be managed successfully with medical therapy .

fomivirsen

fomivirsen

anterior chamber inflammation

increased intraocular pressure

proportion of patients with events

number of injections increased .

Adverse ocular events


Step-down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis . OBJECTIVE To evaluate the feasibility and outcome of the step-down approach using either cyclosporin A ( CSA ) or methotrexate ( MTX ) as maintenance therapy following 6 months treatment with these 2 agents in combination in early , nonerosive rheumatoid arthritis ( RA ) . METHODS Fifty-seven patients younger than 65 years with early , nonerosive RA were first treated with CSA and MTX in combination for 6 months . They were then randomly stepped down to single-agent maintenance treatment for another 18 months . Safety , clinical efficacy , survival on treatment , and radiographic progression were evaluated . RESULTS When being treated with combination therapy , 7 of the 57 patients ( 12.3 % ) withdrew because of adverse events . Of the remaining 50 patients , 42 ( 84.0 % ) were American College of Rheumatology ( ACR ) 20 % responders , 30 ( 60.0 % ) were ACR 50 % responders , and 23 ( 46.0 % ) were ACR 70 % responders . At month 6 , 22 patients were randomized to CSA and 27 to MTX . During this trial period , the treatment was discontinued by 16 patients taking CSA ( mainly because of loss of efficacy ) and by 4 taking MTX . At month 24 , the probability ( +/- SEM ) of survival on treatment was 0.273 +/- 0.09 for CSA and 0.852 +/- 0.07 for MTX . Of the 6 CSA patients who completed the trial , 4 ( 66.7 % ) were ACR 20 % responders , and 3 ( 50 % ) were both ACR 50 % and ACR 70 % responders . Of the 23 completers in the MTX arm , 21 ( 91.3 % ) were ACR 20 % responders , 18 ( 78.3 % ) were ACR 50 % , and 10 ( 43.5 % ) were ACR 70 % responders . The treatment was not responsible for severe adverse events . Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups . CONCLUSION Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX . Because this treatment did not prevent some radiographic progression , other approaches ( e.g. , step-up approach ) may be more appropriate in early RA .

cyclosporin A

methotrexate

cyclosporin A ( CSA )

methotrexate ( MTX )

CSA

MTX in combination

single-agent

CSA

MTX

CSA

MTX

CSA

MTX

MTX

CSA

MTX

MTX

feasibility and outcome

Safety , clinical efficacy

survival on treatment

radiographic progression

adverse events

efficacy

survival

adverse events

radiographic progression

rheumatoid arthritis .

nonerosive RA

7 of the 57 patients

early RA


Detection of recurrent or persistent nasopharyngeal carcinomas after radiotherapy with technetium-99m methoxyisobutylisonitrile single photon emission computed tomography and computed tomography : comparison with 18-fluoro-2-deoxyglucose positron emission tomography . BACKGROUND The diagnostic accuracy of technetium-99m methoxyisobutylisonitrile ( Tc-MIBI ) single photon emission computed tomography ( SPECT ) and computed tomography ( CT ) of the head and neck for differentiating recurrent or residual nasopharyngeal carcinomas ( NPC ) from benign lesions after radiotherapy was compared with positron emission tomography ( PET ) with 18-fluoro-2-deoxyglucose ( FDG ) . METHODS Thirty six NPC patients underwent head and neck CT , Tc-MIBI SPECT , and FDG-PET four months after radiotherapy to differentiate recurrent or residual NPC from benign lesions . Histopathologic examinations of nasopharyngeal biopsies were performed for all 36 patients . No patients had multiple foci of NPC . RESULTS Based on biopsy results , the sensitivity , specificity , and accuracy of CT for differentiating recurrent or residual NPC from benign lesions were 73 % , 88 % , and 83 % , respectively . The sensitivity , specificity , and accuracy of Tc-MIBI SPECT were 73 % , 96 % , and 89 % , respectively . The sensitivity , specificity , and accuracy of FDG-PET were 100 % , 96 % , and 97 % , respectively . Combination CT and Tc-MIBI SPECT for 28 NPC patients with congruent results showed the same sensitivity , specificity , and accuracy of 100 % , 96 % , and 96 % , respectively , as FDG-PET for differentiating recurrent or residual NPC from benign lesions . In eight patients with incongruent results between CT and Tc-MIBI SPECT , FDG-PET correctly differentiated two benign lesions and six recurrent or residual NPCs . CONCLUSIONS In detecting recurrent or residual NPC , FDG-PET is the best tool . However , combined use of CT and Tc-MIBI SPECT can result in the same accuracy as FDG-PET .

computed tomography

computed tomography ( CT )

radiotherapy

CT

Tc-MIBI SPECT

FDG-PET

CT

Tc-MIBI SPECT

FDG-PET

FDG-PET

FDG-PET

CT

Tc-MIBI SPECT

FDG-PET

recurrent

recurrent or residual NPC

accuracy

NPC

Thirty six


A role for error training in surgical technical skill instruction and evaluation . BACKGROUND During the evaluation of many instances of the same basic surgical skill , we observed that there were several errors that occurred frequently . Two studies were undertaken to examine the use of these errors for improving the instruction and evaluation of the skill . MATERIALS AND METHODS For both studies , two types of rater training videotapes were developed . One involved the use of examples of common errors ( error ) and the other demonstrated the skill being performed correctly ( correct ) . A testing videotape was created consisting of 24 performances of the skill that ranged in quality of the performance . The first study was designed to assess the impact of error instruction on skill acquisition . In this study , a group of 30 senior medical students were randomly assigned to one of four different training groups : none , error only , correct only , and error+correct . Subjects were videotaped performing the skill before and after the training and three experts evaluated these performances independently using a 7-point rating scale . The second study was designed to assess the impact of error training on skill evaluation and was done using both novice and expert raters . The same group of 30 senior medical students used in the first study was used as novice raters . Following training in one of the four training groups , each subject rated the 24 performances on the testing videotape and interrater reliability was assessed for each group . Surgical faculty served as expert raters in this study and were randomly assigned to receive either error training or no training . Each subject viewed the testing videotape , rating the performances and giving " feedback " commentary . Interrater reliability was calculated for the two groups and the precision of the feedback was assessed . RESULTS Significant improvement in posttest performance scores was seen only in the " error+correct " training group . Interrater reliability was somewhat lower for the " correct only " and " error only " training groups in both the student and faculty studies . Faculty raters receiving error training had a higher proportion of specific comments than the group that received no training although this difference was not statistically significant . CONCLUSIONS Instruction about common errors , when combined with instruction about the correct performance enhanced the acquisition of this surgical skill . This suggests a role for the use of errors in surgical technical skill instruction . Our study provides no support for a role for error training in improving skill evaluation .

error training

two types of rater training videotapes

examples of common errors ( error )

error instruction

error training

error training

no training .

" error+correct "

surgical technical skill instruction .

skill acquisition

performances

Interrater reliability

posttest performance scores

Interrater reliability


Regional ischemic preconditioning enhances myocardial performance in off-pump coronary artery bypass grafting . OBJECTIVES We intended to investigate whether ischemic preconditioning ( IP ) enhances myocardial performance in patients who undergo off-pump coronary artery bypass grafting ( CABG ) . DESIGN A controlled , randomized , prospective study . SETTING A university hospital . PATIENTS Thirty-two patients with left anterior descending coronary artery ( LAD ) or two-vessel heart disease ( including LAD ) who were to undergo off-pump CABG were randomized into an IP group and a control group . INTERVENTIONS IP was induced by occluding the LAD twice for a 2-min period followed by 3-min LAD reperfusion before bypass grafting of the first coronary vessel . MEASUREMENTS AND RESULTS Registration included hemodynamic data from the peripheral artery and the pulmonary artery , and the measurement of cardiac troponin I ( CTnI ) and creatine kinase isoenzyme MB ( CK-MB ) values . IP resulted in a complete recovery of the mean stroke volume index ( SVI ) after the operation . In the control subjects , the mean SVI showed a significant reduction postoperatively ( p = 0.039 ) . On the first postoperative day , the increase in the mean heart rate ( HR ) was also significantly lower in the IP patients . The CTnI level was statistically significantly lower in the IP group ( p = 0.043 ) , and IP patients tended to have a smaller CK-MB release after surgery ( not significant ) . The duration of mechanical ventilation , the length of stay in the ICU , and the use of inotropic medication did not increase after the IP protocol . CONCLUSIONS Two cycles of regional 2-min IP in the LAD , followed by 3 min of reperfusion , proved to be applicable and safe in patients undergoing off-pump myocardial revascularization , it tended to decrease the immediate myocardial enzyme release , it prohibited the postoperative increase in HR , and it enhanced the recovery of SVI .

Regional ischemic preconditioning

myocardial

myocardial

cardiac troponin I ( CTnI )

mean SVI

mean heart rate ( HR )

CTnI level

CK-MB release

use of inotropic medication

myocardial enzyme

HR

SVI


Endometrial cytodiagnosis using a new softcyte versus a conventional endocyte . A new endometrial cytologic sampling device , softcyte , was used in cytological screening for endometrial cancer , and was compared with the endocyte with regard to manipulability , adverse effects ( including pain and hemorrhage ) , and cellular findings ( including the quantity of cells collected , the success rate , cell freshness , and cellular clumping ) . A total of 315 women ( premenopause 251 , postmenopause 64 ) were randomly assigned to two groups who underwent the endometrial cytological screening with either the softcyte or the endocyte . To assess the value of the softcyte we compared it with the endocyte . Endometrial cytology using a softcyte or an endocyte achieved high correct diagnosis rate for cancer , and both instruments are valuable as endometrial cytologic sample devices . The softcyte causes only mild pain on introduction and during collection , and a large quantity of cells could be harvested . These results suggest that the softcyte is a useful cytologic sampling device in screening for endometrial cancer .

softcyte

endocyte

endocyte

endometrial cytological screening

softcyte

endocyte

softcyte

endocyte

softcyte

endocyte

correct diagnosis rate for

cancer

quantity of cells

315 women


[ One-year effect of health counseling on life style and risk factors of heart disease ] . INTRODUCTION We examined the need for counselling and the effect on willingness and ability to change life-style , and subsequent changes in risk factors for CHD . MATERIAL AND METHODS All 152 male employees in a computer company , 25-45 years of age , were invited to participate in a controlled intervention study over one year . The subjects were randomised to an intervention group ( I group ) and a control group . The I group was divided into subgroups based on baseline behaviour and risk factor status . Changes were evaluated after one year . After an initial health examination , participants in the I group were counselled at baseline and at 5 months . RESULTS Eighty-five ( 56 % ) men participated . Twenty-nine were assigned to a control group and 56 to an intervention group ( I group ) ( dropouts = 8 ) . An exercise group ( E group ) was advised to take up aerobics exercise three times/week , a diet group to reduce the intake of saturated fat and increase fish products , and smokers to stop smoking . Forty were recommended one or more behavioural changes and eight had no need . Thirty-four were willing to make behavioural changes . Compared to the control group , the fitness level increased ( p < 0.01 ) and body weight decreased in the I group ( p < 0.05 ) . DISCUSSION Individual counselling promotes regular exercise with subsequent improvements in CHD risk factors . The diet and smoking counselling models were less successful in terms of compliance .

health counseling

intervention group

control group .

counselled

exercise group

aerobics exercise

diet group

stop smoking .

one or more behavioural changes

Individual counselling

diet and smoking counselling models

life-style

subsequent

changes in risk factors for CHD

fitness level

body weight

CHD risk factors

male

employees in a computer company

25-45 years of age

Eighty-five

men


Short-term intravenous antibiotic treatment of acute hematogenous bone and joint infection in children : a prospective randomized trial . Thirty-three cases of acute hematogenous bone or joint infection in children were randomly treated with short-term ( 7 days for joint infection , 10 days for bone infection ) or long-term ( 14 days and 21 days , respectively ) intravenous antibiotics after surgical drainage . The treatment outcome was measured through a detailed scoring system that included the ability to eradicate infection , the functional status of the limb , and the radiographic appearance of the bone and joint . The results were similar in both groups , showing the added benefit of a shorter hospital stay for children with blood-borne musculoskeletal infection . The use of this scoring system in choosing the route of antibiotic administration is recommended .

short-term

long-term

intravenous antibiotics

surgical drainage

antibiotic

ability to eradicate infection

functional status of the limb

children

Thirty-three

musculoskeletal infection


Diet and tobacco use : analysis of data from the diabetic control and complications trial , a randomized study . CONTEXT The Diabetic Control and Complications Trial ( DCCT ) researchers kept careful records of the food consumption and tobacco using habits of type 1 diabetic subjects . However , they did not report the relationship of tobacco using habits with dietary intake . OBJECTIVE Analyze the relationship between tobacco smoking and intake of macro and micronutrients . DESIGN Randomized controlled trial . SETTING Referral clinics in 27 academic centers . PATIENTS Type 1 diabetics . INTERVENTION Using the data sets of the DCCT , this study analyzed the strengths of the associations between smoking and macronutrient consumption , hemoglobin A1c ( HbA1c ) , body mass index ( BMI ) , and serum lipid levels at the study baseline , 2 years , and 4 years . MAIN OUTCOME MEASURES Statistically significant correlations between smoking and nutrient intake , HbA1c , and serum lipid levels . RESULTS Cigarette , cigar , or pipe use at each time interval correlated with significantly increased caloric intake in males but not in females . In both males and females , tobacco users consumed more fat , cholesterol , and alcohol . Female smokers had higher serum low-density lipoprotein ( LDL ) /high-density lipoprotein ( HDL ) ratios and triglycerides . Serum cholesterols , LDL/HDL ratios , LDL cholesterols , and triglyceride determinations in male tobacco users significantly exceeded those in nonsmoking males . HDL cholesterols were lower in both female and male tobacco users . Nutrient intake of former tobacco users resembled that of nonusers rather than current users . CONCLUSIONS A significant association exists between smoking and a diet with higher risks of atherosclerosis , cancer , and other degenerative diseases . The strong association of tobacco with heart disease , stroke , vasculopathies , and various malignancies may be in part due to its association with a higher fat diet . The higher fat diet of tobacco users probably accounts in part for their higher risk of developing type 2 diabetes and hyperlipidemia . Tobacco users should be informed about the diet and tobacco use association .

Diet

intake of macro and micronutrients

data sets of the DCCT

macronutrient consumption

tobacco using habits

dietary intake

macronutrient consumption

serum lipid levels

nutrient intake

Cigarette , cigar , or pipe use

caloric intake

Serum cholesterols

LDL/HDL ratios

LDL cholesterols

triglyceride determinations

HDL cholesterols

Nutrient intake

diet

tobacco use

type 1 diabetic

diabetics

males

females


Oat ingestion reduces systolic and diastolic blood pressure in patients with mild or borderline hypertension : a pilot trial . OBJECTIVES We assessed the short-term antihypertensive effects of soluble fiber-rich whole oat cereals when added to a standard American diet . In addition , multiple assessments of insulin sensitivity were conducted . STUDY DESIGN This was a randomized , controlled , parallel-group pilot study designed to compare an oat cereal group ( standardized to 5.52 g/day beta-glucan ) to a low-fiber cereal control group ( less than 1.0 g/day total fiber ) over 6 weeks . POPULATION A total of 18 hypertensive and hyperinsulinemic ( = 10 U/mL or more ) men and women completed the trial . OUTCOMES MEASURED Primary study outcomes were changes in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) . Secondary outcomes included blood lipid , fasting glucose , and insulin levels and side effects related to elevated blood pressure and increased dietary fiber intake . RESULTS The oat cereal group experienced a 7.5 mm Hg reduction in SBP ( P & lt.01 ) and a 5.5 mm Hg reduction in DBP ( P & lt.02 ) , while there was virtually no change in either SBP or DBP in the control group . In the oat cereal group , a trend was observed for a lower total insulin response to a glucose load , suggesting improved insulin sensitivity . However , this could not be confirmed using estimates from the Bergman Minimal Model , perhaps because of our small sample size . The oats group experienced a significant reduction in both total cholesterol ( 9 % ) and low-density lipoprotein cholesterol ( 14 % ) . CONCLUSIONS The addition of oat cereals to the normal diet of patients with hypertension significantly reduces both SBP and DBP . Soluble fiber-rich whole oats may be an effective dietary therapy in the prevention and adjunct treatment of hypertension .

Oat ingestion

soluble fiber-rich whole oat cereals

oat cereals

Soluble fiber-rich whole oats

systolic blood pressure ( SBP )

diastolic blood pressure ( DBP )

blood lipid

fasting glucose

insulin levels

SBP

DBP

total insulin response

total cholesterol

low-density lipoprotein cholesterol

SBP

DBP


Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis : long-term follow-up . OBJECTIVE To assess post-treatment effects in endometriosis patients of a 12-month course of GnRH agonist alone or with one of three " add-back " regimens . METHODS This is a post-treatment follow-up analysis of a randomized , double-masked , placebo-controlled 52-week trial . All patients had received monthly leuprolide acetate and were randomized to one of four groups : A-daily placebo ; B-daily norethindrone acetate 5 mg ; C-daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg ; and D-daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial , 123 completed at least 280 days of therapy and entered the follow-up period . Physical findings and symptoms were quantified , and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post-therapy . RESULTS Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups ( P < .05 ) . Findings were not affected by endometriosis scores noted on screening laparoscopy . Mean bone mineral density values remained at or above baseline in all add-back groups . The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow-up visit ( P < .001 ) . CONCLUSION GnRH agonist and norethindrone acetate alone or combined with low-dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy .

Prolonged GnRH agonist

add-back therapy

GnRH agonist

" add-back " regimens

placebo-controlled

leuprolide acetate

placebo

norethindrone acetate

C-daily norethindrone acetate

conjugated equine estrogens

norethindrone acetate

conjugated equine estrogens

GnRH agonist

norethindrone acetate alone

low-dose conjugated equine estrogens

symptomatic endometriosis

lumbar spine bone mineral density

Symptom and pelvic examination scores

endometriosis scores

Mean bone mineral density values

loss in bone density

pain relief

bone mineral density

symptomatic endometriosis

endometriosis

symptomatic endometriosis


Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis . BACKGROUND We previously reported urinary podocytes to be a marker of glomerular injury . The aim of the present study was to determine whether cerivastatin , a newly developed , potent synthetic statin , affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis ( CGN ) . METHODS We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day ( n=20 ) or placebo ( n=20 ) . Subjects comprised 24 men and 16 women , with a mean age of 40.8+/-14.4 years ; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis . Treatment was continued for 6 months . Plasma total cholesterol , HDL-cholesterol , LDL-cholesterol and triglycerides , urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment . RESULTS After 6 months , a significant reduction in total cholesterol ( P < 0.001 ) , LDL-cholesterol ( P < 0.001 ) and triglycerides ( P < 0.05 ) , and a significant increase in HDL-cholesterol ( P < 0.001 ) were observed in the group treated with cerivastatin . Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day , ( P < 0.01 ) in this group , and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml ( P < 0.01 ) . However , placebo showed little effect on these lipid levels , urinary protein excretion and urinary podocyte excretion . The differences between the cerivastatin group and the placebo group were significant ( cholesterol , P < 0.001 ; LDL-cholesterol , P < 0.001 ; triglycerides , P < 0.05 ; HDL-cholesterol , P < 0.001 ; urinary protein , P < 0.01 ; and urinary podocytes , P < 0.01 ) . CONCLUSION Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia .

cerivastatin

cerivastatin

cerivastatin

placebo

cerivastatin

placebo

Plasma total cholesterol

HDL-cholesterol

LDL-cholesterol and triglycerides

urinary protein excretion

number of podocytes

total cholesterol

LDL-cholesterol

triglycerides

increase in HDL-cholesterol

Urinary protein excretion

urinary podocyte excretion

lipid levels

urinary protein excretion

urinary podocyte excretion

LDL-cholesterol

triglycerides

HDL-cholesterol

urinary protein

urinary podocytes

chronic glomerulonephritis .

chronic glomerulonephritis ( CGN )

hypercholesterolemic

CGN

men

women

IgA nephropathy

CGN

hypercholesterolaemia


Effects of clonidine on postoperative nausea and vomiting in breast cancer surgery . BACKGROUND Postoperative nausea and vomiting ( PONV ) is still common , especially among female patients . Our hypothesis is that coinduction with clonidine reduces the incidence of PONV in adult patients undergoing breast cancer surgery . METHODS Sixty-eight women premedicated with midazolam were randomly allocated to coinduction with intravenous clonidine ( group C ) or placebo ( group P ) in this prospective , double-blind study . Anesthesia was standardized ( laryngeal mask airway , fentanyl , propofol , sevoflurane , nitrous oxide , and oxygen ) . Hemodynamic parameters and the requirements for propofol , sevoflurane , and the postoperative need for ketobemidone were noted . The primary endpoints studied were the number of PONV-free patients and patient satisfaction with respect to PONV . RESULTS Patients in group C had a significantly reduced need for propofol ( P < 0.04 ) and sevoflurane ( P < 0.01 ) and a reduced early need for ketobemidone ( P < 0.04 ) . There were significantly more PONV-free patients in group C compared with group P ( 20 and 11 of 30 , respectively ; P < 0.04 ) . The number needed to treat was 3.3 ( 95 % confidence interval , 1.8 , 16.9 ) . Intraoperative blood pressure , postoperative heart rate , and postoperative blood pressure were all significantly lower in group C compared with group P , but were not considered to be of clinical importance . No negative side effects were recorded . CONCLUSION Coinduction with clonidine significantly increased the number of PONV-free patients after breast cancer surgery with general anesthesia .

clonidine

clonidine

clonidine

placebo

laryngeal mask airway

fentanyl

propofol

sevoflurane

nitrous oxide , and oxygen

clonidine

number of PONV-free patients

reduced need for propofol

early need for ketobemidone

PONV-free patients

side effects

PONV-free patients

breast cancer surgery .


Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice . AIMS To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome ( PCOS ) in an infertility clinic . METHODS This was a randomized placebo controlled double-blind crossover study of 3 months metformin ( 1500 mg day-1 ) /placebo , followed by 3 months metformin/placebo together with clomiphene ( 50-100 mg for 5 days ) for three cycles in clomiphene resistant women with PCOS . The primary outcomes were restoration of spontaneous menses , ovulation induction ( spontaneous or clomiphene induced ) and pregnancy . Secondary endpoints were changes in biochemical parameters related to androgens and insulin . RESULTS Twelve women completed the metformin arm and 14 the placebo arm . Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women , P=0.63 . No women given metformin spontaneously ovulated , although one patient given placebo did , P=0.30 . There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five ( out of 12 ) metformin treated women and four ( out of 14 ) placebo treated women , P=0.63 . Pregnancy occurred in three ( out of 12 ) women given metformin and two ( out of 14 ) women given placebo , P=0.59 . CONCLUSIONS Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice .

Metformin

metformin

metformin

/placebo

metformin/placebo

metformin

placebo

metformin

placebo

placebo

metformin

placebo

metformin

placebo

Metformin

beneficial effects

Spontaneous menstruation

spontaneously ovulated

efficacy of clomiphene

ovulation being induced

Pregnancy

clomiphene resistant infertile

women

polycystic ovary syndrome

PCOS

clomiphene resistant

women

PCOS

Twelve

women

clomiphene resistant infertile

women

PCOS


Rizatriptan 5 mg for the acute treatment of migraine in adolescents : a randomized , double-blind , placebo-controlled study . OBJECTIVE To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs . METHODS Randomized , double-blind , placebo-controlled study . Patients aged 12 to 17 years received rizatriptan 5 mg ( n = 149 ) or placebo ( n = 147 ) for a moderate or severe headache and for up to two recurrences . Headache severity , presence or absence of associated symptoms , and functional disability were assessed over a 4-hour postdose period , and any adverse events were recorded . The primary efficacy measure was pain-free status at 2 hours postdose . RESULTS Rizatriptan 5 mg was well tolerated . The most commonly reported adverse events ( all with incidence of 5 % or less ) among patients receiving rizatriptan were dry mouth , dizziness , asthenia/fatigue , nausea , and somnolence . The percentage of patients pain-free at 2 hours was 32 % for rizatriptan 5 mg versus 28 % for placebo ( P=.474 ) . The percentage of patients with pain relief ( reduction of predose pain intensity to mild or none ) at 2 hours was 66 % for rizatriptan versus 56 % for placebo ( P=.079 ) . Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults . Compared with placebo , rizatriptan significantly improved functional disability at 1.5 and 2 hours , and nausea at 1 and 1.5 hours . Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends ( 65 % versus 36 % , P=.046 ) compared with weekdays ( 66 % versus 61 % , P=.365 ) , and the weekend placebo response rate was similar to that seen in adults . CONCLUSIONS Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack .

Rizatriptan

placebo-controlled

rizatriptan

rizatriptan

placebo

Rizatriptan

rizatriptan

rizatriptan

placebo

Placebo

rizatriptan

placebo

rizatriptan

tolerability and efficacy

Headache severity

functional disability

adverse events

pain-free status at 2 hours postdose

adverse events

pain-free

percentage of patients with pain relief

predose pain intensity

Placebo response rates

functional disability

nausea

pain relief

response rate

tolerated and effective

migraine

adolescents

12 to 17 years

attack


N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations : results of a prospective , randomized , multi-center trial . BACKGROUND AND PURPOSE Liquid N-butyl cyanoacrylate ( n-BCA ) use for the treatment of arteriovenous malformations ( AVM ) in the brain has become part of medical practice . However , no study has led to the Food and Drug Administration 's approval of n-BCA for intravascular use . The purpose of this study was to verify the effectiveness and safety of an n-BCA/Tantalum Powder/Ethiodized Oil mixture , compared with conventional treatment ( Trufill polyvinyl alcohol [ PVA ] ) for preoperative embolization of cerebral AVM . METHODS Between October 15 , 1996 , and March 24 , 1999 , 104 patients at 13 centers were prospectively randomized to undergo embolization using an n-BCA/Tantalum Powder/Ethiodol mixture or Trufill PVA . The pre-embolization therapy goals were determined in terms of the number of pedicles to be embolized and the percent of nidus reduction expected . Embolization results were evaluated by a central laboratory . Subsequent surgical resection data were recorded . Safety evaluation data included recording device complications , procedure complications , and intracranial events/overall neurologic outcomes , which could be either device-related , procedure-related , or both . RESULTS The reduction of AVM dimensions ( 79.4 % in the n-BCA group and 86.9 % in the PVA group ) and the mean number of vessels embolized ( 2.2 in the n-BCA group and 2.1 in the PVA group ) was similar in the two groups . Coils were used more commonly with PVA embolization ( P < .0001 ) . No differences were detected in surgical resection time , number of patients who required transfusion , volume and number of transfusion units , or type and volume of fluid replacement . Glasgow Outcome Scale scores were not significantly different between the two groups before treatment , after embolization , or after resection . Two of 42 patients who underwent resection and had been treated with n-BCA experienced post-resection hematoma , compared with eight of 45 patients who underwent resection and had been treated with PVA ( P < .05 ) . CONCLUSION This prospective , randomized trial showed that n-BCA is equivalent to PVA as a preoperative embolic agent for treatment of cerebral AVM as determined by percent of nidus reduction and number of feeding pedicles embolized .

Trufill PVA

device complications

procedure complications

AVM dimensions

mean number of vessels embolized

surgical resection time

volume and number of transfusion units

type and volume of fluid replacement

Glasgow Outcome Scale scores

post-resection hematoma

cerebral AVM


Effect of four intermediate layer treatments on microleakage of Class II composite restorations . This in vitro study examines the marginal sealing ability of four different intermediate materials applied before placement of a condensable composite . Class II preparations were made with gingival margins placed 1.0 mm apical to the cementoenamel junction of 60 extracted teeth , randomly assigned to five groups of 12 . Following restoration , teeth were thermocycled , soaked in 0.5 % basic fuchsin , and sectioned longitudinally . The resin-modified glass ionomer cement demonstrated significantly less microleakage than the use of a dentin bonding agent alone or in combination with flowable composite , flowable compomer , or autoploymerizing composite ( p < 0.05 , Dunn 's test ) . This study supports the use of the glass ionomer open sandwich technique in deep Class II direct composite restorations .

four intermediate layer treatments

four different intermediate materials

condensable composite

fuchsin

resin-modified glass ionomer cement

dentin bonding agent

combination with

flowable composite

glass ionomer open sandwich technique

less microleakage

extracted teeth


Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus . The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial ( DCCT ) , a randomized controlled clinical trial , and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications ( EDIC ) study , regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus . The DCCT proved that intensive treatment reduced the risks of retinopathy , nephropathy , and neuropathy by 35 % to 90 % compared with conventional treatment . The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin ( HbA ( 1c ) ) level over the follow-up period preceding each event . Intensive treatment was most effective when begun early , before complications were detectable . These risk reductions , achieved at a median HbA ( 1c ) level difference of 9.1 % for conventional treatment vs 7.3 % for intensive treatment have been maintained through 7 years of EDIC , even though the difference in mean HbA ( 1c ) levels of the 2 former randomized treatment groups was only 0.4 % at 1 year ( P < .001 ) ( 8.3 % in the former conventional treatment group vs 7.9 % in the former intensive treatment group ) , continued to narrow , and became statistically nonsignificant by 5 years ( 8.1 % vs 8.2 % , P =.09 ) . The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group . Thus , the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation . Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter , aiming for a practicable target HbA ( 1c ) level of 7.0 % or less .

intensive therapy

intensive treatment

intensive treatment

Intensive treatment

intensive treatment

intensive treatment

intensive treatment

Intensive treatment

microvascular complications

microvascular complications

retinopathy

nephropathy

neuropathy

retinopathy

nephropathy

median HbA ( 1c ) level

difference in mean HbA ( 1c ) levels

rate of progression of complications

target HbA ( 1c ) level

type 1 diabetes mellitus

type 1 diabetes mellitus


The influence of placebo awareness on stimulant drug response in a double-blind trial . RATIONALE Critics have called into question findings from double-blind placebo-controlled studies because subjects are given drug administration instructions informing them of a placebo condition . The assertion that these drug administration instructions bias estimates of effectiveness has undergone surprisingly little empirical investigation . OBJECTIVES The primary objective of this study was to determine whether drug administration instructions informing subjects of a placebo condition affect the drug response and affect the saliva concentration of the stimulant . METHODS We assessed caffeine responses and levels of saliva concentration of caffeine in 52 subjects who were randomly assigned to receive one of two drug administration instructions : ( a ) placebo-informed instructions ( i.e. , individuals informed of the placebo ) analogous to those used in double-blind studies and ( b ) placebo-uninformed instructions ( i.e. , individuals informed they are taking an active stimulant ) . RESULTS On most measures ( systolic blood pressure , heart rate , hand steadiness , reaction time , fatigue , and tension ) , drug administration instructions did not significantly influence caffeine response . Instructions also had no significant effect on saliva concentration of caffeine . However , only individuals who were uninformed of the placebo condition showed significant diastolic blood pressure and vigor increases with 125 mg caffeine , and significant hand steadiness impairment and vigor increases with 325 mg caffeine compared to placebo . CONCLUSIONS These overall findings suggest that a limited bias is introduced by drug administration instructions . The results do not support any suggestion that information about the existence of a placebo condition dramatically influences conclusions drawn about drug responses in placebo-controlled trials .

placebo

placebo-informed instructions

individuals informed of the placebo

placebo-uninformed instructions

caffeine

caffeine

saliva concentration

caffeine response

saliva concentration

diastolic blood pressure and vigor

hand steadiness impairment and vigor


Treatment of acute ischaemic stroke with the low-affinity , use-dependent NMDA antagonist AR-R15896AR . A safety and tolerability study . BACKGROUND AND PURPOSE A low-affinity , use-dependent N-Methyl-D-Aspartate ( NMDA ) antagonist AR-R15896AR has neuroprotective properties in animal models of ischaemic stroke . The aim of the present study was to examine the safety and tolerability of a new and higher dosage regimen that would enable acute stroke patients to achieve and maintain neuroprotective plasma concentrations . METHODS A randomised , multi-centre , double-blind , placebo-controlled , parallel group study was carried out at 19 centres in France , Germany and the Netherlands in patients with a clinical diagnosis of acute ischaemic stroke , and onset of symptoms within 12 hours before start of study drug administration . Two loading doses of 3.5 mg/kg of AR-R15896AR over 60 minutes , followed by a 2.5 mg/kg infusion over the next 120 minutes were given . Eight hours after the start of the loading dose infusion , the first maintenance dose ( 120 mg ) was administered over 60 minutes . Eight further maintenance infusions were administered at intervals of 8 hours over a total treatment period of 3 days . Main variables were safety , tolerability and pharmacokinetics . Follow-up assessments also included the Barthel Index ( BI ) and the NIH Stroke Scale ( NIHSS ) at 4-7 days after the end of the last infusion and at 30 days after the onset of stroke . RESULTS 103 patients with acute ischaemic stroke were randomised to either treatment with AR-R15896AR ( 70 patients ) or placebo ( 33 patients ) . Mortality was not significantly different in the AR-R15896AR group compared with the placebo group ( 10 % vs. 6 % ) . Serious adverse events during treatment due to psychiatric conditions were associated with AR-R15896AR ( 3 vs. 0 ) . Other side effects were more common in the group treated with AR-R15896AR : vomiting ( 29 % vs. 9 % ) , nausea ( 23 % vs. 12 % ) , fever ( 17 % vs. 12 % ) , agitation ( 7 % vs. 3 % ) , dizziness ( 7 % vs. 0 % ) , and hallucinations ( 6 % vs. 0 % ) . No significant difference between the two groups ( with respect to the proportions of patients with favourable outcome ) was detected in either the analysis of the BI or the NIHSS . Pharmacokinetic data showed that plasma concentrations of AR-R15896AR were in the expected neuroprotective range . CONCLUSION In most of the patients with acute stroke receiving AR-R15896AR the intended high plasma levels were reached within a short time period . However , active treatment produced more side effects than placebo , thus indicating safety concerns and tolerability issues for use in high doses in an acute stroke population .

NMDA antagonist AR-R15896AR

placebo-controlled

placebo

placebo

placebo

safety and tolerability

Barthel Index ( BI )

NIH Stroke Scale ( NIHSS )

Mortality

Serious adverse events

vomiting

nausea

fever

agitation

dizziness

hallucinations

plasma concentrations of AR-R15896AR

high plasma levels

side effects

animal models of ischaemic stroke

acute ischaemic stroke

103 patients


Improved fibrinolysis after 1-year treatment with HMG CoA reductase inhibitors in patients with coronary heart disease . The study was aimed to investigate the effect of two different statins on the levels of haemostatic variables reflecting procoagulant and fibrinolytic activity in patients with coronary heart disease ( CHD ) , with the hypothesis that statins might beneficially modify these levels . Fifty-eight patients were randomized to treatment with atorvastatin ( n=28 ) or simvastatin ( n=30 ) for 1 year . The starting dose in both groups was 20 mg/day . Fasting blood samples were collected before and after 12-month treatment for determinations of fibrinogen , prothrombin fragment 1+2 ( F1+2 ) , plasma D-dimer , soluble tissue factor , tissue plasminogen activator ( tPA ) antigen , tPA activity , plasminogen activator inhibitor type-1 activity ( PAI-1 activity ) and serum D-dimer as a global test of fibrinolytic activity . In the total population , improved fibrinolytic activity was observed after 1 year with increased levels of serum D-dimer ( P=.001 ) and tPA activity ( P=.024 ) and a reduction in tPA antigen ( P=.048 ) . No statistically significant changes were observed in any of the measured coagulation variables . Separately examined , an improved fibrinolytic profile was seen in the atorvastatin group with a significant increase in serum D-dimer ( P=.005 ) , a borderline increase in tPA activity ( P=.083 ) and a borderline reduction in tPA antigen ( P=.069 ) . Within the simvastatin group , a reduction in prothrombin F1+2 was observed ( P=.038 ) . The differences in changes between the groups were statistically significant only for global fibrinolysis ( serum D-dimer , P=.046 ) . In conclusion , an improved fibrinolytic profile was observed after statin treatment , most pronounced with atorvastatin . The results indicate that the drugs promote a profibrinolytic profile , and may in part explain the benefit of statin treatment rendered in the prevention of CHD .

HMG CoA reductase inhibitors

statins

statins

atorvastatin

simvastatin

atorvastatin

simvastatin

statin

atorvastatin

statin

Fasting blood samples

fibrinogen

soluble tissue factor

tPA activity

improved fibrinolytic activity

serum D-dimer

tPA activity

reduction in tPA antigen

increase in serum D-dimer

increase in tPA activity

reduction in tPA antigen

reduction in prothrombin F1+2

global fibrinolysis

fibrinolytic profile

patients with coronary heart disease

Fifty-eight patients


Thiabendazole for the prophylaxis of strongyloidiasis in immunosuppressed patients with hematological diseases : a randomized double-blind placebo-controlled study .

Thiabendazole

placebo-controlled

immunosuppressed

hematological diseases :


Lack of benefit of an active pectoral pulse generator on atrial defibrillation thresholds . INTRODUCTION Atrial defibrillation can be achieved with standard implantable cardioverter defibrillator leads , which has led to the development of combined atrial and ventricular devices . For ventricular defibrillation , use of an active pectoral electrode ( active can ) in the shocking pathway markedly reduces defibrillation thresholds ( DFTs ) . However , the effect of an active pectoral can on atrial defibrillation is unknown . METHODS AND RESULTS This study was a prospective , randomized , paired comparison of two shock configurations on atrial DFTs in 33 patients . The lead system evaluated was a dual-coil transvenous defibrillation lead with a left pectoral pulse generator emulator . Shocks were delivered either between the right ventricular coil and proximal atrial coil ( lead ) or between the right ventricular coil and an active can in common with the atrial coil ( active can ) . Delivered energy at DFT was 4.2 +/- 4.1 J in the lead configuration and 5.0 +/- 3.7 J in the active can configuration ( P = NS ) . Peak current was 32 % higher with an active can ( P < 0.01 ) , whereas shock impedance was 18 % lower ( P < 0.001 ) . Moreover , a low threshold ( < or = 3 J ) was observed in 61 % of subjects in the lead configuration but in only 36 % in the active can configuration ( P < 0.05 ) . There were no clinical predictors of the atrial DFT . CONCLUSION These results indicate that low atrial DFTs can be achieved using a transvenous ventricular defibrillation lead . Because no benefit was observed with the use of an active pectoral electrode for atrial defibrillation , programmable shock vectors may be useful for dual-chamber implantable cardioverter defibrillators .

active pectoral pulse generator

active pectoral can

comparison of two shock configurations

dual-coil transvenous defibrillation

left pectoral pulse generator emulator

active can

active can

active can

active pectoral electrode

Delivered energy at DFT

Peak current

shock impedance

low threshold

no clinical predictors


Do colonic short-chain fatty acids contribute to the long-term adaptation of blood lipids in subjects with type 2 diabetes consuming a high-fiber diet ? BACKGROUND We recently obtained evidence of long-term adaptation of blood lipids to changes in intakes of carbohydrate and fiber in subjects with type 2 diabetes . OBJECTIVE We determined the effect of increased carbohydrate and fiber intakes on serum short-chain fatty acids ( SCFAs ) and the relation between changes in serum acetate and changes in blood lipids . DESIGN Subjects with type 2 diabetes ( n = 62 ) were randomly assigned to receive approximately 10 % of energy from low-fiber breakfast cereal ( LF diet ) , high-fiber breakfast cereal ( HF diet ) , or monounsaturated fatty acids ( MUFA diet ) for 6 mo . RESULTS Carbohydrate intakes were higher in the LF and HF groups than in the MUFA group ( 54 % compared with 43 % ) , and more fiber was consumed by the HF group ( approximately 50 g/d ) than by the LF or MUFA group ( approximately 23 g/d ) . Fasting serum SCFAs did not change significantly over the first 3 mo . Between 3 and 6 mo , serum acetate tended ( NS ) to decrease in the LF group ( from 69 +/- 4 to 59 +/- 5 micromol/L ) and increase in the HF group ( from 100 +/- 18 to 107 +/- 17 micromol/L ) , with no significant change in the MUFA group . Serum butyrate did not change significantly in the LF or MUFA group but increased in the HF group ( from 2.5 +/- 0.5 to 3.1 +/- 0.6 micromol/L ; P < 0.001 ) . Changes in serum acetate from 0 to 3 mo were not related to changes in lipids . However , changes in serum acetate from 3 to 6 mo were positively related to changes in the ratio of total to HDL cholesterol ( P = 0.041 ) and in fasting ( P = 0.013 ) and postprandial ( P = 0.016 ) triacylglycerols . CONCLUSIONS In subjects with type 2 diabetes , changes in serum SCFAs in response to changes in carbohydrate and fiber intakes took many months to occur , and the changes in serum acetate were significantly related to the long-term adaptive changes in blood lipids .

high-fiber diet

carbohydrate and fiber

high-fiber breakfast cereal ( HF diet )

long-term adaptation of blood lipids

long-term adaptation of blood lipids

serum short-chain fatty acids ( SCFAs )

Carbohydrate intakes

Fasting serum SCFAs

serum acetate

Serum butyrate

Changes in serum acetate

changes in lipids

changes in serum acetate

postprandial

triacylglycerols

serum SCFAs

carbohydrate and fiber intakes

serum acetate

type 2 diabetes

type 2 diabetes

type 2 diabetes

type 2 diabetes


The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis . Hypertension is associated with impaired fibrinolysis . Both angiotensin receptor blockers ( ARB ) and the DASH ( Dietary Approaches to Stop Hypertension ) diet effectively lower blood pressure in hypertensive patients . Some evidence suggests that treatment with ARBs could increase fibrinolysis , however , data is conflicting . The impact of the DASH diet on fibrinolytic parameters is not known . Fifty-five hypertensive participants ( 35 African-American , 20 white ) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet . The diets did not differ in sodium content ( approximately 3 g/day ) . Within each diet , individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind , cross-over fashion . Tissue plasminogen activator ( t-PA ) antigen , t-PA activity , plasminogen activator inhibitor-1 ( PAI-1 ) activity and plasma renin activity ( PRA ) were measured at the end of a 2-week run-in period on the control diet and after each treatment period . The DASH diet did not affect markers of fibrinolysis . Losartan significantly lowered t-PA antigen levels ( -1.8 ng/mL , P = 0.045 ) , but had no effect on t-PA or PAI-1 activities . This effect was more pronounced in whites ( -4.1 ng/mL ( P = 0.003 ) ) compared with African-Americans ( -0.3 ng/mL ( P = 0.7 ) , P-interaction = 0.03 ) . Results were not materially affected by adjustment for basline values or changes in blood pressure . This study demonstrates that losartan reduces t-PA antigen levels in white , but not African-American hypertensive individuals . In contrast , the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans .

angiotensin II receptor blockade

DASH diet

angiotensin receptor blockers ( ARB )

control diet

DASH diet

losartan

placebo

diet

markers

blood pressure

fibrinolytic parameters

t-PA activity

plasma renin activity ( PRA )

t-PA antigen levels

t-PA

blood pressure

t-PA antigen levels

markers of fibrinolysis

hypertensive patients .


Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia . BACKGROUND Little evidence exists to indicate whether community psychiatric nurses can achieve the results reported by expert cognitive-behavioural therapists in patients with schizophrenia . AIMS To assess the effectiveness and safety of a brief cognitive-behavioural therapy ( CBT ) intervention in a representative community sample of patients with schizophrenia in secondary care settings . METHOD A pragmatic randomised trial was performed involving 422 patients and carers to compare a brief CBT intervention against treatment as usual . RESULTS Patients who received CBT ( n=257 ) improved in overall symptomatology ( P=0.015 ; number needed to treat [ NNT ] =13 ) , insight ( P < 0.001 ; NNT=10 ) and depression ( P=0.003 ; NNT=9 ) compared with the control group ( n=165 ) . Insight was clinically significantly improved ( risk ratio=1.15 , 95 % CI 1.01-1.31 ) . There was no increase in suicidal ideation . CONCLUSIONS Community psychiatric nurses can safely and effectively deliver a brief CBT intervention to patients with schizophrenia and their carers .

cognitive-behavioural therapists

CBT intervention

CBT ( n=257 )

CBT intervention

overall symptomatology

number needed to treat

insight

depression

Insight

suicidal ideation

safely

effectively

patients with schizophrenia

schizophrenia


A single infusion of intravenous ketamine improves pain relief in patients with critical limb ischaemia : results of a double blind randomised controlled trial . We report the first double blind randomised controlled trial of regular opioids and an infusion of low dose ( 0.6 mg/kg ) intravenous ketamine compared with opioids and placebo in patients with allodynia , hyperalgesia and hyperpathia secondary to critical limb ischaemia . Thirty-five patients completed the study , 18 received regular opioids plus ketamine , while 17 received regular opioids plus placebo . Using the Brief Pain Inventory , the % pain relief that the patients in the ketamine group attributed to their medication improved significantly from 50 % immediately pre-infusion to 65 % 24 h post-infusion and 69 % 5 days post infusion . Over the same period , the pain relief achieved by the placebo group rose from 58 % pre-infusion to 56 % 24 h post infusion and then 50 % relief 5 days later . This was statistically significant ( P < 0.05 ) using both the t-test and the Wilcoxon Rank Sum test . The ketamine group also showed a statistically significant difference 24 h post infusion of the effect of pain on their general activity ( P=0.03 ) and on their enjoyment of life ( P=0.004 ) . This study shows that combining a single infusion of low dose ketamine with regular opioid analgesia can result in a significant improvement in pain relief for this patient group .

ketamine

opioids

ketamine

opioids

placebo

opioids plus ketamine

regular opioids plus placebo .

pain relief achieved

statistically significant

t-test and the Wilcoxon Rank Sum test .

pain

pain relief

patients with critical limb ischaemia :

allodynia

hyperalgesia

Thirty-five


Prospective study of C-reactive protein , homocysteine , and plasma lipid levels as predictors of sudden cardiac death . BACKGROUND Sudden cardiac death ( SCD ) is an important cause of mortality even among apparently healthy populations . However , our ability to identify those at risk for SCD in the general population is poor , and more specific markers are needed . METHODS AND RESULTS To compare and contrast the relative importance of C-reactive protein ( CRP ) , homocysteine , and lipids as long-term predictors of SCD , we performed a prospective , nested , case-control analysis involving 97 cases of SCD among apparently healthy men enrolled in the Physician 's Health Study . Of these plasma markers measured , only baseline CRP levels were significantly associated with the risk of SCD over the ensuing 17 years of follow-up ( P for trend=0.001 ) . The increase in risk associated with CRP levels was primarily seen among men in the highest quartile , who were at a 2.78-fold increased risk of SCD ( 95 % CI 1.35 to 5.72 ) compared with men in the lowest quartile . These results were not significantly altered in analyses that ( in addition to the matching variables of age and smoking status ) controlled for lipid parameters , homocysteine , and multiple cardiac risk factors ( relative risk for highest versus lowest quartile 2.65 , 95 % CI 0.79 to 8.83 ; P for trend=0.03 ) . In contrast to the positive relationship observed for CRP , neither homocysteine nor lipid levels were significantly associated with risk of SCD . CONCLUSIONS These prospective data suggest that CRP levels may be useful in identifying apparently healthy men who are at an increased long-term risk of SCD .

C-reactive protein ( CRP )

homocysteine

lipids

CRP

CRP

Sudden cardiac death ( SCD )

CRP levels

CRP levels

SCD

SCD

long-term risk of SCD .

SCD

apparently healthy

men

at an increased long-term risk of SCD


Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery : a randomised double-blind trial . BACKGROUND Elective hip-replacement surgery carries significant risk of venous thromboembolism , despite use of thromboprophylaxis . We aimed to see whether the pentasaccharide fondaparinux , the first drug of a new class of synthetic antithrombotic agents , could reduce this risk to a greater extent than other available treatments . METHODS In a double-blind study , we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily . The primary efficacy outcome was venous thromboembolism to day 11 . The main safety outcomes were bleeding and death . Patients were followed up for 6 weeks . FINDINGS We assessed venous thromboembolism to day 11 in 1584 ( 70 % ) of 2275 patients . By day 11 , venous thromboembolisms were recorded in 48 ( 6 % ) of 787 patients on fondaparinux and in 66 ( 8 % ) of 797 patients on enoxaparin . The relative reduction in risk was 26.3 % ( 95 % CI -10.8 to 52.8 , p=0.099 ) . The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding . INTERPRETATION In patients undergoing elective hip-replacement surgery , 2.5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism . However , the lower risk recorded with fondaparinux than enoxaparin was clinically important , with no increase in clinically relevant bleeding .

Postoperative fondaparinux

postoperative enoxaparin

thromboprophylaxis

pentasaccharide fondaparinux

synthetic antithrombotic agents

fondaparinux

enoxaparin

fondaparinux

enoxaparin

fondaparinux

enoxaparin

fondaparinux

enoxaparin

venous thromboembolism

venous thromboembolism

venous thromboembolism

bleeding

death

venous thromboembolism

venous thromboembolisms

risk

patients who died

clinically relevant bleeding .

venous thromboembolism .

clinically relevant bleeding .

2275 consecutive patients

18 years or older

hip-replacement surgery


Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors . PURPOSES Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light . We performed a prospective , single institution , randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis . MATERIALS AND METHODS A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis . Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate . To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology . Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis . RESULTS A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis . The residual tumor rate was 25.2 % in the white light arm versus 4.5 % in the fluorescence diagnosis arm ( p < 0.0001 ) . Median followup in the white light arm in 103 cases was 21.2 months ( range 4 to 40 ) compared with 20.5 ( range 3 to 40 ) in the 88 in the fluorescence diagnosis arm . Recurrence-free survival in the fluorescence diagnosis group was 89.6 % after 12 and 24 months compared with 73.8 % and 65.9 % , respectively , in the white light group ( p = 0.004 ) . This superiority proved to be independent of risk group . The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 ( 95 % confidence interval 0.16 to 0.67 ) . CONCLUSIONS Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival . The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences .

5-aminolevulinic acid

5-aminolevulinic acid

transurethral resection

white light

fluorescence diagnosis

Transurethral resection

white light cystoscopy

urine cytology

recurrence-free survival

recurrence-free survival

Recurrence-free survival

residual tumor rate

Recurrence-free survival

residual tumor rate

recurrence-free survival

recurrence-free survival

number of tumor recurrences .

superficial bladder tumors

superficial bladder carcinoma

superficial bladder carcinoma


Impact of interviewer 's body mass index on underreporting energy intake in overweight and obese women . OBJECTIVE To determine if overweight and obese women provide more accurate reports of their energy intake by 1 ) in-person recall with an obese interviewer , 2 ) in-person recall with a lean interviewer , or 3 ) telephone recall with an unknown interviewer . RESEARCH METHODS AND PROCEDURES Eighty-eight overweight and obese women participated in this study . Subjects completed one telephone-administered multiple-pass 24-hour recall ( MP24R ) with an unknown interviewer and were then randomly assigned to an in-person MP24R with either a lean or obese interviewer to gather reported energy intake ( rEI ) . Basal metabolic rate ( BMR ) was measured using a Deltrac monitor , and physical activity ( EEPA ) was estimated using a Caltrac accelerometer . Therefore , estimated energy expenditure was determined by : estTEE = ( BMR + EEPA ) x 1.10 . RESULTS No significant differences were found between the two in-person interview modes for subject age , weight , body mass index , percentage of body fat , total energy expenditure , rEI , and misreporting of energy intake . In-person recall data were combined for comparison with the telephone recalls . No significant difference was found between the in-person and telephone recalls for rEI and misreporting . Mean reported energy intake was significantly lower than estimated total energy expenditure for the telephone recalls and combined ( lean and obese modes ) in-person recalls . CONCLUSIONS This study found that interviewer body mass index had no impact on self-reported energy intake during an in-person MP24R , and that telephone recall data were comparable with in-person recalls . Underreporting was a widespread problem ( approximately 26 % ) for all modes in this sample .

unknown interviewer

reported energy intake ( rEI )

Basal metabolic rate ( BMR )

physical activity ( EEPA )

rEI

misreporting

Mean reported energy intake

total energy expenditure

overweight and obese

women

overweight

obese

women

Eighty-eight

overweight

obese

women


Clinical evaluation of the WOMAC 3.0 OA Index in numeric rating scale format using a computerized touch screen version . BACKGROUND The Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index is a previously described self-administered questionnaire covering three domains : pain , stiffness and function . It has been validated in patients with osteoarthritis ( OA ) of the hip or knee in a paper-based format . AIM To validate the WOMAC 3.0 using a numerical rating scale in a computerized touch screen format allowing immediate evaluation of the questionnaire . In the computed version cartoons , written and audio instruments were included in order facilitate application . METHODS Fifty patients , demographically balanced , with radiographically proven primary hip or knee OA completed the classical paper and the new computerized WOMAC version . Subjects were randomized either to paper format or computerized format first to balance possible order effects . RESULTS The intra-class correlation coefficients for pain , stiffness and function values were 0.915 , 0.745 and 0.940 , respectively . The Spearman correlation coefficients for pain , stiffness and function were 0.88 , 0.77 and 0.87 , respectively . CONCLUSION These data indicate that the computerized WOMAC OA index 3.0 is comparable to the paper WOMAC in all three dimensions . The computerized version would allow physicians to get an immediate result and if present a direct comparison with a previous exam .

computerized touch screen version

classical paper

new computerized WOMAC version

computerized version

pain , stiffness and function .

pain , stiffness and function values

pain , stiffness and function

osteoarthritis

OA

Fifty


Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention : : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial ( TARGET ) 1-year follow-up . BACKGROUND The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab , a monoclonal antibody , has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention ( PCI ) . It is unknown whether small-molecule agents confer similar benefits . METHODS AND RESULTS In 18 countries , 4809 patients undergoing PCI with stent implantation were randomized to tirofiban or abciximab . At the time of enrollment , patients were stratified according to diabetes status . As compared with non-diabetic patients , patients with diabetes ( n=1117 ) showed similar 30-day ischemic outcomes , an increased incidence of any target vessel revascularization ( TVR ) at 6 months ( 10.3 % versus 7.8 % ; P= 0.008 ) , and a trend toward higher 1-year mortality ( 2.5 % versus 1.6 % ; P=0.056 ) . Among diabetic patients randomized to tirofiban ( n=560 ) , the incidence of death , myocardial infarction ( MI ) , or urgent TVR at 30 days was 6.2 % , and among those randomized to abciximab ( n=557 ) it was 5.4 % ( hazard ratio [ HR ] 1.16 ; P=0.540 ) . At 6 months , the composite of death , MI , or any TVR occurred in 15.7 % and in 16.9 % of tirofiban and abciximab patients , respectively ( HR 0.93 ; P=0.610 ) . Any TVR occurred in 9.5 % and 11.1 % , respectively ( HR 0.84 ; P= 0.366 ) . The 1-year mortality was 2.1 % in the tirofiban group and 2.9 % in the abciximab group ( HR 0.74 ; P= 0.436 ) . CONCLUSIONS Among diabetic patients undergoing PCI , tirofiban and abciximab were associated with comparable event rates , including similar rates of 6-month TVR and 1-year mortality . These findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do not translate into a discernible long-term clinical benefit among diabetic patients .

tirofiban

abciximab

higher 1-year mortality

death

myocardial infarction ( MI ) ,

urgent TVR

death

TVR

TVR

1-year mortality

diabetic

percutaneous coronary intervention

stent implantation

diabetic patients undergoing PCI


Brief report : imitation effects on children with autism . Twenty children with autism ( mean age , 5 years ) were recruited for the study from a school for children with autism . The children were randomly assigned to an imitation ( n = 10 ) or contingently responsive ( n = 10 ) interaction group based on a stratification table for gender and developmental and chronological age . The sessions consisted of four phases , with each phase lasting 3 minutes . In the first phase , the child walked into a room that was furnished with a sofa , a table , chairs , and two sets of identical toys . An adult was in the room sitting very still like a statue ( first still-face condition ) . In the second phase , the adult either imitated the child or was contingently responsive to the child . In the third phase , the adult sat still again ( second still-face condition ) , and in the fourth phase , the adult engaged in a spontaneous interaction . During the third phase ( the second still-face condition ) , the children in the imitation group spent less time in gross motor activity and more time touching the adult , as if attempting to initiate an interaction . The contingency condition appeared to be a more effective way to facilitate a distal social behavior ( attention ) , whereas the imitative condition was a more effective way to facilitate a proximal social behavior ( touching ) .

imitation

imitation

contingently responsive

contingently responsive

imitation

contingency

imitative

spent less time

more time touching the adult

more effective

distal social behavior ( attention )

more effective

proximal social behavior ( touching ) .

children

autism

Twenty

children

autism

mean age , 5 years )

children

autism


Can sedation reduce the cardiac stress during gastrointestinal endoscopy ? A study with non-invasive automated cardiac flow measurement by color Doppler echocardiography . BACKGROUND Upper gastrointestinal endoscopy ( UGIE ) may cause some cardiac stress . The effect of sedation on hemodynamics during UGIE has not been fully studied , and therefore the aim of this study was to clarify whether or not sedation can reduce cardiac stress dufing UGIE . METHODS Eight normal male volunteers undergoing UGIE with sedation ( 0.1 mg/kg of midazolam ) and without it ( two endoscopies per volunteer in random order ) were monitored throughout the procedure by means of electrocardiogram , blood pressure and peripheral oxygen saturation ( SpO2 ) . Cardiac output was measured at six points before , during and after endoscopy from automated cardiac flow measurement by color Doppler echocardiography . Serum norepinephrine , epinephrine , dopamine and ACTH concentrations were measured before and after the examination . RESULTS No significant differences in heart rate , systolic blood pressure , rate-pressure product , cardiac output and left ventricular work index were observed between the sedated and non-sedated groups . SpO2 hardly changed during endoscopy in the non-sedated group , but decreased slightly in the sedated group ( P = 0.075 ) . Although all serum catecholamine concentration changes were within normal limits in both groups , after endoscopy only epinephrine concentration was significantly lower in the sedated group than in the non-sedated group ( P = 0.0027 ) . CONCLUSIONS Conscious sedation with midazolam does not reduce the cardiac stress during UGIE .

UGIE

endoscopies

electrocardiogram

endoscopy

color Doppler echocardiography .

midazolam

electrocardiogram

blood pressure

peripheral oxygen saturation

Cardiac output

Serum norepinephrine

epinephrine

dopamine

ACTH concentrations

heart rate

systolic blood pressure

rate-pressure product

cardiac output

left ventricular work index

Upper gastrointestinal endoscopy

Eight

male


Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer : phase III trial results . PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in preclinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m ( 2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m ( 2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m ( 2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P =.0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P =.0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P =.006 ) compared with docetaxel . Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m ( 2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m ( 2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC .

capecitabine

docetaxel combination therapy

Docetaxel

capecitabine

capecitabine/docetaxel therapy

single-agent docetaxel

capecitabine

docetaxel

docetaxel

Capecitabine/docetaxel

docetaxel

combination therapy

single-agent docetaxel

docetaxel

addition of capecitabine to docetaxel

single-agent docetaxel

Docetaxel/capecitabine therapy

survival

efficacy and tolerability

efficacy

time to disease progression ( TTP )

overall survival

objective tumor response rate

myalgia , arthralgia

neutropenic fever/sepsis

grade 3 adverse events

grade 4 events

TTP and survival

toxicity profile

women

anthracycline-pretreated MBC


The effects of physical and emotional status on adherence to a low-fat dietary pattern in the Women 's Health Initiative . OBJECTIVE To examine whether the effects of physical and emotional status on adherance to a low-fat ( 20 % energy ) dietary pattern are mediated by participation in an intervention program ( attending sessions and self-monitoring ) . DESIGN The Baron and Kenny mediator model , a series of 4 regression analyses , was used to evaluate whether : a ) physical and emotional status predicted program participation , b ) program participation predicted dietary adherence , c ) physical and emotional status factors predicted dietary adherence , and , ultimately d ) the effects of physical and emotional status on dietary adherence were mediated by program participation . SUBJECTS/SETTING Data from 13,277 postmenopausal women randomly assigned to the low-fat intervention arm of the Women 's Health Initiative Dietary Modification Trial . INTERVENTION The nutrition goals for women randomly assigned to the low-fat intervention were to reduce total fat intake to 20 % or less of energy from fat and to consume 5 or more fruit/vegetable servings daily and 6 or more grain servings daily . MAIN OUTCOME MEASURES Year 1 program participation ( degree of attending group sessions and submitting fat scores ) and adherence to the low-fat dietary pattern ( percent energy from fat ) as predicted by baseline physical and emotional status ( eight SF-36 Health Survey subscales ) . RESULTS Participating in the dietary intervention program reduced ( mediated ) the negative effect of poorer mental health on dietary adherence by 15 % . Additional findings included that a 10 % increase in physical functioning increased session attendance by 0.4 % ( P < .001 ) and a 10 % increase in mental health predicted a decrease in percent energy from fat of 0.3 % ( P < .001 ) . Program participation had a marked effect on dietary adherence : a 10 % increase in session attendance predicted a 1.2 % decrease in percent energy from fat ( P < .001 ) . APPLICATIONS/CONCLUSIONS Understanding and using instruments to assess the physical and emotional status of a target population will help dietetic professionals promote healthful dietary change and maintenance .

physical and emotional status

low-fat dietary pattern

low-fat ( 20 % energy ) dietary pattern

dietary adherence

low-fat intervention

low-fat intervention

low-fat dietary pattern

dietary intervention program

effect of poorer mental health

dietary adherence

physical functioning

session attendance

mental health

dietary adherence

session attendance

energy from fat

low-fat ( 20 % energy ) dietary pattern

postmenopausal

women

Women


Heparan sulfate in the treatment of intermittent claudication : results of a randomized , double-blind , placebo-controlled multicenter trial . Peripheral arterial disease ( PAD ) is by far the most common cause of intermittent claudication . This disease can greatly reduce the affected individual 's walking capacity and can seriously affect daily life activities . Few therapeutic options are aimed at improving walking capacity . This was a randomized , doubleblind , placebo-controlled , multicenter trial , performed in 24 Italian centers . Two hundred seventeen patients with intermittent claudication ( stages IIa and IIb of Fontaine 's PAD classification ) were randomly assigned to heparan sulfate ( 40 mg orally twice a day ) or placebo for 6 months . The primary end-point was an increase in pain-free walking distance [ initial claudication distance ( ICD ) ] during the 24 weeks of treatment . The pain-free and the absolute walking distance ( ACD ) were monitored by standardized treadmill test at baseline and at 4 , 12 and 24 weeks . The change in initial claudication distance during treatment , expressed as integrated change over time , was significantly greater with heparan sulfate than with placebo ( 306 +/- 494 vs. 250 +/- 510 meters x months , p = 0.019 ) . Significantly fewer treated patients worsened during treatment ( decreased initial claudication distance ) compared with controls ( 9.1 % vs. 19.6 % ; p = 0.027 ) . Functional recovery in the most severely affected subgroup of patients ( stage IIb of Fontaine 's classification ) was more clearly detected and significantly greater among treated than among control patients ( absolute increase in ICD : 70 +/- 113 vs. 58 +/- 172 meters , p = 0.028 ; integrated increase : 304 +/- 422 vs. 208 +/- 503 meters x months ; p = 0.004 ) . Heparan sulfate appeared to increase the walking capacity of patients with intermittent claudication to a significantly greater extent than did placebo . The treatment was well tolerated .

Heparan sulfate

placebo

heparan sulfate

walking capacity

pain-free walking distance

claudication distance ( ICD ) ]

initial claudication distance

Functional recovery

walking capacity

intermittent claudication


Double-blind placebo-controlled trial of aprindine and digoxin for the prevention of symptomatic atrial fibrillation . A multicenter , placebo-controlled , randomized , double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation ( AF ) with placebo , and also compare the effectiveness of these 2 drugs in the prevention of AF . Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm ( SR ) were randomly assigned aprindine ( 40 mg/day ) , digoxin ( 0.25 mg/day ) or placebo and followed up on an outpatient basis every 2 weeks for 6 months . Of the 141 patients from 36 participating centers , 47 were given aprindine , 47 digoxin , and 47 were on placebo . After the 6-month follow-up , the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine , digoxin and placebo were 33.3 % , 29.2 % and 21.5 % , respectively . In patients remaining in SR for 15 days after from the start of follow-up , freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group ( p=0.0414 ) , but there was no significant difference between the digoxin and placebo groups . The rate of adverse events was similar in the 3 groups . In conclusion , neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF ; however , recurrence of AF occurred later with aprindine than with placebo or digoxin .

placebo-controlled

aprindine

digoxin

placebo-controlled

aprindine

digoxin

placebo

aprindine

digoxin

placebo

aprindine

digoxin

placebo

aprindine

digoxin

placebo

placebo

digoxin

aprindine

placebo

digoxin

preventive effect

effectiveness

prevention of AF .

Kaplan-Meier

recurrent symptomatic AF

freedom from recurrence

significant difference

rate of adverse events

preventing relapse of symptomatic AF

recurrence of AF

symptomatic atrial fibrillation

atrial fibrillation ( AF

symptomatic paroxysmal

persistent AF

sinus rhythm ( SR

47 were given aprindine

47 digoxin

47 were on placebo


[ Effect of valociclovir hydrochloride on patients with herpes zoster ] .

valociclovir hydrochloride

herpes zoster ]

patients with herpes zoster


A randomized trial of a brief alcohol intervention for needle exchangers ( BRAINE ) . AIMS To test motivational interviewing ( MI ) as a brief intervention for reducing alcohol use among needle exchange clients . DESIGN Randomized clinical trial . SETTING Needle exchange program-Providence , Rhode Island , USA . PARTICIPANTS Between 2/98 and 10/99 , we recruited 187 AUDIT-positive ( > 8 ) active injection drug users . INTERVENTION Those assigned to a brief motivational intervention ( MI ) condition received two 1-hour therapist sessions following assessment visits , 1 month apart , focusing on alcohol use and HIV risk-taking . MEASUREMENTS Control and MI subjects received identical research assessments at baseline , 1 and 6 months following study enrollment . At 6 months , study outcomes included days of alcohol use measured using the time-line follow-back method . FINDINGS Study retention was 96.8 % at 6 months . Participants reported an average of 12.0 drinking days at baseline and 8.3 at 6 months . Significant reductions in drinking days were observed in both treatment conditions . We found significant treatment x baseline drinking day interaction effects . Tests for simple main effects were significant for subjects with above median ( > 9 ) baseline drinking day frequency , but not for those with below median baseline drinking frequency . Comparisons on dichotomous outcomes provided supporting evidence of treatment efficacy ; those in MI were over two times more likely than controls to report reductions of 7 days or more ( P < 0.05 ) . CONCLUSIONS This study provides the first direct evidence that brief MI can decrease alcohol use among active injection drug users with drinking problems . Heavier drinkers seem best suited for this intervention , but the optimal intensity of treatments and which components of brief intervention are most effective deserve further study .

brief alcohol intervention

motivational interviewing ( MI )

brief motivational intervention ( MI )

Control

MI

brief MI

alcohol use

days of alcohol use

Study retention

drinking days

baseline drinking frequency .

treatment efficacy ;


Marimastat as maintenance therapy for patients with advanced gastric cancer : a randomised trial . This randomised , double-blind , placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor , marimastat , to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma . Three hundred and sixty-nine patients with histological proof of adenocarcinoma , who had received no more than a single regimen of 5-fluorouracil-based chemotherapy , were randomised to receive either marimastat ( 10 mg b.d . ) or placebo . Patients were treated for as long as was tolerable . The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life . At the point of protocol-defined study completion ( 85 % mortality in the placebo arm ) there was a modest difference in survival in the intention-to-treat population in favour of marimastat ( P=0.07 log-rank test , hazard ratio=1.23 ( 95 % confidence interval 0.98-1.55 ) ) . This survival benefit was maintained over a further 2 years of follow-up ( P=0.024 , hazard ratio=1.27 ( 1.03-1.57 ) ) . The median survival was 138 days for placebo and 160 days for marimastat , with 2-year survival of 3 % and 9 % respectively . A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy ( P=0.045 , hazard ratio=1.53 ( 1.00-2.34 ) ) . This benefit increased with 2 years additional follow-up ( P=0.006 , hazard ratio=1.68 ( 1.16-2.44 ) ) , with 2-year survival of 5 % and 18 % respectively . Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo ( P=0.009 , hazard ratio=1.32 ( 1.07-1.63 ) ) . Marimastat treatment was associated with the development of musculoskeletal pain and inflammation . Events of anaemia , abdominal pain , jaundice and weight loss were more common in the placebo arm . This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients . The greatest benefit was observed in patients who had previously received chemotherapy . A further randomised study of marimastat in these patients is warranted .

Marimastat

marimastat

marimastat

placebo

marimastat

placebo

marimastat

marimastat

Marimastat

marimastat

survival

overall survival

disease progression

quality of life

survival benefit

median survival

significant survival benefit

2-year survival

Progression-free survival

musculoskeletal pain and inflammation

advanced gastric cancer

Three hundred and sixty-nine

histological proof of adenocarcinoma


Improving patient involvement in chronic disease management : the views of patients , GPs and specialists on a guidebook for ulcerative colitis . Patient information , shared care and decision-making are recognised as beneficial to chronic disease management . As part of an RCT , opinions of ulcerative colitis patients and their doctors were sought on a guidebook designed to support self-care and mediate doctor/patient interaction during consultations . Semi-structured interviews were conducted with 6 specialists and 16 GPs . Patients ' views were obtained from written responses to a postal questionnaire ( 136 replies ) . Inclusion of lay knowledge and clarification of treatment decision processes increased patients ' perception of involvement in disease management through increased identification and awareness of others ' self-management experiences . Doctors focused on the importance of improving patients ' compliance and use of services . However , the guidebook was seldom used as it had been intended during consultations . Patients felt constrained by time limits and consultants did not actively encourage guidebook use . Based on the findings , we suggest an approach utilising the guidebook to improve patient participation in disease management .

patient involvement

support self-care

mediate doctor/patient interaction

Semi-structured interviews

postal questionnaire

utilising the guidebook

patient participation


Onset of action following formoterol Turbuhaler and salbutamol pMDI in reversible chronic airway obstruction . Short-acting beta ( 2 ) -agonists are currently recommended for symptom relief in asthma and the treatment of mild , acute exacerbations in COPD . However , formoterol has as fast an onset of action as salbutamol with the additional benefit of longer-lasting bronchodilation ( approximately 12 h ) . Furthermore , systemic side effects observed with formoterol are of a similar duration but less pronounced than with short-acting beta ( 2 ) -agonists . In this double-blind , randomized , cross-over study , 20 adult patients with reversible chronic airway obstruction ( intrinsic asthma or COPD ) inhaled single doses of formoterol 9 microg or salbutamol 100 microg ( group A ) or formoterol 18 microg or salbutamol 200 microg ( group B ) . FEV ( 1 ) was measured prior to and 5 , 10 , 15 , 20 , 25 and 30 min following inhalation of study drug . No significant differences in FEV ( 1 ) values were observed between group A ( P=0.704 ) or group B ( P=0.270 ) at baseline , or at 5 ( Group A : P=0.340 ; Group B : P=0.559 ) and 15 min ( Group A : P=0.526 ; Group B : P=0.818 ) post dose . No adverse events were reported during the study . Formoterol Turbuhaler has as rapid an onset of action as salbutamol pMDI when given at the recommended doses .

formoterol

salbutamol

formoterol

salbutamol

formoterol

formoterol 9 microg

salbutamol 100 microg ( group A )

formoterol 18 microg

salbutamol 200 microg

Formoterol

salbutamol

FEV ( 1 )

FEV ( 1 )

adverse events

reversible chronic airway obstruction .