Comparative drug effects and abuse liability of lorazepam , buspirone , and secobarbital in nondependent subjects . The pharmacologic effects of lorazepam ( 2 mg ) , buspirone ( 20 mg , 10 mg ) , secobarbital ( 100 mg ) , and placebo were compared in 15 male , experienced , intermittent nontherapeutic drug users . All drugs produced a " drug effect , " however , buspirone 20 mg was significantly less liked than were lorazepam , secobarbital , or buspirone 10 mg ( p less than .05 ) but not placebo . Lorazepam was liked better than were other drugs only at 1 hour and only compared with buspirone 20 and placebo . Compared with other drugs , lorazepam drug effects were greater and resulted in more prolonged impairment of a motor tracking task , standing steadiness , and memory . Buspirone 20 mg significantly impaired memory at 1 hour compared with placebo . Subjects were more likely to identify buspirone as unfamiliar . Because buspirone 20 mg was less liked than were other drugs , dose escalation as part of drug abuse is not likely to occur . Lorazepam also was not particularly liked and was not different from placebo on most subjective abuse-relevant measures .

lorazepam

buspirone

secobarbital

lorazepam

buspirone

secobarbital

placebo

buspirone 20

lorazepam

secobarbital

buspirone 10 mg

placebo

Lorazepam

buspirone

placebo

lorazepam

Buspirone

placebo

buspirone

buspirone

Lorazepam

placebo

drug effects

greater

prolonged impairment

memory

significantly

impaired memory

drug abuse

not particularly liked

not different

nondependent subjects


Is successful rehabilitation of complex regional pain syndrome due to sustained attention to the affected limb ? A randomised clinical trial . In complex regional pain syndrome ( CRPS1 ) initiated by wrist fracture , a motor imagery program ( MIP ) , consisting of hand laterality recognition followed by imagined movements and then mirror movements , reduces pain and disability , but the mechanism of effect is unclear . Possibilities include sustained attention to the affected limb , in which case the order of MIP components would not alter the effect , and sequential activation of cortical motor networks , in which case it would . Twenty subjects with chronic CRPS1 initiated by wrist fracture and who satisfied stringent inclusion criteria , were randomly allocated to one of three groups : hand laterality recognition , imagined movements , mirror movements ( RecImMir , MIP ) ; imagined movements , recognition , imagined movements ( ImRecIm ) ; recognition , mirror movements , recognition ( RecMirRec ) . At 6 and 18 weeks , reduced pain and disability were greater for the RecImMir group than for the other groups ( P < 0.05 ) . Hand laterality recognition imparted a consistent reduction in pain and disability across groups , however , this effect was limited in magnitude . Imagined movements imparted a further reduction in pain and disability , but only if they followed hand laterality recognition . Mirror movements also imparted a reduction in pain and disability , but only when they followed imagined movements . The effect of the MIP seems to be dependent on the order of components , which suggests that it is not due to sustained attention to the affected limb , but is consistent with sequential activation of cortical motor networks .

motor imagery program

imagined movements

mirror movements

pain

disability

pain

disability

pain

disability

pain

disability

pain

disability

effect

complex regional pain syndrome

Twenty


The effect of vitamin A-fortified coconut cooking oil on the serum retinol concentration of Filipino children 4-7 years old . A 6-month intervention trial was conducted among 542 Filipino children aged 4 to 7 years to determine the effect of vitamin A-fortified coconut cooking oil intake on their vitamin A status and to identify factors that influence this . Children were randomly assigned to the Experimental group , with vitamin A-fortified cooking oil ration ; to Control-1 group with unfortified cooking oil ration ; and to Control-2 group without cooking oil ration . In all groups , children 's serum retinol concentration improved . Relative change in serum retinol concentration was significantly higher among the Experimental group , with one-third of total vitamin A intake coming from vitamin A-fortified cooking oil intake , than in the Control groups , with more than half of intake from other vitamin A-rich foods . Determinants of post-intervention serum retinol concentration included baseline serum retinol concentration , caregiver 's education , receipt of high-dose vitamin A capsule , interaction between consumption of vitamin A-fortified cooking oil and of other vitamin A-rich foods , and between households purchasing cooking oil and food expenditure . Intake of vitamin A-fortified cooking oil combined with vitamin A-rich foods was necessary to increase serum retinol concentration . It is recommended to vigorously promote the consumption of vitamin A-fortified cooking oil together with other vitamin A-rich sources to sustain the prevention and control of vitamin A deficiency .

vitamin A-fortified coconut cooking oil

vitamin A-fortified coconut cooking oil

vitamin A-fortified cooking oil

unfortified cooking oil ration

without cooking oil ration

vitamin A-fortified cooking oil

vitamin A-fortified cooking oil

vitamin A-fortified cooking oil

serum retinol concentration

retinol concentration

serum retinol concentration

serum retinol concentration

prevention

control

serum retinol concentration

Filipino

4-7 years old

4 to 7


Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone ( BMS-247550 ) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer . PURPOSE To evaluate the antitumor activity and safety of the epothilone B analog , ixabepilone , with or without estramustine phosphate ( EMP ) , in chemotherapy-naive patients with progressive castrate metastatic prostate cancer . PATIENTS AND METHODS Patients were randomly assigned to receive ixabepilone ( 35 mg/m ( 2 ) ) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5 . RESULTS Between December 2001 and October 2003 , 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone ( 45 patients ) or in combination with EMP ( 47 patients ) . Grades 3 and 4 toxicities experienced by more than 5 % of patients included neutropenia ( 22 % ) , fatigue ( 9 % ) , and neuropathy ( 13 % ) on the ixabepilone arm , and neutropenia ( 29 % ) , febrile neutropenia ( 9 % ) , fatigue ( 9 % ) , neuropathy ( 7 % ) , and thrombosis ( 6 % ) on the ixabepilone + EMP arm . Post-treatment declines in prostate-specific antigen of > or = 50 % were achieved in 21 of 44 patients ( 48 % ; 95 % CI , 33 % to 64 % ) on the ixabepilone arm , and 31 of 45 patients ( 69 % ; 95 % CI , 55 % to 82 % ) on the ixabepilone + EMP arm . In patients with measurable disease , partial responses were observed in eight of 25 patients ( 32 % ; 95 % CI , 14 % to 50 % ) on the ixabepilone arm , and 11 of 23 ( 48 % ; 95 % CI , 27 % to 68 % ) on the ixabepilone + EMP arm . Time to prostate-specific antigen progression was 4.4 months ( 95 % CI , 3.1 to 6.9 months ) on the ixabepilone-alone arm and 5.2 months ( 95 % CI , 4.5 to 6.8 months ) on the combination arm . CONCLUSION Ixabepilone , with or without estramustine phosphate , is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer .

ixabepilone

EMP

ixabepilone alone

combination with EMP

Ixabepilone

estramustine phosphate

antitumor activity

safety

Grades 3 and 4 toxicities

neutropenia

fatigue

neuropathy

neutropenia

febrile neutropenia

fatigue

neuropathy

thrombosis

prostate-specific antigen

partial responses

tolerated

antitumor activity


Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer : a randomized , placebo-controlled trial . PURPOSE To investigate the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer . PATIENTS AND METHODS Women with bone metastases ( N = 228 ) were randomly assigned to receive 4 mg zoledronic acid ( n = 114 ) or placebo ( n = 114 ) via 15-minute infusions every 4 weeks for 1 year . The primary efficacy end point was the skeletal-related event ( SRE ) rate ratio between treatment groups . An SRE was defined as pathologic fracture , spinal cord compression , and radiation or surgery to bone . Secondary end points included percentage of patients with at least one SRE , time-to-first SRE , and Andersen-Gill multiple-event analysis . RESULTS The SRE rate ratio at 1 year ( excluding HCM and adjusted for prior fracture ) was 0.61 ( permutation test ; P = .027 ) , indicating that zoledronic acid reduced the rate of SRE by 39 % compared with placebo . The percentage of patients with at least one SRE ( excluding HCM ) was significantly reduced by 20 % by zoledronic acid ( 29.8 % v 49.6 % for placebo ; P = .003 ) . Zoledronic acid significantly delayed time-to-first SRE ( median not reached v 364 days ; Cox regression ; P = .007 ) and reduced the risk of SREs by 41 % in multiple event analysis ( risk ratio = 0.59 ; P = .019 ) compared with placebo . Zoledronic acid was well tolerated with a safety profile similar to placebo . No patient treated with zoledronic acid had grade 3 or 4 serum creatinine increase . CONCLUSION Zoledronic acid significantly reduced skeletal complications compared with placebo across multiple end points in Japanese women with bone metastases from breast cancer .

Zoledronic acid

placebo

zoledronic acid

4 mg zoledronic acid

placebo

zoledronic acid

placebo .

Zoledronic acid

placebo .

Zoledronic acid

Zoledronic acid

placebo

SRE rate ratio

rate of SRE

significantly delayed time-to-first SRE

reduced the risk of SREs

tolerated

women

breast cancer

Women

N = 228 )


Phase III trial of satraplatin , an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer . Satraplatin is a novel oral platinum ( IV ) complex that shows activity against hormone-refractory prostate cancer ( HRPC ) in cisplatin-resistant human tumor lines in phase I and phase II trials . A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC . After 50 randomized patients , the trial was closed to further accrual by the sponsoring company . An ad hoc analysis of all available data is reported here . Eligibility criteria included pathological proof of prostate cancer , documented progression despite prior hormonal manipulation , WHO PS 0-2 , and no daily intake of narcotic analgesics . Patients were randomized between satraplatin 100 mg/m ( 2 ) for 5 days plus prednisone 10 mg orally BID or prednisone alone . Compliance was excellent . 48/50 patients have progressed and 42 have died , mostly due to prostate cancer . Median overall survival was 14.9 months ( 95 % CI : 13.7-28.4 ) on the satraplatin plus prednisone arm and 11.9 months ( 95 % CI : 8.4-23.1 ) on prednisone alone ( hazard ratio , HR = 0.84 , 95 % CI : 0.46-1.55 ) . A > 50 % decrease in prostrate specific antigen ( PSA ) was seen in 9/27 ( 33.3 % ) in the satraplatin plus prednisone arm vs. 2/23 ( 8.7 % ) on the prednisone alone arm . Progression-free survival was 5.2 months ( 95 % CI : 2.8-13.7 ) on the satraplatin plus prednisone arm as compared to 2.5 months ( 95 % CI : 2.1- 4.7 ) on the prednisone alone arm ( HR = 0.50 , 95 % CI : 0.28-0.92 ) . This difference is statistically significant ( p = 0.023 ) . Toxicity was generally minimal in both arms . This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination . Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting .

satraplatin

platinum plus prednisone

prednisone alone

Satraplatin

platinum

cisplatin-resistant

narcotic analgesics

satraplatin

prednisone

prednisone

satraplatin

prednisone

prednisone

satraplatin plus prednisone

prednisone

satraplatin

prednisone

prednisone

satraplatin

prednisone

progressed

died

Median overall survival

prostrate specific antigen

Progression-free survival

Toxicity

men

HRPC .

prostate cancer


Enjoyment mediates effects of a school-based physical-activity intervention . PURPOSE The study evaluated whether targeted changes in factors influencing enjoyment of physical education ( PE ) , physical activity enjoyment , and self-efficacy beliefs about participating in physical activity mediated the effect of the Lifestyle Education for Activity Program ( LEAP ) intervention on participation in physical activity . METHODS High schools ( N=24 ) paired on enrollment size , racial composition , urban or rural location , and class structure were randomized into control ( N=12 ) or experimental ( N=12 ) groups . Of the 4044 girls enrolled and eligible , 2087 ( 51.6 % ) participated in the measurement component of the study . There were 1038 girls in the control group and 1049 girls in the experimental group . INTERVENTION LEAP was a comprehensive school-based intervention emphasizing changes in instruction and school environment designed to increase physical activity among black and white adolescent girls . It was organized according to the Coordinated School Health Program and included a PE component with core objectives of promoting enjoyment of PE , physical activity enjoyment , and self-efficacy . RESULTS Latent variable structural equation modeling indicated that : 1 ) the intervention had direct , positive effects on physical activity and factors influencing enjoyment of PE , which subsequently explained the effects of increased physical activity enjoyment and self-efficacy on increased physical activity ; and 2 ) an additional , indirect effect of physical activity enjoyment on physical activity operated by an influence on self-efficacy . CONCLUSIONS Increases in enjoyment partially mediated the positive effect of the LEAP intervention . To our knowledge , we have provided the first experimental evidence from a randomized controlled trial linking increased enjoyment with increased physical activity among black and white adolescent girls .

control

experimental

control

LEAP

PE component with core objectives

LEAP intervention

self-efficacy

self-efficacy

girls

2087 ( 51.6 %

girls

girls

adolescent

girls

adolescent

girls


Online conductivity monitoring : validation and usefulness in a clinical trial of reduced dialysate conductivity . Relatively low dialysate conductivity ( Cndi ) may improve outcomes by reducing the overall sodium burden in dialysis patients . Excess sodium removal , however , could lead to hemodynamic instability . We performed a randomized controlled trial of reduction of Cndi . For the study , 28 patients were randomized to maintenance of Cndi at 13.6 mS/cm ( equivalent to 135 mmol/L of Na+ ) or serial reduction of Cndi in steps of 0.2 mS/cm , guided by symptoms and blood pressure . Sodium removal estimated from pre- and postplasma concentrations correlated well with removal measured by conductivity monitoring as ionic mass balance ( R2 0.66 , p < 0.0001 ) . Of the 16 patients randomized to reduction of Cndi , 6 achieved Cndi 13.4 mS/cm , 6 achieved 13.2 mS/cm , and 4 achieved 13.0 mS/cm . No episodes of disequilibrium occurred . Interdialytic weight gain was reduced from 2.34 +/- 0.10 kg to 1.57 +/- 0.11 kg ( p < 0.0001 ) . Predialysis systolic blood pressure fell from 144 +/- 3 mm Hg to 137 +/- 4 mm Hg ( p < 0.05 ) . The reduction in convective sodium removal was balanced by an increase in diffusive sodium removal ( 95 +/- 9 mmol cf . 175 +/- 14 mmol , p < 0.0001 ) . Reduction in Cndi monitored by IMB is safe and practical and leads to improved interdialytic weight gains and blood pressure control , while avoiding excessive sodium removal .

Online conductivity monitoring

reduced dialysate conductivity

reduction of Cndi

reduction of Cndi

sodium burden

ionic mass balance

Interdialytic weight gain

Predialysis systolic blood pressure

reduction in convective sodium removal

diffusive sodium removal

dialysis


Phase I pharmacokinetic , food effect , and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors . PURPOSE To characterize the maximum-tolerated dose , recommended dose , dose-limiting toxicities ( DLT ) , pharmacokinetic profile , and food effect of orally administered irinotecan formulated as new semisolid matrix capsules . EXPERIMENTAL DESIGN Irinotecan was given orally in fasted patients once daily for 5 consecutive days and repeated every 3 weeks . Patients were randomly assigned to take the drug along with a high-fat , high-calorie breakfast for the administration at day 1 of the first or second cycle . Dosages tested were 70 and 80 mg/m ( 2 ) /day . RESULTS Twenty-five patients received 101 cycles of therapy ( median two cycles , range 1-15 ) . During the first cycle , grade 3 delayed diarrhea and grade 3 fever were the DLTs at the dosage of 80 mg/m ( 2 ) /day in three out of five patients . Hematologic and nonhematologic toxicities were mild to moderate . Exposure to the active metabolite SN-38 was relatively high compared with i.v . infusion , but no relevant accumulation was observed . Food had no significant effect on irinotecan pharmacokinetics . One confirmed partial remission and 10 disease stabilizations were observed in previously treated patients . No association was found between the UGT1A1*28 genotype and the risk of severe irinotecan-induced toxicity . CONCLUSIONS For oral irinotecan , a dose of 70 mg/m ( 2 ) /day for 5 consecutive days every 3 weeks is recommended for further studies . Delayed diarrhea was the main DLT , similar to that observed with intravenously administered irinotecan . This study confirms that oral administration of irinotecan is feasible and may have favorable pharmacokinetic characteristics .

irinotecan

irinotecan

Irinotecan

high-fat , high-calorie breakfast

irinotecan

irinotecan

irinotecan

Exposure to the active metabolite SN-38

severe irinotecan-induced toxicity .


The overt aggression scale for rating aggression in outpatient youth with autistic disorder : preliminary findings . Aggression is a common and costly problem in youth with developmental disabilities . Rating scales that accurately capture and measure subtypes of aggression phenomenology , frequency and severity are urgently needed , in both clinical practice and research . The authors studied the Overt Aggression Scale ( OAS ) in a preliminary sample of eight outpatients who participated in an ongoing placebo-controlled study of valproate for aggression in autism . Subjects ' OAS aggression scores showed significant correlation with the already validated retrospectively rated Aberrant Behavior Checklist Community Scale irritability subscale . Further study of the OAS in outpatients with aggression and developmental disabilities is warranted .

overt aggression scale

Overt Aggression Scale ( OAS )

placebo-controlled

valproate

OAS aggression scores

OAS

Overt Aggression Scale ( OAS )

OAS aggression scores

OAS


Magnesium sulphate only slightly reduces the shivering threshold in humans . BACKGROUND Hypothermia may be an effective treatment for stroke or acute myocardial infarction ; however , it provokes vigorous shivering , which causes potentially dangerous haemodynamic responses and prevents further hypothermia . Magnesium is an attractive anti-shivering agent because it is used for treatment of postoperative shivering and provides protection against ischaemic injury in animal models . We tested the hypothesis that magnesium reduces the threshold ( triggering core temperature ) and gain of shivering without substantial sedation or muscle weakness . METHODS We studied nine healthy male volunteers ( 18-40 yr ) on two randomly assigned treatment days : ( 1 ) control and ( 2 ) magnesium ( 80 mg kg ( -1 ) followed by infusion at 2 g h ( -1 ) ) . Lactated Ringer 's solution ( 4 degrees C ) was infused via a central venous catheter over a period of approximately 2 h to decrease tympanic membrane temperature by approximately 1.5 degrees C h ( -1 ) . A significant and persistent increase in oxygen consumption identified the threshold . The gain of shivering was determined by the slope of oxygen consumption vs core temperature regression . Sedation was evaluated using a verbal rating score ( VRS ) from 0 to 10 and bispectral index ( BIS ) of the EEG . Peripheral muscle strength was evaluated using dynamometry and spirometry . Data were analysed using repeated measures anova ; P < 0.05 was statistically significant . RESULTS Magnesium reduced the shivering threshold ( 36.3 [ SD 0.4 ] degrees C vs 36.6 [ 0.3 ] degrees C , P = 0.040 ) . It did not affect the gain of shivering ( control , 437 [ 289 ] ml min ( -1 ) degrees C ( -1 ) ; magnesium , 573 [ 370 ] ml min ( -1 ) degrees C ( -1 ) ; P=0.344 ) . The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength . CONCLUSIONS Magnesium significantly reduced the shivering threshold . However , in view of the modest absolute reduction , this finding is considered to be clinically unimportant for induction of therapeutic hypothermia .

Magnesium sulphate

Hypothermia

Magnesium

magnesium

control

magnesium

Lactated Ringer 's solution

Magnesium

magnesium

Magnesium

shivering threshold

shivering

sedation

tympanic membrane temperature

oxygen

gain of shivering

verbal rating score ( VRS )

bispectral index ( BIS ) of the EEG

Peripheral muscle strength

shivering threshold

gain of shivering

muscle strength

shivering threshold

shivering threshold in humans .


Effectiveness of once-daily monotherapy with a new nifedipine sustained release calcium antagonist . Data from 2 separate multicenter , double-blind clinical studies following the same protocol , except for the selection of doses , were pooled to evaluate the efficacy and tolerability of fixed doses of a new sustained-release ( SR ) formulation of nifedipine compared with placebo in 388 patients with mild to moderate uncomplicated essential hypertension . After a 3-6 week placebo washout period , the patients were randomized to receive either placebo or nifedipine SR-20 mg ( study I only ) , 50 mg , 100 mg , or 150 mg ( study II only ) . Among the 278 patients who completed 6 weeks of active therapy , mean supine diastolic blood pressure reductions from pretreatment baseline were 5.9 , 9.3 , 9.2 , 11.1 , and 13.2 mm Hg in the placebo , 20- , 50- , 100- , and 150-mg groups , respectively . The reductions achieved in each of the nifedipine SR groups were statistically significant versus baseline values ( p less than 0.001 ) . All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo ( p less than 0.001 ) . In addition , there was a significant linear relationship between the log of the dose and the blood pressure reduction ( p less than 0.05 ) . Automated ambulatory blood pressure recordings performed in 221 of the patients showed that the blood pressure was lowered evenly through the entire 24-hour dosing period . The doses that were effective and associated with the fewest adverse reactions were 20 mg and 50 mg once daily .

once-daily monotherapy

placebo

placebo or nifedipine

nifedipine

placebo

Effectiveness

efficacy and tolerability

reduced supine systolic blood pressure

log of the dose

blood pressure reduction

blood pressure

2 separate multicenter


Low-dose angiotensin II receptor antagonists and angiotensin II-converting enzyme inhibitors alone or in combination for treatment of primary glomerulonephritis . OBJECTIVE The renin-angiotensin system is thought to be involved in the progression of chronic renal diseases of both diabetic and non-diabetic origin . It has been confirmed that angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin II receptor blockers ( ARBs ) reduce urinary protein excretion and attenuate the development of renal injury . Clinical data comparing the renal effects of ACEIs and ARBs , either singly or in combination , are scarce and usually concern the use of standard or high doses . MATERIAL AND METHODS This was a prospective , randomized , 9-month study of the effects of low doses of losartan ( 25 mg ; n = 18 ) versus enalapril ( 10 mg ; n = 18 ) versus the combination of losartan ( 25 mg ) and enalapril ( 10 mg ) ( n = 16 ) on proteinuria , kidney function and metabolic profile in 54 patients with biopsy-proven chronic glomerulonephritis , hypertension and normal or slightly impaired kidney function . The clinical evaluation and laboratory tests were performed before treatment ( baseline ) and after 3 and 9 months of therapy . RESULTS After 3 months , significant decreases in proteinuria were observed in all groups : losartan , 22.6 % ( p = 0.02 ) ; enalapril , 43 % ( p = 0.012 ) ; and combined therapy , 63 % ( p = 0.001 ) . This anti-proteinuric effect was even greater after 9 months of therapy : losartan , 44.2 % ( p = 0.02 ) ; enalapril , 49.6 % ( p = 0.02 ) ; and combined therapy , 51 % ( p = 0.003 ) . There was no significant difference between losartan and enalapril with respect to their impact on proteinuria level . Proteinuria reduction was significantly greater in patients receiving combined therapy in comparison with losartan treatment after 3 months of therapy ( p = 0.02 ) . Creatinine clearance and serum creatinine were stable during the entire study period in all patients . No significant changes in lipids , serum uric acid or protein levels were observed . CONCLUSIONS These results indicate that proteinuria is reduced by low doses of losartan or enalapril . The combination of these drugs seems to be beneficial and may offer an additional renoprotective effect . This needs to be confirmed in a study with a larger sample size .

losartan

enalapril

proteinuria

anti-proteinuric effect

proteinuria

Proteinuria reduction

chronic glomerulonephritis

hypertension

impaired kidney function


Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults : results of the Ziagen Once Daily in Antiretroviral Combination Study . The long intracellular half-life of abacavir ( ABC ) supports its once-daily use , and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen . A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily ( n = 384 ) versus 300 mg of ABC administered twice daily ( n = 386 ) in combination with 300 mg of lamivudine ( 3TC ) and 600 mg of efavirenz ( EFV ) administered once daily in antiretroviral-naive patients over 48 weeks . The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL ( 44 % with viral load > 100,000 copies/mL ) , and the median CD4 cell count was 262 cells/mm . ABC administered once daily was non-inferior to the twice-daily regimen , with 66 % and 68 % of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level < 50 copies/mL ( 95 % confidence interval : -8.4 % , 4.9 % ) . The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure ( 10 % vs. 8 % ) , emergence of resistance mutations , CD4 cell increases from baseline ( median , 188 vs. 200 cells/mm ) , safety profile , and incidence of ABC-related hypersensitivity reactions ( 9 % vs. 7 % ) . ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks .

Abacavir

lamivudine and efavirenz

Ziagen

abacavir ( ABC )

ABC

ABC

ABC

lamivudine ( 3TC )

efavirenz ( EFV )

ABC

ABC

ABC-related

ABC

EFV

ABC

EFV

antiretroviral-naive

efficacy

safety

baseline median plasma HIV-1 RNA level

plasma HIV-1 RNA level

infrequency of virologic failure

safety profile

antiretroviral-naive HIV-infected

adults

antiretroviral-naive


Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus . BACKGROUND Severe neurological involvement in systemic lupus erythematosus ( NPSLE ) is one of the most dreadful complications of the disease . OBJECTIVE To identify the best drug , dose , and treatment . PATIENTS AND METHODS The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria , with incident ( no more than 15 days ) onset of severe NP manifestations such as seizures , optic neuritis , peripheral or cranial neuropathy , coma , brainstem disease , or transverse myelitis . Induction treatment with 3 g of IV methylprednisolone ( MP ) followed by either IV monthly cyclophosphamide ( Cy ) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year . The primary end point was response to treatment : at least 20 % improvement from basal conditions on clinical , laboratory , or specific neurological testing variables . RESULTS Overall , a response rate of 75 % was observed . Of the 32 patients studied , 18/19 receiving Cy and 7/13 receiving MP responded to treatment ( p < 0.03 ) . CONCLUSIONS Cy seems to be more effective than MP in the treatment of acute , severe NPSLE .

cyclophosphamide

methylprednisolone

methylprednisolone

cyclophosphamide

IV MP bimonthly

response to treatment

20 % improvement from basal conditions

response rate

effective


Effects of long-term vitamin E supplementation on cardiovascular events and cancer : a randomized controlled trial . CONTEXT Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events . Clinical trials have generally failed to confirm benefits , possibly due to their relatively short duration . OBJECTIVE To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer , cancer death , and major cardiovascular events . DESIGN , SETTING , AND PATIENTS A randomized , double-blind , placebo-controlled international trial ( the initial Heart Outcomes Prevention Evaluation [ HOPE ] trial conducted between December 21 , 1993 , and April 15 , 1999 ) of patients at least 55 years old with vascular disease or diabetes mellitus was extended ( HOPE-The Ongoing Outcomes [ HOPE-TOO ] ) between April 16 , 1999 , and May 26 , 2003 . Of the initial 267 HOPE centers that had enrolled 9541 patients , 174 centers participated in the HOPE-TOO trial . Of 7030 patients enrolled at these centers , 916 were deceased at the beginning of the extension , 1382 refused participation , 3994 continued to take the study intervention , and 738 agreed to passive follow-up . Median duration of follow-up was 7.0 years . INTERVENTION Daily dose of natural source vitamin E ( 400 IU ) or matching placebo . MAIN OUTCOME MEASURES Primary outcomes included cancer incidence , cancer deaths , and major cardiovascular events ( myocardial infarction , stroke , and cardiovascular death ) . Secondary outcomes included heart failure , unstable angina , and revascularizations . RESULTS Among all HOPE patients , there were no significant differences in the primary analysis : for cancer incidence , there were 552 patients ( 11.6 % ) in the vitamin E group vs 586 ( 12.3 % ) in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.84-1.06 ; P = .30 ) ; for cancer deaths , 156 ( 3.3 % ) vs 178 ( 3.7 % ) , respectively ( RR , 0.88 ; 95 % CI , 0.71-1.09 ; P = .24 ) ; and for major cardiovascular events , 1022 ( 21.5 % ) vs 985 ( 20.6 % ) , respectively ( RR , 1.04 ; 95 % CI , 0.96-1.14 ; P = .34 ) . Patients in the vitamin E group had a higher risk of heart failure ( RR , 1.13 ; 95 % CI , 1.01-1.26 ; P = .03 ) and hospitalization for heart failure ( RR , 1.21 ; 95 % CI , 1.00-1.47 ; P = .045 ) . Similarly , among patients enrolled at the centers participating in the HOPE-TOO trial , there were no differences in cancer incidence , cancer deaths , and major cardiovascular events , but higher rates of heart failure and hospitalizations for heart failure . CONCLUSION In patients with vascular disease or diabetes mellitus , long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure .

long-term vitamin E supplementation

vitamin E supplementation

placebo

vitamin E

placebo

vitamin E

long-term vitamin E supplementation

cardiovascular events and cancer

risk of cancer ,

cancer death

, and major cardiovascular events

cancer incidence ,

cancer deaths

cancer incidence

cancer deaths

major cardiovascular events

risk of heart failure

hospitalization for heart failure

cancer incidence

cancer deaths

major cardiovascular events

rates of heart failure

hospitalizations for heart failure

cancer

major cardiovascular events

risk for heart failure

cardiovascular events

cancer

cancer

cardiovascular events

cancer

cardiovascular events

at least 55 years old

vascular disease or diabetes mellitus

vascular disease or diabetes mellitus


Effect of a nutritional supplement containing vitamin E , selenium , vitamin c and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate : a randomised placebo-controlled study . OBJECTIVE To assess the effect of a nutritional supplement containing vitamin E , selenium , vitamin C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated carcinoma of the prostate and rising serum PSA levels . METHODS Eighty patients were randomised to receive a daily supplement with either vitamin E , selenium , vitamin C , coenzyme Q10 ( intervention group ) or placebo over 21 weeks . Serum levels of PSA were assessed at baseline ( -2 , -1 , 0 weeks ) and after 6 , 13 , 19 , 20 and 21 weeks . Mean changes in log serum level of PSA , testosterone , dihydrotestosterone , luteinizing hormone and sex hormone binding globulin over 21 weeks between the verum and the placebo group were compared by analysis of covariance . RESULTS Seventy patients completed the study ( 36 verum ; 34 placebo ) . Compliance was > 90 % in all patients . In the intervention group , plasma levels of vitamin E , selenium and coenzyme Q10 increased significantly over the 21 weeks study period . No significant differences in serum levels of PSA , testosterone , dihydrotestosterone , luteinizing hormone or sex hormone binding globulin ( p > 0.2 ) were observed between the intervention and control group . CONCLUSION Our results indicate that supplementation of a combination of vitamin E , selenium , vitamin C and coenzyme-Q10 does not affect serum level of PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate .

selenium

vitamin c

coenzyme Q10

vitamin E

selenium

vitamin C

coenzyme Q10

vitamin E

selenium

vitamin C

coenzyme Q10

placebo

vitamin E

selenium

coenzyme Q10

vitamin E

selenium

vitamin C

serum levels of PSA

serum PSA levels

Serum levels of PSA

serum level of PSA or hormone levels

rising serum PSA levels

Eighty patients were randomised

Seventy patients

36 verum

34 placebo )


Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation . In this prospective multicentre trial , 90 patients undergoing autologous stem cell transplantation ( ASCT ) were randomised to receive ( n=43 ) or not receive ( n=47 ) amifostine 910 mg/m ( 2 ) prior to melphalan 200 mg/m ( 2 ) . Patients were monitored for regimen-related toxicity , engraftment , supportive care , response and survival . Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics , prior therapy and pre-ASCT disease responsiveness . Amifostine infusional side-effects were frequent , occurring in 65 % of patients , but of mild severity . Amifostine use was associated with a reduction in the median grade of oral mucositis ( 1 vs 2 , P=0.01 ) and the frequency of severe ( WHO grades 3 or 4 ) mucositis ( 12 vs 33 % , P=0.02 ) , but no reduction in the requirement for parenteral nutrition or analgesic use . Conversion to complete remission post-ASCT occurred in 30 and 14 % of the amifostine and control groups , respectively ( P=0.09 ) . With a median follow-up of 35 months , there was no statistically significant difference between the median progression-free or overall survival times for the two groups . We conclude that amifostine can be safely administered prior to high-dose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis .

amifostine cytoprotection

high-dose melphalan

Amifostine

Amifostine

amifostine

amifostine

reduction

median grade of oral mucositis

post-ASCT


A comparison of the efficacy of heparinized and nonheparinized solutions for maintenance of perioperative radial arterial catheter patency and subsequent occlusion . In a randomized , double-blind , controlled study , we compared heparinized and nonheparinized infusions for the maintenance of perioperative arterial catheter patency and the incidence of subsequent radial arterial occlusion . Two-hundred patients were randomized into 2 groups to receive heparinized ( group H , n = 100 ) or nonheparinized ( group S , n = 100 ) flush solutions . Radial and ulnar blood flows were assessed using Doppler probe and pulse oximetry before , just after , and 24 h after decannulation by the same investigator . The cannulation site was examined for complications such as hematoma , nerve injury , and infection . The mean duration of cannulations was 378 +/- 159.0 min in group H and 332 +/- 154.6 min in group S. The mean number of corrective interventions caused by dampening of the pressure wave ( mean number of positional changes [ group S , 1.5 +/- 2.0 ; group H , 1.4 +/- 3.8 ] and mean number of manual flushes [ group S , 1.3 +/- 1.7 ; group H , 1.2 +/- 1.2 ] ) was not significantly different in both groups . After decannulation , partial or total occlusion developed in 20 group H patients and 16 group S patients ( not significant ) . The incidence of occlusion was correlated to the presence of hematoma at the puncture site after decannulation ( P = 0.013 ) , long duration of cannulation ( P = 0.04 ) , and age < 65 yr ( P = 0.009 ) . In conclusion , there is no significant difference between heparinized and nonheparinized flush solutions for the maintenance of perioperative radial artery catheter patency .

heparinized

nonheparinized

flush solutions

subsequent occlusion

Radial and ulnar blood flows

Doppler probe and pulse oximetry

decannulation

cannulations

partial or total occlusion

occlusion

hematoma

long duration of cannulation

perioperative radial arterial catheter


The effect of levetiracetam on essential tremor . The effect of a single dose of 1,000 mg of levetiracetam on essential tremor was investigated in 24 patients in a double-blind , placebo-controlled trial . There was a significant reduction of hand tremor for at least 2 hours as measured by accelerometry and functional tests .

levetiracetam

1,000 mg of levetiracetam

placebo-controlled

essential tremor

hand tremor


DNA as a carrier for anthracyclines in the treatment of acute myelocytic leukemia ( AML ) .

anthracyclines

acute myelocytic leukemia ( AML ) .

acute myelocytic leukemia ( AML )


Stapled hemorrhoidopexy vs. Harmonic Scalpel hemorrhoidectomy : a randomized trial . PURPOSE A randomized trial was undertaken to evaluate and compare stapled hemorrhoidopexy with excisional hemorrhoidectomy in which the Harmonic Scalpel was used . METHODS Patients with Grade III hemorrhoids who were employed during the trial period were recruited and randomized into two groups : ( 1 ) Harmonic Scalpel hemorrhoidectomy , and ( 2 ) stapled hemorrhoidopexy . All operations were performed by a single surgeon . In the stapled group , the doughnut obtained was sent for histopathologic examination to determine whether smooth muscles were included in the specimen . Operative data and complications were recorded , and patients were followed up through a structured pro forma protocol . An independent assessor was assigned to obtain postoperative pain scores and satisfaction scores at six-month follow-up . Patients were also administered a simple questionnaire at follow-up to assess continence functions . RESULTS Over a 20-month period , 88 patients were recruited . The two groups were matched for age and gender distribution . No significant difference was identified between the two groups in terms of operation time , blood loss , day of first bowel movement after surgery , and complication rates . Despite a similar parenteral and oral analgesic requirement , the stapled group had a significantly better pain score ( P = 0.002 ) ; these patients also had a significantly shorter length of stay ( P = 0.02 ) , and on average resumed work nine days earlier than the group treated with the Harmonic Scalpel ( 6.7 vs. 15.6 , P = 0.002 ) . Although 88 percent of doughnuts obtained in the stapled group contained some smooth muscle fibers , no association was found between smooth muscle incorporation and postoperative continence function , and as a whole the continence outcomes of the stapled group were similar to those after Harmonic Scalpel hemorrhoidectomy . Finally , at six-month follow-up , patients who underwent the stapled procedure had significantly better satisfaction scores ( P = 0.001 ) . CONCLUSION Stapled hemorrhoidopexy is a safe and effective procedure for Grade III hemorrhoidal disease . Patients derive greater short-term benefits of reduced pain , shorter length of stay , and earlier resumption to work . Long-term follow-up is necessary to determine whether these initial results are lasting .

Stapled hemorrhoidopexy

Harmonic Scalpel hemorrhoidectomy

Harmonic Scalpel hemorrhoidectomy

stapled hemorrhoidopexy

simple questionnaire

stapled

Stapled hemorrhoidopexy

pain scores

satisfaction scores

operation time

blood loss

complication rates

pain score

length of stay

smooth muscle fibers

smooth muscle incorporation

postoperative continence function

satisfaction scores

safe and effective

pain

shorter length of stay

earlier resumption to work


Comparison of intravenous and intra-arterial urokinase thrombolysis for acute ischaemic stroke . Intravenous fibrinolysis ( IVF ) with rt-PA ( alteplase ) provides significant benefits in acute ischaemic stroke when it is given within the first three hours following stroke onset . Intra-arterial fibrinolysis ( IAF ) with pro-urokinase in PROACT II study provides quite the same benefit in the first 6 hours . IVF and IAF have never been compared . To compare the efficacy and safety of IVF and IAF with urokinase given within the first 6 hours of acute ischaemic stroke . Patients fulfilling the selection criteria were randomly assigned to receive urokinase 900,000 units via intravenous or intra-arterial routes . This randomised monocentre study was done between December 1995 and August 1997 . The primary outcome was defined as the number of patients with a modified Rankin score of 2 or less . Secondary outcomes included mortality , frequency of symptomatic intracranial haemorrhage ( SIH ) , neurological and functional scores . Fourteen patients were given IVF and 13 IAF . The study was terminated by the National Health Authorities when 27 patients had been included because of the mortality rate . Seven patients ( 26 % ) died , 4 in the IV group ( oedematous infarct in 3 and recurrence in 1 ) , 3 in the IA group ( SIH in 2 , and oedematous infarct in 1 ) . Patients given IVF were treated significantly earlier ( 4:16 h vs 5:24 h ; p=.007 ) . Although IA patients showed greater and earlier improvement there was no significant difference in primary and secondary outcomes . Because of premature termination , the trial was too small to provide any reliable and conclusive results . Intra-arterial fibrinolysis began significantly later than IV fibrinolysis but it gave non-significantly better results in this prematurely terminated study .

IVF

IAF

IVF

IAF

urokinase

IVF

IAF

IVF

efficacy and safety

mortality

neurological and functional scores

acute ischaemic stroke

Fourteen


Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis . BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke . Warfarin is commonly used in preference to aspirin for this disorder , but these therapies have not been compared in a randomized trial . METHODS We randomly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin ( target international normalized ratio , 2.0 to 3.0 ) or aspirin ( 1300 mg per day ) in a double-blind , multicenter clinical trial . The primary end point was ischemic stroke , brain hemorrhage , or death from vascular causes other than stroke . RESULTS After 569 patients had undergone randomization , enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin . During a mean follow-up period of 1.8 years , adverse events in the two groups included death ( 4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group ; hazard ratio for aspirin relative to warfarin , 0.46 ; 95 percent confidence interval , 0.23 to 0.90 ; P=0.02 ) , major hemorrhage ( 3.2 percent vs. 8.3 percent , respectively ; hazard ratio , 0.39 ; 95 percent confidence interval , 0.18 to 0.84 ; P=0.01 ) , and myocardial infarction or sudden death ( 2.9 percent vs. 7.3 percent , respectively ; hazard ratio , 0.40 ; 95 percent confidence interval , 0.18 to 0.91 ; P=0.02 ) . The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group ( P=0.16 ) ; the rate of death from nonvascular causes was 1.1 percent and 3.8 percent , respectively ( P=0.05 ) . The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group ( hazard ratio , 1.04 ; 95 percent confidence interval , 0.73 to 1.48 ; P=0.83 ) . CONCLUSIONS Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial . Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis .

warfarin

aspirin

warfarin

aspirin

warfarin .

aspirin

aspirin

warfarin

Warfarin

Aspirin

ischemic stroke

brain hemorrhage

death

stroke

adverse events

death

major hemorrhage

myocardial infarction

sudden death

rate of death

rate of death


B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate : a randomized , three-way crossover study . BACKGROUND Deletion of the B-domain of recombinant blood coagulation factor VIII ( BDDrFVIII ) increases the manufacturing yield of the product but does not impair in vitro or in vivo functionality . BDDrFVIII ( ReFacto ) has been developed with the additional benefit of being formulated without human albumin . OBJECTIVE The primary objective of this three-way crossover-design study was to compare the pharmacokinetic ( PK ) parameters of two BDDrFVIII formulations ( one reconstituted with 5 mL of sterile water , the other reconstituted with 4 mL sodium chloride 0.9 % USP ) with those of a plasma-derived , full-length FVIII preparation ( Hemofil M ) in patients with haemophilia A to determine bioequivalence . METHODS A series of blood samples were collected over a period of 48 h after i.v . administration of each of the FVIII preparations . Plasma FVIII activity was determined using a validated chromogenic substrate assay . Plasma FVIII activity vs. time curves was characterized for a standard set of PK parameter estimates . Two parameter estimates , the maximum plasma concentration ( Cmax ) and the area under plasma concentration vs. time curves ( AUCs ) , were used to evaluate bioequivalence . The two preparations were considered bioequivalent if the 90 % confidence intervals for the ratio of geometric means for Cmax and AUCs fell within the bioequivalence window of 80 % to 125 % . RESULTS/CONCLUSION Results show that each BDDrFVIII formulation is bioequivalent to Hemofil M and the two formulations of BDDrFVIII are bioequivalent to each other .

FVIII preparations

BDDrFVIII formulation

blood samples

Plasma FVIII activity

Plasma FVIII activity

time curves

bioequivalent

haemophilia A


Development of the WAIS-III general ability index estimate ( GAI-E ) . The WAIS-III General Ability Index ( GAI ; Tulsky , Saklofske , Wilkins , & Weiss , 2001 ) is a recently developed , 6-subtest measure of global intellectual functioning . However , clinical use of the GAI is currently limited by the absence of a method to estimate premorbid functioning as measured by this index . The purpose of this study was to develop regression equations to estimate GAI scores from demographic variables and WAIS-III subtest performance . Participants consisted of those subjects in the WAIS-III standardization sample that has complete demographic data ( N=2,401 ) and were randomly divided into two groups . The first group ( n=1,200 ) was used to develop the formulas ( i.e. , Development group ) and the second ( n=1,201 ) group was used to validate the prediction algorithms ( i.e. , Validation group ) . Demographic variables included age , education , ethnicity , gender and region of country . Subtest variables included vocabulary , information , picture completion , and matrix reasoning raw scores . Ten regression algorithms were generated designed to estimate GAI . The GAI-Estimate ( GAI-E ) algorithms accounted for 58 % to 82 % of the variance . The standard error of estimate ranged from 6.44 to 9.57 . The correlations between actual and estimated GAI ranged from r=.76 to r=.90 . These algorithms provided accurate estimates of GAI in the WAIS-III standardization sample . Implications for estimating GAI in patients with known or suspected neurological dysfunction is discussed and future research is proposed .

develop the formulas

validate the prediction algorithms

GAI scores

WAIS-III subtest performance

Demographic variables

age

ethnicity

gender

region of country

vocabulary

information

picture completion

matrix reasoning raw scores

GAI

GAI-Estimate ( GAI-E ) algorithms


The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study . BACKGROUND AND PURPOSE Reduction of the overall treatment time of radiotherapy has increased locoregional control and disease specific survival in squamous cell carcinomas of the head and neck ( HNSCC ) , but the response is heterogeneous . EGFr is often overexpressed in HNSCC and has been related to the repopulation taking place during radiotherapy . The aim of the current study was to address the influence of EGFr and histopathological differentiation when the overall treatment time of radiotherapy was moderately reduced . PATIENTS AND METHODS Eight hundred and three patients with representative pretreatment tissue samples from the randomized DAHANCA 6 and 7 study of 5 vs. 6 fx/wk of radiotherapy . EGFr was visualized using immunohistochemistry and separated into high and low expression before correlation with clinical data . RESULTS Tumors with high EGFr ( 84 % ) responded better to moderately accelerated radiotherapy , than carcinomas with low EGFr , using locoregional control as endpoint and a similar pattern was seen , stratifying by well/moderate vs. poor tumor differentiation . Therefore , a combined parameter was constructed showing a more prominent separation of response : tumors with high EGFr and well/moderate differentiation did benefit from moderate acceleration of treatment regarding locoregional control , HR 0.54 ( 0.37-0.78 ) , whereas such an effect was not seen in tumors with low EGFr and/or poor differentiation , HR 0.8 ( 0.51-1.25 ) . These results reflected the disease specific survival as well and were confirmed in multivariable analyses . CONCLUSIONS Moderately accelerated fractionation is superior to conventional treatment in HNSCC but the response is heterogeneous and may be predicted by high expression of EGFr and well/moderate tumor differentiation .

epidermal growth factor receptor

radiotherapy

tumor differentiation

prominent separation of response

disease specific survival

expression of EGFr

tumor differentiation

Eight hundred and three patients


Stress reduction and analgesia in patients exposed to calming music postoperatively : a randomized controlled trial . BACKGROUND AND OBJECTIVES This randomized controlled trial was designed to evaluate , first , whether intra- or postoperative music therapy could influence stress and immune response during and after general anaesthesia and second , if there was a different response between patients exposed to music intra- or postoperatively . METHOD Seventy-five patients undergoing open hernia repair as day care surgery were randomly allocated to three groups : intraoperative music , postoperative music and silence ( control group ) . Anaesthesia and postoperative analgesia were standardized and the same surgeon performed all the operations . Stress response was assessed during and after surgery by determining the plasma cortisol and blood glucose levels . Immune function was evaluated by studying immunoglobulin A ( IgA ) levels . Patients ' postoperative pain , anxiety , blood pressure ( BP ) , heart rate ( HR ) and oxygen saturation were also studied as stress markers . RESULTS There was a significantly greater decrease in the level of cortisol in the postoperative music group vs. the control group ( 206 and 72 mmol L ( -1 ) decreases , respectively ) after 2 h in the post anaesthesia care unit . The postoperative music group had less anxiety and pain and required less morphine after 1 h compared with the control group . In the postoperative music group the total requirement of morphine was significantly lower than in the control group . The intraoperative music group reported less pain after 1 h in the post anaesthesia care unit . There was no difference in IgA , blood glucose , BP , HR and oxygen saturation between the groups . CONCLUSION This study suggests that intraoperative music may decrease postoperative pain , and that postoperative music therapy may reduce anxiety , pain and morphine consumption .

randomly allocated to three groups :

intraoperative music

postoperative music

and

silence

( control group )

surgeon performed all the operations

plasma cortisol

blood glucose levels

Patients ' postoperative

pain

anxiety

stress

immune response

Stress response

plasma cortisol

blood glucose levels

Immune function

immunoglobulin A ( IgA ) levels

Patients ' postoperative pain

anxiety

stress markers

level of cortisol

anxiety

pain

morphine

morphine

pain

anxiety

pain

morphine consumption


Dairy products do not lead to alterations in body weight or fat mass in young women in a 1-y intervention . BACKGROUND Previous results suggested that increased intake of dairy calcium is associated with reduced weight and fat mass . OBJECTIVE The purpose of this study was to determine whether long-term increases in consumption of dairy calcium alter body weight and fat mass in young , healthy women . DESIGN We used a randomized , 1-y intervention for dairy calcium . Subjects were 155 young ( aged 18-30 y ) , healthy , normal-weight women with intake of dietary calcium < 800 mg/d and energy intake < /= 2200 kcal/d . Women were randomly assigned to 1 of 3 groups : 1 ) control : continue established dietary intake ; 2 ) medium dairy : substitute dairy products to achieve intake of calcium of approximately 1000-1100 mg/d and maintain isocaloric intake ; 3 ) high dairy : substitute dairy products to achieve intake of calcium of 1300-1400 mg/d and maintain isocaloric intake . The main outcome measures were 1-y changes in body weight ( in kg ) and fat mass ( in kg ) . One hundred thirty-five women completed the trial . RESULTS Mean intakes of calcium during the intervention were 742.4 +/- 321.5 , 1026.4 +/- 311.3 , and 1131.29 +/- 337.2 mg/d for the control , medium-dairy , and high-dairy groups , respectively ( P < 0.0001 ) . No significant differences were observed in the mean 1-y change in body weight between the control , medium-dairy , and high-dairy groups ( 0.8 +/- 2.8 , 0.7 +/- 3.0 , and 1.5 +/- 4.1 kg , respectively ; P = 0.45 ) . No significant differences were observed in the mean 1-y change in fat mass between the control , medium-dairy , and high-dairy groups ( -0.5 +/- 2.5 , 0.3 +/- 2.7 , and 0.5 +/- 3.5 kg , respectively ; P = 0.26 ) . CONCLUSION Increased intake of dairy products does not alter body weight or fat mass in young , healthy women over 1 y .

Dairy products

dairy calcium

dairy calcium

dietary calcium

isocaloric intake

intake of calcium of 1300-1400 mg/d

isocaloric intake

dairy products

body weight or fat mass in young women

reduced weight and fat mass

intakes of calcium

mean 1-y change in body weight

mean 1-y change in fat mass

young women

young

healthy women

18-30 y

healthy , normal-weight

One hundred thirty-five

young

healthy women


Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement : a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study . OBJECTIVE To assess the relationship between inflammation and joint destruction in rheumatoid arthritis ( RA ) patients who have not responded clinically to treatment . METHODS Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab ( 3 mg/kg or 10 mg/kg every 4 or 8 weeks ) plus methotrexate ( MTX ) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy trial . RESULTS At week 54 , patients who did not show 20 % improvement by American College of Rheumatology criteria ( ACR20 nonresponders ) while receiving infliximab plus MTX exhibited mild but statistically significant improvement in clinical variables , including the 28-joint Disease Activity Score ( DAS28 ) ( P < 0.001 ) , tender joint count ( P = 0.014 ) , swollen joint count ( P < 0.001 ) , and C-reactive protein ( CRP ) level ( P < 0.001 ) . Whereas the clinical and CRP changes among ACR20 nonresponders to infliximab plus MTX were small and much lower than among ACR20 responders to this treatment , radiographic progression among ACR20 nonresponders to infliximab plus MTX was significantly inhibited ( P < 0.001 ) compared with ACR20 nonresponders to MTX plus placebo . Radiographic progression was much greater in patients receiving MTX plus placebo than in patients receiving infliximab plus MTX , irrespective of ACR response status ( mean change in modified Sharp/van der Heijde score 6.0 in ACR20 responders and 7.2 in ACR20 nonresponders in the MTX plus placebo-treated group , versus 0.1 in ACR20 responders and 1.2 in ACR20 nonresponders in the infliximab plus MTX-treated group ) . Furthermore , among patients who were ACR20 nonresponders through week 54 , patients who were DAS nonresponders at weeks 30 and 54 , and patients without any improvement in individual clinical variables , those receiving infliximab plus MTX still demonstrated inhibition of structural damage that was statistically significant compared with inhibition in patients who received MTX plus placebo ( P < 0.05 to P < 0.001 ) . CONCLUSION Even in patients without clinical improvement , treatment with infliximab plus MTX provided significant benefit with regard to the destructive process , suggesting that in such patients these 2 measures of disease are dissociated .

infliximab plus methotrexate

infliximab

methotrexate ( MTX )

MTX plus placebo

infliximab plus MTX

infliximab plus MTX

infliximab plus MTX

MTX plus placebo

MTX

infliximab plus MTX-treated

infliximab plus MTX

MTX plus placebo

infliximab plus MTX

radiographic benefit

assess the relationship

tender joint count

swollen joint count

C-reactive protein ( CRP ) level

radiographic progression

clinical improvement

rheumatoid arthritis

rheumatoid arthritis ( RA )


Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction : a pilot clinical study . BACKGROUND Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage . This study evaluated the effects of low amounts of nitric oxide , iloprost ( prostacyclin analog ) , and their combination administered directly into the oxygenator on platelet function , platelet-leukocyte interactions , and postoperative blood loss in patients undergoing coronary artery bypass grafting . METHODS Blood samples from 41 patients randomized to the control , nitric oxide ( 20 ppm ) , iloprost ( 2 ng x kg -1 x min -1 ) , or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass . Platelets and leukocytes were enumerated . Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa , P-selectin , platelet-derived microparticles , leukocyte CD11b/CD18 ( Mac-1 ) , and platelet-leukocyte aggregate were quantified by means of flow cytometry . Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry . RESULTS Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia , reduction of glycoprotein Ib and glycoprotein IIb levels , translocation of P-selectin , microparticle formation , Mac-1 upregulation , and suppression of collagen-induced aggregation . Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia , microparticle formation , and P-selectin translocation . Moreover , this treatment preserved thrombin receptor-activating peptide-induced aggregation , which was not rescued by single treatments . Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss . CONCLUSIONS Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass , such as thrombocytopenia , platelet activation , platelet-leukocyte aggregate formation , and suppression of platelet aggregative responses . The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass .

nitric oxide gas and iloprost

nitric oxide

iloprost

nitric oxide plus iloprost

Platelet membrane glycoprotein Ib

platelet-leukocyte aggregate

thrombocytopenia

glycoprotein Ib

glycoprotein IIb levels

P-selectin

Mac-1 upregulation

collagen-induced aggregation .

thrombocytopenia

microparticle formation

P-selectin translocation

blood loss .

thrombocytopenia

platelet activation

platelet-leukocyte aggregate formation

platelet aggregative responses

cardiopulmonary bypass

coronary artery bypass

cardiopulmonary bypass

cardiopulmonary bypass


Simvastatin blunts endotoxin-induced tissue factor in vivo . BACKGROUND Beyond lipid lowering , various antiinflammatory properties have been ascribed to statins . Moreover , in vitro studies have suggested the presence of anticoagulant effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors , as lipopolysaccharide ( LPS ) -induced monocyte tissue factor ( TF ) was suppressed . In this study , we examined the role of statins in experimental endotoxemia on inflammatory and procoagulant responses in vivo . METHODS AND RESULTS In this double-blind , placebo-controlled , parallel-group study , 20 healthy , male subjects were randomized to receive either simvastatin ( 80 mg/d ) or placebo for 4 days before intravenous administration of LPS ( 20 IU/kg IV ) . Plasma high-sensitive C-reactive protein ( hsCRP ) , monocyte chemoattractant protein ( MCP-1 ) , sCD40L , sCD40 , and prothrombin fragment F1+2 ( F1.2 ) were determined by ELISAs at baseline and at 4 and 8 hours after LPS administration . Monocyte TF expression and monocyte-platelet aggregates were measured by whole-blood flow cytometry over the same time course . The increases in hsCRP and MCP-1 , both known inducers of TF , were significantly suppressed by statin treatment after LPS challenge . Statin premedication blunted the increase of monocyte TF expression in response to LPS . In parallel , endotoxin-induced formation of F1.2 was significantly reduced by simvastatin after 4 and 8 hours . LPS infusion affected neither the formation and activation of monocyte-platelet aggregates nor plasma levels of sCD40 and sCD40L . CONCLUSIONS Simvastatin suppresses the inflammatory response to endotoxin and blunts monocyte TF expression but does not affect platelet activation .

Simvastatin

statins

placebo-controlled

simvastatin

placebo

Statin

simvastatin

Simvastatin

sCD40L , sCD40

prothrombin fragment F1+2 ( F1.2 )

hsCRP

monocyte TF expression

formation of F1.2

plasma levels of sCD40 and sCD40L

monocyte TF expression

platelet activation

endotoxemia

healthy

male


Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma : a randomized phase II study of the Hellenic Cooperative Oncology Group . PURPOSE Temozolomide ( TMZ ) is an oral alkylating agent that produces methyl adducts at the 0.6 position of guanine . The methyl adducts are removed by the DNA repair enzyme AGAT . As demonstrated by in vitro studies , cisplatin ( CDDP ) is able to down-regulate the AGAT activity , suggesting that CDDP could enhance the antitumor activity of TMZ . We designed a randomized phase II study to evaluate and compare the activity and safety profile of the combination versus single-agent TMZ in patients with advanced melanoma . PATIENTS AND METHODS From January 2000 to April 2002 , 132 patients were enrolled on the study . Patient and tumor characteristics were well balanced between the two arms . Patients with cerebral metastases were included . Patients received TMZ 200 mg/m ( 2 ) /day orally for five consecutive days every 4 weeks or TMZ + CDDP 200 mg/m ( 2 ) daily on days 1-5 and 75 mg/m ( 2 ) of CDDP on day 1 . RESULTS Tumor responses ( complete and partial responses ) were seen in 16 patients ( 26 % ) in arm A and 19 patients ( 29 % ) in arm B . The median time to progression ( TTP ) was 3.8 months in arm A and 5.8 months in arm B . The median overall survival ( OS ) was 11.5 months in arm A and 12 months in arm B . The difference between treatment arms regarding objective response rates , TTP and OS were not statistically significant . Toxicity was comparable between the two arms for anemia , leukopenia , neutropenia , thrombocytopenia , fatigue , constipation and arthralgias/myalgias . There was significantly more grade 3 and 4 emesis in the combination arm . CONCLUSIONS No clear benefit in terms of response rates , median TTP or OS was shown with the combination of TMZ + CDDP . Additionally , the combination was associated with higher incidence of grade 3 and 4 emesis .

Temozolomide and cisplatin

temozolomide

Temozolomide ( TMZ )

cisplatin ( CDDP )

CDDP

TMZ .

combination versus single-agent TMZ

TMZ 200 mg/m ( 2 ) /day orally

TMZ + CDDP

CDDP

TMZ + CDDP .

antitumor activity of TMZ

Tumor responses

median time to progression ( TTP )

median overall survival ( OS )

objective response rates

grade 3 and 4 emesis

No clear benefit

response rates

median TTP

grade 3 and 4 emesis

advanced melanoma

advanced melanoma

cerebral metastases


Phase III study of the Eastern Cooperative Oncology Group ( ECOG 2597 ) : induction chemotherapy followed by either standard thoracic radiotherapy or hyperfractionated accelerated radiotherapy for patients with unresectable stage IIIA and B non-small-cell lung cancer . PURPOSE To compare once-daily radiation therapy ( qdRT ) with hyperfractionated accelerated radiation therapy ( HART ) after two cycles of induction chemotherapy . PATIENTS AND METHODS Eligible patients were treatment naive , and had stage IIIA and B unresectable non-small-cell lung cancer , Eastern Cooperative Oncology Group performance status 0/1 , and normal organ function . Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL . min plus paclitaxel 225 mg/m2 on day 1 . RT consisted of arm 1 ( qdRT ) , 64 Gy ( 2 Gy/d ) , versus arm 2 ( HART ) , 57.6 Gy ( 1.5 Gy tid for 2.5 weeks ) . A total of 388 patients were needed to detect a 50 % increase in median survival from 14 months of qdRT to 21 months of HART ; accrual was not achieved and the study closed prematurely . RESULTS Of 141 patients enrolled , 83 % were randomly assigned after chemotherapy to qdRT ( n = 59 ) or HART ( n = 60 ) . Median survival was 20.3 and 14.9 months for HART and qdRT , respectively ( P = .28 ) . Overall response was 25 % and 22 % for HART and qdRT , respectively ( P = .69 ) . Two- and 3-year survival was 44 % and 34 % for HART , and 24 % and 14 % for qdRT , respectively . Grade > or = 3 toxicities included esophagitis in 14 v nine patients , and pneumonitis in 0 v 6 patients for HART and qdRT , respectively . Any subsequent trials of the HART regimen must address the issues that led to early closure , including slow accrual , logistics of HART , mucosal toxicity , and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment . CONCLUSION After two cycles of induction chemotherapy with carboplatin-paclitaxel , HART is feasible with an acceptable toxicity profile . Although statistical significance was not achieved and the study closed early , there was a positive statistical trend suggesting a survival advantage with the HART regimen .

induction chemotherapy

standard thoracic radiotherapy

once-daily radiation therapy ( qdRT )

induction chemotherapy

Induction chemotherapy

carboplatin

paclitaxel

qdRT

HART

qdRT

HART

HART

qdRT

HART

qdRT

HART

qdRT

HART

qdRT

HART

HART

induction chemotherapy

carboplatin-paclitaxel , HART

HART

Median survival

Overall response

Two- and 3-year survival

Grade > or = 3 toxicities


Loss of tooth substance during root planing with various periodontal instruments : an in vitro study . Ultrasonic and power-driven instrumentation is gaining in significance as an acceptable alternative to manual periodontal root treatment . Some question whether they do not remove too much tooth substance . Various ultrasonic scalers , hand instruments and two power-driven systems were compared by assessing the loss of tooth substance due to root instrumentation . Quantitative analysis of this effect of the instruments used was performed on 20 freshly extracted , non-periodontally involved , large human molars . In the first study , 40 specimens were randomly assigned to four groups of treatment : combined use of ultrasonic scaler and Periopolisher diamond-coated inserts ( US-POL ) , hand instruments ( MANUAL ) , Perioplaner-Periopolisher system ( PPL-POL ) and Periokit ultrasonic-designed scalers ( PERIOKIT ) . The second study involved two treatment groups , ultrasonic scaler alone and hand instruments , each allocated with 20 teeth ( small root fragments ) . An unpaired two-tailed t test was carried out for both studies to compare the average weight loss of root substance with the modes of instrumentation . The level of significance was set at p < or=0.05 . The overall results of the first and second experimental trials did not reveal obvious differences in weight loss between the manual , ultrasonic or power-driven root treatments . Based on the results of these two comparative studies , the power-driven inserts or the various ultrasonic scalers tested did not remove more tooth substance than conventional hand instruments . They may thus be a useful alternative for the debridement of root surfaces .

root planing

Various

ultrasonic scalers

hand instruments

and

two power-driven systems

hand instruments ( MANUAL )

and

loss of tooth substance

weight loss of root substance

weight loss

remove more tooth substance

freshly extracted

non-periodontally involved

large human molars


Topical quinolone vs. antiseptic for treating chronic suppurative otitis media : a randomized controlled trial .

quinolone

antiseptic


Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus . BACKGROUND The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited . The median survival is less than 10 months , and less than 10 percent of patients survive for 5 years . Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival . METHODS This phase III prospective , randomized , and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil ( 1000 mg per square meter of body-surface area daily for four days ) and cisplatin ( 75 mg per square meter on the first day ) plus 5000 cGy of radiation therapy , as compared with 6400 cGy of radiation therapy alone , in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus . The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy . RESULTS The median survival was 8.9 months in the radiation-treated patients , as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy . In the former group , the survival rates at 12 and 24 months were 33 percent and 10 percent , respectively , whereas they were 50 percent and 38 percent in the patients receiving combined therapy ( P less than 0.001 ) . Seven patients in the radiotherapy group and 25 in the combined-therapy group were alive at the time of the analysis . The patients who received combined treatment had fewer local ( P less than 0.02 ) and fewer distant ( P less than 0.01 ) recurrences . Severe and life-threatening side effects occurred in 44 percent and 20 percent , respectively , of the patients who received combined therapy , as compared with 25 percent and 3 percent of those treated with radiation alone . CONCLUSIONS Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus , as measured by control of local tumors , distant metastases , and survival , but at the cost of increased side effects .

Combined chemotherapy and radiotherapy

radiotherapy alone

5000 cGy of radiation therapy

6400 cGy of radiation therapy

chemotherapy and radiation therapy

chemotherapy and radiation therapy

combined therapy

radiotherapy

combined-therapy

radiation therapy

median survival

survival rates

alive

local

distant

recurrences


Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients . We conducted a randomized unblinded parallel clinical trial to compare the effectiveness , side effects and tolerance between calcium acetate ( CA ) and calcium carbonate ( CC ) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus ( P ) levels with aluminum hydroxide ( AH ) . All patients were dialyzed against the same calcium dialyzate ( 1.62 mmol/l ) . The serum analytical tests included : calcium corrected to total protein , P , PTH ( intact molecule ) and bicarbonate . The study was divided into the following periods : P0 : baseline measurements ; P1 : washout ( withdrawal of AH for 15 days ) ; P2 : random allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium , stratified according to previous doses of AH ( 2 months ) ; P3 : adjustment of doses until control P ( 2 months ) . CA was poorly tolerated in 7 patients and CC in 2 ( NS ) . The changes in serum P levels between P0 and P2 periods were lower in the CA group ( 1.73 +/- 0.25 vs. 1.80 +/- 0.50 mmol/l ; p = 0.26 ) than in the CC group ( 1.77 +/- 0.35 vs. 1.93 +/- 0.48 mmol/l ; p = 0.03 , paired t test ) . Serum calcium was hardly modified by CA ( 2.42 +/- 0.20 vs. 2.47 +/- 0.17 mmol/l ; NS ) while in the CC group , it rose significantly ( 2.40 +/- 0.12 vs. 2.55 +/- 0.22 mmol/l ; p = 0.0004 ) . There were no differences in the control of PTH or bicarbonate . ( ABSTRACT TRUNCATED AT 250 WORDS )

Calcium acetate

calcium carbonate

calcium acetate ( CA )

calcium carbonate ( CC )

calcium dialyzate

CA

CC

effectiveness

side effects

CA was poorly tolerated

changes in serum P levels

Serum calcium

hemodialysis patients

chronic hemodialysis


Outcome at 7 years of children diagnosed with autism at age 2 : predictive validity of assessments conducted at 2 and 3 years of age and pattern of symptom change over time . OBJECTIVE To examine the predictive validity of symptom severity , cognitive and language measures taken at ages 2 and 3 years to outcome at age 7 in a sample of children diagnosed with autism at age 2 . METHOD Twenty-six children diagnosed with autism at age 2 were re-assessed at ages 3 and 7 years . At each age symptom severity , cognitive and language assessments were completed . RESULTS The pattern of autistic symptom severity varied over time by domain . Across time , children moved across diagnostic boundaries both in terms of clinical diagnosis and in terms of instrument diagnosis on the Autism Diagnostic Interview-Revised ( ADI-R ) . On all measures group variability in scores increased with age . Although non-verbal IQ ( NVIQ ) for the group as a whole was stable across the 3 assessments , this masked considerable individual instability . Standard assessments at age 2 did not predict outcome at age 7 even within the same domain of functioning . In contrast , standard assessments at age 3 did predict outcome . However , a measure of rate of non-verbal communicative acts taken from an interactive play-based assessment at age 2 was significantly associated with language , communication and social outcomes at age 7 . CONCLUSIONS The trajectory of autism symptoms over time differed in different domains , suggesting that they may be , at least in part , separable . Variability in language , NVIQ and symptom severity increased over time . Caution is required when interpreting the findings from assessments of children with autism at age 2 years . At this age measures of rate of non-verbal communication might be more informative than scores on standard psychometric tests . Predictive validity of assessments at age 3 years was greater .

symptom severity

cognitive and language measures

symptom severity

cognitive and language assessments

rate of non-verbal communicative acts

language

communication

social outcomes

language , NVIQ

and

symptom severity

children

autism

age 2

2 and 3 years of age

children

autism

age 2

Twenty-six

children

autism

age 2

children

autism

age 2 years


Treatment outcome of appliance therapy in temporomandibular disorder patients with myofascial pain after 6 and 12 months . AIM To compare the long-term effect of treatment with a stabilization appliance ( group T ) and treatment with a control appliance ( group C ) in temporomandibular disorder ( TMD ) patients with myofascial pain . METHODS In this controlled trial , 60 patients ( mean age 29 years ) with myofascial pain were evaluated after 10 weeks of treatment with either a stabilization appliance or a control appliance . All 60 patients were then assigned to 1 of 3 groups according to demand for treatment . Seventeen patients from group C requested another appliance and were given a stabilization appliance , thus creating a mixed group ( group M ) . RESULTS A significant difference in improvement of overall subjective symptoms in an intent-to-treat analysis between groups T and C was found at the follow-ups . In a survival analysis of treatment compliance , a significant difference was found between groups T and C. At the 6- and 12-month follow-ups , a significant reduction in myofascial pain , as measured on a visual analog scale , was found in all three groups . A significant decrease in frequency and intensity of myofascial pain was found in group T at the follow-ups . A significant decrease in number of tender sites on the masticatory muscles was found in group T at the follow-ups . CONCLUSION The results support the conclusion that the positive treatment outcome obtained by use of a stabilization appliance to alleviate the signs and symptoms in patients with myofascial pain persisted after 6 and 12 months . Most patients in groups T and M reported positive changes in overall subjective symptoms in this trial . We therefore recommend use of the stabilization appliance in the treatment of TMD patients with myofascial pain .

appliance therapy

stabilization appliance

control appliance

stabilization appliance

control appliance

stabilization appliance

stabilization appliance

stabilization appliance

myofascial pain

myofascial

visual analog scale

overall subjective symptoms

myofascial pain .

temporomandibular disorder

temporomandibular disorder

TMD

29 years

myofascial pain

myofascial pain

TMD

myofascial pain


Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer . This experiment examined the efficacy of an acustimulation wrist band for the relief of chemotherapy-induced nausea using a randomized three-arm clinical trial ( active acustimulation , sham acustimulation , and no acustimulation ) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment . Five outcomes related to wrist band efficacy ( acute nausea , delayed nausea , vomiting , QOL , and total amount of antiemetic medication used ) were examined . The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea . There were no significant differences in any of these study measures among the three treatment conditions ( P > 0.1 for all ) . Study results do not support the hypothesis that acustimulation bands are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients .

Acustimulation wrist bands

chemotherapy-induced

acustimulation wrist band

chemotherapy-induced

active acustimulation

sham acustimulation

no acustimulation

chemotherapy treatment

wrist band

antiemetic medication

acustimulation bands

chemotherapy-induced nausea

chemotherapy-induced nausea

wrist band efficacy

acute nausea

delayed nausea

vomiting

QOL

total

amount of antiemetic medication used

severity of past nausea

chemotherapy-related nausea

breast cancer

women

breast cancer

female

breast cancer


Problem-based learning : is anatomy a casualty ? INTRODUCTION The teaching of medical anatomy is changing . Medical schools worldwide are moving away from dissection and lectures to a more integrated course , where basic science and clinical skills are taught simultaneously . Medical students on these integrated courses have reported a lack of confidence in their basic science knowledge , especially concerning anatomy . Our aim was to perform a randomised controlled trial ( RCT ) to compare anatomical knowledge of two groups of second-year medical students , the first group taught on a traditional course , the second on an integrated course . MATERIALS AND METHODS Testing was done using a Questionnaire in a " True/False " format . There were 80 students in each group . There was no penalty for an incorrect answer . The test was performed under examination conditions . Papers were marked under blind conditions . Results were analysed using a Student 's t test analysis . RESULTS Those students taught on a traditional course exhibited a significantly higher level of basic anatomical knowledge ( p < 0.001 ) than those taught on an integrated course . The students taught on an integrated course showed a much greater range of results . CONCLUSIONS Students taught on a traditional course have a higher level of anatomical knowledge than those taught on an integrated course . Our results differ from previous studies done in Europe which show no difference between the courses .

Problem-based learning :

level of basic anatomical knowledge

range of results

anatomical knowledge

80 students in each group


Treatment of peri-implantitis by the Vector system . AIM To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device , the Vector system , with that of subgingival debridement with carbon fiber curettes . MATERIAL AND METHODS The study , comprising 11 patients with at least two screw type implants with bleeding on probing ( BOP ) , probing pocket depth ( PPD ) > or =5 mm , and at least 1.5 mm radiographic bone loss and exposed implant threads , was carried out as a single blind randomized clinical trial . At baseline one randomly chosen implant in each patient was treated by the Vector system ( test ) while the other implant ( control ) was treated by submucosal debridement with a carbon fiber curette . After 3 months , the same treatments were repeated . Plaque , BOP , and PPD were recorded on all implant surfaces at baseline , and after 3 and 6 months . Bone levels were recorded on radiographs taken prior to the start of the study , and after 6 months . RESULTS Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline . At 6 months , four of the Vector-treated sites , and only one site treated with curettes , had stopped to bleed . In neither the test nor the control group , were there any differences between baseline and 6 months regarding PPD and bone levels . CONCLUSION Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes , there was no significant difference between the two methods .

Vector system

Vector system

Vector system

carbon fiber curette

Vector-treated

sites

Vector system

effectiveness of treatment

bleeding on probing ( BOP )

probing pocket depth ( PPD )

bone loss

Plaque

BOP

PPD

Bone levels

Oral hygiene

bleed

PPD

bone levels

number of sites with BOP


Racial differences in primary and repeat lower extremity amputation : results from a multihospital study . OBJECTIVE African Americans have a much higher risk of major ( above- or below-knee ) lower extremity amputation and a lower rate of limb-preserving vascular surgery or angioplasty than white patients . This article analyzes two potential pathways for racial disparities : primary amputation , defined as a major amputation performed without any prior attempt at revascularization , and repeat amputation , defined as a major amputation subsequent to a previous through-foot or major amputation . METHODS Randomly selected medical records were reviewed for 248 African American , 30 Hispanic , and 235 white or other-race patients undergoing above- or below-knee amputation between 1995 and 2003 at three Chicago teaching hospitals . Chronic disease prevalence and severity , preadmission functional status , clinical presentation , and vascular history were used to test the risk-adjusted effect of race and ethnicity on rates of primary and repeat amputation . RESULTS Controlling for demographic , functional , chronic disease , and clinical characteristics , African American patients were 1.7 times more likely to have undergone both primary ( P = .01 ) and repeat ( P = .03 ) amputation than white or other-race amputees . Race remained a significant independent risk factor even after controlling for the higher severity of illness , greater disability , and more complex presentation of African American amputees . CONCLUSIONS Higher rates of primary and repeat amputation for African American patients at study hospitals , which all have significant vascular surgery capacity and an aggressive policy of limb salvage , suggest that these rates may be even higher at less well equipped institutions . Improving access to primary and preventive care for lower-income patients could reduce amputation rates among African Americans .

amputation

amputation

amputation

above- or below-knee amputation

primary

repeat amputation

amputation

primary

repeat amputation

primary and repeat amputation

amputation rates

248 African American

30 Hispanic

235 white or other-race patients


Automatic detection of red lesions in digital color fundus photographs . The robust detection of red lesions in digital color fundus photographs is a critical step in the development of automated screening systems for diabetic retinopathy . In this paper , a novel red lesion detection method is presented based on a hybrid approach , combining prior works by Spencer et al . ( 1996 ) and Frame et al . ( 1998 ) with two important new contributions . The first contribution is a new red lesion candidate detection system based on pixel classification . Using this technique , vasculature and red lesions are separated from the background of the image . After removal of the connected vasculature the remaining objects are considered possible red lesions . Second , an extensive number of new features are added to those proposed by Spencer-Frame . The detected candidate objects are classified using all features and a k-nearest neighbor classifier . An extensive evaluation was performed on a test set composed of images representative of those normally found in a screening set . When determining whether an image contains red lesions the system achieves a sensitivity of 100 % at a specificity of 87 % . The method is compared with several different automatic systems and is shown to outperform them all . Performance is close to that of a human expert examining the images for the presence of red lesions .

novel red lesion detection method

red lesion candidate detection system

red lesions

vasculature and red lesions

red lesions

sensitivity

Performance

diabetic


Comparative study of the efficacy of eprinomectin versus ivermectin , and field efficacy of eprinomectin only , for the treatment of chorioptic mange in alpacas . The efficacy of eprinomectin versus ivermectin ( Study 1 : a single-centre , randomised , treatment-controlled , blinded field trial ) , and the field efficacy of eprinomectin ( Study 2 : a single-centre , open , un-controlled field trial ) for the treatment of chorioptic infestation in naturally infested alpacas were assessed in two studies . Thirty alpacas , all positive for Chorioptes sp . mite , were randomly allocated to two treatment groups in Study 1 . Group A received a single topical administration of a 0.5 % formulation of eprinomectin at the dose rate of 500mug/kg . Group B received three subcutaneous administrations at 14 days interval of a 1 % formulation of ivermectin at the dose rate of 400mug/kg . Response to treatment was assessed by periodic mite count , and skin lesions scored . In Study 2 , one group of 19 alpacas received four administrations at weekly interval of topical eprinomectin at the dose rate of 500mug/kg , and response to treatment was monitored by mite counts . No localised or systemic side effects were observed in either trial . There was a statistically significant decrease in mite counts on day 7 ( P < 0.001 ) within treatment Groups A and B of Study 1 , but mite counts increased again on day 14 and remained high for the duration of the trial in both treatment groups . On day 14 of Study 2 , there was a statistically significant reduction in mite counts ( P < 0.008 ) and the mite counts remained very low throughout the remainder of the study . The eprinomectin protocol employed in Study 2 , consisting of four weekly topical administrations at the dose rate of 500mug/kg of body weight , proved highly effective at reducing the Chorioptes mite burden in alpacas .

eprinomectin

ivermectin

eprinomectin

eprinomectin

ivermectin

eprinomectin

eprinomectin

ivermectin

eprinomectin

eprinomectin

efficacy

field efficacy

efficacy

field efficacy

Response to treatment

periodic mite count

skin lesions scored

mite counts

localised or systemic side effects

mite counts

mite counts

mite counts

mite counts

Chorioptes mite burden

chorioptic mange

Thirty

Chorioptes mite burden


Use of an inspiratory impedance threshold device on a facemask and endotracheal tube to reduce intrathoracic pressures during the decompression phase of active compression-decompression cardiopulmonary resuscitation . INTRODUCTION Use of an inspiratory impedance threshold device ( ITD ) significantly increases coronary perfusion pressures and survival in patients ventilated with an endotracheal tube ( ETT ) during active compression-decompression cardiopulmonary resuscitation . We tested the hypothesis that the ITD could lower intratracheal pressures when attached to either a facemask or ETT . METHODS An active and sham ITD were randomly applied first to a facemask and then to an ETT during active compression-decompression cardiopulmonary resuscitation in 13 out-of-hospital cardiac arrest patients in a randomized , double-blinded , prospective clinical trial . The compression-to-bag-valve ventilation ratio was 15:2 . Airway pressures ( surrogate for intrathoracic pressure ) were measured with a pressure transducer . A sham and an active ITD were used for 1 min each in a randomized order , first on a facemask and then on an ETT . Statistical analyses were made using Friedman 's and Wilcoxon 's rank-sum tests . RESULTS For the primary end point , mean +/- sd maximum negative intrathoracic pressures ( mm Hg ) during the decompression phase of cardiopulmonary resuscitation were -1.0 +/- 0.73 mm Hg with a sham vs. -4.6 +/- 3.7 mm Hg with an active ITD on the facemask ( p = .003 ) and -1.3 +/- 1.3 mm Hg with a sham ITD vs. -7.3 +/- 4.5 mm Hg with an active ITD on an ETT ( p = .0009 ) . Decompression phase airway pressures with the facemask and ETT were not statistically different . CONCLUSIONS Use of an active ITD attached to a facemask or an ETT resulted in a significantly lower negative intratracheal pressure during the decompression phase of active compression-decompression cardiopulmonary resuscitation when compared with controls . Airway pressures with an ITD on either a facemask or ETT were similar . The ITD-facemask combination was practical and enables rapid deployment of this life-saving technology .

endotracheal tube ( ETT )

ITD

facemask or ETT

active and sham ITD

facemask

ETT

sham and an active ITD

facemask

ETT

sham

active ITD

facemask and ETT

ITD

facemask

ETT

ITD-facemask combination

intrathoracic pressures

Decompression phase airway pressures

negative intratracheal pressure


Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation . OBJECTIVE To examine further the relations of plasma von Willebrand factor ( vWf , an index of endothelial damage and dysfunction ) and soluble P-selectin ( sP-sel , an index of platelet activation ) concentrations to the presence and onset of clinical congestive heart failure ( CHF ) and the degree of left ventricular ( LV ) dysfunction in patients taking part in the SPAF ( stroke prevention in atrial fibrillation ) study . METHODS Plasma concentrations of vWf and sP-sel were measured by enzyme linked immunosorbent assay ( ELISA ) in 1321 participants in the SPAF III study and related to the presence and onset of clinical CHF , as well as echocardiographic findings . Of the 1321 patients with atrial fibrillation ( AF ) , 331 ( 25 % ) had a documented history of clinical heart failure , of which 168 cases were related to a new or recurrent episode of acute decompensated heart failure occurring within the preceding three months . RESULTS Mean plasma vWf was higher among patients with AF and CHF ( 154 ( 29 ) v 144 ( 31 ) IU/dl , p < 0.001 ) , particularly those with acute or recent decompensated symptoms . Patients with severe LV dysfunction on two dimensional echocardiography and low fractional shortening also had significantly higher vWf concentrations than those with no LV dysfunction . CHF patients with clinical features -- with ( 156 ( 28 ) IU/dl ) and without ( 152 ( 31 ) IU/dl ) LV dysfunction -- also had higher mean vWf concentrations than patients with asymptomatic LV dysfunction ( 146 ( 31 ) IU/dl , p < 0.001 ) . The presence of mitral regurgitation in CHF was associated with lower vWf concentrations . Plasma sP-sel concentrations were not affected by presence , onset , or severity of heart failure . CONCLUSIONS CHF may contribute to hypercoagulability and thrombotic risk in AF through increased endothelial damage and dysfunction . Patients with acute or recent decompensated features have the highest degree of endothelial damage and dysfunction . The presence of CHF clinical features was an important determinant of plasma vWf concentrations .

Willebrand factor

P-selectin

vWf

and

sP-sel

plasma von Willebrand factor

soluble P-selectin concentrations

Plasma concentrations of vWf

sP-sel

Mean plasma vWf

severe LV dysfunction

vWf concentrations

mean vWf concentrations

mitral regurgitation in CHF

Plasma sP-sel concentrations

endothelial damage and dysfunction

endothelial damage and dysfunction