Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia : a randomised trial . BACKGROUND 6-mercaptopurine has been a standard component of long-term continuing treatment for childhood lymphoblastic leukaemia , whereas 6-thioguanine has been mainly used for intensification courses . Since preliminary data have shown that 6-thioguanine is more effective than 6-mercaptopurine , we compared the efficacy and toxicity of the two drugs for childhood lymphoblastic leukaemia . METHODS Consecutive children with lymphoblastic leukaemia diagnosed in the UK and Ireland between April , 1997 , and June , 2002 , were randomly assigned either 6-thioguanine ( 750 patients ) or 6-mercaptopurine ( 748 patients ) during interim maintenance and continuing therapy . All patients received 6-thioguanine during intensification courses . We analysed event-free and overall survival on an intention-to-treat basis . We obtained toxicity data using an adverse-event reporting system , with follow-up questionnaires to seek detailed information for specific toxicities . This trial is registered with the International Standard Randomised Controlled Number 26727615 with the name ALL97 . FINDINGS After a median follow up of 6 years , there was no difference in event-free or overall survival between the two treatment groups . Although 6-thioguanine conferred a significantly lower risk of isolated CNS relapse than did 6-mercaptopurine ( odds ratio [ OR ] 0.53 , 95 % CI 0.30-0.92 , p=0.02 ) , the benefit was offset by an increased risk of death in remission ( 2.22 , 1.20-4.14 , p=0.01 ) , mainly due to infections during continuing therapy . Additionally , 95 patients developed veno-occlusive disease of the liver . Of these , 82 were randomly assigned 6-thioguanine , representing 11 % of all 6-thioguanine recipients . On long-term follow-up , about 5 % of 6-thioguanine recipients have evidence of non-cirrhotic portal hypertension due to periportal liver fibrosis or nodular regenerative hyperplasia . INTERPRETATION Compared with 6-mercaptopurine , 6-thioguanine causes excess toxicity without an overall benefit . 6-mercaptopurine should remain the thiopurine of choice for continuing therapy of childhood lymphoblastic leukaemia .

Toxicity and efficacy

efficacy and toxicity

event-free and overall survival

toxicity

event-free or overall survival

CNS relapse

risk of death

veno-occlusive disease of the liver

non-cirrhotic portal hypertension

toxicity

overall benefit

childhood

lymphoblastic leukaemia

childhood

lymphoblastic leukaemia

children

lymphoblastic


Prevention of bone loss in survivors of breast cancer : A randomized , double-blind , placebo-controlled clinical trial . BACKGROUND Few data are available on the safety and efficacy of once-weekly oral bisphosphonate therapy in breast cancer survivors . OBJECTIVE Our objective was to determine whether risedronate , 35 mg weekly , is efficacious and safe in preventing bone loss associated with chemotherapy-induced menopause . DESIGN The study was a randomized , double-blind , placebo-controlled clinical trial over 12 months . SETTING AND PARTICIPANTS Participants included 87 newly postmenopausal women with status post chemotherapy , recruited from a breast cancer clinic in an academic medical center . INTERVENTION Participants were randomly assigned to receive risedronate 35 mg/wk or placebo . MAIN OUTCOME MEASURES The primary outcomes were the 12-month changes in spine and hip bone mineral density . Secondary outcomes included changes in markers of bone resorption ( urine N-telopeptide cross-linked collagen type I ) and formation ( osteocalcin , N-terminal propeptide of type I procollagen , and bone-specific alkaline phosphatase ) . RESULTS After 12 months , bone mineral density increased by 1.2 % at the spine and 1.3 % at the hip in women on risedronate vs. significant decreases for women in the placebo group of 0.9 % at the spine and 0.8 % at the hip ( P < 0.01 , difference between groups ) . N-telopeptide cross-linked collagen type I , a marker of bone resorption , decreased by 19.3 % , and N-terminal propeptide of type I procollagen , a marker of bone formation , decreased by 26.6 % in participants on active therapy compared with increases in the control group . Risedronate was well tolerated , and the retention rate was 95 % at 1 yr . CONCLUSIONS Risedronate once weekly prevented bone loss and reduced bone turnover in women with breast cancer treated with chemotherapy . Early measures to prevent bone loss should be considered in this cohort of breast cancer survivors .

bisphosphonate therapy

risedronate

placebo-controlled

risedronate

placebo

risedronate

Risedronate

Risedronate

bone mineral density

tolerated

retention rate

survivors of breast cancer :

breast cancer survivors .


Classroom intervention for illness-related problem behavior in children with developmental disabilities . There is growing evidence of an association between physical illness and problem behavior in children with developmental disabilities . Such behavior can compromise school performance . Therefore , the purpose of the present study was to evaluate , using a group design , the effectiveness of medical intervention alone ( N = 11 ) versus behavioral plus medical intervention ( N = 10 ) for illness-related problem behavior in a school setting . Following intervention , the behavioral plus medical intervention group showed lower levels of problem behavior and completed more academic tasks than did the medical intervention alone group . The results are discussed with respect to the concept of illness and pain as a setting event for problem behavior . The need for research to develop algorithms that allow one to select the best combination of medical and behavioral interventions for specific illnesses and contexts is noted .

Classroom intervention

medical intervention alone

behavioral

medical intervention

medical

behavioral interventions

problem behavior

completed more academic tasks

concept of illness and pain

children

developmental disabilities

children

developmental disabilities


The Social Communication Assessment for Toddlers with Autism ( SCATA ) : an instrument to measure the frequency , form and function of communication in toddlers with autism spectrum disorder . The Social Communication Assessment for Toddlers with Autism ( SCATA ) was designed to measure non-verbal communication , including early and atypical communication , in young children with autism spectrum disorder . Each communicative act is scored according to its form , function , role and complexity . The SCATA was used to measure communicative ability longitudinally in two samples of toddlers with autism spectrum disorder . Overall frequency of non-verbal communicative acts did not change between the two assessments . However , the form and complexity , the function and the role the child took in the interaction did change with time . Both frequency and function of communicative acts in toddlerhood were positively associated with later language ability : social acts , comments and initiations showed greater predictive association than requests and responses .

SCATA

frequency

function of communication


Endocrine response to cataract surgery under total intravenous anaesthesia , local anaesthesia under sedation or local anaesthesia alone : a comparative study .

Endocrine response


Effect of patient withdrawal on a study evaluating pharmacist management of hypertension . STUDY OBJECTIVES To examine potential threats to internal and external study validity caused by differential patient withdrawal from a randomized controlled trial evaluating pharmacist management of hypertension , to compare the characteristics of patients who withdrew with those of patients who completed the study , and to identify characteristics that predispose patients to withdraw from hypertension management . DESIGN Prospective , randomized , comparative study . SETTING Network of primary care clinics . PATIENTS Four hundred sixty-three patients with a diagnosis of hypertension and a last documented systolic blood pressure of 160 mm Hg or greater and/or diastolic blood pressure of 100 mm Hg or greater . INTERVENTION Patients were randomly allocated to the pharmacist intervention or usual-care ( control ) group . Those in the pharmacist intervention group were collaboratively managed by a primary care clinical pharmacy specialist and their primary care provider . Patients in the control group received usual care from only their primary care provider . MEASUREMENTS AND MAIN RESULTS Of the 463 patients , 191 ( 41 % ) withdrew from the study after randomization and 272 ( 59 % ) completed the study . Patients who withdrew from the pharmacist intervention group were similar to patients who withdrew from the usual-care group with respect to age , sex , insurance status , and chronic conditions . Patients who smoked or had commercial insurance were more likely to withdraw from the study than the other participants . However , multivariate analysis of all variables , when adjusted for the effect of the intervention , revealed that insurance status was the only variable associated with a heightened probability of withdrawal ( p=0.002 ) . CONCLUSION Although this study had a high withdrawal rate , between-group patient characteristics remained balanced . Therefore , internal validity was preserved , and outcomes from the study groups could be reliably compared . A lack of significant differences between patients who withdrew versus those who completed , with the exception of insurance status , suggests that external validity was not jeopardized .

pharmacist management of hypertension

pharmacist intervention

usual-care ( control ) group

pharmacist intervention

withdraw

insurance status

withdrawal

patient withdrawal on a study

hypertension

Four hundred sixty-three patients

hypertension

diastolic blood pressure


Effect of CX516 , an AMPA-modulating compound , on cognition and behavior in fragile X syndrome : a controlled trial . A Phase II , 4-week randomized , double-blind , placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome ( FXS ) . After baseline screening , subjects with FXS ( n = 49 ) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period . Cognitive and behavioral outcome measures were administered prior to treatment , at the end of treatment , and 2 weeks posttreatment . There were minimal side effects , no significant changes in safety parameters , and no serious adverse events . There was a 12.5 % frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash . There was also no significant improvement in memory , the primary outcome measure , or in secondary measures of language , attention/executive function , behavior , and overall functioning in CX516-treated subjects compared to placebo . This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population , yet some were too difficult or variable . Adult subjects with FXS were able to complete an intensive clinical trial , and some valid outcome measures were identified for future FXS trial design . Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS .

AMPA-modulating compound

placebo-controlled

Ampakine

placebo

placebo

placebo

cognition

and

behavior

safety and efficacy

Cognitive and behavioral

minimal side effects

no serious adverse events .

12.5 % frequency

allergic rash

substantial rash

significant improvement

memory

measures

viable therapeutic strategy

n = 49

Adult subjects

FXS


A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder . Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders ( PDDs ) , but they require assessment of potential side effects . This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD . Eleven patients with a diagnosis of either autism , Asperger 's syndrome , or PDD not otherwise specified ( PDD-NOS ) and aged 6-14 years were randomized into an 8-week double-blind , placebo-controlled , parallel treatment study with olanzapine . There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement ( CGI-I ) and 50 % on olanzapine versus 20 % on placebo were responders . Olanzapine was associated with significant weight gain ( 7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo ) . Olanzapine may be a promising treatment for improving global functioning of PDDs , but the risk of significant weight gain remains a concern . Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD .

placebo-controlled

olanzapine

placebo-controlled

olanzapine

placebo-controlled

olanzapine

disruptive and repetitive behaviors

side effects

significant weight gain

global functioning of PDDs

weight gain

childhood/adolescent

pervasive developmental disorder

Eleven

autism

Asperger 's syndrome

PDD

PDD-NOS

6-14 years


Neuropsychological effects of risperidone in children with pervasive developmental disorders : a blinded discontinuation study . OBJECTIVE Little is known about the neuropsychological effects of risperidone in children with pervasive developmental disorders . METHOD Twenty-four children ( aged 5-17 years ) with pervasive developmental disorders and co-morbid disruptive behavior who responded favorably to open-label treatment with risperidone as part of a previously described controlled discontinuation study completed two different computerized attention tasks at baseline , weeks 4 , 8 , and 24 of open-label treatment , and , at 8 weeks after random assignment to either placebo or risperidone . The primary efficacy measures were response latencies to visually presented stimuli requiring two different types of attention-controlled processing , i.e. , focused and divided attention . RESULTS About half of the clinical responders did not produce valid performance measures . These could be shown to be of younger mental age and less adaptive as measured by the Vineland Behavior Scales . For the valid task performers divided attention ( serial search in working memory ) was shown to regress in the placebo group ( n = 7 ) , while in the risperidone group ( n = 7 ) there was further improvement . No such group difference was found for focused attention . CONCLUSIONS The study suggests a beneficial effect of risperidone after several months of treatment , enhancing divided attention in children with pervasive developmental disorders .

risperidone

risperidone

risperidone

placebo

risperidone

risperidone

response latencies

attention-controlled processing , i.e.

focused and divided attention

valid performance measures

Vineland Behavior Scales

serial search in working memory

children

pervasive developmental disorders

pervasive developmental disorders

Twenty-four children

aged 5-17 years


Evolution of neuropathy and myopathy during intensive vincristine/corticosteroid chemotherapy for non-Hodgkin 's lymphoma . Neuropathy and myopathy are common sequelae of intensive chemotherapy protocols that contain vincristine and corticosteroids . The authors prospectively monitored the evolution of neuropathy and myopathy during an intensive 12-week chemotherapy program for patients with intermediate and high-grade non-Hodgkin 's lymphoma . In this study , vincristine was administered by bolus injection followed by a 3-day continuous intravenous ( IV ) infusion ( total dose of 2.0 mg/m2 every other week ) ; the maximum dose of vincristine was not arbitrarily limited . Cronassial , a mixture of four naturally occurring gangliosides , was administered in a randomized double-blind test to evaluate whether this agent could prevent vincristine-induced neuropathy . High doses of dexamethasone ( 50 mg/d for 3 days weekly or every other week ) were also prescribed . Patients were monitored every 4 weeks with comprehensive physical and neurologic examinations and electrophysiologic studies of peripheral nerve function . Twenty-seven patients were fully evaluable . Weakness was a prominent adverse reaction in this study , and all patients had moderate to severe signs and symptoms of neuropathy and myopathy . Cronassial ( 100 mg ) administered by intramuscular ( IM ) injection daily provided no protection against the development of neuropathic symptoms . Vincristine typically impaired fine-motor coordination initially , whereas corticosteroids were associated with delayed development of proximal muscle weakness . Results of electrodiagnostic studies did not add to the clinical examination results . The authors conclude that symptomatic weakness due to neuropathy or myopathy appears in a predictable manner during intensive vincristine/corticosteroid-based treatment protocols . Simple clinical tests can be used to rapidly distinguish between toxic effects due either to vincristine or corticosteroids , and routine implementation of these tests can prevent inappropriate dose attenuation of these agents .

vincristine/corticosteroid chemotherapy

chemotherapy

vincristine

bolus

vincristine

vincristine-induced

dexamethasone

Cronassial

Vincristine

corticosteroids

vincristine or corticosteroids

Weakness

development of neuropathic symptoms

fine-motor coordination

development of proximal muscle weakness

symptomatic weakness

Twenty-seven


Polydioxanone sternal sutures for prevention of sternal dehiscence . BACKGROUND Sternal dehiscence and wound instability are troublesome complications following median sternotomy . Classic sternal approximation with stainless steel wires may not be the ideal approach in patients predisposed to these complications . We tested the efficacy of polydioxanone ( PDS ) suture in sternal closure and in prevention of complications in comparison to steel wires in high-risk individuals . METHODS Three hundred sixty-six patients undergoing elective cardiac surgery with full median sternotomy and having body surface area ( BSA ) less than 1.5 m ( 2 ) were randomly assigned to receive PDS ( n = 181 ) or stainless steel ( SS , n = 185 ) sternal approximation . The study was focused on aseptic sternal complications , namely bone dehiscence and superficial wound instability . RESULTS Both bone dehiscence and superficial wound instability were less frequent in the PDS Group ( 4 and 3 cases in the SS Group , respectively , vs. no cases in the PDS Group ) . Cox proportional hazards regression model in the whole study population identified female sex , chronic renal insufficiency , diabetes , advanced age , lower sternal thickness , osteoporosis , corticosteroid therapy , and prolonged CPB or ventilation times as predisposing factors to any of the two studied sternal complications . DISCUSSION Data suggest that PDS suture can protect against development of aseptic sternal complications following median sternotomy in high-risk patients with little body mass . The adoption of PDS in other subsets of patients , i.e. , obese individuals , is to be questioned .

Polydioxanone sternal sutures

polydioxanone ( PDS ) suture

PDS

stainless steel

PDS

PDS

PDS

Sternal dehiscence

wound instability

efficacy

sternal closure

complications

bone dehiscence

superficial wound instability

bone dehiscence

superficial wound instability

diabetes

osteoporosis

aseptic sternal complications


[ The effects of antidepressant treatment on efficacy of antihypertensive therapy in elderly hypertension ] . OBJECTIVE To explore the effect of antidepressant treatment on antihypertensive therapy of senile hypertension . METHODS 138 cases of senile hypertension complicating with depression were studied . 103 senile hypertensive patients without depression in the same period served as controls . The patients were randomly divided into 3 groups as A , B and C for study . 12.5 mg/d hydrochlorothiazide and 30 mg/d release-controlling tablets of nifedipine were orally administrated as basic antihypertensive medication each group . Besides , 20 mg/d fluoxetine was additionally given to groups A and one tablet of almitrine l/d and 20 mg oryzanol 3/d were given to group B . The treatment lasted 12 weeks . RESULTS In comparison with pre-treatment , the blood pressure at base line in sitting position and the average circadian SBP and DBP monitored with 24-hour ambulatory blood pressure monitoring ( ABPM ) was remarkably decreased in group A with statistical significance ( P < 0.01 ) . These blood pressure parameters in group B were also decreased as compared ith the pretreatment level brt with less statistical significance ( P > 0.05 ) . It was also noted tha with the addition of antidepressant fluoxetine , the manifestations of depression ere alleviated as shown by Hamilton depression ( HAMD ) scale . untoward reactions such as nausea , perspiration and skin rash were noted in a few patients , but none withdrew from the study . CONCLUSIONS Antidepressant and antianxiety treatment is of benefit to the antihypertensive therapy in senile hypertensive patients with complications of depression and/or anxiety neurosis . Based on the results of this study , it is suggested that routine administration of antidepressants and antianxiety drugs should be carried out in senile hypertensive patients complicating with depression or anxiety .

antidepressant treatment

hydrochlorothiazide

nifedipine

fluoxetine

almitrine l/d

oryzanol 3/d

efficacy

hypertension

blood pressure

blood pressure parameters

depression

Hamilton depression ( HAMD ) scale

nausea , perspiration and skin rash

elderly

hypertension

senile hypertension

senile hypertension

depression

senile hypertensive patients


A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma . AIMS The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal , choroidal , and retrobulbar hemodynamics and visual function in primary open-angle glaucoma ( OAG ) subjects . METHODS Sixteen ( 16 ) OAG patients ( age , 63.5 +/- 10.8 years ; 9 male ) were evaluated in a randomized , crossover , double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide . After randomization , 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study . Measurements included : adverse events check , visual acuity , contrast sensitivity , blood pressure , heart rate , intraocular pressure ( IOP ) , and fundus examination . Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry , color Doppler imaging , and scanning laser ophthalmoscopy . RESULTS Both therapies were effective at lowering IOP , whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide ( 13.9 % and 12.2 % reduction , respectively ; P = 0.5533 ) . Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity ( P = 0.0168 ) and lowered resistance to flow ( P = 0.0279 ) . Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide ( P = 0.0125 and 0.0238 , respectively ) . Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment . There were no statistically significant differences in adverse events , blood pressure , heart rate , visual acuity , contrast sensitivity scanning laser ophthalmoscopy , or Heidelberg Retinal Flowmeter for any treatment period . CONCLUSIONS Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol . Visual function , however , was not different in this short-term comparison between the two treatments .

combination of timolol and dorzolamide

latanoprost with timolol

timolol and dorzolamide .

combination of timolol and dorzolamide

Latanoprost plus timolol

ocular hemodynamics

visual function

adverse events check

visual acuity

contrast sensitivity

blood pressure

heart rate

intraocular pressure ( IOP )

fundus examination

Ocular blood flow

IOP

resistance to flow

ocular blood flow

adverse events

blood pressure

heart rate

visual acuity

Heidelberg Retinal Flowmeter

blood flow

IOP

Visual function

Sixteen ( 16 )

age , 63.5 +/- 10.8 years

male

OAG patients


The instruction to refrain from blinking affects auditory P3 and N1 amplitudes . Often subjects have been instructed to refrain from blinking lest their evoked EEG potentials should be distorted . We studied whether these very instructions have any impact on P3 amplitude . Two tones were presented in random order , and subjects had to count the high-pitched tones . Half the subjects were instructed not to blink , whereas this instruction was omitted for the other subjects . Target tones evoked larger P3s than non-targets in the latter group but not in the former , in particular not in those subjects that actually blinked rarely . The groups also differed in their N1 amplitudes . These findings might be relevant to P3 studies working with patients and controls : the harder some frequently blinking subjects try to refrain from blinking , the smaller might become their P3 amplitudes . Omitting the instruction and using off-line blink subtraction procedures seems a viable alternative . This study was actually motivated by discrepant findings on the effects of the preceding tone sequence on P3 . These discrepancies could be largely resolved by the instructional variable , in conjunction with different tone intensities . It is suggested that subjects who are discouraged from blinking try to protect themselves against the arousing effects of stimuli .

refrain from blinking

refrain from blinking

instructed not to blink

auditory P3

N1 amplitudes

P3 amplitude

N1 amplitudes

P3 amplitudes

tone intensities

not to blink


Treatment of psoriasis vulgaris by oral administration of yin xie ping granules -- a clinical report of 60 cases .

yin xie ping granules -- a

psoriasis vulgaris


A randomized controlled trial of a cognitive behavioural intervention for anger management in children diagnosed with Asperger syndrome . The purpose of the study described was to evaluate the effectiveness of a cognitive behavioural intervention for anger management with children diagnosed with Asperger syndrome . Forty-five children and their parents were randomly assigned to either intervention or wait-list control conditions . Children in the intervention participated in six 2-h weekly sessions while parents participated in a larger parent group . Parent reports indicated a significant decrease in episodes of anger following intervention and a significant increase in their own confidence in managing anger in their child . Qualitative information gathered from parents and teachers indicated some generalization of strategies learned in the clinic setting to both home and school settings . Limitations of the study and suggestions for future research are also discussed .

cognitive behavioural intervention

wait-list control conditions

six 2-h weekly sessions

episodes of anger

confidence

managing anger in their child


The protective effects of angiotensin II blockade with olmesartan medoxomil on resistance vessel remodeling ( The VIOS study ) : rationale and baseline characteristics . BACKGROUND The VIOS ( Vascular Improvement with Olmesartan medoxomil Study ) study is a randomized , parallel study to determine the relative effects of suppressing the renin-angiotensin system ( RAS ) with the angiotensin receptor antagonist olmesartan medoxomil versus suppressing sympathetic drive with the beta-adrenoceptor antagonist atenolol on remodeling of the subcutaneous small resistance vessel . Remodeling of small resistance vessels may be the earliest pathologic finding associated with hypertension . It may predate the onset of clinically apparent hypertension . METHODS In this study , 100 patients with stage I hypertension are characterized at baseline before being treated for 1 year to obtain a goal BP of less than 140/90 mm Hg as defined by Joint National Committee ( JNC ) -7 . Resistance vessel remodeling is determined using the gluteal fat biopsy technique in the hypertensive patients and a group of normotensive healthy volunteers . Additionally , efforts will be made to define whether noninvasive hemodynamic parameters , retinal vessel measurement changes , or biologic markers may predict and track the underlying vascular morphologic and physiologic changes induced by either regimen during the 12-month treatment period . RESULTS The primary endpoint will be the degree of vascular remodeling as obtained from percutaneous biopsy of gluteal subcutaneous resistance vessels in each of two treatment arms compared with the normal volunteers . The design of the study and the pertinent baseline characteristics of these patients with uncomplicated essential hypertension are presented . CONCLUSION The suppression of the RAS by the blockade of angiotensin II type 1 ( AT ( 1 ) ) receptors may demonstrate remodeling effects on the ubiquitous small resistance vessels similar to that seen in the myocardium and renal glomeruli , thus affording more complete end-organ protection .

olmesartan medoxomil

Olmesartan medoxomil

olmesartan medoxomil

atenolol

gluteal fat biopsy technique

biologic markers

stage I hypertension


Predictors of mental health problems and negative caregiving experiences in carers of adolescents with bulimia nervosa . OBJECTIVE This exploratory study focuses on the mental health ( MH ) and caregiving experience of carers of adolescents with Bulimia Nervosa ( BN ) /Eating Disorder not otherwise specified ( EDNOS ) , aiming to determine : levels of MH problems in carers and if a negative experience of caregiving predicts carer MH status and which factors predict a negative experience of caregiving . METHOD Hundred and twelve carers and 68 adolescents with BN/EDNOS completed self-report measures ( General Health Questionnaire , Experience of Caregiving Inventory , Level of Expressed Emotion , Self-report Family Inventory , Inventory of Interpersonal Problems ) . RESULTS Over half of the carers reported some MH problems and a minority ( 5.4 % ) were experiencing considerable difficulties . A negative experience of caregiving predicted carer MH status . Higher weekly contact hours and patient ratings of expressed emotion ( EE ) predicted a negative experience of caregiving . CONCLUSIONS Interventions focusing on reducing EE and contact hours could prove beneficial for both patient and caregiver outcomes .

Experience of Caregiving Inventory

Level of Expressed Emotion

Self-report Family Inventory

Inventory of Interpersonal Problems

MH problems

A negative experience of caregiving

EE

contact hours

adolescents

bulimia nervosa

adolescents

Hundred and twelve carers

adolescents

BN/EDNOS


Folate and arsenic metabolism : a double-blind , placebo-controlled folic acid-supplementation trial in Bangladesh . BACKGROUND Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic-contaminated drinking water . To various degrees , ingested inorganic arsenic ( InAs ) is methylated to monomethylarsonic acid ( MMA ) and dimethylarsinic acid ( DMA ) via folate-dependent one-carbon metabolism ; impaired methylation is associated with adverse health outcomes . Consequently , folate nutritional status may influence arsenic methylation and toxicity . OBJECTIVE The objective of this study was to test the hypothesis that folic acid supplementation of arsenic-exposed adults would increase arsenic methylation . DESIGN Two hundred adults in a rural region of Bangladesh , previously found to have low plasma concentrations of folate ( < /=9 nmol/L ) were enrolled in a randomized , double-blind , placebo-controlled folic acid-supplementation trial . Plasma concentrations of folate and homocysteine and urinary concentrations of arsenic metabolites were analyzed at baseline and after 12 wk of supplementation with folic acid at a dose of 400 microg/d or placebo . RESULTS The increase in the proportion of total urinary arsenic excreted as DMA in the folic acid group ( 72 % before and 79 % after supplementation ) was significantly ( P < 0.0001 ) greater than that in the placebo group , as was the reduction in the proportions of total urinary arsenic excreted as MMA ( 13 % and 10 % , respectively ; P < 0.0001 ) and as InAs ( 15 % and 11 % , respectively ; P < 0.001 ) . CONCLUSIONS These data indicate that folic acid supplementation to participants with low plasma folate enhances arsenic methylation . Because persons whose urine contains low proportions of DMA and high proportions of MMA and InAs have been reported to be at greater risk of skin and bladder cancers and peripheral vascular disease , these results suggest that folic acid supplementation may reduce the risk of arsenic-related health outcomes .

placebo-controlled

folic acid-supplementation

folic acid supplementation

placebo-controlled

folic acid-supplementation

supplementation with folic acid

placebo

placebo

folic acid

folic acid

arsenic methylation

proportion of total urinary arsenic

total urinary arsenic excreted

Two hundred

adults

low plasma folate


Topical retapamulin ointment ( 1 % , wt/wt ) twice daily for 5 days versus oral cephalexin twice daily for 10 days in the treatment of secondarily infected dermatitis : results of a randomized controlled trial . BACKGROUND New antibacterial agents with activity against pathogenic strains resistant to established antibiotics are needed to treat patients with secondarily infected dermatitis ( SID ) . OBJECTIVE We sought to determine the clinical safety and efficacy of topical retapamulin ointment 1 % versus oral cephalexin for the treatment of SID . METHODS Patients with SID were randomly assigned to retapamulin ointment 1 % ( twice daily [ bid ] ) for 5 days , or oral cephalexin ( 500 mg bid ) for 10 days . The primary efficacy end point was clinical response at follow-up . Secondary outcomes included microbiologic response at follow-up , safety , and compliance . RESULTS Retapamulin was as effective as cephalexin ( clinical success rates at follow-up : 85.9 % and 89.7 % , respectively ) . Microbiologic success rates at follow-up were 87.2 % for retapamulin and 91.8 % for cephalexin . Retapamulin was well tolerated and the topical formulation was preferred over the oral drug . LIMITATIONS An imbalance existed in the number of patients with the clinical outcome " unable to determine " ( 15 retapamulin , 2 cephalexin ) , mainly because of their failure to attend the study visit . If those who failed to attend visits ( who did not withdraw as a result of drug-related events ) are removed from the analysis , the clinical success rates are 89.9 % for retapamulin and 89.7 % for cephalexin . CONCLUSIONS Retapamulin ointment 1 % ( bid ) for 5 days was as effective as oral cephalexin ( bid ) for 10 days in treatment of patients with SID , and was well tolerated .

Topical retapamulin ointment

cephalexin

topical retapamulin ointment

cephalexin

retapamulin ointment

oral cephalexin

Retapamulin

cephalexin

retapamulin

cephalexin

Retapamulin

oral drug

retapamulin

cephalexin

retapamulin

cephalexin

Retapamulin ointment

cephalexin

clinical response

microbiologic response

safety

compliance .

Microbiologic success rates

tolerated

secondarily infected dermatitis :

Patients with SID

patients with SID


New hope for children with Kawasaki disease . Kawasaki disease is now the most common cause of acquired heart disease in America 's children . It is an acute febrile illness that may cause coronary artery aneurysm formation in infected children . The results of a multicenter , randomized trial on the effect of intravenous administration of gamma globulin ( IVGG ) plus aspirin versus aspirin alone upon coronary aneurysm formation show a decrease in coronary aneurysm formation from the usual 20 % -30 % to 3 % . Administration of IVGG presents some unique challenges for nurses . Also , the pediatric nurse must educate parents and children about this disease to prepare them for discharge and long-term follow-up care .

aspirin

aspirin alone

IVGG

coronary aneurysm formation

children

Kawasaki

heart


B-vitamins reduce plasma levels of beta amyloid . Elevated plasma homocysteine ( tHcy ) is a risk factor for Alzheimer 's disease ( AD ) , and thus B vitamins may have a role in the prevention of AD . The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1-40 ( A beta 40 ) . We randomized 299 older men to treatment with 2mg of folate , plus 25mg of B6 and 400 microg of B12 , or placebo . After 2 years of treatment the mean ( S.E . ) increase of A beta 40 was 7.0 pg/ml ( 8.4 ) in the vitamin group ( 4.9 % ) , and 26.8 pg/ml ( 7.7 ) ( 18.5 % ) in the placebo group . We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD .

B-vitamins

B vitamins

2mg of folate

plus 25mg of B6

400 microg of B12

placebo

plasma levels

mean ( S.E . ) increase of A beta 40

the plasma level of A beta 40


A randomized controlled trial to evaluate the efficacy of ultrasound-guided laser photocoagulation for treatment of benign thyroid nodules . This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound ( US ) -guided laser photocoagulation ( PLP ) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk . Twenty six subjects were randomized to the intervention ( no . 13 , age 68+/-3 yr , mean+/-SEM ) or observation ( no . 13 , age 71+/-2 yr ) groups . In the control group , the volume of nodules did not significantly change over the 30 week period of observation . In the intervention group , median nodule volume at baseline was 8.2 ml ( range 2.8-26.9 ) and was not significantly different from that of the control group . Nodules decreased significantly ( p < 0.0001 ) by 22 % after 2 weeks ( 6.5 ml ; range 2.4-16.7 ) and by 44 % after 30 weeks ( 4.6 ml ; range 0.69-14.2 ) . Energy given was correlated ( p < 0.05 ) with the reduction of thyroid nodule volume . All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints ( p < 0.05 ) . At the time of enrolment 7/13 ( 54 % ) and 6/13 ( 46 % ) of patients in the intervention and control groups , respectively , had sub clinical hyperthyroidism . PLP normalized thyroid function at 6 and 30 weeks after treatment . In conclusion , PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk .

intervention

observation

efficacy

efficacy

safety

benign thyroid nodules

volume of nodules

median nodule volume

Nodules

thyroid nodule volume

compressive and cosmetic complaints

sub clinical hyperthyroidism

PLP normalized thyroid function

safe

effective

benign thyroid nodules

Twenty six

68+/-3 yr

71+/-2 yr

benign thyroid nodules


The effects of chewing versus caffeine on alertness , cognitive performance and cardiac autonomic activity during sleep deprivation . Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day . This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity . Fourteen adults participated in a randomized , counterbalanced protocol employing a chewing , placebo and caffeine condition . Participants completed tasks assessing psychomotor vigilance , tracking , grammatical reasoning , alertness and sleepiness each hour across the night . All participants received either placebo or caffeine ( 200 mg ) , while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour . Heart rate ( HR ) , root mean square of the successive differences in R-R intervals on the ECG ( RMSSD ) , and preejection period ( PEP ) were simultaneously recorded . Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo . Similarly , measures of HR and RMSSD remained the same between these two conditions ; however , PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo . Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing . Relative increases in RMSSD and reductions in HR were demonstrated following caffeine ; however , no change in PEP was seen . Strong associations between cardiac parasympathetic activity and complex cognitive tasks , as well as between subjective alertness and simpler cognitive tasks , suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation .

chewing

caffeine

Chewing

chewing

chewing

placebo

caffeine

placebo

caffeine

chewing

chewing

Caffeine

chewing

effects

effect

psychomotor vigilance

tracking

grammatical reasoning

alertness

sleepiness

Heart rate ( HR )

preejection period ( PEP )

Alertness and cognitive performance

HR

RMSSD

PEP

improved speed

and

accuracy on cognitive tasks

and

increased alertness

Relative increases in RMSSD

reductions in HR

no change in PEP

alertness

simpler cognitive tasks


Parent satisfaction in a multi-site acute trial of risperidone in children with autism : a social validity study . RATIONALE Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures . Designing studies that consider the consumer 's perspective will help to forge a better alliance between participants and researchers . OBJECTIVE Participant satisfaction is seldom assessed in pharmacological research . In this paper , we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior . METHOD Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures . RESULTS Ninety-six ( 95.0 % ) parents returned the questionnaire . Of these , 80.0 to 96.8 % , depending on the question , expressed satisfaction with their child 's research participation regardless of treatment outcome or assignment to active drug or placebo . In all , 90.5 % of parents indicated that they would " definitely " recommend the clinical trial to other families with similar children . A total of 92.7 % indicated that they would rejoin the clinical trial if they had to do it all over again . Ethnic minority subjects were more satisfied than white participants with the use of " learning tests " . CONCLUSIONS Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures . Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views . Further satisfaction studies of this sort are encouraged .

risperidone

risperidone

placebo

placebo

autistic disorder

severely disruptive behavior

children

autism


Effect of age and radiation dose on local control after breast conserving treatment : EORTC trial 22881-10882 . PURPOSE To determine whether the effect of an additional " boost " radiation after breast conservative therapy ( BCT ) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age . PATIENTS AND METHODS We used data from EORTC 22881-10882 trial , with median follow-up of 77.4 months . Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost ( N=5318 ) . RESULTS In univariate analysis , a boost reduced local failure by a factor of 2 ( P < 0.0001 ) . Multivariate analysis showed local control increased with age ( P=0.0003 ) . There was no evidence that the relative effect of a boost on local control depends on age ( P=0.97 ) However in younger patients the 5-year local failure was higher , therefore the absolute reduction was greater . If the threshold-age for boost treatment were set at 40 years , 8.4 % of the study population would receive a boost , resulting in a 5-year local failure of 6.1 % in the study population . Changing the threshold-age to 60 years , 67 % of the study population would receive a boost and the 5-year local failure would be reduced to 4.4 % . CONCLUSIONS In younger patients a boost dose resulted in a greater absolute reduction of local failure . The relative risk reduction was however similar for all ages . Applying a treatment policy with a threshold-age of 60 would result in 0.6 % increase in local failure in the total study population , while sparing the boost to 1/3 of the patients .

radiation

breast conserving treatment

" boost " radiation

breast conservative therapy ( BCT )

BCT and 50Gy whole breast irradiation

no boost and 16Gy boost

boost

boost

boost

boost

local control

local failure

local control

local control

local failure

local failure

local failure

local failure

relative risk reduction

local failure

BCT and 50Gy whole breast irradiation

younger patients


Effect of daily etidronate on the osteolysis of multiple myeloma . Progressive bone disease in multiple myeloma frequently leads to osteolysis , bone resorption , pathologic fractures , vertebral compression , and hypercalcemia . We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium ( EHDP ) , a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity . The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal . The extent of vertebral deformity was measured by a vertebral index as well as height . The frequency of pathologic fractures , hypercalcemia , and bone pain was regularly assessed , as well as size and number of osteolytic lesions . All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease . Although the repeated measures analysis showed a significant height loss , there was no difference between treatment arms ( P = .98 ) . There was no significant difference in bone pain , episodes of hypercalcemia , or development of pathologic fractures . Patients on EHDP showed less deterioration in their vertebral index , but this difference only approached statistical significance ( P = .07 ) . We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma .

etidronate

oral EHDP 5 mg/kg/d

placebo

melphalan

prednisone

EHDP

EHDP

frequency of pathologic fractures

hypercalcemia

bone pain

height loss

bone pain

episodes of hypercalcemia

development of pathologic fractures

deterioration in their vertebral index

multiple myeloma

etidronate disodium ( EHDP )

Patients on EHDP


Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C : Lessons from the HALT-C trial . In patients with chronic hepatitis C , advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response ( SVR ) to interferon ( IFN ) -based therapy . In this study , we assessed virologic response to retreatment with peginterferon alfa-2a and ribavirin ( RBV ) , as a function of the baseline fibrosis score ( Ishak staging ) and platelet count , in 1,046 patients enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis ( HALT-C ) Trial . All patients had failed prior treatment with IFN or peginterferon +/- RBV and had Ishak fibrosis scores > or = 3 . Four groups of patients with increasingly severe liver disease were compared : ( A ) bridging fibrosis ( Ishak 3 and 4 ) with platelet counts > 125,000/mm3 ( n = 559 ) ; ( B ) bridging fibrosis with platelet counts < or =125,000/mm3 ( n = 96 ) ; ( C ) cirrhosis ( Ishak 5 and 6 ) with platelet counts > 125,000/mm3 ( n = 198 ) ; and ( D ) cirrhosis with platelet counts < or =125,000/mm3 ( n = 193 ) . SVR rates were 23 % , 17 % , 10 % , and 9 % in groups A , B , C , and D , respectively ( P < .0001 for trend ) . Reduction in SVR as a function of increasingly severe disease was independent of age , percent African American , HCV genotype , HCV level , and type of prior therapy . Dose reduction lowered SVR frequencies , but to a lesser extent than disease severity . By logistic regression , cirrhosis ( P < .0001 ) was the major determinant that impaired virologic response , independent of dose reduction or platelet count . In conclusion , disease severity is a major independent determinant of rate of SVR in patients with advanced chronic hepatitis C. New strategies are needed to optimize antiviral therapy in these " difficult-to-cure " patients .

antiviral therapy

peginterferon alfa-2a

ribavirin ( RBV )

IFN

peginterferon +/- RBV

sustained virologic response ( SVR )

virologic response

SVR rates

Reduction in SVR

SVR frequencies

cirrhosis

virologic response

rate of SVR

chronic hepatitis C :

1,046 patients

Four groups

severe liver disease were compared


The use of the Antenatal Psychosocial Health Assessment ( ALPHA ) tool in the detection of psychosocial risk factors for postpartum depression : a randomized controlled trial . OBJECTIVE Eliciting known risk factors for postpartum depression ( PPD ) during pregnancy may enable primary health care providers to identify women at increased risk of becoming depressed . The purpose of this study was to examine how well the Antenatal Psychosocial Health Assessment ( ALPHA ) form identified antenatal risk factors for PPD , compared with routine care , in a sample of pregnant women . METHODS A randomized controlled trial was conducted to assess the effectiveness of the ALPHA form in detecting antenatal risk factors associated with the adverse postpartum outcomes of postpartum depression , intimate partner violence , child abuse , and couple dysfunction . The participants were primary antenatal care providers -- family physicians , obstetricians , and midwives -- from four diverse communities in Ontario . These providers were matched and then randomly allocated into the intervention group , who used the ALPHA form , or into the control group , who administered usual care . In total , 227 pregnant women were recruited : 98 in the ALPHA group and 129 in the control group . The data presented in this paper are from a secondary analysis focusing on PPD as the outcome . RESULTS Providers randomized to the ALPHA group identified a statistically significantly higher proportion of women with antenatal psychosocial risk factors for PPD ( 36 % vs. 26 % ) and a significantly higher number of risk factors per woman compared with the control group ( mean 2.1 vs.1.8 ) ( z = -1.96 , P = 0.05 ) . Providers in the ALPHA group also identified significantly more women having a " previous history of depression " ( 16 % vs. 6 % ) ( chi2 = 5.243 , df = 1 , P = 0.03 ) and " [ having ] witnessed or experienced abuse as a child " ( 17 % vs. 3 % ) ( chi2 = 12.488 , df = 1 , P = 0.0005 ) , which are both established risk factors for PPD . CONCLUSION The ALPHA provides a systematic means of eliciting antenatal psychosocial risk factors for PPD for primary care providers , and it may be particularly useful for raising and discussing sensitive issues . The detection of depressive symptomatology during pregnancy remains problematic , however , and detection may be improved by administering a simple standardized measure of depressive symptomatology during routine antenatal care .

ALPHA

who used the ALPHA form

ALPHA

ALPHA

psychosocial risk factors

risk factors for postpartum depression

effectiveness of the ALPHA

postpartum depression

intimate partner violence

child abuse

couple dysfunction

risk factors

previous history of depression

PPD

depressive symptomatology

women

primary antenatal care providers

women


Further validation of the alcohol dependence scale as an index of severity . OBJECTIVE The Alcohol Dependence Scale ( ADS ) yields continuous scores purported to reflect the severity of the dependence syndrome . We evaluated the concurrent validity of the ADS as a general measure of severity and the screening accuracy of the total score and subscales to detect Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) , physiological dependence . METHOD Treatment-seeking , alcohol-dependent individuals entering the Combining Pharmacotherapies and Behavioral Interventions for Alcohol Dependence ( COMBINE ) Study ( N = 1,372 ; 69 % men ) completed the ADS , diagnostic interviews , and other measures before randomization . Analyses of variance tested differences between ADS quartiles on alcohol- related measures . Areas under the receiver operating characteristic ( AUROC ) curve assessed screening accuracy for DSM-IV physiological dependence ( tolerance or withdrawal ) or withdrawal alone . RESULTS ADS quartiles differed on age , other demographics , and prior treatment episodes . Linear correlation showed moderate to large magnitude associations with alcohol-related self-report measures and most indices of consumption . ADS quartiles differed significantly on proportion with DSM-IV physiological dependence , but AUROC curves indicated that the ADS had limited accuracy as a continuous measure to detect DSMIV physiological dependence ( AUROC = .75 [ 95 % confidence interval { CI } : .70-.79 ] and .67 [ 95 % CI : .60-.74 ] for men and women , respectively ; p = .08 ) or withdrawal alone ( AUROC = .77 [ 95 % CI : .74-.80 ] and .74 [ 95 % CI : .69-.79 ] for men and women , respectively ; p = .30 ) . Screening accuracy was comparably limited based on ADS subscales reflecting psychoperceptual or psychophysical withdrawal . CONCLUSIONS The ADS reflected variation in symptom severity but did not adequately identify physiological dependence or withdrawal in treatment-seeking individuals with DSM-IV alcohol dependence .

Alcohol Dependence Scale

ADS

accuracy

DSMIV physiological dependence

Screening accuracy

alcohol-dependent

Alcohol Dependence

69 %

DSM-IV alcohol dependence


A double-blind placebo-controlled trial of zonisamide ( zonegran ) in the treatment of essential tremor . Medical therapy for essential tremor ( ET ) , a common movement disorder , is often inadequate . We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide ( ZNS ) , an antiepileptic agent , in treating ET . Twenty patients ( mean age , 60 +/- 15 years ) with ET were randomized to receive ZNS or placebo . ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14 . Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin ( FTM ) rating scale at baseline and days 14 and 28 , as well as the Clinical Global Impression ( CGI-C ) scale at day 28 . At endpoint , subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day . There were no significant improvements in the FTM total score or its subsections . Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline ( -0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s ( 2 ) ; P = 0.03 ) . On the CGI-C , 60 % ( n = 6 ) of patients in the ZNS group felt that their tremor was unchanged , while the remaining patients felt that their tremor was " minimally improved . " Thirty percent ( n = 3 ) of patients taking ZNS discontinued the study due to side effects ( fatigue , headache , paresthesias ) while taking 100 mg per day . ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated . ZNS was effective in reducing tremor amplitude as measured by accelerometry .

zonisamide ( zonegran )

zonisamide ( ZNS )

ZNS

placebo

ZNS

ZNS

ZNS

ZNS

essential tremor

essential tremor ( ET )

efficacy

tolerability

ET

ET

Fahn-Tolosa-Marin ( FTM ) rating scale

FTM total score or its subsections

Tremor amplitude

tremor

tremor

fatigue

headache

paresthesias

clinical rating scales

tolerated .

tremor amplitude

essential tremor ( ET )

Twenty patients

age , 60 +/- 15 years )

ET


Cognitive-behavioural stress management with HIV-positive homosexual men : mechanisms of sustained reductions in depressive symptoms . BACKGROUND We examined the sustained efficacy of a group-based cognitive-behavioural stress management ( CBSM ) intervention in comparison to a modified wait-list control condition on measures of mood , coping and social support in mildly symptomatic HIV-positive homosexual and bisexual men . Participants were recruited largely during the era prior to highly active antiretroviral therapy ( HAART ; 1992-1997 ) . METHODS Men were randomized to either a 10-week , group-based CBSM intervention ( n = 83 ) or a psychoeducational seminar group ( n = 46 ) . All participants completed a battery of psychosocial questionnaires administered by a research assistant at baseline , immediately following the 10-week CBSM intervention period , and at a 6-month follow-up . RESULTS Men in the CBSM group maintained previously observed effects on depressive symptoms and perceived social support . These sustained effects of CBSM on depressive symptoms were mediated by 10-week increases in cognitive coping ( i.e . positive reframing ) . DISCUSSION CBSM appears to be a potentially efficacious treatment that reduces and maintains lower levels of depressive symptoms and enhances social support in HIV-positive homosexual and bisexual men . In particular , changes in positive reframing during the 10-week intervention period remain a crucial factor contributing to sustained reductions in depressive symptoms .

Cognitive-behavioural stress management

wait-list control condition

CBSM intervention

psychoeducational seminar group

10-week CBSM intervention

reductions in depressive symptoms

mood

coping

social support

psychosocial questionnaires

depressive symptoms

perceived social support

10-week increases in cognitive coping

changes in positive reframing

reductions in depressive symptoms

HIV-positive

men

HIV-positive

Men

Men


[ A randomized trial of PVB , VAB-6 , BVP regimen versus PEB chemotherapy in patients with disseminated testicular tumors ] . During 2 years and 7 months from June , 1985 to December , 1987 , a randomized multi-center trial of PVB , VAB-6 , BVP regimen ( group A ) without etoposide versus PEB chemotherapy ( bleomycin , etoposide and cisplatinum ) ( group B ) was given to patients with disseminated testicular tumors . Of 34 patients registered , 10 patients were with minimal disease in stages IIA , IIIO and IIIA and 24 with extensive disease in IIB , IIIB2 and IIIC . Seminomas were found in 10 patients , while non-seminomatous tumors in 24 . Among groups A and B , there was no statistical difference in clinicopathological profiles . A group patients were given either PVB , VAB-6 or BVP according to the physician 's discretion . In groups A and B , 35 % and 43 % of the patients achieved complete response , and 45 % and 50 % achieved partial response , respectively . The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping . Salvage treatments mainly with surgical resection of residual tumors after the chemotherapy , however , were more successful in group B ( 88 % ) than group A ( 61 % ) . It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A . The 3 year survival rate was 100 % in group B , whereas it was 76 % in group A . Although the incidence of myelosuppression and alopecia was significantly higher in group B , neuropathy was significantly more frequent in group A . From the above results , PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors .

PVB , VAB-6 , BVP regimen

etoposide

chemotherapy

surgery

complete response

partial response

3 year survival rate

neuropathy


Midazolam vs ondansetron for preventing postoperative nausea and vomiting : a randomised controlled trial . We compared the prophylactic anti-emetic efficacy of midazolam and ondansetron in 90 patients scheduled for minor gynaecological ( hysteroscopy ) or urological ( ureteroscopy ) procedures planned to last 1-2 h under sevoflurane anaesthesia with spontaneous ventilation of the lungs via a laryngeal mask airway . Midazolam 2 mg or ondansetron 4 mg were administered intravenously 30 min before the end of surgery . The proportions of patients who experienced postoperative nausea and vomiting in the first 24 h ( 30 % and 27 % for the midazolam and ondansetron groups , respectively ) were similar in the two groups . The incidence of postoperative nausea and vomiting was significantly smaller in both groups than predicted according to the patients ' underlying risks ( midazolam group : p = 0.018 ; ondansetron group : p = 0.017 ) . There were no significant differences in average sedation scores or pain scores . Treatment using ondansetron for anti-emetic prophylaxis did not provide a superior benefit compared to midazolam in the present study .

Midazolam

ondansetron

midazolam

ondansetron

Midazolam 2 mg

ondansetron 4 mg

midazolam

ondansetron

midazolam

ondansetron

ondansetron

midazolam

postoperative nausea and vomiting

postoperative nausea and vomiting

postoperative nausea and vomiting

no significant differences

average sedation scores

pain scores

90 patients

sevoflurane anaesthesia

postoperative nausea and vomiting


[ Efficacy and safety of extended-release niacin alone or with atorvastatin for lipid profile modification ] . OBJECTIVE To evaluate the efficacy and safety of extended-release niacin ( niacin ER ) either alone or in combination with atorvastatin for the lipid profile modification in the patients with coronary heart disease ( CHD ) and its equivalents . METHODS One hundred and ten patients with CHD and its equivalents with serum total cholesterol ( TC ) > or = 3.5 mmol/L were randomly assigned into three treatment groups : ( 1 ) atorvastatin group ( n = 38 ) , receiving atorvastatin 10 mg/d for 8 weeks ; ( 2 ) niacin ER group ( n = 38 ) , given niacin ER 500 mg/d for 4 weeks and then 1000 mg/d for 4 weeks ; ( 3 ) combination treatment group ( n = 34 ) , treated with atorvastatin ( 10 mg/d ) plus niacin ER , with the dose initiating from 500 mg/d , and increasing to 1000 mg/d after 4 weeks , for 8 weeks . The serums lipid profiles and adverse effects were assessed in all the patients before treatment , and 4 and 8 weeks after treatment . RESULTS ( 1 ) After 8 weeks of treatment , the serum level of triglyceride ( TG ) and high-density lipoprotein cholesterol ( HDL-C ) were reduced by 30 % and 16 % respectively in the niacin ER group compared with the baseline values ( both P < 0.05 ) . After 8 weeks , the TC , low-density lipoprotein cholesterol ( LDL-C ) , and TG in the atorvastatin group decreased by 19 % , 26 % , and 17 % respectively compared with the baseline values ( all P < 0.05 ) . Combination treatment decreased the TC , LDL-C , and TG levels by 28 % , 38 % , and 39 % respectively , and increased the HDL-C level by 23 % ( all P < 0.05 ) . The improvement in TC and LDL-C achieved by combination treatment was superior to treatment of atorvastatin alone and treatment of niacin ER alone ( all P < 0.05 ) . ( 2 ) The rate of achieving the LDL-C goal of The National Cholesterol Education Program ( NCEP ) in Adult Treatment Panel III ( ATP III ) in the combination therapy group was 73.5 % , significantly higher than those of the atorvastatin and niacin groups ( 47.7 % and 42.1 % respectively , both P < 0.05 ) . ( 3 ) Adverse effect , such as flushing ( 15.8 % ) and gastrointestinal symptoms ( 23.7 % ) were found in the niacin ER group , however , no more adverse effects were found in the combination therapy group . There were no serious adverse events in all groups . CONCLUSION Niacin ER has a favorable effect in modulating the blood lipid profile , especially in reducing TG and elevating HDL-C . Combined statin with niacin may produce a more global and effective improvement in lipid blood levels than monotherapy and is generally safe and well tolerable .

niacin alone

atorvastatin

extended-release niacin ( niacin ER )

atorvastatin

atorvastatin

atorvastatin

niacin ER

niacin ER

combination treatment

atorvastatin ( 10 mg/d )

niacin ER

Efficacy

safety

efficacy

safety

serums lipid profiles

adverse effects

serum level of triglyceride ( TG )

TC

TG

atorvastatin

TC

LDL-C

TG levels

HDL-C level

TC

LDL-C

LDL-C

flushing

gastrointestinal symptoms

reducing

TG

elevating

HDL-C

safe

well tolerable


[ Sentinel lymph node detection in colorectal cancer : importance , techniques and results ] . BACKGROUND AND AIM Considering that lymph node status is a key factor in colorectal cancer staging , and the main determinant for adjuvant therapy of colorectal cancer being this therapy , responsible for a significant increase in colorectal cancer patients survival , the staging methods should be the most accurate possible in order to offer this individuals the opportunity to be adequate treated in order to achieve the best survival possible . Sentinel lymph node study is progressively being popularized as a method that increases sensibility in detect positive nodes to reveal a more accurate stage and prognosis in colorectal cancer patients . PATIENTS AND METHODS Thirty one colorectal cancer patients were prospectively studied and sentinel lymph node was identified in 100 % of the cases utilizing either patent blue alone , or in association with radiotracer based on technetium 99m colloid solution in a randomized fashion . RESULTS The mean number of sentinel nodes per patient was 1.96 ranging from 1 to 3 nodes . With the addition of transoperative lympho-scintigraphy five extra sentinel nodes , not identified by the blue dye alone , were identified and considered for histopathology study . In four cases ( 12.9 % ) the sentinel lymph node was the only site of metastasis , all of them being detected by association of hematoxylin and eosin and immunohistochemical examination . CONCLUSION Sentinel lymph node detection and analysis is feasible , technique is relatively simple and is able to produce upstage in colorectal cancer . Blue staining and radio guided techniques are both safe and their superposition has shown good results in terms of increase accuracy in our experience . There was no aberrant lymph drainage that would alter resection margins in patients studied . Upstaging rate , identifying potential candidates for adjuvant therapy was 12.9 % ( 4/31 ) . To this individuals chemotherapy could be a chance to increase their global survival .

adjuvant therapy

adjuvant therapy

chemotherapy

Sentinel lymph node detection

sensibility in detect positive nodes

stage and prognosis

transoperative lympho-scintigraphy

extra sentinel nodes

feasible

simple

produce upstage

safe

accuracy

lymph drainage

Upstaging rate


Assisted exercise and bone strength in preterm infants . Studies have previously demonstrated that brief ( 4 weeks ) passive range-of-motion exercise is beneficial for bone development in very low birth weight ( VLBW ) preterm infants . However , the optimal duration of exercise for bone development in preterm infants is yet unknown . The aim of the present study was to examine the effect of 8 weeks of assisted exercise on bone strength and metabolism in VLBW premature infants . Sixteen infants ( mean +/- standard error of the mean birth weight 1,009 +/- 55 g and gestational age 27.3 +/- 0.3 weeks ) were randomly assigned into exercise ( n = 8 ) and control ( n = 8 ) groups . The intervention started at the first week of life and involved 8 weeks of daily passive extension and flexion range-of-motion exercise of the upper and lower extremities . Biochemical markers of bone turnover were measured at enrollment and after 8 weeks . Bone strength was measured weekly by quantitative ultrasound measurement of tibial bone speed of sound ( SOS ) . Bone SOS decreased significantly in the control group ( -108.1 +/- 33.7 m/second , P < 0.0001 ) during the study period , while remaining stable in the exercise group ( 11.3 +/- 22.8 m/second ) . The main beneficial effect of exercise occurred in the first 4 weeks of the intervention . There were no significant differences in the bone turnover marker changes between the groups . There is a significant postnatal decrease in bone SOS in VLBW preterm infants . Eight weeks of assisted range-of-motion exercise attenuates the decrease in bone strength and may decrease the risk of osteopenia in premature infants .

Assisted exercise

exercise

assisted exercise

control

exercise

Biochemical markers of bone turnover

Bone strength

tibial bone speed of sound

Bone SOS

main beneficial effect of exercise

bone turnover marker changes

postnatal decrease in bone SOS

bone strength

risk of osteopenia

preterm infants

premature infants

Sixteen

infants

27.3 +/- 0.3 weeks


[ Observation on therapeutic effect of picking therapy on Graves ' disease ] . OBJECTIVE To observe therapeutic effect of picking therapy on Graves ' disease ( GD ) and its effects on thyroid function . METHODS Sixty cases of GD were randomly divided into a treatment group ( pricking therapy group ) and a control group ( medication group ) . They were treated respectively with pricking thyroid gland high point or oral administration of tapazole . And changes of total triiodothyronine ( TT3 ) , total thyroxine ( TT4 ) , free T3 ( FT3 ) , free T4 ( FT4 ) , thyroxine receptor antibody ( TRAb ) , supersensitive thyrotropin ( S-TSH ) after treatment were investigated . RESULTS The total effective rate was 93.33 % in the treatment group and 76.67 % in the control group with a significant difference between the two groups ( P < 0.05 ) . After treatment , serum TT3 , TT4 , FT3 , FT4 and S-TSH contents had very significant change in the two groups ( P < 0.01 ) , TRAb had very significant change in the treatment group ( P < 0.01 ) and no significant change in the control group ( P > 0.05 ) there were significant differences in decrease of TT3 , FT3 , TRAb ( P < 0.05 ) and no significant difference in decrease of TT4 , FT4 and increase of S-TSH between the two groups ( P > 0.05 ) . CONCLUSION Pricking therapy has a definite therapeutic effect on Graves ' disease , which is carried out through regulating thyroid function .

pricking therapy

medication

pricking thyroid gland high point

or

oral administration of tapazole

TT3 , FT3 , TRAb

TT4 , FT4 and increase of S-TSH

Graves ' disease

Graves ' disease

GD

Sixty


Treating anxiety disorders in children with high functioning autism spectrum disorders : a controlled trial . A family-based , cognitive behavioural treatment for anxiety in 47 children with comorbid anxiety disorders and High Functioning Autism Spectrum Disorder ( HFA ) was evaluated . Treatment involved 12 weekly group sessions and was compared with a waiting list condition . Changes between pre- and post-treatment were examined using clinical interviews as well as child- , parent- and teacher-report measures . Following treatment , 71.4 % of the treated participants no longer fulfilled diagnostic criteria for an anxiety disorder . Comparisons between the two conditions indicated significant reductions in anxiety symptoms as measured by self-report , parent report and teacher report . Discussion focuses on the implications for the use of cognitive behaviour therapy with HFA children , for theory of mind research and for further research on the treatment components .

anxiety disorders

children

children

children


A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors , protease inhibitors , or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy ( CPCRA 058 FIRST Study ) : a long-term randomised trial . BACKGROUND Long-term data from randomised trials on the consequences of treatment with a protease inhibitor ( PI ) , non-nucleoside reverse transcriptase inhibitor ( NNRTI ) , or both are lacking . Here , we report results from the FIRST trial , which compared initial treatment strategies for clinical , immunological , and virological outcomes . METHODS Between 1999 and 2002 , 1397 antiretroviral-treatment-naive patients , presenting at 18 clinical trial units with 80 research sites in the USA , were randomly assigned in a ratio of 1:1:1 to a protease inhibitor ( PI ) strategy ( PI plus nucleoside reverse transcriptase inhibitor [ NRTI ] ; n=470 ) , a non-nucleoside reverse transcriptase inhibitor ( NNRTI ) strategy ( NNRTI plus NRTI ; n=463 ) , or a three-class strategy ( PI plus NNRTI plus NRTI ; n=464 ) . Primary endpoints were a composite of an AIDS-defining event , death , or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison , and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison . Analyses were by intention-to-treat . This study is registered ClinicalTrials.gov , number NCT00000922 . FINDINGS 1397 patients were assessed for the composite endpoint . A total of 388 participants developed the composite endpoint , 302 developed AIDS or died , and 188 died . NNRTI versus PI hazard ratios ( HRs ) for the composite endpoint , for AIDS or death , for death , and for virological failure were 1.02 ( 95 % CI 0.79-1.31 ) , 1.07 ( 0.80-1.41 ) , 0.95 ( 0.66-1.37 ) , and 0.66 ( 0.56-0.78 ) , respectively . 1196 patients were assessed for the three-class versus combined two-class primary endpoint . Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies ( p=0.62 ) , respectively . HRs ( three-class vs combined two-class ) for AIDS or death and virological failure were 1.15 ( 0.91-1.45 ) and 0.87 ( 0.75-1.00 ) , respectively . HRs ( three-class vs combined two-class ) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 ( p=0.38 for interaction ) , and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100,000 copies per mL or more ( p=0.26 for interaction ) . Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies ( HR 1.58 ; p < 0.0001 ) . INTERPRETATION Initial treatment with either an NNRTI-based regimen or a PI-based regimen , but not both together , is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV .

NNRTI-based regimen

PI-based regimen

AIDS-defining event

death

CD4 cell count decline

change in CD4 cell count

composite endpoint

AIDS or death

death

virological failure

Mean change in CD4 cell count

HRs

AIDS or death

virological failure

HRs

AIDS or death

discontinue treatment

toxic effects

antiretroviral-treatment-naive

AIDS

HIV


Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning : a randomised controlled trial . BACKGROUND The role of oximes for the treatment of organophosphorus pesticide poisoning has not been conclusively established . We aimed to assess the effectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides . METHODS 200 patients were recruited to our single-centre , open randomised controlled trial after moderately severe poisoning by anticholinesterase pesticide . All were given a 2 g loading dose of pralidoxime over 30 min . Patients were then randomly assigned to control and study groups . Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h. The study group had a constant infusion of 1 g over an hour every hour for 48 h. Thereafter , all patients were given 1 g every 4 h until they could be weaned from ventilators . Analysis was by intention to treat . Primary outcome measures were median atropine dose needed within 24 h , proportion of patients who needed intubation , and number of days on ventilation . The study is registered at http : //www.clinicaltrials.gov with the identifier NCT00333944 . FINDINGS 100 patients were assigned the high-dose regimen , and 100 the control regimen . There were no drop-outs . Patients receiving the high-dose pralidoxime regimen required less atropine during the first 24 h than controls ( median 6 mg vs 30 mg ; difference 24 mg [ 95 % CI 24-26 , p < 0.0001 ] ) . 88 ( 88 % ) and 64 ( 64 % ) of controls and high-dose patients , respectively , needed intubation during admission to hospital ( relative risk=0.72 , 0.62-0.86 , p=0.0001 ) . Control patients required ventilatory support for longer ( median 10 days vs 5 days ; difference 5 days [ 5-6 , p < 0.0001 ] ) . INTERPRETATION A high-dose regimen of pralidoxime , consisting of a constant infusion of 1 g/h for 48 h after a 2 g loading dose , reduces morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning .

pralidoxime

pralidoxime

pralidoxime

number of days on ventilation

atropine

intubation during admission to hospital

ventilatory support

morbidity and mortality

organophosphorus pesticide poisoning

200 patients

100 patients

pralidoxime regimen


No association between dinucleotide repeat polymorphism in intron 1 of the epidermal growth factor receptor gene EGFR and risk of lung cancer . The tyrosine kinase receptor EGFR pathway is one of the oncogenic signaling cascades involved in lung cancer , mediating the epidermal growth factor receptor gene EGFR . First-intron polymorphisms with greater numbers of CA dinucleotide repeats tend to downregulate EGFR expression , which suggests that this polymorphism may modulate susceptibility to lung cancer . The present hospital-based case-control study evaluated the possible association of CA repeat polymorphism in the EGFR gene with risk of lung cancer in a Korean population . A bimodal pattern appeared , with a frequency of 57.1 % for 20 CA repeats and 18.6 % for 16 CA repeats . There was , however , no significant difference in distribution of allele genotypes between all lung cancer cases and the controls , nor among histological types for the cases .

First-intron polymorphisms

polymorphism

polymorphism in the EGFR gene

EGFR gene

risk of lung cancer .

susceptibility to lung cancer .


The additional value of a night splint to eccentric exercises in chronic midportion Achilles tendinopathy : a randomised controlled trial . AIM To assess whether the use of a night splint is of added benefit on functional outcome in treating chronic midportion Achilles tendinopathy . METHODS This was a single-blind , prospective , single centre , randomised controlled trial set in the Sports Medical Department , The Hague Medical Centre , The Netherlands . Inclusion criteria were : age 18-70 years , active participation in sports , and tendon pain localised at 2-7 cm from distal insertion . Exclusion criteria were : insertional disorders , partial or complete ruptures , or systemic illness . 70 tendons were included and randomised into one of two treatment groups : eccentric exercises with a night splint ( night splint group , n = 36 ) or eccentric exercises only ( eccentric group , n = 34 ) . INTERVENTIONS Both groups completed a 12-week heavy-load eccentric training programme . One group received a night splint in addition to eccentric exercises . At baseline and follow-up at 12 weeks , patient satisfaction , Victorian Institute of Sport Assessment-Achilles questionnaire ( VISA-A ) score and reported compliance were recorded by a single-blind trained researcher who was blinded to the treatment . RESULTS After 12 weeks , patient satisfaction in the eccentric group was 63 % compared with 48 % in the night splint group . The VISA-A score significantly improved in both groups ; in the eccentric group from 50.1 to 68.8 ( p = 0.001 ) and in the night splint group from 49.4 to 67.0 ( p < 0.001 ) . There was no significant difference between the two groups in VISA-A score ( p = 0.815 ) and patient satisfaction ( p = 0.261 ) . CONCLUSION A night splint is not beneficial in addition to eccentric exercises in the treatment of chronic midportion Achilles tendinopathy .

night splint to eccentric exercises

use of a night splint

eccentric exercises with a night splint

eccentric exercises only

heavy-load eccentric training programme

night splint

night splint

patient satisfaction

reported compliance

patient satisfaction

VISA-A score

VISA-A score

patient satisfaction

age 18-70 years

active participation in sports


Dofequidar fumarate ( MS-209 ) in combination with cyclophosphamide , doxorubicin , and fluorouracil for patients with advanced or recurrent breast cancer . PURPOSE To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) therapy in comparison with CAF alone , in patients with advanced or recurrent breast cancer . Dofequidar is a novel , orally active quinoline derivative that reverses multidrug resistance . PATIENTS AND METHODS In this randomized , double-blind , placebo-controlled trial , patients were treated with six cycles of CAF therapy : 28 days/cycle , with doxorubicin ( 25 mg/m2 ) and fluorouracil ( 500 mg/m2 ) administered on days 1 and 8 and cyclophosphamide ( 100 mg orally [ PO ] ) administered on day 1 through 14 . Patients received dofequidar ( 900 mg PO ) 30 minutes before each dose of doxorubicin . Primary end point was overall response rate ( ORR ; partial or complete response ) . In total , 221 patients were assessable . RESULTS ORR was 42.6 % for CAF compared with 53.1 % for dofequidar + CAF , a 24.6 % relative improvement and 10.5 % absolute increase ( P = .077 ) . There was a trend for prolonged progression-free survival ( PFS ; median 241 days for CAF v 366 days for dofequidar + CAF ; P = .145 ) . In retrospectively defined subgroups , significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal , had no prior therapy , and were stage IV at diagnosis with an intact primary tumor . Except for neutropenia and leukopenia , there was no statistically significant excess of grade 3/4 adverse events compared with CAF . Treatment with dofequidar did not affect the plasma concentration of doxorubicin . CONCLUSION Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy .

Dofequidar fumarate

CAF alone

placebo-controlled

CAF

doxorubicin

fluorouracil

cyclophosphamide

dofequidar ( 900 mg PO )

doxorubicin

CAF

dofequidar + CAF

dofequidar

Dofequidar + CAF

efficacy and tolerability

ORR

PFS

neutropenia and leukopenia

plasma concentration of doxorubicin .

advanced or recurrent breast cancer

advanced or recurrent breast cancer

premenopausal

no prior therapy

intact primary tumor

not received prior therapy


Depression and anxiety in women with breast cancer and their partners . BACKGROUND Psychosocial interventions can improve psychological quality of life ( symptoms of depression and anxiety ) of both women with breast cancer and their partners , but are not offered routinely to women and their partners . OBJECTIVE To test the hypotheses that telephone-delivered psychosocial interventions decrease depression and anxiety in women with breast cancer and their partners . METHODS The design of the study was a three-wave repeated measures with a between-subjects factor ( treatment group ) . Ninety-six women and their 96 partners were assigned randomly to participate in one of three different 6-week programs : ( a ) telephone interpersonal counseling ( TIP-C ) ; ( b ) self-managed exercise ; or ( c ) attention control ( AC ) . RESULTS The mixed-model analysis of variance for symptoms of depression among women with breast cancer revealed women 's depressive symptom scores decreased over time in all groups . For anxiety , women 's symptoms of anxiety decreased in the TIP-C and exercise groups over time , but not in the AC group . A parallel set of analyses was conducted on partners ' depression and anxiety data . Symptoms of depression and anxiety among the partners decreased substantially over the course of the investigation . Similar to the women , partners ' symptoms of anxiety decreased significantly in the TIP-C and exercise groups , but not in the AC group . DISCUSSION Findings from this study support that these telephone-delivered psychosocial interventions were effective for decreasing symptoms of depression and anxiety to improve psychological quality of life when compared to an AC group .

Psychosocial interventions

telephone interpersonal counseling

( TIP-C )

self-managed exercise

attention control

( AC )

TIP-C

TIP-C

Depression

anxiety

depression

anxiety

symptoms of depression

women 's depressive symptom scores

symptoms of anxiety

partners ' depression and anxiety

depression and anxiety

symptoms of anxiety

effective

depression

anxiety

psychological quality of life

women

breast cancer

partners

women

breast cancer

partners

women

partners

women

breast cancer

partners

Ninety-six women

96 partners

women

breast cancer

women

partners '

partners

women

partners


Music or guided imagery for women undergoing colposcopy : a randomized controlled study of effects on anxiety , perceived pain , and patient satisfaction . OBJECTIVE It was hypothesized that music or guided imagery versus usual care would result in less anxiety and perceived pain for colposcopy patients . MATERIALS AND METHODS Patients were randomized to music , guided imagery , or usual care after completing a baseline questionnaire . All patients completed a postprocedure questionnaire . RESULTS Study participants ( N=170 ) had a mean age of 28.4 years ( SD=9.6 ; range 18-60 ) and formed a racially diverse group . Education/income levels were low . No between-group differences were found for postprocedure anxiety or pain rating . CONCLUSIONS Mind-body interventions had no statistically significant impact on reported anxiety , perceived pain , or satisfaction with care , even for those who anticipated the most pain or started with high anxiety .

Music or guided imagery

colposcopy :

music , guided imagery , or usual care

baseline questionnaire .

postprocedure questionnaire .

Mind-body interventions

anxiety

perceived pain

patient satisfaction

anxiety

perceived pain

postprocedure anxiety

pain rating

anxiety

perceived pain

satisfaction with care


Xuezhikang , an extract of cholestin , decreases plasma inflammatory markers and endothelin-1 , improve exercise-induced ischemia and subjective feelings in patients with cardiac syndrome X . Previous studies have demonstrated that Xuezhikang , an extract of cholestin , available from Chinese red yeast rice , could effectively modify lipid profile . The present study was undertaken to investigate whether Xuezhikang could modify endothelin-1 ( ET-1 ) , interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( CRP ) and exercise-induced ischemia in patients with cardiac syndrome X ( CSX ) . Thirty-six patients with CSX were randomly assigned to 1200 mg/d of Xuezhikang or placebo group ( n=18 respectively ) . Blood samples were drawn at day 0 and day 90 for measuring above parameters . The treadmill exercise tests and subjective feelings were also assessed at day 0 and day 90 . The data showed that Xuezhikang therapy resulted in significant reductions in total cholesterol ( TC , 19 % ) , low-density lipoprotein cholesterol ( LDL-C ) ( 26 % ) , and triglycerides ( TG ) compared with baseline ( 16 % , p < 0.01 respectively ) . The data also showed that Xuezhikang led significantly to reductions in median and log-CRP levels ( 38 % and 44 % , p < 0.01 respectively ) , IL-6 ( 20 % , p < 0.01 ) , and ET-1 ( 47 % , p < 0.01 ) compared with baseline . The exercise duration , and time to 1 mm ST-segment depression was significantly prolonged after Xuezhikang therapy ( 9 % and 6 % , p < 0.05 respectively ) accompanied by improvement of subjective feelings . Data suggested that the benefit of Xuezhikang resulted in significant modification vascular function by reduction of ET-1 , inflammatory markers and LDL cholesterol , which may be clinically important for patients with CSX .

Xuezhikang

Xuezhikang

Xuezhikang

Xuezhikang

placebo

Xuezhikang

Xuezhikang

Xuezhikang

Xuezhikang

total cholesterol ( TC

triglycerides ( TG )

reductions in median and log-CRP levels

time to 1 mm ST-segment depression

improvement of subjective feelings

vascular function

ET-1 , inflammatory markers

LDL cholesterol


Do readers with autism make bridging inferences from world knowledge ? Individuals with autism frequently show impairments in text reading comprehension . This often is attributed to poor ability to draw inferences during reading and to inadequate access to relevant knowledge . The current study tested this hypothesis by measuring the time taken to read the same question , relating to either physical or social world knowledge , when it was either relevant or irrelevant to the bridging inference evoked by a preceding two-sentence vignette . In the study , 16 normally developing adolescents and 16 adolescents with autism were matched on word reading accuracy , chronological age , and vocabulary but differed significantly in text comprehension . A strong priming effect was found , robust over participants and over items ; participants read those questions that were relevant to the inference evoked by the vignette faster than they read those questions that were irrelevant , and no interaction with group membership or type of knowledge was found . This indicates that readers with autism , just like controls , were activating appropriate world knowledge primed by implicit inferences while reading the vignettes . Thus , the comprehension problems in these readers can not be attributed to an inability to make implicit inferences or to draw on relevant world knowledge . Instead , we suggest that these problems must be sought at a higher level of text processing .

autism

16 normally developing

autism

autism


Principal findings from a multicenter trial investigating the safety of follicular-fluid meiosis-activating sterol for in vitro maturation of human cumulus-enclosed oocytes . OBJECTIVE To evaluate the safety of applying follicular-fluid meiosis-activating sterol ( FF-MAS ) in vitro to immature human oocytes . DESIGN Phase I bicenter , randomized , parallel-group , controlled , partially blinded trial . SETTING Third-level referral academic centers , including reproductive biology and genetics laboratories . PATIENTS Endocrinologically normal women with a medical indication for IVF or intracytoplasmic sperm injection , or healthy volunteers . INTERVENTION ( S ) Subjects were randomized at a ratio 1 to 6 into either conventional GnRH-agonist and recombinant FSH stimulation ( IVO ) for oocyte retrieval , or minimally stimulated in vitro maturation ( IVM ) with the use of recombinant FSH . Retrieved immature oocyte cumulus complexes were cultured for 30 or 36 hours in one of six IVM culture conditions containing FF-MAS ( range , 0.1-20 microM ) . Polar body-extruded oocytes from the IVO and IVM groups were processed for chromosomal analysis . MAIN OUTCOME MEASURE ( S ) The primary endpoint was the incidence of metaphase II stage oocytes with numeric chromosomal abnormalities , using full ( spectral karyotyping ) or partial ( fluorescent in situ hybridization with seven probes ) karyotyping or Giemsa count . A secondary objective was to document the frequency of metaphase II oocytes after IVM with FF-MAS supplements . RESULT ( S ) Oocyte cumulus complexes obtained from the IVO ( mean , 8.9 ) and IVM ( mean , 6.2 ) groups had equal maturation rates . Compared to IVO , exposure of germinal-vesicle oocytes for a maturation period of 30 hours did not increase aneuploidy . An exposure period of 36 hours doubled the aneuploidy rate , but this was significant only for the 20-muM dose of FF-MAS . CONCLUSION Inclusion of 1-10 microM FF-MAS in a 30-hour IVM protocol is safe .

frequency of metaphase II oocytes

equal maturation rates .

aneuploidy .

aneuploidy rate

women


[ The effects of mexicor on thrombocyte aggregation , blood viscosity , hemodynamics , and the clinical course of coronary artery disease ] . The authors analyze their experience in the application of mexicor , a Russian cytoprotector , in 50patients with chronic coronary artery disease ( CAD ) and 51 patients with acute coronary syndrome . In additional to cytoprotective action , the use of mexidor in complex therapy of CAD lowers the functional activity of thrombocytes , eliminates high blood viscosity syndrome , and lowers low density lipoprotein cholesterol level . These favorable changes in hemorheological parameters improves myocardial perfusion , lowers the strength and frequency of coronary pain attacks , retards postinfarction left ventricular remodeling , and increases the quality of life of patients with various CAD forms .

mexicor

mexicor

, a Russian cytoprotector

mexidor

thrombocyte aggregation

blood viscosity

hemodynamics

functional activity of thrombocytes

high blood viscosity syndrome

myocardial perfusion

quality of life of patients

chronic coronary artery disease ( CAD )

51 patients

acute coronary syndrome


Unpacking attitude certainty : attitude clarity and attitude correctness . Attitude certainty has been the subject of considerable attention in the attitudes and persuasion literature . The present research identifies 2 aspects of attitude certainty and provides evidence for the distinctness of the constructs . Specifically , it is proposed that attitude certainty can be conceptualized , and empirically separated , in terms of attitude clarity ( the subjective sense that one knows what one 's attitude is ) and attitude correctness ( the subjective sense that one 's attitude is correct or valid ) . Experiment 1 uses factor analysis and correlational data to provide evidence for viewing attitude clarity and attitude correctness as separate constructs . Experiments 2 and 3 demonstrate that attitude clarity and attitude correctness can have distinct antecedents ( repeated expression and consensus feedback , respectively ) . Experiment 4 reveals that these constructs each play an independent role in persuasion and resistance situations . As clarity and correctness increase , attitudes become more resistant to counterattitudinal persuasive messages . These findings are discussed in relation to the existing attitude strength literature .

attitude clarity

attitude correctness

attitude clarity

attitude correctness

attitude clarity

attitude correctness

attitudes become more resistant


Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders . BACKGROUND Gastrointestinal ( GI ) symptoms and abnormalities in stool consistency are frequently reported by parents of children with autism spectrum disorders ( ASD ) . The purpose of this study was to 1 ) describe dietary intake of a cohort of children with ASD compared with normative data and 2 ) determine whether GI symptoms and stool consistency are related to dietary intake . METHODS Data from diet diaries of children ( 3-8 years ) with ASD ( n = 62 ) were analyzed by a registered pediatric dietician to compare to RDA standards for total calories , protein , carbohydrate , and fat . Dietary intake was correlated with descriptors of stool consistency using cumulative logistic regression methods . RESULTS Intake of calories , carbohydrates , and fat were in the average range ; protein intake was increased ( 211 % of RDA ) . Reported frequency of GI abnormalities , including abnormal stool consistency ( e.g. , bulky or loose ) , was increased ( 54 % ) . No statistically significant relationships between stool consistency and dietary intake were observed . CONCLUSIONS In this sample , there was a high rate of reported gastrointestinal symptoms , despite lack of medical causes . Intake was adequate for calories and carbohydrates and increased for protein . The children did not exhibit excessive carbohydrate intake . There was no association of nutrient intake to changes in stool consistency .

dietary intake

Data from diet diaries

gastrointestinal symptoms

frequency of GI abnormalities

abnormal stool consistency

bulky

loose

gastrointestinal symptoms