Rapid-sequence intubation of head trauma patients : prevention of fasciculations with pancuronium versus minidose succinylcholine . INTRODUCTION Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration . Standard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration . HYPOTHESIS Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium . DESIGN A prospective , randomized , double-blind study . SETTING An inner-city county trauma center with 70,000 patient visits per year . PARTICIPANTS Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium . INTERVENTIONS Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine ( 1 mg/kg ) IV . Patients were randomized to receive either minidose succinylcholine ( 0.1 mg/kg ) or pancuronium ( 0.03 mg/kg ) IV one minute prior to the full paralytic dose of succinylcholine ( 1.5 mg/kg ) IV . Fasciculations were recorded using a graded visual scale . RESULTS Of 46 patients , eight of 19 ( 42 % ) in the pancuronium group and six of 27 ( 22 % ) in the succinylcholine group experienced fasciculations . No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis . Complete relaxation of the cords was present in all but two patients , one in each group . No patient in either group experienced emesis or significant dysrhythmias . CONCLUSION Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting . Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients .

Rapid-sequence intubation

pancuronium

minidose succinylcholine

succinylcholine administration

succinylcholine

succinylcholine

pancuronium

rapid-sequence intubation maneuvers

lidocaine

minidose succinylcholine ( 0.1 mg/kg )

pancuronium

full paralytic dose of succinylcholine

pancuronium

succinylcholine

succinylcholine

pancuronium

succinylcholine

fasciculations

Fasciculations

emesis

fasciculations

Fasciculations

graded visual scale

fasciculations

fasciculations

Complete relaxation of the cords

emesis

significant dysrhythmias

fasciculations

head trauma

adult


Body asymmetry affects conjugate lateral eye movement . A. H. Baker ( 1989 ) and A. H. Baker and A. I. Ledner ( 1990 ) reported that asymmetrical visual stimulation affects conjugate lateral eye movement ( CLEM ) . In the present article , the authors explored whether asymmetrical body position similarly affects CLEM . The authors assessed CLEMs twice in a counterbalanced design . In the control ( symmetric ) condition , each participant sat in a completely symmetrical position facing a wall devoid of any asymmetrical features . In the experimental ( asymmetrical ) condition , half the participants rotated their heads 68 degrees clockwise relative to their bodies to face the experimenter , and the other half rotated their heads 68 degrees counterclockwise , also to face the experimenter . CLEM was predominantly toward the body 's position in the asymmetrical condition rather than toward the body 's position in the symmetrical condition .

Body asymmetry

completely symmetrical position

conjugate lateral eye movement

conjugate lateral eye movement ( CLEM )

Body asymmetry

conjugate lateral eye movement ( CLEM )

control ( symmetric ) condition


Clinical effects of naltrexone on autistic behavior . Eight young adults who were diagnosed with autism were given the opiate antagonist naltrexone to control self-injurious behavior and maladaptive idiosyncratic mannerisms . The drug and placebo were administered in a double-blind crossover design over 17 weeks . Although one subject appeared to have partial decreases in maladaptive behaviors associated with naltrexone use , the drugs , as administered in this study , did not reduce the self-injurious and other maladaptive behaviors of the subjects .

naltrexone

opiate antagonist naltrexone

placebo

naltrexone

autistic behavior .


Pretreatment with thiopental for prevention of pain associated with propofol injection . UNLABELLED Propofol causes pain on IV injection in 28 % -90 % of patients . A number of techniques have been tried to minimize propofol-induced pain , with variable results . We compared the efficacy of pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg and lidocaine 40 mg after venous occlusion for prevention of propofol-induced pain . One-hundred-twenty-four adult patients , ASA physical status I-II , undergoing elective surgery were randomly assigned into 4 groups of 31 each . Group I received normal saline , group II received lidocaine 2 % ( 40 mg ) , and groups III and IV received thiopental 0.25 mg/kg and 0.5 mg/kg , respectively . All pretreatment drugs were made in 2 mL and were accompanied by manual venous occlusion for 1 min . Propofol was administered after release of venous occlusion . Pain was assessed with a four-point scale : 0 = no pain , 1 = mild pain , 2 = moderate pain , and 3 = severe pain at the time of propofol injection . Twenty-four patients ( 77 % ) complained of pain in the group pretreated with normal saline as compared with 12 ( 39 % ) , 10 ( 32 % ) , and 1 ( 3 % ) in the groups pretreated with lidocaine 40 mg , thiopental 0.25 mg/kg , and thiopental 0.5 mg/kg , respectively ( P < 0.05 ) . Thiopental 0.5 mg/kg was the most effective treatment . We therefore suggest routine pretreatment with thiopental 0.5 mg/kg along with venous occlusion for 1 min for prevention of pain associated with propofol injection . IMPLICATIONS Pain associated with IV injection of propofol is seen in 28 % -90 % patients . Pretreatment with thiopental 0.25 mg/kg and 0.5 mg/kg after manual venous occlusion for 1 min effectively attenuated pain associated with propofol injection . Thiopental 0.5 mg/kg was the most effective in prevention of propofol pain and can be used routinely .

thiopental

propofol injection

Propofol

thiopental

lidocaine

normal saline

lidocaine

thiopental

manual venous occlusion

Propofol

lidocaine

thiopental

thiopental

Thiopental

thiopental

thiopental

Thiopental

pain on IV injection

propofol-induced pain

Pain

pain

effective

pain

Pain

pain

propofol pain

One-hundred-twenty-four

adult


Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis . BACKGROUND Glucocorticosteroids are effective in the treatment of allergic rhinitis , a disease characterized by a variety of symptoms , e.g . rhinorrhea and itching . The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date , although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids . We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge . METHODS Six female and 18 male volunteers ( median age 26 years ) with a history of allergic rhinitis but currently free of symptoms were included in this randomized , placebo-controlled , double-blind , three-period crossover study . A single dose of either betamethasone ( 60 mg ) , methylprednisolone ( 400 mg ) or placebo was given intravenously , 5 min after intranasal allergen provocation . After 10 , 20 , 60 , 150 and 240 min , nasal itching and nasal obstruction were assessed using a standardized visual analogue scale . In addition , nasal airflow was measured by anterior rhinomanometry . RESULTS Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug . Itching was depressed by 38 % following betamethasone ( P < 0.05 ) and by 18 % following methylprednisolone ( P=0.07 ) compared with placebo . Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study . However , after 150 min , nasal airflow was 21 % rsp . 19 % higher after methylprednisolone and betamethasone ( P < 0.05 ) compared with placebo . After 240 min , nasal airflow was increased by 20 % following betamethasone ( P < 0.05 ) and by 19 % following methylprednisolone . Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo ( P < 0.05 for both time points following betamethasone ) . CONCLUSION This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans . Itching , a pathophysiologically complex sensation , is favourably influenced by steroids within 10 min , therefore presumably via nongenomic mechanisms . Though no detailed mechanisms can be derived from this study , steroid interaction with receptors in the central nervous system may play an important role in mediating this effect .

Glucocorticosteroids

placebo-controlled

betamethasone ( 60 mg )

methylprednisolone ( 400 mg )

placebo

betamethasone

methylprednisolone

placebo

methylprednisolone

betamethasone

placebo

betamethasone

methylprednisolone

placebo

glucocorticosteroids

nasal affection

nasal itching

nasal obstruction

standardized visual analogue scale

nasal airflow

anterior rhinomanometry

Nasal itching

Itching

Nasal airflow

nasal obstruction

nasal airflow

nasal airflow

Nasal obstruction

Itching

seasonal allergic rhinitis

allergic rhinitis

Six

female

male

26 years

allergic rhinitis


Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin . BACKGROUND Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration ; however , kinetic information is limited . OBJECTIVES The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the possible influence of other carotenoids on plasma zeaxanthin concentrations . DESIGN After a run-in of 3 d , 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either 1 mg ( 1.76 micro mol ) or 10 mg ( 17.6 micro mol ) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42 , concentrations immediately before zeaxanthin intake during the dosing period , and concentrations after the last dose until day 76 were monitored . RESULTS all-E-Zeaxanthin concentrations increased from 0.048 +/- 0.026 micro mol/L at baseline to 0.20 +/- 0.07 and 0.92 +/- 0.28 micro mol/L with 1 and 10 mg zeaxanthin , respectively . The dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40 % lower ( P < 0.001 ) than after the 1-mg dose . Other kinetic parameters did not differ significantly between groups . After 17 d of dosing , > 90 % of steady state concentrations were reached , which was compatible with an effective half-life for accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d ( n = 20 ) . The time course of plasma all-E-3-'dehydro-lutein concentrations resembled that of all-E-zeaxanthin . The data provided evidence that all-E-3-'dehydro-lutein was derived from all-E-zeaxanthin . Concentrations of other carotenoids were not affected . Zeaxanthin was well tolerated . CONCLUSION Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximately 4- and 20-fold , respectively . Evidence that all-E-3-dehydro-lutein is formed from zeaxanthin was strong .

synthetic zeaxanthin

Zeaxanthin

zeaxanthin

zeaxanthin

zeaxanthin

all-E-Zeaxanthin

all-E-zeaxanthin

Zeaxanthin

zeaxanthin

zeaxanthin

plasma kinetics of synthetic zeaxanthin

plasma zeaxanthin concentrations

Plasma concentration-time profiles

all-E-Zeaxanthin concentrations

kinetic parameters

concentrations

terminal elimination half-life

all-E-zeaxanthin

Concentrations of other carotenoids

plasma zeaxanthin concentrations

macular degeneration

healthy


[ Clinical study on dan shao tang in treating IgA nephropathy of deficiency of yin with damp-heat symptom ] . OBJECTIVE To explore the effect of Dan Shao Tang ( DST ) in treating IgA nephropathy ( IgAN ) of deficiency of Yin with damp-heat symptom . METHODS 90 patients with IgAN of deficiency of Yin with damp-heat symptom were randomly divided into two groups . 50 patients in treatment group were treated with DST and western medicine and 40 patients in control group were treated only with western medicine . The effects and changes of the indexes including renal function , hematuria , proteinuria , blood IgA before and after treatment were observed . RESULTS After six months treatment , the general effective rate in treatment group was 70.00 % , which was markedly higher than that in control group ( 37.50 % , P < 0.01 ) . Treatment group is obviously better than control group on decreasing hematuria , proteinuria , blood IgA and improving renal function ( P < 0.05 ) . CONCLUSION DST is effective on IgAN of deficiency of Yin with damp-heat symptom .

dan shao tang

Dan Shao Tang ( DST )

DST

western medicine

with western medicine

DST

general effective rate

IgAN of deficiency of Yin

damp-heat symptom


Skin concentrations of thromboxane synthetase inhibitor after topical application with bioelastic membrane . Elevated thromboxane levels are associated with a number of disease states , including dermal pressure ulcers . When dazmegrel was orally administered to greyhound dogs wearing leg casts , it resulted in a sparring effect on the skin areas of potential pressure ulcer development . The objective of this research was to determine if bioelastic matrices could provide controlled release of thromboxane A2 synthetase inhibitor ( dazmegrel ) at tissue concentrations sufficient for inhibition of thromboxane synthesis . The animal used for these studies was the greyhound , which has thin skin , angular conformation , limited body fat and is predisposed to pressure ulcers similar to those occurring in humans . In vivo skin penetration studies showed that epidermal exposure to bioelastic thromboxane synthetase inhibitor ( TSI ) matrix resulted in local tissue concentrations of TSI sufficient for thromboxane synthetase inhibition . There were no significant differences between dazmegrel in the skin layers ( epidermis , dermis and subcutaneous layers ) on 1 , 7 and 14-day exposures .

dazmegrel

Skin concentrations

controlled release

local tissue concentrations of TSI

greyhound dogs wearing leg casts


Short-term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression - low manic switch rate . OBJECTIVES Current guidelines for the initial treatment of bipolar type II ( BP II ) major depressive episode ( MDE ) recommend using either a mood stabilizer alone or a combination of a mood stabilizer plus a selective serotonin re-uptake inhibitor ( SSRI ) . This recommendation is the result of concern over antidepressant-induced manic switch episodes . However , recent evidence suggests that the manic switch rate may be low in BP II MDE during SSRI therapy . METHODS As part of a randomized , double-blind , placebo-controlled relapse-prevention study of fluoxetine monotherapy in BP II MDE , 37 patients received open-label fluoxetine 20 mg every day for up to 8 weeks . Outcome measures included the Hamilton Depression Rating ( HAM-D 17 ) rating and the Young Mania Rating ( YMR ) scale . RESULTS Eleven of 23 patients ( 48 % ) who completed 8 weeks of fluoxetine treatment showed a HAM-D 17 reduction of > or =50 % , while 14 ( 38 % ) of all treated patients had > or =50 % reduction in baseline HAM-D 17 score . Using a conservative YMR score of > or =8 to identify hypomanic symptoms , the frequency of patients with YMR score > or =8 during fluoxetine did not differ from that seen during the screen and baseline period . Only three patients ( 7.3 % ) had symptoms suggestive of hypomania , and only one patient stopped treatment because of a rapid mood swing into depression . LIMITATIONS Fluoxetine was given at a fixed dose of 20 mg everyday . Fluoxetine was prescribed in an open-label manner , and the sample size was limited . CONCLUSIONS These observations support the findings of a low manic switch rate during SSRI monotherapy of BP II MDE , and suggest that fluoxetine monotherapy may be a safe and effective initial treatment of BP II MDE .

fluoxetine monotherapy

placebo-controlled

fluoxetine monotherapy

open-label fluoxetine 20 mg

every day for up to 8 weeks

fluoxetine

Fluoxetine

Fluoxetine

fluoxetine monotherapy

HAM-D 17 reduction

YMR score of > or =8

hypomania

rapid mood swing into depression

bipolar type II

BP II

BP II

BP II MDE


Comparison of quality of life , work productivity and medical resource utilization of peginterferon alpha 2a vs the combination of interferon alpha 2b plus ribavirin as initial treatment in patients with chronic hepatitis C. The on-treatment impact of interferon-based therapies on quality of life ( QOL ) , work productivity , and medical resource utilization has not been systematically studied . We evaluated the effects of treatment with peginterferon alpha ( pegIFNalpha ) 2a monotherapy and the combination of interferon alpha ( IFNalpha ) 2b plus ribavirin ( RBV ) on health-related QOL , work productivity and resource utilization . A total of 412 patients with hepatitis C infection were randomized to open-label treatment with either pegIFNalpha 2a ( n = 206 ) or IFNalpha 2b/RBV ( n = 206 ) . PegIFNalpha 2a was administered subcutaneously at a dose of 180 microg once weekly for 48 weeks ; and IFNalpha 2b/RBV at doses of 3 MU thrice weekly subcutaneously and 1000-1200 mg/day orally . Outcome measures included the SF-36 Health Survey Questionnaire and additional generic and specific scales . During treatment , for all SF-36 summary and Hepatitis Quality of Life Questionnaire ( HQLQ ) -specific scales , the pegIFNalpha 2a group experienced less impairment than did the IFNalpha 2b/RBV patients . The between-treatment differences were significant for many of the scores particularly in the first 24 weeks of treatment . Across all measures of work functioning and productivity at each visit , patients randomized to pegIFNalpha 2a treatment showed less impairment relative to the group treated with IFNalpha 2b/RBV . Hence treatment with pegIFNalpha 2a relative to IFNalpha 2b/RBV minimizes the adverse impact of therapy on health-related QOL . Patients randomized to pegIFNalpha 2a had improved work productivity , less activity impairment , decreased need for prescription drugs to treat adverse effects , and better adherence to therapy .

peginterferon alpha 2a

interferon alpha 2b plus ribavirin

peginterferon alpha ( pegIFNalpha )

monotherapy

IFNalpha 2b/RBV ( n = 206 )

PegIFNalpha 2a

IFNalpha 2b/RBV

pegIFNalpha 2a

IFNalpha 2b/RBV

pegIFNalpha 2a

IFNalpha 2b/RBV

pegIFNalpha 2a

IFNalpha 2b/RBV

pegIFNalpha 2a

quality of life

work productivity

medical resource utilization

quality of life ( QOL )

work productivity

medical resource utilization

health-related QOL

work productivity

resource utilization

health-related QOL

work productivity

less activity impairment

decreased need for prescription drugs

adverse effects

better adherence to therapy

hepatitis C infection


Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl ( CAELYX/Doxil ) versus conventional doxorubicin for first-line treatment of metastatic breast cancer . BACKGROUND This study was designed to demonstrate that efficacy [ progression-free survival ( PFS ) ] of CAELYX [ pegylated liposomal doxorubicin HCl ( PLD ) ] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer ( MBC ) . PATIENTS AND METHODS Women ( n=509 ) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 ( every 4 weeks ) or doxorubicin 60 mg/m2 ( every 3 weeks ) . Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose . RESULTS PLD and doxorubicin were comparable with respect to PFS [ 6.9 versus 7.8 months , respectively ; hazard ratio ( HR ) =1.00 ; 95 % confidence interval ( CI ) 0.82-1.22 ] . Subgroup results were consistent . Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD ( HR=3.16 ; 95 % CI 1.58-6.31 ; P < 0.001 ) . Overall survival was similar ( 21 and 22 months for PLD and doxorubicin , respectively ; HR=0.94 ; 95 % CI 0.74-1.19 ) . Alopecia ( overall , 66 % versus 20 % ; pronounced , 54 % versus 7 % ) , nausea ( 53 % versus 37 % ) , vomiting ( 31 % versus 19 % ) and neutropenia ( 10 % versus 4 % ) were more often associated with doxorubicin than PLD . Palmar-plantar erythrodysesthesia ( 48 % versus 2 % ) , stomatitis ( 22 % versus 15 % ) and mucositis ( 23 % versus 13 % ) were more often associated with PLD than doxorubicin . CONCLUSIONS In first-line therapy for MBC , PLD provides comparable efficacy to doxorubicin , with significantly reduced cardiotoxicity , myelosuppression , vomiting and alopecia .

conventional doxorubicin

doxorubicin

PLD

doxorubicin 60 mg/m2

anthracycline

PLD

doxorubicin

doxorubicin

PLD

PLD

doxorubicin

doxorubicin

PLD

PLD

doxorubicin

PLD

doxorubicin

progression-free survival ( PFS )

Cardiac event rates

PFS

Overall risk of cardiotoxicity

Overall survival

Alopecia

nausea

vomiting

neutropenia

Palmar-plantar erythrodysesthesia

stomatitis

mucositis

cardiotoxicity

myelosuppression

vomiting

alopecia

metastatic breast cancer

Women

MBC and normal cardiac function


A randomised controlled trial comparing Drawtex with standard dressings for exuding wounds . OBJECTIVE This randomised controlled clinical trial compared a capillary dressing ( Drawtex , now rebranded as Vibriant RCD [ Vibriant Technology Services ] ) with routine practice for exuding wounds greater than 2.5 x 2.5 cm . METHOD The target population was 300 control and 300 test subjects across three sites in the UK , but recruitment difficulties resulted in only 125 patients being evaluable . Wound progress was recorded by nurses ' perception of the progress of wound healing and by objective digital imaging . In the final analysis digital images were randomised ( in time order ) and a panel of nurses who were not otherwise involved in the research project graded the wound 's progress . RESULTS After deconvolution of the data , the subjective ( nurse perception ) method of evaluation determined that the new dressing resulted in wound improvement in 12.7 % more patients than did routine practice , but the blinded assessment method ( based on the digital images ) showed that routine practice was better by 6.6 % . CONCLUSION Evaluation of wound progress is clearly difficult . Human nature makes us favour novelty if we believe it is going to be better . Making interpretation more objective removed that bias and did not demonstrate a significant advantage for the test dressing . The findings suggest that unblinded assessment by trial nurses is unacceptable on its own . Blinded assessments may miss finer nuances of wound progression , but are likely to be more accurate . The authors suggest that the true result lies somewhere in the middle , with the trial dressing likely to be as effective as , but not more effective than , a standard dressing .

Drawtex with standard dressings

capillary dressing

Drawtex , now rebranded as Vibriant RCD

Vibriant Technology Services

Wound progress

wound improvement

wound progress

wound progression


Retrograde tracing and electrophysiological findings of collateral sprouting after end-to-side neurorrhaphy . The aim of this study was to seek more potent evidences of collateral sprouting for both motor and sensory nerve fibres after end-to-side neurorrhaphy using a modified double-labelling retrograde tracing method and to investigate the function of regenerated motor axons with electrophysiological evaluation . Four groups ( n=4 for each group ) were used : end-to-end coaptation ( six months postoperatively ) , end-to-side coaptation ( four months and six months postoperatively ) and normal control . Two fluorescent tracers ( true blue and diamidino yellow ) were applied to the proximal ends of tibial and common peroneal nerves , respectively after four or six months of nerve coaptation . Five days later , we only found single-labelled motor and sensory neurons in the normal and end-to-end coaptation groups , while some dual-labelled neurons can be identified in end-to-side coaptation groups . Four months after surgery , the motor nerve conduction velocity in end-to-side coaptation was significantly slower than in the normal control . But no difference was found in the sixth month . These results suggest that end-to-side neurorrhaphy can induce the functional collateral sprouting of both motor and sensory axons in the peripheral nerve .

end-to-side coaptation

normal control .

fluorescent tracers

end-to-side neurorrhaphy

after end-to-side neurorrhaphy .

after end-to-side neurorrhaphy


Does aerobic training lead to a more active lifestyle and improved quality of life in patients with chronic heart failure ? BACKGROUND Due to dyspnea and fatigue , patients with chronic heart failure ( CHF ) are often restricted in the performance of everyday activities , which gradually may lead to hypoactivity . AIMS To assess whether aerobic training leads to a more active lifestyle and improved quality of life ( QoL ) in patients with CHF . METHODS Patients with stable CHF ( NYHA II/III ; 59 ( 11 ) years ) were randomly assigned to a training group ( n=18 ; 3-month aerobic program above standard treatment ) or control group ( n=16 ; standard treatment without special advice for exercise ) . Measurements were performed on level of everyday physical activity ( PA , novel accelerometry-based activity monitor ) and QoL , and on several related parameters . RESULTS Training did not result in a more active lifestyle or improved QoL , but improved ( P < 0.05 ) peak power ( 17 % ) , 6-min walk distance ( 10 % ) , muscle strength ( 13-15 % ) and depression ( -1.3 unit ) . Changes in level of everyday PA were related to changes in peak Vo ( 2 ) ( r=0.58 , P=0.01 ) and knee extension strength ( r=0.48 , P=0.05 ) . CONCLUSIONS At group level training did not result in a more active lifestyle or improved QoL . However , correlations between training-related changes in parameters suggest that aerobic training has the potential to increase levels of everyday PA in CHF .

aerobic training

aerobic training

training

control

active lifestyle

improved quality of life

active lifestyle

quality of life ( QoL )

active lifestyle

QoL

peak power

6-min walk distance

muscle strength

depression

peak Vo ( 2 )

knee extension strength

active lifestyle

QoL


The influence of pre- and intraoperative positioning of the condyle in the centre of the articular fossa on the position of the disc in orthognathic surgery . A magnetic resonance study . OBJECTIVE We investigated the changes in the temporomandibular joint ( TMJ ) after bilateral sagittal split osteotomy of the mandible for orthognathic surgery and the influence of positioning of the condylar process in the centre of the articular fossa before and during the operation for preventing changes in the TMJ postoperatively . STUDY DESIGN A total of 28 patients with mandibular retrognathism had bilateral sagittal split osteotomies for mandibular advancement . In one group of 14 patients ( 28 TMJ ) , the condyles were placed in the centre of the articular fossa before and during the operation , and in the other group they were not . Differences on magnetic resonance imaging ( MRI ) were calculated and the results were evaluated . RESULTS The main differences were found at maximal mouth opening . 15/28 TMJs ( 54 % ) that had not been positioned changed the position of the disc from physiological to anterior disc derangement with and without reduction postoperatively . In the 28 that had been positioned , changes were found in only 3 TMJs ( 11 % ) postoperatively . CONCLUSIONS Fixing the condylar process in the centre of the articular fossa intraoperatively before bilateral sagittal split osteotomy is a factor in preventing postoperative structural changes in the temporomandibular joint .

orthognathic surgery .

positioning of the condylar process

magnetic resonance imaging ( MRI )

maximal mouth opening

TMJs

orthognathic

temporomandibular joint ( TMJ )

bilateral sagittal split osteotomy

orthognathic

mandibular retrognathism

bilateral sagittal split osteotomies

TMJ

TMJs

TMJs


Strength of vital force in classical homeopathy : bio-psycho-social-spiritual correlates within a complex systems context . OBJECTIVE To explore associations between a global rating for the classical homeopathic construct of vital force and clinician and patient ratings on previously validated bio-psycho-social-spiritual questionnaires . METHODS Sixty-two ( 62 ) community-recruited patients with fibromyalgia ( FM ) were assessed at baseline prior to a clinical trial of individualized homeopathy . Two homeopaths jointly performed case-taking interviews . A conventional medical provider independently evaluated patients with a standardized history and physical examination . Homeopaths rated each patient 's vital force ( five-point Likert scale , with 1 = very weak to 5 = very strong ) . Homeopaths and the conventional medical provider rated their Clinical Global Impression ( CGI ) of the severity of illness ( 1 = normal ; 7 = among the most extremely ill ) . Patients completed self-rating scales on pain , global health , mood , quality of life , coping style , health locus of control , multidimensional well-being , spirituality , sense of coherence , positive states of mind , and social desirability . RESULTS Greater vital force ratings ( mean 2.9 standard deviation [ SD ] 0.6 ) correlated moderately ( p < or = 0.005 ) with less severe CGI illness ratings by the homeopaths ( r =-0.59 ) , decreased patient-rated mental confusion ( r =-0.43 ) , higher vigor ( r = 0.38 ) , and greater positive states of mind ( r = 0.36 ) . Vital force also showed correlations ( p < 0.05 ) with lower CGI ratings by the conventional medical provider ( r =-0.32 ) , better selfrated quality of life ( r = 0.33 ) , lesser fatigue ( r =-0.31 ) , better global health ( r = 0.29 ) , greater sense of coherence ( r = 0.28 ) , powerful-others health locus of control ( r = 0.27 ) , increased emotional well-being ( r = 0.27 ) , and higher social desirability ( r = 0.27 ) , but not with age , pain , or illness duration . CONCLUSION Homeopathic vital force ratings reflect better perceived mental function , energy , and positive dimensions of the individual , beyond absence of disease .

case-taking interviews

self-rating scales

self-rating scales on pain

global health

mood

quality of life

coping style

health locus of control

multidimensional well-being

spirituality

sense of coherence

positive states of mind

social desirability

vital force ratings

CGI illness

patient-rated mental confusion

vigor

positive states of mind

CGI ratings

quality of life

fatigue

better global health

greater sense of coherence

powerful-others health locus of control

increased emotional well-being

higher social desirability


Correlates of cognitive deficits in first episode schizophrenia . OBJECTIVE The presence of cognitive dysfunction in schizophrenia has been well documented , but questions remain about whether there are relationships between this dysfunction and clinical symptomatology . If present , such relationships should be most clearly observable in patients with first episode schizophrenia ; that is , before the effects of chronic illness , institutionalization , or treatment might confound them . METHOD 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone . The psychopathology , cognitive functioning , early treatment history , and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized , double-blind treatment . Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment ; however , the duration of treatment was limited to 12 weeks or less . RESULTS The severity of negative symptoms at the time of assessment was associated with deficits in memory , verbal fluency , psychomotor speed and executive function . Positive symptoms were not associated with cognitive deficits . Also , the duration of untreated illness ( DUI ) prior to assessment was not significantly associated with cognitive impairment . CONCLUSIONS The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction . However , that relationship accounts for only a minor portion of the variance ( i.e. , 10-15 % ) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors . This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping .

haloperidol and risperidone

antipsychotic treatment

cognitive deficits

cognitive dysfunction

dysfunction

clinical symptomatology .

severity of negative symptoms

deficits in memory

verbal fluency

psychomotor speed

executive function

Positive symptoms

cognitive deficits

duration of untreated illness ( DUI )

cognitive impairment

negative symptoms

cognitive dysfunction

severity of cognitive dysfunction

symptomatology

cognitive dysfunction

first episode schizophrenia

schizophrenia

first episode schizophrenia

chronic illness

schizophrenia

first episode of illness

two-thirds

first episode schizophrenia

schizophrenia


A randomized , double-blinded , placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury . STUDY OBJECTIVE We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury . METHODS Children younger than 16 years and experiencing moderate to severe blunt head injury were randomized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers . The primary endpoint was posttraumatic seizures within 48 hours ; secondary endpoints were survival and neurologic outcome 30 days after injury . A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group . RESULTS One hundred two patients were enrolled , with a median age of 6.1 years . Sixty-eight percent were boys . The 2 treatment groups were well matched . During the 48-hour observation period , 3 ( 7 % ) of 46 patients given phenytoin and 3 ( 5 % ) of 56 patients given placebo experienced a posttraumatic seizure . There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days . According to these results , the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5 % is 0.0053 . The probability that phenytoin has any prophylactic efficacy is 0.383 . The median effect size in this trial was -0.015 ( seizure rate increased by 1.5 % in the phenytoin group ) , 95 % probability interval -0.127 to 0.091 ( 12.7 % higher rate of posttraumatic seizures to a 9.1 % lower rate of posttraumatic seizures with phenytoin ) . CONCLUSION The rate of early posttraumatic seizures in children may be much lower than previously reported . Phenytoin did not substantially reduce that rate .

phenytoin

phenytoin

phenytoin

placebo

phenytoin

placebo

phenytoin

phenytoin

phenytoin

phenytoin

Phenytoin

posttraumatic seizures

posttraumatic seizure

survival

neurologic outcome

rate of early posttraumatic seizures

prophylactic efficacy

posttraumatic seizures

group .


LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women . BACKGROUND Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol , and the effects of docosahexaenoic acid ( DHA ) are uncertain . OBJECTIVE The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women . DESIGN Men and women aged 40-65 y ( n = 38 ) underwent a double-blind , randomized , placebo-controlled , crossover trial of treatment with 0.7 g DHA/d for 3 mo . RESULTS DHA supplementation increased the DHA concentration in plasma by 76 % ( P < 0.0001 ) and the proportion in erythrocyte lipids by 58 % ( P < 0.0001 ) . Values for serum total cholesterol , LDL cholesterol , and plasma apolipoprotein B concentrations were 4.2 % ( 0.22 mmol/L ; P = 0.04 ) , 7.1 % ( 0.23 mmol/L ; P = 0.004 ) , and 3.4 % ( P = 0.03 ) higher , respectively , with DHA treatment than with placebo . In addition , the LDL cholesterol : apolipoprotein B ratio was 3.1 % higher with DHA treatment than with placebo ( P = 0.04 ) , which suggested an increase in LDL size . Plasma lathosterol and plant sterol concentrations were unaffected by treatment . CONCLUSION A daily intake of approximately 0.7 g DHA increases LDL cholesterol by 7 % in middle-aged men and women . It is suggested that DHA down-regulates the expression of the LDL receptor .

docosahexaenoic acid

docosahexaenoic acid ( DHA )

DHA

placebo-controlled

DHA/d

DHA

placebo

placebo

DHA

DHA

effect on blood lipids

DHA concentration in plasma

proportion in erythrocyte lipids

increase in LDL size

increases LDL cholesterol

men

women

40-65 y


Metoprolol CR/XL improves systolic and diastolic left ventricular function in patients with chronic heart failure . AIMS To investigate whether metoprolol controlled release/extended release ( CR/XL ) once daily would improve diastolic and systolic left ventricular function in patients with chronic heart failure and decreased ejection fraction . METHODS In an echocardiographic substudy to the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure ( MERIT-HF ) , 66 patients were examined three times during a 12-month period blinded to treatment group , assessing left ventricular dimensions and ejection fraction , and Doppler mitral inflow parameters , all measured in a core laboratory . RESULTS In the metoprolol CR/XL group left ventricular ejection fraction increased from 0.26 to 0.31 ( P = 0.009 ) after a mean observation period of 10.6 months , and deceleration time of the early mitral filling wave ( E ) increased from 189 to 246 ms ( P = 0.0012 ) , time velocity integral of E-wave increased from 8.7 to 11.2 cm ( P = 0.018 ) , and the duration of the late mitral filling wave ( A ) increased from 122 to 145 ms ( P = 0.014 ) . No significant changes were seen in the placebo group regarding any of these variables . CONCLUSION Metoprolol CR/XL once daily in addition to standard therapy improved both diastolic and systolic function in patients with chronic heart failure and decreased ejection fraction .

Metoprolol CR/XL

Metoprolol CR/XL

metoprolol CR/XL

placebo

Metoprolol CR/XL

left ventricular ejection fraction

time of the early mitral filling wave

time velocity integral of E-wave

diastolic and systolic function

chronic heart failure


Reflexive orienting in response to eye gaze and an arrow in children with and without autism . BACKGROUND This study investigated whether another person 's social attention , specifically the direction of their eye gaze , and a non-social directional cue , an arrow , triggered reflexive orienting in children with and without autism in an experimental situation . METHODS Children with autism and typically developed children participated in one of two experiments . Both experiments involved the localization of a target that appeared to the left or right of the fixation point . Before the target appeared , the participant 's attention was cued to the left or right by either an arrow or the direction of eye gaze on a computerized face . RESULTS Children with autism were slower to respond , which suggests a slight difference in the general cognitive ability of the groups . In Experiment 1 , although the participants were instructed to disregard the cue and the target was correctly cued in only 50 % of the trials , both groups of children responded significantly faster to cued targets than to uncued targets , regardless of the cue . In Experiment 2 , children were instructed to attend to the direction opposite that of the cues and the target was correctly cued in only 20 % of the trials . Typically developed children located targets cued by eye gaze more quickly , while the arrow cue did not trigger such reflexive orienting in these children . However , both social and non-social cues shifted attention to the cued location in children with autism . CONCLUSION These results indicate that eye gaze attracted attention more effectively than the arrow in typically developed children , while children with autism shifted their attention equally in response to eye gaze and arrow direction , failing to show preferential sensitivity to the social cue . Difficulty in shifting controlled attention to the instructed side was also found in children with autism .

arrow

localization of a target

arrow

attention

reflexive orienting

slower to respond

cognitive ability

responded

located targets cued by eye gaze

reflexive orienting

attention

attention

sensitivity

attention

children

with and without autism


Perispinal analgesia for labour followed by patient-controlled infusion with bupivacaine and sufentanil : combined spinal-epidural vs. epidural analgesia alone . BACKGROUND AND OBJECTIVE Combined spinal-epidural is an alternative technique to epidural analgesia for labour , but its benefits are not clearly identified . METHODS A prospective , blinded , randomized study was undertaken involving 113 women attending a university hospital obstetric department . Analgesia was initiated with intrathecal bupivacaine 0.25 % 1 mL + sufentanil 5 microg in the combined spinal-epidural group ( n = 54 ) , and with bupivacaine 0.125 % + epinephrine 2.5 microg mL ( -1 ) + sufentanil 7.5 microg in the epidural group ( n = 59 ) . In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125 % ( + sufentanil 0.25 microg mL ( -1 ) ) . Duration of labour , quality of analgesia and side-effects were compared between groups . RESULTS In the combined spinal-epidural group , the onset of analgesia was faster ( 5 vs. 15 min , P < 0.001 ) , the consumption of bupivacaine was lower ( 7.5 vs. 11.3 mg h ( -1 ) , P = 0.003 ) and there was less unilateral analgesia ( 14.8 % vs. 40.7 % , P = 0.002 ) than in the epidural group . The characteristics of labour were similar in both groups . However , in the combined spinal-epidural group , there was a higher incidence of posterior presentation ( 25.9 % vs. 10 % , P = 0.03 ) , pruritus ( P < 0.001 ) , hypotension ( P = 0.002 ) , somnolence ( P = 0.01 ) , nausea ( P = 0.02 ) and one case of meningitis . CONCLUSIONS The combined spinal-epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage . It induced more adverse effects and this should be considered before routinely using the combined spinal-epidural technique .

bupivacaine

sufentanil

spinal-epidural vs. epidural

bupivacaine 0.25 % 1 mL

sufentanil 5 microg

bupivacaine 0.125 %

epinephrine 2.5 microg mL ( -1 )

sufentanil 7.5 microg

sufentanil 0.25 microg mL ( -1 ) )

bupivacaine

quality of analgesia

side-effects

unilateral analgesia

characteristics of labour

incidence of posterior presentation

pruritus

hypotension

somnolence

nausea

meningitis

women

during labour


Cyproheptadine in the treatment of autistic disorder : a double-blind placebo-controlled trial . OBJECTIVE Autism is a childhood-onset disorder of unknown , possibly of multiple aetiologies . The core symptoms of autism are abnormalities in social interaction , communication and behaviour . The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder . Increased platelet 5-HT levels were found in 40 % of the autistic population , suggesting that hyperserotonaemia may be a pathologic factor in infantile autism . Therefore , it is of interest to assess the efficacy of cyproheptadine , a 5-HT2 antagonist in the treatment of autistic disorder . In this 8-week double-blind , placebo-controlled trial , we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder . METHODS Children between the ages 3 and 11 years ( inclusive ) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited . The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder . Patients were randomly allocated to cyproheptadine + haloperidol ( Group A ) or haloperidol + placebo ( Group B ) for an 8-week , double-blind , placebo-controlled study . The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively . Patients were assessed by a third-year resident of psychiatry at baseline and after 2 , 4 , 6 and 8 weeks of starting medication . The primary measure of the outcome was the Aberrant Behaviour Checklist-Community ( ABC-C ) and the secondary measure of the outcome was the Childhood Autism Rating Scale ( relating to people and verbal communication ) . Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale , administered by a resident of psychiatry during weeks 1 , 2 , 4 , 6 and 8 . RESULTS The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine . The behaviour of the two treatments was not homogeneous across time ( groups-by-time interaction , Greenhouse-Geisser correction ; F = 7.30 , d.f . = 1.68 , P = 0.002 ; F = 8.21 , d.f . = 1.19 , P = 0.004 respectively ) . The difference between the two treatments was significant as indicated by the effect of group , and the between-subjects factor ( F = 4.17 , d.f . = 1 , P = 0.048 ; F = 4.29 , d.f . = 1 , P = 0.045 respectively ) . No significant difference was observed between the two groups in terms of extrapyramidal symptoms ( P = 0.23 ) . The difference between the two groups in the frequency of side effects was not significant . CONCLUSION The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder . However the results need confirmation by a larger randomized controlled trial .

Cyproheptadine

placebo-controlled

cyproheptadine

5-HT2 antagonist

placebo-controlled

cyproheptadine plus haloperidol

cyproheptadine + haloperidol

haloperidol

+ placebo

haloperidol and cyproheptadine

cyproheptadine

cyproheptadine

conventional antipsychotic

conventional antipsychotic alone

extrapyramidal symptoms

frequency of side effects

autistic disorder :

infantile autism

DSM IV clinical diagnosis of autism

outpatients

children

autistic disorder

children

autistic disorder


Efficacy of prophylactic ondansetron in a patient-controlled analgesia environment . We conducted a prospective , randomized , double-blind , placebo-controlled trial to examine the efficacy of prophylactic ondansetron on post-operative nausea and vomiting ( PONV ) during opioid patient-controlled analgesia ( PCA ) . In total , 374 patients using opioid PCA , but otherwise considered to be low risk for PONV , were randomly allocated to ondansetron ( 4 mg given intravenously and 16 mg added into the PCA pump ) or saline ( control group ) . PONV was evaluated in terms of nausea graded on a visual analogue scale , and the number of patients who experienced emetic episodes or needed rescue anti-emetics in the 48-h post-operative period . Patient satisfaction for PCA was scored at the end of the evaluation period . The only difference between the two groups was the higher number of headaches in the ondansetron group . In patients using opioid PCA , but with no other high risk factors for PONV , prophylactic ondansetron does not have any clinical benefit .

placebo-controlled

prophylactic ondansetron

ondansetron

saline

PONV

Patient satisfaction

higher number of headaches

PONV

PONV


Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer . PURPOSE To determine whether addition of the farnesyltransferase inhibitor tipifarnib ( Zarnestra , R115777 ; Johnson and Johnson Pharmaceutical Research and Development , Beerse , Belgium ) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer . PATIENTS AND METHODS This randomized , double-blind , placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy . Tipifarnib was given at 200 mg bid orally continuously ; gemcitabine was given at 1,000 mg/m ( 2 ) intravenously weekly x 7 for 8 weeks , then weekly x 3 every 4 weeks . The primary end point was overall survival ; secondary end points included 6-month and 1-year survival rates , progression-free survival , response rate , safety , and quality of life . RESULTS Six hundred eighty-eight patients were enrolled . Baseline characteristics were well balanced between the two treatment arms . No statistically significant differences in survival parameters were observed . The median overall survival for the experimental arm was 193 v 182 days for the control arm ( P =.75 ) ; 6-month and 1-year survival rates were 53 % and 27 % v 49 % and 24 % for the control arm , respectively ; median progression-free survival was 112 v 109 days for the control arm . Ten drug-related deaths were reported for the experimental arm and seven for the control arm . Neutropenia and thrombocytopenia grade > or = 3 were observed in 40 % and 15 % in the experimental arm versus 30 % and 12 % in the control arm . Incidences of nonhematologic adverse events were similar in two groups . CONCLUSION The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine .

gemcitabine

tipifarnib

gemcitabine

placebo

tipifarnib

gemcitabine + tipifarnib

gemcitabine and tipifarnib

overall survival

overall survival

6-month and 1-year survival rates

progression-free survival

response rate

safety

quality of life

survival parameters

median overall survival

6-month and 1-year survival rates

median progression-free survival

drug-related deaths

nonhematologic adverse events

advanced pancreatic adenocarcinoma

Six hundred eighty-eight


Bisphosphonate infusions : patient preference , safety and clinic use . GOALS OF WORK We set out to assess the preference of patients with common cancers involving bone receiving intravenous bisphosphonate therapy for either pamidronate ( P ) or zoledronic acid ( Z ) and their preference for the location of the infusion ( clinic or home ) . We also aimed to monitor these patients ' renal safety , and to compare their time in clinic to receive P and Z infusions . PATIENTS AND METHODS Enrolled in the study were 184 patients , and all received initial infusions of Z ( so any first infusion reactions did not confound preferences for P ) . For their second and third infusions , patients were randomized to receive Z then P or P then Z , and questioned on their preferences . For up to 1 year they continued on Z infusions every 3-4 weeks , while their renal safety was monitored . Where practical , later infusions were given at home ( rather than in the clinic ) and patients questioned on their preferred infusion location . In a convenience subset of 43 patients , clinic use for Z and P infusions was also measured by timing infusions and other procedures . MAIN RESULTS Of 144 patients who received a third infusion , 138 responded to questions on bisphosphonate preference , and of these 138 , 92 % ( 127 ) preferred Z to P , because shorter infusions caused less disruption to their day . Only 12 % of eligible patients ( 16/138 ) received home infusions , but 13/14 questioned preferred this location . Among 184 patients , 19 episodes of renal impairment were noted , mostly owing to disease progression ( e.g . obstructive uropathy ) , with none linked to Z therapy . The mean clinic time taken to receive Z and any concomitant therapy was about half that for P ( 78 vs 161 min ) . CONCLUSIONS Cancer patients prefer shorter bisphosphonate infusions-and at home , where practical . Regular Z 4 mg infusions appear to be safe in these patients , with routine monitoring of serum creatinine . Using Z rather than P could save busy cancer centres time and improve patient satisfaction .

Bisphosphonate infusions

bisphosphonate

pamidronate ( P )

zoledronic acid ( Z )

P and Z infusions

infusions of Z

Z then P

P then Z

Z infusions

Z and P infusions

Z

P

Z

bisphosphonate

Z

Z rather than P

patient preference

safety

clinic use

renal safety

disruption to their day

renal impairment

disease progression

bisphosphonate infusions-and

safe

patient satisfaction

cancers

12 %

Cancer


Should insertion of intramedullary nails for tibial fractures be with or without reaming ? A prospective , randomized study with 3.8 years ' follow-up . OBJECTIVE To determine if any differences exist in healing and complications between reamed and unreamed nailing in patients with tibial shaft fractures . DESIGN Prospective , randomized . SETTING Level 1 trauma center . PATIENTS Forty-five patients with displaced closed and open Gustilo type I-IIIA fractures of the central two thirds of the tibia . INTERVENTION Stabilization of tibial fractures either with a slotted , stainless steel reamed nail or a solid , titanium unreamed nail . MAIN OUTCOME MEASUREMENTS Nonunions , time to fracture healing , and rate of malunions . RESULTS The average time to fracture healing was 16.7 weeks in the reamed group and 25.7 weeks in the unreamed group . The difference was statistically significant ( P = 0.004 ) . There were three nonunions , all in the unreamed nail group . Two of these fractures healed after dynamization by removing static interlocking screws . The third nonunion did not heal despite exchange reamed nailing 2 years after the primary surgery and dynamization with a fibular osteotomy after an additional 1 year . There were two malunions in the reamed group and four malunions in the unreamed group . There were no differences for all other outcome measurements . CONCLUSION Unreamed nailing in patients with tibial shaft fractures may be associated with higher rates of secondary operations and malunions compared with reamed nailing . The time to fracture healing was significantly longer with unreamed nails .

reamed and unreamed nailing

reamed

unreamed

unreamed nail

reamed

reamed nailing .

Nonunions

average time to fracture healing

nonunions

heal

malunions

malunions

time to fracture healing

tibial


Calcium chloride before i.v . diltiazem in the management of atrial fibrillation . Diltiazem is commonly used to treat atrial fibrillation or flutter ( AFF ) with rapid ventricular response ( RVR ) . Although it is very effective for rate control , up to an 18 % prevalence of reported diltiazem-induced hypotension [ defined by systolic blood pressure ( SBP ) < 90 mm Hg ] , and a mean of 9.7 % hypotension have been reported from several studies totaling over 450 patients . This hypotension may complicate therapy . Our objective was to determine if calcium chloride ( CaCl ( 2 ) ) pre-treatment would blunt a SBP drop after i.v . diltiazem , while allowing diltiazem to maintain its efficacy . A prospective , randomized , double-blind , placebo-controlled study was conducted . Seventy-eight patients with AFF and a ventricular rate of > /= 120 beats per minute were enrolled . Half received i.v . CaCl ( 2 ) pre-treatment ; the other half received placebo . All patients then received i.v . diltiazem in a standard , weight-based dose . A second dose of CaCl ( 2 ) pre-treatment or placebo and diltiazem was given if clinically indicated for additional rate control . Both CaCl ( 2 ) and placebo pre-treatment groups had equal lowering of heart rate ( p < 0.001 ) . There were no adverse events in the calcium pre-treatment study arm . One patient in the placebo group became paradoxically more tachycardic and apneic after the diltiazem infusion . Although i.v . CaCl ( 2 ) seems to be equally safe compared to placebo as a pre-treatment in the management of AFF with RVR , we were unable to find a statistically significant blunting of SBP drop with CaCl ( 2 ) i.v . pre-treatment . Until further research determines a benefit exists , we can not recommend i.v . CaCl ( 2 ) pre-treatment before diltiazem in the treatment of AFF with RVR .

Calcium chloride before i.v

diltiazem

Diltiazem

diltiazem-induced

calcium chloride ( CaCl ( 2 ) )

diltiazem

CaCl ( 2 )

placebo

diltiazem

placebo

diltiazem

placebo

CaCl ( 2 )

diltiazem

management of atrial fibrillation .

rate control

hypotension

hypotension

SBP drop

heart rate

adverse events

tachycardic and apneic

atrial fibrillation

flutter ( AFF )

Seventy-eight

AFF

One


Improved intraoperative management of anastomotic bleeding during aortic reconstruction : results of a randomized controlled trial . In a randomized controlled trial , the effectiveness of a polymeric surgical sealant ( CoSeal ) was compared to Gelfoam/thrombin for managing anastomotic bleeding after implantation of Dacron grafts during aortic reconstruction for nonruptured aneurysms . Each treatment was directly applied to the suture line after confirmation of anastomotic bleeding . The proportion of suture line sites that achieved immediate sealing and the proportion sealed within 5 minutes were determined among 37 experimental ( 59 sites ) and 17 control subjects ( 27 sites ) . A significantly greater proportion of bleeding suture line sites treated with the polymeric sealant achieved immediate sealing following reestablishment of blood flow compared with control-treated sites [ 48 of 59 ( 81 % ) vs 10 of 27 ( 37 % ) ; P = 0.002 ] . The difference between treatment groups was maintained after 5 minutes with approximately 85 per cent ( 50 of 59 ) of CoSeal sites compared to just over one-half ( 14 of 27 ) of control sites demonstrating ultimate sealing ( P = 0.01 ) . There were no adverse events related to the use of the polymeric sealant in this study . These results support the use of this novel sealant for the intraoperative management of anastomotic bleeding during aortic reconstruction procedures .

polymeric surgical sealant ( CoSeal )

implantation

polymeric sealant

CoSeal

polymeric sealant

Improved intraoperative management

effectiveness

anastomotic bleeding

immediate sealing

immediate sealing

ultimate sealing

anastomotic bleeding

anastomotic bleeding

nonruptured aneurysms

anastomotic bleeding


The reversibility of increased airways resistance in chronic heart failure measured by impulse oscillometry . BACKGROUND Patients with chronic heart failure complain of breathlessness and fatigue on exercise . Airways resistance is increased and lung compliance is reduced in chronic heart failure patients . The aim of this study was to determine whether the pulmonary abnormalities are reversible and whether any improvements lead to changes to exercise capacity or symptoms . METHODS Twelve patients with stable chronic heart failure and 10 matched controls underwent repeated assessment of airways resistance using impulse oscillometry and peak exercise testing with metabolic gas exchange after receiving nebulized saline as placebo or combined salbutamol and ipratropium bromide in a double-blind crossover randomized fashion . RESULTS Patients had lower peak oxygen consumption and a steeper slope relating ventilation to carbon dioxide production than controls . Bronchodilators reduced peripheral airways resistance in patients ( 0.53 versus 0.38 , P < .02 ) and controls ( 0.21 versus 0.19 , P < .005 ) and increased measures of compliance in both groups . There was no effect on the peak oxygen consumption , exercise time , ventilation to carbon dioxide slope , or anaerobic threshold . There was an increase in peak tidal volume ( VT ) in both groups but this did not lead to an increase in peak ventilation . The slope relating symptoms to ventilation ( ie , Borg/VE ) was significantly reduced in the patients after bronchodilators ( 17 % +/-8 % , P < .05 ) . The relationship between the improvement in VT and reduction in gradient of the Borg/VE slope was significant ( r=.40 , P < .05 ) . CONCLUSIONS Nebulized bronchodilators improve airways resistance , lung reactance , and peak tidal volume during exercise in chronic heart failure but do not increase peak exercise capacity . They do , however , reduce the symptom of breathlessness .

nebulized saline as placebo

combined salbutamol

ipratropium bromide

peak oxygen consumption

peak oxygen consumption , exercise time

ventilation to carbon dioxide slope

anaerobic threshold

peak tidal volume ( VT )

peak ventilation

ventilation

Borg/VE slope

airways resistance , lung reactance

peak tidal volume

symptom of breathlessness

chronic heart failure

Twelve patients

stable chronic heart failure

10 matched controls


Bitewing film quality : a clinical comparison of the loop vs. holder techniques . OBJECTIVE To compare in vivo bitewing film quality using the holder versus the paper loop technique . METHOD AND MATERIALS Four bitewing films were taken from the right and left premolar and molar regions of 45 dental students using both the bitewing holder and paper loop techniques . A total of 360 films were taken and assessed by an experienced practitioner not apprised of the bitewing technique used . Of interest were : ( 1 ) the number of overlaps and the percentage of teeth showing the alveolar crest ; ( 2 ) proper film positioning ; and ( 3 ) the percentage of cone cutting . A Poisson regression using generalized estimating equations ( GEEs ) was used to estimate the difference in overlap between the two techniques . For proper positioning and cone cutting , logistic regressions using GEEs were used . RESULTS The average number of horizontal overlaps for the loop and holder techniques at the right premolar , right molar , left premolar , and left molar were 1.64 , 2.11 , 2.16 , 2.78 , and 1.64 , 2.00 , 2.00 , 2.18 , respectively . The loop technique was 1.11 times more likely to cause overlapping than the holder technique . The highest percentage of teeth showing the alveolar crest by the loop technique was 97.8 % in the mandibular second premolar and first molar . With respect to film positioning , the loop technique was 1.12 times more likely to cause improper positioning than the holder technique . Both techniques demonstrated minimal cone cutting ( 1 in the loop versus 0 in the holder ) . CONCLUSION The quality of bitewing films taken by the loop and holder techniques was not significantly different .

loop

holder techniques

holder

the paper loop technique

bitewing holder

paper loop techniques

bitewing technique

loop

holder techniques

loop technique

holder technique

loop technique

loop technique

holder technique

loop

holder techniques

overlapping

improper positioning

minimal cone cutting


Primary stenting of occluded native coronary arteries : final results of the Primary Stenting of Occluded Native Coronary Arteries ( PRISON ) study . BACKGROUND Primary intracoronary stent placement after successfully crossing chronic total coronary occlusions may decrease the high restenosis rate at long-term follow-up compared with conventional balloon angioplasty . METHODS In a prospective , randomized trial , balloon angioplasty was compared with stent implantation for the treatment of chronic total occlusions . Patients were followed for 12 months with angiographic follow-up at 6 months . Quantitative coronary analysis was performed by an independent core lab . RESULTS A total of 200 patients were enrolled . Baseline characteristics were evenly distributed . After the procedure the mean minimal luminal diameter in the conventional group was 2.34 +/- 0.46 mm versus 2.90 +/- 0.41 mm in the stented group ( P < .0001 ) . The 6-month angiographic follow-up showed a mean minimal luminal diameter of 1.57 +/- 0.74 mm in the conventional group versus 1.93 +/- 0.85 mm in the stented group ( P =.009 ) and a mean diameter stenosis of 44.7 % +/- 25.0 % versus 35.5 % +/- 26.5 % ( P =.036 ) . Binary angiographic restenosis ( > 50 % diameter stenosis ) was seen in 33 % in the conventional group versus 22 % in the stented group ( P =.137 ) . The reocclusion rates were 7.3 % and 8.2 % , respectively ( P = 1.00 ) . At 12 month follow-up , the rate of target lesion revascularization was significantly higher in the conventional group ( 29 % versus 13 % , P < .0001 ) . CONCLUSION These data demonstrate that stenting of chronic total occlusions is superior to balloon angioplasty alone with a statistically significant reduction in the need for target lesion revascularization and a lower , but not significant , restenosis rate .

Primary stenting

Primary intracoronary stent placement

conventional balloon angioplasty .

balloon angioplasty

stent implantation

conventional

stented

stented

conventional

stenting

balloon angioplasty alone

mean minimal luminal diameter

mean minimal luminal diameter

mean diameter stenosis

Binary angiographic restenosis

reocclusion rates

rate of target lesion revascularization

target lesion revascularization

restenosis rate

chronic total occlusions


Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders . Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains : repetitive behaviours , social deficits , and language abnormalities . There is evidence that abnormalities exist in the serotonin ( 5-HT ) system in autism spectrum patients . Furthermore , 5-HT is known to play a role in repetitive and social behaviours . This study examined the effect of m-chlorophenylpiperazine ( m-CPP ) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind , m-CPP and placebo challenges . The primary outcome measure was an instrument rating six repetitive behaviours : need to know , repeating , ordering , need to tell/ask , self-injury , and touching . Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo . Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls , with neither group responding to placebo . This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders , as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system .

m-chlorophenylpiperazine

m-chlorophenylpiperazine ( m-CPP )

placebo

oral m-CPP

placebo

m-CPP

repetitive behaviours

oral m-CPP

prolactin response to m-CPP

adults with autism spectrum disorders .


A comparison of laparoscopically assisted and open colectomy for colon cancer . BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and randomly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups -- 16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P < 0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P < 0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer .

laparoscopically assisted surgery

laparoscopically assisted colectomy

open colectomy

time to tumor recurrence .

rates of recurrence

Recurrence rates in surgical wounds

overall survival rate

hazard ratio for death

time to recurrence

overall survival

Perioperative recovery

median hospital stay

intraoperative complications

30-day postoperative mortality

complications at discharge and 60 days

hospital readmission , and reoperation

rates of recurrent cancer

colon cancer

adenocarcinoma of the colon


Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma . Immediately before first hemi-body irradiation , 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance . 13 patients ( 22 % ) [ 8 of 31 ( 26 % ) controls , 5 of 28 ( 18 % ) in the interferon arm ] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure . Mean time between upper and lower hemi-body irradiation was 69 days ( range 35-294 ) . Of 23 patients randomised to receive interferon and completing double hemi-body irradiation , 15 ( 65 % ) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days ( 61-241 ) from time of study entry . The mean period of interferon therapy , starting at a mean 65 days ( 26-160 ) post second hemi-body irradiation , is 16.4 months ( 2-33.5 ) . There was no significant difference in median survival durations ( 10 months ) from time of initial radiotherapy between control and interferon patients .

hemi-body irradiation

recombinant alpha 2b interferon

alpha-2b interferon maintenance

single hemi-body irradiation alone

interferon therapy

survival

peripheral blood counts

median survival durations


ROMEO : rethink organization to improve education and outcomes . AIMS Scarcity of resources , expertise and evidence-based models have so far limited delivery of patient-centred diabetes education . We have developed and validated a group care approach that is applicable to everyday clinical practice and cost-effective in improving metabolic control , knowledge of diabetes , health behaviours , and quality of life in Type 2 diabetes . A clinical trial ( ROMEO ) was planned to evaluate applicability and reproducibility of group care in other outpatients facilities and assess its impact on a larger patient population . METHODS Multicentre , randomized , controlled clinical trial of group vs. individual care in the routine management of Type 2 diabetes . Nine hundred patient aged < 80 , with diabetes of > or =1 year known duration , treated by either diet alone or diet and oral agents , will be recruited in 15 centres and followed for 4 years . Training of physicians , nurses and dietitians included preparation of operating manual and videos , interactive sessions , and evaluation of local facilities and resources . RESULTS PRIMARY MEASUREMENTS 3-monthly HbA1c , fasting blood glucose , body weight , waist-hip ratio , yearly blood lipids , and bi-yearly assessment of knowledge of diabetes , health behaviours and quality of life . SECONDARY OUTCOMES systolic and diastolic blood pressure , evaluation of ECG for ischaemia and QT interval , hypoglycaemic and anti-hypertensive medication and cardiovascular events . Analysis will be by intention-to-treat . DISCUSSION If ROMEO confirms that group care can be successfully implemented in different clinics , a novel clinico-pedagogic tool will have been acquired to support patient-centred education , improve lifestyle and outcomes , support team work , enhance providers ' attitudes and competencies and ameliorate diabetes care organization .

group

individual care

diet alone

diet and oral agents

metabolic control

knowledge of diabetes

health behaviours

quality of life

3-monthly HbA1c

fasting blood glucose

body weight

waist-hip ratio

yearly blood lipids

health behaviours

quality of life

systolic and diastolic blood pressure

cardiovascular events

improve lifestyle

support team work

enhance providers ' attitudes

larger patient population .

Nine hundred

< 80

diabetes


Role of the placebo effect in evaluating antidepressant efficacy .

placebo effect

antidepressant efficacy .

antidepressant efficacy


A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial ( COMET ) . BACKGROUND & AIMS The COMET trial was a prospective , double-blind , randomised trial comparing carvedilol , a comprehensive adrenergic receptor antagonist , with metoprolol , a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction . The trial showed a reduction in mortality with carvedilol that was consistent across subgroups . The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity , age and gender on patient characteristics . METHODS A descriptive report using data entered in the COMET study data-base . RESULTS The characteristics of the population studied were similar to those reported in previous trials of beta-blockers . Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers . As expected , older patients had more co-morbidity . Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction . NT-proBNP was higher in patients with more severe symptoms and older patients but not in women , although differences in NT-proBNP may have been confounded by differences in renal function . CONCLUSION Age and gender , as well as the severity of cardiac dysfunction , appear to have an important effect on the severity of heart failure symptoms and patient 'well-being ' . This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment . This will be the subject of further analyses .

Carvedilol

Metoprolol

COMET

carvedilol

antagonist

metoprolol

beta-1-selective agent

carvedilol

COMET

diuretics

ACE inhibitors

angiotensin receptor blockers

mortality

co-morbidity .

symptoms

and

poorer well-being

renal function .

heart failure symptoms

patient 'well-being '

heart failure

left ventricular systolic dysfunction


Double blind comparison of Iomeprol 350 and Iopamidol 340 in intravenous digital subtraction angiography for peripheral vascular disease . A randomized double blind study was undertaken to compare the diagnostic efficacy and side effects of a new non-ionic contrast medium Iomeprol with a commonly used one -- Iopamidol . Visual and densitometric comparison was made of intravenous digital subtraction angiograms performed for peripheral vascular disease . The results show the two media to be similar both in imaging quality and in the incidence of associated side effects . Ninety-eight per cent of the intravenous digital subtraction angiograms were assessed as adequate for clinical management by the vascular surgeon .

Iomeprol 350 and Iopamidol 340

non-ionic contrast medium Iomeprol

commonly used one -- Iopamidol

diagnostic efficacy

side effects

imaging quality

incidence of associated side effects

peripheral vascular disease


Mouth closing device ( chinstrap ) reduces mouth leak during nasal CPAP . BACKGROUND AND PURPOSE Mouth leak occasionally complicates continuous positive airway pressure ( CPAP ) therapy , which leads to discomfort . While a chinstrap prevents the mouth from opening during sleep , its efficacy in diminishing mouth leak has not been studied . PATIENTS AND METHODS Fifteen patients with mouth leak complaining of mouth dryness and nasal obstruction underwent two consecutive overnight polysomnographies , one with a chinstrap , in random order . Cephalometry with and without a chinstrap was randomly performed on six patients . RESULTS With the chinstrap , both mouth leak and the arousal index decreased significantly , from ( mean+/-SD ) 42.9+/-23.5 to 23.8+/-13.3 % of total sleep time ( TST ) , and from 33.4+/-18.6 to 23.6+/-9.3/sleep hour , respectively . However , snoring time showed a concomitant increase from 6.7+/-14.3 to 24.0+/-13.2 % of TST . The arousal index was significantly higher during leak periods , and its changes correlated positively with changes in mouth leak . Cephalometric measures showed a significant decrease in anterior lower facial height . CONCLUSIONS The chinstrap , by closing the mouth during CPAP , reduces mouth leak and therefore the arousal index in most patients . Nevertheless , the indices remained unacceptably high . The chinstrap may also increase snoring and , in rare cases , can worsen the respiratory disturbance index . Consideration of these potential effects is important before instituting regular home use of the chinstrap .

chinstrap

mouth leak

Cephalometry

mouth leak

the arousal index

total sleep time

snoring time

arousal index

mouth leak

Cephalometric measures

anterior lower facial height


Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent . BACKGROUND The efficacy of angiotensin-converting enzyme ( ACE ) inhibitors in decreasing blood pressure in African patients is controversial . OBJECTIVE We examined the ambulatory blood pressure ( ABP ) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy . DESIGN A single-blind randomized AB/BA crossover design . SETTING Hypertensive families of East African descent from the general population in the Seychelles . PARTICIPANTS Fifty-two ( 29 men and 23 women ) out of 62 eligible hypertensive patients were included.Main outcome measures ABP response to 20 mg lisinopril ( LIS ) daily and 25 mg hydrochlorothiazide ( HCT ) daily given for a 4-week period . Results The daytime systolic/diastolic ABP response to HCT was 4.9 [ 95 % confidence interval ( CI ) 1.2-8.6 ] /3.6 ( 1.0-6.2 ) mmHg for men and 12.9 ( 9.2-16.6 ) /6.3 ( 3.7-8.8 ) mmHg for women . With LIS the response was 18.8 ( 15.0-22.5 ) /14.6 ( 12.0-17.1 ) mmHg for men and 12.4 ( 8.7-16.2 ) /7.7 ( 5.1-10.2 ) mmHg for women . The night-time systolic/diastolic response to HCT was 5.0 ( 0.6-9.4 ) /2.7 [ ( -0.4 ) -5.7 ] mmHg for men and 11.5 ( 7.1-16.0 ) /5.7 ( 2.6-8.8 ) mmHg for women , and to LIS was 18.7 ( 14.2-22.1 ) /15.4 ( 12.4-18.5 ) mmHg for men and 3.5 [ ( -1.0 ) -7.9 ] /2.3 [ ( -0.8 ) -5.4 ] mmHg for women . Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS . CONCLUSIONS Hypertensive patients of African descent responded better to LIS than to HCT . Men responded better to LIS than to HCT and women responded similarly to both drugs .

angiotensin-converting enzyme inhibitor

diuretic

diuretic

ACE inhibitor

lisinopril ( LIS )

hydrochlorothiazide ( HCT )

HCT

LIS

HCT

LIS

LIS

HCT

HCT

decreasing blood pressure

characteristics

treatment efficacy

ABP response

daytime systolic/diastolic ABP response

night-time systolic/diastolic response

Men responded better

women responded similarly

Fifty-two

men

women


Weight and leptin changes among risperidone-treated youths with autism : 6-month prospective data . OBJECTIVE The authors examined the developmental impact and temporal characteristics of risperidone-associated weight change . METHOD Weight change was measured for 63 children and adolescents with autism treated with risperidone for 6 months . Change in serum leptin levels after 2 months was examined as a predictor of final weight gain in mixed regression models that controlled for site , gender , age , and risperidone dose . RESULTS Age- and gender-standardized weight increased after 6 months of treatment ( gross : mean=5.6 kg [ SD=3.9 ] ; standardized : mean=0.6 z [ SD=0.5 ] ) and was positively correlated with weight gained after 1 month . Change in leptin levels after 2 months of treatment ( mean=-0.3 ng/ml , SD=6.2 ) ( N=48 ) did not predict final weight gain . CONCLUSIONS Chronic risperidone exposure in children with autism causes weight gain in excess of developmentally expected norms that follows a curvilinear trajectory and decelerates over time . Serum leptin change does not reliably predict risperidone-associated weight gain .

risperidone-treated

risperidone-associated

risperidone

risperidone

risperidone

Weight

leptin changes

weight change

Weight change

Change in serum leptin levels

final weight gain

weight increased

weight gained

Change in leptin levels

final weight gain

weight gain

Serum leptin change

weight gain


Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy . OBJECTIVES To compare the effects of the angiotensin receptor blocker ( ARB ) valsartan versus the calcium channel blocker amlodipine , reactive oxygen species ( ROS ) formation by monocytes , C-reactive protein ( CRP ) , and left ventricular ( LV ) mass were studied in 104 hypertensive patients with left ventricular hypertrophy ( LVH ) . BACKGROUND There is evidence that ARBs have blood pressure ( BP ) -independent effects on LV mass . Whether regression of LV mass by ARBs is correlated to ROS formation by monocytes and CRP is not fully understood yet . METHODS A cross-sectional and prospective study was performed . Participants were randomly assigned to either the 80-mg valsartan ( n = 52 ) or 5-mg amlodipine ( n = 52 ) group and were treated for eight months . The left ventricular mass index ( LVMI ) was calculated from two-dimensional M-mode echocardiography . Formation of ROS by monocytes was measured by gated flow cytometry . In addition , CRP , plasma renin activity , plasma aldosterone , and traditional risk factors were assessed . RESULTS Multiple regression analysis showed a significant correlation between LVMI and ROS formation by monocytes and between LVMI and CRP . Treatment reduced BP to a similar extent in both groups . Valsartan significantly reduced LVMI after eight months , but amlodipine had less effect ( 16 % vs. 1.2 % , n = 50 , p < 0.01 ) . Formation of ROS by monocytes was reduced to a greater extent with valsartan than with amlodipine ( 28 % vs. 2 % , n = 50 , p < 0.01 ) . Valsartan but not amlodipine reduced CRP levels . A significant correlation between changes in ROS formation by monocytes and LVMI or between CRP and LVMI was observed . CONCLUSIONS The ARB valsartan has BP-independent effects on LVH , ROS formation by monocytes , and CRP in hypertensive patients with LVH .

valsartan

amlodipine

calcium channel blocker amlodipine

ARBs

ARBs

80-mg valsartan

5-mg amlodipine

Valsartan

amlodipine

valsartan

amlodipine

Valsartan

amlodipine

ARB valsartan

Treatment reduced BP

similar extent

Valsartan significantly reduced LVMI

less effect

Formation of ROS by monocytes

reduced CRP levels

significant correlation


Bevacizumab plus irinotecan , fluorouracil , and leucovorin for metastatic colorectal cancer . BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has shown promising preclinical and clinical activity against metastatic colorectal cancer , particularly in combination with chemotherapy . METHODS Of 813 patients with previously untreated metastatic colorectal cancer , we randomly assigned 402 to receive irinotecan , bolus fluorouracil , and leucovorin ( IFL ) plus bevacizumab ( 5 mg per kilogram of body weight every two weeks ) and 411 to receive IFL plus placebo . The primary end point was overall survival . Secondary end points were progression-free survival , the response rate , the duration of the response , safety , and the quality of life . RESULTS The median duration of survival was 20.3 months in the group given IFL plus bevacizumab , as compared with 15.6 months in the group given IFL plus placebo , corresponding to a hazard ratio for death of 0.66 ( P < 0.001 ) . The median duration of progression-free survival was 10.6 months in the group given IFL plus bevacizumab , as compared with 6.2 months in the group given IFL plus placebo ( hazard ratio for disease progression , 0.54 ; P < 0.001 ) ; the corresponding rates of response were 44.8 percent and 34.8 percent ( P=0.004 ) . The median duration of the response was 10.4 months in the group given IFL plus bevacizumab , as compared with 7.1 months in the group given IFL plus placebo ( hazard ratio for progression , 0.62 ; P=0.001 ) . Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo ( 11.0 percent vs. 2.3 percent ) but was easily managed . CONCLUSIONS The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer .

Bevacizumab

IFL plus placebo .

IFL plus bevacizumab

IFL plus placebo

IFL plus bevacizumab

IFL plus placebo

IFL plus bevacizumab

IFL plus placebo

IFL plus bevacizumab

IFL plus placebo

bevacizumab

overall survival

progression-free survival

the response rate

the duration of the response

safety

quality of life

median duration of survival

median duration of the response

Grade 3 hypertension

survival

metastatic colorectal cancer

metastatic colorectal cancer

untreated metastatic colorectal cancer

metastatic colorectal cancer .


Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma . A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic , clarithromycin , on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma . Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d . and salbutamol 200 microg p.r.n . less than twice weekly were studied . Arm A ( 16 males/six females , aged 48 +/- 16 yrs ) received clarithromycin 250 mg b.i.d . for 8 weeks , arm B ( eight males/12 females , aged 42 +/- 12 yrs ) clarithromycin 250 mg t.id . and arm C ( six males/15 females , aged 41 +/- 16 yrs ) placebo dextrose tablets . Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20 % fall in forced expiratory volume in one second ( PD20 ) . Median ( interquartile range ) PD20 in the three groups before and after treatment with clarithromycin were : arm A : 0.3 ( 0.1-1 ) and 1.3 ( 0.6-2 ) mg ; arm B : 0.4 ( 0.1-0.9 ) and 2 ( 2-2 ) mg ; and arm C : 0.4 ( 0.1-0.9 ) and 0.3 ( 0.1-0.6 ) mg , respectively . Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients . It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma .

Clarithromycin

placebo-controlled

semisynthetic macrolide antibiotic

clarithromycin

methacholine

salbutamol

clarithromycin

placebo dextrose

methacholine

clarithromycin

clarithromycin-treated

clarithromycin

evaluate the effects

provocative dose of methacholine

Serum free cortisol levels

degree of bronchial hyperresponsiveness

asthma

asthma

Adult

asthma

males/six females

48 +/- 16

eight

males/12 females

42 +/- 12

clarithromycin-treated

asthma


Prospective randomized evaluation of diode-laser and cryotherapy in prethreshold retinopathy of prematurity . PURPOSE To study the efficacy of indirect diode laser photocoagulation and cryotherapy in prethreshold retinopathy of prematurity ( ROP ) . METHODS Thirty-six eyes of 18 premature infants less than 34 weeks gestational age and/or less than 1600 g birth weight with prethreshold ROP were prospectively randomized to treatment with either indirect laser photocoagulation or cryotherapy . Prethreshold ROP was defined as any stage of ROP in zone I with plus disease ; or stage 3 with three or more contiguous clock hours or five or more total clock hours of involvement of retina in zone II with plus disease but less than threshold disease . Regression of the ROP was assessed for a minimum period of 6 months . RESULTS Regression of ROP occurred in all 36 eyes ( 100 % ) in both groups . CONCLUSIONS Excellent results are achieved if ROP is treated at the prethreshold stage with both indirect laser photocoagulation and cryotherapy . Although laser has definite advantages , cryotherapy can be considered as an alternative modality of treatment in developing countries due to economic reasons .

indirect laser photocoagulation

cryotherapy

prethreshold retinopathy

Regression of the ROP

Regression of ROP

ROP

prethreshold retinopathy of prematurity

18 premature infants

34 weeks gestational age

prethreshold ROP

Regression of ROP


[ Cardiac protection is a clinical evidence ] . AIM Anaesthetics may have protective effect against myocardial ischemia . We aimed to investigate if sevoflurane administration could exert myocardial protection during following coronary occlusion in patients with coronary artery disease . METHODS a ) . EXPERIMENTAL DESIGN prospective , randomized study . b ) . SETTING University Hospital , cardiac surgical operative theatre . c ) . PATIENTS 42 patients with coronary artery disease , scheduled to undergo coronary surgery . INCLUSION CRITERIA severe coronary stenosis of anterior descending coronary artery ; no collateral flow on angiography ; at least two normokinetic segments in the myocardial region supplied by the vessel being bypassed . PATIENTS were randomized to receive ( group S ) or not ( group C ) sevoflurane administration for 15 min just before coronary occlusion . d ) . INTERVENTIONS Transoesophageal Tissue Doppler echocardiographic examination of myocardial systolic and early diastolic velocities in both groups basally and 60 s after coronary occlusion by the surgeon . e ) . MEASURES systolic and early diastolic velocities were registered by Tissue Doppler from a long-axis view of the interventricular septum or the anterior wall of the left ventricle . RESULTS In group C a significant reduction of systolic and diastolic intramyocardial velocities was found during myocardial ischemia due to coronary occlusion . CONCLUSION Treatment with sevoflurane before coronary occlusion seem effective in reducing functional myocardial impairment due to ischemia .

myocardial protection

systolic and early diastolic velocities

functional myocardial impairment

coronary artery disease

no collateral flow on angiography


Predicting completion of treatment among foreign-born adolescents treated for latent tuberculosis infection in Los Angeles . SETTING Two health clinics in Los Angeles County , California . OBJECTIVE To identify factors associated with completion of care among foreign-born adolescents treated for latent tuberculosis infection ( LTBI ) . DESIGN A total of 766 low-income adolescents ( 79 % participation rate ) , including 610 foreign-born , were recruited . In prospective face-to-face interviews , data were obtained on socio-demographic and lifestyle characteristics , psychosocial factors and clinic-related variables . Medical chart data were abstracted regarding clinic appointment keeping and completion of treatment . Univariate and multivariate logistic regression analyses were performed to identify factors associated with completion of care . RESULTS Foreign-born adolescents were more likely to complete care than US-born adolescents , with 82 % completion of care rate . In logistic regression analyses after controlling for age , medication taking behavior ( OR 1.26 , 95 % CI 1.15-1.39 ) , living with both parents ( OR 1.74 , 95 % CI 1.02-2.97 ) , sexual intercourse ( OR 0.66 , 95 % CI 0.36-1.19 ) and speaking mostly or only English with parents ( OR 0.39 , 95 % CI 0.15-1.03 ) were independently associated with completion of care . CONCLUSION These findings contribute to our understanding of the factors that may explain why some adolescents complete care whereas others do not . They provide supportive evidence that tailored intervention programs should be developed to support the screening and completion of treatment of foreign-born adolescents .

face-to-face interviews

Medical chart data were abstracted

complete care

medication taking behavior

living with both parents

sexual intercourse

foreign-born

adolescents

latent tuberculosis infection

foreign-born

adolescents

latent tuberculosis infection ( LTBI )

low-income

adolescents

foreign-born

Foreign-born

adolescents

foreign-born

adolescents


Analgesic effect of expressed breast milk in procedural pain in term neonates : a randomized , placebo-controlled , double-blind trial . AIM To assess the effectiveness of expressed breast milk ( EBM ) in reducing pain due to venepuncture , in term neonates , as measured by behavioural and physiological observations . METHODS This randomized , placebo-controlled , double-blind trial involved 81 full-term neonates , up to 4 wk of postnatal age , who needed venepuncture for blood investigations . Two minutes before the venepuncture , in the intervention arm , 40 babies received 5 ml of EBM , while 41 babies in control group received 5 ml of distilled water ( DW ) as placebo . Two observers who were blinded to the intervention recorded the physiological ( heart rate and oxygen saturation ) and behavioural parameters [ duration of crying and modified Neonatal Facial Coding Scores ( NFCS ) ] after the venepuncture . RESULTS There was no difference in the baseline characteristics of the neonates in the two groups . The duration of crying was significantly shorter in babies fed EBM [ median 38.5 s , interquartile range ( IQR ) 9.5-57.5 s ] than in those fed DW ( median 90 s , IQR 28-210 s ) . The mean duration of crying in EBM group was shorter by 70.7 ( 95 % confidence interval 36.6-104.9 ) s. The modified NFCS at 0 , 1 and 3 min was significantly lower ( p < 0.01 ) in the EBM than in the DW group . The change in heart rate and oxygen saturation was significantly lower in the EBM group and returned to baseline values sooner than in the DW group . CONCLUSION Feeding 5 ml of EBM before venepuncture is effective in reducing symptoms due to pain in term neonates .

placebo-controlled

expressed breast milk

placebo-controlled

venepuncture

venepuncture

EBM

EBM

EBM

EBM

venepuncture

pain

mean duration of crying

symptoms

neonates

4 wk

pain