Echocardiographic evaluation of children with systemic ventricular dysfunction treated with carvedilol . Echocardiography is used to measure the therapeutic effectiveness of heart failure therapy in adults and children . The purposes of this study were ( 1 ) to assess baseline echocardiographic predictors of clinical outcome , ( 2 ) to investigate changes in echocardiographic parameters , and ( 3 ) to compare these echocardiographic changes with changes in plasma levels of b-type natriuretic peptide ( BNP ) in a population of children with systemic ventricular dysfunction and symptomatic heart failure treated with carvedilol or placebo . All available baseline and 6-month echocardiograms from Pediatric Carvedilol Trial ( PCT ) participants ( carvedilol n = 161 ; placebo n = 55 ) were reviewed . Systolic and diastolic sphericity index ( SI ; n = 110 ) , TEI index ( n = 145 ) , and systemic ventricular dP/dt ( n = 70 ) were measured . The PCT composite definition of clinical outcome ( i.e. , worsened , improved , or unchanged ) was used . For all patients , baseline TEI index was a predictor of worsened outcome . Only children treated with carvedilol showed a significant decrease in systolic SI ( P B 0.0001 ) , diastolic SI ( P B 0.0001 ) , and TEI index ( P = 0.02 ) . An inverse correlation between changes in BNP and changes in dP/dt ( r = -0.45 , P = 0.04 ) was found only in the carvedilol group . In conclusion , TEI index predicted outcome in children with systemic ventricular dysfunction and heart failure . Carvedilol may have a beneficial effect on reversal of left ventricular remodeling and global ventricular function in pediatric heart failure .

carvedilol

Echocardiography

carvedilol

placebo

carvedilol

placebo

carvedilol

carvedilol

Carvedilol

Systolic

diastolic sphericity index

worsened outcome

systolic SI

diastolic SI

TEI index

changes in BNP

changes in dP/dt

children

systemic ventricular dysfunction

adults

children

children

systemic ventricular dysfunction

symptomatic heart failure


The pulsed-dye laser as an adjuvant treatment modality in acne vulgaris : a randomized controlled single-blinded trial . BACKGROUND Acne vulgaris is the most common skin disease and can pose a substantial therapeutic challenge . Recently , several phototherapeutic modalities , most notably pulsed-dye laser ( PDL ) treatment , have been introduced , but the published results - albeit promising - are controversial . OBJECTIVES To assess the efficacy of an adjuvant PDL treatment when combined with a proven topical treatment [ fixed-combination clindamycin 1 % -benzoyl peroxide 5 % hydrating gel ( C/BPO ) ] . METHODS Eighty patients ( 38 males and 42 females , mean +/- SD age 19.7 +/- 5.9 years ) were randomized in a 1 : 2 ratio to receive C/BPO alone or in combination with PDL treatment ( wavelength 585 nm , energy fluence 3 J cm ( -2 ) , pulse duration 0.35 ms , spot size 7 mm ) . Patients were evaluated at baseline and at 2 and 4 weeks after initial treatment . The primary end points were the Investigator 's Static Global Assessment ( ISGA ) score and lesion count ; the secondary end point was the Dermatology Life Quality Index ( DLQI ) . RESULTS Both groups showed a significant improvement during observation [ ISGA 27.1 % ( C/BPO ) and 24.6 % ( C/BPO + laser ) , total lesion count 9.2 % and 9.0 % , inflammatory lesion count 36.3 % and 36.9 % , DLQI 54.5 % and 42.5 % ] , but there was no significant or otherwise appreciable difference between treatment modalities as far as the extent of improvement was concerned . Patients with more severe findings at baseline had a greater benefit from either therapy regimen . CONCLUSIONS Our findings do not support the concept of a substantial benefit of PDL treatment in acne vulgaris .

pulsed-dye laser

pulsed-dye laser ( PDL )

PDL

C/BPO

C/BPO + laser

PDL

efficacy

lesion count ;

observation

total lesion count

inflammatory lesion count

Eighty

males

females

mean +/- SD age 19.7 +/- 5.9 years )


The ScanBrit randomised , controlled , single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders . There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders ( ASDs ) . We report results from a two-stage , 24-month , randomised , controlled trial incorporating an adaptive 'catch-up ' design and interim analysis . Stage 1 of the trial saw 72 Danish children ( aged 4 years to 10 years 11 months ) assigned to diet ( A ) or non-diet ( B ) groups by stratified randomisation . Autism Diagnostic Observation Schedule ( ADOS ) and the Gilliam Autism Rating Scale ( GARS ) were used to assess core autism behaviours , Vineland Adaptive Behaviour Scales ( VABS ) to ascertain developmental level , and Attention-Deficit Hyperactivity Disorder - IV scale ( ADHD-IV ) to determine inattention and hyperactivity . Participants were tested at baseline , 8 , and 12 months . Based on per protocol repeated measures analysis , data for 26 diet children and 29 controls were available at 12 months . At this point , there was a significant improvement to mean diet group scores ( time*treatment interaction ) on sub-domains of ADOS , GARS and ADHD-IV measures . Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment . Stage 2 data for 18 group A and 17 group B participants were available at 24 months . Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention . Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD . In the absence of a placebo condition to the current investigation , we are , however , unable to disqualify potential effects derived from intervention outside of dietary changes . Further studies are required to ascertain potential best- and non-responders to intervention . The study was registered with ClincialTrials.gov , number NCT00614198 .

gluten- and casein-free diets

non-diet

dietary intervention

placebo

core autism behaviours

developmental level

ADOS , GARS and ADHD-IV measures .

children

autism spectrum disorders

aged 4 years to 10 years 11 months

26 diet children

29 controls


The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy . OBJECTIVE 11-Beta-hydroxysteroid dehydrogenase type 1 ( 11betaHSD1 ) converts inactive cortisone into active cortisol , thereby amplifying intracellular glucocorticoid action . The efficacy and safety of the 11betaHSD1 inhibitor INCB13739 were assessed when added to ongoing metformin monotherapy in patients with type 2 diabetes exhibiting inadequate glycemic control ( A1C 7-11 % ) . RESEARCH DESIGN AND METHODS This double-blind placebo-controlled paralleled study randomized 302 patients with type 2 diabetes ( mean A1C 8.3 % ) on metformin monotherapy ( mean 1.5 g/day ) to receive one of five INCB13739 doses or placebo once daily for 12 weeks . The primary end point was the change in A1C at study end . Other end points included changes in fasting glucose , lipids , weight , adverse events , and safety . RESULTS After 12 weeks , 200 mg of INCB13739 resulted in significant reductions in A1C ( -0.6 % ) , fasting plasma glucose ( -24 mg/dl ) , and homeostasis model assessment-insulin resistance ( HOMA-IR ) ( -24 % ) compared with placebo . Total cholesterol , LDL cholesterol , and triglycerides were all significantly decreased in hyperlipidemic patients . Body weight decreased relative to placebo after INCB13739 therapy . A reversible dose-dependent elevation in adrenocorticotrophic hormone , generally within the normal reference range , was observed . Basal cortisol homeostasis , testosterone in men , and free androgen index in women were unchanged by INCB13739 . Adverse events were similar across all treatment groups . CONCLUSIONS INCB13739 added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone . 11BetaHSD1 inhibition offers a new potential approach to control glucose and cardiovascular risk factors in type 2 diabetes .

placebo-controlled

metformin monotherapy

INCB13739 doses

placebo

hyperglycemia

efficacy and safety

change in A1C at study end

changes in fasting glucose

lipids

weight

adverse events

safety

fasting plasma glucose

Total cholesterol

LDL cholesterol

triglycerides

Body weight

adrenocorticotrophic hormone

Basal cortisol homeostasis

testosterone in men

free androgen index in women

efficacious

tolerated

glucose and cardiovascular risk factors


A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients ( BENEFIT study ) . Belatacept , a costimulation blocker , may preserve renal function and improve long-term outcomes versus calcineurin inhibitors in kidney transplantation . This Phase III study ( Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial ) assessed a more intensive ( MI ) or less intensive ( LI ) regimen of belatacept versus cyclosporine in adults receiving a kidney transplant from living or standard criteria deceased donors . The co-primary endpoints at 12 months were patient/graft survival , a composite renal impairment endpoint ( percent with a measured glomerular filtration rate ( mGFR ) < 60 mL/min/1.73 m ( 2 ) at Month 12 or a decrease in mGFR > or =10 mL/min/1.73 m ( 2 ) Month 3-Month 12 ) and the incidence of acute rejection . At Month 12 , both belatacept regimens had similar patient/graft survival versus cyclosporine ( MI : 95 % , LI : 97 % and cyclosporine : 93 % ) , and were associated with superior renal function as measured by the composite renal impairment endpoint ( MI : 55 % ; LI : 54 % and cyclosporine : 78 % ; p < or = 0.001 MI or LI versus cyclosporine ) and by the mGFR ( 65 , 63 and 50 mL/min for MI , LI and cyclosporine ; p < or = 0.001 MI or LI versus cyclosporine ) . Belatacept patients experienced a higher incidence ( MI : 22 % , LI : 17 % and cyclosporine : 7 % ) and grade of acute rejection episodes . Safety was generally similar between groups , but posttransplant lymphoproliferative disorder was more common in the belatacept groups . Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant , despite a higher rate of early acute rejection .

Belatacept

calcineurin inhibitors

belatacept

cyclosporine

belatacept

cyclosporine :

cyclosporine :

cyclosporine )

cyclosporine ;

cyclosporine )

cyclosporine :

belatacept

Belatacept

cyclosporine

renal function

patient/graft survival

composite renal impairment endpoint

incidence of acute rejection

patient/graft survival

superior renal function

composite renal impairment endpoint

mGFR

grade of acute rejection episodes

Safety

renal function

patient/graft survival

rate of early acute rejection

renal transplant recipients

adults

kidney transplant


Stroke team remote evaluation using a digital observation camera in Arizona : the initial mayo clinic experience trial . BACKGROUND AND PURPOSE Telemedicine techniques can be used to address the rural-metropolitan disparity in acute stroke care . The Stroke Team Remote Evaluation Using a Digital Observation Camera ( STRokE DOC ) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use , improved data collection , low risk of complications , low technical complications , and favorable assessment times . The main objective of the STRokE DOC Arizona TIME ( The Initial Mayo Clinic Experience ) trial was to determine the feasibility of establishing , de novo , a single-hub , multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol . METHODS Methods included prospective , single-hub , 2-spoke , randomized , blinded , controlled trial of a 2-way , site-independent , audiovisual telemedicine system designed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis . The primary outcome measure was whether the decision to give thrombolysis was correct . Secondary outcomes were rate of thrombolytic use , 90-day functional outcomes , incidence of intracerebral hemorrhages , and technical observations . RESULTS From December 2007 to October 2008 , 54 patients were assessed , 27 of whom were randomized to each arm . Mean National Institutes of Health Stroke Scale score at presentation was 7.3 ( SD 6.2 ) points . No consultations were aborted ; however , technical problems ( 74 % ) were prevalent in the telemedicine arm . Overall , the correct treatment decision was established in 87 % of the consultations . Both modalities , telephone ( 89 % correct ) and telemedicine ( 85 % correct ) , performed well . Intravenous thrombolytic treatment was used in 30 % of the telemedicine and telephone consultations . Good functional outcomes at 90 days were not significantly different . There were no statistically significant differences in mortality ( 4 % in telemedicine and 11 % in telephone ) or rates of intracerebral hemorrhage ( 4 % in telemedicine and 0 % in telephone ) . CONCLUSIONS It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub , multispoke rural hospital telestroke research network in Arizona . The trial was not designed to have sufficient power to detect a difference between the 2 consultative modes : telemedicine and telephone-only . Whether by telemedicine or telephone consultative modalities , there were appropriate treatment decisions , high rates of thrombolysis use , improved data collection , low rates of intracerebral hemorrhage , and equally favorable time requirements . The learning curve was steep for the hub and spoke personnel of the new telestroke network , as reflected by frequent technical problems . Overall , the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise .

telephone-only

rate of thrombolytic use

90-day functional outcomes

incidence of intracerebral hemorrhages

technical observations

technical problems

treatment decision

functional outcomes

mortality

rates of intracerebral hemorrhage

treatment decisions

thrombolysis use

data collection

rates of intracerebral hemorrhage

time requirements .

Arizona

adult patients

acute stroke

54 patients


Effects of statins on progression of subclinical brain infarct . BACKGROUND Subclinical brain infarct ( SBI ) is associated with subsequent stroke and cognitive decline . A longitudinal epidemiological study suggests that statins may prevent development of SBI . We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis ( ROCAS ) study . METHODS The ROCAS study is a randomized , double-blind , placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years . A total of 227 subjects were randomized to either placebo ( n = 114 ) or simvastatin 20 mg daily ( n = 113 ) . The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study . The primary outcome measure was the number of new brain infarcts at the end of the study . RESULTS Among the 227 randomized subjects , 33 ( 14.5 % ) had SBI at baseline . At the end of the study , significantly fewer subjects in the active group ( n = 1 ) had new brain infarcts compared with the placebo group ( n = 8 ; p = 0.018 ) . The new brain infarcts of subjects in the active group were subclinical . Among the placebo group , the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical . Among putative variables , multivariate regression analysis showed that only the baseline number of SBIs ( OR = 6.27 , 95 % CI 2.4-16.5 ) and simvastatin treatment ( OR = 0.09 , 95 % CI 0.01-0.82 ) independently predicted the development of new brain infarcts . CONCLUSIONS Consistent with findings of the epidemiological study , our study suggests that statins may prevent the development of a new brain infarct .

statins

statins

statins

simvastatin

placebo

simvastatin

placebo

placebo

simvastatin

subclinical brain infarct

Subclinical brain infarct ( SBI )

SBI

development of brain infarct

number of brain infarcts

number of new brain infarcts

new brain infarcts

brain infarcts

brain infarcts

SBIs

brain infarct

stroke-free individuals over 2 years .

total of 227 subjects


Beneficial effect of etidronate therapy in chronically hospitalized , disabled patients with stroke . Incidence of hip fractures is high in chronically hospitalized , disabled , elderly patients after stroke . Duration of hospitalization was more than 1 year because of insufficiency of nursing homes . Our study showed that immobilization-induced hypercalcemia and 25-hydroxyvitamin D deficiency contribute to reduced bone mineral density ( BMD ) . This study was designed to address the possibility that treatment with etidronate may reduce the bone resorption and lower the incidence of fractures in elderly patients who are chronically hospitalized and disabled as a result of hemiparesis after stroke . Patients with stroke were randomly assigned to daily treatment with 400 mg of etidronate ( n = 40 ) or a placebo ( n = 40 ) , and followed up for 2 years . At baseline , both groups had low BMD with high levels of serum ionized calcium and urinary deoxypyridinoline . In the etidronate group , serum calcium and urinary deoxypyridinoline levels decreased significantly during the study period , whereas the levels in the placebo group were increased . BMD on the hemiplegic side increased by 1.4 % in the etidronate group and decreased by 2.2 % in the placebo group ( P < .001 ) . Two patients sustained hip fractures in the placebo group , and no hip fracture occurred in the etidronate group . Treatment with etidronate increases BMD in chronically hospitalized patients poststroke , and may prevent hip fracture .

etidronate therapy

etidronate

etidronate

placebo

etidronate

placebo

placebo

etidronate

etidronate

BMD

high levels of serum ionized calcium

urinary deoxypyridinoline

serum calcium

urinary deoxypyridinoline levels

BMD on the hemiplegic side

hip fractures

hip fracture

BMD

chronically hospitalized

disabled

stroke

elderly

hemiparesis


Small but important errors in cardiovascular risk calculation by practice nurses : a cross-sectional study in randomised trial setting . BACKGROUND Practice nurses play an increasingly important role in the prevention of cardiovascular diseases but we do not have evidence about the accuracy of their cardiovascular risk assessments during real practice consultations . OBJECTIVES To examine how nurses perform with regard to absolute 10-year cardiovascular risk assessment in actual practice . DESIGN Cross-sectional study . SETTING This study was nested in the IMPALA study , a clustered randomised controlled trial involving 24 general practices in The Netherlands . PARTICIPANTS 24 practice nurses , trained in 10-year cardiovascular risk assessment , calculated the risk of a total of 421 patients without established cardiovascular diseases but eligible for cardiovascular risk assessment . METHODS The main outcome measure was the accuracy of risk assessments , defined as ( 1 ) the difference between the 10-year cardiovascular risk percentage calculated by nurses and an independent assessor , and ( 2 ) the agreement between the treatment categories assigned by the nurses ( low , moderate or high risk ) and those assigned by the independent assessor . RESULTS Thirty-one ( 7.4 % ) of the calculated risk percentages differed by more than our preset limits , 25 ( 81 % ) being underestimations . Elderly patients ( OR 1.1 , 95 % CI 1.0-1.1 ) , male patients ( vs. female OR 3.1 , 95 % CI 1.2-7.3 ) , and smoking patients ( vs. non-smoking OR 3.8 , 95 % CI 1.7-8.9 ) were more likely to have their cardiovascular risk miscalculated . Ten ( 28 % ) of the 36 patients who should be assigned to the high-risk treatment category according to the independent calculation , were missed as high-risk patients by the practice nurses . CONCLUSIONS The overall standard of accuracy of cardiovascular risk assessment by trained practice nurses in actual practice is high . However , a significant number of high-risk patients were misclassified , with the probability that it led to missed opportunities for risk-reducing interventions . As cardiovascular risk assessments are frequently done by nurses in general practice , further specific training should be considered to prevent undertreatment .

accuracy of risk assessments

nurses

nurses

cardiovascular risk assessment

accuracy

cardiovascular risk assessment

cardiovascular risk assessment .

accuracy of risk assessments

cardiovascular risk

miscalculated .


Randomized controlled trial of the focus parent training for toddlers with autism : 1-year outcome . This randomized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone . The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al . ( Eur Child Adolesc Psychiatr 11:266-272 , 2002 ) . Seventy-five toddlers with autism spectrum disorder ( 65 autism , 10 PDD-NOS , mean age = 34.4 months , SD = 6.2 ) were enrolled . Analyses were conducted on a final sample of 67 children ( lost to follow-up = 8 ) . No significant intervention effects were found for any of the primary ( language ) , secondary ( global clinical improvement ) , or mediating ( child engagement , early precursors of social communication , or parental skills ) outcome variables , suggesting that the 'Focus parent training ' was not of additional value to the more general care-as-usual .

language

global clinical improvement

child engagement

parental skills

toddlers

autism


Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer . PURPOSE To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer . METHODS AND MATERIALS Between January 2003 and December 2007 , 168 patients were randomized to receive either hypofractionated ( 62 Gy in 20 fractions within 5 weeks , 4 fractions/wk ) or conventionally fractionated ( 80 Gy in 40 fractions within 8 weeks ) three-dimensional conformal radiotherapy to the prostate and seminal vesicles . All patients had undergone a 9-month course of total androgen deprivation , with radiotherapy starting 2 months after initiation of the total androgen deprivation . RESULTS The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms , respectively . For the patients developing acute toxicity , no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity . Also , no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules , with a 3-year rate of Grade 2 or greater toxicity of 17 % and 16 % for the hypofractionation arm and 14 % and 11 % for the conventional fractionation arm , respectively . A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group . CONCLUSION Our findings suggest that the hypofractionation regimen used in our study is safe , with only a slight , nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule . The severity and frequency of late complications was equivalent between the two treatment groups .

conventional

hypofractionation

conventional fractionation

hypofractionated

conventionally fractionated

hypofractionation

Acute and late toxicity

tolerable and temporary acute toxicity


Response to familiar faces , newly familiar faces , and novel faces as assessed by ERPs is intact in adults with autism spectrum disorders . Individuals with autism spectrum disorders ( ASD ) have pervasive impairments in social functioning , which may include problems with processing and remembering faces . In this study , we examined whether posterior ERP components associated with identity processing ( P2 , N250 and face-N400 ) and components associated with early-stage face processing ( P1 and N170 ) are atypical in ASD . We collected ERP responses to a familiar repeated face ( Familiar ) , an unfamiliar repeated face ( Other ) and novel faces ( Novels ) in 29 high-functioning adults with ASD and matched controls . For both groups , the P2 and N250 were sensitive to repetition ( Other vs. Novels ) and personal familiarity ( Familiar vs. Other ) , and the face-N400 was sensitive to repetition . Adults with ASD did not show significantly atypical processing of facial familiarity and repetition in an ERP paradigm , despite showing significantly poorer performance than controls on a behavioral test of face memory . This study found no evidence that early-stage facial identity processing is a primary contributor to the face recognition deficit in high-functioning ASD .

familiar faces , newly familiar faces

novel faces

ERP responses

familiar repeated face ( Familiar )

unfamiliar repeated face ( Other )

novel faces ( Novels )

Response to familiar faces

face memory

adults

autism spectrum disorders .

29 high-functioning adults with ASD

Adults


Capsaicin jelly against migraine pain . OBJECTIVE Recent studies support the role of extracranial perivascular afferents in a substantial percentage of migraineurs . Perivascular afferent fibres of the superficial temporal artery contain peptides , like calcitonin gene-related peptide ( CGRP ) and substance P ( SP ) . CGRP and SP are considered relevant in the genesis of migraine pain . Capsaicin is an agonist of the transient receptor potential vanilloid type 1 . It causes membrane depolarisation of sensory neurons , which release CGRP , SP and other pain peptides ; excitation is followed by a refractory state , causing inactivation . Topical capsaicin has been found to be efficacious in several types of neuropathic pain . We attempted to verify whether topical periarterial capsaicin could ameliorate pain in absence of and during a migraine attack . METHODS On 23 migraineurs showing pain at pressure on scalp arteries , we administered topical capsaicin 0.1 % or vaseline jelly on painful arteries in absence of migraine attack . In those having pain reduction > 50 % , we made the same comparison during a migraine attack . RESULTS Topical capsaicin caused > 50 % reduction of arterial pain in absence of attack in 17/23 patients , as opposed to two with vaseline . During attacks of mild- to moderate-intensity , > 50 % improvement was obtained in 11/17 with capsaicin and in one with vaseline . CONCLUSIONS Although referring to a small number of patients , our data show that topical capsaicin may relieve arterial pain in absence of and during a migraine attack in a substantial number of patients experiencing scalp arterial tenderness . More active capsacinoids might be tried in the future and could provide a new method for treating migraine attacks .

Capsaicin jelly

Capsaicin

Topical capsaicin

topical periarterial capsaicin

Topical capsaicin

capsaicin

vaseline

topical capsaicin

capsacinoids

migraine pain

neuropathic pain

arterial pain

arterial pain

migraine pain .


Vinegar intake enhances flow-mediated vasodilatation via upregulation of endothelial nitric oxide synthase activity . This study examined the effect of acetate on endothelial nitric oxide synthase ( eNOS ) in human umbilical vein endothelial cells ( HUVECs ) by immunoblotting assay and the ability of acetic acid to upregulate flow-mediated vasodilatation in humans . In HUVECs , acetate induced a biphasic increase in the phosphorylated form of eNOS . The amount of phosphorylated eNOS was significantly increased by exposure to 200 mumol/l acetate for 20 min ( early phase ) and for 4 h ( late phase ) . The inhibitors of cAMP-dependent protein kinase ( PKA ) and AMP-activated protein kinase ( AMPK ) blocked acetate-induced eNOS phosphorylation in the early and the late phase respectively . Furthermore , in postmenopausal women , maximum forearm blood flow ( FBF ) in response to shear stress increased in the vinegar ( acetic acid ) administered group compared to the placebo group . These results suggest that acetic acid-induced eNOS phosphorylation contributes to upregulation of flow-mediated vasodilatation in humans .

Vinegar

acetate

( acetic acid )

maximum forearm blood flow ( FBF )

flow-mediated vasodilatation

women


FloSeal hemostatic matrix in persistent epistaxis : prospective clinical trial . OBJECTIVE Although most cases of epistaxis are managed conservatively , occasionally they can progress to significant hemorrhage requiring more involved management or surgery . Endoscopic ligation surgery is the current institutional standard of care for patients who fail conservative management . However , surgical ligation requires availability of surgical resources and patients who are able to withstand an anesthetic . This study 's objective was to determine the efficacy of FloSeal hemostatic matrix ( Baxter Healthcare Corporation , Hayward , CA ) in epistaxis refractory to nasal packing . METHODS A prospective clinical trial was conducted on epistaxis patients whose nasal hemorrhage persisted despite adequate nasal packing by the otolaryngology-head and neck surgery team . Once enrolled , patients are given a trial of intranasal FloSeal hemostatic matrix to abort the epistaxis . Should this fail , patients then proceed with surgical clipping . RESULTS Our prospective cohort demonstrated significant success in 80 % of patients with persistent epistaxis , who would have otherwise been taken to the operating theatre , avoiding the need for further surgical intervention . The majority of enrolled patients with persistent nasal hemorrhage were adequately managed with the hemostatic matrix alone and were discharged from hospital in a timeframe comparable to that of surgical managment . CONCLUSIONS This study revealed a highly effective tool in the otolaryngologist 's management of persistent epistaxis . Given the ease of use , decreased morbidity to the patient , and cost-effectiveness , FloSeal hemostatic matrix could change clinical practice in managing this common condition .

FloSeal hemostatic matrix

FloSeal hemostatic matrix

FloSeal hemostatic matrix

FloSeal hemostatic matrix

surgical intervention

discharged from hospital

persistent epistaxis :


Effects of fish oil supplementation on markers of the metabolic syndrome . OBJECTIVE To investigate whether fish oil affects cardiovascular risk factors during the adolescent growth spurt . STUDY DESIGN A total of 78 boys age 13-15 years with a mean body fat percentage of 30 % +/-9 % were randomly assigned to consume fish oil ( providing 1.5 g of n-3 long-chain polyunsaturated fatty acid/day ) or vegetable oil ( control ) for 16 weeks . The oils were included in bread . RESULTS After the intervention , the red blood cell ( RBC ) content of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were 1.2 % +/-0.5 % and 6.7 % +/-1.6 % , respectively , in the those receiving fish oil ( FO group ) , compared with 0.6 % +/-0.3 % and 4.1 % +/-0.9 % in the control group . Systolic blood pressure ( SBP ) was 3.8+/-1.4 mm Hg lower ( P < .006 ) and diastolic blood pressure ( DBP ) was 2.6+/-1.1 mm Hg lower ( P < .01 ) in the FO group compared with the control group . Plasma triacylglycerol ( TAG ) concentration and insulin sensitivity were unaffected by either of the treatments . Plasma high-density lipoprotein ( HDL ) and non-HDL cholesterol were increased by 5 % and 7 % , respectively , in the FO group , and by 2 % and 0 % in the control group ( P < .01-.02 ) . The changes in RBC EPA content were inversely correlated with the changes in SBP and DBP and directly correlated with the increases in HDL cholesterol and non-HDL cholesterol concentrations . No association was seen between RBC EPA and plasma TAG concentration or insulin sensitivity . CONCLUSION Fish oil improves BP in normotensive and normolipidemic slightly overweight adolescent boys .

fish oil supplementation

fish oil

fish oil

vegetable oil

fish oil ( FO group )

control

FO

control

Fish oil

red blood cell ( RBC )

Systolic blood pressure ( SBP )

insulin sensitivity

changes in RBC EPA content

changes in SBP and DBP

BP

boys age 13-15 years

mean body fat percentage of 30 % +/-9 %

normotensive and normolipidemic


Efficacy of TeachTown : Basics computer-assisted intervention for the Intensive Comprehensive Autism Program in Los Angeles Unified School District . Computer Assisted Instruction ( CAI ) has shown increased popularity recently and there are many studies showing promise for this approach for children with Autism Spectrum Disorders ( ASD ) . However , there are no between-subject studies to date assessing the efficacy of CAI with this population . In this study , 47 preschool and K-1 students in ASD classrooms participated from Los Angeles Unified School District . TeachTown : Basics , a CAI program which also includes supplementary off-computer activities , was implemented over 3 months for approximately 20 minutes per day on the computer and 20 minutes per day in supplementary TeachTown : Basics activities . Compared to the students in the control group , the TeachTown : Basics students showed more improvement overall on language and cognitive outcome measures . In addition , students who used TeachTown : Basics demonstrated significant progress overall in the software and those students who used the program for more time demonstrated larger gains within the software and in outcome measures . Although not conclusive , these findings offer possibilities for the use of CAI for remediating many deficits for children with ASD and other special needs . In addition , CAI may offer solutions to schools and parents with insufficient funds for more expensive treatments .

computer-assisted intervention

Computer Assisted Instruction ( CAI )

CAI

computer

CAI

CAI

progress overall in the software

children

Autism Spectrum Disorders

ASD

preschool and K-1 students

ASD

ASD

special needs


Biomarkers of dietary exposure are associated with lower risk of breast fibroadenomas in Chinese women . Fibroadenomas are the most common benign breast condition among women and account for up to 50 % of all breast biopsies being performed . Although considered a benign condition , fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies . Dietary factors may influence benign fibrocystic breast conditions , but little is known of their association with fibroadenomas . We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas . Participants were women in a breast self-examination trial in Shanghai , China who were diagnosed with fibroadenomas ( n = 258 ) and 1035 controls . Conditional logistic regression was used to estimate adjusted odds ratios ( OR ) and 95 % CI . Isoflavone concentrations were inversely associated with risk of fibroadenomas . Adjusted OR ( 95 % CI ) for the highest versus the lowest quartile of plasma concentration were 0.36 ( 0.16-0.79 ; P-trend < 0.001 ) for daidzein and 0.39 ( 0.19-0.84 ; P-trend = 0.010 ) for genistein . We also observed inverse associations between higher percentages of the RBC ( n-3 ) fatty acids , eicosapentaenoic acid ( EPA ) ( [ 0.38 ( 0.19-0.77 ) ; P-trend = 0.007 ] and docosapentaenoic acid ( DPA ) [ 0.32 ( 0.15-0.70 ) ; P-trend = 0.024 ] , and fibroadenoma risk . Circulating concentrations of carotenoids , vitamin C , retinol , and ferritin were not associated with fibroadenoma risk . The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas .

dietary exposure

Dietary factors

breast self-examination

daidzein

genistein

soy foods and fatty fish

biomarkers of dietary intake

Isoflavone concentrations

risk of fibroadenomas

docosapentaenoic acid ( DPA )

plasma isoflavone concentrations

RBC EPA and DPA

fibroadenoma risk

risk of fibroadenomas

breast fibroadenomas in Chinese women .


Clonidine clearance matures rapidly during the early postnatal period : a population pharmacokinetic analysis in newborns with neonatal abstinence syndrome . The population pharmacokinetic ( PK ) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome , and significant covariates affecting its PK parameters were identified . Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns , aged 1 to 25 days ( postnatal age , PNA ) and weighing 2.1 to 3.9 kg , were enrolled to take multiple oral doses of clonidine . The population PK model of clonidine was developed by NONMEM , and significant covariates were identified , followed by nonparametric bootstraps ( 2000 replicates ) and simulation experiments . A 1-compartment open linear PK model was chosen to describe plasma concentrations of clonidine , and body weight and PNA were significant covariates for apparent clearance ( CL/F ) as follows : CL/F ( L/h ) = 15.2 × [ body weight ( kg ) /70 ] ( 0.75 ) × [ PNA ( day ) ( 0.441 ) / ( 4.06 ( 0.441 ) + PNA ( day ) ( 0.441 ) ) ] . Furthermore , CL/F of clonidine increased rapidly with PNA during the first month of life after body weight was adjusted . Any optimal dosage regimen for clonidine in term neonates should be based on infant 's age and body weight , and 1.5 µg/kg every 4 hours is proposed starting the second week of life based on the simulation results .

Clonidine

oral clonidine

clonidine

clonidine

clonidine

Clonidine clearance

pharmacokinetic ( PK ) profile

Plasma clonidine concentration data

PK model of clonidine

plasma concentrations of clonidine

body weight and PNA

apparent clearance

newborns

neonatal abstinence syndrome

newborns

neonatal abstinence syndrome

newborns

1 to 25 days


Efficacy and safety of routine blood pressure lowering in older patients with diabetes : results from the ADVANCE trial . OBJECTIVE The efficacy and safety of blood pressure lowering in elderly patients have not been sufficiently investigated in patients with diabetes . Using data from the Action in Diabetes and Vascular disease : preterAx and diamicroN-MR Controlled Evaluation study , we assessed the efficacy and safety of routine blood pressure lowering to prevent major clinical outcomes in elderly patients with type 2 diabetes . METHODS Eleven thousand one hundred and forty patients aged at least 55 years with type 2 diabetes ( mean 66+/-6 years ) were randomly assigned to perindopril-indapamide or placebo . The primary endpoint was a composite of major macrovascular and microvascular disease . The effects of active treatment on outcomes were estimated in subgroups according to age : below 65 , 65-74 and at least 75 years . RESULTS During a mean 4.3-year follow-up , 1799 ( 16.1 % ) patients experienced a major event . Active treatment produced similar relative risk reductions for the primary outcome , major macrovascular disease , death and renal events across age groups ( all P heterogeneity > 0.3 ) . Over 5 years , active treatment was estimated to prevent one primary outcome in every 21 , 71 and 118 patients of at least 75 , 65-74 and below 65 years , respectively . Similar patterns of benefits were observed for secondary outcomes . There were no differences in the tolerability between randomized allocations across age groups ( all P heterogeneity > 0.6 ) CONCLUSION Routine administration of perindopril-indapamide lowers blood pressure safely and reduces the risk of major clinical outcomes in patients of at least 75 years with type 2 diabetes . The greater absolute benefits in older patients in this age group were not offset by an increased risk of side effects .

blood pressure lowering

perindopril-indapamide

placebo

perindopril-indapamide

Efficacy and safety

blood pressure lowering

efficacy and safety

blood pressure lowering

efficacy and safety

blood pressure lowering

relative risk reductions

major macrovascular disease

death

renal events

tolerability

blood pressure

risk

side effects .

older

diabetes

elderly

elderly

type 2 diabetes

Eleven thousand one hundred and forty

aged at least 55 years

type 2 diabetes

mean 66+/-6 years


Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function . We designed a randomized trial to assess whether the early withdrawal of cyclosporine ( CsA ) followed by the initiation of everolimus ( Evr ) monotherapy in de novo liver transplantation ( LT ) patients would result in superior renal function compared to a CsA-based immunosuppression protocol . All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30 , then either continued on Evr monotherapy ( Evr group ) or maintained on CsA with/without mycophenolate mofetil ( CsA group ) in case of chronic kidney disease ( CKD ) . Seventy-eight patients were randomized ( Evr n = 52 ; CsA n = 26 ) . The 1-year freedom from efficacy failure in Evr group was 75 % versus 69.2 % in CsA group , p = 0.36 . There was no statistically significant difference in patient survival between the two groups . Mean modification of diet in renal disease ( MDRD ) was significantly better in the Evr group at 12 months ( 87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min ; p < 0.001 ) . The incidence of CKD stage ≥ 3 ( estimated glomerular filtration rate < 60 mL/min ) was higher in the CsA group at 1 year ( 52.2 % vs. 15.4 % , p = 0.005 ) . The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function , with a similar incidence of rejection and major complications .

calcineurin inhibitors

everolimus monotherapy

cyclosporine ( CsA )

everolimus ( Evr ) monotherapy

CsA

with CsA

Evr monotherapy ( Evr group )

CsA

mycophenolate mofetil

Evr

CsA

Evr

1-year freedom from efficacy failure

patient survival

liver transplant

de novo liver transplantation ( LT )

Seventy-eight


Learning about the equal sign : does comparing with inequality symbols help ? This study investigated whether instruction that involves comparing the equal sign with other relational symbols is more effective at imparting a relational interpretation of the equal sign than instruction about the equal sign alone . Third- and fourth-grade students in a comparing symbols group learned about the greater than , less than , and equal signs and had the opportunity to compare the inequality symbols with the equal sign . Students in an equal sign group learned about the equal sign only . A third group of students served as a control group . Three aspects of students ' knowledge were assessed before and after the lesson : ( a ) conceptual understanding of the equal sign , ( b ) equation encoding , and ( c ) problem solving . Students in the comparing symbols group showed greater gains in conceptual understanding from pretest to posttest than students in the other two groups , and students in the comparing symbols group also scored higher on a posttest that assessed knowledge about inequality symbols and inequality problem solving . Thus , they learned about three symbols in the same amount of time as other students learned about the equal sign alone or not at all . Therefore , an instructional approach involving comparison can be an effective tool for learning about concepts in mathematics .

control group

equation encoding

problem solving

conceptual understanding

Third- and fourth-grade students


Influence of bony defects on implant stability . INTRODUCTION The purpose of this study was to analyze the evolution of implant mechanical stability in different types/sizes of bony defects using both Periotest and Osstell devices as " objective tools . " MATERIALS AND METHODS Thirty-two implants were randomly allocated to one of the four types of bone defects : marginal bone loss , peri-apical bone defect , constant width dehiscence and constant length dehiscences . Periotest/Osstell measurements were completed before and during staged bone removal ( to enlarge defect size ) . RESULTS Significant differences ( P < 0.05 ) with initial values were found after a 2 mm marginal bone removal ( Osstell/Periotest ) ; for a peri-apical bone lesion , after removal of 5 mm ( Osstell ) or 8 mm ( Periotest ) ; for a 6-mm-long dehiscence , after removal up to 180 degrees of the implant perimeter ( Osstell/Periotest ) ; for a 3-mm-wide dehiscence , after removal of 10 mm ( Osstell ) or 6 mm ( Periotest ) . CONCLUSION Periotest and Osstell are in general not very sensitive in the identification of peri-implant bone destruction , except for marginal bone loss .

Periotest

Osstell

Osstell

Periotest

Periotest

Osstell

Periotest/Osstell measurements

peri-apical bone lesion

Periotest

Osstell

bony defects

bony defects

Thirty-two

bone defects

marginal bone loss

peri-apical bone defect

constant width dehiscence

constant length dehiscences


Parent-mediated communication-focused treatment in children with autism ( PACT ) : a randomised controlled trial . BACKGROUND Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children . We therefore investigated the efficacy of such an intervention in a larger trial . METHODS Children with core autism ( aged 2 years to 4 years and 11 months ) were randomly assigned in a one-to-one ratio to a parent-mediated communication-focused ( Preschool Autism Communication Trial [ PACT ] ) intervention or treatment as usual at three specialist centres in the UK . Those assigned to PACT were also given treatment as usual . Randomisation was by use of minimisation of probability in the marginal distribution of treatment centre , age ( < /=42 months or > 42 months ) , and autism severity ( Autism Diagnostic Observation Schedule-Generic [ ADOS-G ] algorithm score 12-17 or 18-24 ) . Primary outcome was severity of autism symptoms ( a total score of social communication algorithm items from ADOS-G , higher score indicating greater severity ) at 13 months . Complementary secondary outcomes were measures of parent-child interaction , child language , and adaptive functioning in school . Analysis was by intention to treat . This study is registered as an International Standard Randomised Controlled Trial , number ISRCTN58133827 . RESULTS 152 children were recruited . 77 were assigned to PACT ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=25 ] ) ; and 75 to treatment as usual ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=23 ] ) . At the 13-month endpoint , the severity of symptoms was reduced by 3.9 points ( SD 4.7 ) on the ADOS-G algorithm in the group assigned to PACT , and 2.9 ( 3.9 ) in the group assigned to treatment as usual , representing a between-group effect size of -0.24 ( 95 % CI -0.59 to 0.11 ) , after adjustment for centre , sex , socioeconomic status , age , and verbal and non-verbal abilities . Treatment effect was positive for parental synchronous response to child ( 1.22 , 0.85 to 1.59 ) , child initiations with parent ( 0.41 , 0.08 to 0.74 ) , and for parent-child shared attention ( 0.33 , -0.02 to 0.68 ) . Effects on directly assessed language and adaptive functioning in school were small . INTERPRETATION On the basis of our findings , we can not recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms ; however , a clear benefit was noted for parent-child dyadic social communication . FUNDING UK Medical Research Council , and UK Department for Children , Schools and Families .

treatment as usual

PACT

treatment as usual

PACT intervention

efficacy

severity of symptoms

parental synchronous response

children

autism

autism

children

Children

core autism


Chumnguh thleum : understanding liver illness and hepatitis B among Cambodian immigrants . Cambodian immigrants are over 25 times more likely to have evidence of chronic hepatitis B infection than the general US population . Carriers of HBV are over 100 times more likely to develop liver cancer than non-carriers . Liver cancer incidence is the second leading cancer for Cambodian men and the sixth for Cambodian women . Despite this , this underserved population has received very little attention from health disparities researchers . Culturally and linguistically appropriate interventions are necessary to increase hepatitis B knowledge , serologic testing , and vaccination among Cambodian Americans . Eight group interviews were held with Cambodian American men ( 48 ) and women ( 49 ) . Focus group discussion revealed unanticipated information about sociocultural influences on participants ' understanding about hepatitis B transmission , disease course , and prevention and treatment informed by humoral theories underlying Khmer medicine , by biomedicine , and by migration experiences . Our findings reveal the value of qualitative exploration to providing cultural context to biomedical information -- a formula for effective health promotion and practice .

Eight group interviews

hepatitis B knowledge

serologic testing

vaccination

sociocultural influences

disease course

prevention and treatment


Efficacy and safety of de novo or early everolimus with low cyclosporine in deceased-donor kidney transplant recipients at specified risk of delayed graft function : 12-month results of a randomized , multicenter trial . Immediate or early use of proliferation signal inhibitor ( PSI ) /mammalian target of rapamycin ( mTOR ) inhibitor therapy can avoid high exposure to calcineurin inhibitors but concerns exist relating to the risk of delayed graft function ( DGF ) and impaired wound healing with the mTOR sirolimus . CALLISTO was a 12-month , prospective , multicenter , open-label study . Deceased-donor kidney transplant patients at protocol-specified risk of DGF were randomized to start everolimus on day 1 ( immediate everolimus , IE ; n = 65 ) or week 5 ( delayed everolimus , DE ; n = 74 ) . Incidence of the primary endpoint ( biopsy-proven acute rejection , BPAR ; graft loss , death , DGF , wound healing complications related to transplant surgery or loss to follow-up ) was 64.6 % and 66.2 % in the IE and DE groups , respectively , at month 12 ( P = 0.860 ) . The overall incidence of BPAR was 20.1 % . Median estimated glomerular filtration rate was 48 ml/min/1.73 m ( 2 ) and 49 ml/min/1.73 m ( 2 ) in the IE and DE groups , respectively , at month 12 . DGF and wound healing complications were similar between groups . Adverse events led to study drug discontinuation in 17 IE patients ( 26.2 % ) and 28 DE patients ( 37.8 % ) ( NS ) . In conclusion , introduction of everolimus immediately or early posttransplant in DGF-risk patients is associated with good efficacy , renal function and safety profile . There seems no benefit in delaying initiation of everolimus .

everolimus

everolimus

immediate everolimus

delayed graft function

( DGF

impaired wound healing


Effects of a leisure programme on quality of life and stress of individuals with ASD . BACKGROUND Even though there is research demonstrating a positive relationship between leisure participation and the two constructs of quality of life and stress reduction , current conceptualisation of leisure as a contributor to quality of life is limited . In addition , in spite of improvements in accurate diagnosis of autism spectrum disorder ( ASD ) at increasingly earlier ages and proliferation of interventions , research associated with leisure and quality of life for people with ASD is lacking . METHODS Therefore , a study using a repeated measures design was used to measure effects of a 1-year group leisure programme intended to facilitate interaction with media , engagement in exercise , playing games and doing crafts , attending events , and participating in other recreation activities on quality of life and stress of 37 participants ( 22 male , 15 female ) , ages 17-39 ( M = 31.49 ) years at the beginning of the programme ) diagnosed with an ASD and a group of 34 adults with ASD as control group ( waiting list ) ( 19 male , 15 female ) , ages 24-38 ( M = 30 at programme initiation ) years . RESULTS There was a significant decrease in overall scores of stress levels for participants over the course of the study and there was a significant increase in the four factors of quality of life that were measured ( satisfaction , independence , competence and social interaction ) as well as the total score for quality of life from baseline to the end of the intervention 12 months later . In contrast , the control group demonstrated no significant improvements related to stress or quality of life . Implications of these findings to leisure services and the quality of life of individuals with ASD are discussed . CONCLUSION Findings support the contention that participation in recreation activities positively influenced the stress and quality of life of adults with ASD .

leisure programme

1-year group leisure programme

interaction with media

engagement in exercise

playing games and doing crafts

attending events

quality of life

stress

quality of life

stress

stress levels

quality of life

satisfaction

independence

competence

social interaction

total score for quality of life

stress

quality of life

quality of life

stress

quality of life

ASD

autism spectrum disorder ( ASD )

ASD

22 male , 15 female

ages 17-39 ( M = 31.49 ) years

ASD

34 adults

ASD

19 male , 15 female

ages 24-38

ASD

adults

ASD


Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant : a randomized , controlled trial . BACKGROUND Persons infected with human immunodeficiency virus ( HIV ) are often hyporesponsive to immunization , including pneumococcal vaccines . We hypothesized that adding CPG 7909 , a toll-like receptor 9 ( TLR9 ) agonist and vaccine adjuvant , to 7-valent pneumococcal conjugate vaccine ( 7vPnC ) would increase its immunogenicity in HIV-infected adults . METHODS We performed a double-blind , placebo-controlled , phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC ( Prevnar ) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine ( PPV-23 ; Pneumo Novum ) at 9 months , with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses ; control patients had phosphate-buffered saline added instead . Immunogenicity and safety were evaluated for up to 10 months . The primary end point was the proportion of vaccine high responders at 9 months , defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes . RESULTS Ninety-seven participants were included in the study . The proportion of vaccine high responders was higher in the experimental group ( n = 48 ) than among controls ( n = 49 ; 48.8 % vs 25.0 % ; P = .02 ) at 9 months . Greater proportions of high responders were also observed at 3 ( 51.1 % vs 39.6 % ; P = .26 ) , 4 ( 77.3 % vs 56.3 % ; P = .03 ) , and 10 months ( 87.8 % vs 51.1 % ; P < .001 ) . Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group ( 100 % vs 81.3 % ; P = .002 ) . CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization . No adverse effects on CD4 ( + ) cell count or organ functions occurred in either group . CONCLUSIONS The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders . TRIAL REGISTRATION ClinicalTrials.gov identifier : NCT00562939 .

placebo-controlled

7vPnC ( Prevnar )

CPG 7909

phosphate-buffered saline

immunogenicity

Immunogenicity

safety

proportion of vaccine high responders

proportions of high responders

non-7vPnC IgG levels

CD4 ( + ) cell count

organ functions

vaccine high responders


[ Pleural tent after upper lobectomy -- randomized study of it 's efficacy and duration of the effect ] . UNLABELLED The aim of our study is to evaluate the safety , efficacy and also the maximum duration of effect of the pleural tent in reducing the incidence of air leak after upper lobectomy . METHODS Sixty patients who underwent upper lobectomy were prospectively randomized into two groups : 30 patients had creation of pleural tent ( group 1 ) and 30 did not ( group 2 ) . The preoperative , operative , and postoperative characteristics of both groups were compared . Then multivariate analyses were used to identify factors predictive of prolonged air leaks and their duration . The reduction of incidences of air leak in the two groups was subsequently compared during successive postoperative periods . RESULTS Demographic and clinical profiles of both groups were not statistically different . The tented patients had statistically significant reduction of mean duration of air leak in days ( 4.9 +/- 1.79 vs 8.2 +/- 4.2 ) , the number of days of a chest tube duration ( 7.3 +/- 1.14 vs 12.46 +/- 3.6 ) , the length of postoperative in-hospital stay in days ( 9.4 +/- 1.86 vs 13.6 +/- 2.49 ) , and the hospital stay cost per patient ( leva , 3840 +/- 298 vs 5160 +/- 3890 ) . Logistic regression analyses showed that no having creation a pleural tent procedure was the most significant predictive factor of the occurrence and duration of prolonged air leaks . A greater reduction in the duration of air leaks was observed before postoperative day 4 in group 1 , and logistic regression analysis showed that having a pleural tent procedure was the most significant predictive factor of air leaks that persisted for less than 4 days . CONCLUSIONS Pleural tent creation after upper lobectomy is a simple and safe procedure that reduces the duration of air leaks and the hospital stay costs . The benefit from that procedure is achieved before postoperative day 4 .

Pleural tent

pleural tent

creation of

pleural tent

did not

pleural tent

incidences of air leak

mean duration of air leak

number of days of a chest tube duration

hospital stay cost per patient

duration of air leaks

air leaks

simple

safe

duration of air leaks

hospital stay

upper lobectomy -- randomized

30 patients


Effects of cognitive behavioral therapy on daily living skills in children with high-functioning autism and concurrent anxiety disorders . CBT is a promising treatment for children with autism spectrum disorders ( ASD ) and focuses , in part , on children 's independence and self-help skills . In a trial of CBT for anxiety in ASD ( Wood et al . in J Child Psychol Psychiatry 50:224-234 , 2009 ) , children 's daily living skills and related parental intrusiveness were assessed . Forty children with ASD ( 7-11 years ) and their primary caregiver were randomly assigned to an immediate treatment ( IT ; n = 17 ) or 3-month waitlist ( WL ; n = 23 ) condition . In comparison to WL , IT parents reported increases in children 's total and personal daily living skills , and reduced involvement in their children 's private daily routines . Reductions correlated with reduced anxiety severity . These results provide preliminary evidence that CBT may yield increased independence and daily living skills among children with ASD .

cognitive behavioral therapy

CBT

CBT

immediate treatment ( IT

daily living skills

independence and self-help skills

parental intrusiveness

total and personal daily living skills

severity

independence and daily living skills


Magnocellular visual evoked potential delay with high autism spectrum quotient yields a neural mechanism for altered perception . Everyone has autistic characteristics to a greater or lesser degree , encapsulated in the Autism Spectrum Quotient , a scale that measures the degree to which an adult of normal intelligence displays traits associated with autism spectrum disorders . Recent psychophysical analyses of autism spectrum disorders point to superior local processing , and impaired or ignored global and contextual processing . The aim of this study was to test whether low- and high-scoring individuals on the Autism Spectrum Quotient differ on a measure of local and global processing , motion processing and visual pathway integrity . Fifteen low-scoring individuals and 14 high-scoring individuals derived from a normal population participated in the study . The results indicate that the initial cortical response to the magnocellular afferents is weaker at low contrast in the high autistic tendency group and that a second-order response , reflecting magnocellular activity , demonstrated a delay for high versus low scorers when the parvocellular pathway was also active in response to a high contrast stimulus . High-scoring individuals also demonstrated difficulty in identifying the global components of locally salient hierarchical Navon figures . Furthermore , cross-validated discriminant analysis , using four physiologically and three psychophysically derived parameters , correctly classified 83 % of individuals who scored either high or low on the Autism Spectrum Quotient . These findings in the group scoring high on the Autism Spectrum Quotient indicate that a delay in primary visual/prestriate cortical processing of magnocellular input diminishes the advantage of its early arrival to primary visual cortex . This appears to be associated with impaired global visual perception , predicting with high accuracy behavioural tendencies associated with autism spectrum disorders . It has been proposed that perceptual impairment in autism may be attributed to a dysfunction of horizontal connections within early visual areas , presumably parvocellular in nature . However , the timing of such form processing aberrations is much later than the timing of abnormal magnocellular visual processing measured directly here . Thus it is proposed that a magnocellular processing delay decreases the ability of autistic individuals to benefit perceptually from feedback normally associated with the magnocellular advantage .

Magnocellular visual

local and global processing

motion processing

visual pathway integrity

Autism Spectrum Quotient

local and global processing

cortical response

a delay

identifying the global components

impaired global visual perception

behavioural tendencies

high autism spectrum quotient

adult of normal intelligence


Recombinant human thyrotropin-stimulated radioiodine therapy of nodular goiter allows major reduction of the radiation burden with retained efficacy . CONTEXT AND OBJECTIVE Stimulation with recombinant human TSH ( rhTSH ) before radioiodine ( 131I ) therapy augments goiter volume reduction ( GVR ) . Observations indicate that rhTSH has a preconditioning effect beyond increasing thyroid ( 131 ) I uptake . We test the hypothesis that an equivalent GVR might be obtained by an absorbed thyroid dose well below what has been used previously . PATIENTS AND DESIGN In a double-blinded setup , 90 patients ( 78 women ; median age , 52 yr ; range , 22-83 ) with a nontoxic nodular goiter ( median size , 63 ml ; range , 25-379 ml ) were randomized to either 0.1 mg rhTSH ( n=60 ) followed by a thyroid dose of 50 Gy or placebo followed by 100 Gy ( n=30 ) . RESULTS At 12 months , the mean relative GVR in the placebo and the rhTSH group was identical ( 35+/-3 % ; P=0.81 ) . The median administered 131I-activity was 170 MBq ( 45-1269 ) in the rhTSH group and 559 MBq ( 245-3530 ) in the placebo group ( 70 % reduction , P < 0.0001 ) . According to the official radiation regulation , hospitalization was required in 14 patients in the placebo group vs. one patient in the rhTSH group ( P < 0.0001 ) . In both groups , goiter-related symptoms were effectively relieved in the majority of patients . The prevalence of myxedema ( 10 % ) did not differ among groups . CONCLUSIONS This is the first study to demonstrate that rhTSH not only increases the thyroid 131I uptake , but per se potentiates the effect of 131I-therapy , allowing a major reduction of the 131I-activity without compromising efficacy . This approach is attractive in terms of minimizing posttherapeutic restrictions and in reducing the potential risk of radiation-induced malignancy .

recombinant human TSH ( rhTSH )

radioiodine ( 131I ) therapy

rhTSH

rhTSH

thyroid dose of 50 Gy

placebo

placebo

rhTSH

rhTSH

placebo

placebo

rhTSH

rhTSH

radiation burden

efficacy .

goiter volume reduction ( GVR )

relative GVR

hospitalization

goiter-related symptoms

myxedema

thyroid 131I uptake

efficacy .

posttherapeutic restrictions


Alvimopan for the management of postoperative ileus after bowel resection : characterization of clinical benefit by pooled responder analysis . BACKGROUND A pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan , a peripherally acting mu-opioid receptor ( PAM-OR ) antagonist , for the management of postoperative ileus after bowel resection . METHODS Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days . The proportion of responders and numbers needed to treat ( NNT ) were examined on postoperative days ( POD ) 3-8 for GI-2 recovery ( first bowel movement , toleration of solid food ) and hospital discharge order ( DCO ) written . RESULTS Alvimopan significantly increased the proportion of patients with GI-2 recovery and DCO written by each POD ( P < 0.001 for all ) . More patients who received alvimopan achieved GI-2 recovery on or before POD 5 ( alvimopan , 80 % ; placebo , 66 % ) and DCO written before POD 7 ( alvimopan , 87 % ; placebo , 72 % ) , with corresponding NNTs equal to 7 . CONCLUSIONS On each POD analyzed , alvimopan significantly increased the proportion of patients who achieved GI-2 recovery and DCO written versus placebo and was associated with relatively low NNTs . The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection .

Alvimopan

alvimopan

laparotomy

oral alvimopan

placebo

Alvimopan

alvimopan

alvimopan

placebo

alvimopan

placebo

GI-2 recovery

POD 5

GI-2 recovery


Ventilator-delivered mask ventilation compared with three standard methods of mask ventilation in a manikin model . BACKGROUND Little is known regarding the variations in effective ventilation during bag and mask resuscitation with standard methods compared with that delivered by ventilator-delivered mask ventilation ( VDMV ) . AIM To measure the variations in delivered airway pressure , tidal volume ( TV ) , minute ventilation ( MV ) and inspiratory time during a 3-min period of mask ventilation comparing VDMV with three commonly used hand-delivered methods of bag and mask ventilation : Laerdal self-inflating bag ( SIB ) ; anaesthetic bag and T-piece Neopuff . METHODS A modified resuscitation manikin was used to measure variation in mechanical ventilation during 3-min periods of mask ventilation . Thirty-six experienced practitioners gave positive pressure mask ventilation targeting acceptable chest wall movement with a rate of 60 inflations/min and when pressures could be targeted or set , a peak inspiratory pressure ( PIP ) of 18 cm water , positive end-expiratory pressure ( PEEP ) of 5 cm water , for 3 min with each of the four mask ventilation methods . Each mode was randomly sequenced . RESULTS A total of 21 136 inflations were recorded and analysed . VDMV achieved PIP and PEEP closest to that targeted and significantly lower variation in all measured parameters ( p < 0.001 ) other than with PIP . SIB delivered TV and MV over twice that delivered by VDMV and Neopuff . CONCLUSION During 3-min periods of mask ventilation on a manikin , VDMV produced the least variation in delivered ventilation . SIB produced wide variation and unacceptably high TV and MV in experienced hands .

Ventilator-delivered mask ventilation

bag and mask resuscitation

VDMV

Laerdal self-inflating bag ( SIB )

anaesthetic bag

T-piece Neopuff

mask ventilation

mask ventilation

VDMV

VDMV

Neopuff

VDMV

effective ventilation

delivered ventilation .


Comparison of inguinal approach , scrotal sclerotherapy and subinguinal antegrade sclerotherapy in varicocele treatment : a randomized prospective study . We compared outcome and complications of three simple varicocelectomy techniques . Groups were divided according to whether they would receive the Ivanissevich technique ( n = 55 ) , Tauber 's technique ( n = 51 ) or subinguinal sclerotherapy ( n = 49 ) . Selection criteria were : infertility > 1 year , subnormal semen , sonographic diameter of veins > 3 mm and time of regurge > 2 s. Patients were randomly assigned to the groups of treatment , with follow-up every 3 months for 1 year . Improvement was only in sperm count and total motility for all groups . Pregnancy rates were 20 , 13.73 and 12.24 % , respectively , with no significant difference between groups . Hydrocele occurred only in the group which received the Ivanissevich technique ( 5.5 % ) . Tauber 's technique is simple ; however , it has the disadvantage of multiple branching of small veins .

inguinal approach

scrotal sclerotherapy

subinguinal antegrade sclerotherapy

Ivanissevich technique

Tauber 's technique

subinguinal sclerotherapy

sperm count

total motility

Pregnancy rates

Hydrocele

multiple branching of small veins

varicocele

infertility


Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies : a randomised controlled crossover trial . Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind , randomised , controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study . There were no significant differences between sleep variables at baseline . Melatonin significantly improved sleep latency ( by an average of 47 min ) and total sleep ( by an average of 52 min ) compared to placebo , but not number of night wakenings . The side effect profile was low and not significantly different between the two arms .

Melatonin

placebo

placebo

melatonin

Melatonin

placebo

sleep variables

improved sleep latency

total sleep

side effect profile

children

autism spectrum

sleep problems

Twenty-two

autism spectrum disorders

dysomnias

children


Standard versus newer antibacterial agents in the treatment of severe acute exacerbation of chronic obstructive pulmonary disease : a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin . BACKGROUND . Although the use of antibiotics in the treatment of acute exacerbation of chronic obstructive pulmonary disease ( COPD ) is largely accepted , controversy remains regarding whether the choice of antibiotic has any impact on outcome . Our aim was to compare the effects of the combination of trimethoprim and sulfamethoxazole and ciprofloxacin in patients treated for severe COPD exacerbation requiring mechanical ventilation . METHODS . In a randomized , double-blind trial , we included 170 patients with an acute exacerbation of COPD requiring mechanical ventilation . Enrolled patients received trimethoprim-sulfamethoxazole ( n = 85 ) or ciprofloxacin ( n = 85 ) for 10 days . Main outcomes were hospital death and need for an additional course of antibiotics . Secondary outcomes were duration of mechanical ventilation , length of hospital stay , and exacerbation-free interval . RESULTS . Combined hospital death and additional antibiotic prescription rates were similar in the 2 groups ( 16.4 % vs 15.3 % for trimethoprim-sulfamethoxazole group vs ciprofloxacin group ; difference , 1.1 % ; 95 % confidence interval [ CI ] -9.8 % to 12.0 % ; P = .832 ) . Hospital death occurred in 7 patients ( 8.2 % ) receiving trimethoprim-sulfamethoxazole and 8 patients ( 9.4 % ) receiving ciprofloxacin ( difference , -1.2 % ; 95 % CI , -9.7 to 7.3 ; P = .90 ) . The need for an additional antibiotic course was observed in 8 patients in the trimethoprim-sulfamethoxazole group and 5 patients in the ciprofloxacin group ( difference , 2.3 % ; 95 % CI , -5.4 to 10.0 ; P = .549 ) . The mean exacerbation-free interval ( +/- standard deviation ) was similar in both treatment groups ( 83 +/- 25 vs 79 +/- 22 for the trimethoprim-sulfamethoxazole group vs ciprofloxacin group ; difference , 4 days ; 95 % CI , -15 to 19 days ; P = .41 ) . Duration of mechanical ventilation and hospital stay was not significantly different between the 2 groups . CONCLUSIONS . In patients with acute exacerbation of COPD requiring mechanical ventilation , efficacy of trimethoprim-sulfamethoxazole was not inferior to ciprofloxacin . Trial registration . ClinicalTrials.gov identifier : NCT00791505 .

trimethoprim-sulfamethoxazole

trimethoprim and sulfamethoxazole

trimethoprim-sulfamethoxazole

ciprofloxacin

trimethoprim-sulfamethoxazole

trimethoprim-sulfamethoxazole

trimethoprim-sulfamethoxazole

trimethoprim-sulfamethoxazole

hospital death

duration of mechanical ventilation

length of hospital stay

exacerbation-free interval

hospital death

Hospital death

mean exacerbation-free interval

Duration of mechanical ventilation

hospital stay

efficacy

COPD


Comparing the effectiveness of peer mentoring and student mentoring in a 35-week fitness program for older adults . To investigate the applicability and effectiveness of a peer-mentored exercise program , this study compared the retention and participation rates , and physical improvements of older adults trained by peer mentors ( PM ) to a group trained by young qualified student mentors ( SM ) . A group of older adults were prepared as peer mentors through a 30-week preparation program . Later , 60 older adults ( mean ± SD age : 68.7 ± 6.1 years ) were recruited and randomly assigned to either the PM or SM group . Both groups completed an identical 35-week fitness program . Pre- , midterm- and post-training assessments of fitness were completed and rates of participation and retention were documented . The same retention rates were observed in the two groups , but SM group had higher participation . Both groups improved significantly in all measures of fitness and there were no significant post-test differences between the groups in the fitness measures . Findings suggest that the peer mentor model is applicable in an older adult exercise program and may be as effective as a program mentored by young professionals .

peer mentoring

student mentoring

peer-mentored exercise program

effectiveness

applicability

effectiveness

retention and participation rates

physical improvements

post-training assessments of fitness

had higher participation

groups improved significantly

all measures of fitness

older adults .

older adults

older adults

older adult


A first-in-man , randomized , placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome . OBJECTIVES This study aimed to determine whether serial autologous infusions of selective high-density lipoprotein ( HDL ) delipidated plasma are feasible and well tolerated in patients with acute coronary syndrome ( ACS ) . BACKGROUND Low HDL is associated with increased risk of cardiovascular disease . Plasma selective delipidation converts alphaHDL to prebeta-like HDL , the most effective form of HDL for lipid removal from arterial plaques . METHODS ACS patients undergoing cardiac catheterization with > or=1 nonobstructive native coronary artery atheroma were randomized to either 7 weekly HDL selective delipidated or control plasma apheresis/reinfusions . Patients underwent intravascular ultrasound ( IVUS ) evaluation of the target vessel during the catheterization for ACS and up to 14 days following the final apheresis/reinfusion session . 2-D gel electrophoresis of delipidated plasmas established successful conversion of alphaHDL to prebeta-like HDL . The trial was complete with 28 patients randomized . RESULTS All reinfusion sessions were tolerated well by all patients . The levels of prebeta-like HDL and alphaHDL in the delipidated plasma converted from 5.6 % to 79.1 % and 92.8 % to 20.9 % , respectively . The IVUS data demonstrated a numeric trend toward regression in the total atheroma volume of -12.18 +/- 36.75 mm ( 3 ) in the delipidated group versus an increase of total atheroma volume of 2.80 +/- 21.25 mm ( 3 ) in the control group ( p = 0.268 ) . CONCLUSIONS In ACS patients , serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated . This therapy may offer a novel adjunct treatment for patients presenting with ACS . Further study will be needed to determine its ability to reduce clinical cardiovascular events .

placebo-controlled

delipidated plasma

HDL selective delipidated

control plasma apheresis/reinfusions

intravascular ultrasound

apheresis/reinfusion

selective HDL delipidated plasma

safety and feasibility

feasible

tolerated

tolerated

levels of prebeta-like HDL and alphaHDL

atheroma volume

total atheroma volume

clinically feasible

tolerated .

clinical cardiovascular events .

acute coronary syndrome

acute coronary syndrome

ACS

ACS

undergoing cardiac catheterization

ACS

ACS


Cognitive-behavioral therapy for psychogenic nonepileptic seizures : a pilot RCT . OBJECTIVE To compare cognitive-behavioral therapy ( CBT ) and standard medical care ( SMC ) as treatments for psychogenic nonepileptic seizures ( PNES ) . METHODS Our randomized controlled trial ( RCT ) compared CBT with SMC in an outpatient neuropsychiatric setting . Sixty-six PNES patients were randomized to either CBT ( plus SMC ) or SMC alone , scheduled to occur over 4 months . PNES diagnosis was established by video-EEG telemetry for most patients . Exclusion criteria included comorbid history of epilepsy , < 2 PNES/month , and IQ < 70 . The primary outcome was seizure frequency at end of treatment and at 6-month follow-up . Secondary outcomes included 3 months of seizure freedom at 6-month follow-up , measures of psychosocial functioning , health service use , and employment . RESULTS In an intention-to-treat analysis , seizure reduction following CBT was superior at treatment end ( group x time interaction p < 0.0001 ; large to medium effect sizes ) . At follow-up , the CBT group tended to be more likely to have experienced 3 months of seizure freedom ( odds ratio 3.125 , p = 0.086 ) . Both groups improved in some health service use measures and on the Work and Social Adjustment Scale . Mood and employment status showed no change . CONCLUSIONS Our findings suggest that cognitive-behavioral therapy is more effective than standard medical care alone in reducing seizure frequency in PNES patients . CLASSIFICATION OF EVIDENCE This study provides Class III evidence that CBT in addition to SMC , as compared to SMC alone , significantly reduces seizure frequency in patients with PNES ( change in median monthly seizure frequency : baseline to 6 months follow-up , CBT group , 12 to 1.5 ; SMC alone group , 8 to 5 ) .

Cognitive-behavioral therapy

cognitive-behavioral therapy

CBT

standard medical care ( SMC )

CBT

SMC

CBT

SMC

SMC

CBT

CBT

cognitive-behavioral therapy

CBT

SMC

SMC

seizure frequency

measures of psychosocial functioning

health service use

employment

seizure reduction following CBT

seizure freedom

health service use measures

Work and Social Adjustment Scale

Mood

employment status

psychogenic nonepileptic seizures

Sixty-six

PNES

PNES


Dose-response relationship of sertindole and haloperidol using the pharmacopsychometric triangle . OBJECTIVE Renewed insight into dose-related effects of sertindole and haloperidol was sought by re-analysing published data for antipsychotic effect , extrapyramidal effect , and patient wellbeing - i.e. , the important pharmacopsychometric triangle domains . METHOD Selected Positive and Negative Syndrome Scale ( PANSS ) subscales and the Simpson-Angus scale were tested for validity . Standardized effect sizes [ last observation carried forward ( LOCF ) ] at endpoint were calculated . RESULTS The scales were found to be valid instruments . The PANSS ( 11 ) psychotic subscale showed clinically significant effect sizes for all doses of sertindole ( 12 , 20 , and 24 mg ) and haloperidol ( 4 , 8 , and 16 mg ) . Extrapyramidal effects were evident for all doses of haloperidol , but absent for the lower doses of sertindole . The PANSS ( 6 ) depression subscale , a proxy measure of quality of life , showed a clinically significant effect for sertindole 20 mg and no effect for haloperidol . CONCLUSION This re-analysis confirmed the antipsychotic effect and absence of extrapyramidal effects for sertindole and , in addition , showed a clinically significant antidepressant effect . A profile for bipolar states emerged .

sertindole

haloperidol

sertindole

haloperidol

sertindole

haloperidol

haloperidol

sertindole

sertindole

haloperidol

sertindole

effect sizes

Extrapyramidal effects

quality of life


Hematologic patients ' clinical and psychosocial experiences with implanted long-term central venous catheter : self-management versus professionally controlled care . BACKGROUND A significant decrease in catheter-related infections was demonstrated in our earlier randomized controlled trial of central venous catheter ( CVC ) care in hematologic patients . OBJECTIVE This article focuses on patients ' clinical and psychosocial experiences with CVC self-care compared with professionally controlled CVC care . METHODS Eighty-two patients with tunneled CVCs were enrolled in the randomized controlled trial . The intervention group ( n = 42 ) was trained to perform CVC self-care . The control group ( n = 40 ) followed standard CVC procedure provided by nurses . Eighteen patients were selected for semistructured interviews focusing on patients ' clinical and psychosocial experiences with CVCs . RESULTS Methods of CVC care have different influences on the patients ' clinical and psychosocial outcomes , depending on whether they were hospitalized or outpatients . Central venous catheter was viewed as important because it was the main port of treatment toward a cure , although patients constantly fear complications . Central venous catheter self-care increased patients ' independence from health professionals and supported perceived self-efficacy and control . Central venous catheters cause psychosocial problems including altered body perception , sexual activity avoidance , and feeling stigmatized . CONCLUSIONS Patients experience increased perceived self-control and independence when individually supervised and trained in CVC self-management . Assuming ownership of CVC care can encourage patients to feel less inhibited about sexual activity and socialization . IMPLICATIONS FOR PRACTICE Placement of a tunneled CVC should engage nurses to organize individualized structured and supervised patient education . Stigma originating from CVCs should be carefully considered by health professionals when maintaining CVC insertion for longer periods . Central venous catheters should be removed whenever the potential risks exceed the catheter 's functional necessity .

CVC self-care

CVC self-care

Central venous catheter

Central venous catheter self-care

CVC self-management

clinical and psychosocial outcomes

patients ' independence

self-efficacy

psychosocial problems

perceived self-control and independence

sexual activity and socialization .

Hematologic

central venous catheter

hematologic

Eighty-two

CVCs


A multicenter , open-label study of vernakalant for the conversion of atrial fibrillation to sinus rhythm . BACKGROUND The efficacy and safety of vernakalant , a relatively atrial-selective antiarrhythmic agent , in converting atrial fibrillation ( AF ) to sinus rhythm ( SR ) were evaluated in this multicenter , open-label study of patients with AF lasting > 3 hours and < or =45 days ( RCT no . NCT00281554 ) . METHODS Adult patients with AF and an indication for conversion to SR received a 10-minute intravenous infusion of vernakalant ( 3 mg/kg ) . If after a 15-minute observation period AF was present , a second 10-minute infusion of intravenous vernakalant ( 2 mg/kg ) was given . The primary efficacy end point was the proportion of patients with recent-onset AF ( AF lasting > 3 hours to < or =7 days ) who converted to SR within 90 minutes of the start of the first infusion . Safety evaluations included vital signs , telemetry and Holter monitoring , 12-lead electrocardiography , clinical laboratory tests , physical examinations , and adverse events ( AEs ) . RESULTS A total of 236 hemodynamically stable patients with AF received intravenous vernakalant . Among them , 167 ( 71 % ) had recent-onset AF and were eligible for the primary efficacy end point . Vernakalant rapidly converted recent-onset AF to SR in 50.9 % of patients , with a median time to conversion of 14 minutes among responders . The most common AEs were dysgeusia , sneezing , and paresthesia . These occurred at the time of vernakalant infusion , were transient , and resolved spontaneously . Ten patients ( 4.2 % ) discontinued vernakalant treatment because of AEs , most commonly ( in 4 of 10 ) hypotension . There were no episodes of torsades de pointes , ventricular fibrillation , or sustained ventricular tachycardia . CONCLUSIONS Vernakalant rapidly converted recent-onset AF to SR , was well tolerated , and may be a valuable therapeutic alternative for reestablishing SR in patients with recent-onset AF .

intravenous vernakalant

efficacy and safety

atrial fibrillation ( AF )

sinus rhythm ( SR )

SR

AF

vital signs

telemetry and Holter monitoring

12-lead electrocardiography

clinical laboratory tests

physical examinations

adverse events ( AEs )

recent-onset AF

recent-onset AF to SR

dysgeusia

sneezing

, and

paresthesia

hypotension

torsades de pointes

ventricular fibrillation

, or

sustained ventricular tachycardia

atrial fibrillation

Adult patients


Losartan vs. amlodipine treatment in elderly oncologic hypertensive patients : a randomized clinical trial . Elderly neoplastic patients frequently may show hypertension and hyperuricemia , before and after chemotherapeutic treatments . The purpose of this study was to evaluate the efficacy of losartan which is an antihypertensive drug with uricosuric properties vs. amlodipine in hypertensive neoplastic elderly patients . This was an open-labeled , randomized , comparative trial . The study was performed as a 30-day study . Seventy patients with cancer were randomly assigned to receive losartan or amlodipine . Blood pressure ( BP ) , blood urea nitrogen ( BUN ) levels , creatinine , serum and urinary uric acid , creatinine and uric acid clearance were determined before and after chemotherapy . One day after chemotherapy in losartan group vs. amlodipine group we observed a significant difference in urinary uric acid ( p < 0.001 ) of 18 mg/24 h vs. 40 mg/24 h. Thirty days after chemotherapy we observed a significant difference in azotemia of 0.0 mg/dl vs. 3.8 mg/dl ( p < 0.001 ) , serum uric acid of 0.05 mg/dl vs. 0.49 mg/dl ( p < 0.001 ) , urinary uric acid ( p < 0.001 ) of 23 mg/24 h vs. 0.0 mg/24 h , GFR of 2 ml/min/1.73 m ( 2 ) vs. -8 ml/min/1.73 m ( 2 ) ( p < 0.05 ) and systolic BP ( SBP ) of 3.6 mmHg vs. 0.8 mmHg ( p < 0.05 ) . The findings of the present study support the effective role of losartan compared to amlodipine in treating hypertension and hyperuricemia in elderly patients under chemotherapeutic treatment .

Losartan vs. amlodipine

losartan

antihypertensive drug

uricosuric

amlodipine

losartan or amlodipine .

chemotherapy

losartan

amlodipine

chemotherapy

losartan

amlodipine

Blood pressure

blood urea nitrogen ( BUN ) levels

creatinine

serum and urinary uric acid

creatinine and uric acid clearance

urinary uric acid

azotemia

serum uric acid

urinary uric acid

systolic BP

elderly

oncologic hypertensive

neoplastic

hypertension

hyperuricemia

hypertensive neoplastic

elderly

Seventy

cancer

hypertension

hyperuricemia

chemotherapeutic treatment


Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis : the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial . INTRODUCTION Early treatment of rheumatoid arthritis ( RA ) has been shown to retard the development of joint damage for a period of up to 5 years . The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs ( DMARDs ) or a single DMARD . METHODS A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate , sulfasalazine , and hydroxychloroquine with prednisolone ( FIN-RACo ) , or treatment with a single DMARD ( initially , sulfasalazine ) with or without prednisolone ( SINGLE ) . After 2 years , the drug-treatment strategy became unrestricted , but still targeted remission . The radiographs of hands and feet were analyzed by using the Larsen score at baseline , 2 , 5 , and 11 years , and the radiographs of large joints , at 11 years . RESULTS Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years . The mean change from baseline to 11 years in Larsen score was 17 ( 95 % CI , 12 to 26 ) in the FIN-RACo group and 27 ( 95 % CI , 22 to 33 ) in the SINGLE group ( P=0.037 ) . In total , 87 % ( 95 % CI , 74 to 94 ) and 72 % ( 95 % CI , 58 to 84 ) of the patients in the FIN-RACo and the SINGLE treatment arms , respectively , had no erosive changes in large joints at 11 years . CONCLUSIONS Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients . Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy . TRIAL REGISTRATION Current Controlled Trials ISRCTN18445519 .

antirheumatic drug therapy

single DMARD

methotrexate

sulfasalazine

prednisolone ( SINGLE )

FIN-RACo

SINGLE

FIN-RACo

SINGLE

combination of DMARDs

DMARD monotherapy

long-term radiologic outcome

evaluate the radiologic progression

radiographs

analyzed by using the Larsen score

Larsen score

erosive changes

radiologic progression

long-term radiologic damage

rheumatoid arthritis ( RA )


Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease . BACKGROUND Blocking the renin-angiotensin system ( RAS ) with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors protects against renal injury in patients with chronic kidney disease ( CKD ) . The aim of this study was to compare the chronic effects of telmisartan and enalapril on proteinuria , urinary liver-type fatty acid-binding protein ( L-FABP ) and endothelin ( ET ) -1 levels in patients with mild CKD . MATERIALS AND METHODS Thirty CKD patients with mild to moderate renal insufficiency ( 20 men and 10 women ; mean age , 37 years ; estimated glomerular filtration rate ( eGFR ) > 60 mL min ( -1 ) and blood pressure > 130/85 mmHg ) were included in the study . Patients were randomly assigned to receive telmisartan at 80 mg day ( -1 ) ( n = 15 ) or enalapril at 10 mg day ( -1 ) ( n = 15 ) . We measured blood pressure , serum creatinine , eGFR , urinary protein , L-FABP and ET-1 before the start of treatment and 6 and 12 months after the start of treatment . RESULTS The blood pressure reduction rate was similar between the two groups . Urinary protein , L-FABP and ET-1 levels were significantly reduced in both groups 6 and 12 months ( P < 0.001 ) after treatment , but the reduction rates were more pronounced in patients receiving telmisartan than in those receiving enalapril ( P < 0.001 ) . Estimated glomerular filtration rate was increased similarly in both groups at 12 months . CONCLUSIONS The study results suggest that telmisartan results in a greater reduction of urinary markers than does enalapril and that this effect occurs by a mechanism independent of blood pressure reduction . It would be needed to investigate whether the differences may be distinct or not the same when other dosages are used .

telmisartan

enalapril

telmisartan

enalapril

telmisartan at 80 mg day ( -1 )

enalapril at 10 mg day ( -1 )

telmisartan

enalapril

telmisartan

enalapril

Effects

endothelin ( ET ) -1 levels

blood pressure

serum creatinine , eGFR

urinary protein

L-FABP

blood pressure reduction rate

Urinary protein

L-FABP

ET-1 levels

reduction rates

glomerular filtration rate

urinary markers

mild to moderate chronic kidney disease

chronic kidney disease ( CKD ) .

mild CKD

Thirty CKD patients

mild to moderate renal insufficiency

20 men and 10 women


Abnormal cardiac contractility in long-term exogenous subclinical hyperthyroid patients as demonstrated by two-dimensional echocardiography speckle tracking imaging . BACKGROUND Subclinical hyperthyroidism is associated with cardiovascular morbidity . Recent advances in echocardiography imaging have allowed sophisticated evaluation of myocardial tissue properties . OBJECTIVE To investigate the myocardial effects of long-term exogenous subclinical hyperthyroidism using two-dimensional speckle tracking echocardiography imaging ( 2D-STE ) . DESIGN Prospective , single-blinded , placebo-controlled randomized trial of 6 months duration with two parallel groups . PATIENTS AND METHODS Totally 25 patients with a history of differentiated thyroid carcinoma on long-term TSH-suppressive levothyroxine ( l-T ( 4 ) ) substitution were randomized to persistent TSH-suppressive l-T ( 4 ) substitution ( low-TSH group ) or restoration of euthyroidism . Additionally 40 euthyroid controls were studied . RESULTS ( PROPOSAL ) : At baseline , the group of patients showed normal left ventricular ( LV ) systolic function but impaired diastolic function as assessed with conventional echocardiographic parameters . Importantly , 2D-STE analysis demonstrated the presence of subclinical LV systolic and diastolic dysfunction with impaired circumferential and longitudinal strain and strain rate at the isovolumic relaxation time . After restoration of euthyroidism , a significant improvement in LV systolic and diastolic function as assessed with 2D-STE strain was observed . CONCLUSION Prolonged subclinical hyperthyroidism leads to systolic and diastolic dysfunction , which is reversible after restoration of euthyroidism . 2D-STE is a more sensitive technique to evaluate subtle changes in LV performance of these patients .

exogenous subclinical hyperthyroidism

TSH-suppressive l-T ( 4 ) substitution

restoration of euthyroidism

Prolonged subclinical hyperthyroidism

cardiovascular morbidity .

myocardial

impaired diastolic function

systolic and diastolic dysfunction

long-term


A randomized clinical trial of St. John 's wort for smoking cessation . INTRODUCTION St. John 's wort ( SJW ) is a widely used herbal supplement . The predominant mechanism ( s ) accounting for the activity of SJW in vivo are , however , unclear . The purpose of this study was to investigate the efficacy of SJW for smoking cessation . METHODS We conducted a randomized , blinded , placebo-controlled , three-arm , dose-ranging clinical trial . A total of 118 subjects were randomly allocated to receive SJW 300 mg , 600 mg , or a matching placebo tablet 3 times a day combined with a behavioral intervention for 12 weeks . Self-reported smoking abstinence was biochemically confirmed with expired air carbon monoxide . RESULTS Mean age of the study participants was 37.6 +/- 12.4 years ; they smoked an average of 20.0 +/- 6.6 cigarettes per day for 20 +/- 12.1 years . The study dropout rate was high ( 43 % ) . By intention-to-treat analysis , no significant differences were observed in abstinence rates at 12 and 24 weeks between SJW dose groups and placebo . SJW did not attenuate withdrawal symptoms among abstinent subjects . Abstinence rates did not differ by study group among subjects who took at least 75 % of their study medication . No significant side-effects were noted with SJW . CONCLUSIONS In this randomized trial , SJW did not increase smoking abstinence rates . Our data , in combination with data from other studies , suggest that SJW has little role in the treatment of tobacco dependence .

John 's wort ( SJW )

SJW

SJW 300 mg , 600 mg

placebo

SJW

SJW .

SJW

smoking cessation .

smoking cessation

smoking abstinence

expired air carbon monoxide

abstinence

withdrawal symptoms

Abstinence rates

abstinence