Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival : 10-year follow-up of a 2-year randomised trial . OBJECTIVE To examine the long-term effects of early low-dose prednisolone use in patients with rheumatoid arthritis ( RA ) on cardiovascular ( CV ) morbidity and mortality . DESIGN Retrieval of data from a 2-year open randomised trial comparing prednisolone 7.5 mg/day in addition to disease-modifying antirheumatic drugs ( DMARDs ) with DMARD therapy alone . Participants were followed for 10 years since inclusion into the original prednisolone trial or until occurrence of the studied outcomes . SETTING Secondary level of care ; six participating centres from southern Sweden ; both urban and rural populations . PARTICIPANTS Overall , 223 patients with early RA were included . The participants had no history of CV events at baseline and incident cases were identified via the Swedish Hospital Discharge and Cause of Death Registries . OUTCOMES Composite CV events , that is , ischaemic coronary and cerebrovascular events , components of the composite CV outcome , and death . Relative HRs from Cox proportional-hazards regression models were calculated . RESULTS Within 2041 person-years , 17 incident composite CV events occurred in 112 patients ( 15 % ) randomised to prednisolone , and 15 events of 111 patients ( 14 % ) who were assigned not to receive prednisolone . There were nine deaths ( 8 % ) in each group . The age-adjusted relative hazards ( HRs ; 95 % CI ) for the first composite CV event , first coronary event and death in the prednisolone group versus the group not treated with prednisolone were 1.8 ( 0.9 to 3.6 ) , 0.98 ( 0.4 to 2.6 ) and 1.6 ( 0.6 to 4.1 ) , respectively . The risk for the first cerebrovascular event showed a 3.7-fold increased relative hazard ( 95 % CI 1.2 to 11.4 ) among prednisolone treated patients . CONCLUSIONS In this inception cohort study of low-dose prednisolone use during the first 2 years of RA disease , the incidence of ischaemic coronary artery events was similar in the two treatment groups , whereas the long-term risk of ischaemic cerebrovascular events was higher in the prednisolone group . There was a trend towards reduced survival in the prednisolone group . TRIAL REGISTRATION NUMBER ISRCTN20612367 .

Low-dose prednisolone treatment

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

prednisolone

late cardiovascular outcome

survival

long-term effects

cardiovascular ( CV ) morbidity

mortality

CV events

Composite CV events

death

composite CV events

deaths

death

reduced survival

early rheumatoid arthritis

six

had no history of CV events at baseline


Effect of body mass index on hemiparetic gait . OBJECTIVE To evaluate the relationship between body mass index ( BMI ) and spatiotemporal , kinematic , and kinetic gait parameters in chronic hemiparetic stroke survivors . DESIGN Secondary analysis of data collected in a randomized controlled trial comparing two 12-week ambulation training treatments . SETTING Academic medical center . PARTICIPANTS Chronic hemiparetic stroke survivors ( N = 108 , > 3 months poststroke ) METHODS Linear regression analyses were performed of BMI , and selected pretreatment gait parameters were recorded using quantitative gait analysis . MAIN OUTCOME MEASURES Spatiotemporal , kinematic , and kinetic gait parameters . RESULTS A series of linear regression models that controlled for age , gender , stroke type ( ischemic versus hemorrhagic ) , interval poststroke , level of motor impairment ( Fugl-Meyer score ) , and walking speed found BMI to be positively associated with step width ( m ) ( β = 0.364 , P < .001 ) , positively associated with peak hip abduction angle of the nonparetic limb during stance ( deg ) ( β = 0.177 , P = .040 ) , negatively associated with ankle dorsiflexion angle at initial contact of the paretic limb ( deg ) ( β = -0.222 , P = .023 ) , and negatively associated with peak ankle power at push-off ( W/kg ) of the paretic limb ( W/kg ) ( β = -0.142 , P = .026 ) . CONCLUSIONS When walking at a similar speed , chronic hemiparetic stroke subjects with a higher BMI demonstrated greater step width , greater hip hiking of the paretic lower limb , less paretic limb dorsiflexion at initial contact , and less paretic ankle power at push-off as compared to stroke subjects with a lower BMI and similar level of motor impairment . Further studies are necessary to determine the clinical relevance of these findings with respect to rehabilitation strategies for gait dysfunction in hemiparetic patients with higher BMIs .

body mass index

body mass index ( BMI

ambulation training treatments

with ankle dorsiflexion angle

with peak ankle power at push-off

less paretic ankle power at push-off

chronic hemiparetic stroke

Chronic hemiparetic stroke

poststroke

chronic hemiparetic stroke

BMIs


Hemodialysis catheter design and catheter performance : a randomized controlled trial . BACKGROUND A complication of long-term use of tunneled cuffed catheters for hemodialysis is the high rate of infection and thrombus-related dysfunction . Specific mechanical features of tunneled cuffed catheters may improve hemodynamic performance and decrease thrombosis and infection rates . However , there currently is no proven advantage of one design over another . STUDY DESIGN Single-center randomized clinical trial . SETTING & PARTICIPANTS 302 hemodialysis patients who required a tunneled cuffed catheter as temporary or definite vascular access . INTERVENTION Palindrome Symmetric Tip Dialysis Catheter or HemoStar Long-Term Hemodialysis Catheter . OUTCOMES & MEASUREMENTS The primary end point was primary assisted patency . Secondary end points were incidence of catheter-related bloodstream infections ( CRBSIs ) , thrombosis , and 2 indicators of rheologic function : mean effective blood flow rate and urokinase use . RESULTS Mean primary assisted patency was 135.9 days for Palindrome and 136.5 days for HemoStar ( P=0.8 ) . Definite CRBSI occurred in 0.24 and 0.10/1,000 catheter-days for Palindrome and HemoStar , respectively ( P=0.3 ) . Removal rates for thrombosis that could not be resolved with thrombolysis were 0.53 and 0.43/1,000 catheter-days for Palindrome and HemoStar , respectively ( P=0.7 ) . Urokinase use was lower for Palindrome than for HemoStar , as evidenced by a lower number of urokinase infusions/1,000 catheter-days ( 17 and 35 ; P < 0.001 ) and higher number of catheters that never required thrombolysis ( 58 % and 45 % ; P=0.03 ) . Mean effective blood flow rate was higher for Palindrome than for HemoStar ( 333 and 304mL/min ; P < 0.001 ) . LIMITATIONS Single-center nonblinded trial . CONCLUSIONS Primary assisted patency and incidence of infection and thrombosis were similar for both catheter types . The Palindrome catheter required less thrombolysis and achieved higher blood flow rates than the HemoStar catheter . These findings suggest that mechanical catheter design may improve catheter rheology , but does not affect risks for thrombosis and infection and hence catheter survival .

tunneled cuffed catheters

tunneled cuffed catheters

tunneled cuffed catheter

Palindrome

HemoStar

infection

thrombus-related dysfunction .

primary assisted patency .

Mean primary assisted patency

CRBSI

Removal rates for thrombosis

Urokinase use

urokinase

Mean effective blood flow rate

thrombolysis

blood flow rates

thrombosis

infection


Salivary testosterone and immunoglobulin A were increased by resistance training in adults with Down syndrome . This study was designed to assess the influence of resistance training on salivary immunoglobulin A ( IgA ) levels and hormone profile in sedentary adults with Down syndrome ( DS ) . A total of 40 male adults with DS were recruited for the trial through different community support groups for people with intellectual disabilities . All participants had medical approval for participation in physical activity . Twenty-four adults were randomly assigned to perform resistance training in a circuit with six stations , 3 days per week for 12 weeks . Training intensity was based on functioning in the eight-repetition maximum ( 8RM ) test for each exercise . The control group included 16 age- , gender- , and BMI-matched adults with DS . Salivary IgA , testosterone , and cortisol levels were measured by ELISA . Work task performance was assessed using the repetitive weighted-box-stacking test . Resistance training significantly increased salivary IgA concentration ( P=0.0120 ; d=0.94 ) and testosterone levels ( P=0.0088 ; d=1.57 ) in the exercising group . Furthermore , it also improved work task performance . No changes were seen in the controls who had not exercised . In conclusion , a short-term resistance training protocol improved mucosal immunity response as well as salivary testosterone levels in sedentary adults with DS .

resistance training

resistance training

exercise

resistance training

Salivary IgA

testosterone

cortisol levels

salivary IgA concentration

testosterone levels

improved work task performance

immunity response

salivary testosterone

adults

Down syndrome

adults

Down syndrome ( DS )

male

adults

people with intellectual disabilities

Twenty-four

adults

age-

gender-

adults

DS

adults

DS


Application of the Itch Severity Score in patients with moderate-to-severe plaque psoriasis : Clinically important difference and responder analyses . The Itch Severity Score ( ISS ) , a 0-10 numeric rating scale , was used to assess pruritus due to psoriasis in a Phase 2 b trial of tofacitinib , a novel oral Janus kinase inhibitor . 197 patients with moderate-to-severe plaque psoriasis were randomized to tofacitinib 2 , 5 or 15 mg twice daily , or placebo . The ISS was recorded daily from baseline to week 2 and at study visits . Following good and recommended research practice , we performed analyses to examine the clinically important differences ( CID ) ( between-group difference or within-group difference ) and clinically important responders ( CIR ) ( within-patient change ) for the ISS . The CID and CIR were defined using Patient Global Assessment of psoriasis as an anchor and were estimated with a longitudinal model . A CID on the ISS was 1.64 and , by day 10 , the mean changes from baseline in ISS values for the tofacitinib doses ( placebo-adjusted ) exceeded CID . A CIR on the ISS was a 30 % improvement from baseline and , at week 12 , 87.2 % to 100 % of patients receiving tofacitinib reached ≥30 % improvement versus 29.4 % of patients receiving placebo ( p < 0.0001 ) . Overall , the CID and CIR analyses play vital roles in the interpretation of the treatment effects measured by ISS .

tofacitinib

tofacitinib

baseline in ISS values

inhibitor

197 patients

plaque psoriasis


Spironolactone for heart failure with preserved ejection fraction . BACKGROUND Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction . We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction . METHODS In this randomized , double-blind trial , we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45 % or more to receive either spironolactone ( 15 to 45 mg daily ) or placebo . The primary outcome was a composite of death from cardiovascular causes , aborted cardiac arrest , or hospitalization for the management of heart failure . RESULTS With a mean follow-up of 3.3 years , the primary outcome occurred in 320 of 1722 patients in the spironolactone group ( 18.6 % ) and 351 of 1723 patients in the placebo group ( 20.4 % ) ( hazard ratio , 0.89 ; 95 % confidence interval [ CI ] , 0.77 to 1.04 ; P=0.14 ) . Of the components of the primary outcome , only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group ( 206 patients [ 12.0 % ] vs. 245 patients [ 14.2 % ] ; hazard ratio , 0.83 ; 95 % CI , 0.69 to 0.99 , P=0.04 ) . Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone . Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia ( 18.7 % , vs. 9.1 % in the placebo group ) but reduced hypokalemia . With frequent monitoring , there were no significant differences in the incidence of serious adverse events , a serum creatinine level of 3.0 mg per deciliter ( 265 μmol per liter ) or higher , or dialysis . CONCLUSIONS In patients with heart failure and a preserved ejection fraction , treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes , aborted cardiac arrest , or hospitalization for the management of heart failure . ( Funded by the National Heart , Lung , and Blood Institute ; TOPCAT ClinicalTrials.gov number , NCT00094302 . ) .

Spironolactone

spironolactone

spironolactone

placebo

spironolactone

placebo

spironolactone

placebo

spironolactone .

spironolactone

effects

death from cardiovascular causes

aborted cardiac arrest

hospitalization for heart failure

total deaths

hospitalizations

serum creatinine levels

rate of hyperkalemia

serum creatinine level

heart failure


Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome : a randomized trial . INTRODUCTION This preliminary study aimed to investigate the effects of the probiotic Saccharomyces boulardii on proinflammatory and anti-inflammatory cytokines in patients with diarrhea-dominant irritable bowel syndrome ( IBS-D ) . The other objectives were to document any clinical improvement as judged by symptoms , quality of life , and histology . PATIENTS AND METHODS This was a randomized , double blind , placebo-controlled trial in which S. boulardii , 750 mg/day , or placebo was administered for 6 weeks in IBS-D patients , in addition to ispaghula husk standard treatment . RESULTS Thirty-seven patients received S. boulardii and 35 patients received the placebo . As compared with placebo , the S. boulardii group showed a significant decrease in blood and tissue levels of proinflammatory cytokines interleukin-8 ( IL-8 ) and tumor necrosis factor-α ( P < 0.001 ) and an increase in anti-inflammatory IL-10 levels , as well as an increase in the tissue IL-10/IL-12 ratio ( P < 0.001 ) . No significant change in the blood and tissue levels of cytokines was found in the placebo group . Bowel-related IBS-D symptoms reported in the patients ' daily diary improved in both groups . However , overall improvement in the quality of life was more marked in the S. boulardii group . Although baseline histological findings were mild , an improvement was observed in the probiotic group in the lymphocyte and neutrophil infiltrates ( P=0.017 and 0.018 ) , epithelial mitosis ( P=0.003 ) , and intraepithelial lymphocytes ( P=0.024 ) . No serious adverse events were found in either group . CONCLUSION S. boulardii with ispaghula husk was superior to placebo with ispaghula husk in improving the cytokine profile , histology , and quality of life of patients with IBS-D . These preliminary results need to be confirmed in a well-powered trial .

Cytokine

Saccharomyces boulardii therapy

probiotic Saccharomyces boulardii

placebo-controlled

boulardii

placebo

boulardii

placebo

placebo

boulardii

tumor necrosis factor-α

anti-inflammatory IL-10 levels

tissue IL-10/IL-12 ratio

blood and tissue levels of cytokines

Bowel-related IBS-D symptoms

quality of life

Thirty-seven


Directed forgetting in high-functioning adults with autism spectrum disorders . Rehearsal strategies of adults with autism spectrum disorders ( ASDs ) and demographically matched typically developed ( TD ) adults were strategically manipulated by cueing participants to either learn , or forget each list word prior to a recognition task . Participants were also asked to distinguish between autonoetic and noetic states of awareness using the Remember/Know paradigm . The ASD group recognised a similar number of to-be-forgotten words as the TD group , but significantly fewer to-be-learned words . This deficit was only evident in Remember responses that reflect autonoetic awareness , or episodic memory , and not Know responses . These findings support the elaborative encoding deficit hypothesis and provide a link between the previously established mild episodic memory impairments in adults with high functioning autism and the encoding strategies employed .

Directed forgetting

learn

forget

recognition task

to-be-forgotten words

to-be-learned words

deficit

evident in Remember responses

autonoetic awareness

episodic memory

not Know responses

findings support

adults

autism spectrum disorders

adults

ASD


Association study of the let-7 miRNA-complementary site variant in the 3 ' untranslated region of the KRAS gene in stage III colon cancer ( NCCTG N0147 Clinical Trial ) . PURPOSE A let-7 microRNA-complementary site ( LCS6 ) polymorphism in the 3 ' untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression . We evaluated the LCS6 genotype and its association with KRAS mutation status , clinicopathologic features , and disease-free survival ( DFS ) in patients with stage III colon cancer who enrolled in a phase III clinical trial ( NCCTG N0147 ) . EXPERIMENTAL DESIGN The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood ( n = 2,834 ) and compared with paired tumor tissue ( n = 977 ) . χ ( 2 ) and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status . Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS , respectively . RESULTS We identified 432 ( 15.2 % ) blood samples and 143 ( 14.6 % ) tumor samples heterozygous or homozygous for the LCS6 G-allele , and 2,402 of 2,834 ( 84.8 % ) blood samples and 834 of 977 ( 85.4 % ) tumor samples homozygous for the LCS6 T-allele . Genotype results were highly concordant ( 99.8 % ) in cases with paired blood and tumor tissue ( n = 977 ) . G-allele carriers were significantly more frequent in Caucasians versus other races ( χ ( 2 ) test , P < 0.0001 ) . The LCS6 genotype was not associated with KRAS mutation status , clinicopathologic features ( all P > 0.2 ) , or DFS ( log-rank P = 0.49 ; HR , 0.929 ; 95 % confidence interval , 0.76-1.14 ) , even after combining LCS6 genotype with KRAS mutation status . CONCLUSIONS In the largest association study investigating the LCS6 polymorphism in colon cancers , the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors .

compared with paired tumor tissue

disease-free survival ( DFS )

patients defined by LCS6 variant status

in Caucasians versus other races

patients with stage III tumors


Effect of propranolol on facial scanning in autism spectrum disorder : a preliminary investigation . BACKGROUND Autism spectrum disorder ( ASD ) is a neurodevelopmental disorder characterized by social communication impairments and restricted , repetitive behaviors . Whereas current pharmacological interventions for ASD focus primarily on psychiatric symptoms , including agitation and obsessive behaviors , few agents target core symptomatology . It has been previously hypothesized that abnormalities in facial scanning , such as reduced eye contact or increased mouth fixation , contribute to social communication deficits in ASD . In addition , previous reports have suggested elevated stress and anxiety in ASD , symptoms that are believed to impact facial scanning patterns . OBJECTIVES The present pilot study sought to explore the effects of pharmacological intervention via propranolol , a nonselective β-adrenergic antagonist and known anxiolytic , on facial scanning in ASD . Specifically , we wished to determine whether there is an increase in eye contact and a decrease in mouth fixation with administration of propranolol . METHOD A sample of 14 participants with ASD and 14 matched controls participated in two study sessions in which propranolol and placebo were administered in a counterbalanced , double-blinded manner . At each session , ocular fixation data were collected during presentation of video stimuli of 16 human faces . Fixation time on the eye , nose , and mouth regions of the face stimuli was analyzed . RESULTS The baseline fixation patterns for the ASD and control groups did not significantly differ ; however , administration of propranolol was associated with a significant reduction in mouth fixation for the ASD group . Additionally , mouth fixation was positively related to nonverbal communication impairment in the ASD group . CONCLUSIONS Although eye fixation in ASD appears typical in the present study , the effect of propranolol in reducing mouth fixation suggests an important focus for further research . Future studies are needed to better characterize the relationship between stress and anxiety and facial scanning in ASD , as well as the effects of pharmacological intervention .

propranolol

propranolol

ocular fixation data

mouth fixation

autism spectrum disorder :

Autism spectrum disorder ( ASD )

14 participants

the ASD and control groups


Effect of a mixed kinesio taping-compression technique on quality of life and clinical and gait parameters in postmenopausal women with chronic venous insufficiency : double-blinded , randomized controlled trial . OBJECTIVE To investigate the short-term effect of a mixed Kinesio taping ( KT ) model on range of ankle motion ( ROAM ) , gait , pain , perimeter of lower limbs , and quality of life in postmenopausal women with chronic venous insufficiency ( CVI ) . DESIGN Double-blinded , randomized controlled trial . SETTING Clinical setting . PARTICIPANTS Consecutive postmenopausal women ( N=130 ; mean age ± SD , 65.44±14.7y ) with mild CVI . No participant withdrew because of adverse effects . INTERVENTION Participants were randomly assigned to either ( 1 ) an experimental group to receive a mixed KT-compression treatment following KT recommendations for gastrocnemius muscle enhancement and functional correction of the ankle , and adding 2 tapes to simulate traditional compression bandages ( no KT guidelines ) ; or ( 2 ) a placebo control group for sham KT . Both interventions were performed 3 times a week during a 4-week period . MAIN OUTCOME MEASURES ROAM , gait , pain , perimeter of right and left lower limb , and quality of life were assessed at baseline and 48 hours posttreatment . RESULTS Quality of life was better in the intervention group by a mean of 8.76 points ( 95 % confidence interval [ CI ] , 4.96-12.55 ) . The experimental group also showed significant pre-/posttreatment improvements in both lower limbs in gait dorsiflexion ROAM ( 95 % CI , 1.02-2.49 ) , cadence ( 95 % CI , 3.45-1.47 ) , stride length ( 95 % CI , 21.48-10.83 ) , step length ( 95 % CI , 1.68-6.61 ) , stance phase ( 95 % CI , 61-107 ) , and foot ( 95 % CI , .56-.92 ) and malleolus ( 95 % CI , 1.15-1.63 ) circumference . None of these variables were significantly modified in the placebo group . Both groups reported a significant reduction in pain . CONCLUSIONS Ankle dorsiflexion during gait , walking parameters , peripheral edema , venous pain , and quality of life remain improved in patients with CVI at 1 month after mixed KT-compression therapy . KT may have a placebo effect on pain perception .

Kinesio taping

quality of life

clinical

gait parameters

range of ankle motion ( ROAM ) , gait ,

pain

postmenopausal

women

chronic venous insufficiency

postmenopausal

chronic venous insufficiency ( CVI )


The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905 . OBJECTIVE To explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk , as well as the association of microRNA ( miRNA ) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials . METHODS/MATERIALS The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls . miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics , and survival outcomes were evaluated by variant allele type . RESULTS The KRAS-variant was not significantly associated with overall endometrial cancer risk ( 14 % controls and 17 % type 1 cancers ) , although was enriched in type 2 endometrial cancers ( 24 % , p = 0.2 ) . In the combined analysis of RTOG 9708/9905 , miRNA expression differed by age , presence of lymphovascular invasion and KRAS-variant status . Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100 % and 77 % ( HR 0.3 , p = 0.24 ) , respectively , favoring the variant . CONCLUSIONS The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers . In addition , tumor miRNA expression appears to be associated with patient age , lymphovascular invasion and the KRAS-variant , supporting the hypothesis that altered tumor biology can be measured by miRNA expression , and that the KRAS-variant likely impacts endometrial tumor biology .

overall endometrial cancer risk

9708/9905 , miRNA expression

status

Overall survival rates

endometrial cancer

women

type 1 or 2 endometrial cancer

tumor

type 1 endometrial cancer

variant and wild-type alleles


Classification of motor imagery performance in acute stroke . OBJECTIVE Effective motor imagery performance , seen as strong suppression of the sensorimotor rhythm , is the key element in motor imagery therapy . Therefore , optimization of methods to classify whether the subject is performing the imagery task is a prerequisite . An optimal classification method should have high performance accuracy and use a small number of channels . We investigated the additional benefit of the common spatial pattern filtering ( CSP ) to a linear discriminant analysis ( LDA ) classifier , for different channel configurations . METHODS Ten hemispheric acute stroke patients and 11 healthy subjects were included . EEGs were recorded using 60 channels . The classifier was trained with a motor execution task . For both healthy controls and patients , analysis of recordings was initially limited to 3 and 11 electrodes recording from the motor cortex area , and later repeated using 45 electrodes . RESULTS No significant improvement on the addition of CSP to LDA was found ( in both cases , the area under the receiving operating characteristic ( AU-ROC ) ≈ 0.70 ( acceptable ) ) . We then repeated the LDA+CSP method on recordings of 45 electrodes , since the use of imagery neuronal circuits may well extend beyond the motor area . AU-ROC rose to 0.90 , but no virtual 'most responsible ' electrode was observed . Finally , in mild-to-moderate stroke patients we could successfully use the EEG data recorded from the healthy hemisphere to train the classifier ( AU-ROC ≈ 0.70 ) . SIGNIFICANCE Including only the channels on the unaffected motor cortex is sufficient to train a classifier .

motor imagery therapy .

EEGs

motor imagery performance

Effective motor imagery performance

LDA

acute stroke

Ten

in mild-to-moderate stroke patients


Effectiveness and Safety of Tapentadol Prolonged Release ( PR ) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe , Chronic Low Back Pain With a Neuropathic Component : A Randomized , Double-blind , Phase 3b Study . OBJECTIVE To evaluate the effectiveness and tolerability of tapentadol PR monotherapy versus tapentadol PR/pregabalin combination therapy for severe , chronic low back pain with a neuropathic component . METHODS Eligible patients had painDETECT " unclear " or " positive " ratings and average pain intensity ≥ 6 ( 11-point NRS-3 [ average 3-day pain intensity ] ) at baseline . Patients were titrated to tapentadol PR 300 mg/day over 3 weeks . Patients with ≥ 1-point decrease in pain intensity and average pain intensity ≥ 4 were randomized to tapentadol PR ( 500 mg/day ) or tapentadol PR ( 300 mg/day ) /pregabalin ( 300 mg/day ) during an 8-week comparative period . RESULTS In the per-protocol population ( n = 288 ) , the effectiveness of tapentadol PR was clinically and statistically comparable to tapentadol PR/pregabalin based on the change in pain intensity from randomization to final evaluation ( LOCF ; LSMD [ 95 % CI ] , -0.066 [ -0.57 , 0.43 ] ; P < 0.0001 for noninferiority ) . Neuropathic pain and quality-of-life measures improved significantly in both groups . Tolerability was good in both groups , in line with prior trials in the high dose range of 500 mg/day for tapentadol PR monotherapy , and favorable compared with historical combination trials of strong opioids and anticonvulsants for combination therapy . The incidence of the composite of dizziness and/or somnolence was significantly lower with tapentadol PR ( 16.9 % ) than tapentadol PR/pregabalin ( 27.0 % ; P = 0.0302 ) . CONCLUSIONS Tapentadol PR 500 mg is associated with comparable improvements in pain intensity and quality-of-life measures to tapentadol PR 300 mg/pregabalin 300 mg , with improved central nervous system tolerability , suggesting that tapentadol PR monotherapy may offer a favorable treatment option for severe low back pain with a neuropathic component .

Tapentadol

tapentadol PR

tapentadol PR/pregabalin

tapentadol

Effectiveness and Safety

effectiveness and tolerability

decrease in pain intensity

average pain intensity

( n = 288 ) , the

for noninferiority ) .

Neuropathic pain and quality-of-life

of the composite of dizziness

severe low back pain


LNH-84 regimen : a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma . From July 1984 to September 1987 , 737 patients with aggressive malignant lymphoma ( ML ) were treated by an intensive regimen ( LNH-84 ) comprising three or four courses of doxorubicin , 75 mg/m2 ; cyclophosphamide , 1,200 mg/m2 ; vindesine , 2 mg/m2 x 2 ; bleomycin , 10 mg x 2 ; and prednisolone , 60 mg/m2 x 5 ( ACVB ) , consolidation with high-dose methotrexate , ifosfamide , etoposide , asparaginase , and cytarabine , and a randomized late intensification with two courses of cytarabine , cyclophosphamide , teniposide , bleomycin , and prednisone ( AraCVmB ) . Four hundred forty-two patients had intermediate-grade ML , 221 highgrade ML , and 74 unclassified ML . Most of the patients had advanced disease : stage IIE ( 23 % ) , III ( 13 % ) , or IV ( 47 % ) ; 38 % disseminated nodes ; 38 % two or more extranodal sites ; and 41 % a tumoral mass greater than 10 cm . Five hundred fifty-three patients ( 75 % ) went into complete remission ( CR ) , 63 ( 9 % ) into partial remission , 62 ( 8 % ) failed to respond , and 59 ( 8 % ) died during ACVB courses , 17 of them from progression of the disease . With a median follow-up of 23 months , the estimated 2-year overall survival time to failure ( TTF ) , and time to relapse ( TTR ) survival are 67 % , 56 % , and 67 % , respectively . Patients receiving a late intensification had the same relapse rate as the other patients . A persistent fibronecrotic mass was found in 150 patients ( 20 % ) and did not influence the relapse rate . Toxicity was mainly neutropenia and infection during the ACVB courses , with 40 patients ( 5 % ) dying from septic complications while responding to treatment . Fifty-three percent of the patients had a neutropenia less than 0.500 x 10 ( 9 ) /L , 58 % fever ( 6 % grade 4 ) , and 49 % a documented infection ( 8 % grade 4 ) . These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML .

intensive regimen ( LNH-84 )

doxorubicin

cyclophosphamide

vindesine

bleomycin

prednisolone

complete remission ( CR )

partial remission

failed to respond

died

time to relapse ( TTR ) survival

relapse rate

persistent fibronecrotic mass

relapse rate .

Toxicity

neutropenia

infection

dying from septic complications

neutropenia

documented infection

Four hundred forty-two patients


Correlations between the clinical , histological and neurophysiological examinations in patients before and after parotid gland tumor surgery : verification of facial nerve transmission . Parotid gland tumor surgery sometimes leads to facial nerve paralysis . Malignant more than benign tumors determine nerve function preoperatively , while postoperative observations based on clinical , histological and neurophysiological studies have not been reported in detail . The aims of this pilot study were evaluation and correlations of histological properties of tumor ( its size and location ) and clinical and neurophysiological assessment of facial nerve function pre- and post-operatively ( 1 and 6 months ) . Comparative studies included 17 patients with benign ( n = 13 ) and malignant ( n = 4 ) tumors . Clinical assessment was based on House-Brackmann scale ( H-B ) , neurophysiological diagnostics included facial electroneurography [ ENG , compound muscle action potential ( CMAP ) ] , mimetic muscle electromyography ( EMG ) and blink-reflex examinations ( BR ) . Mainly grade I of H-B was recorded both pre- ( n = 13 ) and post-operatively ( n = 12 ) in patients with small ( 1.5-2.4 cm ) benign tumors located in superficial lobes . Patients with medium size ( 2.5-3.4 cm ) malignant tumors in both lobes were scored at grade I ( n = 2 ) and III ( n = 2 ) pre- and mainly VI ( n = 4 ) post-operatively . CMAP amplitudes after stimulation of mandibular marginal branch were reduced at about 25 % in patients with benign tumors after surgery . In the cases of malignant tumors CMAPs were not recorded following stimulation of any branch . A similar trend was found for BR results . H-B and ENG results revealed positive correlations between the type of tumor and surgery with facial nerve function . Neurophysiological studies detected clinically silent facial nerve neuropathy of mandibular marginal branch in postoperative period . Needle EMG , ENG and BR examinations allow for the evaluation of face muscles reinnervation and facial nerve regeneration .

parotid gland tumor surgery

pre- and post-operatively

facial electroneurography

mimetic muscle electromyography

blink-reflex examinations

H-B

CMAP amplitudes

CMAPs

BR results . H-B and ENG

Needle EMG , ENG and BR examinations

parotid gland tumor surgery

benign

malignant

tumors

benign tumors


Moderate sodium restriction , angiotensin converting enzyme inhibition , and thiazide diuretic in the management of essential hypertension . Dietary sodium restriction alone is effective in lowering blood pressure in some , but not all , patients with essential hypertension . Homeostatic mechanisms , including activation of the renin-aldosterone system , may counteract the effects of sodium restriction . Angiotensin converting enzyme ( ACE ) inhibitors are also effective as sole therapy in many patients with essential hypertension , but may be less effective in those with low-renin hypertension . The combination of dietary sodium restriction with blockade of the renin system by an ACE inhibitor is a particularly effective way to improve blood pressure control . Addition of a thiazide diuretic will reduce pressure further .

Moderate sodium restriction

thiazide diuretic

Dietary sodium restriction

sodium

combination of

dietary sodium restriction

ACE inhibitor

thiazide diuretic

blood pressure

effective

blood pressure control .

pressure

essential hypertension


[ Dexmedetomidine use for postoperative adrenergic analgesia and sedation in abdominal surgery ] . Comparative study of postoperative analgesia and sedation with trimeperidine and dexmedetomidine and their effects on haemodynamics and vegetative nervous system was performed . Assessment of analgesia and sedation during vagotonia ( first part of the study ) and hypokinetic type of haemodynamics ( second part of the study ) was carried out with visual analogue scale ( VAS ) and Richmond scale . Results of the study showed that dexmedetomidine is more effective and safer than trimeperidine for analgesia and sedation in patients with spontaneous breathing after abdominal surgery . Dexmedetomidine use allows keeping optimal type of haemodynamics and vegetative nervous system parameters on first day of postoperative period .

Dexmedetomidine

trimeperidine

dexmedetomidine

dexmedetomidine

trimeperidine

Dexmedetomidine

visual analogue scale ( VAS )

Richmond scale

effective and safer

analgesia and sedation


Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients . The aim of this study was to investigate the association of PAX4 variants with therapeutic effect of oral antidiabetic drugs in Chinese type 2 diabtes mellitus ( T2DM ) patients . A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks , and the therapeutic effects were compared . In the rosiglitazone cohort , rs6467136 GA+AA carriers showed greater decrease in 2-h glucose levels ( P=0.0063 ) and higher cumulative attainment rates of target 2-h glucose levels ( Plog rank=0.0093 ) than GG homozygotes . In the subgroup with defective β-cell function , rs6467136 GA+AA carriers exhibited greater decrements of 2-h glucose level and improvement of homeostasis model assessment of insulin resistance ( P=0.0143 ) . Moreover , GA+AA carriers were more likely to attain the target fasting and 2-h glucose level ( Plog rank=0.0091 and 0.007 , respectively ) . However , these single-nucleotide polymorphisms showed no effect on repaglinide efficacy . In conclusion , PAX4 variant rs6467136 was associated with the therapeutic effect of rosiglitazone in Chinese T2DM patients .

oral antidiabetic drugs

oral antidiabetic drugs

repaglinide

rosiglitazone

rosiglitazone

Chinese type 2 diabetes patients

PAX4 variants

A total

in Chinese


Evidence-based narratives to improve recall of opioid prescribing guidelines : a randomized experiment . OBJECTIVES Physicians adopt evidence-based guidelines with variable consistency . Narratives , or stories , offer a novel dissemination strategy for clinical recommendations . The study objective was to compare whether evidence-based narrative versus traditional summary improved recall of opioid prescribing guidelines from the American College of Emergency Physicians ( ACEP ) . METHODS This was a prospective , randomized controlled experiment to compare whether narrative versus summary promoted short-term recall of six themes contained in the ACEP opioid guideline . The experiment was modeled after the free-recall test , an established technique in studies of memory . At a regional conference , emergency physicians ( EPs ) were randomized to read either a summary of the guideline ( control ) or a narrative ( intervention ) . The fictional narrative was constructed to match the summary in content and length . One hour after reading the text , participants listed all content that they could recall . Two reviewers independently scored the responses to assess recall of the six themes . The primary outcome was the total number of themes recalled per participant . Secondary outcomes included the proportion of responses in each study arm that recalled individual themes and the proportion of responses in each arm that contained falsely recalled or extraneous information . RESULTS Ninety-five physicians were randomized . Eighty-two physicians completed the experiment , for a response rate of 86 % . The mean of the total number of themes recalled per participant was 3.1 in the narrative arm versus 2.0 in the summary arm ( difference = 1.1 , 95 % confidence interval [ CI ] = 0.6 to 1.7 ) . For three themes , the proportion of responses that recalled the theme was significantly greater in the narrative arm compared to the summary arm , with the differences ranging from 20 % to 51 % . For one theme , recall was significantly greater in the summary arm . For two themes , there was no statistically significant difference in recall between the arms . In the summary arm , 54 % of responses were found to contain falsely recalled or extraneous information versus 21 % of responses in the narrative arm ( difference = 33 % , 95 % CI = 14 % to 53 % ) . CONCLUSIONS Physicians exposed to a narrative about opioid guidelines were more likely to recall guideline content at 1 hour than those exposed to a summary of the guidelines . Future studies should examine whether the incorporation of narratives in dissemination campaigns improves guideline adoption and changes clinical practice

Evidence-based narratives

evidence-based narrative

traditional summary

narrative

summary

opioid guidelines

recall

assess recall

proportion of responses

recalled individual

proportion of responses

recall

recall

Ninety-five

Eighty-two


MRI-detected skull-base invasion : prognostic value and therapeutic implication in intensity-modulated radiotherapy treatment for nasopharyngeal carcinoma . PURPOSE With advances in imaging and radiotherapy , the prognostic value of skull-base invasion in nasopharyngeal carcinoma ( NPC ) needs to be reassessed . We aimed to define a classification system and evaluate the prognostic value of the classification of magnetic resonance imaging ( MRI ) -detected skull-base invasion in NPC treated with intensity-modulated radiotherapy ( IMRT ) . PATIENTS AND MATERIALS We retrospectively reviewed 749 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated NPC and treated with IMRT . RESULTS MRI-detected skull-base invasion was not found to be an independent prognostic factor for overall survival ( OS ) , distant metastasis-free survival ( DMFS ) , local relapse-free survival ( LRFS ) , or disease-free survival ( DFS ; p > 0.05 for all ) . Skull-base invasion was classified according to the incidence of each site ( type I sites inside pharyngobasilar fascia and clivus vs. type II sites outside pharyngobasilar fascia ) . The 5-year OS , DMFS , LRFS , and DFS rates in the classification of skull-base invasion in NPC were 83 vs. 67 % , 85 vs.75 % , 95 vs. 88 % , and 76 vs. 62 % , respectively ( p < 0.05 for all ) . Multivariate analysis indicated the classification of skull-base invasion was an independent prognostic factor . CONCLUSION MRI-detected skull-base invasion is not an independent prognostic factor in patients with NPC treated with IMRT . However , classification according to the site of invasion has prognostic value . Therefore , patients with various subclassifications of stage T3 disease may receive treatment with different intensities ; however , further studies are warranted to prove this .

intensity-modulated radiotherapy

5-year OS

DMFS

LRFS

DFS

nasopharyngeal carcinoma .

nondisseminated NPC


Cognitive control therapy and transcranial direct current stimulation for depression : a randomized , double-blinded , controlled trial . BACKGROUND Based on findings that major depressive disorder ( MDD ) is associated to decreased dorsolateral prefrontal cortical ( DLPFC ) activity ; interventions that increase DLPFC activity might theoretically present antidepressant effects . Two of them are cognitive control therapy ( CCT ) , a neurocognitive intervention that uses computer-based working memory exercises , and transcranial direct current stimulation ( tDCS ) , which delivers weak , electric direct currents over the scalp . METHODS We investigated whether tDCS enhanced the effects of CCT in a double-blind trial , in which participants were randomized to sham tDCS and CCT ( n=17 ) vs. active tDCS and CCT ( n=20 ) . CCT and tDCS were applied for 10 consecutive workdays . Clinicaltrials.gov identifier : NCT01434836 . RESULTS Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up , with a response rate of approximately 25 % . Older patients and those who presented better performance in the task throughout the trial ( possibly indicating greater engagement and activation of the DLPFC ) had greater depression improvement in the combined treatment group . LIMITATIONS Our exploratory findings should be further confirmed in prospective controlled trials . DISCUSSION CCT and tDCS combined might be beneficial for older depressed patients , particularly for those who have cognitive resources to adequately learn and improve task performance over time . This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy .

Cognitive control therapy

transcranial direct current stimulation

cognitive control therapy ( CCT )

transcranial direct current stimulation

CCT

sham tDCS

CCT

active tDCS

CCT

CCT

tDCS

stimulation for depression :

effects of CCT

ameliorated depressive symptoms

response rate

depression improvement

task performance

Older patients

older


[ The effects of tirofiban on acute non-ST segment elevation myocardial infarction patients not receiving early reperfusion intervention ] . OBJECTIVE To study the efficacy and safety of tirofiban in patients with acute non-ST- segment elevation myocardial infarction ( NSTEMI ) without early reperfusion intervention . METHODS A total of 151 NSTEMI patients without early reperfusion intervention were enrolled in the study and randomized to the tirofiban group ( n = 76 ) and the control group ( n = 75 ) . Coronary angiography was performed at day 3 and day 7 , while percutaneous coronary intervention ( PCI ) was performed when necessary . Parameters including thrombolysis in myocardial infarction ( TIMI ) flow , bleeding complications and clinic events within 30 days were compared between the two groups . RESULTS Before PCI , no increase in the percentage of patient with TIMI flow better than TIMI-2 was observed by the treatment of tirofiban ( 69.3 % vs 78.9 % , P = 0.10 ) . While after PCI , significant increase in the percentage of patient with TIMI flow better than TIMI-2 was manifested in the tirofiban group ( 96.0 % vs 100.0 % , P = 0.04 ) . Tirofiban treatment also significantly decreased the rate of poor myocardial perfusion after PCI ( 19.7 % vs 34.7 % , P = 0.04 ) . There were 0 and 4 major adverse cardiovascular events ( MACE ) within 30 days observed in the tirofiban group and the control group ( 0.0 % vs 5.3 % , P = 0.05 ) . No difference between the two groups was found in the bleeding complications within 30 days including the mild hemorrhage ( 5 vs 4 cases , P = 0.75 ) , severe hemorrhage ( 2 vs 1 cases , P = 0.56 ) or severe thrombocytopenia ( 2 vs 0 cases , P = 0.49 ) . CONCLUSIONS Tirofiban treatment does not increase the bleeding complications in NSTEMI patients without early PCI . Tirofiban can improve the TIMI flow and the myocardial perfusion after PCI with less MACE within 30 days .

tirofiban

tirofiban

tirofiban

control group

Coronary angiography

intervention

tirofiban

tirofiban

tirofiban

myocardial infarction

efficacy and safety

bleeding complications

percentage of patient with TIMI flow

percentage of patient with TIMI flow

rate of poor myocardial perfusion

bleeding complications

mild hemorrhage

severe hemorrhage

severe thrombocytopenia

bleeding complications

myocardial infarction

NSTEMI

NSTEMI


To excise or ablate endometriosis ? A prospective randomized double-blinded trial after 5-year follow-up . STUDY OBJECTIVE To compare reduction of pain after laparoscopy for ablation or excision of endometriosis . DESIGN Prospective , randomized , double-blind study ( Canadian Task Force classification I ) . SETTING Endometriosis and pelvic pain clinic at a university teaching hospital . PATIENTS Women of reproductive age with pelvic pain and visually proved endometriosis . INTERVENTIONS Subjects completed a questionnaire rating various kinds of pain using visual analog scales ( VAS ) . After visual identification subjects were randomized to treatment via ablation or excision by supervised training gynecologists as primary surgeons . Follow-up questionnaires documented pain levels every 3 months for 1 year and then every 6 months for 5 years . MEASUREMENTS AND MAIN RESULTS Change in pain VAS scores during 5 years after the operation and rates of pregnancy , repeat surgery , and use of hormone therapy were evaluated . There was a reduction in all pain scores over the 5-year follow-up in both treatment groups . A significantly greater reduction in dyspareunia VAS scores was observed in the excision group at 5 years ( p = .03 at univariate analysis , and p = .007 at multivariate analysis ) . More women in the ablation group continued to receive medical treatment of endometriosis at 5 years ( p = .004 ) . CONCLUSIONS Surgical treatment of endometriosis provides symptom reduction for up to 5 years . In some limited areas such as deep dyspareunia , excision is more effective than ablation .

excise

or

ablate

ablation

excision

questionnaire rating

ablation

or

excision

excision

ablation

pain levels

Change in pain VAS scores

rates of pregnancy

repeat surgery

use of hormone therapy

pain scores

dyspareunia VAS scores

medical treatment of endometriosis

endometriosis

Endometriosis

pelvic pain

Women

pelvic pain

endometriosis


Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention . OBJECTIVE Weight losses in lifestyle interventions are variable , yet prediction of long-term success is difficult . The utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes was examined . METHODS Participants included 2327 adults with type 2 diabetes ( BMI:35.8 ± 6.0 ) randomized to the intensive lifestyle intervention ( ILI ) of the Look AHEAD trial . ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake . 1-month , 2-month , and 1-year weight changes were calculated . RESULTS Participants failing to achieve a ≥2 % weight loss at Month 1 were 5.6 ( 95 % CI:4.5 , 7.0 ) times more likely to also not achieve a ≥10 % weight loss at Year 1 , compared to those losing ≥2 % initially . These odds were increased to 11.6 ( 95 % CI:8.6 , 15.6 ) when using a 3 % weight loss threshold at Month 2 . Only 15.2 % and 8.2 % of individuals failing to achieve the ≥2 % and ≥3 % thresholds at Months 1 and 2 , respectively , go on to achieve a ≥10 % weight loss at Year 1 . CONCLUSIONS Given the association between initial and 1-year weight loss , the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts . TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT00017953 .

early weight loss

increase physical activity

reduce caloric intake

1-year weight changes

achieve a ≥2 % weight loss at Month

a ≥10 % weight loss at

using a 3 % weight

on to achieve a ≥10 % weight

adults

type 2 diabetes


Comparison of olanzapine long-acting injection and oral olanzapine : a 2-year , randomized , open-label study in outpatients with schizophrenia . We compared long-term treatment effectiveness of monthly olanzapine long-acting injection ( LAI ) with that of oral olanzapine . Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI ( n = 264 ) or 10 mg/d of oral olanzapine ( n = 260 ) for 2 years of open-label treatment . Dosing thereafter was flexible ( 150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral ) . Primary outcome was time to all-cause discontinuation . At baseline , patients were clinically stable ( mean Positive and Negative Syndrome Scale total score of 57 ) . Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months , and 4.6 % were rated nonadherent in the month before study entry . The groups did not differ significantly in median time to all-cause discontinuation ( 645 days for LAI , 678 days for oral ; P = 0.61 ) , discontinuation rate ( 53.8 % for LAI , 51.2 % for oral ; P = 0.60 ) , or relapse rate ( 20.1 % for LAI , 18.5 % for oral ; P = 0.66 ) . Postbaseline psychiatric hospitalization rate was low for both groups ( 7.6 % for LAI , 9.2 % for oral ) , but mean hospitalization duration was significantly longer for oral patients ( 1.80 days [ 20 for those hospitalized ] vs 0.43 days [ 6 for those hospitalized ] , P = 0.02 ) . There were no clinically significant group differences in adverse events or safety measures . No post-injection delirium/sedation syndrome events occurred . In conclusion , olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia . Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine , despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome .

olanzapine long-acting injection

oral olanzapine

oral olanzapine .

olanzapine LAI

oral olanzapine

LAI

LAI

LAI

olanzapine LAI

olanzapine

olanzapine LAI

olanzapine

schizophrenia .

psychiatric

delirium/sedation syndrome

effective

tolerated

schizophrenia .

Treatment discontinuation


Sedation depth during spinal anesthesia and survival in elderly patients undergoing hip fracture repair . Low intraoperative Bispectral Index ( BIS ) values may be associated with increased mortality . In a previously reported trial to prevent delirium , we randomized patients undergoing hip fracture repair under spinal anesthesia to light ( BIS > 80 ) or deep ( BIS approximately 50 ) sedation . We analyzed survival of patients in the original trial . Among all patients , mortality was equivalent across sedation groups . However , among patients with serious comorbidities ( Charlson score > 4 ) , 1-year mortality was reduced in the light ( 22.2 % ) vs deep ( 43.6 % ) sedation group ( hazard ratio [ HR ] , 0.43 ; 95 % confidence interval , 0.19-0.97 ; P = 0.04 ) during spinal anesthesia . Similarly , among patients with Charlson score > 6 , 1-year mortality was reduced in the light ( 28.6 % ) vs deep ( 52.6 % ) sedation group ( HR 0.33 ; 95 % confidence interval , 0.12-0.94 ; P = 0.04 ) during spinal anesthesia . Further research on reduced mortality after light sedation during spinal anesthesia is needed .

spinal anesthesia

spinal anesthesia

light ( BIS > 80 )

deep ( BIS approximately 50 )

light

deep

sedation

light

deep

sedation

spinal anesthesia

light sedation

spinal anesthesia

Sedation depth

hip fracture repair

survival

mortality

1-year mortality

1-year mortality

reduced mortality


Hysteroscopic morcellation compared with electrical resection of endometrial polyps : a randomized controlled trial . OBJECTIVE To evaluate whether hysteroscopic morcellation or bipolar electrosurgical resection is more favorable for removing endometrial polyps in an office setting in terms of feasibility , speed , pain , and acceptability . METHODS A multicenter , single-blind , randomized , controlled trial of office hysteroscopic morcellation compared with electrosurgical resection was conducted . A total of 121 women were randomly allocated to polyp removal by one of the two methods in an office setting . The outcomes assessed were time taken to complete the endometrial polypectomy , defined as the time from insertion to removal of vaginal instrumentation , completeness of polyp removal , acceptability , and pain measured on a 100-mm visual analog scale . RESULTS The median time taken to complete the procedure was 5 minutes and 28 seconds for morcellation compared with 10 minutes and 12 seconds for electrosurgical resection ( P < .001 ) . The polyps were completely removed in 61 out of 62 ( 98 % ) women assigned to morcellation compared with 49 out of 59 ( 83 % ) women treated with electrosurgical resection ( odds ratio 12.5 ; 95 % confidence interval [ CI ] 1.5-100.6 ; P=.02 ) . The mean pain scores during the procedure favored morcellation by 16.1 points on average ( 35.9 compared with 52.0 ; 95 % CI for difference , -24.7 to -7.6 ; P < .001 ) . Overall , 99 % of women found office polypectomy to be acceptable , with only one woman in the electrosurgical resection group considering the procedure unacceptable . CONCLUSION In comparison to electrosurgical resection during hysteroscopic polypectomy , morcellation was significantly quicker , less painful , more acceptable to women , and more likely to completely remove endometrial polyps compared with electrosurgical resection . CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , www.clinicaltrials.gov , NCT01509313 .

Hysteroscopic morcellation

electrical resection

hysteroscopic morcellation

bipolar electrosurgical resection

office hysteroscopic morcellation

electrosurgical resection

morcellation

electrosurgical resection

morcellation

electrosurgical resection

electrosurgical resection

morcellation

electrosurgical resection

endometrial polyps

feasibility

speed

pain

acceptability

pain

polyps were completely removed

mean pain scores

acceptable

unacceptable

quicker

painful

acceptable

completely remove endometrial polyps

endometrial polyps


Development and in vitro/in vivo evaluation of immediate release perindopril tablets . Perindopril erbumine ( PE ) is a BCS ( Biopharmaceutics Classification System ) class 3 drug with high solubility and low permeability . It is an inhibitor of the enzyme that converts angiotensin I ( Angiotensin Converting Enzyme , ACE ) into angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide . The aim of this study was to develop an alternative drug product by using a different salt of perindopril and to evaluate the bioequivalence between PE , not still licensed , and perindopril arginine ( PA ) , licensed in many countries , and to prepare PE tablets by using direct compression method . Many different formulations were prepared , among which F3-coded formulation was only selected due to releasing of 98.03 % active substance at 45th minute . Bioequivalence study was planned as a cross-designed , randomized , open-labeled , single-dose , single-center study and conducted in 24 male healthy volunteers via peroral route . The results of bioequivalence study were evaluated for Perindopril and Perindoprilat according to Cmax , tmax and AUC criteria . The geometric mean ratios ( 90 % CI ) of perindopril and perindoprilat followed test and reference drug were calculated for AUC0-t and Cmax , 105.946 % ( 100.218-112.002 % ) and 110.437 % ( 102.534-118.948 % ) ; 109.542 % ( 98.364-121.992 % ) and 115.729 % ( 101.031-132.565 % ) , respectively . The 90 % confidence intervals of them were found within the standard bioequivalence range ( 80-125 % ) .

perindopril tablets

Perindopril erbumine ( PE )

perindopril

F3-coded formulation

Perindopril

Perindoprilat

perindopril

perindoprilat

Cmax

tmax and AUC criteria

geometric mean ratios

Cmax

bioequivalence range

male

healthy volunteers via peroral route


Virtual reality job interview training in adults with autism spectrum disorder . The feasibility and efficacy of virtual reality job interview training ( VR-JIT ) was assessed in a single-blinded randomized controlled trial . Adults with autism spectrum disorder were randomized to VR-JIT ( n = 16 ) or treatment-as-usual ( TAU ) ( n = 10 ) groups . VR-JIT consisted of simulated job interviews with a virtual character and didactic training . Participants attended 90 % of laboratory-based training sessions , found VR-JIT easy to use and enjoyable , and they felt prepared for future interviews . VR-JIT participants had greater improvement during live standardized job interview role-play performances than TAU participants ( p = 0.046 ) . A similar pattern was observed for self-reported self-confidence at a trend level ( p = 0.060 ) . VR-JIT simulation performance scores increased over time ( R ( 2 ) = 0.83 ) . Results indicate preliminary support for the feasibility and efficacy of VR-JIT , which can be administered using computer software or via the internet .

Virtual reality job interview training

VR-JIT

treatment-as-usual ( TAU )

VR-JIT

VR-JIT

TAU

VR-JIT

VR-JIT

easy to use

enjoyable

prepared for future interviews .

self-reported self-confidence

VR-JIT simulation performance scores

feasibility

efficacy

adults

autism spectrum disorder

Adults

autism spectrum disorder


Poor prognosis patients with inoperable locally advanced NSCLC and large tumors benefit from palliative chemoradiotherapy : a subset analysis from a randomized clinical phase III trial . INTRODUCTION Poor prognosis patients with bulky stage III locally advanced non-small-cell lung cancer may not be offered concurrent chemoradiotherapy ( CRT ) . Following a phase III trial concerning the effect of palliative CRT in inoperable poor prognosis patients , this analysis was performed to explore how tumor size influenced survival and health-related quality of life ( HRQOL ) . METHODS A total of 188 poor prognosis patients recruited in a randomized clinical trial received four courses intravenous carboplatin day 1 and oral vinorelbine day 1 and 8 , at 3-week intervals . The experimental arm ( N = 94 ) received radiotherapy with fractionation 42 Gy/15 , starting at the second chemotherapy course . This subset study compares outcomes in patients with tumors larger than 7 cm ( N = 108 ) versus tumors 7 cm or smaller ( N = 76 ) . RESULTS Among those with tumors larger than 7 cm , the median overall survival in the chemotherapy versus CRT arm was 9.7 and 13.4 months , respectively ( p = 0.001 ) . The 1-year survival was 33 % and 56 % , respectively ( p = 0.01 ) . Except for a temporary decline during treatment , HRQOL was maintained in the CRT arm , regardless of tumor size . Among those who did not receive CRT , patients with tumors larger than 7 cm experienced a gradual decline in the HRQOL . The CRT group had significantly more esophagitis and hospitalizations because of side effects regardless of tumor size . CONCLUSION In patients with poor prognosis and inoperable locally advanced non-small-cell lung cancer , large tumor size should not be considered a negative predictive factor . Except for performance status 2 , patients with tumors larger than 7 cm apparently benefit from CRT .

palliative chemoradiotherapy :

CRT

intravenous carboplatin

oral vinorelbine

chemotherapy

CRT

CRT

CRT

CRT

CRT .

effect

survival

and health-related

quality of life

( HRQOL )

median overall survival

1-year survival

HRQOL

HRQOL

significantly more esophagitis

side effects

Poor prognosis

poor prognosis


Reliable LC-MS/MS assay for the estimation of rilpivirine in human plasma : application to a bioequivalence study and incurred sample reanalysis . A simple , precise , and rapid stable isotope dilution liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of rilpivirine , a non-nucleoside reverse transcriptase inhibitor in human plasma . Rilpivirine and its deuterated analogue , rilpivirine-d6 , used as an internal standard ( IS ) were quantitatively extracted by liquid-liquid extraction with methyl-tert-butyl ether and diethyl ether solvent mixture from 50 μL plasma . The chromatography was achieved on Gemini C18 ( 150 × 4.6 mm , 5 µm ) analytical column in a run time of 2.2 min . The precursor → product ion transitions for rilpivirine ( m/z 367.1 → 128.0 ) and IS ( m/z 373.2 → 134.2 ) were monitored on a triple quadrupole mass spectrometer in the positive ionization mode . The linearity of the method was established in the concentration range of 0.5-200 ng/mL . The mean extraction recovery for rilpivirine ( 94.9 % ) and IS ( 99.9 % ) from spiked plasma samples was consistent and reproducible . The IS-normalized matrix factors for rilpivirine ranged from 0.98 to 1.02 across three quality controls . Bench top , freeze-thaw , wet extract , and long-term stability of rilpivirine was examined in spiked plasma samples . The application of the method was demonstrated by a bioequivalence study with 25 mg rilpivirine tablet formulation in 40 healthy subjects . The assay reproducibility was shown by reanalysis of 200 study samples and the % change in the concentration of repeat values from the original values was within ±15 % .

LC-MS/MS assay

estimation of rilpivirine

range of 0.5-200 ng/mL .

consistent

and

reproducible

. The IS-normalized

across three quality controls .

rilpivirine in human plasma :

rilpivirine

human plasma


Sociopsychological tailoring to address colorectal cancer screening disparities : a randomized controlled trial . PURPOSE Interventions tailored to sociopsychological factors associated with health behaviors have promise for reducing colorectal cancer screening disparities , but limited research has assessed their impact in multiethnic populations . We examined whether an interactive multimedia computer program ( IMCP ) tailored to expanded health belief model sociopsychological factors could promote colorectal cancer screening in a multiethnic sample . METHODS We undertook a randomized controlled trial , comparing an IMCP tailored to colorectal cancer screening self-efficacy , knowledge , barriers , readiness , test preference , and experiences with a nontailored informational program , both delivered before office visits . The primary outcome was record-documented colorectal cancer screening during a 12-month follow-up period . Secondary outcomes included postvisit sociopsychological factor status and discussion , as well as clinician recommendation of screening during office visits . We enrolled 1,164 patients stratified by ethnicity and language ( 49.3 % non-Hispanic , 27.2 % Hispanic/English , 23.4 % Hispanic/Spanish ) from 26 offices around 5 centers ( Sacramento , California ; Rochester and the Bronx , New York ; Denver , Colorado ; and San Antonio , Texas ) . RESULTS Adjusting for ethnicity/language , study center , and the previsit value of the dependent variable , compared with control patients , the IMCP led to significantly greater colorectal cancer screening knowledge , self-efficacy , readiness , test preference specificity , discussion , and recommendation . During the followup period , 132 ( 23 % ) IMCP and 123 ( 22 % ) control patients received screening ( adjusted difference = 0.5 percentage points , 95 % CI -4.3 to 5.3 ) . IMCP effects did not differ significantly by ethnicity/language . CONCLUSIONS Sociopsychological factor tailoring was no more effective than nontailored information in encouraging colorectal cancer screening in a multiethnic sample , despite enhancing sociopsychological factors and visit behaviors associated with screening . The utility of sociopsychological tailoring in addressing screening disparities remains uncertain .

screening

multiethnic sample

enrolled 1,164 patients

multiethnic sample


A trial of D-cycloserine to treat stereotypies in older adolescents and young adults with autism spectrum disorder . OBJECTIVES Autism spectrum disorders ( ASDs ) have core impairments in social communication as well as the presence of repetitive , stereotypic behaviors and restricted interests . Older adolescents and young adults are particularly impacted by these deficits . Preclinical data implicate glutamatergic dysfunction in the pathophysiology of ASDs . D-Cycloserine ( DCS ) , a partial glycineB agonist at the N-methyl-D-aspartic acid receptor site , has been shown to improve sociability in mouse models and a small human study . The sensitivity of the obligatory glycineB co-agonist binding site may change with daily administration of DCS as a result of agonist-induced desensitization . The efficacy of a " pulsed " once-weekly administration versus " daily " administration of DCS was compared . METHODS Males and females , ages 14 to 25 years , with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition Text Revision diagnosis of an ASD were enrolled in a double-blind , randomized 10-week trial consisting of 8 weeks of active drug with either weekly or daily administration of 50 mg of DCS followed by a 2-week follow-up visit . RESULTS For the purposes of this study , no statistical or clinical differences existed between the 2 dosage groups on the Aberrant Behavior Checklist subscale 3 , which measures stereotypies/repetitive movements . When combining groups , a statistically significant decrease of 37 % was found from baseline to week 8 when study drug was completed using a linear mixed effects model ( P = 0.003 ) . CONCLUSIONS D-Cycloserine was shown to be effective in improving stereotypic symptoms in older adolescents and young adults with ASDs measured by the Aberrant Behavior Checklist subscale 3 . In addition , DCS was safe and well tolerated .

D-cycloserine

D-Cycloserine ( DCS )

DCS

D-Cycloserine

DCS

efficacy

stereotypic symptoms

safe and well tolerated .

older adolescents

young adults

autism spectrum disorder

Males

females

ages 14 to 25 years ,


Caudal epidural analgesia using lidocaine alone or in combination with ketamine in dromedary camels Camelus dromedarius . This study was performed to investigate the analgesic effect of lidocaine and a combination of lidocaine and ketamine following epidural administration in dromedary camels . Ten 12-18-month-old camels were randomly divided into two equal groups . In group L , the animals received 2 % lidocaine ( 0.22 mg/kg ) and in group LK the animals received a mixture of 10 % ketamine ( 1 mg/kg ) and 2 % lidocaine ( 0.22 mg/kg ) administered into the first intercoccygeal ( Co1-Co2 ) epidural space while standing . Onset time and duration of caudal analgesia , sedation level and ataxia were recorded after drug administration . Data were analysed by U Mann-Whitney tests and significance was taken as p & lt ; 0.05 . The results showed that epidural lidocaine and co-administration of lidocaine and ketamine produced complete analgesia in the tail , anus and perineum . Epidural administration of the lidocaine-ketamine mixture resulted in mild to moderate sedation , whilst the animals that received epidural lidocaine alone were alert and nervous during the study . Ataxia was observed in all test subjects and was slightly more severe in camels that received the lidocaine-ketamine mixture . It was concluded that epidural administration of lidocaine plus ketamine resulted in longer caudal analgesia in standing conscious dromedary camels compared with the effect of administering lidocaine alone .

Caudal epidural analgesia

lidocaine alone

combination with ketamine

lidocaine

ketamine

lidocaine

epidural lidocaine

lidocaine and ketamine

lidocaine-ketamine mixture

epidural lidocaine

lidocaine-ketamine mixture .

lidocaine plus ketamine

lidocaine


Oral magnesium supplementation improves the metabolic profile of metabolically obese , normal-weight individuals : a randomized double-blind placebo-controlled trial . BACKGROUND AND AIMS We undertook this study to determine the efficacy of oral magnesium supplementation in the improvement of the metabolic profile and blood pressure in metabolically obese , normal-weight ( MONW ) individuals . METHODS A total of 47 MONW individuals with hypomagnesemia were enrolled in clinical a randomized double-blind placebo-controlled trial . Individuals in the intervention group received 30 mL of MgCl2 5 % solution ( equivalent to 382 mg of magnesium ) and individuals in the control group 30 mL of placebo solution , once daily during 4 months . In the absence of obesity or overweight , the presence of fasting glucose levels ≥100 mg/dL , HOMA-IR index ≥3 , triglyceride levels ≥150 mg/dL and/or systolic and diastolic blood pressure ≥140 and 90 mmHg defined the presence of the MONW phenotype . Hypomagnesemia was defined by serum magnesium concentration ≤1.8 mg/dL . RESULTS At basal conditions there were no significant differences between groups . At the end of follow-up , changes in the mean of systolic ( -2.1 vs. 3.9 % mmHg , p < 0.05 ) and diastolic ( -3.8 vs. 7.5 % mmHg , p < 0.05 ) blood pressures , HOMA-IR index ( -46.5 vs. -5.4 % , p < 0.0001 ) , fasting glucose ( -12.3 vs. -1.8 % mg/dL , p < 0.05 ) and triglyceride levels ( -47.4 % vs. 10.1 % mg/dL , p < 0.0001 ) were significantly lower in the subjects who received MgCl2 compared with individuals in the control group . CONCLUSIONS Oral magnesium supplementation improves the metabolic profile and blood pressure of MONW individuals .

Oral magnesium supplementation

magnesium

magnesium

efficacy

metabolic profile

blood pressure

fasting glucose levels


Changes in spinal inhibitory networks induced by furosemide in humans . During neural development in animals , GABAergic and glycinergic neurons are first excitatory , and then become inhibitory in the mature state . This developmental shift is due mainly to strong expression of the cation-chloride K-Cl cotransporter 2 ( KCC2 ) and down-regulation of Na-K-Cl cotransporter 1 ( NKCC1 ) during maturation . The down-regulation of co-transporter KCC2 after spinal cord transection in animals leads to the depolarising ( excitatory ) action of GABA and glycine and thus results in a reduction of inhibitory synaptic efficiency . Furosemide , a loop diuretic , has been shown to selectively and reversibly block inhibitory postsynaptic potentials without affecting excitatory postsynaptic potentials in animal spinal neurons . Moreover , this diuretic has been also demonstrated to block the cation-chloride co-transporters . Here , we used furosemide to demonstrate changes in spinal inhibitory networks in healthy human subjects . Non-invasive electrophysiological techniques were used to assess presynaptic inhibition , postsynaptic inhibition and the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons in the spinal cord . Orally administered furosemide , at doses commonly used in the clinic ( 40 mg ) , significantly reduced spinal inhibitory interneuronal activity for at least 70 min from intake compared to control experiments in the same subjects while no changes were observed in the efficacy of synaptic transmission between muscle afferent terminals and soleus motoneurons . The reduction of inhibition was dose-dependent . Our results provide indirect evidence that reversible changes in the cation-chloride transport system induce modulations of inhibitory neuronal activity at spinal cord level in humans .

furosemide

Furosemide

furosemide

reduction of inhibition

changes


Communication interventions for minimally verbal children with autism : a sequential multiple assignment randomized trial . OBJECTIVE This study tested the effect of beginning treatment with a speech-generating device ( SGD ) in the context of a blended , adaptive treatment design for improving spontaneous , communicative utterances in school-aged , minimally verbal children with autism . METHOD A total of 61 minimally verbal children with autism , aged 5 to 8 years , were randomized to a blended developmental/behavioral intervention ( JASP+EMT ) with or without the augmentation of a SGD for 6 months with a 3-month follow-up . The intervention consisted of 2 stages . In stage 1 , all children received 2 sessions per week for 3 months . Stage 2 intervention was adapted ( by increased sessions or adding the SGD ) based on the child 's early response . The primary outcome was the total number of spontaneous communicative utterances ; secondary measures were the total number of novel words and total comments from a natural language sample . RESULTS Primary aim results found improvements in spontaneous communicative utterances , novel words , and comments that all favored the blended behavioral intervention that began by including an SGD ( JASP+EMT+SGD ) as opposed to spoken words alone ( JASP+EMT ) . Secondary aim results suggest that the adaptive intervention beginning with JASP+EMT+SGD and intensifying JASP+EMT+SGD for children who were slow responders led to better posttreatment outcomes . CONCLUSION Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel , blended intervention that focuses on joint engagement and play skills and incorporates an SGD . Future studies should further explore the tailoring design used in this study to better understand children 's response to treatment . Clinical trial registration information-Developmental and Augmented Intervention for Facilitating Expressive Language ( CCNIA ) ; http : //clinicaltrials.gov/ ; NCT01013545 .

Communication interventions

speech-generating device ( SGD )

adding the SGD )

spoken words alone ( JASP+EMT ) .

JASP+EMT+SGD

JASP+EMT+SGD

SGD

spontaneous , communicative utterances

spoken spontaneous language

children

autism

school-aged ,

autism

children

aged 5 to 8 years

school-aged children


Internet-based , randomized , controlled trial of omega-3 fatty acids for hyperactivity in autism . OBJECTIVE Preliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder ( ASD ) . We sought to examine the feasibility of a novel , Internet-based clinical trial design to evaluate the efficacy of this supplement . METHOD E-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network . All study procedures , including screening , informed consent , and collection of outcome measures took place over the Internet . The primary outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist ( ABC-H ) . RESULTS During the 6-week recruitment period , 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks . Outcome assessments were obtained from all 57 participants and 57 teachers , and the study was completed in 3 months . Children in the omega-3 fatty acid group had a greater reduction in hyperactivity ( -5.3 points ) compared to the placebo group ( -2.6 points ) , but the difference was not statistically significant ( 1.9-point greater improvement in the omega-3 group , 95 % CI = -2.2 to 5.2 ) . Adverse events were rare and not associated with omega-3 fatty acids . Participant feedback was positive . CONCLUSION Internet-based , randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials . A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids . Clinical trial registration information-Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder ; http : //clinicaltrials.gov ; NCT01694667 .

omega-3 fatty acids

omega-3 fatty acids

E-mail invitations

omega-3 fatty acids

an identical placebo

omega-3 fatty acid

placebo

omega-3 group

omega-3 fatty acids .

omega-3 fatty acids .

information-Omega-3 Fatty Acids

hyperactivity

hyperactivity

efficacy

hyperactivity

Adverse events

feedback

efficacy

hyperactivity in autism .

children

autism spectrum disorder ( ASD ) .

children aged 5 to 8 years

children

children

ASD


A randomized clinical trial comparison between pivotal response treatment ( PRT ) and structured applied behavior analysis ( ABA ) intervention for children with autism . Accumulating studies are documenting specific motivational variables that , when combined into a naturalistic teaching paradigm , can positively influence the effectiveness of interventions for children with autism spectrum disorder ( ASD ) . The purpose of this study was to compare two applied behavior analysis ( ABA ) intervention procedures , a naturalistic approach , pivotal response treatment ( PRT ) with a structured ABA approach in a school setting . A randomized clinical trial design using two groups of children , matched according to age , sex and mean length of utterance was used to compare the interventions . The data showed that the PRT approach was significantly more effective in improving targeted and untargeted areas after 3 months of intervention . The results are discussed in terms of variables that produce more rapid improvements in communication for children with ASD .

naturalistic teaching paradigm

PRT

improving targeted and untargeted areas

autism

children

autism spectrum disorder ( ASD

children


Causes of variation in BCG vaccine efficacy : examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses . BCG protection varies and in some places ( nearest the equator ) is low or absent . Understanding this variation can inform the efforts to develop new vaccines against tuberculosis . Two main hypotheses are used to explain this variation : under masking , new vaccines are unlikely to increase protection ; under blocking new vaccines have a greater potential to be effective when BCG is not . We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second ( revaccination ) time at school age in two sites ( Manaus close and Salvador further south from the equator ) . Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine ( BCG vaccination at school age ) or control group . Protection by first BCG vaccination at school age was high in Salvador ( 34 % , 95 % CI 7-53 % , p=0.017 ) but low in Manaus ( 8 % , 95 % CI t0 39-40 % , p=0.686 ) . For revaccination at school age , protection was modest in Salvador ( 19 % , 95 % CI 3-33 % , p=0.022 ) and absent in Manaus ( 1 % , 95 % CI to 27-23 % , p=0.932 ) . Vaccine efficacy for neonatal vaccination was similar in Salvador ( 40 % , 95 % CI 22-54 % , p < 0.001 ) and Manaus ( 36 % , 95 % CI 11-53 % , p=0.008 ) . Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth , which points towards blocking as the dominant mechanism . New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective .

BCG vaccine

BCG vaccine

BCG vaccination

control group

BCG vaccination

BCG

efficacy :

protection ;

Protection by first BCG vaccination

revaccination at school age

Vaccine efficacy

Variation in BCG efficacy

school age

children


Effect of glycemic load on eating behavior self-efficacy during weight loss . High eating behavior self-efficacy may contribute to successful weight loss . Diet interventions that maximize eating behavior self-efficacy may therefore improve weight loss outcomes . However , data on the effect of diet composition on eating behavior self-efficacy are sparse . To determine the effects of dietary glycemic load ( GL ) on eating behavior self-efficacy during weight loss , body weight and eating behavior self-efficacy were measured every six months in overweight adults participating in a 12-mo randomized trial testing energy-restricted diets differing in GL . All food was provided during the first six months and self-selected thereafter . Total mean weight loss did not differ between groups , and GL-level had no significant effect on eating behavior self-efficacy . In the combined cohort , individuals losing the most weight reported improvements in eating behavior self-efficacy , whereas those achieving less weight loss reported decrements in eating behavior self-efficacy . Decrements in eating behavior self-efficacy were associated with subsequent weight regain when diets were self-selected . While GL does not appear to influence eating behavior self-efficacy , lesser amounts of weight loss on provided-food energy restricted diets may deter successful maintenance of weight loss by attenuating improvements in eating behavior self-efficacy .

Diet interventions

provided-food energy restricted diets

eating behavior self-efficacy

body weight

eating behavior self-efficacy

Total mean weight loss

eating behavior self-efficacy

eating behavior self-efficacy

weight loss

eating behavior self-efficacy

eating behavior self-efficacy

weight

adults

diets


The Randomised Intervention Treatment of Angina ( RITA ) Trial protocol : a long term study of coronary angioplasty and coronary artery bypass surgery in patients with angina . The Randomised Intervention Treatment of Angina ( RITA ) Trial is a prospective , randomised study to compare the short term and long term effects of percutaneous transluminal coronary angioplasty and coronary artery bypass surgery . During the study a register of patients undergoing coronary arteriography at the fourteen participating centres is being maintained to assess the overall context of patient recruitment . Patients with arteriographically proven coronary artery disease are considered for the trial if the participating cardiologist and surgeon agree that equivalent revascularisation could be achieved by either treatment method . Patients who satisfy the trial entry criteria are randomised to treatment by coronary angioplasty or coronary artery bypass surgery , with prospective stratification into groups with one , two , or three treatment vessels . Randomisation implies an intention to treat the patient by the assigned procedure and the analysis of long term results will include all randomised cases . The trial will recruit at least 1000 patients who will be followed for five years . The major trial end points include death , new myocardial infarction , and new coronary angioplasty or coronary artery bypass procedures . Other outcome measures include symptom and employment status , quality of life , exercise tolerance , and left ventricular function .

coronary angioplasty

coronary artery bypass surgery

coronary artery bypass surgery

coronary arteriography

coronary angioplasty

coronary artery bypass surgery

coronary angioplasty

coronary artery bypass procedures

death

new myocardial infarction

new coronary angioplasty

coronary artery bypass procedures

symptom and employment status

quality of life

exercise tolerance

left ventricular function

angina

coronary arteriography


Effects of surfactant on biofilm formation on silicone nasal splints . Biofilms are sessile communities of bacteria embedded in self-produced extracellular polysaccharide matrix and are considered to be responsible for bacterial infections in humans . Topical surfactant use on silicone nasal splints may have a preventive effect on biofilm formation . The objective of this study is to investigate the effect of surfactant-containing nasal solutions on biofilm formation over the surface of silicone nasal splints . Forty patients were randomized after septoplasty to receive surfactant-containing saline solution ( group 1 ) or saline without surfactant ( group 2 ) . At the postoperative 48th , 72th and 96th hours , pieces of splint samples were taken and prepared for scanning electron microscopic evaluation . Biofilm formation was observed in 3 , 6 and 14 of 20 samples in group 1 ( surfactant used ) and 3 , 14 and 20 of 20 samples in group 2 ( control ) at 48th , 72th and 96th hours , respectively . Biofilm formation incidences of groups at 48th hour were similar ( p > 0.05 ) , whereas it was significantly lower at group 1 regarding 72th and 96th hours ( p < 0.05 ) . Surfactant-containing nasal solutions have an inhibitory effect on biofilm formation over the surface of silicone nasal splints especially after 48 h. Surfactant-containing nasal solutions may have an important role in nasal septal dressing in the future .

surfactant

silicone nasal splints

Biofilms

septoplasty

saline without surfactant

Surfactant-containing nasal solutions

Surfactant-containing nasal solutions

Effects of surfactant

biofilm formation .

biofilm formation

silicone nasal splints .

Biofilm formation

Biofilm formation

biofilm formation

nasal septal dressing

Forty patients

septoplasty


The effect of arm support combined with rehabilitation games on upper-extremity function in subacute stroke : a randomized controlled trial . BACKGROUND Use of rehabilitation technology , such as ( electro ) mechanical devices or robotics , could partly relieve the increasing strain on stroke rehabilitation caused by an increasing prevalence of stroke . Arm support ( AS ) training showed improvement of unsupported arm function in chronic stroke . OBJECTIVE To examine the effect of weight-supported arm training combined with computerized exercises on arm function and capacity , compared with dose-matched conventional reach training in subacute stroke patients . METHODS In a single-blind , multicenter , randomized controlled trial , 70 subacute stroke patients received 6 weeks of training with either an AS device combined with computerized exercises or dose-matched conventional training ( CON ) . Arm function was evaluated pretraining and posttraining by Fugl-Meyer assessment ( FM ) , maximal reach distance , Stroke Upper Limb Capacity Scale ( SULCS ) , and arm pain via Visual Analogue Scale , in addition to perceived motivation by Intrinsic Motivation Inventory posttraining . RESULTS FM and SULCS scores and reach distance improved significantly within both groups . These improvements and experienced pain did not differ between groups . The AS group reported higher interest/enjoyment during training than the CON group . CONCLUSIONS AS training with computerized exercises is as effective as conventional therapy dedicated to the arm to improve arm function and activity in subacute stroke rehabilitation , when applied at the same dose .

rehabilitation technology

Arm support ( AS ) training

weight-supported arm training

computerized exercises

conventional reach training

training

AS device combined with

computerized exercises

or

training with computerized exercises

upper-extremity function

arm function

arm function

capacity

Fugl-Meyer assessment ( FM )

maximal reach distance

arm pain via Visual Analogue Scale

FM

SULCS scores

reach distance

pain

higher interest/enjoyment

arm function

activity

subacute stroke :

subacute stroke patients .

subacute stroke


Quantitative measurements of HER2 and phospho-HER2 expression : correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab . BACKGROUND Preoperative therapy with chemotherapy and the HER2-targeted monoclonal antibody trastuzumab is valuable for patients with large or locally advanced HER2-positive ( HER2+ ) breast cancers but traditional methods of measuring HER2 expression do not accurately stratify patients for likelihood of response . Quantitative immunofluorescent approaches have the potential to provide a mathematically continuous measure of HER2 . Here we seek to determine whether quantitative measurement of HER2 or phospho-HER2 correlates with likelihood of response to trastuzumab- containing neoadjuvant therapy . METHODS We evaluated core biopsy samples from 27 HER2+ breast cancer patients enrolled in a preoperative clinical trial using trastuzumab , nab-paclitaxel and carboplatin combination therapy ( BrUOG BR-211B ( NCT00617942 ) ) . Tumor core biopsies were taken before initiation of treatment and 9-13 days after patients received " run-in " doses of either single agent trastuzumab or nab-paclitaxel . The AQUA method of quantitative immunofluorescence was used for analysis of in situ protein expression . Patients then received 18 weeks of treatment , followed by surgery to assess pathologic response to the neoadjuvant regimen . RESULTS A HER2 score of 2111 by AQUA analysis has been shown to be equivalent to HER2 3+ by immunohistochemical staining in previous studies . Of 20 evaluable patients , 10 cases who achieved a pathologic complete response ( pathCR ) with neoadjuvant treatment had a mean HER2 level of 10251 compared with 4766 in the patients without pathCR ( p = 0.0021 ) . Measurement of phospho-HER2 showed no difference in pathCR vs non-pathCR groups . In 9 patients who had HER2 levels repeated after a single treatment with trastuzumab there was no evidence of a reduction in the HER2 or phospho-HER2 levels following that exposure . CONCLUSIONS High levels of HER2 are associated with achievement of a pathCR in the preoperative setting , while levels of Phospho-HER2 were not predictive of response . This data suggests that accurate measurement of HER2 may help determine the likelihood of response in the pre-surgical setting . Further validation in larger cohorts is required , but this pilot data shows the feasibility of this approach .

Preoperative therapy with chemotherapy

trastuzumab

nab-paclitaxel

pathologic response

pathologic complete response ( pathCR )

Measurement of phospho-HER2

in the HER2 or phospho-HER2 levels

High levels of

levels of Phospho-HER2


Efficacy and cost-effectiveness of an experimental short-term inpatient Dialectical Behavior Therapy ( DBT ) program : study protocol for a randomized controlled trial . BACKGROUND Borderline Personality Disorder ( BPD ) is a serious psychiatric condition associated with substantial mortality , burden and public health costs . DBT is the treatment model with the largest number of published research articles showing effectiveness . However , some patients are not sufficiently engaged in outpatient treatment while presenting severe parasuicidal behavior , making hospitalization necessary . The Center for Personality Disorders Jelgersma developed an intensive 12-week inpatient DBT program that ( i ) rapidly reduces core borderline symptoms like suicidal behavior , ( ii ) minimizes the negative effects of an inpatient setting , and ( iii ) enhances compliance with outpatient treatment . We evaluate the ( cost- ) effectiveness of this experimental program . METHODS/DESIGN Seventy patients , aged 18 to 45 years with a primary diagnosis of BPD , showing a chronic pattern of parasuicidal gestures and/or reporting high degrees of severity of other borderline symptoms , are randomly allocated to the control and intervention groups . Subjects in the control group receive standard outpatient DBT , provided in one of three regular mental health settings in GGZ Rivierduinen . Subjects in the intervention group receive 12 weeks of intensified inpatient DBT plus six months of standard DBT , provided in the Center for Personality Disorders Jelgersma . The primary outcome is the number of suicide attempts/self-harming acts . Secondary outcomes are severity of other borderline complaints , quality of life , general psychopathological symptoms and health care utilization and productivity costs . Data are gathered using a prospective , two ( group : intervention and control ) by five ( time of measurement ) repeated measures factorial design.Participants will complete three-monthly outcome assessments in the course of therapy : at baseline , and 12 , 24 , 36 and 52 weeks after the start of the treatment . The period of recruitment started in March 2012 and the study will end in December 2014 . DISCUSSION Highly suicidal outpatient patients can pose a dilemma for mental health care professionals . Although hospitalization seems inevitable under some circumstances , it has proven to be harmful in its own right . This paper outlines the background and methods of a randomized trial evaluating the possible surplus value of a short-term inpatient DBT program .

Efficacy and cost-effectiveness

( cost- ) effectiveness

Borderline Personality Disorder ( BPD )

aged 18 to 45 years

GGZ Rivierduinen

Personality Disorders Jelgersma

Highly suicidal outpatient


Impact of additional counselling sessions through phone calls on smoking cessation outcomes among smokers in Penang State , Malaysia . BACKGROUND Studies all over the world reported that smoking relapses occur during the first two weeks after a quit date . The current study aimed to assess the impact of the additional phone calls counselling during the first month on the abstinence rate at 3 and 6 months after quit date among smokers in Penang , Malaysia . METHODS The study was conducted at Quit Smoking Clinic of two major hospitals in Penang , Malaysia . All the eligible smokers who attended the clinics between February 1st and October 31st 2012 were invited . Participants were randomly assigned by using urn design method either to receive the usual care that followed in the clinics ( control ) or the usual care procedure plus extra counselling sessions through phone calls during the first month of quit attempt ( intervention ) . RESULTS Participants in our cohort smoked about 14 cigarettes per day on average ( mean = 13.78 ± 7.0 ) . At 3 months , control group was less likely to quit smoking compared to intervention group ( 36.9 % vs. 46.7 % , verified smoking status ) but this did not reach statistical significance ( OR = 0.669 ; 95 % CI = 0.395-1.133 , P = 0.86 ) . However , at 6 months , 71.7 % of the intervention group were successfully quit smoking ( bio-chemically verified ) compared to 48.6 % of the control group ( P < 0.001 ) . The control group were significantly less likely to quit smoking ( OR = 0.375 ; 95 % CI = 0.217-0.645 , P < 0.001 ) . CONCLUSIONS Smoking cessation intervention consisting of phone calls counselling delivered during the first month of quit attempt revealed significantly higher abstinence rates compared with a standard care approach . Therefore , the additional counselling in the first few weeks after stop smoking is a promising treatment strategy that should be evaluated further . TRIAL REGISTRATION TCTR20140504001 .

additional phone calls counselling

smoking cessation outcomes

abstinence rate

less likely to quit

significantly

smokers in Penang State , Malaysia

among smokers in Penang , Malaysia


Effects of ranolazine on quality of life among patients with diabetes mellitus and stable angina .

ranolazine

quality of life