An intervention for sensory difficulties in children with autism : a randomized trial . This study evaluated a manualized intervention for sensory difficulties for children with autism , ages 4-8 years , using a randomized trial design . Diagnosis of autism was confirmed using gold standard measures . Results show that the children in the treatment group ( n = 17 ) who received 30 sessions of the occupational therapy intervention scored significantly higher ( p = 0.003 , d = 1.2 ) on Goal Attainment Scales ( primary outcome ) , and also scored significantly better on measures of caregiver assistance in self-care ( p = 0.008 d = 0.9 ) and socialization ( p = 0.04 , d = 0.7 ) than the Usual Care control group ( n = 15 ) . The study shows high rigor in its measurement of treatment fidelity and use of a manualized protocol , and provides support for the use of this intervention for children with autism . Findings are discussed in terms of their implications for practice and future research .

Usual Care control

Goal Attainment Scales

caregiver assistance in self-care

socialization

children

autism

ages 4-8 years

children

n = 17

( n = 15 )

children

autism


QT/QTc study conducted in Japanese adult healthy subjects : a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation . A QT/QTc study was conducted in compliance with ICH E14 guideline to evaluate the effects of a new xanthine oxidase inhibitor topiroxostat in Japanese healthy subjects . Forty-eight Japanese healthy subjects ( males 24 ; females 24 ) received a single oral dose of topiroxostat ( 60 or 180 mg ) , moxifloxacin ( 400 mg ) or placebo in a single-center , double-blind , four-period crossover design . Fridericia 's formula ( QTcF = QT/RR ( 0.33 ) ) was used as a primary method for QT-interval correction . The mean QTcF was prolonged by moxifloxacin , of which largest time-matched difference from placebo administration was 13.6 milliseconds with 90 % confidence interval ( CI ) of 11.2 and 15.9 milliseconds at 4 hours post-dose . The mean QTcF was hardly affected by either dose of topiroxostat , of which largest time-matched difference from placebo administration was 2.9 milliseconds with 90 % CI of 0.6 and 5.3 milliseconds at 4 hours post-dose for 60 mg , and 2.3 milliseconds with 90 % CI of 0 and 4.7 milliseconds at 1 hour post-dose for 180 mg . The results were essentially the same in the sex subgroup analysis . Moxifloxacin can be used as a positive control for QT/QTc studies in Japanese subjects ; and topiroxostat may not cause QT-interval prolongation in males as well as females .

topiroxostat

oral dose of topiroxostat

QT-interval correction

Japanese

adult

healthy subjects :

Japanese healthy subjects


Promoting gynecologic cancer awareness at a critical juncture -- where women and providers meet . Given the absence of effective population-based screening tests for ovarian , uterine , vaginal , and vulvar cancers , early detection can depend on women and health care providers recognizing the potential significance of symptoms . In 2008 , the Centers for Disease Control and Prevention 's ( CDC ) Inside Knowledge campaign began distributing consumer education materials promoting awareness of gynecologic cancer symptoms . We investigated providers ' in-office use of CDC gynecologic cancer materials and their recognition of the symptoms highlighted in the materials . We analyzed data from a national 2012 survey of US primary care physicians , nurse practitioners , and gynecologists ( N = 1,380 ) . Less than a quarter of providers ( 19.4 % ) reported using CDC gynecologic cancer education materials in their offices . The provider characteristics associated with the use of CDC materials were not consistent across specialties . However , recognition of symptoms associated with gynecologic cancers was consistently higher among providers who reported using CDC materials . The possibility that providers were educated about gynecologic cancer symptoms through the dissemination of materials intended for their patients is intriguing and warrants further investigation . Distributing consumer education materials in health care provider offices remains a priority for the Inside Knowledge campaign , as the setting where women and health care providers interact is one of the most crucial venues to promote awareness of gynecologic cancer symptoms .

awareness

recognition of symptoms

nurse practitioners


Menopausal quality of life : RCT of yoga , exercise , and omega-3 supplements . OBJECTIVE The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms . STUDY DESIGN We conducted a 12-week 3 × 2 randomized , controlled , factorial design trial . Peri- and postmenopausal women , 40-62 years old , were assigned randomly to yoga ( n = 107 ) , exercise ( n = 106 ) , or usual activity ( n = 142 ) and also assigned randomly to a double-blind comparison of omega-3 ( n = 177 ) or placebo ( n = 178 ) capsules . We performed the following interventions : ( 1 ) weekly 90-minute yoga classes with daily at-home practice , ( 2 ) individualized facility-based aerobic exercise training 3 times/week , and ( 3 ) 0.615 g omega-3 supplement , 3 times/day . The outcomes were assessed with the following scores : Menopausal Quality of Life Questionnaire ( MENQOL ) total and domain ( vasomotor symptoms , psychosocial , physical and sexual ) . RESULTS Among 355 randomly assigned women who average age was 54.7 years , 338 women ( 95 % ) completed 12-week assessments . Mean baseline vasomotor symptoms frequency was 7.6/day , and the mean baseline total MENQOL score was 3.8 ( range , 1-8 from better to worse ) with no between-group differences . For yoga compared to usual activity , baseline to 12-week improvements were seen for MENQOL total -0.3 ( 95 % confidence interval , -0.6 to 0 ; P = .02 ) , vasomotor symptom domain ( P = .02 ) , and sexuality domain ( P = .03 ) scores . For women who underwent exercise and omega-3 therapy compared with control subjects , improvements in baseline to 12-week total MENQOL scores were not observed . Exercise showed benefit in the MENQOL physical domain score at 12 weeks ( P = .02 ) . CONCLUSION All women become menopausal , and many of them seek medical advice on ways to improve quality of life ; little evidence-based information exists . We found that , among healthy sedentary menopausal women , yoga appears to improve menopausal quality of life ; the clinical significance of our finding is uncertain because of the modest effect .

RCT of yoga

exercise

omega-3 supplements

nonhormonal therapies

yoga

exercise

usual activity

placebo

omega-3 supplement

yoga

exercise

omega-3 therapy

yoga

Menopausal quality of life :

menopause-related quality of life

menopause-related

vasomotor symptoms


The cardiovascular effects of sevoflurane and isoflurane after premedication of healthy dogs undergoing elective surgery . Sevoflurane and isoflurane are commonly used in veterinary anesthesia . The objective of this prospective , randomized , open-label clinical study was to compare the cardiovascular effects of sevoflurane and isoflurane via direct arterial blood pressure measurements and the lithium dilution cardiac output ( LDCO ) on premedicated healthy dogs undergoing elective tibial plateau leveling osteotomy ( TPLO ) . Nineteen client-owned dogs were included . All dogs were premedicated with hydromorphone ( 0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg subcutaneously ) . Ten dogs were anesthetized with sevoflurane and nine dogs were anesthetized with isoflurane . Eighteen dogs were instrumented with a dorsal pedal arterial catheter , and one dog had a femoral arterial catheter . All dogs had continuous , direct systolic ( SAP ) , diastolic ( DAP ) , and mean arterial ( MAP ) blood pressure readings as well as heart rate ( HR ) , cardiac output ( CO ) , cardiac index ( CI ) , systemic vascular resistance ( SVR ) , systemic vascular resistance index ( SVRI ) , stroke volume variation ( SVV ) , and pulse pressure variation ( PPV ) recorded q 5 min during the surgical procedure . There was no significant statistical difference in all parameters between the sevoflurane and isoflurane treatment groups . Both sevoflurane and isoflurane inhalant anesthetics appear to have similar hemodynamic effects when used as part of a multimodal anesthetic protocol in premedicated healthy dogs undergoing an elective surgical procedure .

sevoflurane

isoflurane

Sevoflurane

isoflurane

sevoflurane

isoflurane

hydromorphone

glycopyrrolate

sevoflurane

isoflurane

sevoflurane

isoflurane

sevoflurane

isoflurane

elective surgery

Nineteen client-owned


Improving maternal mental health after a child 's diagnosis of autism spectrum disorder : results from a randomized clinical trial . IMPORTANCE The prevalence of psychological distress among mothers of children with autism spectrum disorder ( ASD ) suggests a need for interventions that address parental mental health during the critical period after the child 's autism diagnosis when parents are learning to navigate the complex system of autism services . OBJECTIVE To investigate whether a brief cognitive behavioral intervention , problem-solving education ( PSE ) , decreases parenting stress and maternal depressive symptoms during the period immediately following a child 's diagnosis of ASD . DESIGN , SETTING , AND PARTICIPANTS A randomized clinical trial compared 6 sessions of PSE with usual care . Settings included an autism clinic and 6 community-based early intervention programs that primarily serve low-income families . Participants were mothers of 122 young children ( mean age , 34 months ) who recently received a diagnosis of ASD . Among mothers assessed for eligibility , 17.0 % declined participation . We report outcomes after 3 months of follow-up ( immediate postdiagnosis period ) . INTERVENTIONS Problem-solving education is a brief , cognitive intervention delivered in six 30-minute individualized sessions by existing staff ( early intervention programs ) or research staff without formal mental health training ( autism clinic ) . MAIN OUTCOMES AND MEASURES Primary outcomes were parental stress and maternal depressive symptoms . RESULTS Fifty-nine mothers were randomized to receive PSE and 63 to receive usual care . The follow-up rate was 91.0 % . Most intervention mothers ( 78.0 % ) received the full PSE course . At the 3-month follow-up assessment , PSE mothers were significantly less likely than those serving as controls to have clinically significant parental stress ( 3.8 % vs 29.3 % ; adjusted relative risk [ aRR ] , 0.17 ; 95 % CI , 0.04 to 0.65 ) . For depressive symptoms , the risk reduction in clinically significant symptoms did not reach statistical significance ( 5.7 % vs 22.4 % ; aRR , 0.33 ; 95 % CI , 0.10 to 1.08 ) ; however , the reduction in mean depressive symptoms was statistically significant ( Quick Inventory of Depressive Symptomatology score , 4.6 with PSE vs 6.9 with usual care ; adjusted mean difference , -1.67 ; 95 % CI , -3.17 to -0.18 ) . CONCLUSIONS AND RELEVANCE The positive effects of PSE in reducing parenting stress and depressive symptoms during the critical postdiagnosis period , when parents are asked to navigate a complex service delivery system , suggest that it may have a place in clinical practice . Further work will monitor these families for a total of 9 months to determine the trajectory of outcomes . TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT01021384 .

problem-solving education ( PSE )

PSE

usual care

Problem-solving education

usual care

maternal mental health

parental mental health

parenting stress

maternal depressive symptoms

parental stress

maternal depressive symptoms

parental stress

depressive symptoms

depressive symptoms

parenting stress

depressive symptoms

maternal mental health

mothers

122 young children

Fifty-nine


Etomidate with or without flumazenil anesthesia for stem cell transplantation in autistic children . BACKGROUND The aim of this study was to investigate etomidate administration with or without flumazenil in autistic children who underwent intrathecal transplantation of stem cells by lumbar puncture . METHODS Forty autistic children aged 2-12 , who were scheduled for stem cell transplantation via lumbar puncture under anesthesia , were randomized for a double-blind study . The children were randomly assigned to two groups : the flumazenil group ( group F , n=20 ) and the etomidate group ( group E , n=20 ) . All children received 0.2 mg/kg of etomidate . In the case of inadequate anesthesia , patients received repeated doses of 0.1 mg/kg of etomidate until reaching deep sedation . After operation , children in group F were given flumazenil ( 0.01 mg/kg ) and children in group E received placebo . Heart rate ( HR ) , mean arterial pressure , oxygen saturation , respiratory rate , the Ramsay sedation score ( RSS ) , and recovery time of all children were continuously monitored and recorded during the entire procedure . RESULTS After anesthesia , blood pressure and HR measurements were not significantly changed in both groups compared with the baseline . There were no respiratory depression , bradycardia , hypotension , nausea , and vomiting . Five patients complained of pain on the site of injection . Myoclonus occurred in seven patients . Recovery time in group F was significantly shorter than in group E ( p < 0.001 ) , and after the injection of flumazenil , RSS in group F significantly decreased than in group E. There were no significant differences in operation time . Physician satisfaction in both groups was similar . CONCLUSIONS Etomidate resulted in stable hemodynamic responses and relatively less adverse effects , and flumazenil antagonized the anesthetic effect of etomidate ; thus , etomidate with flumazenil is suitable for performing stem cell transplantation in autistic children .

Etomidate

flumazenil anesthesia

etomidate

flumazenil

flumazenil

etomidate

etomidate

etomidate

flumazenil

placebo

flumazenil

Etomidate

flumazenil

Heart rate ( HR )

mean arterial pressure

oxygen saturation

respiratory rate

Ramsay sedation score ( RSS )

recovery time

blood pressure

HR measurements

respiratory depression

bradycardia

hypotension

nausea

vomiting

pain on the site of injection

Myoclonus

Recovery time

RSS

operation time

Physician satisfaction

hemodynamic responses

adverse effects

anesthetic effect

autistic children .

autistic children .


Effect of home-based nursing pulmonary rehabilitation on patients with chronic obstructive pulmonary disease : a randomised clinical trial . Fatigue is a common symptom of patients with chronic obstructive pulmonary disease ( COPD ) , and results in a reduction of daily activity and quality of life in patients with the disease . The authors aimed to identify the effect of home-based nursing pulmonary rehabilitation on fatigue , activities of daily living ( ADL ) and quality of life ( QOL ) in patients with COPD . A block randomisation method was used to randomise participants into case and control groups . Fatigue , ADL and QOL were assessed before and after the intervention in both groups . Independent and paired t-tests , chi-squared tests and covariance analysis were used to analysing data . Findings showed the significant decrease in the mean scores of fatigue ( p < 0.001 ) and significant improvement in mean scores of ADL ( p < 0.001 ) and QOL ( p < 0.001 ) after home-based nursing pulmonary rehabilitation in the case group . Home-based nursing pulmonary rehabilitation can be an effective , inexpensive and accessible programme for decreasing fatigue and improving ADL and QOL for patients with COPD .

case

control

Fatigue

ADL

QOL

mean scores of fatigue

mean scores of

ADL

QOL

effective

inexpensive

accessible

decreasing fatigue

improving

ADL

and

QOL

patients with COPD .

patients with COPD .


Study protocol : Rehabilitation including Social and Physical activity and Education in Children and Teenagers with Cancer ( RESPECT ) . BACKGROUND During cancer treatment children have reduced contact with their social network of friends , and have limited participation in education , sports , and leisure activities . During and following cancer treatment , children describe school related problems , reduced physical fitness , and problems related to interaction with peers . METHODS/DESIGN The RESPECT study is a nationwide population-based prospective , controlled , mixed-methods intervention study looking at children aged 6-18 years newly diagnosed with cancer in eastern Denmark ( n=120 ) and a matched control group in western Denmark ( n=120 ) . RESPECT includes Danish-speaking children diagnosed with cancer and treated at pediatric oncology units in Denmark . Primary endpoints are the level of educational achievement one year after the cessation of first-line cancer therapy , and the value of VO2max one year after the cessation of first-line cancer therapy . Secondary endpoints are quality of life measured by validated questionnaires and interviews , and physical performance . RESPECT includes a multimodal intervention program , including ambassador-facilitated educational , physical , and social interventions . The educational intervention includes an educational program aimed at the child with cancer , the child 's schoolteachers and classmates , and the child 's parents . Children with cancer will each have two ambassadors assigned from their class . The ambassadors visit the child with cancer at the hospital at alternating 2-week intervals and participate in the intervention program . The physical and social intervention examines the effect of early , structured , individualized , and continuous physical activity from diagnosis throughout the treatment period . The patients are tested at diagnosis , at 3 and 6 months after diagnosis , and one year after the cessation of treatment . The study is powered to quantify the impact of the combined educational , physical , and social intervention programs . DISCUSSION RESPECT is the first population-based study to examine the effect of early rehabilitation for children with cancer , and to use healthy classmates as ambassadors to facilitate the normalization of social life in the hospital . For children with cancer , RESPECT contributes to expanding knowledge on rehabilitation that can also facilitate rehabilitation of other children undergoing hospitalization for long-term illness . TRIAL REGISTRATION Clinical Trials.gov : file . NCT01772849 and NCT01772862 .

educational intervention

educational program

visit the child with cancer

classmates as ambassadors

Children

Teenagers

Cancer

children

children

6-18 years

newly diagnosed with cancer

children

cancer

child

cancer

Children

cancer

child

cancer

children

cancer


Examination of aggression and self-injury in children with autism spectrum disorders and serious behavioral problems . This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder ( ASD ) who participated in 2 risperidone trials . The narratives were derived from a parent interview about each child 's 2 most pressing problems . Five subtypes of aggression emerged : hot aggression only , cold aggression only , self-injurious behavior ( SIB ) only , aggression and SIB , and nonaggressive . All groups showed a high rate of positive response to risperidone with no differences across subtypes . These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD .

2 risperidone trials .

aggression

nonaggressive .

positive response

children

children

autism spectrum disorder ( ASD )


Humoral immunity after kidney transplantation : impact of two randomized immunosuppressive protocols . BACKGROUND Controlling alloimmune humoral response is a challenge in transplantation . Few studies have evaluated the impact of maintenance immunosuppression on blood humoral parameters . MATERIAL/METHODS We performed a post-hoc analysis on 307 kidney transplant recipients included in a prospective randomized trial comparing tacrolimus/mycophenolate mofetil ( Tac/MMF ) vs. cyclosporine/azathioprine ( CsA/AZA ) , both used with antithymocyte globulin induction and steroids . Humoral parameters were analyzed at D0 , D15 , and M12 . RESULTS IgG , IgA , and IgM levels decreased significantly as soon as D15 in both groups ( –35 % , –26 % , and –35 % respectively , vs. D0 ) . At M12 , although peripheral B-cell counts did not differ between the groups , Tac/MMF regimen was associated with lower IgG , IgA , and IgM levels than CsA/AZA ( –5.9 % , –14.6 % , and –34 % , respectively ) . Hypogammaglobulinemia at D15 was not associated with an increased risk of infections during the first year . The proportion of HLA-sensitized patients decreased in the Tac/MMF group ( 15.9 % at D0 and 6.7 % at M12 , p=0.02 ) and remained stable in the CsA/AZA group ( 10.3 % at D0 and 8.9 % at M12 , p=0.5 ) . More patients sensitized at baseline became non-sensitized at M12 with Tac/MMF than with CsA/AZA . CONCLUSIONS Our results suggest humoral immunosuppression is better with Tac/MMF than with CsA/AZA during the first year of kidney transplantation .

antithymocyte globulin induction

steroids .

IgG , IgA , and IgM levels


Effect of augmented sensorimotor input on learning verbal and nonverbal tasks among children with autism spectrum disorders . Thirty-four children , with autism spectrum disorders , ages 4-14 years , were matched and randomly assigned to one of two conditions for learning a novel juice-making task and producing two novel words about the event . Seventeen sighted children were manually guided to perform the task and tactually prompted during imitated productions of novel words for the event . Their matched controls heard the novel words and watched the juice-making task being performed . Performances on four verbal and two nonverbal measures right after instruction and at 24-48 h post-instruction , revealed higher scores for the ‘ ‘ hands-on ’ ’ , participation than observation group on both verbal and nonverbal tasks . This study offers a paradigm for exploring the instructional advantage of enhanced participatory experience .

augmented sensorimotor input

manually guided

learning verbal and nonverbal tasks

learning a novel juice-making task

novel words

juice-making task

four verbal and two nonverbal measures


Remission in rheumatoid arthritis patients treated with etanercept monotherapy : clinical practice and clinical trial experience . OBJECTIVES To assess , in a randomised controlled trial ( RCT ) and in clinical practice , an association of time to remission and baseline disease activity with both induction of remission and sustained remission in etanercept-treated patients with rheumatoid arthritis ( RA ) . METHODS Data from an RCT ( Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes [ TEMPO ] ; n=682 ) and an observational registry ( Rheumatoid Arthritis DMARD Intervention and Utilization Study [ RADIUS II ] ; n=4341 ) were used to evaluate disease activity ( Clinical Disease Activity Index [ CDAI ] score ) over time in patients initiating etanercept ( monotherapy or with methotrexate ) . CDAI remission ( CDAI≤2.8 ) and sustained remission ( ≥6 months ) were determined through year 3 by treatment group , study , time to remission , and disease severity . RESULTS Patients from TEMPO and RADIUS II who received etanercept monotherapy showed similar CDAI remission rates ( 39 % and 35 % , respectively , at 3 years ) . Among patients who received etanercept with methotrexate , remission rates were 54 % and 36 % , respectively . Remission occurred more rapidly in TEMPO than RADIUS II perhaps from differences in compliance , patient populations , or sequence of combination therapy initiation . Generally , more patients with lower baseline CDAI scores achieved remission than those with higher scores . Continued remission appeared more likely in patients achieving remission earlier in the course of their therapy ( 0-6 months ) . CONCLUSIONS Remission by year 3 in etanercept-treated ( with and without methotrexate ) patients with RA occurred in ≥35 % of patients in both an RCT ( TEMPO ) and a clinical practice setting ( RADIUS II ) , and more frequently in those with lower baseline disease severity . Patients with lower RA disease activity were more likely to reach remission . Continued remission may be more likely in patients who achieved remission earlier .

etanercept monotherapy

etanercept-treated

Etanercept and Methotrexate

Remission in rheumatoid arthritis

time to remission

disease activity

CDAI remission

rheumatoid arthritis

etanercept-treated patients

rheumatoid arthritis ( RA )


Testing the efficacy of an HIV stigma reduction intervention with medical students in Puerto Rico : the SPACES project . INTRODUCTION Stigma associated with HIV has been documented as a barrier for accessing quality health-related services . When the stigma manifests in the health care setting , people living with HIV receive substandard services or even be denied care altogether . Although the consequences of HIV stigma have been documented extensively , efforts to reduce these negative attitudes have been scarce . Interventions to reduce HIV stigma should be implemented as part of the formal training of future health care professionals . The interventions that have been tested with health care professionals and published have several limitations that must be surpassed ( i.e . lack of comparison groups in research designs and longitudinal follow-up data ) . Furthermore , Latino health care professionals have been absent from these intervention efforts even though the epidemic has affected this population disproportionately . METHODS In this article , we describe an intervention developed to reduce HIV stigma among medical students in Puerto Rico . A total of 507 medical students were randomly introduced into our intervention and control conditions . RESULTS The results show statistically significant differences between the intervention and control groups ; intervention group participants had lower HIV stigma levels than control participants after the intervention . In addition , differences in HIV stigma levels between the groups were sustained for a 12-month period . CONCLUSION The results of our study demonstrate the efficacy of the modes of intervention developed by us and serve as a new training tool for future health care professionals with regard to stigma reduction .

HIV stigma reduction intervention

Interventions to reduce HIV stigma

intervention

and

control conditions

intervention

control

HIV stigma reduction

Stigma

HIV stigma

HIV stigma

HIV stigma

lower HIV stigma levels

HIV stigma levels

stigma reduction


A randomised , double-blind , parallel design , multi-institutional , non-inferiority phase IV trial of imidafenacin versus fesoterodine for overactive bladder . AIMS Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder ( OAB ) . METHODS This study is a randomised , double-blind , parallel-group , fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months , daily mean voiding frequency ( DMVF ) ≥ 8 , and daily mean urgency or urgency incontinence frequency ≥ 2 . A twice-daily 0.1 mg imidafenacin with placebo , or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks . The primary efficacy end-point was the difference in DMVF at 12 weeks . The secondary efficacy end-points were differences in daily mean : ( i ) voiding frequency at 4 and 8 weeks ; ( ii ) urgency frequency ; ( iii ) urgency incontinence frequency ; ( iv ) incontinence frequency ; ( v ) nocturia frequency ; and ( vi ) quality of life score . The variables for safety analysis were adverse events , vital signs , residual urine volume and clinical laboratory tests . An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients . RESULTS The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups , respectively , and the difference was not significant between the two groups . Imidafenacin was non-inferior to fesoterodine , and the lower limit of 95 % two-sided confidence intervals was -0.53 . The other six secondary end-points and variables for safety analysis showed no difference between the two groups . CONCLUSIONS Imidafenacin was non-inferior to fesoterodine in terms of efficacy , and showed no significant difference in terms of safety .

imidafenacin versus fesoterodine

imidafenacin

fesoterodine

fesoterodine-controlled

efficacy and safety

clinical laboratory tests

overactive bladder .


The peroxisome proliferator activated receptor-γ pioglitazone improves vascular function and decreases disease activity in patients with rheumatoid arthritis . BACKGROUND Rheumatoid arthritis ( RA ) is associated with heightened mortality due to atherosclerotic cardiovascular disease ( CVD ) . Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD . We hypothesized that the peroxisome proliferator activated receptor-γ ( PPAR-γ ) pioglitazone could promote potent vasculoprotective and anti-inflammatory effects in RA . METHODS AND RESULTS One hundred forty-three non-diabetic adult RA patients ( 76.2 % female , age 55.2 ± 12.1 [ mean ± SD ] ) on stable RA standard of care treatment were enrolled in a randomized , double-blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo , with a 3-month duration/arm and a 2-month washout period . Pulse wave velocity of the aorta ( PWV ) , brachial artery flow mediated dilatation ( FMD ) , nitroglycerin mediated dilatation ( NMD ) , microvascular endothelial function ( reactive hyperemia index [ RHI ] ) , and circulating biomarkers of inflammation , insulin resistance , and atherosclerosis risk all were quantified . RA disease activity was assessed with the 28-Joint Count Disease Activity Score ( DAS-28 ) C-reactive protein ( CRP ) and the Short Form ( 36 ) Health Survey quality of life questionnaire . When added to standard of care RA treatment , pioglitazone significantly decreased pulse wave velocity ( ie , aortic stiffness ) ( P=0.01 ) , while FMD and RHI remained unchanged when compared to treatment with placebo . Further , pioglitazone significantly reduced RA disease activity ( P=0.02 ) and CRP levels ( P=0.001 ) , while improving lipid profiles . The drug was well tolerated . CONCLUSIONS Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues . The clinical implications of these findings remain to be established . CLINICAL TRIAL REGISTRATION URL ClinicalTrials.gov Unique Identifier : NCT00554853 .

receptor-γ pioglitazone

( PPAR-γ ) pioglitazone

pioglitazone

pioglitazone

pioglitazone


Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum . BACKGROUND Unstuck and On Target ( UOT ) is an executive function ( EF ) intervention for children with autism spectrum disorders ( ASD ) targeting insistence on sameness , flexibility , goal-setting , and planning through a cognitive-behavioral program of self-regulatory scripts , guided/faded practice , and visual/verbal cueing . UOT is contextually-based because it is implemented in school and at home , the contexts in which a child uses EF skills . METHODS To evaluate the effectiveness of UOT compared with a social skills intervention ( SS ) , 3rd-5th graders with ASD ( mean IQ = 108 ; UOT n = 47 ; SS n = 20 ) received interventions delivered by school staff in small group sessions . Students were matched for gender , age , race , IQ , ASD symptomotolgy , medication status , and parents ' education . Interventions were matched for 'dose ' of intervention and training . Measures of pre-post change included classroom observations , parent/teacher report , and direct child measures of problem-solving , EF , and social skills . Schools were randomized and evaluators , but not parents or teachers , were blinded to intervention type . RESULTS Interventions were administered with high fidelity . Children in both groups improved with intervention , but mean change scores from pre- to postintervention indicated significantly greater improvements for UOT than SS groups in : problem-solving , flexibility , and planning/organizing . Also , classroom observations revealed that participants in UOT made greater improvements than SS participants in their ability to follow rules , make transitions , and be flexible . Children in both groups made equivalent improvements in social skills . CONCLUSIONS These data support the effectiveness of the first contextually-based EF intervention for children with ASD . UOT improved classroom behavior , flexibility , and problem-solving in children with ASD . Individuals with variable background/training in ASD successfully implemented UOT in mainstream educational settings .

executive function intervention

Unstuck and On Target ( UOT )

executive function ( EF ) intervention

UOT

UOT

social skills intervention ( SS )

improvements in social skills

autism spectrum .

children

3rd-5th graders

n = 20

Students

children

children


[ Preoperative chemotherapy of esophageal cancer ] . A series of 25 patients with advanced esophageal cancer treated from Mar . 1981 to Sep. 1982 by preoperative chemotherapy plus surgery is reported . All the patients came from the hospitals of the cooperative research group and were randomized into chemotherapy and control groups . They were proved by X-ray , cytology and histopathology prior to treatment . By histology , 22 cases were squamous cell carcinoma , 1 adenocarcinoma and 2 squamous adenocarcinoma . The COF chemotherapy consisted of Vincristine 1 mg , cyclophosphamide 600 mg and 5-fluorouracil 500 mg IV on days 1 and 8 with or without the addition of Pingyangmycin , a drug equivalent to Bleomycin A5 , at the dose of 10 mg IM on days 1 , 3 , 6 and 8 . The interval between the ending of chemotherapy and the surgical resection was 5-6 days . The results showed that preoperative chemotherapy caused no myelosuppression , but merely mild gastrointestinal symptoms . All patients were operated and resected without difficulty . The subjective improvement in various degrees and the shrinkage of tumor in the X-ray films were present in 5/25 cases who received preoperative chemotherapy . The histopathological changes in the chemotherapy and control groups ( 16 specimens ) were different . In the chemotherapy group , excessive keratinization in the squamous component of the esophageal cancerous tissue appeared in the resected specimens . The incidence of degeneration and necrosis in the squamous epithelium adjacent to carcinoma was higher in the chemotherapy group ( P less than 0.01 ) . The results suggested that such combined modality is worth further study .

chemotherapy

preoperative chemotherapy

surgery

chemotherapy

control

chemotherapy

Vincristine

cyclophosphamide

Pingyangmycin

Bleomycin A5

chemotherapy

surgical resection

chemotherapy

chemotherapy

chemotherapy

no myelosuppression

mild gastrointestinal symptoms .

shrinkage of tumor in the X-ray films

histopathological changes


Family-centred music therapy to promote social engagement in young children with severe autism spectrum disorder : a randomized controlled study . BACKGROUND Limited capacity for social engagement is a core feature of autism spectrum disorder ( ASD ) , often evident early in the child 's development . While these skills are difficult to train , there is some evidence that active involvement in music-making provides unique opportunities for social interaction between participants . Family-centred music therapy ( FCMT ) endeavours to support social engagement between child and parent within active music-making , yet the extent of benefits provided is unknown . AIM This study investigated the impacts of FCMT on social engagement abilities . METHODS Twenty-three children ( 36-60 months ) with severe ASD received either 16 weeks of FCMT in addition to their early intervention programmes ( n = 12 ) , or their early intervention programme only ( n = 11 ) . Change in social engagement was measured with standardized parent-report assessments , parent interviews and clinician observation . RESULTS Intention-to-treat analysis for the Vineland Social Emotional Early Childhood Scale indicated a significant effect in favour of FCMT . Thematic qualitative analysis of the parent interviews showed that the parent-child relationship grew stronger . CONCLUSION FCMT improves social interactions in the home and community and the parent-child relationship , but not language skills or general social responsiveness . This study provides preliminary support for the use of FCMT to promote social engagement in children with severe ASD .

Family-centred music therapy

Family-centred music therapy ( FCMT )

FCMT

FCMT .

FCMT

FCMT

young children

severe autism spectrum disorder

Twenty-three

( 36-60 months )

severe ASD

children

severe ASD


Differences in vision between clinic and home and the effect of lighting in older adults with and without glaucoma . IMPORTANCE Patients often report greater visual difficulties at home than expected from vision testing in the clinic . Such discordance may be owing to worse vision in the home than measured in clinic . OBJECTIVE To compare vision measured between the clinic and home and evaluate factors , including lighting , associated with these differences . DESIGN , SETTING , AND PARTICIPANTS This cross-sectional study conducted from 2005-2009 involved 126 patients with glaucoma and 49 without glaucoma recruited from the Glaucoma and Comprehensive Eye Clinics at Washington University , St Louis , Missouri . Patients underwent clinic and home visits , were aged 55 to 90 years , were consecutively recruited , and met inclusion criteria for this study . A total of 166 eligible patients refused participation . EXPOSURE Participants underwent clinic and home visits randomized to order of completion . At each visit , masked and certified examiners measured binocular distance visual acuity ( DVA ) with a nonbacklit chart , near visual acuity ( NVA ) , contrast sensitivity ( CS ) , CS with glare , and lighting . MAIN OUTCOMES AND MEASURES Differences in vision between the clinic and home . RESULTS The mean scores for all vision tests were significantly better in the clinic than home for participants with and without glaucoma ( P < .05 , matched-pair t tests ) . For DVA , 29 % of participants with glaucoma read 2 or more lines better in the clinic than home and 39 % with advanced glaucoma read 3 or more lines better . For the entire sample , 21 % of participants read 2 or more lines better in the clinic than home for NVA and 49 % read 2 or more triplets better in the clinic for CS with glare . Lighting was the most significant factor associated with differences in vision between the clinic and home for DVA , NVA , and CS with glare testing ( P < .05 , multiple regression model ) . Median home lighting was 4.3 times and 2.8 times lower than clinic lighting in areas tested for DVA and NVA , respectively . Home lighting was below that recommended in 85 % or greater of participants . CONCLUSIONS AND RELEVANCE Vision measured in the clinic is generally better than vision measured at home , with differences mainly owing to poor home lighting . Knowledge that vision discrepancies between patient report and clinical testing may be owing to home lighting may initiate clinician-patient discussions to optimize home lighting and improve the vision of older adults in their homes .

older adults

without

glaucoma

without glaucoma

55 to 90 years

older adults


Stimulus over-selectivity in temporal brain injury : mindfulness as a potential intervention . OBJECTIVE The current study aimed to investigate the impact of brief mindfulness training on the performance of a sample of patients with TBI in an over-selectivity task . PARTICIPANTS Twenty-four patients who had suffered TBI and reported problems with focused or sustained attention . METHOD The study was a between-subjects design ( mindfulness intervention vs control ) with difference between number of most and least chosen stimulus selections on an over-selectivity task as the dependent measure . RESULTS The results of this study indicated that stimulus over-selectivity was present in a group of patients with TBI . However , the level of emergent over-selectivity was significantly reduced by a mindfulness induction when compared to a no- intervention control group . CONCLUSIONS The findings are discussed in terms of the efficacy of mindfulness training in reducing TBI-related cognitive deficits .

mindfulness training

( mindfulness intervention

control )

control

mindfulness training

Stimulus over-selectivity

over-selectivity

stimulus over-selectivity

level of emergent over-selectivity

efficacy

TBI-related cognitive deficits


The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids : results from an open-label comparative study . This study evaluated the safety and efficacy of a sirolimus , corticosteroid , and cyclosporine reduction regimen in an open-label , 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers . One month post-transplantation , 357 patients were randomized to receive standard-dose cyclosporine ( sCsA , n = 179 ) or reduced-dose cyclosporine ( rCsA , n = 178 ) . All patients also received sirolimus and corticosteroids . The primary end points were the rate of biopsy-confirmed acute rejection ( BCAR ) and renal function , as measured by serum creatinine . Baseline demographic and donor characteristics were similar between groups . BCAR rates at 12 months were not significantly different : 11.2 % for rCsA patients and 16.2 % for sCsA patients . Mean serum creatinine ( ±SEM ) was significantly lower ( 1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl , P < 0.001 ) , and creatinine clearance ( ±SEM ; Nankivell method ) was significantly higher ( 57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min , P < 0.001 ) in patients receiving rCsA versus sCsA at 1 year , respectively . Patient and graft survival exceeded 98 % in both groups . No significant differences in infection or malignancy were noted between groups . The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12-month patient and graft survival , a low incidence of BCAR , and improved renal function in renal allograft recipients . Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine . These findings may help to improve long-term renal allograft outcomes .

cyclosporine

standard-dose cyclosporine

reduced-dose cyclosporine

sirolimus

corticosteroids

efficacy and safety

safety and efficacy

renal function

serum creatinine

BCAR

Mean serum creatinine

receiving sirolimus and corticosteroids

de novo renal allograft


Low-fluence photodynamic therapy versus ranibizumab for chronic central serous chorioretinopathy : one-year results of a randomized trial . PURPOSE To compare the efficacy and safety between low-fluence photodynamic therapy ( PDT ) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy ( CSC ) . DESIGN Prospective , randomized , single-center , parallel-arm , controlled trial . PARTICIPANTS Thirty-four eyes of 32 patients with chronic CSC with > 6 months ' duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group ( n = 18 ) or the ranibizumab group ( n = 16 ) . INTERVENTION The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab . Rescue treatment was available from month 3 if the subretinal fluid ( SRF ) persisted or recurred after primary treatment ; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group . MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment . Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity ( BCVA ) , central retinal thickness ( CRT ) , and angiographic findings from baseline to 12 months . RESULTS At month 12 , 16 eyes ( 88.9 % ) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes ( 12.5 % ) in the ranibizumab group ( P < 0.001 ) . Two eyes ( 11.1 % ) in the low-fluence PDT group and 11 eyes ( 68.8 % ) in the ranibizumab group met the criteria for rescue treatment ( P = 0.001 ) . In the low-fluence PDT group , the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 ( P < 0.05 ) , but the differences became insignificant thereafter . The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group , but the differences were not statistically significant except at month 3 ( P = 0.025 ) . On indocyanine green angiography , a significantly greater proportion of the low-fluence PDT group ( 16 eyes ; 88.9 % ) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group ( 0 eyes ; P < 0.001 ) . No serious adverse events related to the drugs or procedures were observed . CONCLUSIONS This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC .

Low-fluence photodynamic therapy

ranibizumab

low-fluence PDT

Rescue treatment

efficacy

safety

central retinal thickness ( CRT )

angiographic findings

mean decrease in CRT

improvement in BCVA

choroidal hyperpermeability

serious adverse events


Does alliance predict symptoms throughout treatment , or is it the other way around ? OBJECTIVE Scholars increasingly recognize that therapeutic alliance and symptomatic change are associated with one another . A common assumption is that alliance predicts symptomatic change . However , the issue is far from settled . One challenge in determining the causality is the establishment of temporal precedence showing that alliance , as opposed to previous symptomatic change , drives subsequent symptomatic reduction . METHOD To make further advances in untangling this chicken-and-egg question , we employed autoregressive cross-lagged modeling over 4 time points in a sample of 149 depressive patients receiving supportive-expressive psychotherapy or clinical management combined with pharmacotherapy or clinical management combined with placebo . RESULTS Using this methodology , we found that both alliance and symptoms across treatment made significant and unique contributions in predicting subsequent symptomatic levels throughout treatment . Additionally , alliance , but not symptoms , predicted subsequent alliance levels . No differences were found between treatments . CONCLUSIONS Our findings imply that alliance temporally precedes symptomatic levels throughout treatment .

supportive-expressive psychotherapy

alliance predict symptoms

alliance predicts symptomatic change .

symptomatic reduction .

alliance and symptoms

contributions

alliance

subsequent alliance levels .

alliance

symptomatic levels


Neuropsychological outcomes after psychosocial intervention for depression in Parkinson 's disease . The authors describe neuropsychological outcomes in people with Parkinson 's disease ( PD ) after their participation in an NIH-sponsored , randomized , controlled trial of cognitive-behavioral treatment for depression . Improvements in mood were associated with modest gains in verbal memory and executive functioning over the 10-week treatment period and accounted for greater variance in neuropsychological outcomes at the end of treatment than other known correlates of cognitive functioning in PD , such as disease severity , age , and education . Baseline working memory and executive skills were also associated with depression improvement over time .

psychosocial intervention

cognitive-behavioral treatment

Improvements in mood

neuropsychological outcomes

cognitive functioning

depression in Parkinson 's disease .


Comparative evaluation of percutaneous laser and radiofrequency ablation in patients with HCC smaller than 4 cm . OBJECTIVE This study was done to compare percutaneous laser ablation ( PLA ) and radiofrequency thermoablation ( RFA ) for the treatment of hepatocellular carcinoma ( HCC ) ≤ 4 cm , in patients with liver cirrhosis . MATERIALS AND METHODS Thirty patients with single HCC ≤ 4 cm in diameter were randomly assigned to one of two treatments : 15 patients were treated with PLA , using a multifibre system connected to a neodymium yttrium-aluminium-garnet laser source ; 15 patients were treated with RFA , using an expandable needle electrode . Patients were followed up for up to 12 months . RESULTS A complete response was obtained in 87 % lesions treated with PLA and in 93 % lesions treated with RFA ( p = ns ) . The overall local recurrence-free survival rates at 3 , 6 and 12 months were comparable . However , a higher rate of recurrence was observed in the PLA group for lesions ≥ 21 mm ( p = 0.0081 ) . A postablation syndrome was documented in 13 patients ( 1 PLA ; 12 RFA ) . Tumour necrosis factor-α was significantly higher in the RFA group ( p < 0.05 ) . CONCLUSIONS RFA is more effective in the treatment of HCC compared to PLA for lesions ≥ 21 mm . However , PLA should be considered a viable treatment option for HCC ≤ 20 mm , in view of the lower incidence of complications .

percutaneous laser

radiofrequency ablation

percutaneous laser ablation ( PLA )

radiofrequency thermoablation ( RFA )

rate of recurrence

postablation syndrome

Tumour necrosis factor-α

HCC

hepatocellular carcinoma

liver cirrhosis


A double-blind , randomized trial of deep repetitive transcranial magnetic stimulation ( rTMS ) for autism spectrum disorder . BACKGROUND Biomedical treatment options for autism spectrum disorder ( ASD ) are extremely limited . Repetitive transcranial magnetic stimulation ( rTMS ) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder , and a similar approach could yield therapeutic benefits in ASD , if applied to relevant cortical regions . OBJECTIVE The aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD . METHODS 28 adults diagnosed with either autistic disorder ( high-functioning ) or Asperger 's disorder completed a prospective , double-blind , randomized , placebo-controlled design with 2 weeks of daily weekday treatment . This involved deep rTMS to bilateral dorsomedial prefrontal cortex ( 5 Hz , 10-s train duration , 20-s inter-train interval ) for 15 min ( 1500 pulses per session ) using a HAUT-Coil . The sham rTMS coil was encased in the same helmet of the active deep rTMS coil , but no effective field was delivered into the brain . Assessments were conducted before , after , and one month following treatment . RESULTS Participants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up , and a significant reduction in social relating symptoms ( relative to sham participants ) for both post-treatment assessments . Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up . There were no changes for those in the sham condition . CONCLUSION Deep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety . Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response .

rTMS

placebo-controlled

deep rTMS

rTMS

rTMS

ASD .

self-reported social relating symptoms

social relating symptoms

self-oriented anxiety

autism spectrum disorder .

adults


Predictors of postdischarge outcomes from information acquired shortly after admission for acute heart failure : a report from the Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function ( PROTECT ) Study . BACKGROUND Acute heart failure is a common reason for admission , and outcome is often poor . Improved prognostic risk stratification may assist in the design of future trials and in patient management . Using data from a large randomized trial , we explored the prognostic value of clinical variables , measured at hospital admission for acute heart failure , to determine whether a few selected variables were inferior to an extended data set . METHODS AND RESULTS The prognostic model included 37 clinical characteristics collected at baseline in PROTECT , a study comparing rolofylline and placebo in 2033 patients admitted with acute heart failure . Prespecified outcomes at 30 days were death or rehospitalization for any reason ; death or rehospitalization for cardiovascular or renal reasons ; and , at both 30 and 180 days , all-cause mortality . No variable had a c-index > 0.70 , and few had values > 0.60 ; c-indices were lower for composite outcomes than for mortality . Blood urea was generally the strongest single predictor . Eighteen variables contributed independent prognostic information , but a reduced model using only 8 items ( age , previous heart failure hospitalization , peripheral edema , systolic blood pressure , serum sodium , urea , creatinine , and albumin ) performed similarly . For prediction of all-cause mortality at 180 days , the model c-index using all variables was 0.72 and for the simplified model , also 0.72 . CONCLUSIONS A few simple clinical variables measured on admission in patients with acute heart failure predict a variety of adverse outcomes with accuracy similar to more complex models . However , predictive models were of only moderate accuracy , especially for outcomes that included nonfatal events . Better methods of risk stratification are required . CLINICAL TRIAL REGISTRATION URL : http : //www.clinicaltrials.gov . Unique identifiers : NCT00328692 and NCT00354458 .

rolofylline

placebo

death

rehospitalization for any reason

death

Blood urea

all-cause mortality

variety of adverse outcomes

accuracy

moderate accuracy

acute heart failure

Acute heart failure

admitted with acute heart failure

acute heart failure


Prediction of gestational diabetes mellitus in the first trimester , comparison of fasting plasma glucose , two-step and one-step methods : a prospective randomized controlled trial . Our aim was to evaluate and compare the diagnostic performance of three methods commonly used for GDM screening : fasting plasma glucose ( FPG ) , two-step 50 g glucose challenge test ( GCT ) , and 75 g glucose tolerance test ( GTT ) in a randomized study design to predict GDM in the first trimester and determine the best approach in predicting GDM . In a non-blind , parallel-group prospective randomized controlled study ; 736 singleton pregnant women underwent FPG testing in the first trimester and randomly assigned to two groups ; two-step 50 g GCT and 75 g GTT . GDM diagnosis was made according to Carpenter-Coustan or ADA ( American Diabetes Association ) criteria in two-step 50 g GCT and 75 g GTT groups , respectively . Subsequent testing was performed by two-step 50 g GCT at 24-28 weeks for screen negatives . After excluding the women who were lost to follow-up or withdrawn as a result of pregnancy loss , 486 pregnant women were recruited in the study . The FPG , two-step GCT , and one-step GTT methods identified GDM in 25/486 ( 5.1 % ) , 15/248 ( 6.0 % ) , and 27/238 ( 11.3 % ) women , respectively . Area under ROC curves were 0.623 , 0.708 , and 0.792 , respectively . Sensitivities were 47.17 , 68.18 , and 87.1 % , respectively . Specificities were 77.37 , 100 , and 100 % , respectively . Positive predictive values were 20.33 , 100 , and 100 % , respectively . Negative predictive values were 92.29 , 97 , and 98.1 % , respectively . Until superior screening alternatives become available , the 75 g GTT may be preferred for GDM screening in the first trimester .

fasting plasma glucose ( FPG )

glucose challenge test ( GCT )

75 g glucose tolerance test ( GTT )

two-step 50 g GCT

75 g GTT

diagnostic performance

Area under ROC curves

Sensitivities

Positive predictive values

Negative predictive values

first trimester

first trimester

women

women

women

first trimester


Continuous glucose monitoring in acute coronary syndrome . BACKGROUND Diabetes mellitus is an independent risk factor for cardiovascular disease . OBJECTIVE To compare the efficacy of devices for continuous glucose monitoring and capillary glucose monitoring in hospitalized patients with acute coronary syndrome using the following parameters : time to achieve normoglycemia , period of time in normoglycemia , and episodes of hypoglycemia . METHODS We performed a pilot , non-randomized , unblinded clinical trial that included 16 patients with acute coronary artery syndrome , a capillary or venous blood glucose ≥ 140 mg/dl , and treatment with a continuous infusion of fast acting human insulin . These patients were randomized into 2 groups : a conventional group , in which capillary measurement and recording as well as insulin adjustment were made every 4h , and an intervention group , in which measurement and recording as well as insulin adjustment were made every hour with a subcutaneous continuous monitoring system . Student 's t-test was applied for mean differences and the X ( 2 ) test for qualitative variables . RESULTS We observed a statistically significant difference in the mean time for achieving normoglycemia , favoring the conventional group with a P = 0.02 . CONCLUSION Continuous monitoring systems are as useful as capillary monitoring for achieving normoglycemia .

efficacy of devices

time to achieve normoglycemia

period of time in normoglycemia

episodes of hypoglycemia

Student 's t-test

the X ( 2 ) test

time for achieving normoglycemia

acute coronary syndrome

Diabetes mellitus

cardiovascular disease .

acute coronary artery syndrome


A novel methodology for generating 3D finite element models of the hip from 2D radiographs . Finite element ( FE ) modelling has been proposed as a tool for estimating fracture risk and patient-specific FE models are commonly based on computed tomography ( CT ) . Here , we present a novel method to automatically create personalised 3D models from standard 2D hip radiographs . A set of geometrical parameters of the femur were determined from seven a-p hip radiographs and compared to the 3D femoral shape obtained from CT as training material ; the error in reconstructing the 3D model from the 2D radiographs was assessed . Using the geometry parameters as the input , the 3D shape of another 21 femora was built and meshed , separating a cortical and trabecular compartment . The material properties were derived from the homogeneity index assessed by texture analysis of the radiographs , with focus on the principal tensile and compressive trabecular systems . The ability of these FE models to predict failure load as determined by experimental biomechanical testing was evaluated and compared to the predictive ability of DXA . The average reconstruction error of the 3D models was 1.77 mm ( ±1.17 mm ) , with the error being smallest in the femoral head and neck , and greatest in the trochanter . The correlation of the FE predicted failure load with the experimental failure load was r ( 2 ) =64 % for the reconstruction FE model , which was significantly better ( p < 0.05 ) than that for DXA ( r ( 2 ) =24 % ) . This novel method for automatically constructing a patient-specific 3D finite element model from standard 2D radiographs shows encouraging results in estimating patient-specific failure loads .

3D finite element models

2D radiographs

Finite element ( FE ) modelling

patient-specific FE models

computed tomography

a-p hip radiographs

3D femoral shape obtained from CT

FE models

fracture risk

homogeneity index

failure load

average reconstruction error

models of the hip


Exercise for methamphetamine dependence : rationale , design , and methodology . BACKGROUND Effective pharmacotherapies to treat methamphetamine ( MA ) dependence have not been identified , and behavioral therapies are marginally effective . Based on behavioral studies demonstrating the potential efficacy of aerobic exercise for improving depressive symptoms , anxiety , cognitive deficits , and substance use outcomes , the study described here is examining exercise as a potential treatment for MA-dependent individuals . METHODS This study is randomizing 150 participants with MA dependence at a residential treatment facility for addictive disorders to receive either a thrice-weekly structured aerobic and resistance exercise intervention or a health education condition . Recruitment commenced in March , 2010 . Enrollment and follow-up phases are ongoing , and recruitment is exceeding targeted enrollment rates . CONCLUSIONS Seeking evidence for a possibly effective adjunct to traditional behavioral approaches for treatment of MA dependence , this study is assessing the ability of an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use during a 12-week follow-up period after discharge from residential-based treatment . The study also is evaluating improvements in health and functional outcomes during and after the protocol . This paper describes the design and methods of the study .

Exercise

methamphetamine

aerobic exercise

exercise

aerobic and resistance exercise

MA dependence

relapse to MA

health and functional outcomes

methamphetamine dependence :

MA-dependent individuals .


Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation : a randomized trial . To evaluate the effect of the different doses of antithymocyte globulin ( ATG ) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors , 224 patients with standard-risk hematological malignancy were randomized in this study . One hundred and twelve patients received 6 mg/kg ATG , whereas the remaining patients received 10 mg/kg ATG . This study was registered at http : //www.chictr.org as No . ChiCTR-TRC-11001761 . The incidence of grade III-IV acute GVHD was higher in the ATG-6 group ( 16.1 % , 95 % confidence interval ( CI ) , 9.1-23.1 % ) than in the ATG-10 group ( 4.5 % , CI , 0.7-8.3 % , P=0.005 , 95 % CI for the difference , -19.4 % to -3.8 % ) . EBV reactivation occurred more frequently in the ATG-10 group ( 25.3 % , 17.1-33.5 % ) than in the ATG-6 group ( 9.6 % ( 4.0-15.2 % ) , P=0.001 ) . The 1-year disease-free survival rates were 84.3 % ( 77.3-91.3 % ) and 86.0 % ( 79.2-92.8 % ) for the ATG-6 group and ATG-10 groups , respectively ( P=0.88 ) . In conclusion , although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG , this treatment exposes patients to a higher risk for severe acute GVHD .

antithymocyte globulin

antithymocyte globulin ( ATG )

standard-risk disease

haploidentical transplantation

224 patients

standard-risk hematological malignancy

One hundred and twelve patients


Short-term amiodarone therapy after reversion of persistent atrial fibrillation reduces recurrences at 18 months . BACKGROUND The aim of this study was to compare the outcome of 3 months vs. 18 months of amiodarone treatment after atrial fibrillation ( AF ) conversion in patients who experienced the first episode of persistent AF . METHODS We included 51 patients who experienced the first episode of persistent AF receiving amiodarone ( 600 mg ) daily for 4-6 weeks . If AF persisted , electrical cardioversion ( ECV ) was performed . All patients received amiodarone ( 200 mg daily ) for 3 months and then were randomized to amiodarone ( Group I ) or placebo ( Group II ) and followed for 15 months . The control group comprised 9 untreated patients undergoing ECV . Treatment effectiveness was evaluated using a Bayesian model . RESULTS Eighteen months after AF reversion , 22 ( 81.5 % ) patients in Group I , 13 ( 54.2 % ) patients in Group II , and 1 ( 11.1 % ) patient in the control group remained in sinus rhythm . No differences were found between Group I patients who required ECV and Group II patients . Sinus rhythm was preserved in all Group I patients when it was achieved during amiodarone administration . Limiting adverse effects occurred in 3 ( 11.1 % ) patients in Group I . CONCLUSIONS In patients regaining sinus rhythm after the first episode of persistent AF , a 3-month amiodarone treatment after reversion is a reasonable option for rhythm control .

Short-term amiodarone therapy

amiodarone

amiodarone

electrical cardioversion ( ECV )

amiodarone

amiodarone

placebo

ECV

ECV

amiodarone

recurrences

effectiveness

remained in sinus rhythm .

Sinus rhythm

Limiting adverse effects

persistent atrial fibrillation

persistent AF


An intervention to decrease stigma in young adults with sickle cell disease . Young adults with sickle cell disease ( SCD ) are often stigmatized when they seek care for pain . The purpose of this pilot study was to test an intervention to decrease health-related stigma during care-seeking . Young adults with SCD ages 18 to 35 years ( n = 90 ) were randomized to either the care-seeking intervention ( CSI ) or an attention control group that participated in life review interviews . The two groups were compared by t tests and longitudinal data analyses on the change from baseline to the last time point in total health-related stigma and health-related stigma by doctors . Findings suggest that the CSI was associated with significant increased awareness of perceived total stigma and stigma by doctors compared with the attention control group . These findings are promising in terms of lessons learned from a pilot intervention that focused on the role communication skills play in decreasing health-related stigma in young adults with SCD .

attention control group

CSI

stigma

health-related stigma

total health-related stigma

health-related stigma by doctors .

awareness of perceived total stigma

stigma by doctors

young adults

sickle cell disease

Young adults

sickle cell disease ( SCD )

Young adults

SCD

ages 18 to 35 years

n = 90

young adults

SCD


Radiation and contrast agent doses reductions by using 80-kV tube voltage in coronary computed tomographic angiography : a comparative study . OBJECTIVE To investigate the effects of 80-kilovoltage ( kV ) tube voltage coronary computed tomographic angiography ( CCTA ) with a reduced amount of contrast agent on qualitative and quantitative image quality parameters and on radiation dose in patients with a body mass index ( BMI ) < 23.0 kg/m ( 2 ) . METHODS One hundred and twenty consecutive patients with a BMI < 23.0 kg/m ( 2 ) and a low calcium load undergoing retrospective electrocardiogram ( ECG ) -gated dual-source CCTA were randomized into two groups [ standard-tube voltage ( 120-kV ) vs. low-tube voltage ( 80-kV ) ] . The injection flow rate of contrast agent ( 350 mg I/mL ) was adjusted to body weight of each patient ( 4.5-5.5 mL/s in the 120-kV group and 2.8-3.8 mL/s in the 80-kV group ) . Radiation and contrast agent doses were evaluated . Quantitative image quality parameters and figure of merit ( FOM ) of coronary artery were evaluated . Each coronary segment was evaluated for image quality on a 4-point scale . RESULTS Compared with the 120-kV group , effective dose and amount of contrast agent in the 80-kV group were decreased by 57.8 % and 30.5 % ( effective dose:2.7 ± 0.5 vs. 6.4 ± 1.3 mSv ; amount of contrast agent:57.1 ± 3.2 vs. 82.1 ± 6.1 mL ; both p < 0.0001 ) , respectively . Image noise was 22.7 ± 2.1HU for 120-kV images and 33.2 ± 5.2 HU for 80-kV images ( p < 0.0001 ) . Signal-to-noise ratio ( SNR ) and contrast-to-noise ratio ( CNR ) in the proximal right coronary artery ( RCA ) and left main coronary artery ( LMA ) were all lower in 80-kV than 120-kV images ( SNR in the proximal RCA : 16.5 ± 1.8 vs. 19.4 ± 2.8 ; SNR in the LMA : 16.3 ± 2.0 vs.19.6 ± 2.7 ; CNR in the proximal RCA : 19.4 ± 2.3 vs.22.9 ± 3.0 ; CNR in the LMA : 18.8 ± 2.4 vs. 22.7 ± 2.9 ; all p < 0.0001 ) . FOM were all significantly higher in 80-kV than 120-kV images ( proximal RCA : 146.7 ± 45.1 vs. 93.4 ± 32.0 ; LMA : 139.1 ± 47.2 vs. 91.6 ± 31.1 ; all p < 0.0001 ) . There was no significant difference in image quality score between the two groups ( 3.3 ± 0.8 vs. 3.3 ± 0.8 , p=0.068 ) despite decreased SNR and CNR of coronary artery in the 80-kV group . CONCLUSION The 80-kV protocol significantly reduces radiation and contrast agent doses in CCTA in patients with a low BMI < 23.0 kg/m ( 2 ) and a low calcium load while maintaining image quality .

standard-tube voltage

( 120-kV )

low-tube voltage

( 80-kV ) ]

Radiation and contrast agent doses

image quality

Image noise

Signal-to-noise ratio ( SNR )

contrast-to-noise ratio ( CNR )

One hundred and twenty

CCTA


Randomized clinical trial of cutting balloon angioplasty versus high-pressure balloon angioplasty in hemodialysis arteriovenous fistula stenoses resistant to conventional balloon angioplasty . PURPOSE To compare the efficacy and safety of cutting balloon angioplasty ( CBA ) versus high-pressure balloon angioplasty ( HPBA ) for the treatment of hemodialysis autogenous fistula stenoses resistant to conventional percutaneous transluminal angioplasty ( PTA ) . MATERIALS AND METHODS In a prospective , randomized clinical trial involving patients with dysfunctional , stenotic hemodialysis arteriovenous fistulas ( AVFs ) , patients were randomized to receive CBA or HPBA if conventional PTA had suboptimal results ( ie , residual stenosis > 30 % ) . A total of 516 patients consented to participate in the study from October 2008 to September 2011 , 85 % of whom ( n = 439 ) had technically successful conventional PTA . The remaining 71 patients ( mean age , 60 y ; 49 men ) with suboptimal PTA results were eventually randomized : 36 to the CBA arm and 35 to the HPBA arm . Primary and secondary target lesion patencies were determined by Kaplan-Meier analysis . RESULTS Clinical success rates were 100 % in both arms . Primary target lesion patency rates at 6 months were 66.4 % and 39.9 % for CBA and HPBA , respectively ( P = .01 ) . Secondary target lesion patency rates at 6 months were 96.5 % for CBA and 80.0 % for HPBA ( P = .03 ) . There was a single major complication of venous perforation following CBA . The 30-day mortality rate was 1.4 % , with one non-procedure-related death in the HPBA group . CONCLUSIONS Primary and secondary target lesion patency rates of CBA were statistically superior to those of HPBA following suboptimal conventional PTA . For AVF stenoses resistant to conventional PTA , CBA may be a better second-line treatment given its superior patency rates .

cutting balloon angioplasty

high-pressure balloon angioplasty

CBA

HPBA

CBA

CBA

HPBA

CBA

HPBA

CBA

HPBA

CBA

HPBA

CBA

efficacy and safety

Clinical success rates

Primary target lesion patency rates

Secondary target lesion patency rates

major complication

venous perforation

30-day mortality rate

mean age , 60 y


Activation and intermuscular coherence of distal arm muscles during proximal muscle contraction . In the human upper extremity ( UE ) , unintended effects of proximal muscle activation on muscles controlling the hand could be an important aspect of motor control due to the necessary coordination of distal and proximal segments during functional activities . This study aimed to elucidate the effects of concurrent activation of elbow muscles on the coordination between hand muscles performing a grip task . Eleven healthy subjects performed precision grip tasks while a constant extension or flexion moment was applied to their elbow joints , inducing a sustained submaximal contraction of elbow muscles to counter the applied torque . Activation of four hand muscles was measured during each task condition using surface electromyography ( EMG ) . When concurrent activation of elbow muscles was induced , significant changes in the activation levels of the hand muscles were observed , with greater effects on the extrinsic finger extensor ( 23.2 % increase under 30 % elbow extensor activation ; p = 0.003 ) than extrinsic finger flexor ( 14.2 % increase under 30 % elbow flexor activation ; p = 0.130 ) . Elbow muscle activation also induced involuntary changes in the intrinsic thumb flexor activation ( 44.6 % increase under 30 % elbow extensor activation ; p = 0.005 ) . EMG-EMG coherence analyses revealed that elbow muscle activation significantly reduced intermuscular coherence between distal muscle pairs , with its greatest effects on coherence in the β-band ( 13-25 Hz ) ( average of 17 % decrease under 30 % elbow flexor activation ) . The results of this study provide evidence for involuntary , muscle-specific interactions between distal and proximal UE muscles , which may contribute to UE motor performance in health and disease .

surface

electromyography

( EMG ) .

activation levels of the hand muscles

Elbow muscle activation

intrinsic thumb flexor activation

elbow muscle activation

Eleven healthy subjects


Intraluminal exfoliated cancer cells and effectiveness of bowel ligatures during sigmoidectomy for sigmoid colon cancer . PURPOSES To establish the efficiency of bowel ligatures in colon cancer surgery , focusing on the extent to which exfoliated cancer cells are shed in the colonic lumen during sigmoidectomy . METHODS Twenty consecutive patients who underwent sigmoidectomy for sigmoid colon cancer were prospectively randomized into two groups : the " ligatures group " , in which bowel ligatures were placed , 3 , 5 , 10 cm from the tumor proximally and distally before dissection ; and the " no ligatures group " , in which the corresponding sites were ligated only immediately before taking the specimen out . Each colonic segment ligated was irrigated with saline and samples were sent for blind cytological examination . RESULTS Cancer cells were found in the colonic segment where the tumor was located , in 18 of 20 samples . The frequency of free cancer cells decreased from 50 to 0 % ( p < 0.04 ) in the distal 3-5 cm colonic segment and from 80 to 20 % ( p < 0.03 ) in the proximal colonic segment after performing bowel ligatures . Free cancer cells were confirmed in 1 of 10 samples at both colonic segments 5-10 cm from the tumor , even after bowel ligatures . CONCLUSIONS Intraluminal exfoliated cancer cells could be eliminated by placing bowel ligatures during sigmoidectomy . Measures should be considered to eliminate exfoliated cancer cells during colectomy , even after placing bowel ligatures .

sigmoidectomy

colon cancer surgery

sigmoidectomy

sigmoidectomy

ligatures group

ligatures group

irrigated with saline

colon cancer surgery

Twenty consecutive patients

sigmoidectomy for sigmoid colon cancer

during colectomy


Learning the 'traceback ' approach for interscalene block .

'traceback ' approach

interscalene block .


Randomized , placebo-controlled , phase III trial of sunitinib plus prednisone versus prednisone alone in progressive , metastatic , castration-resistant prostate cancer . PURPOSE We evaluated angiogenesis-targeted sunitinib therapy in a randomized , double-blind trial of metastatic castration-resistant prostate cancer ( mCRPC ) . PATIENTS AND METHODS Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo . Patients also received oral prednisone 5 mg twice daily . The primary end point was overall survival ( OS ) ; secondary end points included progression-free survival ( PFS ) . Two interim analyses were planned . RESULTS Overall , 873 patients were randomly assigned to receive sunitinib ( n = 584 ) or placebo ( n = 289 ) . The independent data monitoring committee stopped the study for futility after the second interim analysis . After a median overall follow-up of 8.7 months , median OS was 13.1 months and 11.8 months for sunitinib and placebo , respectively ( hazard ratio [ HR ] , 0.914 ; 95 % CI , 0.762 to 1.097 ; stratified log-rank test , P = .168 ) . PFS was significantly improved in the sunitinib arm ( median 5.6 v 4.1 months ; HR , 0.725 ; 95 % CI , 0.591 to 0.890 ; stratified log-rank test , P < .001 ) . Toxicity and rates of discontinuations because of adverse events ( AEs ; 27 % v 7 % ) were greater with sunitinib than placebo . The most common treatment-related grade 3/4 AEs were fatigue ( 9 % v 1 % ) , asthenia ( 8 % v 2 % ) , and hand-foot syndrome ( 7 % v 0 % ) . Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia ( 20 % v 11 % ) , anemia ( 9 % v 8 % ) , and neutropenia ( 6 % v < 1 % ) . CONCLUSION The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC . The role of antiangiogenic therapy in mCRPC remains investigational .

sunitinib 37.5 mg/d

placebo

oral prednisone 5 mg twice daily

angiogenesis-targeted sunitinib therapy

overall survival

progression-free survival ( PFS )

median OS

PFS

fatigue

asthenia

hand-foot syndrome

hematologic abnormalities

lymphopenia

anemia

neutropenia

OS


Conduit artery structure and function in lowlanders and native highlanders : relationships with oxidative stress and role of sympathoexcitation . Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology ( e.g. , chronic mountain sickness ) and methodological issues . We examined vascular function and structure in : ( 1 ) healthy lowlanders during acute hypoxia and prolonged ( ∼2 weeks ) exposure to high altitude , and ( 2 ) high-altitude natives at 5050 m ( highlanders ) . In 12 healthy lowlanders ( aged 32 ± 7 years ) and 12 highlanders ( Sherpa ; 33 ± 14 years ) we assessed brachial endothelium-dependent flow-mediated dilatation ( FMD ) , endothelium-independent dilatation ( via glyceryl trinitrate ; GTN ) , common carotid intima-media thickness ( CIMT ) and diameter ( ultrasound ) , and arterial stiffness via pulse wave velocity ( PWV ; applanation tonometry ) . Cephalic venous biomarkers of free radical-mediated lipid peroxidation ( lipid hydroperoxides , LOOH ) , nitrite ( NO2- ) and lipid soluble antioxidants were also obtained at rest . In lowlanders , measurements were performed at sea level ( 334 m ) and between days 3-4 ( acute high altitude ) and 12-14 ( chronic high altitude ) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level , acute high altitude reduced lowlanders ' FMD ( 7.9 ± 0.4 vs. 6.8 ± 0.4 % ; P = 0.004 ) and GTN-induced dilatation ( 16.6 ± 0.9 vs. 14.5 ± 0.8 % ; P = 0.006 ) , and raised central PWV ( 6.0 ± 0.2 vs. 6.6 ± 0.3 m s ( -1 ) ; P = 0.001 ) . These changes persisted at days 12-14 , and after allometrically scaling FMD to adjust for altered baseline diameter . Compared to lowlanders at sea level and high altitude , highlanders had a lower carotid wall : lumen ratio ( ∼19 % , P ≤ 0.04 ) , attributable to a narrower CIMT and wider lumen . Although both LOOH and NO2- increased with high altitude in lowlanders , only LOOH correlated with the reduction in GTN-induced dilatation evident during acute ( n = 11 , r = -0.53 ) and chronic ( n = 7 , r = -0.69 ; P ≤ 0.01 ) exposure to 5050 m. In a follow-up , placebo-controlled experiment ( n = 11 healthy lowlanders ) conducted in a normobaric hypoxic chamber ( inspired O2 fraction ( F IO 2 ) = 0.11 ; 6 h ) , a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline ( 5.7 ± 1.6 vs. 8.0 ±1.3 % ; P < 0.01 ) ; this decline in FMD was largely reversed following α1-adrenoreceptor blockade . In conclusion , high-altitude exposure in lowlanders caused persistent impairment in vascular function , which was mediated partially via oxidative stress and sympathoexcitation . Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure , chronic high-altitude exposure appears to be associated with arterial remodelling .

carotid wall : lumen

lowlanders and native highlanders :


Using the virtual reality-cognitive rehabilitation approach to improve contextual processing in children with autism . BACKGROUND This pilot study investigated the efficacy of a novel virtual reality-cognitive rehabilitation ( VR-CR ) intervention to improve contextual processing of objects in children with autism . Previous research supports that children with autism show deficits in contextual processing , as well as deficits in its elementary components : abstraction and cognitive flexibility . METHODS Four children with autism participated in a multiple-baseline , single-subject study . The children were taught how to see objects in context by reinforcing attention to pivotal contextual information . RESULTS All children demonstrated statistically significant improvements in contextual processing and cognitive flexibility . Mixed results were found on the control test and changes in context-related behaviours . CONCLUSIONS Larger-scale studies are warranted to determine the effectiveness and usability in comprehensive educational programs .

contextual processing

contextual processing

contextual processing

abstraction

cognitive flexibility

contextual processing

cognitive flexibility

context-related behaviours

children

autism

children

autism

children

autism

Four

children

autism

children

children


Randomized study comparing use of THUNDERBEAT technology vs standard electrosurgery during laparoscopic radical hysterectomy and pelvic lymphadenectomy for gynecologic cancer . STUDY OBJECTIVE To compare operative time with use of THUNDERBEAT ( TB ) vs standard electrosurgery ( SES ) during laparoscopic radical hysterectomy and pelvic lymphadenectomy to treat gynecologic tumors . DESIGN Evidence obtained from a properly designed , randomized , controlled trial ( Canadian Task Force classification I ) . SETTING Gynecologic Oncology Unit of the Catholic University of the Sacred Heart in Rome , Italy . PATIENTS Fifty patients with early cervical cancer ( FIGO stages IA2 , IB1 , IIA < 2 cm ) or locally advanced cervical cancer ( FIGO stages IB2 , IIA > 2cm , IIB ) who received neoadjuvant treatment ( chemotherapy or radiochemotherapy ) and demonstrated a complete or partial clinical response and early stage endometrioid endometrial cancer ( FIGO stages IB , II ) were randomly assigned to undergo TB ( arm A ) or SES ( arm B ) . INTERVENTION Laparoscopic radical hysterectomy with bilateral pelvic lymphadenectomy , using an easily reproducible technique was performed . MEASUREMENTS AND MAIN RESULTS Fifty patients were available for analysis , with 25 women randomly assigned to TB ( arm A ) and 25 to SES ( arm B ) . The median operative time was 85 minutes for TB vs 115 minutes for SES ( p = .001 ) . At multivariate analysis , endometrial cancer ( p = .001 ) and TB ( p = .001 ) were independently associated with shorter operating time . No differences in perioperative outcomes and postoperative complications were observed between the 2 arms . Patients who underwent TB reported less postoperative pain , both at rest ( p = .005 ) and after the Valsalva maneuver ( p = .008 ) , with less additional analgesic therapy other than standard therapy required in patients who underwent SES ( p = .02 ) . CONCLUSION TB is associated with shorter operative time and less postoperative pain than is the standard technique ( SES ) in patients with uterine cancer .

THUNDERBEAT

standard electrosurgery

neoadjuvant treatment (

chemotherapy

or radiochemotherapy )

median operative time

shorter operating time .

postoperative pain

operative time

postoperative pain

gynecologic cancer

gynecologic tumors .

Fifty

cervical cancer

cervical cancer

Fifty

women

uterine cancer


Impact of vitamin D supplementation on inflammatory markers in African Americans : results of a four-arm , randomized , placebo-controlled trial . African Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [ 25 ( OH ) D ] . The effect of vitamin D3 ( cholecalciferol ) supplementation on inflammatory markers is uncertain . We conducted a randomized , double-blind , placebo-controlled trial of supplemental oral vitamin D ( placebo , 1,000 , 2,000 , or 4,000 IU/day of vitamin D3 orally for 3 months ) in 328 African Americans ( median age , 51 years ) of public housing communities in Boston , MA , who were enrolled over three consecutive winter periods ( 2007-2010 ) . Change from 0 to 3 months of plasma levels of 25 ( OH ) D , high-sensitivity C-reactive protein ( CRP ) , interleukin ( IL ) -6 , IL-10 , and soluble TNF-α receptor type 2 ( sTNF-R2 ) in 292 ( 89 % ) participants were measured . Overall , no statistically significant changes in CRP , IL-6 , IL-10 , and sTNF-R2 were observed after the vitamin D supplementation period . Baseline CRP was significantly inversely associated with the baseline 25 ( OH ) D level ( P < 0.001 ) in unadjusted and adjusted models . An interaction between baseline 25 ( OH ) D and vitamin D supplementation was observed for outcome change in log CRP ( month 3-month 0 ; P for interaction = 0.04 ) . Within an unselected population of African Americans , short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers . This study confirms the strong independent association of CRP with 25 ( OH ) D status even after adjusting for body mass index . Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African Americans .

vitamin D supplementation

supplemental oral vitamin D

inflammatory markers

inflammatory markers


Short- and long-term effects of tactile massage on salivary cortisol concentrations in Parkinson 's disease : a randomised controlled pilot study . BACKGROUND Parkinson 's disease ( PD ) is a chronic neurodegenerative disorder with limited knowledge about the normal function and effects of non-pharmacological therapies on the hypothalamic-pituitary-adrenal ( HPA ) axis . The aim of the study was to analyse the basal diurnal and total secretion of salivary cortisol in short- and long-term aspects of tactile massage ( TM ) . METHODS DESIGN Prospective , Controlled and Randomised Multicentre Trial . SETTING AND INTERVENTIONS Forty-five women and men , aged 50-79 years , were recruited . Twenty-nine of them were blindly randomised to tactile massage ( TM ) and 16 of them to the control group , rest to music ( RTM ) . Ten interventions were given during 8 weeks followed by a 26 weeks of follow up . Salivary cortisol was collected at 8 am , 1 pm , 8 pm , and 8 am the next day , on five occasions . With the first and eighth interventions , it was collected immediately before and after intervention . MAIN OUTCOME MEASURES The primary aim was to assess and compare cortisol concentrations before and immediately after intervention and also during the follow-up period . The secondary aim was to assess the impact of age , gender , body mass index ( BMI ) , duration and severity of PD , effects of interventional time-point of the day , and levodopa doses on cortisol concentration . RESULTS The median cortisol concentrations for all participants were 16.0 , 5.8 , 2.8 , and 14.0 nmol/L at baseline , later reproduced four times without significant differences . Cortisol concentrations decreased significantly after TM intervention but no change in diurnal salivary cortisol pattern was found . The findings of reduced salivary cortisol concentrations immediately after the interventions are in agreement with previous studies . However , there was no significant difference between the TM and control groups . There were no significant correlations between cortisol concentrations and age , gender , BMI , time-point for intervention , time interval between anti-parkinson pharmacy intake and sampling , levodopa doses , duration , or severity of PD . CONCLUSIONS Diurnal salivary cortisol rhythm was normal . Salivary cortisol concentrations were significantly reduced after the TM intervention and after RTM , but there were no significant differences between the groups and no sustained long-term effect . No associations were seen between salivary cortisol concentration and clinical and/or pharmacological characteristics . TRIAL REGISTRATION ClinicalTrial.gov , NCT01734876 and FoU Sweden 108881 .

tactile massage

non-pharmacological therapies

tactile massage ( TM )

tactile massage ( TM )

control

rest to music ( RTM )

TM

TM

TM

RTM

Short- and long-term effects

salivary cortisol concentrations

Salivary cortisol

median cortisol concentrations

Cortisol concentrations

salivary cortisol concentrations

cortisol concentrations

Diurnal salivary cortisol rhythm

Salivary cortisol concentrations

salivary cortisol concentration

Parkinson 's disease

Forty-five

women and men

aged 50-79 years

Twenty-nine


Vitamin D supplementation increases calcium absorption without a threshold effect . BACKGROUND The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency . OBJECTIVE The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D , or concentrations of serum 25-hydroxyvitamin D [ 25 ( OH ) D ] , no longer increase calcium absorption . DESIGN This was a placebo-controlled , dose-response , randomized , double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women . Seventy-six healthy postmenopausal women were randomly assigned to placebo or 800 IU ( 20 μg ) , 2000 IU ( 50 μg ) , or 4000 IU ( 100 μg ) vitamin D₃ for 8 wk . The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk . RESULTS Seventy-one women with a mean ± SD age of 58.8 ± 4.9 y completed the study . The mean calcium intake was 1142 ± 509 mg/d and serum 25 ( OH ) D was 63 ± 14 nmol/L at baseline . A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D₃ dose or serum 25 ( OH ) D concentration was observed . A 6.7 % absolute increase in calcium absorption was found in the highest vitamin D₃ group ( 100 μg ) . No evidence of nonlinearity was observed in the dose-response curve . CONCLUSIONS No evidence of a threshold of calcium absorption was found with a serum 25 ( OH ) D range from 40 to 130 nmol/L . Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin D .

Vitamin D supplementation

vitamin D

vitamin D

vitamin D

serum 25-hydroxyvitamin D

placebo-controlled

vitamin D

placebo

calcium absorption

calcium absorption

postmenopausal

women

Seventy-six

postmenopausal

women


TGF-beta receptor type-2 expression in cancer-associated fibroblasts regulates breast cancer cell growth and survival and is a prognostic marker in pre-menopausal breast cancer . Transforming growth factor-beta ( TGF-β ) is a pleiotropic cytokine with the capability to act as tumour suppressor or tumour promoter depending on the cellular context . TGF-beta receptor type-2 ( TGFBR2 ) is the ligand-binding receptor for all members of the TGF-β family . Data from mouse model experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts was linked to tumour initiation and metastasis . Using a randomised tamoxifen trial cohort including in total 564 invasive breast carcinomas , we examined TGFBR2 expression ( n=252 ) and phosphorylation level of downstream target SMAD2 ( pSMAD2 ) ( n=319 ) in cancer-associated fibroblasts ( CAFs ) and assessed links to clinicopathological markers , prognostic and treatment-predictive values . The study revealed that CAF-specific TGFBR2 expression correlated with improved recurrence-free survival . Multivariate analysis confirmed CAF-TGFBR2 to be an independent prognostic marker ( multivariate Cox regression , hazard ratio : 0.534 , 95 % ( CI ) : 0.360-0.793 , P=0.002 ) . CAF-specific pSMAD2 levels , however , did not associate with survival outcome . Experimentally , TGF-β signalling in fibroblasts was modulated using a TGF-β ligand and inhibitor or through lentiviral short hairpin RNA-mediated TGFBR2-specific knockdown . To determine the role of fibroblastic TGF-β pathway on breast cancer cells , we used cell contact-dependent cell growth and clonogenicity assays , which showed that knockdown of TGFBR2 in CAFs resulted in increased cell growth , proliferation and clonogenic survival . Further , in a mouse model transfected CAFs were co-injected with MCF7 and tumour weight and proportion was monitored . We found that mouse xenograft tumours comprising TGFBR2 knockdown fibroblasts were slightly bigger and displayed increased tumour cell capacity . Overall , our data demonstrate that fibroblast-related biomarkers possess clinically relevant information and that fibroblasts confer effects on breast cancer cell growth and survival . Regulation of tumour-stromal cross-talk through fibroblastic TGF-β pathway may depend on fibroblast phenotype , emphasising the importance to characterise tumour microenvironment subtypes .

P=0.002 ) .

CAF-specific pSMAD2 levels

TGF-β signalling in fibroblasts

cell growth

proliferation

clonogenic survival

MCF7 and tumour weight and proportion

from mouse model experiments

breast carcinomas

in a mouse model


Humour-related interventions for people with mental illness : a randomized controlled pilot study . This study explored the feasibility and effects of humour-related interventions for mentally ill adults . Twelve , randomly assigned , participated in each of 3 arms -- stand up comedy training ( the experimental arm ) , discussing comedy videos ( the active control arm ) , and no humour-related intervention ( the passive control arm ) . Quantitative and qualitative data were collected at baseline , end of interventions ( 3 months ) and follow up ( after another 3 months ) . Scale comparisons were largely negative , although self-esteem marginally increased in the experimental arm . Interview responses indicated benefits for the interventions , including improved self-esteem in the experimental arm . These results , though mixed , justify further study .

humour-related

no

humour-related intervention

Quantitative and qualitative data

Scale comparisons

self-esteem

improved self-esteem

mental illness

mentally ill

Twelve ,


Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer : a randomized phase II trial-an update . Prolonged infusion of low-dose gemcitabine and cisplatin ( GC ) proved to be an effective treatment for patients with advanced bladder cancer . One hundred and twenty untreated patients with stage III/IV bladder cancer were randomized to receive either gemcitabine ( 250 mg/m ( 2 ) ) 6-h infusion on days 1 and 8 , and cisplatin ( 70 mg/m ( 2 ) ) on day 2 every 21-day cycle ( arm 1 ) or gemcitabine ( 1,250 mg/m ( 2 ) ) 30-min infusion on days 1 and 8 , with the same dose of cisplatin ( arm 2 ) . The 92 males and 28 females included in the study had a median age of 62 years ( range 40-85 years ) . Among the 120 patient , complete response was achieved in 11.7 % ( 7/60 patients of arm 1 ) and 5 % ( 3/60 patients of arm 2 ) . Eighteen patients in arm 1 ( 30 % ) and 17 patients ( 28.3 % ) in arm 2 had partial response on therapy . Thus , the overall response rate of patients in arm 1 and arm 2 was 41.7 % ( 25/60 patients ) and 33.3 % ( 20/60 patients ) , respectively ( p = 0.37 ) . No significant difference in median time to disease progression ( 26 vs. 24 months , p = 0.4 ) , median survival ( 12 vs. 16 months , p = 0.8 ) , and 1-year survival ( 49.9 vs. 54.7 % , p = 0.8 ) was detected between arms 1 and 2 , respectively . Main toxicities were similar in both arms with no statistically significant differences . Low-dose , prolonged infusion gemcitabine in combination with cisplatin is not inferior to the standard GC regimen with favorable toxicity profile and less financial costs .

gemcitabine infusion

cisplatin

gemcitabine and cisplatin ( GC )

gemcitabine

cisplatin

gemcitabine

cisplatin

gemcitabine

cisplatin

standard GC regimen

overall response rate

median time to disease progression

median survival

1-year survival

Main toxicities

toxicity profile

financial costs

advanced bladder cancer

advanced bladder cancer

One hundred and twenty

stage III/IV bladder cancer

males

28 females

median age of 62 years

40-85 years