Duration of chemotherapy in small cell lung cancer : a Cancer Research Campaign trial . A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival . Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide , vincristine and etoposide and also randomised to receive , on disease progression , either second line chemotherapy ( methotrexate and doxorubicin ) or symptomatic treatment only . In the whole study 196 ( 32.1 % ) had limited disease and 414 ( 67.9 % ) extensive disease . During initial chemotherapy the response rate ( complete and partial responses ) after four courses of treatment was 61 % with no significant increase in patients receiving eight courses ( 63 % ) . In those randomised to receive relapse chemotherapy the response rate was improved slightly for those who had originally received four courses of chemotherapy ( 25.6 % ) over those receiving eight ( 18.7 % ) . The overall results show that of the four possible treatment randomizations , four courses of chemotherapy alone is inferior in terms of overall survival ( 30 weeks median survival ) to the other three treatment options ( 39 weeks median survival , P less than 0.01 ) . In patients responding to initial chemotherapy the disadvantage of four courses of chemotherapy alone was apparent ( median survival of 40 weeks versus 49 weeks , P = 0.003 ) but not if drug treatment was given on relapse . The study shows that limiting treatment to four courses of chemotherapy alone is associated with inferior survival , but this is not the case if chemotherapy is given at relapse .

Duration of chemotherapy

response rate


A randomized controlled trial of cognitive-behavioral therapy versus treatment as usual for adolescents with autism spectrum disorders and comorbid anxiety . OBJECTIVE Examine the efficacy of a personalized , modular cognitive-behavioral therapy ( CBT ) protocol among early adolescents with high-functioning autism spectrum disorders ( ASDs ) and co-occurring anxiety relative to treatment as usual ( TAU ) . METHOD Thirty-one children ( 11-16 years ) with ASD and clinically significant anxiety were randomly assigned to receive 16 weekly CBT sessions or an equivalent duration of TAU . Participants were assessed by blinded raters at screening , posttreatment , and 1-month follow-up . RESULTS Youth randomized to CBT demonstrated superior improvement across primary outcomes relative to those receiving TAU . Eleven of 16 adolescents randomized to CBT were treatment responders , versus 4 of 15 in the TAU condition . Gains were maintained at 1-month follow-up for CBT responders . CONCLUSIONS These data extend findings of the promising effects of CBT in anxious youth with ASD to early adolescents .

cognitive-behavioral therapy

versus

treatment as usual

treatment as usual ( TAU )

CBT sessions

or an

equivalent duration of TAU

CBT

TAU

CBT

TAU

CBT

efficacy

superior improvement

primary outcomes

Gains

promising effects

adolescents

autism spectrum disorders

adolescents

Thirty-one children

( 11-16 years )

ASD

ASD

adolescents


Evaluating the efficacy of thoracoscopy and talc poudrage versus pleurodesis using talc slurry ( TAPPS trial ) : protocol of an open-label randomised controlled trial . INTRODUCTION The management of recurrent malignant pleural effusions ( MPE ) can be challenging . Various options are available , with the most efficacious and widely used being talc pleurodesis . Talc can either be applied via a chest drain in the form of slurry , or at medical thoracoscopy using poudrage . Current evidence regarding which method is most effective is conflicting and often methodologically flawed . The TAPPS trial is a suitably powered , multicentre , open-label , randomised controlled trial designed to compare the pleurodesis success rate of medical thoracoscopy and talc poudrage with chest drain insertion and talc slurry . METHODS AND ANALYSIS 330 patients with a confirmed MPE requiring intervention will be recruited from UK hospitals . Patients will be randomised ( 1:1 ) to undergo either small bore ( < 14 Fr ) Seldinger chest drain insertion followed by instillation of sterile talc ( 4 g ) , or to undergo medical thoracoscopy and simultaneous poudrage ( 4 g ) . The allocated procedure will be performed as an inpatient within 3 days of randomisation taking place . Following discharge , patients will be followed up at regular intervals for 6 months . The primary outcome measure is pleurodesis failure rates at 3 months . Pleurodesis failure is defined as the need for further pleural intervention for fluid management on the side of the trial intervention . ETHICS AND DISSEMINATION The trial has received ethical approval from the National Research Ethics Service Committee North West-Preston ( 12/NW/0467 ) . There is a trial steering committee which includes independent members and a patient and public representative . The trial results will be published in a peer-reviewed journal and presented at international conferences , as well as being disseminated via local and national charities and patient groups . All participants who wish to know the study results will also be contacted directly on their publication . TRIAL REGISTRATION NUMBER ISRCTN47845793 .

thoracoscopy

talc poudrage

pleurodesis using talc slurry

talc pleurodesis

Talc

medical thoracoscopy using poudrage

medical thoracoscopy

talc poudrage

chest drain insertion

talc slurry

efficacy

measure is pleurodesis failure

Pleurodesis


Randomized clinical trial of a bladder neck plication stitch during robot-assisted radical prostatectomy . Urinary incontinence after robot-assisted radical prostatectomy ( RARP ) is one of the most bothersome complications affecting patients ' daily lives . The efficacy of the bladder neck plication stitch technique in promoting an earlier return of continence was prospectively evaluated in 158 patients who underwent RARP for clinically localized prostate cancer by a single surgeon at our institute from March 2012 to January 2013 . Patients were randomized 1:1 to undergo surgery with ( n = 79 ) or without ( n = 79 ) the bladder neck plication stitch , and their time to recovery from incontinence , defined as being pad free , was compared . Recovery from incontinence at 1 , 3 , and 6 months were observed in 22 ( 27.8 % ) , 42 ( 53.2 % ) , and 57 ( 72.2 % ) patients , respectively , treated with , and 23 ( 29.1 % ) , 47 ( 59.5 % ) , and 59 ( 74.7 % ) patients , respectively , treated without the bladder neck plication stitch , with no significant difference in time to recovery from incontinence between the two groups . Multivariate analysis showed that age , membranous urethral length and shape of the prostatic apex on magnetic resonance imaging were independent predictors of early recovery from urinary incontinence after RARP . The bladder neck plication stitch had no effect on time to recovery from postoperative urinary incontinence following RARP .

bladder neck plication stitch

bladder neck plication stitch technique

with

or without

the bladder neck plication stitch

bladder neck plication stitch

bladder neck plication stitch

robot-assisted radical prostatectomy .

prostate cancer


Effectiveness of a fundamental motor skill intervention for 4-year-old children with autism spectrum disorder : A pilot study . A wait-list control experimental design was employed to investigate the effectiveness of a fundamental motor skill intervention at improving the motor skills , adaptive behavior , and social skills of 4-year-old children with autism spectrum disorder ( experimental n = 5 , control n = 4 ) ; the impact of intervention intensity was also explored . The experimental group significantly improved their object manipulation and overall motor scores from pre- to post-intervention . The wait-list control design revealed no group-by-time interactions ; however , with the groups combined time was a significant factor for all motor variables . There were no significant changes in adaptive behavior and social skills . These preliminary findings suggest that a fundamental motor skill intervention may benefit young children with autism spectrum disorder . Future research with larger samples is warranted .

fundamental motor skill intervention

wait-list control

fundamental motor skill intervention

improved their

object manipulation

and

overall motor

for all motor variables

changes in adaptive behavior and social

4-year-old children

autism spectrum disorder

4-year-old children

autism spectrum disorder

n = 5

n = 4

young children

autism spectrum disorder


Time to onset of clinically meaningful improvement with tadalafil 5 mg once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia : analysis of data pooled from 4 pivotal , double-blind , placebo controlled studies . PURPOSE Tadalafil once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia consistently shows statistically significant I-PSS improvements . However , physicians and patients wish to know whether tadalafil provides rapid , clinically meaningful improvement in lower urinary tract symptoms . In this post hoc analysis we integrated results from 4 placebo controlled studies to determine the duration of tadalafil once daily required to achieve clinically meaningful improvement . MATERIALS AND METHODS We performed post hoc analysis of data integrated from 4 double-blind studies of tadalafil 5 mg and placebo once daily in 742 and 735 men , respectively , 45 years old or older with total I-PSS 13 or greater . Two clinically meaningful improvement categories were assessed , including 1 ) 3-point or greater baseline to end point total I-PSS improvement and 2 ) 25 % or greater baseline to end point total I-PSS improvement . I-PSS was assessed at weeks 4 , 8 and 12 in all studies , week 1 in 2 and week 2 in 1 . Results in men treated with tadalafil who showed clinically meaningful improvement ( responders ) were further examined to determine the earliest time to clinically meaningful improvement . RESULTS Of 742 tadalafil treated patients 513 ( 69.1 % ) and 444 ( 59.8 % ) demonstrated category 1 and 2 clinically meaningful improvement , respectively , at the study end point . Of 234 category 1 responders with week 1 assessments 140 ( 59.8 % ) achieved clinically meaningful improvement by week 1 and 407 of the total of 513 category 1 responders ( 79.3 % ) showed it by week 4 . Of the 205 category 2 responders with week 1 assessments 103 ( 50.2 % ) achieved clinically meaningful improvement by week 1 while 322 of the 444 category 2 responders ( 72.5 % ) did so by week 4 . CONCLUSIONS Tadalafil 5 mg once daily led to clinically meaningful improvement in approximately two-thirds of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia . More than half of this group of tadalafil treated responders achieved clinically meaningful improvement after 1 week of therapy and more than 70 % did so within 4 weeks .

tadalafil

placebo

Tadalafil

tadalafil

placebo

tadalafil

tadalafil

and placebo

tadalafil

tadalafil

Tadalafil

tadalafil


Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy : a randomized trial . STUDY OBJECTIVE To investigate whether melatonin administered intraoperatively reduced pain following laparoscopic cholecystectomy . DESIGN Randomized , placebo-controlled , double-blinded study . SETTING Two surgical departments in Copenhagen . PATIENTS 44 women between 18 and 70 years of age , who were surgical candidates for laparoscopic cholecystectomy . INTERVENTIONS Patients were anesthetized by a standard protocol and received a standard multimodal postoperative analgesic regimen . Patients undergoing surgery were admitted on the day of surgery and were discharged the day after surgery . Ten mg of intravenous ( IV ) melatonin or placebo were administered at the time of surgical incision . MEASUREMENTS Pain was assessed by a set of questionnaires documenting " pain at rest " using a visual analog scale ( VAS ) . The use of rescue medication was recorded . Sleep quality and general well-being were measured on separate VAS scales . Sleepiness was assessed by the Karolinska Sleepiness Scale . MAIN RESULTS Forty-four patients were included and randomized to the study . Three patients did not complete the study . No differences in VAS pain scores , sleep quality , general well-being , or sleepiness were found between the two groups in the postoperative period . The use of postoperative rescue medication did not differ between the groups . CONCLUSIONS The use of 10mg of IV melatonin administered during laparoscopic cholecystectomy did not affect postoperative pain or use of analgesic medication .

melatonin

melatonin

intravenous ( IV ) melatonin

placebo

melatonin

pain

Pain

visual analog scale ( VAS )

Sleep quality and general well-being

VAS scales . Sleepiness

laparoscopic cholecystectomy .

women

18 and 70 years of age

laparoscopic cholecystectomy

surgery

Forty-four


Does cognition predict treatment response and remission in psychotherapy for late-life depression ? OBJECTIVES To identify cognitive predictors of geriatric depression treatment outcome . METHOD Older participants completed baseline measures of memory and executive function , health , and baseline and post-treatment Hamilton Depression Scales ( HAM-D ) in a 12-week trial comparing psychotherapies ( problem-solving vs. supportive ; N = 46 ) . We examined cognitive predictors to identify treatment responders ( i.e. , HAM-D scores reduced by ≥50 % ) and remitters ( i.e. , post-treatment HAM-D score ≤10 ) . RESULTS Empirically derived decision trees identified poorer performance on switching ( i.e. , Trails B ) , with a cut-score of ≥82 predicting psychotherapy responders . No other cognitive or health variables predicted psychotherapy outcomes in the decision trees . CONCLUSIONS Psychotherapies that support or improve the executive skill of switching may augment treatment response for older patients exhibiting executive dysfunction in depression . If replicated , Trails B has potential as a brief cognitive tool for clinical decision-making in geriatric depression .

psychotherapy

psychotherapies ( problem-solving vs.

late-life depression

geriatric depression

Older participants

Hamilton Depression Scales ( HAM-D )

supportive ; N = 46

decision-making in geriatric depression


Treatment of Wilms ' tumor . Results of the Third National Wilms ' Tumor Study . The Third National Wilms ' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse . Eligible patients ( 1439 ) were randomized according to stage ( I-IV ) and histology ( favorable [ FH ] or unfavorable [ UH ] ) , and contributed data to survival and relapse-free survival ( RFS ) analyses . Four-year ( postnephrectomy ) survival percentages and randomized treatment regimens for low-risk patients were 96.5 % for 607 Stage I/FH patients who received dactinomycin ( Actinomycin D [ AMD ] , Merck Sharp & Dohme , West Point , PA ) and vincristine ( VCR ) for 10 weeks versus 6 months ; 92.2 % for 278 Stage II/FH patients ; and 86.9 % for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin ( ADR , Adria Laboratories , Columbus , OH ) for 15 months . Stage II/FH patients also had either zero or 2000 cGy irradiation ( RT ) postoperatively and Stage III/FH patients either 1000 or 2000 cGy . Four-year survival was 73.0 % for 279 high-risk patients ( any Stage IV , all UH ) who received postoperative radiation therapy ( RT ) and AMD + VCR + ADR +/- cyclophosphamide ( CPM ) . Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk .

chemotherapy

dactinomycin ( Actinomycin D [ AMD ]

vincristine ( VCR )

AMD + VCR +/- Adriamycin ( ADR

postoperative radiation therapy ( RT )

CPM

Four-year survival

survival

RFS experience shows

Wilms ' tumor .

Wilms ' Tumor


Selective attention effects on early integration of social signals : same timing , modulated neural sources . Humans combine co-emitted social signals to predict other 's immediate intentions and prepare an adapted response . However , little is known about whether attending to only one of co-emitted social signals impacts on its combination with other signals . Here , using electroencephalography , we address selective attention effects on early combination of social signals . We manipulated three visual cues : gaze direction , emotional expression , and pointing gesture , while participants performed either emotion or gaze direction judgments . Results showed that a temporal marker of social cues integration emerges 170ms after the stimulus onset , even if the integration of the three visual cues was not required to perform the task , as only one feature at a time was task relevant . Yet in addition to common temporal regions , the relative contribution of specific neural sources of this integration changed as a function of the attended feature : integration during emotion judgments was mainly implemented in classic limbic areas but in the dorsal pathway during gaze direction judgments . Together , these findings demonstrate that co-emitted social cues are integrated as long as they are relevant to the observer , even when they are irrelevant to the ongoing task .

electroencephalography

selective attention effects

co-emitted social cues are integrated


Differences in quality of life outcomes among depressed spinal cord injury trial participants . OBJECTIVE To assess the role that treatment response plays in a randomized controlled trial of an antidepressant among people with spinal cord injury ( SCI ) diagnosed with major depressive disorder ( MDD ) in explaining quality of life ( QOL ) , assessed both globally as life satisfaction and in terms of physical and mental health-related QOL . DESIGN Multivariable analyses were conducted , controlling for demographic , neurologic , and participatory factors and perceived functional limitations . SETTING Rehabilitation centers . PARTICIPANTS Of the 133 persons who were randomized into the Project to Improve Symptoms and Mood after Spinal Cord Injury randomized controlled trial , 124 participated in this study . All participants were between the ages of 18 and 64 years , at least 1 month post-SCI , met the Diagnostic and Statistical Manual of Mental Disorders , 4th edition , criteria for MDD , and completed the core measures used in this study . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The Satisfaction with Life Scale and the physical and mental component summary scores of the Medical Outcomes Study 12-Item Short-Form Health Survey . RESULTS Reduction in depressive symptoms over the course of a 12-week trial was predictive of increased QOL , which was measured as life satisfaction and mental well-being , within the context of other explanatory factors . However , reduction in symptoms did not explain differences in physical well-being among those with MDD . Perceived functional disability explained all 3 indices of QOL . CONCLUSIONS Greater recognition has been given to QOL outcomes as endpoints of clinical trials because these often reflect participants ' reported outcomes . Our findings support the association of QOL to the reduction of depression symptoms among trial participants . This association differs depending on how QOL is defined and measured , with stronger relations observed with life satisfaction and mental well-being among those diagnosed with MDD . The lack of association between depression and physical well-being may be explained by participants ' subjective interpretation of physical well-being after SCI and their expectations and perceptions of improved physical health-related QOL based on the use of assistive technology . Consistent with our findings , pain is likely to play a role in decreasing physical QOL among those with incomplete injuries . Practicing caution is suggested in using physical well-being as an endpoint in trials among people with SCI .

antidepressant

Project to Improve Symptoms and Mood

The

Satisfaction with Life Scale

and the physical and

Reduction in depressive symptoms

reduction in symptoms

Perceived functional disability

depressed spinal cord injury

spinal cord injury ( SCI )

major depressive disorder ( MDD

Spinal Cord Injury

incomplete injuries

SCI


A randomized double-blind placebo-controlled clinical trial of adjuvant buspirone for irritability in autism . BACKGROUND The brain serotonin level is decreased in individuals with autism . Buspirone is a 5-HT ( 1A ) receptor agonist with antiaggressive effects increasing prosocial behaviors . METHODS We conducted an 8-week randomized double-blind placebo-controlled clinical trial . Participants included 40 outpatient children and adolescents with autism . The patients took buspirone plus risperidone or risperidone plus placebo during 8 weeks . The patients were assessed at baseline , week 4 , and week 8 using the Aberrant Behavior Checklist-Community Rating Scale . RESULTS Eighteen patients in the placebo group and 16 patients in the buspirone group completed this trial . The mean dose of buspirone was 6.7 ( SD 2.7 ) mg/day . Irritability subscale score significantly decreased during this trial in both groups ( buspirone group : declined from 25.7 [ SD 5.7 ] to 16.3 [ SD 8.5 ] ; placebo group : declined from 24.7 [ SD 7.6 ] to 18.2 [ SD 7.7 ] ) . The Cohen d effect size was .45 . Thirteen ( 81.2 % ) of 16 patients in the buspirone group and 7 ( 38.9 % ) of 18 patients in the placebo group showed a ≥30 % decline in irritability score . The relative risk for treatment was 2.1 . There were no serious adverse effects . The most common adverse effects in the buspirone group were increased appetite , drowsiness , and fatigue . CONCLUSION This clinical trial supports that low dose buspirone plus risperidone is more effective than risperidone plus placebo for treating irritability in individuals with autism .

buspirone

placebo-controlled

buspirone plus risperidone

risperidone

plus placebo

irritability

Irritability subscale score

in irritability score

The relative risk

no serious adverse effects

were increased appetite

drowsiness

fatigue

treating irritability

irritability in autism

40 outpatient

children

adolescents

Eighteen patients

16 patients

in individuals with autism


Randomized trial of a secondhand smoke exposure reduction intervention among hospital-based pregnant women . OBJECTIVE This study sought to assess the effectiveness of a secondhand tobacco smoke ( SHS ) prevention program based on an expanded Health Belief Model ( HBM ) incorporating self-efficacy among pregnant women in a hospital setting in Taiwan . METHODOLOGY This study utilized a two-group longitudinal randomized controlled trial design . Participants in the intervention group ( n=50 ) enrolled in a SHS prevention program based on the HBM , while participants in the comparison group ( n=50 ) received standard government-mandated counseling care . Both groups were given questionnaires as a pre-test , two weeks into the intervention , and one month following the conclusion of the intervention . The questionnaire and intervention were developed based on the understanding gained through a series of in-depth interviews and a focus-group conducted among pregnant women . Exhaled carbon monoxide was also measured and used as a proxy for SHS exposure . RESULTS Intervention group scores were all significantly higher than comparison group scores ( p < 0.001 ) , indicating a significant increase in knowledge , HBM scores , cues to action , self-efficacy , preventative behaviors , and a significant decrease in smoking exposure . These differences remained significant at the one-month follow-up assessment ( p < 0.001 ) . CONCLUSIONS These results should encourage health professionals to educate pregnant women regarding the harms of SHS while both empowering and equipping them with the tools to confront their family members and effectively reduce their SHS exposure while promoting smoke-free social norms .

SHS prevention program based on the HBM

effectiveness

Health Belief Model

questionnaires

Exhaled carbon monoxide

SHS exposure

SHS exposure

hospital-based pregnant women

pregnant

a hospital setting in Taiwan

( n=50 )

SHS prevention program

comparison group ( n=50 )

groups

pregnant women


A step-by-step introduction to vegetables at the beginning of complementary feeding . The effects of early and repeated exposure . Breastfeeding ( BF ) is associated with willingness to accept vegetables . This may be due to the variety of flavours delivered via breast milk . Some mothers add vegetables to milk during complementary feeding ( CF ) to enhance acceptance . The present study tested a step-by-step exposure to vegetables in milk then rice during CF , on intake and liking of vegetables . Just before CF , enrolled mothers were randomised to an intervention ( IG , n = 18 ; 6 BF ) or control group ( CG , n = 18 ; 6 BF ) . IG infants received 12 daily exposures to vegetable puree added to milk ( days 1-12 ) , then 12 × 2 daily exposures to vegetable puree added to rice at home ( days 13-24 ) . Plain milk and rice were given to CG . Then both received 11 daily exposures to vegetable puree . Intake was weighed and liking rated on days 25-26 and 33-35 after the start of CF in the laboratory , supplemented by the same data recorded at home . Vegetables were rotated daily ( carrots , green beans , spinach , broccoli ) . Intake , liking and pace of eating were greater for IG than CG infants . Intake and liking of carrots were greater than green beans . However , at 6m then 18m follow up , vegetable ( carrot > green beans ) but not group differences were observed . Mothers reported appreciation of the structure and guidance of this systematic approach . Early exposure to vegetables in a step-by-step method could be included in CF guidelines and longer term benefits assessed by extending the exposure period .

vegetables

vegetables in milk then rice

spinach , broccoli

Intake , liking and pace

than CG infants

Intake and liking

Breastfeeding ( BF )

mothers

mothers


Reducing iodine load in hepatic CT for patients with chronic liver disease with a combination of low-tube-voltage and adaptive statistical iterative reconstruction . PURPOSE To prospectively assess the effect of reduced iodine load to contrast enhancement , image quality , and detectability of hepatocellular carcinomas ( HCCs ) in hepatic CT with a combination of 80 kVp tube voltage setting and adaptive statistical iterative reconstruction ( ASIR ) technique in patients with chronic liver disease . MATERIALS AND METHODS This HIPAA-compliant study was approved by our institutional review board and written informed consent was obtained in all patients . During a recent 9-month period , 170 consecutive patients ( 114 men and 56 women ; age range , 40-85 years ; mean , 67.7 years ) with suspected chronic liver diseases were randomized into three CT groups according to the following iodine-load and tube-voltage protocols : 600 milligram per kilogram body weight ( mg/kg ) iodine load and 120 peak kilovolt ( kVp ) tube voltage setting ( 600-120 group ) , 500 mg/kg and 80 kVp ( 500-80 group ) , and 400mg/kg and 80 kVp ( 400-80 group ) . Analysis of variance was conducted to evaluate differences in CT number , background noise , signal-to-noise ratio ( SNR ) , effective dose , HCC-to-liver contrast-to-noise ratio ( CNR ) , and figure of merit ( FOM ) . Sensitivity , specificity , and area under the receiver-operating-characteristic curve ( AUC ) were compared to assess the detectability of HCCs . RESULTS Vascular and hepatic enhancement in the 400-80 and 500-80 groups was comparable to or greater than that in the 600-120 group ( P < .05 ) . Subjective image quality was comparable among the three groups . Sensitivity , specificity , and AUC for detecting HCCs were comparable among the groups . The effective dose was kept low ( 3.3-4.1 mSv ) in all three groups . CONCLUSION Iodine load can be reduced by 33 % in CT of the liver with a combination of 80 kVp tube voltage setting and ASIR technique , without compromising the contrast enhancement , image quality , and detection of HCCs .

80 kVp tube voltage setting

CT number

background noise

signal-to-noise ratio ( SNR

effective dose

figure of merit ( FOM )

Vascular and hepatic enhancement

Subjective image quality

Sensitivity , specificity , and AUC

contrast enhancement , image quality

detection of HCCs .

chronic liver disease

patients with chronic liver disease .

men

women

40-85 years


Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex : 2-year open-label extension of the randomised EXIST-1 study . BACKGROUND In the EXIST-1 trial , initiated on Aug 10 , 2009 , more than 35 % of patients with subependymal giant cell astrocytoma ( SEGA ) associated with tuberous sclerosis complex had at least 50 % reduction in SEGA volume after 9·6 months of treatment with everolimus . In this Article , we report interim data ( up to Jan 11 , 2013 ) to support longer-term tolerability and efficacy of everolimus from the continuing 4-year extension phase of EXIST-1 . METHODS We assessed data from a prospective , open-label extension of a multicentre , phase 3 , randomised , double-blind , placebo-controlled study in patients with tuberous sclerosis complex who had SEGA that was growing and needed treatment . In this extension study , we included all patients who had been assigned everolimus during the double-blind , randomised phase of the trial and those patients who crossed over from the placebo group to receive everolimus during the randomised phase or at the start of the extension phase . All patients received oral everolimus at a starting dose of 4·5 mg/m ( 2 ) per day . Everolimus dose was subsequently adjusted subject to tolerability to attain blood trough concentrations of 5-15 ng/mL . An independent central radiology review team assessed SEGA response ( at least a 50 % reduction from baseline in total volume of all target SEGAs ; the primary endpoint ) by MRI at 12 , 24 , and 48 weeks , then every year thereafter in all patients who received at least one dose of everolimus . This study was registered with ClinicalTrials.gov , number NCT00789828 . FINDINGS Of the original 117 randomly assigned patients , 111 were given everolimus between Aug 20 , 2009 , and Jan 11 , 2013 ( date of data cutoff ) ; we included these patients in our longer-term analysis . Median duration of everolimus exposure was 29·3 months ( IQR 19·4-33·8 ) . Median follow-up was 28·3 months ( IQR 19·3-33·0 ) . 54 ( 49 % ) patients had a response of 50 % or greater reduction in SEGA volume ( 95 % CI 39·0-58·3 ) , and duration of response was between 2·1 and 31·1 months ( median not reached ) . SEGA volume was reduced by 50 % or more in 39 ( 37 % ) of 105 patients at 24 weeks , 48 ( 46 % ) of 104 patients at 48 weeks , 36 ( 47 % ) of 76 patients at 96 weeks , and 11 ( 38 % ) of 29 patients at 144 weeks . Stomatitis ( 48 [ 43 % ] patients ) and mouth ulceration ( 33 [ 30 % ] patients ) were the most frequent treatment-related adverse events ; infections were the most commonly reported treatment-related serious adverse event , occurring in 15 ( 14 % ) patients . 35 ( 32 % ) patients reported treatment-related grade 3 or 4 adverse events , the most common of which were stomatitis ( nine [ 8 % ] ) and pneumonia ( nine [ 8 % ] ) . 18 ( 16 % ) patients had treatment-related serious adverse events . Six ( 5 % ) patients withdrew because of adverse events . INTERPRETATION These results support the longer-term use of everolimus in patients who have few treatment options and who need continued treatment for tuberous sclerosis complex and its varied manifestations . Reduction or stabilisation of tumour volume with everolimus will hopefully provide long-term clinical benefit in patients with SEGA . FUNDING Novartis Pharmaceuticals .

Everolimus

attain blood trough concentrations

reduction in SEGA

39·0-58·3 ) , and duration of

at 144 weeks

patients ) and mouth

adverse events ;

grade 3 or 4 adverse

withdrew because of adverse

Reduction or stabilisation of tumour

tuberous sclerosis complex

tuberous sclerosis


Exercise echocardiography demonstrates biventricular systolic dysfunction and reveals decreased left ventricular contractile reserve in children after tetralogy of Fallot repair . BACKGROUND Long-term biventricular systolic performance is a key determinant of clinical outcomes late after tetralogy of Fallot ( TOF ) repair . A need exists for early indices of both left ventricular ( LV ) and right ventricular ( RV ) compromise in this population . METHODS Twenty-nine children ( age range , 5-18 years ) with repaired TOF and 44 healthy controls were prospectively evaluated . M-mode and tissue Doppler data were obtained for each ventricle and the RV outflow tract at rest and during semisupine bicycle exercise . By making measurements of myocardial acceleration during isovolumic contraction during exercise , at increasing heart rates , LV force-frequency curves were constructed . Patients also underwent cardiac magnetic resonance imaging , cardiopulmonary exercise testing , and measurement of serum neurohormonal markers . RESULTS Children with repaired TOF had dilated right ventricles ( RV end-diastolic volume index = 153 ± 37.3 mL/m ( 2 ) ) but normal ejection fractions as measured on magnetic resonance imaging ( LV ejection fraction = 59.3 ± 6.2 % , RV ejection fraction = 50.2 ± 8.5 % ) and normal serum neurohormonal markers . Detailed resting echocardiography detected abnormal ventricular function , worst in the right ventricle and RV outflow tract . Exercise exacerbated these findings and provoked significant decline in LV indices . The LV force-frequency curves of patients were attenuated , with an early plateau and inadequate increase of isovolumic contraction . Correlations were seen between peak exercise LV isovolumic contraction and percentage predicted peak oxygen uptake ( r = 0.51 , P = .02 ) , LV and RV ejection fractions ( r = 0.41 , P = .03 ) , and RV and LV long-axis fractional shortening ( r = 0.44 , P = .02 ) . CONCLUSIONS The postsurgical pathophysiology of TOF begins early after repair . At a time when clinically well and while routine indices of heart function remain normal , children with repaired TOF exhibit RV dilatation and subtle , interlinked biventricular abnormalities on resting echocardiography . Exercise echocardiography provides additional information and reveals abnormal LV excitation-contractile coupling that may be linked to impaired exercise capacity .

tetralogy of Fallot ( TOF ) repair .

M-mode and tissue Doppler data

semisupine bicycle exercise .

cardiac magnetic resonance imaging

cardiopulmonary exercise testing

after tetralogy of Fallot repair

Twenty-nine

children ( age range , 5-18 years )

with repaired TOF


The durability of endovascular coiling versus neurosurgical clipping of ruptured cerebral aneurysms : 18 year follow-up of the UK cohort of the International Subarachnoid Aneurysm Trial ( ISAT ) . BACKGROUND Previous analyses of the International Subarachnoid Aneurysm Trial ( ISAT ) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling . At 1 year there was a 7 % absolute and a 24 % relative risk reduction of death and dependency in the coiling group compared with the clipping group , but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling . We report the long-term follow-up of patients in this UK cohort . METHODS In ISAT , patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage , assuming treatment equipoise , between Sept 12 , 1994 , and May 1 , 2002 . We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0-18·5 years . We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires . Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records . The Office for National Statistics supplied data on deaths . This study is registered , number ISRCTN49866681 . FINDINGS At 10 years , 674 ( 83 % ) of 809 patients allocated endovascular coiling and 657 ( 79 % ) of 835 patients allocated neurosurgical clipping were alive ( odds ratio [ OR ] 1·35 , 95 % CI 1·06-1·73 ) . Of 1003 individuals who returned a questionnaire at 10 years , 435 ( 82 % ) patients treated with endovascular coiling and 370 ( 78 % ) patients treated with neurosurgical clipping were independent ( modified Rankin scale score 0-2 ; OR 1·25 ; 95 % CI 0·92-1·71 ) . Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group ( OR 1·34 , 95 % CI 1·07-1·67 ) . 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage ( 17 from the target aneurysm ) . INTERPRETATION Although rates of increased dependency alone did not differ between groups , the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group . Rebleeding was more likely after endovascular coiling than after neurosurgical clipping , but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years . FUNDING UK Medical Research Council .

endovascular coiling

neurosurgical clipping

neurosurgical clipping

endovascular coiling

ruptured cerebral aneurysms :


Ranibizumab plus verteporfin photodynamic therapy in neovascular age-related macular degeneration : 12 months of retreatment and vision outcomes from a randomized study . PURPOSE To investigate the injection frequency and visual acuity ( VA ) outcomes with combination therapy ( ranibizumab plus verteporfin photodynamic therapy , PDT ) versus monotherapy ( ranibizumab ) . METHODS A total of 40 patients with exudative age-related macular degeneration were randomized 1:1 to ranibizumab 0.3 mg plus single standard verteporfin PDT or ranibizumab 0.3 mg plus sham PDT . Ranibizumab was administered 3 times monthly followed by 'as needed ' to month 12 based on predetermined vision/anatomical criteria . Retreatment rates , VA outcomes and safety were assessed . RESULTS During months 3-12 , combination therapy patients required fewer ranibizumab injections ( mean 1.3 ) compared with monotherapy patients ( 2.8 ) . Mean VA improved by 9.0 letters with combination therapy versus 7.5 letters in the monotherapy group at month 12 . Both treatment regimens were well tolerated . CONCLUSION The need for ranibizumab retreatment might be reduced by administering a single verteporfin PDT on the same day as the first ranibizumab injection , without compromising VA outcomes or safety .

Ranibizumab

verteporfin

ranibizumab

ranibizumab

single standard verteporfin PDT

ranibizumab

sham PDT

Ranibizumab

ranibizumab

ranibizumab

verteporfin PDT

ranibizumab

40 patients


Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation : a genome-wide analysis among 1,800 South Asians . A large fraction of human genes are regulated by genetic variation near the transcribed sequence ( cis-eQTL , expression quantitative trait locus ) , and many cis-eQTLs have implications for human disease . Less is known regarding the effects of genetic variation on expression of distant genes ( trans-eQTLs ) and their biological mechanisms . In this work , we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association , using Sobel tests of mediation . We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05 , and 189 of these trans-eQTLs were also cis-eQTLs ( enrichment P < 0.0001 ) . Among these 189 trans-eQTL associations , 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P < 10-5 . We attempted to replicate 21 of these mediation signals in two European cohorts , and while only 7 trans-eQTL associations were present in one or both cohorts , 6 showed evidence of cis-mediation . Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants . Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator . Using simulated data , we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true ( unmeasured ) mediator . In conclusion , by applying mediation analysis to eQTL data , we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation . Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology , as well as using mediation analysis to improve eQTL discovery .

genome-wide data on SNPs

array-based expression measures

trans-eQTLs

cis- and trans-eQTLs

trans-eQTL associations

Sobel tests of mediation

trans-eQTL associations

trans-eQTLs

trans-eQTL associations

trans-eQTL associations

trans-eQTL associations

1,800 South Asians

1,799 Bangladeshi individuals


Parents ' Adoption of Social Communication Intervention Strategies : Families Including Children with Autism Spectrum Disorder Who are Minimally Verbal . Notably absent from the intervention literature are parent training programs targeting school-aged children with autism who have limited communication skills ( Tager-Flusberg and Kasari in Autism Res 6:468-478 , 2013 ) . Sixty-one children with autism age 5-8 with minimal spontaneous communication received a 6-month social communication intervention including parent training . Parent-child play interactions were coded for parents ' strategy implementation and children 's time jointly engaged ( Adamson et al . in J Autism Dev Disord 39:84-96 , 2009 ) . Parents mastered an average of 70 % of the strategies . Further analyses indicated some gains in implementation occurred from mere observation of sessions , while the greatest gains occurred in the first month of active coaching and workshops . Children 's joint engagement was associated with parents ' implementation success across time demonstrating parents ' implementation was relevant to children 's social engagement .

strategy implementation

jointly engaged

mastered

gains in implementation

gains

joint engagement

implementation success

social engagement .

Children

Autism Spectrum Disorder

children

autism

Sixty-one

autism

age 5-8

Children 's

children 's


Lifetime history of heroin use is associated with greater drug severity among prescription opioid abusers . BACKGROUND While research suggests primary prescription opioid ( PO ) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers , less is known about whether a lifetime history of heroin use confers greater severity among PO abusers . OBJECTIVE In this secondary analysis , we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations . Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures . METHODS Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 ( H ( + ) ; n=41 ) vs. < 5 ( H ( - ) ; n=48 ) times . Treatment response ( i.e. , illicit opioid abstinence and treatment retention at end of study ) was examined in the subset of H ( + ) and H ( - ) participants randomized to receive the 4-week taper condition ( N=22 ) . RESULTS H ( + ) participants were significantly older and more likely to be male . They reported longer durations of illicit opioid use , greater alcohol-related problems , more past-month cocaine use , greater lifetime IV drug use , and greater lifetime use of cigarettes , amphetamines and hallucinogens . H ( + ) participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory . Finally , there was a trend toward poorer treatment outcomes among H ( + ) participants . CONCLUSION A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers .

prescription opioid abusers .

adults

treatment-seeking PO abusers


Institutional clinical trial accrual volume and survival of patients with head and neck cancer . PURPOSE National Comprehensive Cancer Network guidelines recommend patients with head and neck cancer ( HNC ) receive treatment at centers with expertise , but whether provider experience affects survival is unknown . PATIENTS AND METHODS The effect of institutional experience on overall survival ( OS ) in patients with stage III or IV HNC was investigated within a randomized trial of the Radiation Therapy Oncology Group ( RTOG 0129 ) , which compared cisplatin concurrent with standard versus accelerated fractionation radiotherapy . As a surrogate for experience , institutions were classified as historically low- ( HLACs ) or high-accruing centers ( HHACs ) based on accrual to 21 RTOG HNC trials ( 1997 to 2002 ) . The effect of accrual volume on OS was estimated by Cox proportional hazards models . RESULTS Median RTOG accrual ( 1997 to 2002 ) at HLACs was four versus 65 patients at HHACs . Analysis included 471 patients in RTOG 0129 ( 2002 to 2005 ) with known human papillomavirus and smoking status . Patients at HLACs versus HHACs had better performance status ( 0 : 62 % v 52 % ; P = .04 ) and lower T stage ( T4 : 26.5 % v 35.3 % ; P = .002 ) but were otherwise similar . Radiotherapy protocol deviations were higher at HLACs versus HHACs ( 18 % v 6 % ; P < .001 ) . When compared with HHACs , patients at HLACs had worse OS ( 5 years : 51.0 % v 69.1 % ; P = .002 ) . Treatment at HLACs was associated with increased death risk of 91 % ( hazard ratio [ HR ] , 1.91 ; 95 % CI , 1.37 to 2.65 ) after adjustment for prognostic factors and 72 % ( HR , 1.72 ; 95 % CI , 1.23 to 2.40 ) after radiotherapy compliance adjustment . CONCLUSION OS is worse for patients with HNC treated at HLACs versus HHACs to cooperative group trials after accounting for radiotherapy protocol deviations . Institutional experience substantially influences survival in locally advanced HNC .

Median RTOG accrual

Radiotherapy protocol deviations

OS

death risk

head and neck cancer

head and neck cancer

HNC

stage III or IV HNC

HNC


Effect of L-type calcium channel blocker ( amlodipine ) on myocardial iron deposition in patients with thalassaemia with moderate-to-severe myocardial iron deposition : protocol for a randomised , controlled trial . INTRODUCTION Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia . Control of myocardial iron is thus becoming the cornerstone of thalassaemia management . Recent evidence suggests a role for L-type Ca ( 2+ ) channels in mediating iron uptake by the heart . Blocking the cellular iron uptake through these channels may add to the benefit of therapy to standard chelation in reducing myocardial iron . We aim to determine the efficacy of amlodipine ( a calcium channel blocker ) as an adjunct to standard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy . OUTCOMES The primary outcome is to compare the efficacy of amlodipine+chelation ( intervention ) versus standard chelation ( control ) in retarding myocardial iron deposition . Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function , strain and strain rate and liver iron content . METHODS AND ANALYSIS This is a single-centre , parallel-group , prospective randomised control trial . Twenty patients will be randomised in a 1:1 allocation ratio into the intervention and control arms . In addition to conventional echocardiography , MRI T2* values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months . Cardiac T2* will be reported as the geometric mean and per cent coefficient of variation , and an increase in cardiac T2* values from baseline will be used as an end point to compare the efficacy of therapy . A p Value of < 0.05 will be considered significant . STUDY SETTING Department of Pediatric and Child Health , Aga Khan University Hospital , Karachi , Pakistan . ETHICS AND DISSEMINATION This study has been approved by the Ethics Review Committee and Clinical Trials Unit at The Aga Khan University with respect to scientific content and compliance with applicable research and human subjects regulations . Findings will be reported through scientific publications and research conferences and project summary papers for participants . TRIAL REGISTRATION NUMBER ClinicalTrials.Gov . Registration no : NCT02065492 .

amlodipine

amlodipine

amlodipine+chelation

standard chelation

amlodipine

myocardial iron deposition

myocardial iron deposition :

repeated blood transfusions

myocardial iron

myocardial iron .

myocardial iron deposition

cardiac and liver iron load

Twenty patients


Increased dietary α-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans : re-examination of data from a randomised , placebo-controlled , parallel study . BACKGROUND There is a metabolic pathway by which mammals can convert the omega-3 ( n-3 ) essential fatty acid α-linolenic acid ( ALA ) into longer-chain n-3 polyunsaturated fatty acids ( LC n-3 PUFA ) including eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans , although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men . FINDINGS Available data from a placebo-controlled , randomised study were re-examined to identify whether there are sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans . There was a significant difference between sexes in the response to increased dietary ALA , with women having a significantly greater increase in the EPA content of plasma phospholipids ( mean +2.0 % of total fatty acids ) after six months of an ALA-rich diet compared to men ( mean +0.7 % , P = 0.039 ) . Age and BMI were identified as predictors of response to dietary ALA among women . CONCLUSIONS Women show a greater increase in circulating EPA than men during increased dietary ALA consumption . Further understanding of individual variation in the response to dietary ALA could inform nutrition advice , with recommendations being specifically tailored according to habitual diet , sex , age and BMI .

dietary α-linolenic acid

women

men


Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial ( CE-MARC 2 ) : a prospective , multicenter , randomized trial of diagnostic strategies in suspected coronary heart disease . BACKGROUND A number of investigative strategies exist for the diagnosis of coronary heart disease ( CHD ) . Despite the widespread availability of noninvasive imaging , invasive angiography is commonly used early in the diagnostic pathway . Consequently , approximately 60 % of angiograms reveal no evidence of obstructive coronary disease . Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk . There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance . TRIAL DESIGN CE-MARC 2 is a prospective , multicenter , 3-arm parallel group , randomized controlled trial of patients with suspected CHD ( pretest likelihood 10 % -90 % ) requiring further investigation . A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance-guided care , single-photon emission computed tomography-guided care ( according to American College of Cardiology/American Heart Association appropriate-use criteria ) , or National Institute for Health and Care Excellence guidelines-based management . The primary ( efficacy ) end point is the occurrence of unnecessary angiography as defined by a normal ( > 0.8 ) invasive fractional flow reserve . Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates . Cost-effectiveness and health-related quality-of-life measures will be performed . CONCLUSIONS The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD , with the intension of reducing unnecessary invasive angiography rates . Evaluation of these management strategies has the potential to improve patient care , health-related quality of life , and the cost-effectiveness of CHD investigation .

Magnetic Resonance Imaging

invasive angiography

suspected coronary heart disease

suspected CHD


Intravitreal ranibizumab versus isovolemic hemodilution in the treatment of macular edema secondary to central retinal vein occlusion : twelve-month results of a prospective , randomized , multicenter trial . PURPOSE This is a prospective , randomized , multicenter , investigator-initiated trial to evaluate the 12-month effectiveness of isovolemic hemodilution ( IH ) with prompt versus deferred intravitreal injections ( IVI ) of ranibizumab 0.5 mg for the treatment of macular edema secondary to early central retinal vein occlusion ( CRVO ) . METHODS Eyes with macular edema due to CRVO having occurred not more than 8 weeks previously received either monthly ranibizumab IVI in combination with IH ( group I , n = 28 ) or IH alone ( group II , n = 30 ) . From month 2 to 12 , the patients in both groups could be treated with monthly intravitreal ranibizumab . The main outcome variables were gain of visual acuity and the course of central retinal thickness as measured with optical coherence tomography . RESULTS At 12 months , eyes in group I on average gained +28.1 ( ±19.3 ) letters compared to +25.2 ( ±20.9 ) letters in group II ( p = 0.326 ) . This result was achieved with significantly fewer injections in group II . Additionally , 30 % of the eyes in group II did not need ranibizumab IVI during the 12 months of the trial . CONCLUSION Ranibizumab IVI in addition to IH proved to be highly effective in increasing visual acuity and reducing macular edema secondary to CRVO . Initial IH in early CRVO may be a first treatment option in patients anxious about IVI .

ranibizumab

isovolemic hemodilution

isovolemic hemodilution ( IH )

ranibizumab 0.5 mg

ranibizumab IVI

IH

IH

ranibizumab .

( ±19.3 ) letters


Comparison on therapeutic effect of plasma exchange and intravenous immunoglobulin for Guillian-Barre syndrome . OBJECTIVES To observe and compare the clinical curative effect of the plasma exchange ( PE ) and intravenous immunoglobulin ( IVIg ) for Guillian-Barre Syndrome ( GBS ) . METHODS Overall , 64 adult patients with GBS for PE and IVIg treatment , respectively , and nerve function were observed pre-treatment and at 1 week/2 weeks after completion of treatment ; the blood immunoglobulin , complement , fibrinogen ( Fib ) and monocyte percentage ( MON % ) were detected simultaneously . RESULTS After PE treatment , nerve function defect appeared to improve better than the IVIg group and clinical effect was better than the IVIg group . Treatment effective rates of the two groups after 2 weeks , respectively , are 96 and 79 % . PE and IVIg can significantly reduce the GBS patients ' blood immunoglobulin IgG , IgA , IgM , C3 and C4 , but these were significantly lower in the PE group than in the IVIg group . Fib and MON % were significantly lower in the PE group than in the IVIg group . CONCLUSION Both PE and IVIg have a high response as therapy and are reasonable therapeutic options for GBS . However , PE treatment has a more significantly curative effect , as it can effectively improve symptoms and be helpful in the early rehabilitation of patients .

plasma exchange ( PE )

intravenous immunoglobulin ( IVIg )

PE

IVIg

Guillian-Barre syndrome .

plasma exchange ( PE )

intravenous immunoglobulin ( IVIg )

Guillian-Barre Syndrome ( GBS )

adult patients

GBS for PE

IVIg treatment

nerve function

reduce the GBS patients

rehabilitation of patients


Exploratory Subset Analysis of African Americans From the PointBreak Study : Pemetrexed-Carboplatin-Bevacizumab Followed by Maintenance Pemetrexed-Bevacizumab Versus Paclitaxel-Carboplatin-Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB/IV Nonsquamous Non-Small-Cell Lung Cancer . INTRODUCTION African Americans have a greater incidence of lung cancer than whites and have been underrepresented in clinical trials . In the PointBreak trial ( pemetrexed-carboplatin-bevacizumab and maintenance pemetrexed-bevacizumab [ PemCBev ] vs. paclitaxel-carboplatin-bevacizumab and maintenance bevacizumab [ PacCBev ] ) , 10 % of the patients were African American . PointBreak had negative findings ; PemCBev did not demonstrate superior overall survival ( OS ) . MATERIALS AND METHODS PointBreak subgroup efficacy and safety data were retrospectively analyzed : African Americans versus whites for PemCBev ; PemCBev versus PacCBev in African Americans ; and academic versus community settings for African Americans . Hazard ratios ( HRs ) and P values were derived from a multivariate Cox proportional hazards model after adjusting for covariates . RESULTS Of 939 intent-to-treat ( ITT ) patients , 94 were African American and 805 were white . African-American enrollment was uniform across the study sites ( median , 1 African American per site ) . In the PemCBev arm , OS ( HR , 1.125 ; P = .525 ) , progression-free survival ( PFS ) ( HR , 1.229 ; P = .251 ) , response ( P = .607 ) , and toxicity profiles were similar in African Americans versus whites . For African Americans , OS ( HR , 1.375 ; P = .209 ) , PFS ( HR , 0.902 ; P = .670 ) , response ( P = 1.000 ) , and toxicity profiles were similar in the PemCBev versus PacCBev arm . For African Americans , no significant differences were seen in OS ( HR , 0.661 ; P = .191 ) or PFS ( HR , 0.969 ; P = .915 ) in academic versus community practice settings . CONCLUSION In the PemCBev arm , this exploratory analysis showed no significant differences between African Americans and whites for the efficacy outcomes or toxicity profiles . Consistent with the ITT population negative trial result , for African Americans , the median OS was not superior for either arm . For African Americans , PFS and OS were similar in the academic and community settings . Additional outcomes data for African Americans should be collected in lung cancer studies .

efficacy

safety

Hazard ratios ( HRs ) and P values

a multivariate Cox

progression-free survival ( PFS )

response

toxicity profiles

toxicity profiles

efficacy

toxicity

lung cancer

PemCBev

PemCBev

PacCBev


Sustaining control of schistosomiasis mansoni in moderate endemicity areas in western Côte d'Ivoire : a SCORE study protocol . BACKGROUND Schistosomiasis is a parasitic disease that occurs in the tropics and subtropics . The mainstay of control is preventive chemotherapy with praziquantel . In Africa , an estimated 230 million people require preventive chemotherapy . In western Côte d'Ivoire , infections with Schistosoma mansoni are widespread . To provide an evidence-base for programme decisions about preventive chemotherapy to sustain control of schistosomiasis , a 5-year multi-country study with different treatment arms has been designed by the Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) and is currently being implemented in various African settings , including Côte d'Ivoire . METHODS/DESIGN We report the study protocol , including ethics statement and insight from a large-scale eligibility survey carried out in four provinces in western Côte d'Ivoire . The study protocol has been approved by the ethics committees of Basel and Côte d'Ivoire . A total of 12,110 children , aged 13-14 years , from 264 villages were screened for S. mansoni using duplicate Kato-Katz thick smears from single stool samples . Among the schools with a S. mansoni prevalence of 10-24 % , 75 schools were selected and randomly assigned to one of three treatment arms . In each school , three stool samples are being collected from 100 children aged 9-12 years annually and one stool sample from 100 first-year students at baseline and in the final year and subjected to duplicate Kato-Katz thick smears . Cost and coverage data for the different intervention arms , along with environmental , political and other characteristics that might impact on the infection prevalence and intensity will be recorded in each study year , using a pretested village inventory form . DISCUSSION The study will document changes in S. mansoni infection prevalence and intensity according to different treatment schemes . Moreover , factors that determine the effectiveness of preventive chemotherapy will be identified . These factors will help to develop reasonable measures of force of transmission that can be used to make decisions about the most cost-effective means of lowering prevalence , intensity and transmission in a given setting . The gathered information and results will inform how to effectively sustain control of schistosomiasis at a low level in different social-ecological contexts . TRIAL REGISTRATION ISRCTN99401114 ( date assigned : 12 November 2014 ) .

control of schistosomiasis mansoni

sustain control of schistosomiasis

changes in S.

sustain control of schistosomiasis

total of 12,110 children

aged 13-14 years

100 children

aged 9-12 years

100 first-year students


Most functional outcomes are similar for men and women after hip fracture : a secondary analysis of the enhancing mobility after hip fracture trial . BACKGROUND The impact of gender on functional outcomes after hip fracture is not known . We aimed to determine the extent to which gender influenced functional outcome and response to exercise in older people after hip fracture , and to determine if any differences persisted after adjusting for cognition , weight and age . METHOD Secondary analysis of data from the Enhancing Mobility After Hip Fracture trial in which older people after hip fracture received either a lower or higher intensity exercise program . Functional outcomes included physical performance and self-reported measures . Regression models were used to compare genders at baseline , week 4 and week 16 , with adjustment for baseline values , cognition , weight and age . Interaction terms were used to assess a differential impact of the intervention by gender . RESULTS Outcome data were available for 160 participants , 30 men ( 19 % ) and 130 women ( 81 % ) at baseline , with the withdrawal of 4 men ( 13 % ) and 6 women ( 5 % ) at week 16 . There were no gender differences for any baseline measures or for most of the 19 functional outcome measures at weeks 4 and 16 . At week 4 men performed better in knee extensor strength ( 2.1 kg , 95 % CI 0.6 to 3.7 , p < 0.01 ) . This difference did not persist after adjustment for body weight , however persisted after adjusting for baseline , cognition , and age ( p = 0.038 ) . At week 4 , men performed better in coordinated stability ( -10.0 error score , 95 % CI -17.6 to -2.4 , p=0.010 ) and this persisted after adjusting for baseline values only but not for cognition and age ( p = 0.073 ) . At week 16 , men performed better in coordinated stability ( -10.2 error score , 95 % CI -18.4 to -1.9 , p=0.016 ) and this persisted after adjusting only for cognitive impairment ( p = 0.029 ) but not for age and baseline ( p = 0.135 ) . There was no indication of a differential impact of intervention type on the basis of gender . CONCLUSIONS A few between gender differences were observed in strength and balance , however these appeared to be confounded by body weight , age and/or cognition .

exercise

Functional outcomes

no gender differences

baseline measures

functional outcome measures

knee extensor strength

difference did not persist

body weight

baseline

cognition

age

coordinated stability

persisted

baseline values

cognition

age

coordinated stability

persisted

cognitive impairment

age

baseline

strength and balance

body weight

age

cognition

men

women

older

hip fracture

Hip Fracture

men

women


TRANSCONJUNCTIVAL NONVITRECTOMIZING VITREOUS SURGERY VERSUS 25-GAUGE VITRECTOMY IN PATIENTS WITH EPIRETINAL MEMBRANE : A Prospective Randomized Study . PURPOSE To compare the clinical outcomes and the rate of complications of 27-gauge transconjunctival nonvitrectomizing vitreous surgery ( NVS ) and of 25-gauge transconjunctival sutureless vitrectomy surgery for idiopathic epiretinal membrane removal . METHODS In this prospective randomized study , 83 phakic eyes of 83 consecutive patients with an idiopathic epiretinal membrane were randomized to receive 27-gauge NVS ( NVS-group ) or 25-gauge vitrectomy ( Standard-group ) . Main outcome measures were best-corrected visual acuity , central retinal thickness , nuclear density units ' changes , and rate of complications . RESULTS Thirty-nine eyes of the Standard-group and 40 of the NVS-group were considered in final analysis . Mean best-corrected visual acuity improved significantly in both groups , with a significant better result at 12 months in NVS-group ( P = 0.039 ; t-test ) . Central retinal thickness decreased significantly in both groups ( P < 0.001 , Tukey test ) , without significant difference between the two groups at any time point . At 12 months , nuclear density increased significantly in the Standard-group ( analysis of variance , P < 0.001 ) , and it did not change in the NVS-group ( analysis of variance , P = 0.537 ) . Epiretinal membrane recurred in 5.1 % of eyes in the Standard-group and in 7.5 % of eyes in the NVS-group ( Fisher 's exact test , P = 1.000 ) . CONCLUSION The 27-gauge NVS is an effective surgical procedure in eyes with epiretinal membrane and it induces less progression of nuclear sclerosis than 25-gauge vitrectomy .

27-gauge NVS ( NVS-group )

25-gauge vitrectomy

NVS-group

27-gauge NVS

25-gauge vitrectomy .

Mean best-corrected visual acuity

Central retinal thickness

nuclear density

Epiretinal membrane

EPIRETINAL MEMBRANE

idiopathic epiretinal membrane

vitrectomy

Thirty-nine


Cognitive behavioral therapy for early adolescents with autism spectrum disorders and clinical anxiety : a randomized , controlled trial . Clinically elevated anxiety is a common , impairing feature of autism spectrum disorders ( ASD ) . A modular CBT program designed for preteens with ASD , Behavioral Interventions for Anxiety in Children with Autism ( BIACA ; Wood et al. , 2009 ) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety . Thirty-three adolescents ( 11-15 years old ) were randomly assigned to 16 sessions of CBT or an equivalent waitlist period . The CBT model emphasized exposure , challenging irrational beliefs , and behavioral supports provided by caregivers , as well as numerous ASD-specific treatment elements . Independent evaluators , parents , and adolescents rated symptom severity at baseline and posttreatment/postwaitlist . In intent-to-treat analyses , the CBT group outperformed the waitlist group on independent evaluators ' ratings of anxiety severity on the Pediatric Anxiety Rating Scale ( PARS ) and 79 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 28.6 % of the waitlist group . Group differences were not found for diagnostic remission or questionnaire measures of anxiety . However , parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity . The CBT manual under investigation , enhanced for early adolescents with ASD , yielded meaningful treatment effects on the primary outcome measure ( PARS ) , although additional developmental modifications to the manual are likely warranted . Future studies examining this protocol relative to an active control are needed .

Cognitive behavioral therapy

CBT

Behavioral Interventions

CBT

equivalent waitlist period

CBT

behavioral supports

CBT

CBT

CBT

symptom severity

parent-report data

early adolescents

preteens

ASD

early adolescents

ASD and clinical anxiety

Thirty-three

adolescents ( 11-15 years old )


Improving peer engagement of children with autism on the school playground : a randomized controlled trial . This study aimed to test the effects of a psychosocial intervention , Remaking Recess , on peer engagement for children with autism spectrum disorder ( ASD ) . Using a randomized , wait-list-controlled design , the intervention was implemented during recess at four elementary schools . The immediate treatment ( IT ) group consisted of 13 ( 2 female ) elementary school students with ASD and the wait-list ( WL ) group contained 11 ( 4 female ) students with ASD . All of the children with ASD were fully included in the general education program . Analyses revealed that time spent engaged with peers was significantly increased for the IT group and maintained over the follow-up . School playground staff in the IT group showed increased behaviors aimed at improving peer engagement for children with ASD compared to playground staff at the WL sites . These improvements did not maintain to follow-up . These results suggest that a low dose , brief intervention can be beneficial in increasing peer engagement for children with autism in inclusive settings , but continued support of playground staff is likely needed .

peer engagement

immediate treatment ( IT )

wait-list ( WL ) group

peer engagement

improvements did not maintain

children

autism

children

autism spectrum disorder ( ASD )

female

elementary school students

ASD

female

students

children

ASD

children

ASD


Efficacy of venlafaxine XR for the treatment of pain in patients with spinal cord injury and major depression : a randomized , controlled trial . OBJECTIVES To ( 1 ) determine the efficacy of venlafaxine XR for the treatment of pain ( secondary aim ) in individuals with spinal cord injury ( SCI ) enrolled in a randomized controlled trial ( RCT ) on the efficacy of venlafaxine XR for major depressive disorder ( MDD ) ( primary aim ) ; and ( 2 ) test the hypothesis that venlafaxine XR would be effective for both neuropathic and nociceptive pain . DESIGN Multisite , double-blind , randomized ( 1:1 ) controlled trial with subjects block randomized and stratified by site , lifetime history of substance abuse , and prior history of MDD . SETTING Six Departments of Physical Medicine and Rehabilitation in university-based medical schools . PARTICIPANTS Individuals ( N=123 ) with SCI and major depression between 18 and 64 years of age , at least 1 month post-SCI who also reported pain . INTERVENTION Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule . OUTCOME MEASURES A 0-to-10 numeric rating scale for pain , pain interference items of the Brief Pain Inventory ; 30 % and 50 % responders . RESULTS The effect of venlafaxine XR on neuropathic pain was similar to that of placebo . However venlafaxine XR resulted in statistically significant and clinically meaningful reductions in nociceptive pain site intensity and interference even after controlling for anxiety , depression , and multiple pain sites within the same individual . For those who achieved a minimally effective dose of venlafaxine XR , some additional evidence of effectiveness was noted for those with mixed ( both neuropathic and nociceptive ) pain sites . CONCLUSIONS Venlafaxine XR could complement current medications and procedures for treating pain after SCI and MDD that has nociceptive features . Its usefulness for treating central neuropathic pain is likely to be limited . Research is needed to replicate these findings and determine whether the antinociceptive effect of venlafaxine XR generalizes to persons with SCI pain without MDD .

venlafaxine XR

venlafaxine XR

venlafaxine

venlafaxine

venlafaxine XR

placebo

flexible titration schedule

venlafaxine XR

placebo

venlafaxine XR

venlafaxine XR

Venlafaxine XR

venlafaxine XR

anxiety

depression

, and multiple pain sites

( N=123

18 and 64 years of age


Diet-Related Colorectal Cancer Prevention Beliefs and Dietary Intakes in an Urban Minority Population . In the United States , colorectal cancer ( CRC ) is the third leading cause of cancer-related death and third most commonly diagnosed cancer among adults . This study is the first to examine the relationship between diet-related beliefs for colorectal cancer prevention and dietary intake among an urban , predominantly Black population ( n = 169 ) . More than two-thirds reported diet-related CRC prevention beliefs . Those with diet-related CRC prevention beliefs had healthier intakes for dietary fiber ( p = .005 ) , fruit , vegetable , bean ( p = .027 ) , red meat ( p = .032 ) , vitamin C ( p = .039 ) , and cholesterol ( p = .045 ) . Most people may already have diet-related CRC prevention beliefs and having them is associated with a more healthful dietary intake .

Dietary Intakes

dietary intake

diet-related

dietary fiber

fruit , vegetable , bean

red meat

diet-related CRC prevention beliefs

dietary intake

intakes for dietary fiber

fruit , vegetable , bean

red meat

vitamin C

cholesterol

healthful dietary intake .


Effect of low versus high dialysate sodium concentration on blood pressure and endothelial-derived vasoregulators during hemodialysis : a randomized crossover study . BACKGROUND Intradialytic hypertension affects ∼15 % of hemodialysis patients and is associated with increased morbidity and mortality . While intradialytic hypertension is associated with increases in endothelin 1 relative to nitric oxide ( NO ) , the cause of these imbalances is unknown . In vitro evidence suggests that altering plasma sodium levels could affect endothelial-derived vasoregulators and blood pressure ( BP ) . Thus , we hypothesized that compared to high dialysate sodium , low dialysate sodium concentration would lower endothelin 1 levels , increase NO release , and reduce BP . STUDY DESIGN 3-week , 2-arm , randomized , crossover study . SETTING & PARTICIPANTS 16 patients with intradialytic hypertension . INTERVENTION Low ( 5 mEq/L below serum sodium ) versus high ( 5 mEq/L above serum sodium ) dialysate sodium concentration . OUTCOMES Endothelin 1 , nitrite ( NO2 ( - ) ) , and BP . MEASUREMENTS Mixed linear regression was used to compare the effect of dialysate sodium ( low vs high ) and randomization arm ( low-then-high vs high-then-low ) on intradialytic changes in endothelin 1 , NO2 ( - ) , and BP values . RESULTS The average systolic BP throughout all hemodialysis treatments in a given week was lower with low dialysate sodium concentrations compared with treatments with high dialysate sodium concentrations ( parameter estimate , -9.9 [ 95 % CI , -13.3 to -6.4 ] mm Hg ; P < 0.001 ) . The average change in systolic BP during hemodialysis also was significantly lower with low vs high dialysate sodium concentrations ( parameter estimate , -6.1 [ 95 % CI , -9.0 to -3.2 ] mm Hg ; P < 0.001 ) . There were no significant differences in intradialytic levels of endothelin 1 or NO2 ( - ) with low vs high dialysate sodium concentrations . LIMITATIONS Carryover effects limited the power to detect significant changes in endothelial-derived vasoregulators , and future studies will require parallel trial designs . CONCLUSIONS Low dialysate sodium concentrations significantly decreased systolic BP and ameliorated intradialytic hypertension . Longer studies are needed to determine the long-term effects of low dialysate sodium concentrations on BP and clinical outcomes .

lower endothelin 1 levels

increase NO release

reduce

OUTCOMES Endothelin 1

nitrite ( NO2 ( - ) )

BP

intradialytic changes in endothelin 1

NO2 ( - )

BP values

The average systolic

significantly decreased systolic

ameliorated intradialytic hypertension

concentrations

16 patients

intradialytic hypertension


Cariprazine in the treatment of acute mania in bipolar I disorder : a double-blind , placebo-controlled , phase III trial . BACKGROUND This Phase III , randomized , double-blind , placebo-controlled study investigated the efficacy and tolerability of flexibly-dosed cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder . METHODS Patients were randomized to 3 weeks of double-blind treatment with cariprazine 3-12mg/day ( n=158 ) or placebo ( n=154 ) . The primary efficacy parameter was change from baseline to Week 3 in Young Mania Rating Scale ( YMRS ) total score . The secondary efficacy parameter was change from baseline to Week 3 in Clinical Global Impressions-Severity ( CGI-S ) score . RESULTS Mean change from baseline to Week 3 in YMRS total score was significantly greater for patients receiving cariprazine 3-12mg/day versus placebo ( P=0.0004 ) . Significant differences between groups in YMRS total score mean change were observed by Day 4 ( first postbaseline assessment ) and maintained throughout double-blind treatment ( all assessments , P < 0.01 ) . Cariprazine also demonstrated statistically significant superiority over placebo on YMRS response ( ≥50 % improvement : cariprazine , 58.9 % ; placebo , 44.1 % ; P=0.0097 ) and remission ( YMRS total score≤12 : cariprazine , 51.9 % ; placebo , 34.9 % ; P=0.0025 ) and mean change in CGI-S ( P=0.0027 ) score and Positive and Negative Syndrome Scale ( PANSS ) ( P=0.0035 ) total score . The most common cariprazine-related ( ≥10 % and twice placebo ) treatment emergent adverse events ( TEAEs ) were akathisia , extrapyramidal disorder , tremor , dyspepsia , and vomiting . Mean change from baseline in metabolic parameters were generally small and similar between groups . LIMITATIONS Lack of active comparator arm ; short duration of study . CONCLUSION In this study , cariprazine 3-12mg/day was effective and generally well tolerated in the treatment of manic and mixed episodes associated with bipolar I disorder .

Cariprazine

cariprazine

cariprazine

or placebo

cariprazine

Cariprazine

efficacy and tolerability

YMRS total score

YMRS response

cariprazine 3-12mg/day


Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD . RATIONALE Attention deficit hyperactivity disorder ( ADHD ) and autism spectrum disorder ( ASD ) are often comorbid and have both performance and brain dysfunctions during motor response inhibition . Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders . AIMS We therefore used functional magnetic resonance imaging ( fMRI ) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders , as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine . METHODS Age-matched boys with ADHD ( 18 ) , ASD ( 19 ) and healthy controls ( 25 ) were compared with fMRI during a stop task measuring motor inhibition . Patients were scanned twice , under either an acute dose of fluoxetine or placebo in a double-blind , placebo-controlled randomised design . Repeated measures analyses within patients assessed drug effects . To test for potential normalisation effects of brain dysfunctions , patients under each drug condition were compared to controls . RESULTS Under placebo , relative to controls , ASD boys showed overactivation in left and right inferior frontal cortex ( IFC ) , while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex ( OFC ) and basal ganglia . Under fluoxetine , the prefrontal dysfunctions were no longer observed , due to inverse effects of fluoxetine on these activations : fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD . CONCLUSIONS The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects , downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD , potentially reflecting inverse baseline serotonin levels in both disorders .

functional magnetic resonance imaging

an acute dose of fluoxetine

placebo

placebo-controlled

inhibitory brain activation

motor response inhibition

behavioural effects

inhibitory brain dysfunctions

motor inhibition .

drug effects .

normalisation effects

prefrontal dysfunctions

IFC and OFC activation

frontal lobe dysfunctions

frontal activation

frontal activation

boys

ADHD

ASD

boys

ADHD

ASD

healthy controls

ASD

boys

ADHD

boys


Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients : results from a subset analysis of the CALYPSO phase III trial . AIM To perform a subset analysis of patients with very platinum-sensitive recurrent ovarian cancer ( ROC ) enrolled in the phase III CALYPSO trial . PATIENTS AND METHODS The international non-inferiority trial enrolled women with ROC that relapsed > 6 months following first- or second-line platinum- and paclitaxel-based therapies . Patients were randomised to CD [ carboplatin-pegylated liposomal doxorubicin ( PLD ) ] or CP ( carboplatin-paclitaxel ) and stratified by treatment-free interval ( TFI ) . In this analysis , patients with a TFI > 24 months were analysed separately for progression free survival ( PFS ) , the primary endpoint of CALYPSO , overall survival ( OS ) and safety . RESULTS A total of 259 very platinum-sensitive patients were included ( n=131 , CD ; n=128 , CP ) . Median PFS was 12.0 months for the CD arm and 12.3 months for CP [ HR=1.05 ( 95 % CI , 0.79-1.40 ) ; P=0.73 for superiority ] and median OS was 40.2 months for CD and 43.9 for CP [ HR=1.18 ( 95 % CI 0.85-1.63 ) ; P=0.33 for superiority ] . Overall response rates were 42 % and 38 % , respectively ( P=0.46 ) . Toxicities were more common with CP versus CD , including grade 3/4 neutropenia ( 40.8 % versus 27.5 % ; P=0.025 ) , nausea ( 4.8 % versus 3.1 % ; P=0.47 ) , allergic reaction ( 8 % versus 3.1 % ; P=0.082 ) sensory neuropathy ( 4.8 % versus 2.3 % ; P=0.27 ) and grade 2 alopecia ( 88 % versus 9.2 % ; P < 0.001 ) . Grade 3/4 thrombocytopenia ( 12.2 % versus 3.2 % ; P=0.007 ) and mucositis ( 2.3 % versus 0 % ; P=0.089 ) were more common with CD . Grade 3/4 hand-foot syndrome occurred rarely with CD ( 3 patients versus 0 in CP arm ; P=0.089 ) . CONCLUSION CP and CD were equally effective treatment regimens for patients with very platinum-sensitive ROC . The favourable risk-benefit profile suggests carboplatin-PLD as treatment of choice for these patients .

carboplatin and paclitaxel

CP ( carboplatin-paclitaxel )

CD

CP

CP

CD

CD

CD

carboplatin-PLD

Median PFS

median OS

response rates

Toxicities

grade 3/4 neutropenia

nausea

allergic reaction

sensory neuropathy

grade 2 alopecia

Grade 3/4 thrombocytopenia

mucositis

Grade 3/4 hand-foot syndrome

total of 259

, CD ;

, CP )


Crohn 's disease management after intestinal resection : a randomised trial . BACKGROUND Most patients with Crohn 's disease need an intestinal resection , but a majority will subsequently experience disease recurrence and require further surgery . This study aimed to identify the optimal strategy to prevent postoperative disease recurrence . METHODS In this randomised trial , consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn 's disease , with an endoscopically accessible anastomosis , received 3 months of metronidazole therapy . Patients at high risk of recurrence also received a thiopurine , or adalimumab if they were intolerant to thiopurines . Patients were randomly assigned to parallel groups : colonoscopy at 6 months ( active care ) or no colonoscopy ( standard care ) . We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio . For endoscopic recurrence ( Rutgeerts score ≥i2 ) at 6 months , patients stepped-up to thiopurine , fortnightly adalimumab with thiopurine , or weekly adalimumab . The primary endpoint was endoscopic recurrence at 18 months . Patients and treating physicians were aware of the patient 's study group and treatment , but central reading of the endoscopic findings was undertaken blind to the study group and treatment . Analysis included all patients who received at least one dose of study drug . This trial is registered with ClinicalTrials.gov , number NCT00989560 . FINDINGS Between Oct 13 , 2009 , and Sept 28 , 2011 , 174 ( 83 % high risk across both active and standard care groups ) patients were enrolled and received at least one dose of study drug . Of 122 patients in the active care group , 47 ( 39 % ) stepped-up treatment . At 18 months , endoscopic recurrence occurred in 60 ( 49 % ) patients in the active care group and 35 ( 67 % ) patients in the standard care group ( p=0.03 ) . Complete mucosal normality was maintained in 27 ( 22 % ) of 122 patients in the active care group versus four ( 8 % ) in the standard care group ( p=0.03 ) . In the active care arm , of those with 6 months recurrence who stepped up treatment , 18 ( 38 % ) of 47 patients were in remission 12 months later ; conversely , of those in remission at 6 months who did not change therapy recurrence occurred in 31 ( 41 % ) of 75 patients 12 months later . Smoking ( odds ratio [ OR ] 2.4 , 95 % CI 1.2-4.8 , p=0.02 ) and the presence of two or more clinical risk factors including smoking ( OR 2.8 , 95 % CI 1.01-7.7 , p=0.05 ) increased the risk of endoscopic recurrence . The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups ( 100 [ 82 % ] of 122 vs 45 [ 87 % ] of 52 ; p=0.51 ) and ( 33 [ 27 % ] of 122 vs 18 [ 35 % ] of 52 ; p=0.36 ) , respectively . INTERPRETATION Treatment according to clinical risk of recurrence , with early colonoscopy and treatment step-up for recurrence , is better than conventional drug therapy alone for prevention of postoperative Crohn 's disease recurrence . Selective immune suppression , adjusted for early recurrence , rather than routine use , leads to disease control in most patients . Clinical risk factors predict recurrence , but patients at low risk also need monitoring . Early remission does not preclude the need for ongoing monitoring . FUNDING AbbVie , Gutsy Group , Gandel Philanthropy , Angior Foundation , Crohn 's Colitis Australia , and the National Health and Medical Research Council .

intestinal resection

metronidazole

thiopurine

adalimumab

colonoscopy at 6 months

( active care )

no colonoscopy ( standard care )

recurrence

endoscopic recurrence

endoscopic recurrence

Complete mucosal normality

months recurrence

in remission

endoscopic recurrence

clinical risk of recurrence

disease control

predict recurrence

need monitoring

Early remission

patients with Crohn 's disease

Crohn 's disease

Patients at high risk of recurrence

122 patients in the active care group


Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids . OBJECTIVE To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids . DESIGN Double-blind , randomized administration of two 12-week courses of ulipristal acetate . SETTING Gynecology centers . PATIENT ( S ) A total of 451 patients with symptomatic uterine fibroid ( s ) and heavy bleeding . INTERVENTION ( S ) Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate . MAIN OUTCOME MEASURE ( S ) Amenorrhea , controlled bleeding , fibroid volume , quality of life ( QoL ) , pain . RESULT ( S ) In the 5- and 10-mg treatment groups ( 62 % and 73 % of patients , respectively ) achieved amenorrhea during both treatment courses . Proportions of patients achieving controlled bleeding during two treatment courses were > 80 % . Menstruation resumed after each treatment course and was diminished compared with baseline . After the second treatment course , median reductions from baseline in fibroid volume were 54 % and 58 % for the patients receiving 5 and 10 mg of ulipristal acetate , respectively . Pain and QoL improved in both groups . Ulipristal acetate was well tolerated with less than 5 % of patients discontinuing treatment due to adverse events . CONCLUSION ( S ) Repeated 12-week courses of daily oral ulipristal acetate ( 5 and 10 mg ) effectively control bleeding and pain , reduce fibroid volume , and restore QoL in patients with symptomatic fibroids . CLINICAL TRIAL REGISTRATION NUMBER NCT01629563 ( PEARL IV ) .

ulipristal acetate

ulipristal acetate

ulipristal acetate

5 or 10 mg of ulipristal acetate

Efficacy

safety

efficacy

safety

quality of life ( QoL )

pain

amenorrhea

controlled bleeding

Menstruation resumed

Pain

QoL

tolerated

adverse events .

bleeding

pain

fibroid volume

QoL

uterine fibroids .

symptomatic uterine fibroids .

Gynecology centers .


Relationships of PROP Taste Phenotype , Taste Receptor Genotype , and Oral Nicotine Replacement Use . INTRODUCTION Recommended dosage of oral nicotine replacement therapy ( NRT ) product is often not achieved in smoking cessation attempts . n-6-propylthiouracil ( PROP ) bitter taste phenotype may be a potential risk factor for non-adherence to oral NRT products due to their bitter taste . There is limited literature on this phenotype in the context of smoking and none in relation to oral NRT pharmacotherapy . METHODS The association of PROP taste phenotype with NRT usage and sensory response to products was examined . In a cross-over experimental design , 120 participants received a 1 week supply of nicotine inhalers and 1 week of nicotine lozenges with random assignment to order . Mixed effects linear model analyses were conducted . RESULTS PROP taste phenotype and taste receptor genotype were not associated with NRT usage or sensory response to NRT , after adjusting for other factors . However , PROP non-tasters used a higher number of lozenges per day ( continuous exposure ) than nicotine cartridges ( intermittent exposure ) . Unexpectedly , half of baseline PROP non-tasters shifted to taster phenotype 2 weeks after smoking cessation or reduction . Menthol cigarette smokers identified higher NRT strength of sensation scores than nonmenthol smokers . Taste receptor genotype was related to PROP taste phenotype ( Kendall τ = .591 , p = .0001 ) . CONCLUSIONS A nonsignificant relationship of PROP phenotype and NRT usage may be associated with NRT under-dosing and limited variance in the outcome variable . PROP non-tasters ' greater use of lozenges is consistent with nicotine exposure being less aversive to non-tasters . Further research of this and other factors impacting NRT usage are warranted to effectively inform smoking cessation pharmacotherapy .

number of lozenges per day

higher NRT strength of sensation scores

nicotine inhalers

Menthol cigarette smokers

nonmenthol smokers .


The effect of treatment on pregnancy outcomes in women with one elevated oral glucose tolerance test value . OBJECTIVE The aim of the study was to evaluate whether dietary intervention could reduce maternal and perinatal morbidity in pregnancies with one elevated 100 g oral glucose tolerance test ( OGTT ) value . MATERIAL AND METHODS The study was conducted among patients with positive 50 g glucose challenge test ( GCT ) and one elevated 100 g OGTT value . Plasma glucose value of 140 mg/dL was used as the threshold to define an abnormal GCT result . Carpenter and Coustan criteria were used to evaluate the OGTT results . Seventy-four women with normal GCT values comprised group I. Ninety-nine women with one elevated 100 g OGTT value who were given a caloric diet and 102 women with one elevated OGTT value in group III who received antenatal care with no special diet were randomly assigned to groups II and III , respectively . All women were followed up until the end of pregnancy . Poor maternal outcome was defined as : cesarean delivery performed due to cephalopelvic disproportion , failure to progress or fetal distress , preeclampsia , and/or preterm labor . Poor perinatal outcome was defined as : small for gestational age , large for gestational age or admission to a neonatal intensive care unit . The groups were compared in terms of maternal and perinatal outcomes . RESULTS The rates of macrosomia and large for gestational age incidence were significantly higher in group III as compared to groups I and II . When we examined the multivariate effects of the risk factors considered to be predictive of poor maternal outcomes , group III was the only statistically significant risk factor ( OR=3.90 , 95 % CI:1.95- 7.84 ; p= < 0.001 ) . In terms of poor perinatal outcome , one elevated OGTT value ( group III ) was the only significant risk factor ( OR=2.92 , 95 % CI:1.56-5.46 ; p= < 0.001 ) . CONCLUSION Women with one elevated OGTT value benefit from a structured program of diet therapy aimed to reduce adverse maternal and perinatal outcomes .

dietary intervention

caloric diet

antenatal care with no special diet

diet therapy

women

one elevated 100 g OGTT value

Seventy-four

women

Ninety-nine

women

women

women

Women


Wrist Rehabilitation Assisted by an Electromyography-Driven Neuromuscular Electrical Stimulation Robot After Stroke . BACKGROUND Augmented physical training with assistance from robot and neuromuscular electrical stimulation ( NMES ) may introduce intensive motor improvement in chronic stroke . OBJECTIVE To compare the rehabilitation effectiveness achieved by NMES robot-assisted wrist training and that by robot-assisted training . METHODS This study was a single-blinded randomized controlled trial with a 3-month follow-up . Twenty-six hemiplegic subjects with chronic stroke were randomly assigned to receive 20-session wrist training with an electromyography ( EMG ) -driven NMES robot ( NMES robot group , n = 11 ) and with an EMG-driven robot ( robot group , n = 15 ) , completed within 7 consecutive weeks . Clinical scores , Fugl-Meyer Assessment ( FMA ) , Modified Ashworth Score ( MAS ) , and Action Research Arm Test ( ARAT ) were used to evaluate the training effects before and after the training , as well as 3 months later . An EMG parameter , muscle co-contraction index , was also applied to investigate the session-by-session variation in muscular coordination patterns during the training . RESULTS The improvement in FMA ( shoulder/elbow , wrist/hand ) obtained in the NMES robot group was more significant than the robot group ( P < .05 ) . Significant improvement in ARAT was achieved in the NMES robot group ( P < .05 ) but absent in the robot group . NMES robot-assisted training showed better performance in releasing muscle co-contraction than the robot-assisted across the training sessions ( P < .05 ) . CONCLUSIONS The NMES robot-assisted wrist training was more effective than the pure robot . The additional NMES application in the treatment could bring more improvements in the distal motor functions and faster rehabilitation progress .

NMES robot-assisted wrist training

robot-assisted training .

EMG-driven robot

NMES robot

NMES robot-assisted wrist training

Fugl-Meyer Assessment ( FMA )

Modified Ashworth Score ( MAS )

Action Research Arm Test ( ARAT )

ARAT

better performance

releasing muscle co-contraction

Stroke

Twenty-six

hemiplegic

chronic stroke


Concentrated parenteral nutrition solutions and central venous catheter complications in preterm infants . UNLABELLED Standardised , concentrated neonatal parenteral nutrition ( PN ) regimens can overcome early nutritional deficits in very preterm infants . A PN regimen with increased macronutrient content ( standardised , concentrated , added macronutrients parenteral ( SCAMP ) ) has been shown to improve early head growth in a randomised controlled trial . Line complications including late onset sepsis were secondary outcomes of this study . Infants were started on standardised , concentrated PN at birth and randomised at 2-5 days to either switch to SCAMP or remain on control PN . Central venous catheter ( CVC ) , blood culture ( BC ) and inflammatory marker data were collected for the 28-day intervention period . 150 infants were randomised with mean ( SD ) birth weight ( g ) of 900 ( 158 ) versus 884 ( 183 ) in SCAMP ( n=74 ) and control ( n=76 ) groups , respectively . There were no differences in CVC use/type or duration or in positive/negative BC with/without associated C reactive protein rise in SCAMP versus control groups . Increasing the macronutrient content of a standardised , concentrated neonatal PN regimen does not increase CVC complication rates . TRIAL REGISTRATION NUMBER ISRCTN 76597892 .

parenteral nutrition

concentrated PN

SCAMP

remain on control PN .

SCAMP

PN

central venous catheter complications

Line complications

late onset sepsis

birth weight

CVC complication rates .

central venous catheter complications

preterm infants

very preterm infants