REVIVE Trial : Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure . UNLABELLED Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy . Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure ( IHF ) or nonischemic heart failure ( NIHF ) . This was a prospective randomized , multicenter , open-label study of the safety and feasibility of bone marrow aspirate concentrate ( BMAC ) infused retrograde into the coronary sinus . Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control ( standard heart failure care ) in a 4:1 ratio . Accordingly , 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group . Similarly , 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group . All 60 patients were successfully enrolled in the study . The treatment groups received BMAC infusion without complications . The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline , from 25.1 % at screening to 31.1 % at 12 months ( p=.007 ) in the NIHF group and from 26.3 % to 31.1 % in the IHF group ( p=.035 ) . The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm ( p=.020 ) . Retrograde BMAC delivery is safe . All patients receiving BMAC experienced improvements in left ventricular ejection fraction , but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide . These results provide the basis for a larger clinical trial in HF patients . SIGNIFICANCE This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure . This was a multinational , multicenter study , and it is novel , translatable , and scalable . On the basis of this trial and the safety of retrograde coronary sinus infusion , there are three other trials under way using this route of delivery .

Cell therapy

bone marrow aspirate concentrate

retrograde

BMAC infusion

control

BMAC infusion

BMAC

left ventricular ejection fraction

significant improvement

delivery is safe .

left ventricular ejection fraction


Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance , Inflammation , Glucose , and Free Fatty Acids : A Pilot Study . OBJECTIVE Diet therapy in gestational diabetes mellitus ( GDM ) has focused on carbohydrate restriction but is poorly substantiated . In this pilot randomized clinical trial , we challenged the conventional low-carbohydrate/higher-fat ( LC/CONV ) diet , hypothesizing that a higher-complex carbohydrate/lower-fat ( CHOICE ) diet would improve maternal insulin resistance ( IR ) , adipose tissue ( AT ) lipolysis , and infant adiposity . RESEARCH DESIGN AND METHODS At 31 weeks , 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV ( 40 % carbohydrate/45 % fat/15 % protein ; n = 6 ) or CHOICE ( 60 % /25 % /15 % ; n = 6 ) diet . All meals were provided . AT was biopsied at 37 weeks . RESULTS After ∼7 weeks , fasting glucose ( P = 0.03 ) and free fatty acids ( P = 0.06 ) decreased on CHOICE , whereas fasting glucose increased on LC/CONV ( P = 0.03 ) . Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV ( 56 vs. 31 % , P = 0.005 ) , consistent with improved IR . AT expression of multiple proinflammatory genes was lower on CHOICE ( P < 0.01 ) . Infant adiposity trended lower with CHOICE ( 10.1 ± 1.4 vs. 12.6 ± 2 % , respectively ) . CONCLUSIONS A CHOICE diet may improve maternal IR and infant adiposity , challenging recommendations for a LC/CONV diet .

CHOICE

diet

meals


Cost effectiveness of treatment with percutaneous Kirschner wires versus volar locking plate for adult patients with a dorsally displaced fracture of the distal radius : analysis from the DRAFFT trial . We present an economic evaluation using data from the Distal Radius Acute Fracture Fixation Trial ( DRAFFT ) to compare the relative cost effectiveness of percutaneous Kirschner wire ( K-wire ) fixation and volar locking-plate fixation for patients with dorsally-displaced fractures of the distal radius . The cost effectiveness analysis ( cost per quality-adjusted life year ; QALY ) was derived from a multi-centre , two-arm , parallel group , assessor-blind , randomised controlled trial which took place in 18 trauma centres in the United Kingdom . Data from 460 patients were available for analysis , which includes both a National Health Service cost perspective including costs of surgery , implants and healthcare resource use over a 12-month period after surgery , and a societal perspective , which includes the cost of time off work and the need for additional private care . There was only a small difference in QALYs gained for patients treated with locking-plate fixation over those treated with K-wires . At a mean additional cost of £714 ( 95 % confidence interval 588 to 865 ) per patient , locking-plate fixation presented an incremental cost effectiveness ratio ( ICER ) of £89,322 per QALY within the first 12 months of treatment . Sensitivity analyses were undertaken to assess the ICER of locking-plate fixation compared with K-wires . These were greater than £30,000 . Compared with locking-plate fixation , K-wire fixation is a 'cost saving ' intervention , with similar health benefits .

and

volar locking-plate fixation

locking-plate fixation

K-wires .

costs of surgery , implants

healthcare resource use

cost of time off work

additional private care .

QALYs

the ICER

adult

trauma


Quadratus lumborum block for postoperative pain after caesarean section : A randomised controlled trial . BACKGROUND Effective postoperative analgesia after caesarean section is important because it enables early ambulation and facilitates breast-feeding . Several case reports have shown that local anaesthetic injection around the quadratus lumborum muscle is effective in providing pain relief after various abdominal operations and in patients with chronic pain . The quadratus lumborum block ( QLB ) is performed in close proximity to the surface and uses a fascial compartment path to extend the distribution of local anaesthesia into the posterior abdominal wall and paravertebral space . This central effect can be of vital importance when managing the visceral pain after caesarean section . OBJECTIVE We hypothesised that the QLB after caesarean section can provide adequate pain relief as part of a multimodal approach . DESIGN Double-blind , randomised and controlled clinical trial . SETTING A single centre between June 2014 and December 2014 . PATIENTS Fifty patients who were American Society of Anesthesiologists physical status 1 or 2 , with normal singleton pregnancies with a gestation of at least 37 weeks , and scheduled for elective caesarean section under spinal anaesthesia , were enrolled into the study . They were randomly assigned to receive a QLB ( n = 25 ) with 0.125 % bupivacaine 0.2 ml kg⁻¹ ( Group 1 ) or a QLB ( n = 25 ) with 0.9 % Normal saline 0.2 ml kg⁻¹ ( Group 2 ) . MAIN OUTCOME MEASURES The primary outcome measure for the study was the morphine demands and doses delivered by a patient-controlled analgesia system at predetermined intervals ( 1 , 2 , 4 , 6 , 12 , 24 and 48 h ) after surgery . The secondary endpoints were visual analogue scale ( VAS ) for pain at rest and on movement ( dynamic ) , heart rate , blood pressure , pruritus , itching , nausea , vomiting and sedation . RESULTS The patients who received local anaesthetic used significantly less morphine than the control group ( P < 0.001 ) at 6 and 12 h , but not at 24 and 48 hours after caesarean section . The local anaesthetic group had significantly less morphine demand than the control group ( P < 0.001 ) 6 , 12 , 24 and 48 h after caesarean section . The VAS was significantly lower in the local anaesthetic group than the control group , including VAS for pain at rest at all times except 24 h after caesarean section , and VAS for pain on movement ( dynamic ) at all times . CONCLUSION The QLB after caesarean section was effective and provided satisfactory analgesia in combination with a typical postoperative analgesic regimen . TRIAL REGISTRATION ClinicalTrials.gov identifier : NCT02328378 .

lumborum block

caesarean section

caesarean

local anaesthetic injection

quadratus lumborum block

QLB

bupivacaine

postoperative pain

visceral pain

morphine demands and doses

heart rate

blood pressure

pruritus

itching

used significantly

anaesthetic group had

patients with chronic pain .

Fifty

Anesthesiologists


Total and Partial Prevalence of Cancer Across Kerman Province , Iran , in 2014 , Using an Adapted Generalized Network Scale-Up Method . Due to the lack of nationwide population-based cancer registration , the total cancer prevalence in Iran is unknown . Our previous work in which we used a basic network scale-up ( NSU ) method , failed to provide plausible estimates of total cancer prevalence in Kerman . The aim of the present study was to estimate total and partial prevalence of cancer in southeastern Iran using an adapted version of the generalized network scale-up method . A survey was conducted in 2014 using multi-stage cluster sampling . A total of 1995 face-to-face gender-matched interviews were performed based on an adapted version of the NSU questionnaire . Interviewees were asked about their family cancer history . Total and partial prevalence were estimated using a generalized NSU estimator . The Monte Carlo method was adopted for the estimation of upper/lower bounds of the uncertainty range of point estimates . One-yr , 2-3 yr , and 4-5 yr prevalence ( per 100,000 people ) was respectively estimated at 78 ( 95 % CI , 66 , 90 ) , 128 ( 95 % CI , 118 , 147 ) , and 59 ( 95 % CI , 49 , 70 ) for women , and 48 ( 95 % CI , 38 , 58 ) , 78 ( 95 % CI , 66 , 91 ) , and 42 ( 95 % CI , 32 , 52 ) for men . The 5-yr prevalence of all cancers was estimated at 0.18 percent for men , and 0.27 percent for women . This study showed that the generalized familial network scale-up method is capable of estimating cancer prevalence , with acceptable precision .

NSU questionnaire

Total and Partial Prevalence of Cancer

cancer prevalence

prevalence of cancer

Total and partial prevalence

One-yr , 2-3 yr , and 4-5 yr prevalence

5-yr prevalence of all cancers

cancer prevalence

Cancer


A Comparison of Outcomes Following Laparoscopic and Open Hysterectomy With or Without Lymphadenectomy for Presumed Early-Stage Endometrial Cancer : Results From the Medical Research Council ASTEC Trial . OBJECTIVES Laparoscopic hysterectomy ( LH ) is increasingly used for the management of endometrial malignancy . Its benefits may be particularly pronounced as these women are more likely to be older or obese . The aim of this study was to determine whether outcomes for LH are comparable to the open hysterectomy ( OH ) . DESIGN This was a prospective cohort study nested within the multicenter ASTEC ( A Study in the Treatment of Endometrial Cancer ) randomized controlled trial ( 1998-2005 ) . POPULATION Women with presumed early endometrial cancer were included . METHODS Laparoscopic hysterectomy was compared with OH with or without systematic lymphadenectomy . MAIN OUTCOME MEASURES Overall survival , time to first recurrence , complication rates , and surgical outcomes were the main outcome measures . RESULTS Of 1408 women , 1309 ( 93 % ) received OH , and 99 ( 7 % ) had LH . LH was associated with longer operating time ( median , LH 105 minutes [ interquartile range ( IQR ) , 60-150 ] vs OH 80 minutes [ IQR , 60-95 ] ; P < 0.001 ) but 50 % shorter hospital stay ( median , LH 4 days [ IQR , 3-5 ] vs OH 6 days [ IQR , 5-7 ] ) . The number of harvested lymph nodes was similar ( median , LH 13 [ IQR , 10-16 ] vs OH 12 [ IQR , 11-13 ] ; P = 0.67 ) . LH had fewer intraoperative and postoperative adverse events ( 9 % difference , LH 21 % vs OH 30 % ; borderline significance ; P = 0.07 ) . The rate of conversion to laparotomy for the LH group was high ( 27 % ) . The median follow-up was 37 months . After adjusting for significant prognostic factors , the hazard ratio for overall survival in those who underwent LH compared with those who underwent OH was 0.67 ( 95 % confidence interval , 0.31-1.43 ) ( P = 0.30 ) . CONCLUSIONS Laparoscopic hysterectomy for early endometrial cancer is safe . Although it requires longer operating time it is associated with shorter hospital stay and favorable morbidity profile . Further studies are required to assess the long-term safety .

Laparoscopic

Open Hysterectomy

Laparoscopic hysterectomy ( LH )

Laparoscopic hysterectomy

OH

systematic lymphadenectomy

LH

OH

OH

LH

OH

LH

LH

LH

OH

Laparoscopic hysterectomy

Overall survival

time to first recurrence

complication rates

surgical outcomes

operating time

hospital stay

number of harvested lymph nodes

rate of conversion to laparotomy

hazard ratio for overall survival

operating time

hospital stay

morbidity profile

long-term safety

Presumed Early-Stage Endometrial Cancer

women

older

Women

women

OH

LH


Homocysteine Metabolism Gene Polymorphisms ( MTHFR C677T , MTHFR A1298C , MTR A2756G and MTRR A66G ) Jointly Elevate the Risk of Folate Deficiency . Folate deficiency is strongly associated with cardiovascular disease . We aimed to explore the joint effect of the methylenetetrahydrofolate reductase ( MTHFR ) C677T and A1298C , methionine synthase ( MTR ) A2756G , and methionine synthase reductase ( MTRR ) A66G polymorphisms on folate deficiency in a Chinese hypertensive population . A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions . Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay . Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency ( TT vs. CC + CT , p < 0.001 and AG + GG vs. AA p = 0.030 , respectively ) . However , the MTHFR A1298C mutation may confer protection by elevating the serum folate level ( p = 0.025 ) . Furthermore , patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers , especially those carrying four risk genotypes . These findings were verified by generalized multifactor dimensionality reduction ( p = 0.0107 ) and a cumulative effects model ( p = 0.001 ) . The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk .

methionine synthase ( MTR ) A2756G

MTHFR 677TT

MTR 2756AG + GG

MTHFR A1298C

folate deficiency

serum folate

MTHFR 677TT and MTR 2756AG + GG

folate deficiency

serum folate level

folate deficiency

Chinese hypertensive population

A

aged 28-75 were


Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome : A Randomized , Double-Blind , Placebo-Controlled Trial . BACKGROUND The aim of the present study was to evaluate the beneficial effects of chromium intake on markers of insulin metabolism and lipid profiles in women with polycystic ovary syndrome ( PCOS ) . METHODS In a prospective , randomized , double-blind , placebo-controlled trial , 64 women with PCOS were randomized to receive 200 µg chromium picolinate supplements ( n = 32 ) or placebo ( n = 32 ) for 8 weeks . Fasting blood samples were obtained at baseline and 8 weeks after the intervention to quantify markers of insulin metabolism and lipid concentrations . RESULTS Chromium supplementation in women with PCOS resulted in significant decreases in serum insulin levels ( -3.6 ± 7.4 vs. +3.6 ± 6.2 µIU/ml , p < 0.001 ) , homeostasis model of assessment-insulin resistance ( HOMA-IR ; -0.8 ± 1.6 vs. +0.9 ± 1.5 , p < 0.001 ) , homeostatic model assessment-beta cell function ( HOMA-B ; -15.5 ± 32.3 vs. +13.6 ± 23.1 , p < 0.001 ) , and a significant increase in quantitative insulin sensitivity check index ( QUICKI ) score ( +0.02 ± 0.03 vs. -0.008 ± 0.02 , p = 0.001 ) compared with the placebo . In addition , a trend toward a significant effect of chromium supplementation on decreasing serum triglycerides ( -12.4 ± 74.4 vs. +15.2 ± 32.4 mg/dl , p = 0.05 ) , very low-density lipoprotein-cholesterol ( -2.5 ± 14.9 vs. +3.0 ± 6.5 mg/dl , p = 0.05 ) , and cholesterol concentrations ( -8.6 ± 21.9 vs. +0.7 ± 22.4 mg/dl , p = 0.09 ) was seen . CONCLUSIONS Eight weeks of chromium supplementation among PCOS women had favorable effects on markers of insulin metabolism .

Chromium Supplementation

chromium

placebo-controlled

Chromium

Metabolic Status

insulin metabolism

lipid profiles

Women

Polycystic Ovary Syndrome

women

polycystic ovary syndrome ( PCOS )

women

PCOS


The VA augmentation and switching treatments for improving depression outcomes ( VAST-D ) study : Rationale and design considerations . Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant , we designed a trial of three " next-step " strategies : switching to another antidepressant ( bupropion-SR ) or augmenting the current antidepressant with either another antidepressant ( bupropion-SR ) or with an atypical antipsychotic ( aripiprazole ) . The study will compare 12-week remission rates and , among those who have at least a partial response , relapse rates for up to 6 months of additional treatment . We review seven key efficacy/effectiveness design decisions in this mixed " efficacy-effectiveness " trial .

VA augmentation

and

switching treatments

switching to another antidepressant (

bupropion-SR

12-week remission rates

relapse rates

Major Depressive Disorder


Recruitment and Reasons for Non-Participation in a Family-Coping-Orientated Palliative Home Care Trial ( FamCope ) . Cancer patients and their family caregivers need support to cope with physical , psychosocial , and existential problems early in the palliative care trajectory . Many interventions target patient symptomatology , with health care professionals acting as problem-solvers . Family coping , however , is a new research area within palliative care . The FamCope intervention was developed to test if a nurse-led family-coping-orientated palliative home care intervention would help families cope with physical and psychosocial problems at home -- together as a family and in interaction with health care professionals . However , an unexpectedly high number of families declined participation in the trial . We describe and discuss the recruitment strategy and patient reported reasons for non-participation to add to the knowledge about what impedes recruitment and to identify the factors that influence willingness to participate in research aimed at family coping early in the palliative care trajectory . Patients with advanced cancer and their closest relative were recruited from medical , surgical , and oncological departments . Reasons for non-participation were registered and characteristics of participants and non-participants were compared to evaluate differences between subgroups of non-participants based on reasons not to participate and reasons to participate in the trial . A total of 65.9 % of the families declined participation . Two main categories for declining participation emerged : first , that the " burden of illness is too great " and , second , that it was " too soon " to receive this kind of support . Men were more likely to participate than women . Patients in the " too soon " group had similar characteristics to participants in the trial . Timing of interventions and readiness of patients and their relatives seems to affect willingness to receive a family-coping-orientated care approach and impeded recruitment to this trial . Our findings can be used in further research and in clinical practice in order to construct interventions and target relevant populations for early family-coping-orientated palliative care .

FamCope intervention

palliative care

participation

recruitment strategy

patient reported reasons

non-participation

non-participation

participation

participation

participate


Use of the learning conversation improves instructor confidence in life support training : An open randomised controlled cross-over trial comparing teaching feedback mechanisms . AIMS Feedback is vital for the effective delivery of skills-based education . We sought to compare the sandwich technique and learning conversation structured methods of feedback delivery in competency-based basic life support ( BLS ) training . METHODS Open randomised crossover study undertaken between October 2014 and March 2015 at the University of Birmingham , United Kingdom . Six-hundred and forty healthcare students undertaking a European Resuscitation Council ( ERC ) BLS course were enrolled , each of whom was randomised to receive teaching using either the sandwich technique or the learning conversation . Fifty-eight instructors were randomised to initially teach using either the learning conversation or sandwich technique , prior to crossing-over and teaching with the alternative technique after a pre-defined time period . Outcome measures included skill acquisition as measured by an end-of-course competency assessment , instructors ' perception of teaching with each feedback technique and candidates ' perception of the feedback they were provided with . RESULTS Scores assigned to use of the learning conversation by instructors were significantly more favourable than for the sandwich technique across all but two assessed domains relating to instructor perception of the feedback technique , including all skills-based domains . No difference was seen in either assessment pass rates ( 80.9 % sandwich technique vs. 77.2 % learning conversation ; OR 1.2 , 95 % CI 0.85-1.84 ; p=0.29 ) or any domain relating to candidates ' perception of their teaching technique . CONCLUSIONS & RELEVANCE This is the first direct comparison of two feedback techniques in clinical medical education using both quantitative and qualitative methodology . The learning conversation is preferred by instructors providing competency-based life support training and is perceived to favour skills acquisition .

learning conversation

sandwich technique

learning conversation

learning conversation

assessment pass rates

Six-hundred and forty

Fifty-eight


High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention : Randomised Controlled Trial Comparing Prasugrel and Clopidogrel . BACKGROUND Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes . Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity ( HRPR ) i.e . poor responders , is limited . OBJECTIVES To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome ( ACS ) . PATIENTS Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer , i.e . " poor responders " were randomised to prasugrel ( 60 mg loading and 10 mg maintenance dose ) or clopidogrel ( 600 mg reloading and 150 mg maintenance dose ) . The primary outcome measure was proportion of patients with platelet reactivity < 40 AUC 4 hours after loading with study medication , and also at one hour ( secondary outcome ) . 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors . RESULTS At 4 hours after study medication 100 % of patients treated with prasugrel compared to 91 % of those treated with clopidogrel had platelet reactivity < 40 AUC ( p = 0.49 ) , while at 1 hour the proportions were 95 % and 64 % respectively ( p = 0.02 ) . Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 ( p = 0.005 ) and 19 versus 34 ( p = 0.01 ) respectively . CONCLUSIONS Routine platelet function testing identifies patients with high residual platelet reactivity ( " poor responders " ) on clopidogrel . A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity . Future trials need to identify if this translates into clinical benefit . TRIAL REGISTRATION ClinicalTrials.gov NCT01339026 .

prasugrel

clopidogrel

percutaneous coronary intervention

clopidogrel

PCI

clopidogrel

acute coronary syndromes .

Patients with ACS

44 patients were enrolled


Effects of bench step exercise intervention on work ability in terms of cardiovascular risk factors and oxidative stress : a randomized controlled study . Work ability is partly determined by physical and mental fitness . Bench step exercise can be practiced anywhere at any time . The aim of this study was to determine the effects of a bench step exercise on work ability by examining cardiovascular risk factors and oxidative stress . Thirteen volunteers working in a warehousing industry comprised the bench step exercise group ( n=7 ) and the control group ( n=6 ) . The participants in the step exercise group were encouraged to practice the step exercise at home for 16 weeks . The step exercise improved glucose metabolism and antioxidative capacity and increased work ability by reducing absences from work and improving the prognosis of work ability . The improvement in work ability was related to a reduction in oxidative stress . These results suggest that a bench step exercise may improve work ability by reducing cardiovascular risk factors and oxidative stress .

bench step exercise intervention

Bench step exercise

bench step exercise

bench step exercise

step exercise

step exercise

step exercise

bench step exercise

work ability

cardiovascular

Work ability

work ability

work ability

oxidative stress .

work ability


Oxygen saturation targets in infants with bronchiolitis ( BIDS ) : a double-blind , randomised , equivalence trial . BACKGROUND The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90 % for children with bronchiolitis , which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections . No evidence exists to support this threshold . We aimed to assess whether the 90 % or higher target for management of oxygen supplementation was equivalent to a normoxic 94 % or higher target for infants admitted to hospital with viral bronchiolitis . METHODS We did a parallel-group , randomised , controlled , equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK ( the Bronchiolitis of Infancy Discharge Study [ BIDS ] ) . A central computer randomly allocated ( 1:1 ) infants , in varying length blocks of four and six and without stratification , to be clipped to standard oximeters ( patients treated with oxygen if pulse oxygen saturation [ SpO2 ] < 94 % ) or modified oximeters ( displayed a measured value of 90 % as 94 % , therefore oxygen not given until SpO2 < 90 % ) . All parents , clinical staff , and outcome assessors were masked to allocation . The primary outcome was time to resolution of cough ( prespecified equivalence limits of plus or minus 2 days ) in the intention-to-treat population . This trial is registered with ISRCTN , number ISRCTN28405428 . FINDINGS Between Oct 3 , and March 30 , 2012 , and Oct 1 , and March 29 , 2013 , we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters . Cough resolved by 15·0 days ( median ) in both groups ( 95 % CI for difference -1 to 2 ) and so oxygen thresholds were equivalent . We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group . In the standard care group , eight infants transferred to a high-dependency unit , 23 were readmitted , and one had a prolonged hospital stay . In the modified care group , 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital . Recorded adverse events did not differ significantly . INTERPRETATION Management of infants with bronchiolitis to an oxygen saturation target of 90 % or higher is as safe and clinically effective as one of 94 % or higher . Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children , particularly in developing nations where resources are scarce . FUNDING National Institute for Health Research , Health Technology Assessment programme .

oxygen supplementation

standard oximeters

modified oximeters

oxygen saturation

time to resolution of cough

Cough

35 serious adverse events

25 serious adverse events

were readmitted

a high-dependency unit

were readmitted to hospital

infants

bronchiolitis ( BIDS )

children

lower respiratory tract infections

bronchiolitis

308 infants

infants

bronchiolitis


An endovascular simulation exercise among radiology residents : comparison of simulation performance with and without practice . PURPOSE The purpose was to compare resident endovascular simulator performance with and without prior simulation . METHODS Radiology residents were guided through a practice simulation and lectured on endovascular therapy , then randomized to simulate femoral arterial intervention with or without prior iliac simulation . Simulator measurements , performance grading and resident surveys were recorded . RESULTS Prior simulation of iliac intervention significantly improved resident performance . In particular , it resulted in less catheter placement without a wire ( P=.01 ) , shorter time to proper catheter positioning ( P=.045 ) and use of oblique digital subtraction angiography ( P=.035 ) . Survey respondents valued the experience . CONCLUSION Endovascular simulator training improves simulation skills . Improvement of real-world performance and generalizability remain to be shown .

endovascular simulation exercise

prior simulation

Prior simulation of iliac intervention

Endovascular simulator training

comparison

simulation performance

compare

endovascular simulator performance

Simulator measurements

resident performance

less catheter placement without a wire

simulation skills

performance

radiology residents :

Radiology residents


Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol , with and without skin scrubbing , for prevention of intravascular-catheter-related infection ( CLEAN ) : an open-label , multicentre , randomised , controlled , two-by-two factorial trial . BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care , but incidence can be decreased by improvements in the quality of care . Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections . We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections . METHODS In this open-label , randomised controlled trial with a two-by-two factorial design , we enrolled consecutive adults ( age ≥18 years ) admitted to one of 11 French intensive-care units and requiring at least one of central-venous , haemodialysis , or arterial catheters . Before catheter insertion , we randomly assigned ( 1:1:1:1 ) patients via a secure web-based random-number generator ( permuted blocks of eight , stratified by centre ) to have all intravascular catheters prepared with 2 % chlorhexidine-70 % isopropyl alcohol ( chlorhexidine-alcohol ) or 5 % povidone iodine-69 % ethanol ( povidone iodine-alcohol ) , with or without scrubbing of the skin with detergent before antiseptic application . Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were . The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population . This study is registered with ClinicalTrials.gov , number NCT01629550 and is closed to new participants . FINDINGS Between Oct 26 , 2012 , and Feb 12 , 2014 , 2546 patients were eligible to participate in the study . We randomly assigned 1181 patients ( 2547 catheters ) to chlorhexidine-alcohol ( 594 patients with scrubbing , 587 without ) and 1168 ( 2612 catheters ) to povidone iodine-alcohol ( 580 patients with scrubbing , 588 without ) . Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections ( 0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol ; hazard ratio 0·15 , 95 % CI 0·05-0·41 ; p=0·0002 ) . Scrubbing was not associated with a significant difference in catheter colonisation ( p=0·3877 ) . No systemic adverse events were reported , but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol ( 27 [ 3 % ] patients vs seven [ 1 % ] with povidone iodine-alcohol ; p=0·0017 ) and led to chlorhexidine discontinuation in two patients . INTERPRETATION For skin antisepsis , chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections . FUNDING University Hospital of Poitiers , CareFusion .

chlorhexidine-alcohol

povidone iodine-alcohol

chlorhexidine-alcohol

povidone iodine-alcohol

systemic adverse

adults

age ≥18 years )

2546 patients

1181 patients

2547 catheters


Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins . BACKGROUND There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C , representing a major risk of CVD . The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks . METHODS Lipid changes were assessed in a randomized , multicenter , 12-week , open-label study comparing a high-potency statin ( 10mg of atorvastatin or 1mg of pitavastatin ) plus ezetimibe ( EAT : n = 53 ) with a double dose of statin ( 20mg of atorvastatin or 2mg of pitavastatin ) ( DST : n = 56 ) in DM subjects who had failed to achieve the optimal LDL-C targets . Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C ( remnant like particle cholesterol ) and sd-LDL-C , two characteristic atherogenic risks of DM . RESULTS The reduction of LDL-C ( % ) , the primary endpoint , differed significantly between the two groups ( -24.6 in EAT vs. -10.9 in DST ) . In the analyses of the secondary endpoints , EAT treatment brought about significantly larger reductions in sd-LDL-C ( -20.5 vs. -3.7 ) and RLP-C ( -19.7 vs. +5.5 ) . In total , 89.4 % of the patients receiving EAT reached the optimized treatment goal compared to 51.0 % of the patients receiving DST . The changes in TC ( -16.3 vs. -6.3 ) and non-HDL-C ( -20.7 vs. -8.3 ) differed significantly between the two groups . CONCLUSION Ezetimibe added to high-potency statin ( 10 mg of atorvastatin or 1 mg of pitavastatin ) was more effective than the intensified-dose statin ( 20 mg of atorvastatin or 2 mg of pitavastatin ) treatment not only in helping T2DM patients attain more LDL-C reduction , but also in improving their atherogenic lipid profiles , including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response . TRIAL REGISTRATION The UMIN Clinical Trials Registry UMIN000002593 .

Ezetimibe

ezetimibe

statin

atorvastatin

pitavastatin

DST

Ezetimibe

statin

atorvastatin

pitavastatin

statin

atorvastatin

pitavastatin

LDL-C Lowering

Atherogenic Lipoprotein Profiles

LDL-C

LDL-C

Lipid changes

Lipid variables

LDL-C

LDL-C

levels of RLP-C

sd-LDL-C

reduction of LDL-C

sd-LDL-C

RLP-C

TC

non-HDL-C

LDL-C reduction

atherogenic lipid profiles

sd-LDL-C

RLP-C.

Diabetic


A controlled trial of extended radical versus radical mastectomy . Ten-year results . In view of increasing debate over possible benefit of more complete surgery compared to conservative procedures , a randomized controlled trial contrasting the then standard Halsted radical ( RDL ) operation with the more complete extended radical ( EXT ) mastectomy was initiated in 1973 . Between November 1973 and July 1982 , 123 women younger than 70 years of age and at clinical Stages I and II were enrolled . Of the total series , 112 were treated by the same surgeon and confirmed pathologically as having invasive mammary carcinoma . In this more homogeneous subgroup , the 10-year survival rates ( and standard errors ) were for RDL , 60 % ( +/- 7 % ) and for EXT , 74 % ( +/- 6 % ) ( P value for comparison of survival curves = 0.13 ) . In patients from this subgroup with central-medial tumors , comprising 62 % of the total , survival after RDL at 10 years was 60 % ( +/- 8 % ) , and after EXT 86 % ( +/- 6 % ) ( P = 0.025 ) . In the remaining patients with lateral tumors , survival rates were unaffected by treatment : 58 % ( +/- 13 % ) and 56 % ( +/- 11 % ) , respectively ( P = 0.62 ) . Comparison of a nonrandomized series of 266 RDL and 124 EXT patients treated between 1960 and 1978 found differences consistent with those of the randomized study , although not statistically significant .

extended radical

radical mastectomy

10-year survival rates

survival

survival rates

women

younger than 70 years of age

at clinical Stages I and II

invasive mammary carcinoma

lateral tumors


DESFLURANE COMPARED TO SEVOFLURANE FOR CIRRHOTIC PATIENTS UNDERGOING MAJOR LIVER RESECTION . A RANDOMIZED CONTROL STUDY . BACKGROUND Major liver resection is associated with haemodynamic , hepatic and renal changes as a result of the procedure . AIM To compare Desflurane ( D ) versus Sevoflurane ( S ) on hepatic , renal functions , haemodynamics and perioperative course for cirrhotic patients undergoing major liver resection . PATIENTS AND METHODS A prospective randomized control study with 50 patients ( Child A ) ( D , n = 25 and S , n = 25 ) . End tidal D or S adjusted with Entropy ( 40-60 ) . Haemodynamics monitored with invasive blood pressure and trans-oesophageal Doppler ( TED ) . Liver and kidney function tests , blood Glutathione-S-transferase ( GST ) , urinary microalbuminuria ( Microalb ) were assayed . Extubation time and anaesthetic consumption were recorded . RESULTS Systemic vascular resistance ( SVR ) post-resection and stroke volume of D vs S were 835.04 ± 12.02 vs 778.16 ± 11.97 dyn.sec.cm ( -5 ) , P < 0.01 , and 85.72 ± 2.95 vs 76.16 ± 6.52 ml , P < 0.01 respectively . Doppler corrected flow time ( FTc ) between groups were comparable ( P > 0.05 ) . No difference post-operatively regarding hepatic and renal functions , and urine Microalb ( 14.76 ± 3.95 vs l4.24 ± 8.65 µg/ml , P = 0.78 ) , but a statistically difference was found with GST ( 0.046 ± [ symbols : see text ] , vs 0.043 ± [ symbols : see text ] IU/ml , P < 0.01 ) . Despite a higher D consumption ( 73 ± 17 vs 64 ± 22 ml , P = 0.102 ) , cost in Egyptian pounds ( LE ) was lower with D ( 141.14 ± 32.90 vs 320.60 ± 114.01 , LE , P < 0.01 ) . Extubation time and ICU stay with D vS ( 4.52 ± 2 vs 7.72 ± 2 min , P < 0.01 ) and ( 1.40 0.50 vs 1.64 ± 0.48 , days P = 0.09 ) respectively . CONCLUSION Neither D nor S were clinically superior to the other with respect to liver and kidneys functions , but D was found to preserve better the haemodynamic parameters and enhance recovery at a lower cost .

End tidal D or S adjusted with Entropy

Extubation time

anaesthetic consumption were recorded

50 patients

Child A


The effectiveness of single-dose metronidazole therapy for patients and their partners with bacterial vaginosis . A randomized , placebo-controlled , double-blind clinical trial was performed to test the hypothesis that a 2-g single dose of metronidazole for male partners of women with bacterial vaginosis was more effective than placebo in improving cure rate and decreasing recurrence rate . In addition , the effectiveness of a 2-g single dose of metronidazole was compared with a seven-day course of 500 mg of metronidazole twice a day in patients with bacterial vaginosis . Statistically significant benefits of partner treatment were noted in the initial cure rate by Gram-stained smear criteria ( P less than .01 ) and in percentage of women with symptoms eight weeks after initiating therapy ( P less than .05 ) . The seven-day course of metronidazole was superior to the single-dose regimen in the percentage of patients with clue cells and the percentage of patients with a positive " sniff " test at the first follow-up visit ; however , differences in the initial cure rate assessed by clinical criteria and Gram-stained smear criteria were not statistically significant between the two patient treatment regimens . Recurrence rates by Gram-stained smear criteria between patient and partner treatment groups at five and eight weeks after initiation of treatment were also not significantly different between the two patient regimens . Single-dose metronidazole treatment of the sexual partner of women with bacterial vaginosis improves initial bacterial vaginosis cure rates . The seven-day course of metronidazole was not found by statistical analysis to be significantly superior to single-dose therapy when considering initial cure rates by clinical or Gram-stained smear criteria or recurrence rates . ( ABSTRACT TRUNCATED AT 250 WORDS )

metronidazole

placebo-controlled

metronidazole

single dose of metronidazole

metronidazole

bacterial vaginosis cure rates


U.S. Food and Drug Administration Approval Summary : Ramucirumab for the Treatment of Metastatic Non-Small Cell Lung Cancer Following Disease Progression On or After Platinum-Based Chemotherapy . UNLABELLED On December 12 , 2014 , the U.S. Food and Drug Administration ( FDA ) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer ( NSCLC ) with disease progression on or after platinum-based chemotherapy . Patients with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab . This approval was based on an improvement in overall survival ( OS ) with an acceptable toxicity profile in a randomized , multicenter , double-blinded , placebo-controlled trial of 1,253 patients with metastatic NSCLC previously treated with a platinum-based combination therapy . Patients were randomized 1:1 to receive either ramucirumab in combination with docetaxel or placebo in combination with docetaxel . The primary endpoint was OS . Patients who received ramucirumab in combination with docetaxel had improved OS ( hazard ratio [ HR ] : 0.86 ; 95 % confidence interval [ CI ] : 0.75 , 0.98 ) . Median OS was 10.5 months on the ramucirumab plus docetaxel arm versus 9.1 months on the placebo plus docetaxel arm . The most frequent ( ≥ 30 % ) adverse reactions in ramucirumab-treated patients were fatigue , neutropenia , and diarrhea . The most frequent ( ≥ 5 % ) grade 3 and 4 adverse reactions in the ramucirumab arm were fatigue , neutropenia , febrile neutropenia , leukopenia , and hypertension . IMPLICATIONS FOR PRACTICE This report presents key information on the U.S. Food and Drug Administration approval of ramucirumab , a monoclonal antibody targeting vascular endothelial growth factor receptor-2 , given in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer whose disease has progressed on or after platinum-based chemotherapy . This report specifically addresses the issues of safety in patients with squamous cell tumors , effect of treatment in elderly patients , and uncertainties regarding effects in patients with tumors harboring epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations .

Ramucirumab

ramucirumab

docetaxel

ramucirumab .

placebo

with docetaxel

OS .

improved OS

Median OS

fatigue , neutropenia , and diarrhea

epidermal growth factor receptor

1,253 patients

metastatic non-small cell lung cancer

squamous cell tumors

treatment in elderly patients


Computer Decision Support Changes Physician Practice But Not Knowledge Regarding Autism Spectrum Disorders . OBJECTIVE To examine whether adding an autism module promoting adherence to clinical guidelines to an existing computer decision support system ( CDSS ) changed physician knowledge and self-reported clinical practice . METHODS The CHICA ( Child Health Improvement through Computer Automation ) system , a CDSS , was enhanced with a module to improve management of autism in 2 of the 4 community pediatric clinics using the system . We examined the knowledge and beliefs of pediatric users using cross-sectional surveys administered at 3 time points ( baseline , 12 months and 24 months post-implementation ) between November 2010 and January 2013 . Surveys measured knowledge , beliefs and self-reported practice patterns related to autism . RESULTS A total of 45 , 39 , and 42 pediatricians responded at each time point , respectively , a 95-100 % response rate . Respondents ' knowledge of autism and perception of role for diagnosis did not vary between control and intervention groups either at baseline or any of the two post-intervention time points . At baseline , there was no difference between these groups in rates in the routine use of parent-rated screening instruments for autism . However , by 12 and 24 months post-implementation there was a significant difference between intervention and control clinics in terms of the intervention clinics consistently screening eligible patients with a validated autism tool . Physicians at all clinics reported ongoing challenges to community resources for further work-up and treatment related to autism . CONCLUSIONS A CDSS module to improve primary care management of ASD in pediatric practice led to significant improvements in physician-reported use of validated screening tools to screen for ASDs . However it did not lead to corresponding changes in physician knowledge or attitudes .

Computer Decision Support

computer decision support system

CDSS

CDSS

Practice

Knowledge

management of autism

Surveys

knowledge

physician knowledge or attitudes

Physician Practice

Autism Spectrum Disorders .

autism

pediatric users


Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma . Results of the HD2002 prospective multicentre randomized phase III trial . In the multicentre prospective randomized HD2002 trial , rituximab maintenance therapy ( 375 mg/m ( 2 ) every 3 months for 2 years ) versus observation was evaluated for CD20 ( + ) B-cell lymphoma . Out of 321 patients [ 161 randomized to the treatment group ( TG ) , 160 to the observation group ( OG ) ] , 295 data sets were evaluable for statistical analysis . Estimated 5-year relapse-free survival ( RFS ) was 81 % in the TG and 70 % in the OG ( logrank test , P = 0·047 ) . In the diffuse large B-cell lymphoma ( DLBCL ) subgroup ( n = 152 ) , 5-year RFS was excellent , at 87 % in the TG and 84 % in the OG ( logrank test , P = 0·35 ) . Of note , only in male patients of the DLBCL subgroup was RFS significantly superior in the TG in comparison to the OG ( 5-year RFS : 88 % vs. 74 % ; logrank test , P = 0·05 ) . Cox regression analysis showed a significant interaction between treatment and gender regarding overall survival ( OS ) ( P = 0·006 ) and RFS ( P = 0·02 ) , with a lower hazard in females than males in the OG [ OS : hazard ratio ( HR ) ( female : male ) = 0·11 ; 95 % confidence interval ( CI ) = 0·00-1·03 ; RFS : HR ( female : male ) = 0·27 ; 95 % CI = 0·05-0·97 ] , and no significant differences between males and females in the TG . We conclude that Rituximab maintenance therapy improves survival in male patients with DLBCL .

Rituximab

rituximab maintenance therapy

observation

5-year relapse-free survival ( RFS )

male

diffuse large B-cell lymphoma

321 patients

161 randomized

male

male


The neuropeptide oxytocin modulates consumer brand relationships . Each year , companies invest billions of dollars into marketing activities to embellish brands as valuable relationship partners assuming that consumer brand relationships ( CBRs ) and interpersonal relationships rest upon the same neurobiological underpinnings . Given the crucial role of the neuropeptide oxytocin ( OXT ) in social bonding , this study tests whether OXT-based mechanisms also determine the bond between consumers and brands . We conducted a randomized , placebo-controlled study involving 101 subjects and analyzed the effect of intranasal OXT on consumers ' attribution of relationship qualities to brands , brands paired with human celebrity endorsers , and familiar persons . OXT indeed promoted the attribution of relationship qualities not only in the case of social and semi-social stimuli , but also brands . Intriguingly , for subjects scoring high on autistic-like traits , the effect of OXT was completely reversed , evident in even lower relationship qualities across all stimulus categories . The importance of OXT in a CBR context is further corroborated by a three-fold increase in endogenous release of OXT following exposure to one 's favorite brand and positive associations between baseline peripheral OXT concentrations and brand relationship qualities . Collectively , our findings indicate that OXT not only plays a fundamental role in developing interpersonal relationships , but also enables relationship formation with objects such as brands .

neuropeptide oxytocin

neuropeptide oxytocin ( OXT )

intranasal OXT

OXT

OXT

OXT

OXT

OXT

OXT

attribution of relationship qualities

relationship qualities

endogenous release of OXT

interpersonal relationships

autistic-like traits


Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis ( ACTiMuS ) : study protocol for a randomised controlled trial . BACKGROUND We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis ( MS ) . The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants . The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS . Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS , including mechanisms underlying repair . METHODS/DESIGN A prospective , randomised , double-blind , placebo-controlled , stepped wedge design will be employed at a single centre ( Bristol , UK ) . Eighty patients with progressive MS will be recruited ; 60 will have secondary progressive disease ( SPMS ) but a subset ( n = 20 ) will have primary progressive disease ( PPMS ) . Participants will be randomised to either early or late ( 1 year ) intravenous infusion of autologous , unfractionated bone marrow . The placebo intervention is infusion of autologous blood . The primary outcome measure is global evoked potential derived from multimodal evoked potentials . Secondary outcome measures include adverse event reporting , clinical ( EDSS and MSFC ) and self-assessment ( MSIS-29 ) rating scales , optical coherence tomography ( OCT ) as well as brain and spine MRI . Participants will be followed up for a further year following the final intervention . Outcomes will be analysed on an intention-to-treat basis . DISCUSSION Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis ( ACTiMuS ) is the first randomised , placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS . It will determine whether bone marrow cell therapy can , as was suggested by the phase I safety study , improve conduction in multiple central nervous system pathways affected in progressive MS . Furthermore , laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy . TRIAL REGISTRATION ISRCTN27232902 Registration date 11/09/2012 . NCT01815632 Registration date 19/03/2013 .

bone marrow-derived Cellular Therapy

delivery of autologous bone marrow

bone marrow-derived stem cell infusion

placebo-controlled

placebo intervention

autologous blood

bone marrow-derived Cellular Therapy

bone marrow cell therapy

cell therapy .

safety

feasibility

efficacy

adverse event reporting

progressive Multiple Sclerosis

Eighty patients

secondary progressive disease ( SPMS )

n = 20

primary progressive disease ( PPMS )

progressive MS


Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma . alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects . The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon . We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect , if any , indomethacin might have on the toxic , immunomodulatory , and therapeutic properties of interferon in this disease . 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon , 20 million units per m2 i.v. , 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week , either with or without indomethacin , 25 mg orally three times a day . The overall major response rate was 13 % ( three complete responders and three partial responders among 47 evaluable patients ) and was the same on both arms . The mean maximal temperature elevation induced by interferon was significantly reduced ( from 102.1 to 100.7 , P = 0.0002 ) by indomethacin , but the incidence and severity of interferon-related fatigue , reduction in performance status , headache , depression , confusion , elevations in liver function tests , and myelosuppression were no different in either arm of the study . Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses . Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin . Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy . Immunological changes did not correlate with response status . We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities . Since fever is rarely the dose-limiting toxicity of interferon , indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study .

recombinant alpha 2b-interferon

indomethacin

alpha-Interferon

indomethacin

indomethacin

alpha 2b-interferon

indomethacin

indomethacin

Indomethacin

Indomethacin

indomethacin

toxic side-effects

toxic

immunomodulatory

therapeutic properties

overall major

response rate

mean maximal temperature elevation

reduction in performance status

headache

depression

confusion

elevations in liver function tests

myelosuppression

augmentation of natural killer activity

Immunological changes

fever

fever

metastatic malignant melanoma

malignant melanoma

malignant melanoma

malignant melanoma


Preoperative Local Administration of Morphine as an Add-on Therapy in Patients Undergoing Surgical Removal of an Odontogenic Maxillary Cyst . A Randomized , Double-Blind Pilot Study . AIMS To evaluate whether a combination of locally administered morphine ( 1 mg ) and lidocaine as part of a multimodal analgesic approach is safe , and whether it improves pain control during the first 24 hours after odontogenic maxillary cyst removal under general anesthesia compared to local lidocaine alone . METHODS In a double-blind , sham-controlled , single-center trial , patients scheduled for surgical removal of an odontogenic maxillary cyst under general anesthesia were randomly assigned to receive a local injection of lidocaine solution with either 1 mg of morphine ( MLA group ) or with no morphine ( LA group ) . Pain management included intravenous acetaminophen ( 1 g every 6 hours ) in all patients . Upon request , the patients could additionally receive ketoprofen ( first-line additional analgesia ) or tramadol ( second-line additional analgesia ) . Pain intensity was assessed using a numeric rating scale . Primary outcome measures were ( 1 ) no need for any additional analgesic therapy and ( 2 ) time to the first rescue analgesic therapy during the first 24 hours after the surgery . RESULTS Of 48 eligible patients , 24 were allocated to the MLA group and 24 to the LA group . The necessity of additional ketoprofen therapy did not differ significantly between the groups ( 25.0 % vs 50.0 % , P=.074 ) . According to the Kaplan-Meier analysis , the probability of remaining without additional analgesic intervention was significantly higher in the MLA group ( log-rank test , P=.040 ) , but there were no significant ( P > .05 ) differences in overall and maximum pain severity between the two groups . No adverse effects of morphine were recorded . CONCLUSION Within the limitations of this study , local administration of 1 mg of morphine prior to the surgical removal of an odontogenic maxillary cyst was safe , but it did not prove to be very effective as an add-on therapy for postoperative pain control .

Morphine

morphine

lidocaine

or with no morphine ( LA

acetaminophen

ketoprofen

or tramadol

ketoprofen

morphine

additional ketoprofen therapy

additional analgesic intervention

pain severity

adverse effects

48 eligible patients


Adequacy of " hot biopsy " for the treatment of diminutive polyps : a prospective randomized trial . Patients with diminutive polyps in the rectum or sigmoid colon were randomized to " hot biopsy " treatment for either 1 ) electrocautery for 2 s ( fixed duration cautery ) or 2 ) cautery until visible necrosis of the polyp base was evident ( variable duration cautery ) . Sigmoidoscopy was performed 4 wk after treatment to determine the adequacy of polyp eradication . In the fixed duration cautery group , 11 of 21 polyps ( 52 % ) were eradicated , compared with 12 of 14 polyps ( 86 % ) in the variable duration cautery group ( p = 0.04 ) . When analyzed according to whether or not visible necrosis was achieved ( some of the polyps in the fixed duration cautery group showed necrosis with 2 s cautery ) , 19 of 23 polyps ( 83 % ) were eradicated when necrosis was evident , compared to 5 of 12 ( 42 % ) without necrosis ( p = 0.004 ) . We conclude that hot biopsy treatment for diminutive polyps is significantly more effective when visible necrosis is achieved during cautery . Furthermore , even with visible necrosis , there is a 17 % failure rate of polyp eradication .

electrocautery

Sigmoidoscopy

eradicated

visible necrosis

eradicated


Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease : a randomized clinical trial . BACKGROUND There is emerging research detailing the relationship between balance/gait/falls and cognition . Imaging studies also suggest a link between structural and functional changes in the frontal lobe ( a region commonly associated with cognitive function ) and mobility . People with Parkinson 's disease have important changes in cognitive function that may impact rehabilitation efficacy . Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson 's disease and play a role in rehabilitation efficacy . The purpose of this study is to 1 ) determine if people with Parkinson 's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2 ) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation . METHODS/DESIGN This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory . The study participants will be people with Parkinson 's disease who meet inclusion criteria for the study . The intervention will be 6 weeks of group exercise ( case ) and 6 weeks of group education ( control ) . The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD . The education program is a 6-week program to teach people how to better live with a chronic disease . The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility , cognition and neural imaging . DISCUSSION The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential . TRIAL REGISTRATION This trial is registered at clinical trials.gov ( NCT02231073 ) .

exercise rehabilitation

The education program

MiniBESTest


Effects of propofol and isoflurane on haemodynamics and the inflammatory response in cardiopulmonary bypass surgery . Cardiopulmonary bypass ( CPB ) causes reperfusion injury that when most severe is clinically manifested as a systemic inflammatory response syndrome . The anaesthetic propofol may have anti-inflammatory properties that may reduce such a response . We hypothesised differing effects of propofol and isoflurane on inflammatory markers in patients having CBR Forty patients undergoing elective CPB were randomised to receive either propofol or isoflurane for maintenance of anaesthesia . CRP , IL-6 , IL-8 , HIF-1α ( ELISA ) , CD11 and CD18 expression ( flow cytometry ) , and haemoxygenase ( HO-1 ) promoter polymorphisms ( PCR/electrophoresis ) were measured before anaesthetic induction , 4 hours post-CPB , and 24 hours later . There were no differences in the 4 hours changes in CRP , IL-6 , IL-8 or CD18 between the two groups , but those in the propofol group had higher HIF-1α ( P = 0.016 ) and lower CD11 expression ( P = 0.026 ) . After 24 hours , compared to the isoflurane group , the propofol group had significantly lower levels of CRP ( P < 0.001 ) , IL-6 ( P < 0.001 ) and IL-8 ( P < 0.001 ) , with higher levels CD11 ( P = 0.009 ) and CD18 ( P = 0.002 ) expression . After 24 hours , patients on propofol had increased expression of shorter HO-1 GT ( n ) repeats than patients on isoflurane ( P = 0.001 ) . Use of propofol in CPB is associated with a less adverse inflammatory profile than is isofluorane , and an increased up-regulation of HO-1 . This supports the hypothesis that propofol has anti-inflammatory activity .

propofol

isoflurane

inflammatory markers

CRP

IL-6 , IL-8

HIF-1α ( ELISA )

haemoxygenase ( HO-1

CRP

higher HIF-1α

CD11 expression

CRP

levels CD11

HO-1 GT ( n

of HO-1

Cardiopulmonary bypass ( CPB )

Forty patients


Chronic fatigue syndrome ( CFS ) or myalgic encephalomyelitis ( ME ) is different in children compared to in adults : a study of UK and Dutch clinical cohorts . OBJECTIVE To investigate differences between young children , adolescents and adults with chronic fatigue syndrome/myalgic encephalomyelitis ( CFS/ME ) . STUDY DESIGN Comparison of clinical cohorts from 8 paediatric and 27 adult CFS/ME services in the UK and a paediatric randomised controlled trial from the Netherlands . Outcome measures include : fatigue ( the UK-Chalder Fatigue Scale ) ; Disability ( the UK-SF-36 physical function subscale ; the Netherlands-CHQ-CF87 ) ; school attendance , pain , anxiety and depression ( the UK-Hospital Anxiety & Depression Scale , Spence Children 's Anxiety Scale ; the Netherlands-Spielberger State-Trait Anxiety Inventory for Children , Children 's Depression Inventory ) ; symptoms ; time-to-assessment ; and body mass index . We used multinomial regression to compare younger ( aged < 12 years ) and older ( aged 12-18 years ) children with adults , and logistic regression to compare UK and Dutch adolescents . RESULTS Younger children had a more equal gender balance compared to adolescents and adults . Adults had more disability and fatigue , and had been ill for longer . Younger children were less likely to have cognitive symptoms ( OR 0.18 ( 95 % CI 0.13 to 0.25 ) ) and more likely to present with a sore throat ( OR 1.42 ( 1.07 to 1.90 ) . Adolescents were more likely to have headaches ( 81.1 % , OR 1.56 ( 1.36 % to 1.80 % ) ) and less likely to have tender lymph nodes , palpitations , dizziness , general malaise and pain , compared to adults . Adolescents were more likely to have comorbid depression ( OR 1.51 ( 1.33 to 1.72 ) ) and less likely to have anxiety ( OR 0.46 ( 0.41 to 0.53 ) ) compared to adults . CONCLUSIONS Paediatricians need to recognise that children with CFS/ME present differently from adults . Whether these differences reflect an underlying aetiopathology requires further investigation . TRIAL REGISTRATION NUMBERS FITNET trial registration numbers are ISRCTN59878666 and NCT00893438 . This paper includes secondary ( post-results ) analysis of data from this trial , but are unrelated to trial outcomes .

multinomial regression

disability

fatigue

cognitive symptoms

headaches

pain

comorbid depression

anxiety

children

young children

adolescents

adults

younger ( aged < 12 years )

older ( aged 12-18 years ) children

adults

Younger children

adolescents and adults

Adults

children


The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation . BACKGROUND Reabsorption of bile acids from the intestine by ileal bile acid transporter is pivotal for the enterohepatic circulation of BAs and sterol homoeostasis . AIM To assess tolerability and study , bile acid metabolism in a phase 1 trial with the selective ileal bile acid transporter inhibitor A4250 . METHODS A randomised double-blind , single-ascending dose ( SAD ) and multiple-ascending-dose study consisting of five cohorts comprising 40 individuals with a single administration of A4250 ( 0.1 , 0.3 , 1 , 3 , or 10 mg ) or placebo and three cohorts comprising 24 individuals with a 1-week administration of A4250 ( 1 or 3 mg once daily or 1.5 mg twice daily ) or placebo . For the multiple-ascending-dose study , bile acids were measured by HPLC-MS in plasma and faeces , and fibroblast growth factor 19 ( FGF19 ) and 7α-hydroxy-4-cholesten-3-one ( C4 ) were measured in plasma . RESULTS No serious adverse events occurred and all participants finished the trial per protocol . At the end of the multiple-ascending-dose study , plasma total bile acids and FGF19 decreased by 47 % and 76 % , respectively , at 3 mg/day ( P < 0.01 ) , and by 15 % and 16 % , respectively , at 1.5 mg twice daily ( P < 0.05 ) . Plasma C4 and faecal bile acids increased at all dose regimens , by 555 % , 664 % , 292 % and 338 % , 421 % , 420 % , respectively ( P < 0.01-0.05 ) . The primary bile acids cholic and chenodeoxycholic acids constituted the majority of faecal bile acids in the A4250-treated groups . CONCLUSIONS A4250 is well tolerated . By blocking ileal bile acid transporter in the terminal ileum , it highly efficiently interrupts the enterohepatic circulation of BAs , and should be of benefit to patients with cholestatic liver diseases . Clinical Trial registration EudraCT 2013-001175-21 .

serum bile acids

tolerability

bile acid metabolism

cholestatic liver


Reducing Sitting Time After Stroke : A Phase II Safety and Feasibility Randomized Controlled Trial . OBJECTIVE To test the safety , feasibility , and effectiveness of reducing sitting time in stroke survivors . DESIGN Randomized controlled trial with attention-matched controls and blinded assessments . SETTING Community . PARTICIPANTS Stroke survivors ( N=35 ; 22 men ; mean age , 66.9±12.7y ) . INTERVENTIONS Four counseling sessions over 7 weeks with a message of sit less and move more ( intervention group ) or calcium for bone health ( attention-matched control group ) . MAIN OUTCOME MEASURES Measures included safety ( adverse events , increases in pain , spasticity , or fatigue ) and feasibility ( adherence to trial protocol ) . Secondary measures included time spent sitting ( including in prolonged bouts ≥30min ) , standing , and stepping as measured by the thigh-worn inclinometer ( 7d , 24h/d protocol ) and time spent in physical activity of at least moderate intensity as measured by a triaxial accelerometer . The Multimedia Activity Recall for Children and Adults was used to describe changes in use of time . RESULTS Thirty-three participants completed the full protocol . Four participants reported falls during the intervention period with no other adverse events . From a baseline average of 640.7±99.6min/d , daily sitting time reduced on average by 30±50.6min/d ( 95 % confidence interval [ CI ] , 5.8-54.6 ) in the intervention group and 40.4±92.5min/d in the control group ( 95 % CI , 13.0-93.8 ) . Participants in both groups also reduced their time spent in prolonged sitting bouts ( ≥30min ) and increased time spent standing and stepping . CONCLUSIONS Our protocol was both safe and feasible . Participants in both groups spent less time sitting and more time standing and stepping postintervention , but outcomes were not superior for intervention participants . Attention matching is desirable in clinical trials and may have contributed to the positive outcomes for control participants .

adverse events

pain

spasticity , or fatigue )

standing

and

time spent in physical activity

reported falls

other adverse events

sitting time

time spent in prolonged sitting

spent standing and stepping


Treatments of preterm premature rupture of the membranes : a meta-analysis . The objective of this overview was to critically evaluate published randomized controlled trials on treatments in preterm premature rupture of the membranes . The Oxford data base on perinatal trials , MEDLINE , Excerpta Medica , and Index Medicus were searched . Through primary and secondary review with preset inclusion criteria , two independent judges identified 27 randomized controlled trials , of which 13 met inclusion criteria . The quality of these randomized controlled trials was scored . Five randomized controlled trials regarding antenatal use of corticosteroids to prevent respiratory distress syndrome could be combined meta-analytically and showed a reduction in respiratory distress syndrome in the treatment group ( p = 0.001 ) . However , no significant reduction in respiratory distress syndrome ( p = 0.286 ) was found after one study , with the lowest quality score , was excluded . A significant increase in endometritis and a trend toward an increase in neonatal infections and cesarean section rates were noted with treatment . Tocolysis , prophylactic antibiotics , and other interventions studied were not found to be of proved benefit and therefore should not be used outside of a randomized controlled trial .

corticosteroids

Tocolysis , prophylactic antibiotics

respiratory distress syndrome

respiratory distress syndrome

respiratory distress syndrome

endometritis


Elective Induction of Labor Compared With Expectant Management of Nulliparous Women at 39 Weeks of Gestation : A Randomized Controlled Trial . OBJECTIVE To evaluate whether the elective induction of labor in nulliparous women with an unfavorable cervix affects the cesarean delivery rate . METHODS We conducted a randomized controlled trial at a tertiary care medical center . Nulliparous woman between 38 0/7 and 38 6/7 weeks of gestation who were least 18 years of age with a singleton gestation and a Bishop score of 5 or less were randomized to elective induction of labor or expectant management . The induction of labor group was induced within 1 week of enrollment but not before 39 0/7 weeks of gestation . The control group continued routine prenatal care with admission for labor or obstetric indication . The primary outcome was cesarean delivery . Assuming a 20 % rate in women in a control group , 80 % power , and a goal to detect a twofold increase to 40 % in the induction of labor group , 162 patients were needed . RESULTS From March 2010 to February 2014 , 82 patients were randomly allocated to induction of labor and 80 to expectant management . Baseline characteristics were similar between groups . The cesarean delivery rate in the induction of labor group was 30.5 % ( 25/82 ) compared with 17.7 % ( 14/79 ) in the expectant management group ( relative risk 1.72 , 95 % confidence interval 0.96-3.06 ) . CONCLUSION In nulliparous women with a Bishop score of 5 or less , elective induction after 39 0/7 weeks of gestation compared with expectant management of pregnancy did not double the rate of cesarean delivery . CLINICAL TRIAL REGISTRACTION ClinicalTrials.gov , www.clinicaltrials.gov , NCT01076062 . LEVEL OF EVIDENCE I .

Elective Induction of Labor

elective induction of labor

elective induction of labor

expectant management

induction of labor

prenatal care with admission for labor

obstetric indication

elective induction

expectant management of pregnancy

cesarean delivery rate

Women

Gestation

women

unfavorable cervix

18 years of age

82 patients


Effects of therapeutic horse riding on gait cycle parameters and some aspects of behavior of children with autism . We studied effects of therapeutic riding on the development of children with autism . Experiments in walking is appropriate for assessing the coordination of movement and for following the changes . We found that therapeutic riding should be considered as a new form of rehabilitation . Twenty-six pupils ( 12 boys and 14 girls ) of a special needs school participated in therapeutic riding . We analyzed walking twice during a school-term : full body analyses each time before and after one-month therapy . The research included a non-riding control group . All together 104 analyses were performed . We measured mental skills using Pedagogical Analysis and Curriculum ( PAC ) test consisting of four parts being communication , self care , motor skills and socialization . The Gait Cycle Analysis consists of the time-series analysis , the analysis of part of the gait cycle and the measurement of joint angles in each plane . We found significant differences between before and after the therapy in the length of the gait cycle that became more stable in the sagital plane and concluded that our results proved that horse therapy may be successfully used as an additional therapy for children with autism , and it may be a form of rehabilitation in cases when other therapies are not successful .

therapeutic horse riding

therapeutic riding

therapeutic riding

therapeutic riding

full body analyses

one-month therapy

non-riding control group

gait cycle parameters

aspects of behavior

socialization .

length of the gait cycle

autism

autism .

Twenty-six

boys

girls

children


The role of routinely given hyoscine-N-butylbromide in colonoscopy : a double-blind , randomized , placebo-controlled , clinical trial . OBJECTIVE Hyoscine-N-butylbromide ( HBB ) has been proposed to ease colonoscopy and improve mucosal visualization , yet the results from previous studies are conflicting . In our prospective , double-blind , placebo-controlled , randomized study we aimed at evaluating whether routine administration of HBB , before and during colonoscopy , ease the procedure or increase the detection rate for polyps . MATERIAL AND METHODS One hundred fifty outpatients scheduled for an elective colonoscopy were randomized to receive intravenous injections of either 10 mg hyoscine-N-butylbromide or saline before insertion and at cecum . Patient tolerance and technical ease of colonoscopy were evaluated by visual analogue scale ( VAS ) . Procedure times were recorded . Number of detected polyps per patient was evaluated as well . Heart rate was monitored with a pulse oximetry . RESULTS HBB did not improve patient tolerance or technically ease the procedure as evaluated by VAS . However , HBB led to faster ileal intubation ( 1.5 vs 2.0 min , p < 0.001 ) and shorter total procedure time ( 22.0 vs 24.0 min , p = 0.03 ) . Patients who received HBB also needed less often external abdominal pressure ( 48.6 vs 66.7 % , p = 0.03 ) . HBB did not improve polyp detection rate ( 0.89 vs 0.91 , p = 0.90 ) . HBB induced a significant rise in heart rate ( p < 0.001 ) and more often tachycardia ( 17.6 vs 0 % , p < 0.001 ) . CONCLUSIONS Routine administration of HBB before and during colonoscopy yields only limited improvement in the technical performance of the examination compromised by high incidence of tachycardia .

hyoscine-N-butylbromide

placebo-controlled

Hyoscine-N-butylbromide ( HBB )

placebo-controlled

HBB

HBB

HBB

HBB

HBB

HBB

HBB

ease the procedure

increase the detection rate for polyps

Patient tolerance

technical ease of colonoscopy

Procedure times

Number of detected polyps per patient

Heart rate

patient tolerance

technically ease the procedure

total procedure time

external abdominal pressure

polyp detection rate

heart rate

tachycardia

tachycardia .

colonoscopy :

One hundred fifty

elective colonoscopy


A randomised double-blind placebo-controlled trial investigating the behavioural effects of vitamin , mineral and n-3 fatty acid supplementation in typically developing adolescent schoolchildren . Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren ; hence , correcting them may improve sociability . We therefore tested the effects of vitamin , mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13-16 years ( n 196 ) . Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes , using Conners ' teacher ratings and school disciplinary records . At baseline , the children 's PUFA ( n-3 and n-6 ) , vitamin and mineral levels were low , but they improved significantly in the group treated with n-3 , vitamins and minerals ( P=0·0005 ) . On the Conners disruptive behaviour scale , the group given the active supplements improved , whereas the placebo group worsened ( F=5·555 , d=0·35 ; P=0·02 ) . The general level of disciplinary infringements was low , thus making it difficult to obtain improvements . However , throughout the school term school disciplinary infringements increased significantly ( by 25 % ; Bayes factor=115 ) in both the treated and untreated groups . However , when the subjects were split into high and low baseline infringements , the low subset increased their offences , whereas the high-misbehaviour subset appeared to improve after treatment . But it was not possible to determine whether this was merely a statistical artifact . Thus , when assessed using the validated and standardised Conners teacher tests ( but less clearly when using school discipline records in a school where misbehaviour was infrequent ) , supplementary nutrition might have a protective effect against worsening behaviour .

placebo-controlled

vitamin

mineral

vitamins and minerals

vitamin and mineral levels

the Conners disruptive behaviour scale

term school disciplinary infringements

adolescent schoolchildren

adolescents aged 13-16 years

n 196


Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction . OBJECTIVE To evaluate and compare the effects of neuromuscular electrical stimulation ( NMES ) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction . DESIGN Prospective randomized controlled study . SETTING Department of physical medicine and rehabilitation . PARTICIPANTS Patients with dysphagia with medullary infarction ( N=82 ) . INTERVENTIONS Participants were randomized over 3 intervention groups : traditional swallowing therapy , sensory approach combined with traditional swallowing therapy , and motor approach combined with traditional swallowing therapy . Electrical stimulation sessions were for 20 minutes , twice a day , for 5d/wk , over a 4-week period . MAIN OUTCOME MEASURES Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment , oral intake was evaluated by the Functional Oral Intake Scale , quality of life was evaluated by the Swallowing-Related Quality of Life ( SWAL-QOL ) Scale , and cognition was evaluated by the Mini-Mental State Examination ( MMSE ) . RESULTS There were no statistically significant differences between the groups in age , sex , duration , MMSE score , or severity of the swallowing disorder ( P > .05 ) . All groups showed improved swallowing function ( P≤.01 ) ; the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups , and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group ( P < .05 ) . SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group , and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences ( P=.04 ) . CONCLUSIONS NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction . A sensory approach appears to be better than a motor approach .

Neuromuscular Electrical Stimulation

Swallowing function

swallowing function

Dysphagia With Medullary Infarction

dysphagia with medullary infarction

dysphagia with medullary infarction


Socio-demographic , anthropometric , and psychosocial predictors of attrition across behavioral weight-loss trials . Preventing attrition is a major concern in behavioral weight loss intervention studies . The purpose of this analysis was to identify baseline and six-month predictors associated with participant attrition across three independent clinical trials of behavioral weight loss interventions ( PREFER , SELF , and SMART ) that were conducted over 10 years . Baseline measures included body mass index , Barriers to Healthy Eating , Beck Depression Inventory-II ( BDI ) , Hunger Satiety Scale ( HSS ) , Binge Eating Scale ( BES ) , Medical Outcome Study Short Form ( MOS SF-36 v2 ) and Weight Efficacy Lifestyle Questionnaire ( WEL ) . We also examined early weight loss and attendance at group sessions during the first 6 months . Attrition was recorded at the end of the trials . Participants included 504 overweight and obese adults seeking weight loss treatment . The sample was 84.92 % female and 73.61 % white , with a mean ( ± SD ) age of 47.35 ± 9.75 years . After controlling for the specific trial , for every one unit increase in BMI , the odds of attrition increased by 11 % . For every year increase in education , the odds of attrition decreased by 10 % . Additional predictors of attrition included previous attempts to lose 50-79 lbs , age , not possessing health insurance , and BES , BDI , and HSS scores . At 6 months , the odds of attrition increased by 10 % with reduced group session attendance . There was also an interaction between percent weight change and trial ( p < .001 ) . Multivariate analysis of the three trials showed education , age , BMI , and BES scores were independently associated with attrition ( ps ≤ .01 ) . These findings may inform the development of more robust strategies for reducing attrition .

PREFER , SELF

SMART )

Barriers to Healthy Eating

Beck Depression Inventory-II ( BDI )

Hunger Satiety Scale ( HSS

Binge Eating Scale ( BES )

body mass index

Barriers to Healthy Eating

Beck Depression Inventory-II ( BDI )

Hunger Satiety Scale ( HSS )

Binge Eating Scale ( BES )

early weight loss

attendance

Attrition

in BMI

year increase in education

of attrition

overweight and obese

adults

84.92 %

female

73.61 %

age of 47.35 ± 9.75 years

previous attempts to lose 50-79 lbs

not possessing health insurance


Body Mass Index and Adverse Outcomes in Elderly Patients With Atrial Fibrillation : The AMADEUS Trial . BACKGROUND AND PURPOSE Obesity has been associated with increased cardiovascular risk in atrial fibrillation , but little is known in elderly patients with atrial fibrillation . METHODS Post hoc analysis of data from the AMADEUS ( Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation ) trial . RESULTS We studied 1588 elderly patients , who were categorized as normal body mass index ( BMI , 18.5-25 kg/m ( 2 ) ; n=515 [ 32.4 % ] ) , overweight ( BMI , 25-30 kg/m ( 2 ) ; n=711 [ 44.8 % ] ) , and obese ( BMI≥30 kg/m ( 2 ) ; n=362 [ 22.8 % ] ) . There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category , being 5.0 % , 3.2 % , and 1.5 % per 100 patient-years , respectively ( P for trend=0.01 ) . Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome ( hazard ratio , 0.29 ; 95 % confidence interval , 0.11-0.77 ; P=0.01 ) . In the warfarin arm ( n=814 ) , multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60 % ( odds ratio , 1.84 ; 95 % confidence interval , 1.21-2.80 ; P=0.004 ) . CONCLUSION Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients . Obesity was related to good quality anticoagulation control .

Warfarin

Acenocoumarol

cardiovascular death

stroke/systemic embolism

lower stroke

mortality rate

Elderly

Atrial Fibrillation

elderly

atrial fibrillation

Atrial Fibrillation

elderly

elderly

anticoagulated atrial fibrillation


Influence of ibopamine on heart rate and arrhythmic pattern in patients with congestive heart failure . A double-blind multicentre study . Ibopamine is a dopaminergic and adrenergic receptor agonist , which is active in the treatment of congestive heart failure . Since the long-term prognosis for patients with congestive heart failure remains very poor and the incidence of arrhythmic death is high , every new drug to be employed against this disease should be thoroughly tested in order to rule out any possible arrhythmogenic action . This multicentre study was designed to evaluate the effect of ibopamine versus placebo in double-blind conditions on heart rate , rhythm and electrical safety . Ibopamine was employed at a dose of 100 mg t.i.d . in 97 patients ( aged 31-83 years ) belonging to NYHA class II and III with congestive heart failure of different aetiology , but without any complex ventricular arrhythmias in basal conditions ( couplets with R'-R " less than or equal to 400 msec , ventricular tachycardia , R on T phenomena ) . Using a random cross-over design the patients were submitted to 48 hr . Holter recordings in basal conditions and following 7 days of ibopamine and placebo treatment . No influence on heart rhythm was noted . No significant variations in maximum heart rate ( ibopamine 117.7 +/- 20.9 ; placebo 118.1 +/- 20.7 ) , medium heart rate ( ibopamine 71.8 +/- 10.2 ; placebo 72.6 +/- 10.1 ) or minimum heart rate ( ibopamine 55.3 +/- 11.7 ; placebo 54.6 +/- 10.6 ) were observed . The mean number/hr . of ectopic supraventricular beats was 26.1 +/- 61.9 after ibopamine and 21.7 +/- 35.8 after placebo ( p = ns ) . The complexity of ectopic supraventricular beats did not change . The mean number/hr . of ectopic ventricular beats was 31.1 +/- 52.5 after ibopamine and 30.4 +/- 57.8 after placebo ( p = ns ) . Neither the distribution of the patients among Lown classification nor the Final Score of the Italian Lown Classification ( 26.1 +/- 18.0 and 26.6 +/- 17.9 in the 1st and 2nd day of monitoring after ibopamine and 25.7 +/- 18.6 and 25.7 +/- 18.8 after placebo ; p = ns ) showed any difference between active treatment and placebo . Similar results were achieved when the patients were sub-divided into subgroups according to sequences of treatment ( basal -- -- ibopamine -- -- placebo and basal -- -- placebo -- -- ibopamine ) , NYHA class II or III , aetiology of congestive heart failure ( dilatative cardiomyopathy , ischemic cardiomyopathy and other aetiologies ) , associated treatment with digitalis or diuretics and the number and complexity of base ectopic ventricular beats . None of the patients experienced sustained ventricular tachycardia . ( ABSTRACT TRUNCATED AT 400 WORDS )

ibopamine

Ibopamine

ibopamine

placebo

R on T phenomena

heart rate and arrhythmic pattern

arrhythmogenic action

heart rate , rhythm and

electrical safety

Holter recordings

heart rhythm

maximum heart rate

medium heart rate

minimum heart rate

ectopic supraventricular beats

ectopic supraventricular beats

ectopic ventricular beats


The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children . This double-blind and placebo-controlled clinical trial in autistic children had three objectives : ( a ) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms ; ( b ) to further assess its safety when given on a short-term basis ; and ( c ) to assess whether it has an effect on discrimination learning . Forty-five children , 2.02 to 7.58 years old ( M = 4.49 ) , completed this crossover design , with random assignment to treatment sequences . Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects ; at doses ranging from 0.25 to 4.0 mg/day ( M = 0.844 ) , there was a clinically and statistically significant reduction of a variety of symptoms . Under the given conditions , the children failed to learn on either haloperidol or placebo .

haloperidol

placebo-controlled

haloperidol

Haloperidol

haloperidol

placebo

behavioral symptoms

safety

effect on discrimination learning

side effects

variety of symptoms

autistic

children

Forty-five

children

2.02 to 7.58

M = 4.49


Ultrasound is at least as good as magnetic resonance imaging in predicting tumour size post-neoadjuvant chemotherapy in breast cancer . BACKGROUND The aim of this study was to evaluate the accuracy of clinical imaging of the primary breast tumour post-neoadjuvant chemotherapy ( NAC ) related to the post-neoadjuvant histological tumour size ( gold standard ) and whether this varies with breast cancer subtype . In this study , results of both magnetic resonance imaging ( MRI ) and ultrasound ( US ) were reported . METHODS Patients with invasive breast cancer were enrolled in the INTENS study between 2006 and 2009 . We included 182 patients , of whom data were available for post-NAC MRI ( n=155 ) , US ( n=123 ) , and histopathological tumour size . RESULTS MRI estimated residual tumour size with < 10-mm discordance in 54 % of patients , overestimated size in 28 % and underestimated size in 18 % of patients . With US , this was 63 % , 20 % and 17 % , respectively . The negative predictive value in hormone receptor-positive tumours for both MRI and US was low , 26 % and 33 % , respectively . The median deviation in clinical tumour size as percentage of pathological tumour was 63 % ( P25=26 , P75=100 ) and 49 % ( P25=22 , P75=100 ) for MRI and US , respectively ( P=0.06 ) . CONCLUSIONS In this study , US was at least as good as breast MRI in providing information on residual tumour size post-neoadjuvant chemotherapy . However , both modalities suffered from a substantial percentage of over- and underestimation of tumour size and in addition both showed a low negative predictive value of pathologic complete remission ( Gov nr : NCT00314977 ) .

Ultrasound

magnetic resonance imaging

magnetic resonance imaging ( MRI )

ultrasound ( US )

MRI

US

predicting tumour size

accuracy

residual tumour size

chemotherapy in breast cancer .

breast cancer subtype .

invasive breast cancer

182 patients

histopathological tumour size


NSAID Pretreatment Inhibits Prostaglandin Release in Femtosecond Laser-Assisted Cataract Surgery . PURPOSE To investigate whether short-term nonsteroidal anti-inflammatory drug ( NSAID ) pretreatment on the day of surgery inhibits prostaglandin release . Previous studies detected elevated prostaglandin levels after femtosecond laser treatment and identified them as a potential mediator for laser-induced miosis . METHODS Patients underwent either image-guided femtosecond laser cataract surgery or conventional cataract surgery ( n = 75 ) . Half of the eyes per group received topical NSAID treatment on the day of surgery . Aqueous humor was collected from all patients . ELISA measurements were performed to detect aqueous humor prostaglandin levels . RESULTS Femtosecond laser cataract surgery led to higher prostaglandin levels than conventional cataract surgery ( P = .007 ) . In both groups , NSAID pretreatment led to reduced prostaglandin release . In the femtosecond laser group , patients pretreated with NSAIDs had significantly lower prostaglandin values ( 65.3 ± 13.2 pg/mL ) than patients not pretreated with NSAIDs ( 294.4 ± 66.5 pg/mL ) ( P = .0009 ) . CONCLUSIONS The short-term NSAID treatment prevented prostaglandin release in patients treated with image-guided femtosecond laser . Therefore , it has potential to limit intraoperative laser-induced miosis .

NSAID

femtosecond laser treatment

topical NSAID treatment

Femtosecond laser cataract surgery

conventional cataract surgery

NSAID pretreatment

pretreated with NSAIDs

NSAIDs

Prostaglandin Release

prostaglandin release .

prostaglandin levels

aqueous humor prostaglandin levels .

prostaglandin levels

prostaglandin release

prostaglandin values

prevented prostaglandin release

Cataract

conventional cataract surgery

( n = 75

all patients

femtosecond laser group


Clinical Study to Assess the Stain Removal Effectiveness of a Tooth Whitening Regimen with Added Whitening Booster . OBJECTIVE This randomized , controlled clinical trial was conducted to assess the extrinsic stain reduction achieved by brushing with a whitening dentifrice and powered toothbrush , and to determine whether the addition of a whitening booster paste to this regimen would enhance its stain reducing effectiveness . METHODS Sixty qualifying subjects were randomly assigned either to Regimen One , a whitening dentifrice ( Arm & Hammer Truly Radiant [ TR ] toothpaste ] and powered toothbrush ( Arm & Hammer Truly Radiant [ TR ] Extra Whitening Spinbrush ) ; Regimen Two , the dentifrice and powered toothbrush with the addition of a whitening booster ; or Regimen Three , a negative control ( Colgate Cavity Protection toothpaste and an ADA standard manual brush ) . They were instructed in the use of their assigned products and then brushed unsupervised at home for two minutes , twice daily , for 14 days . Extrinsic tooth stain was assessed at baseline and after two , five , and 14 days using a Modified Lobene Stain Index ( MLSI ) with Lobene inclusion criteria of ≥ 1.5 . RESULTS All three treatment groups had statistically significant ( p < 0.0001 ) mean total MLSI reductions from baseline at each time point , in a time-dependent manner . Day 14 reductions were 22.2 % for Colgate Cavity Protection , 29.1 % for Regimen One , and 34.4 % for Regimen Two . Reductions for Regimen One and Regimen Two were significantly greater compared to Regimen Three , the negative control , at each time period ( p < 0.01 ) , and those for Regimen Two were significantly greater compared to Regimen One on days 2 and 14 ( p < 0.05 ) and directionally more effective on day 5 ( p = 0.0673 ) . CONCLUSION The combination of Truly Radiant toothpaste and Truly Radiant Spinbrush provides safe and effective stain removal that can be further enhanced by the addition of the whitening booster .

a whitening dentifrice

powered toothbrush

the dentifrice

whitening booster ;

negative control (

Colgate Cavity Protection toothpaste

and an ADA standard manual brush )

extrinsic stain reduction

stain reducing effectiveness

Extrinsic tooth

Modified Lobene Stain Index ( MLSI )

0.0001 ) mean total MLSI reductions

Two

Reductions

Sixty qualifying subjects