Bizzy Break ! The effect of a classroom-based activity break on in-school physical activity levels of primary school children . The school has been identified as a key setting to promote physical activity . The purpose of this study was to evaluate the effect of a classroom-based activity break on in-school step counts of primary school children . Data for 90 children ( 49 boys , 41 girls , 9.3 ± 1.4 years ) from three Irish primary schools is presented . In each school one class was randomly assigned as the intervention group and another as controls . Children 's step counts were measured for five consecutive days during school hours at baseline and follow-up . Teachers of the intervention classes led a 10 min activity break in the classroom each day ( Bizzy Break ! ) . Mean daily in-school steps for the intervention at baseline and follow-up were 5351 and 5054 . Corresponding values for the control group were 5469 and 4246 . There was a significant difference in the change in daily steps from baseline to follow-up between groups ( p < .05 ) . There was no evidence that girls and boys responded differently to the intervention ( p > .05 ) . Children participating in a daily 10 min classroom-based activity break undertake more physical activity during school hours than controls .

classroom-based activity break

classroom-based activity break

in-school physical activity levels

in-school step counts

primary school children .

primary school children .

children

boys

girls


Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder . BACKGROUND Autism spectrum disorder ( ASD ) is associated with altered face processing and decreased activity in brain regions involved in face processing . The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults . The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome ( AS ) . METHODS A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging . The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized , placebo-controlled , within-subject , cross-over design . RESULTS Under placebo , the AS group showed decreased activity in the right amygdala , fusiform gyrus , and inferior occipital gyrus compared with the control group during face processing . After oxytocin treatment , right amygdala activity to facial stimuli increased in the AS group . CONCLUSIONS These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction .

intranasal oxytocin

neuropeptide oxytocin

oxytocin

oxytocin

placebo-controlled

placebo

oxytocin

autism spectrum disorder .

Autism spectrum disorder ( ASD )

adults

adults

Asperger syndrome ( AS )

14 individuals

ASD

ASD


A randomized , placebo-controlled phase 2 study of ganitumab or conatumumab in combination with FOLFIRI for second-line treatment of mutant KRAS metastatic colorectal cancer . BACKGROUND Targeted agents presently available for mutant KRAS metastatic colorectal cancer ( mCRC ) are bevacizumab and aflibercept . We evaluated the efficacy and safety of conatumumab ( an agonistic monoclonal antibody against human death receptor 5 ) and ganitumab ( a monoclonal antibody against the type 1 insulin-like growth factor receptor ) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC . PATIENTS AND METHODS Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1 : 1 : 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg ( Arm A ) , ganitumab 12 mg/kg ( Arm B ) , or placebo ( Arm C ) Q2W . The primary end point was progression-free survival ( PFS ) . RESULTS In total , 155 patients were randomized . Median PFS in Arms A , B , and C was 6.5 months ( HR , 0.69 ; P = 0.147 ) , 4.5 months ( HR , 1.01 ; P = 0.998 ) , and 4.6 months , respectively ; median overall survival was 12.3 months ( HR , 0.89 ; P = 0.650 ) , 12.4 months ( HR , 1.27 ; P = 0.357 ) , and 12.0 months ; and objective response rate was 14 % , 8 % , and 2 % . The most common grade ≥3 adverse events in Arms A/B/C included neutropenia ( 30 % /25 % /18 % ) and diarrhea ( 18 % /2 % /10 % ) . CONCLUSIONS Conatumumab , but not ganitumab , plus FOLFIRI was associated with a trend toward improved PFS . Both combinations had acceptable toxicity .

placebo-controlled

ganitumab or conatumumab

bevacizumab

aflibercept .

conatumumab

ganitumab

efficacy

safety

progression-free survival ( PFS ) .

Median PFS

median overall survival

objective response rate


Perioperative myocardial infarctions are common and often unrecognized in patients undergoing hip fracture surgery . BACKGROUND The aim of this prospective cohort study was to assess the incidence and characteristics of acute myocardial infarction in patients undergoing surgery for acute hip fracture . METHODS A consecutive cohort of patients ( n = 200 , 68 men ) referred to acute surgical correction of hip fracture was studied . Troponin T ( TnT ) measurements and electrocardiographic ( ECG ) recordings were performed at admission , before operation , and on the first and 2nd postoperative days , which were used for diagnosis . RESULTS The age of the patients ranged from 32 to 98 years ( mean , 80.8 years ) , and 65 patients had a history of coronary artery disease . A significant rise in TnT as a sign of myocardial infarction was observed in 71 patients ( 35.5 % ) , and 25 of them had a TnT elevation exceeding five times the upper normal limit . TnT elevation was observed in 36 patients ( 51 % ) already before surgery . Seven patients ( 10 % ) had ST elevation myocardial infarction , 23 patients ( 32 % ) had new ST depressions , and 21 patients ( 30 % ) had no new ST segment changes in the serial electrocardiographic recordings . In 40 patients ( 56 % ) , the perioperative myocardial infarction was the first manifestation of coronary artery disease . Multivariate logistic regression revealed that old age ( odds ratio [ OR ] , 1.06 ; 95 % confidence interval [ CI ] , 1.02-1.10 ; p = 0.002 ) , earlier revascularization ( OR , 3.29 ; 95 % CI 1.12-9.73 ; p = 0.03 ) , and heart failure ( OR , 2.42 ; 95 % CI 1.04-5.61 ; p = 0.04 ) were independent predictors of TnT elevation . Majority of myocardial infarctions were asymptomatic or unrecognized . Evidence-based medications of myocardial infarction were seldom started and cardiologist was consulted in 12 patients ( 16.9 % ) . CONCLUSION Patients with hip fracture often develop asymptomatic and clinically unrecognized perioperative myocardial infarctions . Earlier diagnosis and appropriate treatment of cardiac infarction may improve survival of hip fracture patients . LEVEL OF EVIDENCE Epidemiologic study , level III .

Troponin T ( TnT ) measurements

electrocardiographic ( ECG ) recordings

Perioperative myocardial infarctions

rise in TnT

myocardial infarction

TnT elevation

TnT elevation

ST elevation myocardial infarction

new ST depressions

Majority of myocardial infarctions

Evidence-based medications

undergoing hip fracture surgery

surgery for acute hip fracture

history of coronary artery disease


Lengthening the moment arm of the patella confers enhanced extensor mechanism power following total knee arthroplasty . We investigated whether a postulated biomechanical advantage conferred to the extensor mechanism by a change in knee implant design was detectable in patients by direct physical testing . 212 TKA patients were enrolled in a double blind randomized controlled trial to receive either a traditional implant or one which incorporated new design features . Extensor mechanism power output and physical performance on a battery of timed functional activities was assessed pre-operatively and then at 6 , 26 , and 52 weeks post-operatively . Significantly enhanced power output was observed in both groups post-arthroplasty ; however , the new design implant group demonstrated a greater change in power output than the traditional implant group . Posthoc testing of between group differences highlighted greater improvement at all post-operative assessments . At 52 weeks , patients receiving the implant with the postulated biomechanical advantage achieved 116 % of the power output of their contralateral limb , whereas patients with the traditional design achieved 90 % . No between group difference was detected in the patient 's time to complete functional tasks . Thus , patients receiving a knee implant of a modern design ( theoretically able to confer a mechanical advantage to the extensor mechanism ) were found to generate significantly greater extensor power than those receiving a traditional implant without the postulated mechanical advantage .

new design implant

traditional implant

knee implant of a modern design

traditional implant

extensor mechanism power

Extensor mechanism power output

power output

power output

Posthoc testing

post-operative assessments

extensor power

total knee arthroplasty

TKA


Early-stage squamous cell carcinoma of the oropharynx : radiotherapy vs. trans-oral robotic surgery ( ORATOR ) -- study protocol for a randomized phase II trial . BACKGROUND The incidence of oropharyngeal squamous cell carcinoma ( OPSCC ) has markedly increased over the last three decades due to newly found associations with human papillomavirus ( HPV ) infection . Primary radiotherapy ( RT ) is the treatment of choice for OPSCC at most centers , and over the last decade , the addition of concurrent chemotherapy has led to a significant improvement in survival , but at the cost of increased acute and late toxicity . Transoral robotic surgery ( TORS ) has emerged as a promising alternative treatment , with preliminary case series demonstrating encouraging oncologic , functional , and quality of life ( QOL ) outcomes . However , comparisons of TORS and RT in a non-randomized fashion are susceptible to bias . The goal of this randomized phase II study is to compare QOL , functional outcomes , toxicity profiles , and survival following primary RT ( ± chemotherapy ) vs. TORS ( ± adjuvant [ chemo ] RT ) in patients with OPSCC . METHODS/DESIGN The target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection : Tumor stage T1-T2 with likely negative margins at surgery ; Nodal stage N0-2 , ≤3 cm in size , with no evidence of extranodal extension on imaging . Participants will be randomized in a 1:1 ratio between Arm 1 ( RT ± chemotherapy ) and Arm 2 ( TORS ± adjuvant [ chemo ] RT ) . In Arm 1 , patients with N0 disease will receive RT alone , whereas N1-2 patients will receive concurrent chemoradiation . In Arm 2 , patients will undergo TORS along with selective neck dissections , which may be staged . Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy . The primary endpoint is QOL score using the M.D . Anderson Dysphagia Inventory ( MDADI ) , with secondary endpoints including survival , toxicity , other QOL outcomes , and swallowing function . A sample of 68 patients is required . DISCUSSION This study , if successful , will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS . The trial is designed to provide a definitive QOL comparison between the two arms , and to inform the design of an eventual phase III trial for survival outcomes . TRIAL REGISTRATION NCT01590355 .

radiotherapy vs.

Primary radiotherapy ( RT )

concurrent chemotherapy

Transoral robotic surgery ( TORS )

TORS

RT

QOL

functional outcomes

toxicity profiles

survival

squamous cell carcinoma

OPSCC


Effect of phenylephrine on the haemodynamic state and cerebral oxygen saturation during anaesthesia in the upright position . BACKGROUND The upright sitting or beachchair position is associated with hypotension , risk of cerebral hypoperfusion , and cerebral injury . We hypothesized that by increasing arterial pressure with phenylephrine administration , cerebral perfusion , and postoperative recovery would be improved . METHODS Thirty-four patients undergoing elective shoulder surgery were randomized to receive either saline or phenylephrine infusion ( PE ) 5 min before being placed in the upright position . Simultaneous measurements of mean arterial pressure , cerebral oxygen saturation , middle cerebral artery velocity , and cardiac function using transthoracic echocardiography were made . Postoperative neurocognitive function was assessed . RESULTS At the commencement of PE , mean ( SD ) cerebral oxygen saturation significantly decreased from 77 ( 10 ) to 67 ( 13 ) % ( P=0.02 ) , and further to 59 ( 11 ) % on upright positioning . The level of cerebral saturation upright was not significantly different to patients receiving saline ( P=0.07 ) , with values remaining at room-air levels . Middle cerebral artery blood velocity increased by 20 % ( P=0.04 ) . Phenylephrine prevented hypotension in the upright position primarily by maintaining preload and increasing systemic vascular resistance ( P=0.01 ) , and was associated with a decrease in cardiac output . No postoperative neurocognitive dysfunction was identified . CONCLUSIONS Despite maintaining arterial pressure with phenylephrine , cerebral desaturation occurred with upright positioning . Cerebral oxygen saturation can provide a valuable endpoint when evaluating the effect of vasopressor therapy on cerebral perfusion .

phenylephrine

phenylephrine

saline or phenylephrine infusion ( PE )

phenylephrine

cerebral perfusion

postoperative recovery

neurocognitive function

mean ( SD ) cerebral oxygen saturation

level of cerebral saturation upright

Middle cerebral artery blood velocity

hypotension

systemic vascular resistance

cardiac output .

cerebral desaturation

Cerebral oxygen saturation

Thirty-four

elective shoulder surgery


Acute effects of different stretching durations on passive torque , mobility , and isometric muscle force . Static stretching is widely applied in various disciplines . However , the acute effects of different durations of stretching are unclear . Therefore , this study was designed to investigate the acute effects of different stretching durations on muscle function and flexibility , and provide an insight into the optimal duration of static stretching . This randomized crossover trial included 24 healthy students ( 17 men and 7 women ) who stretched their right hamstrings for durations of 20 , 60 , 180 , and 300 seconds in a random order . The following outcomes were assessed using an isokinetic dynamometer as markers of lower-limb function and flexibility : static passive torque ( SPT ) , dynamic passive torque ( DPT ) , stiffness , straight leg raise ( SLR ) , and isometric muscle force . Static passive torque was significantly decreased after all stretching durations ( p < 0.05 ) . Static passive torque was significantly lower after 60 , 180 , and 300 seconds of stretching compared with that after 20-second stretching , and stiffness decreased significantly after 180- and 300-second stretching ( p < 0.05 ) . In addition , DPT and stiffness were significantly lower after 300 seconds than after 20-second stretching ( p < 0.05 ) , and SLR increased significantly after all stretching durations ( p < 0.05 ) . Straight leg raise was higher after 180- and 300-second stretching than after 20-second stretching and higher after 300-second stretching than after 60-second stretching ( p < 0.05 ) . Isometric muscle force significantly decreased after all stretching durations ( p < 0.05 ) . Therefore , increased duration of stretching is associated with a decrease in SPT but an increase in SLR . Over 180 seconds of stretching was required to decrease DPT and stiffness , but isometric muscle force decreased regardless of the stretching duration . In conclusion , these results indicate that longer durations of stretching are needed to provide better flexibility .

stretching durations

Static stretching

stretching

different stretching durations

static stretching

stretched

stretching

stretching

20-second stretching

180- and 300-second stretching

20-second stretching

stretching

300-second stretching

20-second stretching

300-second stretching

60-second stretching

stretching durations

stretching

180 seconds of stretching

stretching duration

stretching

Static passive torque

DPT and stiffness

Straight leg raise

SPT

DPT and stiffness

men

women

stretched their right hamstrings


Clinical benefits of concurrent capecitabine and cisplatin versus concurrent cisplatin and 5-flurouracil in locally advanced squamous cell head and neck cancer . We aimed to assess the efficacy and safety of concurrent capecitabine and cisplatin over concurrent cisplatin and 5-flurouracil ( 5-FU ) in locally advanced squamous cell carcinoma of the head and neck . One hundred and fifty-three patients ( all of whom had stage III or IV unresectable disease with no distant metastases and who had received two cycles of taxol and cisplatin chemotherapy ) were randomly assigned to receive either concurrent cisplatin ( 75 mg/m ( 2 ) in day 1 and 2 ) and 5-FU ( 750 mg/m ( 2 ) in day 1 , 2 , and 3 ) from the first day of radiotherapy at an interval of 3 weeks ( Arm I ) or cisplatin ( 75 mg/m ( 2 ) in day 1 and 2 ) and capecitabine ( 750 mg/m ( 2 ) in two divided doses from day 1-14 ) from the first day of radiotherapy at a 3-week interval ( Arm II ) . Results showed that patients in Arm II had a significantly better rate of complete response , fewer nodes , and better overall response compared to those in Arm I . The two groups had a similar 3-year disease-free survival , progression free survival , and overall survival , i.e . they did not differ significantly . Variables indicating the quality of life of the two groups were compared . Patients in Arm II had a significantly higher quality of life compared to those in Arm I . The two groups had similar treatment-related acute and late toxicity , i.e . they did not differ significantly . These results have thoroughly substantiated the contention that concurrent chemoradiation with capecitabine and cisplatin may be regarded as an effective and well-tolerated regimen in the treatment of the patients with locally advanced head and neck cancer .

capecitabine and cisplatin

concurrent cisplatin and 5-flurouracil

capecitabine and cisplatin

taxol and cisplatin chemotherapy

concurrent cisplatin

and 5-FU

cisplatin

capecitabine

capecitabine and cisplatin

better rate of complete response

fewer nodes

better overall response

3-year disease-free survival

progression free survival

overall survival

quality of life

quality of life

acute and late toxicity

carcinoma

One hundred and fifty-three

unresectable disease

locally advanced head and neck cancer


Process evaluation of Healthy Bodies , Healthy Souls : a church-based health intervention program in Baltimore City . Soaring obesity rates in the United States demand comprehensive health intervention strategies that simultaneously address dietary patterns , physical activity , psychosocial factors and the food environment . Healthy Bodies , Healthy Souls ( HBHS ) is a church-based , community-participatory , cluster-randomized health intervention trial conducted in Baltimore City to reduce diabetes risk among urban African Americans by promoting healthy dietary intake , increased physical activity and improvement to the church food environment . HBHS was organized into five 3-8-week phases : Healthy Beverages , Healthy Desserts , Healthy Cooking , Healthy Snacking and Eating Out and Physical Activity . A three-part process evaluation was adopted to evaluate implementation success : an in-church instrument to assess the reach , dose delivered and fidelity of interactive sessions ; a post-intervention exposure survey to assess individual-level dose received in a sample of congregants and an evaluation form to assess the church food environment . Print materials were implemented with moderate to high fidelity and high dose . Program reach was low , which may reflect inaccuracies in church attendance rather than study implementation issues . Intervention components with the greatest dose received were giveaways ( 42.0-61.7 % ) , followed by taste tests ( 48.7-53.7 % ) and posters ( 34.3-65.0 % ) . The dose received of general program information was moderate to high . The results indicate successful implementation of the HBHS program .

Healthy Bodies , Healthy Souls ( HBHS )

HBHS

Physical Activity

HBHS program

evaluate

fidelity

exposure survey

individual-level dose received

evaluation form

church food environment

giveaways

taste tests

posters


Randomized , controlled , parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A ( SPINART ) . BACKGROUND The benefits of routine prophylaxis vs. on-demand treatment with factor VIII products have not been evaluated in controlled clinical trials in older patients with hemophilia A . OBJECTIVES To report results from a preplanned analysis of data from the first year of the 3-year SPINART study , which compares routine prophylaxis with on-demand treatment with sucrose-formulated recombinant FVIII ( rFVIII-FS ) . PATIENTS/METHODS SPINART is an open-label , randomized , controlled , parallel-group , multinational trial . Males aged 12-50 years with severe hemophilia A , ≥ 150 days of exposure to FVIII , no FVIII inhibitors , no prophylaxis for > 12 consecutive months in the past 5 years and 6-24 bleeding episodes in the preceding 6 months were randomized 1 : 1 to rFVIII-FS prophylaxis ( 25 IU kg ( -1 ) , three times weekly ) or on-demand treatment . The primary efficacy endpoint , number of total bleeding episodes in the intent-to-treat population , was analyzed after the last patient had completed 1 year of follow-up . A negative binomial model was used for the primary endpoint analysis ; analysis of variance was used for confirmatory analysis of annualized bleeding rates . RESULTS Eighty-four patients were enrolled and analyzed ( n = 42 per group ; mean age , 30.6 years ; median treatment duration , 1.7 years ) . The median number of total bleeding episodes and total bleeding episodes per year were significantly lower with prophylaxis than with on-demand treatment ( total , 0 vs. 54.5 ; total per year , 0 vs. 27.9 ; both P < 0.0001 ) . No treatment-related adverse events occurred , and no patients developed FVIII inhibitors . CONCLUSIONS Routine prophylaxis with rFVIII-FS leads to a significant reduction in bleeding as compared with on-demand treatment . Adverse events were consistent with the established rFVIII-FS safety profile .

routine prophylaxis

number of total bleeding episodes

adults

severe hemophilia A ( SPINART )

older patients

hemophilia

trial

Males

aged 12-50 years

Eighty-four patients

n = 42 per group

mean age , 30.6 years

median treatment duration , 1.7 years


A randomized cross-over study of inhalation of diesel exhaust , hematological indices , and endothelial markers in humans . BACKGROUND Exposure to traffic-related air pollution ( TRAP ) is considered a trigger for acute cardiovascular events . Diesel Exhaust ( DE ) is a major contributor to TRAP in the world . We evaluated the effect of DE inhalation on circulating blood cell populations , hematological indices , and systemic inflammatory cytokines in humans using a specialized facility . METHODS In a randomized double-blind crossover study balanced to order , 17 metabolic syndrome ( MetS ) and 15 healthy subjects inhaled filtered air ( FA ) or DE exposure in two-hour sessions on different days with a minimum 2-week washout period . We collected blood pre-exposure , 7 , and 22 hours after exposure initiation and measured the complete blood count and differential . We performed multiplex cytokine assay to measure the changes in the systemic inflammatory cytokines , and endothelial adhesion molecules ( n=15 ) . A paired analysis compared the effect of DE and FA exposures for the change from pre-exposure to the subsequent time points . RESULTS A significant increase in the hematocrit was noted 7 hrs after DE [ 1.4 % ( 95 % CI : 0.9 to 1.9 % ) ] compared to FA exposure [ 0.5 % ( 95 % CI : -0.09 to 1.0 % ) ; p=0.008 . The hemoglobin levels increased non-significantly at 7 hrs post DE [ 0.3 gm/dL ( 95 % CI : 0.2 to 0.5 gm/dL ) ] versus FA exposure [ 0.2 gm/dL ( 95 % CI : 0 to 0.3 gm/dL ) ] ; p=0.06 . Furthermore , the platelet count increased 22 hrs after DE exposure in healthy , but not in MetS subjects [ DE : 16.6 ( 95 % CI : 10.2 to 23 ) thousand platelets/mL versus [ FA : 3.4 ( 95 % CI : -9.5 to 16.3 ) thousand platelets/mL ) ] ; p=0.04 . No DE effect was observed for WBC , neutrophils , lymphocytes or erythrocytes . Using the multiplex assay , small borderline significant increases in matrix metalloproteinase-9 , interleukins ( IL ) -1 beta , 6 and 10 occurred 7 hrs post exposure initiation , whereas E-selectin , intercellular adhesion molecule-1 , and vascular cell adhesion molecule -1 , and myeloperoxidase 22 hrs post exposure . CONCLUSIONS Our results suggest that short-term DE exposure results in hemoconcentration and thrombocytosis , which are important determinants of acute cardiovascular events . Multiplex assay showed a non-significant increase in IL-1β and IL-6 immediately post exposure followed by myeloperoxidase and endothelial activation molecules . Further specific assays in a larger population will improve our understanding of the systemic inflammatory mechanisms following acute exposure to TRAP .

inhaled filtered air ( FA )

DE exposure

blood count and differential .

increase in the hematocrit

hemoglobin levels increased

platelet count

DE effect

WBC , neutrophils , lymphocytes

erythrocytes .

vascular cell adhesion molecule -1

myeloperoxidase 22

hemoconcentration and thrombocytosis

metabolic syndrome

MetS


Erythropoietin treatment in chemotherapy-induced anemia in previously untreated advanced esophagogastric cancer patients . BACKGROUND The impact of erythropoiesis-stimulating agents in chemotherapy-induced anemia has been a constant topic of debate over recent years . We prospectively assessed the efficacy of epoetin beta ( Epo-b ) in improving hemoglobin ( Hb ) levels and outcome in patients within an open label , randomized clinical phase II trial with advanced or metastatic gastric/esophagogastric cancer . METHODS Previously untreated patients were randomized to receive 3-weekly cycles of capecitabine ( 1000 mg/m ( 2 ) bid ) for 14 days plus on day 1 either irinotecan 250 mg/m ( 2 ) or cisplatin 80 mg/m ( 2 ) . Epo-b ( 30000 IU once weekly ) was initiated in patients with Hb < 11 g/dl and continued until Hb ≥12 g/dl was reached . If after 4 weeks the Hb increase was < 0.5 g/dl , Epo-b was increased to 30000 IU , twice weekly . RESULTS Of 118 patients enrolled , 32 received Epo-b treatment ; of these , 65 % achieved an increase in Hb levels of at least 2 g/dl , with 74 % achieving the target Hb of ≥12 g/dl . Within the study population , patients receiving Epo-b showed better overall survival ( median 14.5 vs. 8.0 months , P = 0.056 ) as well as a significantly improved disease control rate ( 78 vs. 55 % , P = 0.025 ) . Patients in the irinotecan group profited significantly ( P < 0.05 ) in terms of progression-free survival and overall survival under Epo-b treatment ( median 6.5 vs 4.1 months and median 15.4 vs 8.4 months , respectively ) . CONCLUSIONS Epo-b was effective in raising Hb levels in patients with advanced esophagogastric cancer . Patients receiving Epo-b had a significantly increased response to chemotherapy and a clear trend to improved survival .

capecitabine

irinotecan

cisplatin

Epo-b

hemoglobin ( Hb ) levels

Hb levels

118 patients enrolled


Effect of beta-alanine , with and without sodium bicarbonate , on 2000-m rowing performance . PURPOSE To examine the effect of beta-alanine only and beta-alanine with sodium bicarbonate supplementation on 2,000-m rowing performance . METHODS Twenty well-trained rowers ( age 23 ± 4 y ; height 1.85 ± 0.08 m ; body mass 82.5 ± 8.9 kg ) were assigned to either a placebo or beta-alanine ( 6.4 g · d ( -1 ) for 4 weeks ) group . A 2,000-m rowing time trial ( TT ) was performed before supplementation ( Baseline ) and after 28 and 30 days of supplementation . The post supplementation trials involved supplementation with either maltodextrin or sodium bicarbonate in a double-blind , crossover design , creating four study conditions ( placebo with maltodextrin ; placebo with sodium bicarbonate ; beta-alanine with maltodextrin ; beta-alanine with sodium bicarbonate ) . Blood lactate , pH , bicarbonate , and base excess were measured pre-TT , immediately post-TT and at TT+5 min . Performance data were analyzed using magnitude based inferences . RESULTS Beta-alanine supplementation was very likely to be beneficial to 2,000-m rowing performance ( 6.4 ± 8.1 s effect compared with placebo ) , with the effect of sodium bicarbonate having a likely benefit ( 3.2 ± 8.8 s ) . There was a small ( 1.1 ± 5.6 s ) but possibly beneficial additional effect when combining chronic beta-alanine supplementation with acute sodium bicarbonate supplementation compared with chronic beta-alanine supplementation alone . Sodium bicarbonate ingestion led to increases in plasma pH , base excess , bicarbonate , and lactate concentrations . CONCLUSIONS Both chronic beta-alanine and acute sodium bicarbonate supplementation alone had positive effects on 2,000-m rowing performance . The addition of acute sodium bicarbonate to chronic beta-alanine supplementation may further enhance rowing performance .

beta-alanine

sodium bicarbonate

rowing performance

2,000-m rowing performance .

A 2,000-m rowing time trial ( TT )

Performance

2,000-m rowing performance

enhance rowing performance


Effects of weighted sled towing with heavy versus light load on sprint acceleration ability . Weighted sled towing is used by athletes to improve sprint acceleration ability . The typical coaching recommendation is to use relatively light loads , as excessively heavy loads are hypothesized to disrupt running mechanics and be detrimental to sprint performance . However , this coaching recommendation has not been empirically tested . This study compared the effects of weighted sled towing with 2 different external loads on sprint acceleration ability . Twenty-one physically active men were randomly allocated to heavy- ( n = 10 ) or light-load weighted sled towing ( n = 11 ) groups . All subjects participated in 2 training sessions per week for 8 weeks . The subjects in the heavy and light groups performed weighted sled towing using external loads that reduced sprint velocity by approximately 30 and 10 % , respectively . Before and after the training , the subjects performed a 10-m sprint test , in which split time was measured at 5 and 10 m from the start . The heavy group significantly improved both the 5- and 10-m sprint time by 5.7 ± 5.7 and 5.0 ± 3.5 % , respectively ( P < 0.05 ) , whereas only 10-m sprint time was improved significantly by 3.0 ± 3.5 % ( P < 0.05 ) in the light group . No significant differences were found between the groups in the changes in 5-m and 10-m sprint time from pre- to posttraining . These results question the notion that training loads that induce greater than 10 % reduction in sprint velocity would negatively affect sprint performance and point out the potential benefit of using a heavier load for weighted sled towing .

weighted sled towing with heavy

light load

Weighted sled towing

weighted sled towing

heavy-

light-load weighted sled towing

sprint acceleration ability .

sprint acceleration ability .

sprint acceleration ability .

sprint velocity

split time

5- and 10-m sprint time

sprint acceleration ability .

athletes

Twenty-one

physically active

men


The Tiotropium Safety and Performance in Respimat Trial ( TIOSPIR ) , a large scale , randomized , controlled , parallel-group trial-design and rationale . BACKGROUND Tiotropium bromide is an effective therapy for COPD patients . Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as efficacious as tiotropium HandiHaler , however , concerns have been raised about tiotropium 's safety when given via Respimat . METHODS The TIOSPIR trial ( NCT01126437 ) compares the safety and efficacy of tiotropium Respimat 5 μg once daily ( marketed ) and 2.5 μg once daily ( investigational ) with tiotropium HandiHaler 18 μ once daily ( marketed ) . The hypotheses to be tested are 1 ) . that tiotropium Respimat 5 μg once daily and Respimat 2.5 μg once daily are non-inferior to HandiHaler in terms of all-cause mortality , and 2 ) . that tiotropium Respimat 5 μg once daily is superior to HandiHaler in terms of time to first exacerbation . A spirometry substudy evaluates the bronchodilator efficacy . The trial is a randomized , double-blind , double dummy , event-driven , parallel group study . Participants can use any background treatment for COPD except inhaled anticholinergic agents . The study encompasses a wide range of COPD patients , e.g . patients with stable cardiac diseases including arrhythmia can be included . Clinical sites are international and include both primary care as well as specialists . RESULTS To date , over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2-3 years . CONCLUSION TIOSPIR will provide precise estimates of the relative safety and efficacy of the Respimat and HandiHaler formulations of tiotropium , assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort .

Tiotropium

Tiotropium bromide

tiotropium Respimat Soft Mist inhaler

tiotropium HandiHaler

tiotropium 's

Safety

Performance

safety

efficacy


Daclizumab high-yield process in relapsing-remitting multiple sclerosis ( SELECT ) : a randomised , double-blind , placebo-controlled trial . BACKGROUND Daclizumab , a humanised monoclonal antibody , modulates interleukin-2 signalling by blocking the α subunit ( CD25 ) of the interleukin-2 receptor . We assessed whether daclizumab high-yield process ( HYP ) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis . METHODS We did a randomised , double-blind , placebo-controlled trial at 76 centres in the Czech Republic , Germany , Hungary , India , Poland , Russia , Ukraine , Turkey , and the UK between Feb 15 , 2008 , and May 14 , 2010 . Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned ( 1:1:1 ) , via a central interactive voice response system , to subcutaneous injections of daclizumab HYP 150 mg or 300 mg , or placebo , every 4 weeks for 52 weeks . Patients and study personnel were masked to treatment assignment , except for the site pharmacist who prepared the study drug for injection , but had no interaction with the patient . The primary endpoint was annualised relapse rate . Analysis was by intention to treat . The trial is registered with ClinicalTrials.gov , number NCT00390221 . FINDINGS 204 patients were assigned to receive placebo , 208 to daclizumab HYP 150 mg , and 209 to daclizumab HYP 300 mg , of whom 188 ( 92 % ) , 192 ( 92 % ) , and 197 ( 94 % ) , respectively , completed follow-up to week 52 . The annualised relapse rate was lower for patients given daclizumab HYP 150 mg ( 0·21 , 95 % CI 0·16-0·29 ; 54 % reduction , 95 % CI 33-68 % ; p < 0·0001 ) or 300 mg ( 0·23 , 0·17-0·31 , 50 % reduction , 28-65 % ; p=0·00015 ) than for those given placebo ( 0·46 , 0·37-0·57 ) . More patients were relapse free in the daclizumab HYP 150 mg ( 81 % ) and 300 mg ( 80 % ) groups than in the placebo group ( 64 % ; p < 0·0001 in the 150 mg group and p=0·0003 in the 300 mg group ) . 12 ( 6 % ) patients in the placebo group , 15 ( 7 % ) of those in the daclizumab 150 mg group , and 19 ( 9 % ) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse . One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess . INTERPRETATION Subcutaneous daclizumab HYP administered every 4 weeks led to clinically important effects on multiple sclerosis disease activity during 1 year of treatment . Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease . FUNDING Biogen Idec and AbbVie Biotherapeutics Inc .

Daclizumab

placebo-controlled

Daclizumab

placebo

daclizumab

daclizumab

daclizumab

daclizumab

daclizumab

relapsing-remitting multiple sclerosis

annualised relapse rate

relapse

aged 18-55 years

relapsing-remitting multiple sclerosis

204 patients

assigned to receive placebo

daclizumab HYP 150 mg

daclizumab


Successful treatment of depressed , distensible acne scars using autologous fibroblasts : a multi-site , prospective , double blind , placebo-controlled clinical trial . BACKGROUND A previous clinical trial evaluating autologous fibroblasts ( human dermal ) injections for the treatment of facial contour deformities found significantly greater improvements in wrinkle and acne scar appearance than with placebo treatment . OBJECTIVE To compare the efficacy and safety of autologous fibroblast treatment of moderate to severe , depressed , distensible facial acne scars with that of vehicle control . METHODS This was a randomized multicenter , double-blind , placebo-controlled trial in subjects with bilateral moderate to severe acne scarring ; subjects served as their own controls . Skin biopsies were obtained from randomized subjects for fibroblast production . Subjects ( n = 99 ) underwent three intradermal injection sessions with 2 mL of autologous fibroblast suspension ( 10-20 million cells/mL ) on one cheek and vehicle control ( cell culture medium ) on the other at 14-day intervals . Efficacy was based on the blinded subject 's , evaluator 's , and independent photographic viewer 's ( IPR ) assessment of acne scarring 1 to 4 months after the last treatment . RESULTS Autologous fibroblast treatment was associated with significantly greater treatment success than vehicle control for the subject ( 43 % vs.18 % ) , evaluator ( 59 % vs. 2 % ) , and IPR assessments . Autologous fibroblast injections were well tolerated , without permanent adverse effects . CONCLUSIONS Autologous fibroblast injections safely and effectively improved the appearance of depressed distensible acne scars .

autologous fibroblasts

placebo

autologous fibroblast

placebo-controlled

vehicle control

Autologous fibroblast treatment

Autologous fibroblast injections

Autologous fibroblast injections

wrinkle and acne scar appearance

acne scarring


Long-term treatment with atomoxetine for attention-deficit/hyperactivity disorder symptoms in children and adolescents with autism spectrum disorder : an open-label extension study . OBJECTIVE The efficacy and tolerability of long-term treatment with atomoxetine for symptoms of attention-deficit/hyperactivity disorder ( ADHD ) in children with autism spectrum disorder ( ASD ) has not been established . METHODS In this study , 88 patients 6-17 years of age , with ADHD and ASD , were treated with 1.2 mg/kg/day atomoxetine for 20 weeks as follow-up of an 8 week double-blind placebo-controlled period . Primary endpoint was the ADHD Rating Scale ( ADHD-RS ) . RESULTS After 8 weeks of initial treatment , the mean total , inattention , and hyperactivity-impulsivity ADHD-RS further decreased significantly from 34.9 to 27.0 for the total ADHD-RS , from 18.3 to 14.5 for the ADHD-RS inattention subscale , and from 16.5 to 12.6 for the hyperactivity-impulsivity subscale . Adverse events were mild and tended to diminish over time during continued treatment , especially regarding nausea and fatigue . There were no serious adverse events . CONCLUSIONS The results of the present analysis suggest that continued treatment with atomoxetine up to 28 weeks further improve ADHD symptoms in children and adolescents with ASD , while adverse events tend to subside . Future studies investigating the long-term efficacy of atomoxetine in children and adolescents with ASD should be randomized and placebo controlled . This study has been registered in ClinicalTrials.gov ( www.clinicaltrials.gov ) under registration number NCT00380692 .

atomoxetine

atomoxetine

atomoxetine

placebo-controlled

atomoxetine

atomoxetine

efficacy and tolerability

ADHD Rating Scale ( ADHD-RS )

mean total , inattention

hyperactivity-impulsivity ADHD-RS

ADHD-RS inattention subscale

hyperactivity-impulsivity subscale

Adverse events

nausea and fatigue .

serious adverse events

improve ADHD symptoms

adverse events

children

adolescents

autism spectrum disorder

children

autism spectrum disorder ( ASD )

88 patients

6-17 years of age

ADHD

ASD

children

adolescents

ASD

children

adolescents

ASD


Altered accuracy of saccadic eye movements in children with fetal alcohol spectrum disorder . BACKGROUND Prenatal exposure to alcohol is a major , preventable cause of neurobehavioral dysfunction in children worldwide . The measurement and quantification of saccadic eye movements is a powerful tool for assessing sensory , motor , and cognitive function . The quality of the motor process of an eye movement is known as saccade metrics . Saccade accuracy is 1 component of metrics , which to function optimally requires several cortical brain structures as well as an intact cerebellum and brain-stem . The cerebellum has frequently been reported to be damaged by prenatal alcohol exposure . This study , therefore , tested the hypothesis that children with fetal alcohol spectrum disorder ( FASD ) will exhibit deficits in the accuracy of saccades . METHODS A group of children with FASD ( n = 27 ) between the ages of 8 and 16 and typically developing control children ( n = 27 ) matched for age and sex , completed 3 saccadic eye movement tasks of increasing difficulty . Eye movement performance during the tasks was captured using an infrared eye tracker . Saccade metrics ( e.g. , velocity , amplitude , accuracy ) were quantified and compared between the 2 groups for the 3 different tasks . RESULTS Children with FASD were more variable in saccade endpoint accuracy , which was reflected by statistically significant increases in the error of the initial saccade endpoint and the frequency of additional , corrective saccades required to achieve final fixation . This increased variability in accuracy was amplified when the cognitive demand of the tasks increased . Children with FASD also displayed a statistically significant increase in response inhibition errors . CONCLUSIONS These data suggest that children with FASD may have deficits in eye movement control and sensory-motor integration including cerebellar circuits , thereby impairing saccade accuracy .

saccadic eye movements

3 saccadic eye movement tasks

Saccade metrics

velocity

amplitude

accuracy

saccade endpoint accuracy

initial saccade endpoint

corrective saccades

accuracy

response inhibition errors


Promoting question-asking in school-aged children with autism spectrum disorders : effectiveness of a robot intervention compared to a human-trainer intervention . OBJECTIVE The purpose of the present study was to investigate the effectiveness of an applied behaviour analysis ( ABA ) -based intervention conducted by a robot compared to an ABA-based intervention conducted by a human trainer in promoting self-initiated questions in children with autism spectrum disorder ( ASD ) . METHODS Data were collected in a combined crossover multiple baseline design across participants . Six children were randomly assigned to two experimental groups . RESULTS Results revealed that the number of self-initiated questions for both experimental groups increased between baseline and the first intervention and was maintained during follow-up . The high number of self-initiated questions during follow-up indicates that both groups maintained this skill . CONCLUSIONS The interventions conducted by a robot and a human trainer were both effective in promoting self-initiated questions in children with ASD . No conclusion with regard to the differential effectiveness of both interventions could be drawn . Implications of the results and directions for future research are discussed .

question-asking

robot intervention

human-trainer intervention

interventions conducted by a

robot

and a

human trainer

self-initiated questions

self-initiated questions


Effects of parecoxib on morphine analgesia after gynecology tumor operation : a randomized trial of parecoxib used in postsurgical pain management . BACKGROUND The analgesic efficacy of parecoxib in postsurgical pain management has been confirmed in minimally invasive surgery . However , little is known about its effects used in combination with opioids and about its potential for opioid-sparing effects in complex operations . This study was performed to investigate the influence of parecoxib on morphine analgesia after gynecological tumor surgery . METHODS Eighty patients undergoing gynecological tumor resection were randomized to receive either intravenous parecoxib at a dose of 40 mg ( Group P , n = 40 ) followed by 40 mg every 12 h for 48 h or saline as a control ( Group C , n = 40 ) 30 min before induction of anesthesia , followed by saline at the same time points after the operation . All patients had access to patient-controlled analgesia with intravenous morphine . Patients were assessed with respect to pain score ( visual analog scale from 0-10 ) , cumulative morphine requirement , satisfaction score , and side effects at 2 , 6 , 12 , 24 , and 48 h after surgery . RESULTS A total of 79 patients were evaluated . The cumulative dose of morphine administered at each time point was lower in Group P than in Group C ( P < 0.05 ) , at 2 h ( 3.81 ± 0.35 versus 4.13 ± 0.45 ; P = 0.01 ) , 6 h ( 16.20 ± 1.49 versus 19.60 ± 0.35 ; P < 0.001 ) , 12 h ( 26.29 ± 2.75 versus 32.49 ± 2.42 ; P < 0.001 ) , 24 h ( 41.72 ± 2.70 versus 49.97 ± 4.53 ; P < 0.001 ) , and 48 h ( 60.06 ± 4.00 versus 65.68 ± 3.23 ; P < 0.001 ) . Compared with Group C , Group P had significantly lower visual analog scale scores at rest and with movement , respectively , at 2 h ( 4.2 , P < 0.001 and 5.0 , P < 0.001 ) , 6 h ( 3.6 , P < 0.001 and 4.5 , P < 0.001 ) , 12 h ( 3.0 , P = 0.017 and 4.0 , P < 0.001 ) , 24 h ( 2.1 , P < 0.001 and 3.4 , P < 0.001 ) , and 48 h ( 1.8 , P < 0.001 and 2.6 , P < 0.001 ) . The satisfaction score was higher in Group P than in Group C ( 8.6 ± 0.3 versus 6.8 ± 0.7 , P < 0.001 ) . There were no significant differences in side effects between the two groups ( P > 0.05 ) . CONCLUSIONS The use of parecoxib with patient-controlled analgesic morphine in postoperative analgesia resulted in comprehensive enhancement of the analgesic efficacy , reducing the opioid requirement and increasing patient satisfaction after gynecological tumor surgery .

parecoxib

parecoxib

parecoxib

parecoxib on morphine

cumulative morphine requirement

satisfaction score

side effects

cumulative dose of morphine


Prevalence and treatment outcome of cervicitis of unknown etiology . BACKGROUND Mucopurulent cervicitis ( MPC ) is a clinical syndrome characterized by mucopurulent discharge from the cervix and other signs of inflammation . This was a phase III , multicenter study designed to evaluate the effectiveness of placebo versus empiric antibiotic treatment for clinical cure of MPC of unknown etiology at 2-month follow-up . Unfortunately , enrollment was terminated because of low accrual of women with cervicitis of unknown etiology , but important prevalence and outcome data were obtained . METHODS Five hundred seventy-seven women were screened for MPC . Women with MPC were randomized to the treatment or placebo arm of the study , and the 2 arms were evaluated based on the etiology , clinical cure rates , adverse events ( AEs ) , and rates of pelvic inflammatory disease . RESULTS One hundred thirty-one ( 23 % [ 131/577 ] ) screened women were found to have MPC . Eighty-seven were enrolled and randomized . After excluding women with sexually transmitted infections and other exclusions , 61 % ( 53/87 ) had cervicitis of unknown etiology . The overall clinical failure rate was 30 % ( 10/33 ) , and the clinical cure rate was only 24 % ( 8/33 ) . Rates were not significantly different between the arms . There were 24 gastrointestinal AEs in the treatment arm compared with 1 AE in the placebo arm . CONCLUSIONS More than half of the cases of MPC were of unknown etiology . Clinical cure rates for the placebo and treatment arms were extremely low , with most women concluding the study with a partial response . Gastrointestinal AEs were higher in the treatment arm .

placebo

empiric antibiotic treatment

placebo

placebo

placebo

cervicitis

MPC

clinical cure rates

adverse events ( AEs )

rates of pelvic inflammatory disease

cervicitis

overall clinical failure rate

clinical cure rate

gastrointestinal AEs

Clinical cure rates

Gastrointestinal AEs

cervicitis

women

Five hundred seventy-seven

MPC .

One hundred thirty-one

Eighty-seven


Is the effect of mobile phone radiofrequency waves on human skin perfusion non-thermal ? OBJECTIVE To establish whether SkBF can be modified by exposure to the radiofrequency waves emitted by a mobile phone when the latter is held against the jaw and ear . METHODS Variations in SkBF and Tsk in adult volunteers were simultaneously recorded with a thermostatic laser Doppler system during a 20-minute " radiofrequency " exposure session and a 20-minute " sham " session . The skin microvessels ' vasodilatory reserve was assessed with a heat challenge at the end of the protocol . RESULTS During the radiofrequency exposure session , SkBF increased ( vs. baseline ) more than during the sham exposure session . The sessions did not differ significant in terms of the Tsk time-course response . The skin microvessels ' vasodilatory ability was found to be greater during radiofrequency exposure than during sham exposure . CONCLUSIONS Our results reveal the existence of a specific vasodilatory effect of mobile phone radiofrequency emission on skin perfusion .

mobile phone radiofrequency waves

radiofrequency exposure session

sham exposure session

mobile phone radiofrequency emission

SkBF

Variations in SkBF

SkBF

Tsk time-course response

vasodilatory


The role of treatment fidelity on outcomes during a randomized field trial of an autism intervention . This randomized field trial comparing Strategies for Teaching based on Autism Research and Structured Teaching enrolled educators in 33 kindergarten-through-second-grade autism support classrooms and 119 students , aged 5-8 years in the School District of Philadelphia . Students were assessed at the beginning and end of the academic year using the Differential Ability Scales . Program fidelity was measured through video coding and use of a checklist . Outcomes were assessed using linear regression with random effects for classroom and student . Average fidelity was 57 % in Strategies for Teaching based on Autism Research classrooms and 48 % in Structured Teaching classrooms . There was a 9.2-point ( standard deviation = 9.6 ) increase in Differential Ability Scales score over the 8-month study period , but no main effect of program . There was a significant interaction between fidelity and group . In classrooms with either low or high program fidelity , students in Strategies for Teaching based on Autism Research experienced a greater gain in Differential Ability Scales score than students in Structured Teaching ( 11.2 vs. 5.5 points and 11.3 vs. 8.9 points , respectively ) . In classrooms with moderate fidelity , students in Structured Teaching experienced a greater gain than students in Strategies for Teaching based on Autism Research ( 10.1 vs. 4.4 points ) . The results suggest significant variability in implementation of evidence-based practices , even with supports , and also suggest the need to address challenging issues related to implementation measurement in community settings .

treatment fidelity

Teaching

Program fidelity

video coding

Program fidelity

Average fidelity

Differential Ability Scales score

Differential Ability Scales score

fidelity

autism

kindergarten-through-second-grade

autism

aged 5-8 years

Autism

Autism


Evaluation of the effect of low level laser on prevention of chemotherapy-induced mucositis . Radiotherapy in the head and neck region and chemotherapy might give rise to oral mucositis which is a severe and painful inflammation . There is no known definite cure for mucositis . A number of studies have attempted to evaluate the effect of low-power laser on radiotherapy- and chemotherapy-induced mucositis . The present study was undertaken to evaluate the effect of low-power laser on the prevention of mucositis , xerostomia and pain as a result of chemotherapy . The subjects in this double-blind randomized controlled study were 24 adult patients who underwent chemotherapy during 2009-2010 . The results showed that low-power laser was able to decrease the effect of chemotherapy on oral mucositis , xerostomia and pain in a variety of malignancies ( P & lt ; 0.05 ) . It can be concluded that low-power laser might decrease the intensity of mucositis .

low level laser

Radiotherapy

chemotherapy

low-power laser

radiotherapy-

chemotherapy-induced

low-power laser

chemotherapy

chemotherapy

chemotherapy

low-power laser

radiotherapy-

chemotherapy-induced mucositis

intensity of mucositis

chemotherapy-induced mucositis .

adult


Clinical pharmacokinetics of buffered propranolol sublingual tablet ( Promptol™ ) -application of a new " physiologically based " model to assess absorption and disposition . Sublingual administration of certain buffered propranolol may improve the rate and extent of absorption compared to oral administration . The main objectives of this study were to ( 1 ) compare the plasma propranolol concentrations ( Cp-prop ) following sublingual administration of a specially buffered formulation ( Promptol™ ) to that following oral administration of Inderal ( ® ) and ( 2 ) evaluate the utility of a special pharmacokinetic model in describing the Cp-prop following sublingual administration . Eighteen healthy volunteers received 10 mg sublingual Promptol™ or oral Inderal ( ® ) . Multiple Cp-prop were determined and their pharmacokinetics compared . Additional data following sublingual 40 mg Promptol™ or Inderal ( ® ) were utilized for evaluation of a special advanced compartmental absorption and transit ( ACAT ) model . For model simulation , the physicochemical parameters were imported from AMET predictor , whereas the pharmacokinetic parameters were calculated and optimized by Gastroplus ( ® ) . Based on this model , the quantity of drug absorbed via buccal/sublingual mucosa was estimated . Cp-prop was higher at earlier times with 3-fold greater relative bioavailability following sublingual Promptol™ compared to that from oral Inderal ( ® ) . The special ACAT model provided excellent goodness of fit of Cp-prop-time curve and estimated a 56.6 % increase in absorption rate from Promptol™ and higher initial Cp-prop compared to the regular formulation . The modified ACAT model provided a useful approach to describe sublingual absorption of propranolol and clearly demonstrated an improvement of absorption of Promptol™ . The sublingual 10 mg Promptol™ achieved not only a similar systemic exposure as 30 mg oral Inderal ( ® ) but an earlier effective Cp-prop which may be advantageous for certain clinical conditions .

propranolol

propranolol

Promptol™

Inderal

Promptol™

administration

Eighteen

healthy


Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia : randomized , double-blind , placebo-controlled study . We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia . In a double-blind placebo-controlled clinical trial , 40 patients with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine ( 20 mg ) or placebo in addition to risperidone , 6 mg/d , for eight weeks . Assessment was done using the Positive and Negative Syndrome Scale at baseline , week 4 , and week 8 . The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms , respectively . All 40 patients had at least one postbaseline measurement , and 38 patients completed the trial . Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point ( P < 0.001 ) . The same effect was observed for the total score ( P < 0.001 ) and the general psychopathology subscale score ( P = 0.002 ) . There was no significant difference in reduction of positive symptoms score between the 2 groups ( P = 0.757 ) . Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups . Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia .

Memantine add-on to risperidone

memantine

risperidone

memantine

placebo

risperidone

placebo

Positive and Negative Syndrome Scale

Hamilton Depression Rating Scale

the Extrapyramidal Symptom Rating Scale

significantly greater

improvement on negative subscale

same effect

general psychopathology subscale score

no significant difference

reduction of positive symptoms score

Hamilton Depression Rating Scale

Extrapyramidal Symptom Rating Scale

stable schizophrenia

stable schizophrenia

schizophrenia


A play and joint attention intervention for teachers of young children with autism : a randomized controlled pilot study . The aim of this study was to pilot test a classroom-based intervention focused on facilitating play and joint attention for young children with autism in self-contained special education classrooms . Thirty-three children with autism between the ages of 3 and 6 years participated in the study with their classroom teachers ( n = 14 ) . The 14 preschool special education teachers were randomly assigned to one of three groups : ( 1 ) symbolic play then joint attention intervention , ( 2 ) joint attention then symbolic intervention , and ( 3 ) wait-list control period then further randomized to either group 1 or group 2 . In the intervention , teachers participated in eight weekly individualized 1-h sessions with a researcher that emphasized embedding strategies targeting symbolic play and joint attention into their everyday classroom routines and activities . The main child outcome variables of interest were collected through direct classroom observations . Findings indicate that teachers can implement an intervention to significantly improve joint engagement of young children with autism in their classrooms . Furthermore , multilevel analyses showed significant increases in joint attention and symbolic play skills . Thus , these pilot data emphasize the need for further research and implementation of classroom-based interventions targeting play and joint attention skills for young children with autism .

play and joint attention intervention

play and joint attention skills


Vilazodone lacks proarrhythmogenic potential in healthy participants : a thorough ECG study . OBJECTIVE Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder ( MDD ) in adults . The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers . METHODS In this Phase 1 , randomized , doubleblind , placebo- and active-controlled , 3-arm , parallel , single-center study , healthy subjects received placebo ; moxifloxacin 400 mg ; or vilazodone ( sequentially escalated every 3 days ) 10 , 20 , 40 , 60 , and 80 mg/day . The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate ( QTc ) using an individual correction method ( QTcI ) . RESULTS Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms , demonstrating no signal for a significant vilazodone effect on cardiac repolarization . Vilazodone had no significant effect on heart rate , PR , or QRS interval duration . The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose ( 156 ng/ml after 40 mg/day ) was < 1 ms . The incidence of adverse events ( AEs ) was higher in the vilazodone group ( 57.6 % ) than in the moxifloxacin ( 37.0 % ) and placebo ( 35.6 % ) groups , though AEs were generally mild to moderate in severity and resulted in few discontinuations . CONCLUSIONS Vilazodone had no significant effect on cardiac repolarization , heart rate , PR or QRS interval duration , or ECG morphology in healthy adult participants .

Vilazodone

Vilazodone

vilazodone

placebo-

placebo

moxifloxacin 400 mg

vilazodone

Placebo-corrected

vilazodone

vilazodone

vilazodone

Vilazodone

vilazodone

vilazodone

moxifloxacin

placebo

Vilazodone

QTcI duration

cardiac repolarization .

heart rate

PR

QRS interval duration

QTcI

QTc at Cmax

adverse events ( AEs )

AEs

cardiac repolarization

heart rate

PR

QRS interval duration

ECG morphology

healthy volunteers .

healthy adult participants .


Home-based versus hospital-based high-intensity interval training in cardiac rehabilitation : a randomized study . BACKGROUND High-intensity interval training ( HIT ) as exercise therapy is gradually implemented in cardiac rehabilitation as the cardiovascular benefits from exercise is intensity dependent . However , in previous studies , HIT has been performed with strict supervision . The aim of the study was to assess the feasibility and effectiveness of different modes of HIT in cardiac rehabilitation . DESIGN a randomized clinical study . METHODS Ninety participants with coronary artery disease ( 80 men/10 women , mean age 57 ± 8 years ) were randomly assigned to one of three exercise modes : group exercise ( GE ) , treadmill exercise ( TE ) , or home-based exercise ( HE ) . HIT was performed twice a week for 12 weeks with an exercise intensity of 85-95 % of peak heart rate . The primary outcome measure was change in peak oxygen uptake ( peak VO2 ) . RESULTS Eighty-three participants ( 92 % ) completed the intervention without any severe adverse events . Peak VO2 increased from 34.7 ± 7.3 to 39.0 ± 8.0 ml/kg/min , 32.7 ± 6.5 to 36.0 ± 6.2 ml/kg/min , and 34.4 ± 4.8 to 37.2 ± 5.2 ml/kg/min in TE , GE , and HE , respectively . Mean group difference for TE vs . HE was 1.6 ml/kg/min ( 95 % confidence interval , CI , 0.7 to 3.1 , p = 0.02 ) , TE vs. GE 1.1 ml/kg/min ( 95 % CI-0.5 to 2.5 , p = 0.27 ) , and GE vs . HE 0.6 ml/kg/min ( 95 % CI -1.0 to 2.1 , p = 1 ) . However , on-treatment analysis showed no significant difference between groups . CONCLUSION HIT was efficiently performed in three settings of cardiac rehabilitation , with respect to target exercise intensity , exercise attendance , and increase in peak VO2 . Exercise mode was not essential for exercise capacity .

cardiac rehabilitation :

cardiac rehabilitation :

Ninety

coronary artery disease

men/10 women

age 57 ± 8 years

Eighty-three


Health-education package to prevent worm infections in Chinese schoolchildren . BACKGROUND Soil-transmitted helminths are among the most prevalent sources of human infections globally . We determined the effect of an educational package at rural schools in Linxiang City District , Hunan province , China , where these worms are prevalent . The intervention aimed to increase knowledge about soil-transmitted helminths , induce behavioral change , and reduce the rate of infection . METHODS We conducted a single-blind , unmatched , cluster-randomized intervention trial involving 1718 children , 9 to 10 years of age , in 38 schools over the course of 1 school year . Schools were randomly assigned to the health-education package , which included a cartoon video , or to a control package , which involved only the display of a health-education poster . Infection rates , knowledge about soil-transmitted helminths ( as assessed with the use of a questionnaire ) , and hand-washing behavior were assessed before and after the intervention . Albendazole was administered in all the participants at baseline and in all the children who were found to be positive for infection with soil-transmitted helminths at the follow-up assessment at the end of the school year . RESULTS At the follow-up assessment , the mean score for the knowledge of helminths , calculated as a percentage of a total of 43 points on a questionnaire , was 90 % higher in the intervention group than in the control group ( 63.3 vs. 33.4 , P < 0.001 ) , the percentage of children who washed their hands after using the toilet was nearly twice as high in the intervention group ( 98.9 % , vs. 54.2 % in the control group ; P < 0.001 ) , and the incidence of infection with soil-transmitted helminths was 50 % lower in the intervention group than in the control group ( 4.1 % vs. 8.4 % , P < 0.001 ) . No adverse events were observed immediately ( within 15 minutes ) after albendazole treatment . CONCLUSIONS The health-education package increased students ' knowledge about soil-transmitted helminths and led to a change in behavior and a reduced incidence of infection within 1 school year . ( Funded by UBS Optimus Foundation , Zurich , Switzerland ; Australian New Zealand Clinical Trials Registry number , ACTRN12610000048088 . ) .

health-education package

health-education poster

Albendazole

behavioral change

rate of infection

Infection rates

hand-washing behavior

nearly twice

incidence of infection

adverse events

schoolchildren

children

9 to 10 years of age


The effects of a multi-component higher-functioning autism anti-stigma program on adolescent boys . A six-session higher-functioning autism anti-stigma program incorporating descriptive , explanatory and directive information was delivered to adolescent boys and the impact upon knowledge , attitudes and behavioural intentions towards peers with autism was evaluated . Participants were seventh- , eighth- and ninth-grade students ( N = 395 ) from regular classes in a mainstream school . Two-eighth-grade classes were randomly allocated to the intervention condition and all remaining students were either allocated to the no-intervention peer or no-intervention non-peer condition . The anti-stigma program improved the knowledge and attitudes , but not the behavioural intentions of participants towards their peers with autism . Knowledge and attitudinal changes were maintained at follow-up . There were no spill-over effects of the program to non-targeted students . These results provide some preliminary evidence for the effectiveness of multi-session anti-stigma programs incorporating combined information for adolescent students in inclusive educational environments .


Double-blind , placebo-controlled , dose-ranging study of new recombinant hypoallergenic Bet v 1 in an environmental exposure chamber . BACKGROUND Recombinant allergens offer a tool for improving specific immunotherapy ( SIT ) . OBJECTIVE To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 ( rBet v 1-FV ) as SIT for patients with birch pollen allergy . METHODS Before SIT , thirty-seven adult patients were exposed for eight hours in an environmental exposure chamber ( EEC ) to birch pollen at an average concentration of 3500 ± 500 grains/m ( 3 ) , then randomized to four maintenance dose groups of rBet v 1-FV and one placebo group : 20 μg ( n = 7 ) , 80 μg ( n = 8 ) , 160 μg ( n = 7 ) , 320 μg ( n = 8 ) , and placebo ( n = 7 ) . Patients were treated for 10 weeks with weekly injections and then re-exposed in the EEC . The optimal dose for SIT was assessed using efficacy results from the EEC , IgG responses , and tolerability . RESULTS Thirty-six patients were evaluable for efficacy assessment . The total symptom score significantly decreased in all active groups compared with placebo ( -18.8 % for placebo patients ; -71.9 % , P = 0.0022 for 20 μg ; -75.6 % , P = 0.0007 for 80 μg ; -81.8 % , P = 0.0009 for 160 μg ; -78.3 % , P = 0.0003 for 320 μg ) . IgG1 increased significantly in all active groups compared to placebo . All four active doses were well tolerated , no serious adverse event occurred ; two Grade II reactions , according to EAACI classification , were observed , one in each of the 160- and 320-μg groups . CONCLUSIONS Considering efficacy , immunological response , and tolerability , a maintenance dose of 80 μg of rBet v 1-FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients .

placebo-controlled

recombinant hypoallergenic Bet v 1

recombinant Bet v 1 ( rBet v 1-FV )

environmental exposure chamber

symptom score

well tolerated

serious adverse

Grade II reactions

birch pollen allergy


Impact of angiotensin II receptor blocker therapy ( olmesartan or valsartan ) on coronary atherosclerotic plaque volume measured by intravascular ultrasound in patients with stable angina pectoris . Coronary plaques can be reduced by some medications . The aim of this study was to compare the effects of 2 angiotensin II receptor blockers ( olmesartan at 20 mg/day or valsartan at 80 mg/day ) on coronary plaque by coronary intravascular ultrasound . One hundred hypertensive patients with stable angina pectoris who underwent elective percutaneous coronary intervention were randomly selected to receive 1 of the 2 angiotensin II receptor blockers after coronary intervention . Nontarget coronary lesions with mild to moderate stenosis were measured by volumetric intravascular ultrasound at baseline and after 6 months . After 6 months , both the olmesartan and the valsartan groups showed significant reduction of the examined coronary plaque volume ( 46.2 ± 24.1 mm³ at baseline vs 41.6 ± 21.1 mm³ at 6 months : 4.7 % decrease , p = 0.0002 ; and 47.2 ± 32.7 mm³ at baseline vs 42.5 ± 30.2 mm³ at 6 months : 4.8 % decrease , p = 0.002 , respectively ) . There was no statistically significant difference of plaque regression between the 2 groups ( p = 0.96 ) . In conclusion , there was a significant decrease from baseline in the coronary plaque volume in patients with stable angina pectoris who received olmesartan or valsartan for 6 months . In addition , there was no significant difference in the reduction of plaque volume achieved by these 2 medications .

angiotensin II receptor blocker therapy

olmesartan

valsartan

olmesartan

valsartan

olmesartan

valsartan

examined coronary plaque volume

stable angina pectoris

One hundred

hypertensive

stable angina pectoris


Are postural responses to backward and forward perturbations processed by different neural circuits ? Startle pathways may contribute to rapid accomplishment of postural stability . Here we investigate the possible influence of a startling auditory stimulus ( SAS ) on postural responses . We formulated four specific questions : ( 1 ) can a concurrent SAS shorten the onset of automatic postural responses ? ; and if so ( 2 ) is this effect different for forward versus backward perturbations ? ; ( 3 ) does this effect depend on prior knowledge of the perturbation direction ? ; and ( 4 ) is this effect different for low- and high-magnitude perturbations ? Balance was perturbed in 11 healthy participants by a movable platform that suddenly translated forward or backward . Each participant received 160 perturbations , 25 % of which were combined with a SAS . We varied the direction and magnitude of the perturbations , as well as the prior knowledge of perturbation direction . Perturbation trials were interspersed with SAS-only trials . The SAS accelerated and strengthened postural responses with clear functional benefits ( better balance control ) , but this was only true for responses that protected against falling backwards ( i.e . in tibialis anterior and rectus femoris ) . These muscles also demonstrated the most common SAS-triggered responses without perturbation . Increasing the perturbation magnitude accelerated postural responses , but again with a larger acceleration for backward perturbations . We conclude that postural responses to backward and forward perturbations may be processed by different neural circuits , with influence of startle pathways on postural responses to backward perturbations . These findings give directions for future studies investigating whether deficits in startle pathways may explain the prominent backward instability seen in patients with Parkinson 's disease and progressive supranuclear palsy .

startling auditory stimulus ( SAS )

perturbations

SAS .

SAS-only

SAS

SAS-triggered

postural responses

postural responses

postural responses

SAS-triggered responses

postural responses

Parkinson 's disease


Study design and rationale of a dose-ranging trial of LX4211 , a dual inhibitor of SGLT1 and SGLT2 , in type 2 diabetes inadequately controlled on metformin monotherapy . Sodium-glucose cotransporters 1 ( SGLT1 ) and 2 ( SGLT2 ) are the major cellular transporters responsible for gastrointestinal ( GI ) glucose absorption and renal glucose reabsorption , respectively . LX4211 , a dual inhibitor of SGLT1 and SGLT2 , reduces glucose absorption from the GI tract and enhances urinary glucose excretion . Although several SGLT2-selective inhibitors have been tested in large phase 2 studies , dual inhibition of SGLT1 and SGLT2 is novel at this stage of drug development , and it has implications for clinical-trial design . In this article , we describe the design and rationale of a phase 2 , multicenter , randomized , double-blind , placebo-controlled , parallel group study to evaluate the safety and efficacy of LX4211 in subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin monotherapy . The primary endpoint is the change in glycated hemoglobin A1c from baseline to week 12 . Secondary endpoints include the proportion of subjects achieving a glycated hemoglobin A1c value of < 7 % , change from baseline in fasting plasma glucose and postprandial glucose ( as part of an oral glucose tolerance test ) , body weight , and blood pressure . Safety is evaluated with particular focus on hypoglycemia , GI symptoms , and incidence of genitourinary tract infections .

placebo-controlled

safety and efficacy

glycemic control

glycated hemoglobin A1c

Safety


The use of transvaginal synthetic mesh for anterior vaginal wall prolapse repair : a randomized controlled trial . INTRODUCTION AND HYPOTHESIS The aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse . METHODS This is a randomized controlled trial in which women with advanced anterior vaginal wall prolapse , at least stage II with Ba ≥ +1 cm according to the Pelvic Organ Prolapse Quantification ( POP-Q ) classification , were randomly assigned to have either anterior colporrhaphy ( n = 39 ) or repair using trocar-guided transvaginal mesh ( n = 40 ) . The primary outcome was objective cure rate of the anterior compartment ( point Ba ) assessed at the 12-month follow-up visit , with stages 0 and I defined as anatomical success . Secondary outcomes included quantification of other vaginal compartments ( POP-Q points ) , comparison of quality of life by the prolapse quality of life ( P-QOL ) questionnaire , and complication rate between the groups after 1 year . Study power was fixed as 80 % with 5 % cutoff point ( p < 0.05 ) for statistical significance . RESULTS The groups were similar regarding demographic and clinical preoperative parameters . Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % ( 95 % confidence interval 0.068-0.54 ) , respectively , and the difference between the groups was statistically significant ( p = 0.018 ) . Similar total complication rates were observed in both groups , with tape exposure observed in 5 % of the patients . There was a significant improvement in all P-QOL domains as a result of both procedures ( p < 0.001 ) , but they were not distinct between groups ( p > 0.05 ) . CONCLUSIONS Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy . Quality of life equally improved after both techniques . However , the trial failed to detect differences in P-QOL scores and complication rates between the groups .

transvaginal synthetic mesh

efficacy and safety

anterior vaginal wall prolapse

anterior vaginal wall prolapse .

women


Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients : a randomised controlled trial . BACKGROUND Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis . We compared a standard diagnostic strategy ( culture and histology ) with a rapid biomarker-based diagnostic strategy ( aspergillus galactomannan and PCR ) for directing the use of antifungal treatment in this group of patients . METHODS In this open-label , parallel-group , randomised controlled trial , eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia , with no history of invasive fungal disease . Enrolled patients were randomly assigned ( 1:1 ) by a computer-generated schedule to follow either a standard diagnostic strategy ( based on culture and histology ) or a biomarker-based diagnostic strategy ( aspergillus galactomannan and PCR ) to direct treatment with antifungal drugs . Patients , were followed up for 26 weeks or until death . Masking of the use of different diagnostic tests was not possible for patients , treating physicians , or investigators . The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment ( for the biomarker-based diagnostic strategy , a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis , so treatment in this context was classified as empirical ) . This outcome was assessed by an independent data review committee from which the study allocations were masked . Analyses were by intention to treat and included all enrolled patients . This study is registered with ClinicalTrial.gov , number NCT00163722 . FINDINGS 240 eligible patients were recruited from six Australian centres between Sept 30 , 2005 , and Nov 19 , 2009 . 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy . 39 patients ( 32 % ) in the standard diagnosis group and 18 ( 15 % ) in the biomarker diagnosis group received empirical antifungal treatment ( difference 17 % , 95 % CI 4-26 ; p=0·002 ) . The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups ( hepatotoxic effects : 21 [ 17 % ] vs 12 [ 10 % ] , p=0·11 ; nephrotoxic effects : 52 [ 43 % ] vs 60 [ 51 % ] , p=0·20 ) . INTERPRETATION Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment . This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients . FUNDING Australian National Health and Medical Research Council , Cancer Council New South Wales , Pfizer , Merck , Gilead Sciences .

Galactomannan

PCR

chemotherapy

standard diagnostic strategy

biomarker-based diagnostic strategy

aspergillus galactomannan

and

PCR

empirical treatment

with

antifungal drugs


Extra virgin olive oil ( EVOO ) consumption and antioxidant status in healthy institutionalized elderly humans . Recent studies show that the elderly have increased oxidative stress and impaired antioxidant defense systems . Our study aims to evaluate the effects of daily consumption of EVOO in the healthy institutionalized elderly . We studied anthropometric , biochemical and antioxidant parameters in 62 subjects aged 65-96 years after a 6-week daily intake of polyphenol-rich EVOO with high oleuropein derivative contents . Subjects were divided into a control group ( CG ) who maintained their dietary habits ( n=39 ) and an olive group ( OG ) who consumed EVOO as the only added fat , plus a daily dose of 50ml ( n=23 ) . We found a significant reduction of total cholesterol ( TC ) , HDL , LDL and TGs in OG subjects and a significant increase of HDL levels . There was no significant variation in the CG parameters . In OG the total antioxidant capacity ( TAC ) in plasma increased with significant differences over CG . Plasma hydroxytyrosol ( OH-Tyr ) concentration showed a significant increase after EVOO intervention . Daily consumption of EVOO was found to have positive effects on lipid profiles , OH-Tyr levels and TAC . The results also show a significant increase of catalase ( CAT ) in erythrocytes and a decrease ( p < 0.05 ) in superoxide dismutase ( SOD ) and glutathione peroxidase ( GH-PX ) activity after EVOO intake . To our knowledge , no other study has examined the effects of EVOO consumption on biochemical parameters , antioxidant capacity and antioxidant enzyme activity in healthy elderly subjects . In conclusion , our results show that nutritional intervention with EVOO improves antioxidant status in healthy elderly people .

Extra virgin olive oil ( EVOO )

EVOO

polyphenol-rich EVOO

high oleuropein derivative contents

control group

maintained their

dietary habits

olive group ( OG )

EVOO

EVOO

EVOO

EVOO

EVOO

anthropometric

biochemical

antioxidant parameters

lipid profiles

OH-Tyr levels

TAC

catalase ( CAT )

superoxide dismutase ( SOD )

biochemical parameters

antioxidant capacity

antioxidant enzyme activity

healthy

elderly

elderly

healthy

elderly

healthy

elderly


Predicting the effect of anthelmintic treatment on milk production of dairy cattle in Canada using an Ostertagia ostertagi ELISA from individual milk samples . Gastrointestinal nematodes , such as Ostertagia ostertagi and several species of Cooperia , are ubiquitous in temperate climates and have been shown to have detrimental effects on production in adult dairy cattle . A published meta-analysis demonstrated that overall , producers lose approximately 0.35 kg of milk per parasitized cow per day . Enzyme-linked immunosorbent assays ( ELISAs ) have the ability to quantify nematode infections in cattle , and thus , could be used to estimate the amount of milk production loss due to differing levels of parasitism at the individual cow level . ELISA results from individual cow milk samples were used to predict milk production response following a randomized anthelmintic treatment in a large field trial . To increase statistical power , the data collected from this field trial was pooled with data from two other published field trials to form an individual patient data meta-analysis ( IPDMA ) . The ability to predict the effect of anthelmintic treatment on milk production depends on the level of parasitism quantified by an ELISA measuring milk antibodies against O. ostertagi , and reported as optical density ratios ( ODRs ) . Therefore , the estimates from the interaction between ODR and treatment on milk production were used to determine how well the ODR predicted the response of the treatment . It was anticipated that the relationship between milk production and ODR was unlikely to be linear , so fractional polynomials were applied to the continuous ODR values . The interaction in the field trial showed a trend ( p=0.138 ) toward a beneficial treatment effect when the individual ODR values , measured in late lactation and using Svanovir ( ® ) , were greater than 0.12 . When individual data from two other similar studies were included in an IPDMA , the interaction terms became statistically significant ( p=0.009 ) indicating that there is a beneficial treatment effect when ODR values are slightly elevated . A graph was used to demonstrate the treatment effect ( the estimated difference of kg/cow/day of milk yield between the treated and placebo cows ) , with 95 % confidence intervals , as the ODR values increase . It is important to note that the methods of quantifying the ODR values differed between the three studies in the IPDMA , therefore some caution should be used when using these final estimated values . However , the shape and magnitude of the treatment effects , as well as the other fixed model estimates , were very similar between the field trial and the IPDMA suggesting that any bias would likely be minimal .

anthelmintic treatment

Enzyme-linked immunosorbent assays

milk production of dairy cattle

milk antibodies

optical density ratios ( ODRs )

milk production

ODR

ODR values

ODR values

Gastrointestinal nematodes

Ostertagia ostertagi

several species of Cooperia

adult dairy cattle


Palliative brachytherapy with or without primary stent placement in patients with oesophageal cancer , a randomised phase III trial . PURPOSE To investigate whether a combination of self-expanding metal stent ( SEMS ) and brachytherapy provided more rapid and prolonged effect on dysphagia without increased pain compared to brachytherapy alone in patients with incurable oesophageal cancer . METHODS 41 Patients were randomised to SEMS followed by brachytherapy , 8 Gy×3 ( n=21 ) or brachytherapy alone , 8 Gy×3 ( n=20 ) . Change in dysphagia and pain three and seven weeks after randomisation ( FU1 and FU2 ) was assessed by patient-reported outcome . Dysphagia , other symptoms and health-related quality of life were assessed every four weeks thereafter . The study was closed before the estimated patient-number was reached due to slow recruitment . RESULTS Patients receiving SEMS followed by brachytherapy had significantly improved dysphagia at FU1 compared to patients receiving brachytherapy alone ( n=35 ) . Difference in pain was not observed . At FU2 , patients in both arms ( n=21 ) had less dysphagia . Four patients in the combined treatment arm experienced manageable complications , no complications occurred after brachytherapy alone . CONCLUSION For the relief of dysphagia , SEMS followed by brachytherapy is preferable and safe for patients in need of immediate alleviation , while brachytherapy with or without preceding SEMS provides relief within a few weeks after treatment .

Palliative brachytherapy

with or without primary stent placement

combination of

self-expanding metal stent ( SEMS )

and brachytherapy

dysphagia

pain

dysphagia

oesophageal cancer

oesophageal cancer


[ Study of setting of ventilator volume tidal and airway pressure alarm threshold with continuous extra-sternum heart compression in cardiopulmonary resuscitation ] . OBJECTIVE To investigate the setting of ventilator volume tidal ( VT ) and airway pressure alarm threshold during cardiopulmonary resuscitation ( CPR ) by continuous extra-sternum heart compression . METHODS Forty cases with respiration and cardiac arrest in the department of critical care medicine were randomly divided into low VT ventilation group and conventional VT group . Both groups were given the volume control mode . In the low VT ventilation group , VT was set on 6 - 7 ml/kg , and high pressure alarm threshold was adjusted to 60 cm H2O by the conventional 40 cm H2O during CPR . In the conventional VT group , VT and high pressure alarm threshold were set at 8 - 12 ml/kg and 40 cm H2O , respectively . Real-time actual VT , peak inspiratory pressure ( PIP ) , and arterial blood gas test , blood lactic acid at 10 minutes and 30 minutes after CPR were observed . RESULTS At 10 minutes after CPR , in the low VT ventilation group , arterial blood pH , arterial partial pressure of oxygen ( PaO2 ) , arterial partial pressure of carbon dioxide ( PaCO2 ) , HCO3 ( - ) , arterial oxygen saturation ( SaO2 ) and blood lactic acid were better as compared with those in the conventional VT ventilation group ( pH : 7.21±0.09 vs. 7.13±0.07 , PaO2 : 45.35±5.92 mm Hg vs. 40.70±4.70 mm Hg , PaCO2 : 57.10±7.59 mm Hg vs. 61.60±5.47 mm Hg , HCO3 ( - ) : 18.50±3.50 mmol/L vs. 14.75±2.65 mmol/L , SaO2 : 0.796±0.069 vs. 0.699±0.066 , blood lactic acid : 7.07±1.60 mmol/L vs. 8.13±1.56 mmol/L , all P < 0.05 ) . The success rate of resuscitation in the low VT ventilation group was higher than that of the conventional VT ventilation group ( 45 % vs. 15 % , P < 0.05 ) , and PIP ( cm H2O ) of low VT ventilation group was lower than that of the conventional VT group ( 37.25±7.99 cm H2O vs. 42.70±7.40 cm H2O , P < 0.05 ) . In all the patients in both groups barotrauma did not occur . CONCLUSION The strategy of low ventilator VT ( 6 - 7 ml/kg ) with appropriate elevation of airway pressure alarm threshold was better than that of conventional ventilation setting , with no increase in incidence of barotraumas during CPR .

setting of ventilator volume tidal

and

airway pressure alarm threshold

ventilator volume tidal ( VT )

and

airway pressure alarm threshold

cardiopulmonary resuscitation ( CPR

low VT ventilation group

and

conventional VT group

low VT ventilation

conventional

conventional VT group

low VT ventilation

conventional VT ventilation

ventilator

cardiopulmonary resuscitation

respiration and cardiac arrest


The effects of ezetimibe/simvastatin versus simvastatin monotherapy on platelet and inflammatory biomarkers in patients with metabolic syndrome . In a randomized , double-blind , crossover study of 15 aspirin-naive patients ( mean age 48.8 ± 10.2 years ) with the metabolic syndrome , statin monotherapy ( simvastatin 40 mg daily ) was compared to combination therapy ( simvastatin 40 mg and ezetimibe 10 mg daily ) on biomarkers of inflammation and platelet activity . The addition of ezetimibe to simvastatin over a 4-week period was associated with reduced expression of CD141 ( thrombomodulin ; p = 0.02 ) , platelet endothelial cell adhesion molecule ( p < 0.0001 ) and CD51/61 ( vitronectin receptor ; p = 0.048 ) compared to statin monotherapy . Ezetimibe added to simvastatin improves several indices of platelet reactivity beyond statin monotherapy . However , the clinical relevance of these findings await results of the IMPROVE-IT trial ( Improved Reduction of Outcomes : Vytorin Efficacy International Trial ) .

ezetimibe/simvastatin

simvastatin monotherapy

aspirin-naive

platelet

inflammatory biomarkers

patients with metabolic syndrome .

15 aspirin-naive patients

mean age 48.8 ± 10.2 years

metabolic syndrome


The efficacy , safety and cost-effectiveness of hydrotalcite versus esomeprazole in on-demand therapy of NERD : A multicenter , randomized , open-label study in China . OBJECTIVE The aim of the study was to investigate whether hydrotalcite was comparable to esomeprazole , a proton pump inhibitor , in on-demand therapy for non-erosive reflux disease ( NERD ) . METHODS This was a multicenter , randomized , open-label clinical trial with initial and on-demand therapy . Patients who had complete symptom relief in the initial therapy were randomized to either hydrotalcite or esomeprazole in the on-demand therapy . The percentage of patients who quit on-demand therapy in the two groups and the cost-effectiveness of the treatment were evaluated as primary end points . The rate of symptom relief and the improvement of symptom score for initial therapy and the weekly average symptom score and weekly average number of days on treatment for on-demand therapy were evaluated as secondary end points . RESULTS In total , 398 patients were recruited in the initial therapy group , among whom 253 were included in on-demand therapy , with 127 patients in the hydrotalcite group and the remaining 126 in the esomeprazole group . 14 ( 11.0 % ) patients in the hydrotalcite group and six ( 4.8 % ) in the esomeprazole group quit the on-demand therapy due to unsatisfactory symptom control ( P = 0.065 ) . Cost-effectiveness calculated as the ratio of the cost of hydrotalcite to that of esomeprazole ( per person/day ) was 35.3 % in the on-demand therapy . Similar number of patients achieved symptom relief in both groups . CONCLUSION Hydrotalcite is a good option of on-demand therapy for NERD patients due to its cost-effectiveness and speed of action .

hydrotalcite

esomeprazole

hydrotalcite

esomeprazole

hydrotalcite

esomeprazole

hydrotalcite

esomeprazole

hydrotalcite

esomeprazole

efficacy

safety

cost-effectiveness

patients who quit

cost-effectiveness

rate of symptom relief

improvement of symptom score

weekly average number of days

quit


[ The effects of early enteral nutrition with addition of probiotics on the prognosis of patients suffering from severe acute pancreatitis ] . OBJECTIVE To investigate the curative effect of early enteral nutrition ( EN ) supplemented with probiotics ( bifidobacterium ) in patients with severe acute pancreatitis ( ASP ) . METHODS Seventy SAP cases admitted from January 2005 to October 2012 were randomly assigned into parenteral nutrition ( PN ) group ( n=22 ) , EN group ( n=25 ) and bifidobacterium added EN ( P+EN ) group ( n=23 ) . In P+EN group , patients were given their nutrition the same as that of EN , and also probiotics ( bifidobacterium , 4 capsules every 12 hours , given through nasal gastric tube , each capsule weighing 210 mg ) . The routine treatment including anti-infection and anti-acid agents , and that of inhibition of pancreatic secretion were given , except for the different nutritional interventions in all groups . The blood samples were collected for e same measurements of interleukin-8 ( IL-8 ) and tumor necrosis factor ( TNF-α ) by enzyme linked immunosorbent assay ( ELISA ) , and for the C-reactive protein ( CRP ) , lactic acid dehydrogenase ( LDH ) , white blood cell ( WBC ) count , amylase and lipase by biochemistry assay 1 day before intervention of nutrition , and 7 days and 14 days after intervention . Changes in organ function and outcome were also recorded at the same time points . RESULTS The plasma levels of IL-8 , TNF-α , CRP , LDH , WBC count , amylase and lipase were significantly reduced after nutritional intervention compared with their levels on day 1 before intervention in all three groups . The plasma IL-8 , TNF-α , CRP , lipase , LDH at 14 days after intervention of nutrition in P+EN group were significantly lower than those in PN group and EN group ( IL-8 : 21.00 ± 7.07 μg/L vs. 48.00 ± 10.32 μg/L , 32.00 ± 9.30 μg/L ; TNF-α : 44.3 ± 10.9 ng/L vs. 132.1 ± 34.1 ng/L , 67.8 ± 22.3 ng/L ; CRP : 35.0 ± 12.4 mg/L vs. 103.2 ± 49.2 mg/L , 63.0 ± 29.2 mg/L ; lipase : 269 ± 79 U/L vs. 670 ± 145 U/L , 310 ± 78 U/L ; LDH : 21.8 ± 10.3 U/L vs. 78.1 ± 37.4 U/L , 37.9 ± 25.1 U/L , P < 0.05 or P < 0.01 ) . The WBC count in P+EN group was significantly lower than that in PN group ( 5.9 ± 3.0 × 10⁹/L , 6.3 ± 3.2 × 10⁹/L vs. 9.6 ± 3.0 ×10⁹/L , both P < 0.05 ) , but there was no significant difference in amylase between P+EN group and PN group ( 211 ± 49 U/L , 236 ± 52 U/L vs. 298 ± 71 U/L , P > 0.05 ) . The gastrointestinal dysfunction score in P+EN , EN , PN groups 14 days after nutritional intervention was 0.28 ± 0.05 , 0.43 ± 0.09 , 0.71 ± 0.11 , respectively , with statistically significant differences ( all P < 0.01 ) . Compared with PN and EN groups , the incidence of upper gastrointestinal bleeding ( 1 vs. 9 , 2 ) , infection and abscess ( 2 vs. 12 , 5 ) was lower ( all P < 0.01 ) , and hospital day was significantly shortened in P+EN group ( 10.4 ± 3.9 days vs. 25.8 ± 6.4 days , 13.4 ± 5.2 days , both P < 0.01 ) . There was no significant statistical difference in mortality rate among three groups . CONCLUSION Our results indicated that early EN with addition of probiotics ( bifidobacterium ) resulted in significant lowering of the level of pro-inflammatory cytokines , earlier restoration of gastrointestinal function , decrease of complications such as infection , and shortening of hospital day in patients with SAP .

parenteral nutrition ( PN )

EN

bifidobacterium added EN ( P+EN )

P+EN

EN

probiotics ( bifidobacterium

anti-infection and anti-acid agents

plasma levels of IL-8 , TNF-α

CRP

LDH

WBC count

amylase

lipase

plasma IL-8 , TNF-α , CRP

lipase

LDH

incidence

upper gastrointestinal bleeding

severe acute pancreatitis

severe acute pancreatitis ( ASP )

Seventy