Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone : preliminary findings and a discussion of therapeutic mechanisms . OBJECTIVES Attenuation of protein kinase C ( PKC ) is a mechanism common to both established ( lithium , valproate ) and some novel ( tamoxifen ) antimanic agents . Verapamil , although primarily known as a calcium channel blocker , also has PKC inhibitory activity . Verapamil has shown antimanic activity in some but not all studies . Therefore , we investigated verapamil , used alone or as an adjunctive treatment , in manic patients who did not respond to an initial adequate trial of lithium . METHODS Each study phase lasted three weeks . Subjects were treated openly with lithium in Phase 1 ( n = 45 ) . Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil ( n = 10 ) or continued-lithium ( n = 8 ) . Phase 2 nonresponders ( n = 10 ) were assigned to combined verapamil/lithium in Phase 3 . RESULTS Response in Phase 2 did not differ significantly between verapamil and continued-lithium . During Phase 3 , response to combined treatment was significantly better than overall response to monotherapy in Phase 2 ( Fisher 's Exact test , p = 0.043 ) . Mania ratings improved during combined treatment in Phase 3 by 88.2 % ( linear mixed model analysis , F = 4.34 , p = 0.013 ) , compared with 10.5 % improvement during Phase 2 . CONCLUSIONS In this preliminary investigation , verapamil monotherapy did not demonstrate antimanic efficacy . By contrast , the combination of verapamil plus lithium was highly efficacious . Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium . This effect may be mediated by additive actions on PKC inhibition , which may be an important mechanism for antimanic agents in general .

Verapamil

lithium

lithium

( lithium , valproate )

Verapamil

Verapamil

lithium

lithium

verapamil

continued-lithium

combined verapamil/lithium

verapamil

continued-lithium

verapamil

verapamil plus lithium

verapamil

lithium

Fisher 's Exact test

Mania ratings


[ Clinical effect of transcatheter arterial chemoembolization combined with high intensity focused ultrasound ablation in treatment of large hepatocellular carcinoma ] . OBJECTIVE To investigate the clinical effect of transcatheter arterial chemoembolization ( TACE ) combined with high intensity focused ultrasound ( HIFU ) ablation in treatment of large hepatocellular carcinoma ( HCC ) . METHODS Sixty-eight patients with unresectable HCC were randomized into 2 age , tumor size , TNM stages , and liver function grade-matched groups : TACE group ( n=30 ) undergoing TACE and TACE+HIFU group ( n=38 ) undergoing 2-3 weeks after TACE . A total of 88 tumors ( 9.3+/-3.2 ) ( 5.0-14.5 ) cm in diameter were detected , and the largest tumor in a specific patients with multiple lesions was selected for observation . Follow-up was conducted for ( 13+/-7 ) ( 3-24 ) months to observe the necrosis of tumor , size of tumor , local recurrence , and survival of patient . RESULTS The clinical symptom remission rate was 90.6 % ( 29/32 ) in the TACE+HIFU group and 70.8 % ( 28/38 ) in the TACE group . The tumor necrosis and minification rates of the TACE+HIFU and TACE groups were 73.7 % and 68.4 % respectively , both significantly higher than those of TACE group ( 26.7 % and 33.3 % respectively , both P < 0.01 ) . The tumor local recurrence rate of the TACE+HIFU group was 21.1 % , not significantly different from that of the TACE group ( 33.3 % , P > 0.05 ) . The median survival duration of the TACE+HIFU group was 18 months , significantly longer than that of the TACE group ( 10 months , P < 0.05 ) . CONCLUSION Compared with the TACE therapy alone , the combination therapy improves the tumor necrosis rate and prolongs the patients ' survival duration .

2 age , tumor size , TNM stages

liver function grade-matched groups

TACE

group ( n=30 ) undergoing

TACE

TACE+HIFU

TACE+HIFU

TACE+HIFU

TACE

TACE

TACE+HIFU

TACE

TACE+HIFU

TACE

TACE

survival of patient .

clinical symptom remission rate

tumor necrosis

minification rates

tumor local recurrence rate

median survival duration

tumor necrosis rate

patients ' survival duration

large hepatocellular carcinoma ]

hepatocellular carcinoma ( HCC ) .

Sixty-eight

patients with multiple lesions


Treatment of hepatitis B virus infection with interferon . Factors predicting response to interferon . Several randomised controlled trials have been undertaken to evaluate the efficacy of alpha-interferon in the therapy of chronic hepatitis B . In patients with HBe antigen-positive disease acquired in adult life the response rates vary from 25-50 % . In those infected at birth , response rates are lower . Twenty-one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given alpha-interferon for chronic hepatitis B virus infection . In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks , a negative anti-human immunodeficiency virus antibody status ( p less than 0.001 ) , chronic active hepatitis on liver biopsy ( p less than 0.005 ) , high AST level ( p less than 0.001 ) , low hepatitis B virus DNA level ( p less than 0.001 ) and a history of acute hepatitis ( p less than 0.005 ) were all associated with an increased likelihood of response on univariate analysis . On stepwise logistic regression analysis , hepatitis B virus DNA , AST and a history of acute hepatitis predicted response independently ( p less than 0.05 ) . The most reliable combination of predictive factors was a negative anti-human immunodeficiency virus antibody status , with either a positive history of acute icteric hepatitis and AST greater than 45 IU per liter or no history of acute icteric hepatitis and AST greater than 85 IU per liter , which predicted response in 77 % with a specificity of 79 % ( p less than 0.001 ) . The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of less than 2 years duration ( p less than 0.001 ) .

interferon

interferon

alpha-interferon

alpha-interferon

response

AST level

hepatitis B virus DNA level

acute hepatitis

acute icteric hepatitis

HBsAg

HBeAg

hepatitis B virus DNA


Seven-star needle stimulation improves language and social interaction of children with autistic spectrum disorders . This is a randomized controlled trial that aimed to evaluate the effect of the Seven-star Needle Stimulation treatment on children with Autistic Spectrum Disorders ( ASD ) . Thirty-two children with ASD were assigned randomly into the treatment and control groups . Children in the treatment group underwent 30 sessions of stimulation over 6 weeks , while children in the control group were on a waiting list and did not receive treatment during this period of time . Intervention consisted of a treatment regime comprising of 30 sessions of Seven-star Needle Stimulation , delivered over 6 weeks . Each session lasted 5 to 10 min , children in the treatment group were stimulated at the front and back sides of their body and the head by using Seven-star Needles . The change in the children 's behavior was evaluated using parents ' report and neurophysiological changes were measured by quantitative EEG ( qEEG ) . Results showed that the treatment group demonstrated significant improvement in language and social interaction , but not in stereotyped behavior or motor function , compared to the control group . qEEG spectral amplitudes in the treatment , but not in the control group , were also reduced significantly . The results suggested that Seven-star Needle Stimulation might be an effective intervention to improve language and social functioning of children with ASD .

Seven-star needle stimulation

Seven-star Needle Stimulation

Seven-star Needles

Seven-star Needle Stimulation

language and social interaction

children 's behavior

language and social interaction

stereotyped behavior or motor function

qEEG spectral amplitudes

language and social functioning

children

autistic spectrum disorders

children

Autistic Spectrum Disorders ( ASD )

Thirty-two

children

ASD

children

ASD


A double-blind placebo-controlled study to evaluate valacyclovir alone and with aspirin for asymptomatic HSV-1 DNA shedding in human tears and saliva . PURPOSE To test the effect of valacyclovir alone and with aspirin on the asymptomatic shedding of HSV-1 DNA in tears and saliva of healthy individuals . METHOD . The subjects ( n = 45 ) were randomized into three groups without regard to age , sex , or race . Group 1 ( n = 14 ) received the placebo , group 2 ( n = 15 ) received a dose of 500 mg valacyclovir once daily , and group 3 ( n = 16 ) received a dose of 500 mg valacyclovir once daily and 350 mg aspirin twice daily for 30 days . Ocular and oral swabs were collected twice daily for 30 days . DNA was extracted from all swabs and HSV-1 DNA copy numbers were determined . Statistical analysis was performed to compare the DNA copy numbers of the three groups . RESULTS There was no significant difference in the HSV-1 DNA copy numbers in the tears or saliva among any of the three treatment groups . The mean copy numbers +/- SE of mean ( SEM ) of HSV-1 DNA in tears were 340 +/- 35 , 1074 +/- 320 , and 630 +/- 51 for groups 1 , 2 , and 3 , and in saliva were 238 +/- 35 , 963 +/- 462 , and 493 +/- 25 , respectively , for groups 1 , 2 , and 3 . CONCLUSIONS No correlation was found between HSV-1 shedding and valacyclovir and valacyclovir with aspirin treatment . The HSV-1 DNA copy number was not reduced by treatment with 500 mg of valacyclovir daily or with a combination of daily valacyclovir ( 500 mg ) plus twice-daily doses of aspirin ( 350 mg ) over 30 days .

placebo-controlled

valacyclovir alone

aspirin

valacyclovir alone

aspirin

placebo

500 mg valacyclovir once daily

valacyclovir

valacyclovir with aspirin

valacyclovir

valacyclovir

aspirin

HSV-1 shedding

healthy

n = 45


Enhancing the working memory of stroke patients using tDCS . OBJECTIVES We investigated whether anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex affected the working memory performance of patients after a stroke . DESIGN Ten patients ( mean age 47.7 yrs ) with cognitive deficits after a first-ever stroke participated in this single-blind , crossover , and sham-controlled experiment . Each patient was randomly assigned to undergo two transcranial direct current stimulation sessions : anodal dorsolateral prefrontal cortex and sham stimulation within 48 hrs of a washout period . All participants performed a two-back working memory task before and after the administration of the transcranial direct current stimulation . Accuracy ( correction rate ) , recognition accuracy ( correction rate-commission error rate ) , and response time were measured during each experiment . RESULTS Repeated-measures analysis of variance indicated a significant interaction effect of transcranial direct current stimulation type and time on the recognition accuracy . Post hoc analyses revealed a significant difference between prestimulation and poststimulation in the anodal stimulation group but not in the sham stimulation group . Regarding the accuracy , the paired t test indicated significant improvement only after anodal transcranial direct current stimulation without a significant interaction effect between the two transcranial direct current stimulation types . The response time was not significantly different in the anodal and sham stimulation groups . CONCLUSION Our results demonstrated that anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex was associated with enhanced working memory performance as indexed by the recognition accuracy in patients after a stroke .

tDCS

transcranial direct current stimulation

sham-controlled

transcranial direct current stimulation

transcranial direct current stimulation

transcranial direct current stimulation

working memory

working memory performance

two-back working memory task

Accuracy ( correction rate )

response time

recognition accuracy

accuracy

response time

working memory performance

stroke patients

stroke

Ten patients

mean age 47.7 yrs

stroke


A prospective comparison of transthoracic and transhiatal resection for esophageal carcinoma in Asians . BACKGROUND/AIMS Transthoracic and transhiatal esophagectomy are two common procedures for esophageal cancer resection . Prospective studies comparing the two methods in Asian people are few . In addition , the data comparing their effects on the quality of life are lacking . METHODOLOGY A prospective randomized study was conducted from January 2003 . Patients of resectable esophageal cancer of comparable stage were allocated to undergo the transthoracic or transhiatal procedure in turn . They were all reconstructed with stomach interposition through the retrosternal route . Discharged patients were followed-up in the outpatient clinic . They were questioned on the topics of ( i ) severity of pain , ( ii ) ease of swallowing , ( iii ) satisfaction of daily activities , ( iv ) dependence on medications , ( v ) working ability , ( vi ) fatigue , ( vii ) appetite , ( viii ) sociality , ( ix ) happiness and ( x ) self respect , in the third , sixth and twelfth month . Also the demographic data , operative results and survival were recorded . RESULTS Up to December 2006 , eighty-seven patients of stage II and III , including 71 patients of middle third lesions and 16 lower third lesions were enrolled . The operation time was significantly longer , and the leakage rate was higher in the transthoracic group ( Student 's t-test and Fischer 's exact test , respectively ) . However , intraoperative blood loss and postoperative hospital stay were not significantly different ( Student t-test ) . Also , the Kaplan-Meier survival curves of these two groups were not significantly different by log-rank test ( p=0.286 ) . The score on the quality of life of transhiatal patients was significantly higher than that of transthoracic patients in the third , sixth and twelfth month . CONCLUSIONS Transhiatal esophagectomy is a safe and fast procedure . The survival was similar to that of transthoracic approach . Its leakage rate was lower and quality of life was better .

transthoracic

transhiatal resection

Transthoracic

transhiatal esophagectomy

transthoracic

transhiatal procedure

Transhiatal esophagectomy

quality of life

severity of pain

ease of swallowing

satisfaction of daily activities

dependence on medications

working ability

fatigue

appetite

sociality

happiness and ( x ) self respect

demographic data , operative results

survival

operation time

leakage rate

intraoperative blood loss

postoperative hospital stay

Kaplan-Meier survival curves

quality of life

leakage rate

esophageal carcinoma in Asians .

71 patients of middle third lesions

16 lower third lesions were enrolled


A psychological intervention reduces inflammatory markers by alleviating depressive symptoms : secondary analysis of a randomized controlled trial . OBJECTIVES To test experimentally whether a psychological intervention reduces depression-related symptoms and markers of inflammation among cancer patients and to test one mechanism for the intervention effects . Depression and inflammation are common among cancer patients . Data suggest that inflammation can contribute to depressive symptoms , although the converse remains untested . METHODS As part of a randomized clinical trial , newly diagnosed breast cancer patients ( n = 45 ) with clinically significant depressive symptoms were evaluated and randomized to psychological intervention with assessment or assessment only study arms . The intervention spanned 12 months , with assessments at baseline , 4 , 8 , and 12 months . Mixed-effects modeling tested the hypothesis that the intervention reduced self-reported depressive symptoms ( Center for Epidemiological Studies Depression scale , Profile of Mood States Depression and Fatigue subscales , and Medical Outcomes Study-Short Form 36 Bodily Pain subscale ) and immune cell numbers that are elevated in the presence of inflammation ( white blood cell count , neutrophil count , and helper/suppressor ratio ) . Mediation analyses tested whether change in depressive symptoms , pain , or fatigue predicted change in white blood cell count , neutrophil count , or the helper/suppressor ratio . RESULTS The intervention reduced significantly depressive symptoms , pain , fatigue , and inflammation markers . Moreover , the intervention effect on inflammation was mediated by its effect on depressive symptoms . CONCLUSIONS This is the first experiment to test whether psychological treatment effective in reducing depressive symptoms would also reduce indicators of inflammation . Data show that the intervention reduced directly depressive symptoms and reduced indirectly inflammation . Psychological treatment may treat effectively depressive symptoms , pain , and fatigue among cancer patients .

psychological intervention

psychological intervention

inflammatory markers

depressive symptoms

depressive symptoms

self-reported depressive symptoms

immune cell numbers

change in depressive symptoms

pain

fatigue

change in white blood cell count

neutrophil count ,

helper/suppressor ratio

depressive symptoms

pain

fatigue

inflammation markers

inflammation

depressive symptoms

depressive symptoms

inflammation

depressive symptoms

pain

fatigue

cancer

cancer

breast cancer

cancer


Efficacy of prepackaged , low residual test meals with 4L polyethylene glycol versus a clear liquid diet with 4L polyethylene glycol bowel preparation : a randomized trial . BACKGROUND AND STUDY AIMS A prepackaged low residue one-day diet ( breakfast , lunch and dinner ) has been recently developed to improve patient tolerance for bowel preparation prior to colonoscopy . The aims of this study were to evaluate the efficacy and tolerability of bowel preparation protocols based on a low residue diet and 4L polyethylene glycol ( PEG ) solution , and to compare these new options with the traditional liquid diet and the PEG 4L lavage . METHODS A total of 214 patients ( mean age : 54.1 years ; 120 male , 94 female ) from four university hospitals were included in the analysis . Patients were randomized to receive a clear liquid diet and the PEG 4L regimen ( 106 patients ) or the low residue test meals and the PEG 4L regimen ( TM-PEG 4L , 108 patients ) . The colon cleansing efficacy of the different preparations was rated using the Ottawa bowel preparation scale . RESULTS No significant differences were observed between the treatment groups according to the Ottawa cleansing scale findings ( PEG 4L : 2.97 vs TM-PEG 4L : 2.46 , P = 0.063 ) . The overall tolerability was higher in the TM-PEG 4L group than in the PEG 4L group ( P = 0.036 ) . No difference was found when the two groups were compared with regard to adverse events ( P = 0.599 ) . CONCLUSIONS A prepackaged low residue one-day diet provided cleansing efficacy similar to that of a clear liquid diet and offered the benefit of improved tolerability compared to the conventional PEG 4L regimen .

low residue diet

4L polyethylene glycol ( PEG ) solution

Efficacy

patient tolerance for bowel preparation

efficacy

tolerability

colon cleansing efficacy

Ottawa bowel preparation scale

Ottawa cleansing scale

overall tolerability

adverse events

cleansing efficacy

improved tolerability


Design , implementation and results of the quality control program for the Australian government 's point of care testing in general practice trial . BACKGROUND From 2005 to 2007 the Australian Government funded a multicentre , clustered randomized controlled trial to determine the clinical effectiveness , cost-effectiveness , satisfaction and safety of point of care testing ( PoCT ) in general practice ( GP ) . PoC tests measured ( and devices used ) in the trial were haemoglobin A1c and urine albumin : creatinine ratio ( DCA 2000 ) , lipids ( Cholestech LDX ) and international normalized ratio ( CoaguChek S ) . METHODS An internal quality control ( QC ) program was developed as part of a quality management framework for the trial . PoCT device operators were provided with a colour-coded QC Result Sheet and QC Action Sheet for on-site recording and interpreting of their results . Within-practice imprecision for QC testing was calculated and compared with the analytical goals for imprecision set prior to the trial . RESULTS The average participation rate for QC testing was 91 % or greater . Median within-practice imprecision met the analytical goals for all PoC tests , except for high-density lipoprotein-cholesterol ( HDL-C ) where observed performance was outside the minimum goal for one level and one lot number of QC . Most practices achieved the imprecision goals for all analytes , with the principal exception of HDL-C . CONCLUSIONS Results from QC testing indicate that PoCT in the GP trial met the analytical goals set for the trial , with the exception of HDL-C .

colour-coded QC Result Sheet

QC Action Sheet

for

lipids ( Cholestech LDX )

Median within-practice imprecision

HDL-C


Isometric contractions reduce plantar flexor moment , Achilles tendon stiffness , and neuromuscular activity but remove the subsequent effects of stretch . The effects of isometric contractions and passive stretching on muscle-tendon mechanics and muscle activity were studied in 16 healthy human volunteers . First , peak concentric and passive ankle joint moment data were recorded on an isokinetic dynamometer with electromyographic monitoring of the triceps surae ; real-time motion analysis of the lower leg and ultrasound imaging of the Achilles-medial gastrocnemius muscle-tendon junction were simultaneously conducted . Second , the subjects performed six 8-s maximal voluntary isometric contractions ( MVICs ) before repeating the passive and active trials . Although there was no decrease in isometric joint moment after MVICs , peak concentric moment was significantly reduced ( 11.5 % , P < 0.01 ) . This was accompanied by , and correlated with ( r = 0.90 , P < 0.01 ) , significant reductions in peak triceps surae electromyographic amplitude ( 21.0 % , P < 0.01 ) . Achilles tendon stiffness ( 10.9 % , P < 0.01 ) and passive joint moment ( 4.9 % , P < 0.01 ) were also significantly reduced . Third , the subjects performed three 60-s static plantar flexor stretches before being retested 2 and 30 min after stretch . The stretch protocol caused no significant change in any measure . At 30 min after stretching , significant recovery in concentric moment and muscle activity was detected at dorsiflexed joint angles , while Achilles tendon stiffness and passive joint moment remained significantly reduced . These data show that the performance of MVICs interrupts the normal stretch-induced losses in active and passive plantar flexor joint moment and neuromuscular activity , largely because concentric strength and tendon properties were already affected . Importantly , the decrease in Achilles tendon stiffness remained 30 min later , which may be an important etiological factor for muscle-tendon strain injury risk .

Isometric contractions

isometric contractions

passive stretching

static plantar flexor stretches

isometric joint moment

peak concentric moment

Achilles tendon stiffness

passive joint moment

concentric moment and muscle activity

Achilles tendon stiffness

passive joint moment

Achilles tendon stiffness

16 healthy human volunteers .


Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer . BACKGROUND The laparoscopic treatment of rectal cancer is controversial . This study compared surgical outcomes after laparoscopic and open approaches for mid and low rectal cancers . METHODS Some 204 patients with mid and low rectal adenocarcinomas were allocated randomly to open ( 103 ) or laparoscopic ( 101 ) surgery . The surgical team was the same for both procedures . Most patients had stage II or III disease , and received neoadjuvant therapy with oral capecitabine and 50-54 Gy external beam radiotherapy . RESULTS Sphincter-preserving surgery was performed in 78.6 and 76.2 per cent of patients in the open and laparoscopic groups respectively . Blood loss was significantly greater for open surgery ( P < 0.001 ) and operating time was significantly greater for laparoscopic surgery ( P = 0.020 ) , and return to diet and hospital stay were longer for open surgery . Complication rates , and involvement of circumferential and radial margins were similar for both procedures , but the number of isolated lymph nodes was greater in the laparoscopic group ( mean 13.63 versus 11.57 ; P = 0.026 ) . There were no differences in local recurrence , disease-free or overall survival . CONCLUSION Laparoscopic surgery for rectal cancer has a similar complication rate to open surgery , with less blood loss , rapid intestinal recovery , shorter hospital stay , and no compromise of oncological outcomes .

laparoscopic

open surgery

laparoscopic treatment

laparoscopic

open

laparoscopic ( 101 ) surgery

neoadjuvant therapy

oral capecitabine and

50-54 Gy external beam radiotherapy

Sphincter-preserving surgery

open

open surgery

laparoscopic surgery

open surgery

laparoscopic

Laparoscopic surgery

open surgery

Blood loss

operating time

hospital stay

blood loss

intestinal recovery

hospital stay

oncological outcomes .

rectal cancer

mid and low rectal adenocarcinomas


A prospective randomized trial of topical pimecrolimus for cetuximab-associated acnelike eruption . BACKGROUND Clinical trials addressing the acneiform rash associated with epidermal growth factor receptor inhibitors are lacking . OBJECTIVE We evaluated the ability of topical pimecrolimus to reduce the severity of cetuximab-related facial rash . METHODS In all , 24 patients with metastatic colorectal cancer with cetuximab facial rash received twice daily pimecrolimus application for 5 weeks to half of the face . At baseline , week 2 , and week 5 , a dermatologist performed facial lesion counts , patients reported perceived severity of rash-related symptoms , and standardized facial photographs were obtained for blinded evaluation of global rash severity . RESULTS Treatment sides had greater decrease in lesion counts than observation sides of face at weeks 2 ( P < .001 ) and 5 ( P = .02 ) . However , there were no significant differences in patients ' assessment of symptoms and in review of facial photographs for rash severity between treatment and observation sides . LIMITATIONS This study was not placebo controlled . CONCLUSIONS Pimecrolimus application did not translate into clinically meaningful benefit for patients with cetuximab-related facial rash .

pimecrolimus

pimecrolimus

pimecrolimus

Pimecrolimus

lesion counts

rash severity

cetuximab-associated acnelike eruption

cetuximab-related facial rash .

cetuximab-related facial rash


Prognostic value of postoperative CEA clearance in rectal cancer patients with high preoperative CEA levels . PURPOSE We determined the prognostic value of carcinoembryonic antigen ( CEA ) clearance after tumor resection with serial evaluation of postoperative CEA levels in rectal cancer . METHODS Between 1994 and 2004 , we retrospectively reviewed 122 patients with rectal cancer whose serum CEA levels were measured on the preoperative day and postoperative days 7 and 30 . Patients with preoperative CEA levels < 5.0 ng/ml were excluded . An exponential trend line was drawn using the three CEA values . Patients were categorized into three groups based on R ( 2 ) values calculated through trend line , which indicates the correlation coefficient between exponential graph and measured CEA values : exponential decrease group ( group 1 : 0.9 < R ( 2 ) < or = 1.0 ) , nearly exponential decrease group ( group 2 : 0.5 < R ( 2 ) < or = 0.9 ) , and randomized clearance group ( group 3 : 0.5 < or = R ( 2 ) ) . We then analyzed the CEA clearance pattern as a prognostic indicator . RESULTS With a median follow-up of 57 months , the 5-year overall survival was 62.3 % vs. 48.1 % vs. 25 % and the 5-year disease-free survival was 58.6 % vs. 52.7 % vs. 25 % among groups 1 , 2 , and 3 ( P = 0.014 , P = 0.027 , respectively ) in patients with stage III rectal cancer . For those with stage II rectal cancer , the 5-year overall survival rate of group 1 was significantly better than groups 2 and 3 ( 88.8 % vs. 74.1 % , respectively , P = 0.021 ) . CONCLUSIONS The postoperative pattern of CEA clearance is a useful prognostic determinant in patients with rectal cancer . Patients with a randomized pattern of CEA clearance after tumor resection should be regarded as having the possibility of a persistent CEA source and may require consideration of intensive follow-up or adjuvant therapy .

postoperative CEA clearance

tumor resection

postoperative pattern of CEA clearance

serum CEA levels

CEA values

5-year overall survival

5-year disease-free survival

5-year overall survival rate

CEA clearance


Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis . BACKGROUND & AIMS Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels , probably because of a combined effect of norfloxacin on bowel flora and neutrophils . METHODS Thirty-one patients with cirrhosis receiving norfloxacin ( 400 mg/day ) were included . Blood samples were collected at 0.5-4 hours ( peak samples group , n = 47 ) and at 22-24 hours ( trough samples group , n = 84 ) after dose . Fifty-nine ascitic fluid samples were obtained . Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients , respectively , ( temporal profile group ) and samples were collected at 0 , 0.5 , 1 , 1.5 , 2 , 4 , and 24 hours . Norfloxacin , trimethoprim/sulfamethoxazole , cytokines , nitric oxide , expression levels of nuclear factor ( NF ) -kappaB and inhibitor of NF-kappaB ( IkB-alpha ) , neutrophil oxidative burst , and rate of apoptotic events were determined . RESULTS All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide . Serum and ascitic levels of tumor necrosis factor-alpha , interferon-gamma , interleukin-12 , and nitric oxide were significantly lower in peak than in trough samples . A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha ( r = -0.68 ; P < .001 ) , interferon-gamma ( r = -0.66 ; P < .001 ) , interleukin-12 ( r = -0.66 ; P < .001 ) , and nitric oxide ( r = -0.68 ; P < .001 ) . Serum norfloxacin 's highest concentrations ( 1 +/- 0.5 microg/mL ) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide . Intracellular norfloxacin 's highest levels ( 2 +/- 1 microg/mL/10 ( 7 ) cells ) were observed at 2 hours and concurred with a lower NF-kappaB expression , a reduced anion superoxide generation , and apoptotic rate in response to phorbol myristate acetate . Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression . CONCLUSIONS Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis .

Norfloxacin

norfloxacin

norfloxacin

norfloxacin

norfloxacin

trimethoprim/sulfamethoxazole

Norfloxacin

trimethoprim/sulfamethoxazole

cytokines

nitric oxide

norfloxacins

interferon-gamma

nitric oxide

Trimethoprim/sulfamethoxazole

Norfloxacin

trimethoprim/sulfamethoxazole

nitric oxide

interferon-gamma

nitric oxide

cytokines and nitric oxide

cytokine expression

decompensated cirrhosis

cirrhosis

Thirty-one

cirrhosis

cirrhosis


Preliminary evaluation of psychoeducational support interventions on quality of life in rural breast cancer survivors after primary treatment . Although most cancer survivors are at risk for being lost in the transition from treatment to survivorship , rural breast cancer survivors face special challenges that might place them at particular risk . This small-scale preliminary study had 2 specific aims : ( aim 1 ) establish the feasibility of rural breast cancer survivors participation in a longitudinal quality of life ( QOL ) intervention trial and ( aim 2 ) determine the effects of the Breast Cancer Education Intervention ( BCEI ) on overall QOL . Fifty-three rural breast cancer survivors were randomized to either an experimental ( n = 27 ) or a wait-control arm ( n = 26 ) . Participants in the experimental arm received the BCEI consisting of 3 face-to-face education and support sessions and 2 face-to-face and 3 telephone follow-up sessions , along with supplemental written and audiotape materials over a 6-month period . Breast Cancer Education Intervention modules and interventions are organized within a QOL framework . To address the possible effects of attention , wait-control participants received 3 face-to-face sessions and 3 telephone sessions during the first 6 months of participation in the study , but not the BCEI intervention . Research questions addressing aim 1 were as follows : ( a ) can rural breast cancer survivors be recruited into a longitudinal intervention trial , and ( b ) can their participation be retained . Research questions for aim 2 were as follows : ( a ) do participants who received the BCEI show improvement in overall QOL , and ( b ) is the QOL improvement sustained over time . Data were analyzed using repeated-measures general linear mixed models . Results demonstrated the ability to recruit and retain 53 rural breast cancer survivors , that the experimental arm showed improvement in overall QOL ( P = .013 ) , and that there were significant differences in overall QOL between the experimental and wait-control groups at both months 3 and 6 . Thus , it appears that at least some rural breast cancer survivors can and will participate in a larger trial and will maintain their participation and that those that do participate experience significant QOL benefit .

psychoeducational support interventions

telephone follow-up sessions

BCEI intervention

quality of life

quality of life ( QOL )

overall QOL .

overall QOL

breast cancer

Fifty-three


Ultrasonographic tissue characterisation of human Achilles tendons : quantification of tendon structure through a novel non-invasive approach . OBJECTIVE To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation ( UTC ) can differentiate between symptomatic and asymptomatic tendons . DESIGN Case-control study . SETTING Sports Medical Department of the Hague Medical Centre . PATIENTS Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included . The " matched " control group consisted of 26 asymptomatic tendons . INTERVENTIONS Symptomatic and asymptomatic tendons were scanned using the UTC procedure . One researcher performed the ultrasonographic data collection . These blinded data were randomised , and outcome measures were determined by two independent observers . MAIN OUTCOME MEASUREMENTS The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echo patterns , qua intensity and distribution over contiguous transverse images . This three-dimensional stability was related to tendon structure in previous studies . UTC categorises four different echotypes that represent ( I ) highly stable ; ( II ) medium stable ; ( III ) highly variable and ( IV ) constantly low intensity and variable distribution . The percentages of echo-types were calculated , and the maximum tendon thickness was measured . Finally , the inter-observer reliability of UTC was determined . RESULTS Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons ( 51.5 % vs 76.6 % , p < 0.001 ) , thus less three-dimensional stability of the echo pattern . The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group ( p < 0.001 ) . The Intraclass Correlation Coefficient ( ICC ) for the interobserver reliability of determining the echo-types I+II was 0.95 . The ICC for tendon thickness was 0.84 . CONCLUSION UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons . As such , UTC might be useful to monitor treatment protocols .

three-dimensional imaging

of the Achilles tendon by

scanned using the UTC procedure

ultrasonographic data collection

UTC

UTC

UTC procedure

qua intensity

echotypes

highly stable

medium stable

highly variable

constantly low

echo-types

tendon thickness

echo pattern

tendon thickness

Intraclass Correlation Coefficient

tendon thickness

Twenty-six

tendons

asymptomatic tendons


Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia : a multicenter phase III trial ( SAKK 32/98 ) . Daily administration of 2-chlorodeoxyadenosine ( Cladribine , CDA ) is a standard treatment for hairy cell leukemia , but may cause severe neutropenia and neutropenic fever . This trial compared toxicity and efficacy of weekly versus daily CDA administration . One hundred patients were randomized to receive standard ( CDA 0.14 mg/kg/day day 1-5 [ Arm A ] ) or experimental treatment ( CDA 0.14 mg/kg/day once weekly for 5 weeks [ Arm B ] ) . The primary endpoint was average leukocyte count within 6 weeks from randomization . Secondary endpoints included response rates , other acute hematotoxicity , acute infection rate , hospital admission , remission duration , event-free , and overall survival . There was no significant difference in average leukocyte count . Response rate ( complete + partial remission ) at week 10 was 78 % ( 95 % confidence interval ( CI ) 64-88 % ) in Arm A and 68 % ( 95 % CI 54-80 % ) in Arm B ( p = 0.13 ) . Best response rates during follow-up were identical ( 86 % ) in both arms . No significant difference was found in the rate of grade 3+4 leukocytopenia ( 94 % vs . 84 % ) , grade 3+4 neutropenia ( 90 % vs . 80 % ) , acute infection ( 44 % vs . 40 % ) , hospitalization ( 38 % vs . 34 % ) , and erythrocyte support ( 22 % vs . 30 % ) within 10 weeks . Overall , these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily .

Cladribine , CDA

CDA

CDA

CDA

CDA

neutropenia and neutropenic fever

average leukocyte count

response rates

other acute hematotoxicity

acute infection rate

hospital admission

remission duration

event-free , and overall survival

leukocyte count

Response rate

response rates

grade 3+4 leukocytopenia

grade 3+4 neutropenia

acute infection

hospitalization

erythrocyte support

toxicity and efficacy


Sustained benefit of continuous glucose monitoring on A1C , glucose profiles , and hypoglycemia in adults with type 1 diabetes . OBJECTIVE To evaluate long-term effects of continuous glucose monitoring ( CGM ) in intensively treated adults with type 1 diabetes . RESEARCH DESIGN AND METHODS We studied 83 of 86 individuals > or=25 years of age with type 1 diabetes who used CGM as part of a 6-month randomized clinical trial in a subsequent 6-month extension study . RESULTS After 12 months , median CGM use was 6.8 days per week . Mean change in A1C level from baseline to 12 months was -0.4 +/- 0.6 % ( P < 0.001 ) in subjects with baseline A1C > or=7.0 % . A1C remained stable at 6.4 % in those with baseline A1C < 7.0 % . The incidence rate of severe hypoglycemia was 21.8 and 7.1 events per 100 person-years in the first and last 6 months , respectively . Time per day with glucose levels in the range of 71-180 mg/dl increased significantly ( P = 0.02 ) from baseline to 12 months . CONCLUSIONS In intensively treated adults with type 1 diabetes , CGM use and benefit can be sustained for 12 months .

continuous glucose monitoring ( CGM )

Mean change in A1C level

incidence rate of severe hypoglycemia

Time per day with glucose levels

adults

type 1 diabetes

intensively treated adults

type 1 diabetes

adults

type 1 diabetes


Clinical effects of nanocrystalline hydroxyapatite paste in the treatment of intrabony periodontal defects : a randomized controlled clinical study . The purpose of the present randomized controlled clinical study was to compare the clinical outcomes of papilla preservation flap surgery with or without the application of a novel nanocrystalline hydroxyapatite ( nano-HA ) bone graft substitute . Fourteen patients with paired intrabony periodontal defects of ≥ 4 mm participated in this split-mouth design study . The defects in each subject were randomly selected to receive nano-HA paste in conjunction with papilla preservation flaps or papilla preservation flaps alone . Probing bone levels ( PBL ) from a customized acrylic stent and probing pocket depths ( PPD ) were measured at baseline and again 6 months following surgery . No differences in any of the investigated parameters were observed at baseline between the two groups . Healing was uneventful in all patients . Both treatments resulted in significant improvements between baseline and 6 months ( p < 0.05 ) . At 6 months after therapy , the sites treated with nano-HA paste showed a reduction in mean PPD from 8.3 ± 1.2 to 4.0 ± 1.1 mm and a gain in PBL of 4.3 ± 1.4 mm , whereas in the control group , the mean PPD changed from 7.9 ± 1.2 mm to 5.0 ± 1.2 mm and PBL gain was 2.6 ± 1.4 mm . Results demonstrated statistically greater PPD reduction and PBL gain ( p < 0.05 ) in the test group as compared with the control group . In conclusion , after 6 months , the treatment of intrabony periodontal defects with a nano-HA paste leads to significantly improved clinical outcomes when compared with papilla preservation flap surgery alone .

nanocrystalline hydroxyapatite paste

Probing bone levels ( PBL )

probing pocket depths ( PPD )

Healing

in mean PPD

mean

PPD reduction

PBL


Clinical trial of tooth whitening with 6 % hydrogen peroxide whitening strips and two whitening dentifrices . PURPOSE To compare tooth whitening with 6 % hydrogen peroxide whitening strips and two whitening dentifrices in a 12-week randomized controlled trial at a Belgian dental school . METHODS After informed consent , 46 healthy adults were randomly assigned to one of three strip + dentifrice treatment groups . Subjects received either 6 % hydrogen peroxide whitening strips ( Crest Whitestrips ) and an anticavity toothpaste ( Crest Cavity Protection ) , placebo strips and a sodium fluoride ( NaF ) whitening dentifrice ( Mentadent Whitening Toothpaste ) or placebo strips and a sodium monofluorophosphate ( MFP ) whitening dentifrice ( Rembrandt Low Abrasion Whitening Toothpaste ) . Strip use ( peroxide or placebo ) was for 30 minutes , twice daily for 2 weeks , while dentifrice use was at least twice daily for 12 weeks . Efficacy was measured from standardized digital images of the maxillary facial tooth surfaces , while safety was evaluated from oral examination and interview . Treatments were compared after 2 weeks ( strip use ) and 12 weeks ( dentifrice use ) using analysis of covariance . RESULTS All subjects completed the 12-week evaluation . Adjusting for baseline and age , the peroxide strip group had -2.45 Deltab* , 2.39 DeltaL* , and -0.96 Deltaa* at Week 2 . Between-group comparisons demonstrated significant ( P < 0.0001 ) reductions in yellowness and redness , and increased brightness favoring the peroxide strip group . The peroxide strip group demonstrated 95 % + color retention ( Deltab* & DeltaL* ) at Week 12 , differing significantly ( P < 0.0001 ) versus either of the continuously used whitening dentifrices . There were no significant ( P > 0.18 ) differences between the whitening dentifrice groups at any timepoints . All treatments were well-tolerated , with minor tooth sensitivity and oral irritation representing the most common findings .

hydrogen peroxide

whitening strips

whitening dentifrices .

hydrogen peroxide whitening strips

whitening dentifrices

strip

dentifrice

anticavity toothpaste

placebo strips

placebo strips

peroxide

placebo

peroxide strip

whitening dentifrices

tooth whitening

tooth whitening

Efficacy

yellowness and redness

brightness favoring

color retention

well-tolerated

minor tooth sensitivity

oral irritation

adults


A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus . BACKGROUND In a recent open pilot trial , R-salbutamol sulphate , a well-known molecule with anti-inflammatory effects , was tested successfully on patients with therapy-resistant discoid lupus erythematosus ( DLE ) . OBJECTIVES To compare the efficacy and safety of R-salbutamol cream 0.5 % vs. placebo on DLE lesions in a multicentre , double-blinded , randomized , placebo-controlled phase II trial . METHODS Thirty-seven patients with at least one newly developed DLE lesion were randomized - 19 to the R-salbutamol cream 0.5 % and 18 to placebo - and treated twice daily for 8 weeks . Efficacy was evaluated through scores of erythema , scaling/hypertrophy and induration as well as pain and itching ; general improvement scored by the investigator and global improvement scored by patients ' assessment were also evaluated . RESULTS The mean area under the curve of improvement for scaling/hypertrophy , pain , itching and global patient assessment was significantly better for the actively treated patients as compared with placebo ( scaling/hypertrophy , P = 0.0262 ; pain , P = 0.0238 ; itching , P = 0.0135 ; global patient assessment , P = 0.045 ) . Moreover , the percentage of patients without induration was significantly higher in the active group compared with the placebo group ( P = 0.013 ) , and a statistically significantly greater decrease in the size of the lesional area was also seen in the overall analysis of the R-salbutamol-treated patients ( P = 0.0197 ) . No serious adverse events were reported . CONCLUSIONS Application of R-salbutamol cream 0.5 % was safe and well tolerated . Statistically significant effects were seen on scaling/hypertrophy , induration , pain and itching as well as patient global assessment , suggesting that R-salbutamol could be a promising new topical therapy alternative for DLE .

R-salbutamol

R-salbutamol sulphate

R-salbutamol cream

placebo

19 to the R-salbutamol cream 0.5 %

placebo

placebo

Efficacy

scores of erythema

scaling/hypertrophy and induration

pain and

itching

general improvement

scaling/hypertrophy

pain

global patient assessment

induration

size of the lesional area

serious adverse events

discoid lupus erythematosus .


Long-term ( 96-week ) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial . BACKGROUND The toxicities , cost and complexity of triple combinations warrant the search for other treatment options , such as boosted protease inhibitor ( PI ) monotherapy . MONotherapy AntiRetroviral Kaletra ( MONARK ) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients . METHODS A total of 136 antiretroviral-naïve patients , with a CD4 cell count above 100 cells/microL and a plasma HIV RNA below 100,000 HIV-1 RNA copies/mL , were randomized and dosed with either lopinavir/ritonavir monotherapy ( n = 83 ) or lopinavir/ritonavir + zidovudine/lamivudine ( n = 53 ) . We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96 . The intent-to-treat ( ITT ) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy ( n = 83 ) , and then focused on patients who had an HIV RNA < 50 copies/mL at week 48 ( n = 56 ) . RESULTS At week 96 , 39 of 83 patients ( 47 % ) had HIV RNA < 50 copies/mL , five of 83 had HIV RNA between 50 and 400 copies/mL , and three of 83 had HIV RNA > 400 copies/mL . Focusing on the 56 patients with an HIV RNA < 50 copies/mL at week 48 , 38 of 56 patients ( 68 % ) had a sustained HIV RNA < 50 copies/mL to week 96 . To week 96 , a total of 28 patients ( 34 % ) had discontinued the study treatment . In addition , the allocated treatment was changed for seven patients . PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96 . CONCLUSION By ITT analysis , 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA < 50 copies/mL at week 96 . The occurrence in some patients of low-level viraemia ( 50-500 copies/mL ) may increase the risk of drug resistance . First-line lopinavir/ritonavir monotherapy can not be systematically recommended .

monotherapy

either lopinavir/ritonavir monotherapy

HIV RNA

HIV RNA

patients

HIV-infected


Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding : a randomized , controlled trial . BACKGROUND The objective was to evaluate efficacy and safety of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding . STUDY DESIGN AND METHODS In a randomized , controlled trial , 477 women with anemia , iron deficiency , and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose ( < or=1000 mg over 15 min , repeated weekly to achieve a total calculated replacement dose ) or 325 mg of ferrous sulfate ( 65 mg elemental iron ) prescribed orally thrice daily for 6 weeks . RESULTS Compared to those assigned to ferrous sulfate , more patients assigned to ferric carboxymaltose responded with a hemoglobin ( Hb ) increase of 2.0 g/dL or more ( 82 % vs. 62 % , 95 % confidence interval for treatment difference 12.2-28.3 , p < 0.001 ) , more achieved a 3.0 g/dL or more increase ( 53 % vs. 36 % , p < 0.001 ) , and more achieved correction ( Hb > or= 12 g/dL ) of anemia ( 73 % vs. 50 % , p < 0.001 ) . Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue ( p < 0.05 ) . There were no serious adverse drug events . CONCLUSIONS In patients with iron deficiency anemia due to heavy uterine bleeding , rapid IV administration of large doses of a new iron agent , ferric carboxymaltose , is more effective than oral iron therapy in correcting anemia , replenishing iron stores , and improving quality of life .

ferric carboxymaltose injection

oral iron

IV ferric carboxymaltose

of ferrous sulfate

ferrous sulfate

ferric carboxymaltose

ferric carboxymaltose

ferrous sulfate

new iron agent , ferric carboxymaltose

oral iron therapy

hemoglobin ( Hb )

correction

vitality and physical function

serious adverse drug events

correcting anemia

replenishing iron stores

improving quality of life

anemia

uterine bleeding

women


Assessment of elementary school students ' sun protection behaviors . BACKGROUND/OBJECTIVES Studies suggest that excessive sun exposure in childhood contributes to the development of skin cancer later in life . METHODS This study explores 4th grade student assessment of their sun protection behaviors . This study used baseline data collected in the Fall of 2006 for the Sun Protection for Florida 's Children ( SPF ) project . In brief , the SPF project is a group randomized trial to test the effectiveness of a school based intervention promoting sun protection in general , and hat use in particular , in Hillsborough County Schools , Florida . The data reported in this study were collected at baseline before any intervention activities was initiated . RESULTS The self-reported use of various methods of sun protection was low . Only a small percentage of students wore long sleeves or a hat with a brim before leaving for school . In addition , few students wore a hat with a wide brim when outside but not at school . Students spent an average of 59.1 minutes per week outdoors while attending school and 35.5 minutes during peak sun exposure . CONCLUSION Sun exposure at school poses a significant risk to student health and more needs to be carried out to promote the use of a wide-brimmed hat and limiting student sun exposure .

sun protection

long sleeves

hat with a brim

hat with a wide brim

wide-brimmed hat

sun protection behaviors .

long sleeves or a hat with a brim

hat with a wide brim when outside

peak sun exposure .

student sun exposure .

elementary school

4th grade


A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer : quality of life outcomes . BACKGROUND A recent randomized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease-specific survival . We report on the quality of life ( QOL ) outcomes for this trial . METHODS From December 1997 through February 2003 , 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT ( median dose 68 Gy ) . All patients received neoadjuvant antiandrogen therapy . Patients completed the EORTC QLQ C30 and the Prostate Cancer Index ( PCI ) before treatment and at 1.5 , 3 , 6 , 12 , 18 , 24 , and 36 months post-treatment . RESULTS Regardless of treatment arm , participants reported high levels of QOL with few exceptions . cryoablation was associated with more acute urinary dysfunction ( mean PCI urinary function cryoablation=69.4 ; mean EBRT=90.7 ; P < .001 ) , which resolved over time . No late arising QOL issues were observed . Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning ( mean cryoablation=7.2 : mean EBRT=32.9 ; P < .001 ) . Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13 % more of the cryoablation men said that sexuality was a moderate or big problem . CONCLUSIONS In this randomized trial , no long-term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation . Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation .

external beam radiotherapy

cryoablation

external beam EBRT

cryoablation

EBRT

neoadjuvant antiandrogen

EBRT

cryoablation

cryoablation

cryoablation

cryoablation

EBRT

cryoablation

quality of life ( QOL )

QOL

acute urinary dysfunction

No late arising QOL issues

decreases in sexual function

Mean sexual function score

QOL

sexual function

sexual function

localized prostate cancer

244 men

localized prostate cancer


Aspirin-associated iron loss as an anticancer mechanism . A consensus view has emerged favoring an anticancer effect of long-term aspirin use . Aspirin-induced loss of stored iron from chronic gastrointestinal bleeding is proposed as a mechanism underlying this beneficial effect . In iron depletion , less iron may be available for carcinogenesis through free-radical mediated mechanisms and for promotion of tumor growth . Low-dose aspirin increases gastrointestinal losses of transfused radiolabeled autologous red cells . Observational studies report lower serum ferritin values with regular aspirin use . A protective effect of induced iron reduction against cancer mortality has been confirmed in a recent trial ( FeAST ) with subjects randomized to iron reduction or observation . Serum ferritin reductions in the FeAST trial were within conventionally normal reference ranges and were quantitatively similar to ferritin reductions in observational studies in regular aspirin users . Delayed anticancer effects of aspirin are compatible with the proposed mechanism , as continual microbleeding has a gradual cumulative effect on stored iron .

Aspirin-induced

Low-dose aspirin

gastrointestinal losses

Serum ferritin reductions

microbleeding

Aspirin-associated iron loss

anticancer

regular aspirin users


Depiction of hypervascular hepatocellular carcinoma with 64-MDCT : comparison of moderate- and high-concentration contrast material with and without saline flush . OBJECTIVE The purpose of this study was to evaluate prospectively the depiction of hypervascular hepatocellular carcinoma on 64-MDCT scans obtained with contrast agents of varying iodine concentrations administered with and without saline flush . SUBJECTS AND METHODS The study included 149 patients , among whom 36 patients with hypervascular hepatocellular carcinoma were identified . Patients were randomly assigned to one of three protocols : A , contrast material of 300 mg I/mL ; B , 370 mg I/mL ; C , 370 mg I/mL plus saline flush . In all protocols , the same iodine load per kilogram of body weight ( 516 mg/kg ) was administered for the same injection duration ( 30 seconds ) . Enhancement values in the aorta , liver , and portal vein and tumor-liver contrast were measured at multiphase CT . RESULTS Aortic enhancement was significantly different between protocols A and B ( p = 0.04 , p < 0.0001 ) and protocols B and C ( p = 0.02 , p < 0.001 ) in the first and second phases . Portal venous enhancement was significantly different between protocols B and C ( p = 0.02 ) in the first phase and between protocols B and C and protocols A and C ( p < 0.01 , p = 0.02 ) in the second phase . Tumor-liver contrast was significantly different between protocols A and B ( p = 0.03 , p = 0.02 ) and protocols B and C ( p = 0.03 , p = 0.04 ) in the first and second phases but not between protocols A and C. There was no significant difference in hepatic enhancement among the three protocols . CONCLUSION Use of moderate concentration was more effective than use of a high concentration of contrast material for depiction of hepatocellular carcinoma . Adding a saline flush to the high-concentration protocol eliminated the difference in depiction of hepatocellular carcinoma between the moderate- and high-concentration protocols .

contrast agents

iodine concentrations

saline flush

high-concentration protocol

Aortic enhancement

Portal venous enhancement

Tumor-liver contrast

hepatic enhancement

depiction of hepatocellular carcinoma

hypervascular hepatocellular carcinoma

149 patients

36 patients

hypervascular hepatocellular carcinoma


Enamel and dentin bond strength following gaseous ozone application . PURPOSE To evaluate the effects of gaseous ozone application on enamel and dentin bond strength produced by two self-etching adhesive systems . MATERIALS AND METHODS The shear bond strength test was conducted to assess adhesion on enamel ( protocol 1 ) , while the microtensile bond strength test was performed on dentin ( protocol 2 ) . Protocol 1 : 96 bovine incisors were randomly divided into 4 groups , and enamel surfaces were bonded in accordance with the following treatments : ( 1E ) ozone + Clearfil Protect Bond ; ( 2E ) Clearfil Protect Bond ( control ) ; ( 3E ) ozone + Xeno III ; ( 4E ) Xeno III ( control ) . Ozone gas was applied for 80 s. Shear bond strength was measured with a universal testing machine . Protocol 2 : 40 noncarious human molars were selected . Middle/deep dentin was exposed and bonded in accordance with the following treatments : ( 1D ) ozone+Clearfil Protect Bond ; ( 2D ) Clearfil Protect Bond ( control ) ; ( 3D ) ozone+Xeno III ( 4D ) Xeno III ( control ) . Four-mm-thick buildups were built on the adhesives , then specimens were sectioned in accordance with the nontrimming technique . Specimens were stressed until failure occurred , and failure modes were analyzed . Shear bond and microtensile bond strength data were analyzed using two-way ANOVA and Tukey 's post-hoc test . RESULTS No statistical differences were found between ozone treated specimens and controls , neither on enamel nor on dentin irrespective of the tested adhesive . Clearfil Protect Bond showed higher bond strength to enamel than Xeno III , irrespective of the ozone treatment ( p < 0.05 ) . CONCLUSION The use of ozone gas to disinfect the cavity before placing a restoration had no influence on immediate enamel and dentin bond strength .

gaseous ozone application

gaseous ozone application

( 1E ) ozone

ozone + Xeno III

Xeno III ( control )

Ozone gas

( 1D ) ozone+Clearfil Protect Bond

( 2D ) Clearfil Protect Bond ( control

Xeno III

ozone treatment

ozone gas

enamel

dentin

bond strength


Effects of digoxin on muscle reflexes in normal humans . Blockade of the skeletal muscle Na ( + ) -K ( + ) -ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise , which in turn could stimulate the mechano- and metaboreceptors . In a randomized , double-blinded , placebo-controlled , and cross-over-design study , we measured mean blood pressure ( MBP ) , heart rate ( HR ) , ventilation ( V ( E ) ) , oxygen saturation ( SpO ( 2 ) ) , muscle sympathetic nerve activity ( MSNA ) , venous plasma potassium and lactic acid during dynamic handgrip exercises , and local circulatory arrest in 11 healthy subjects . Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR , V ( E ) , SpO ( 2 ) , and MSNA . Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na ( + ) -K ( + ) -ATPase blockade . We conclude that digoxin increased MBP during dynamic exercise in healthy humans , independently of changes in potassium and lactic acid . A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms , independent of muscle reflexes and related to the inotropic effects of digoxin , might be implicated .

digoxin

digoxin

Digoxin

digoxin-induced

digoxin

digoxin

11 healthy subjects

healthy humans


Randomized , placebo-controlled , crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders . OBJECTIVE The aim of this study was to investigate the short-term efficacy and safety of methylphenidate ( MPH ) to treat attention-deficit/hyperactivity disorder ( ADHD ) symptoms in an understudied population of preschoolers with pervasive developmental disorder ( PDD ) or intellectual disability ( ID ) . METHODS Fourteen preschoolers with developmental disorders ( DD , n = 14 ; PDD , n = 12 ; ID , n = 2 ) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase . Each child was administered placebo for 2 weeks and " optimal dose " for 2 weeks . The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders , 4 ( th ) edition ( DSM-IV ) ADHD subscale of the Conners ' Parent Rating Scale-Revised ( CPRS-R-DSM-IV-ADHD ) . RESULTS MPH improved parent-rated ADHD symptoms of the preschoolers ; 50 % were rated as responders . The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup ( p = 0.005 , Cohen d = 0.97 ) and marginally significant for the entire DD sample ( p = 0.08 , Cohen d = 0.50 ) . Half of the preschoolers experienced side effects with MPH , including reports of increased stereotypic behavior , upset stomach , sleep-related difficulties , and emotional lability . One child discontinued during titration due to side effects . CONCLUSION The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH , even though the response was more subtle and variable than in older and typically developing children . Due to high rates of adverse effects , preschoolers should be monitored closely .

placebo-controlled

methylphenidate

methylphenidate ( MPH )

MPH titration

placebo

optimal dose

MPH

MPH

MPH

efficacy

parent-rated ADHD symptoms

CPRS-R-DSM-IV-ADHD subscale

side effects

preschoolers


Pharmacokinetic-pharmacodynamic modelling of the antihistaminic ( H1 ) effect of bilastine . OBJECTIVE To model the pharmacokinetic and pharmacodynamic relationship of bilastine , a new histamine H ( 1 ) receptor antagonist , from single- and multiple-dose studies in healthy adult subjects . METHODS The pharmacokinetic model was developed from different single-dose and multiple-dose studies . In the single-dose studies , a total of 183 subjects received oral doses of bilastine 2.5 , 5 , 10 , 20 , 50 , 100 , 120 , 160 , 200 and 220 mg . In the multiple-dose studies , 127 healthy subjects received bilastine 10 , 20 , 40 , 50 , 80 , 100 , 140 or 200 mg/day as multiple doses during a 4- , 7- or 14-day period . The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1 . Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination . For the pharmacodynamic analysis , the inhibitory effect of bilastine ( inhibition of histamine-induced wheal and flare ) was assessed on a preselected time schedule , and the predicted typical pharmacokinetic profile ( based on the pharmacokinetic model previously developed ) was used . An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations . Finally , once values of the concentration that produced 50 % inhibition ( IC ( 50 ) ) had been estimated for wheal and flare effects , simulations were carried out to predict plasma concentrations for the doses of bilastine 5 , 10 and 20 mg at steady state ( 72-96 hours ) . RESULTS A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied . Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase ( first-order absorption rate constant = 1.50 h ( -1 ) ) , plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours or later . Concerning the selected pharmacodynamic model to fit the data ( type I indirect response model ) , this selection is attributable to the presence of inhibitory bilastine plasma concentrations that decrease the input response function , i.e . the production of the skin reaction . This model resulted in the best fit of wheal and flare data . The estimates ( with relative standard errors expressed in percentages in parentheses ) of the apparent zero-order rate constant for flare or wheal spontaneous appearance ( k ( in ) ) , the first-order rate constant for flare or wheal disappearance ( k ( out ) ) and bilastine IC ( 50 ) values were 0.44 ng/mL/h ( 14.60 % ) , 1.09 h ( -1 ) ( 15.14 % ) and 5.15 ng/mL ( 16.16 % ) , respectively , for wheal inhibition , and 11.10 ng/mL/h ( 8.48 % ) , 1.03 h ( -1 ) ( 8.35 % ) and 1.25 ng/mL ( 14.56 % ) , respectively , for flare inhibition . The simulation results revealed that bilastine plasma concentrations do not remain over the IC ( 50 ) value throughout the inter-dose period for doses of 5 and 10 mg . However , with a dose of 20 mg of bilastine administered every 24 hours , plasma concentrations remained over the IC ( 50 ) value during the considered period for the flare effect , and up to 20 hours for the wheal effect . CONCLUSION Pharmacokinetic and pharmacodynamic relationships of bilastine were reliably described with the use of an indirect response pharmacodynamic model ; this led to an accurate prediction of the pharmacodynamic activity of bilastine .

bilastine

bilastine

bilastine

bilastine

bilastine

bilastine

bilastine

bilastine

bilastine

pharmacokinetic

pharmacodynamic

pharmacokinetic profile

concentration-time data

Plasma concentrations

typical pharmacokinetic profile

pharmacodynamic relationships

bilastine plasma concentrations

plasma concentrations

plasma peak concentrations

maximal response

input response function

wheal spontaneous appearance

first-order rate constant for flare

wheal disappearance

bilastine IC

bilastine plasma concentrations

plasma concentrations

healthy

adult

healthy


Qigong massage treatment for sensory and self-regulation problems in young children with autism : a randomized controlled trial . Autism is commonly associated with sensory and self-regulatory disturbances . This article presents a randomized controlled study evaluating the effect of a 5-month intervention directed toward improving sensory impairment , digestion , and sleep in 46 children with autism < age 6 . The intervention , Qigong Sensory Training ( QST ) , is a qigong massage intervention based in Chinese medicine . It is two-pronged : Trainers work with children directly 20 times over 5 months , and parents give the massage daily to their children . Improvement was evaluated in two settings -- preschool and home -- by teachers ( blind to group ) and parents . Teacher evaluations showed that treated children had significant classroom improvement of social and language skills and reduction in autistic behavior compared with wait-list control participants . These findings were confirmed by parent data , indicating that the gains had generalized across contexts . A model and supporting data for understanding and treating sensory and self-regulation problems in autism is presented .

Qigong massage treatment

Qigong Sensory Training ( QST )

qigong massage intervention

sensory and self-regulation problems

sensory impairment

digestion

sleep

social and language skills

reduction in autistic behavior

gains

sensory and self-regulation problems

young children

autism

children

autism

age 6


Arterial cardiovascular risk factors and venous thrombosis : results from a population-based , prospective study ( the HUNT 2 ) . BACKGROUND An explanation for the increased risk of myocardial infarction and stroke in patients with venous thrombosis is lacking . The objective of this study was to investigate whether risk factors for arterial cardiovascular disease also increase the risk of venous thrombosis . DESIGN AND METHODS Cases who had a first venous thrombosis ( n=515 ) and matched controls ( n=1,505 ) were identified from a population-based , nested , case-cohort study ( the HUNT 2 study ) comprising 71 % ( n=66,140 ) of the adult residents of Nord-Trøndelag County in Norway . RESULTS The age- and sex-adjusted odds ratio of venous thrombosis for subjects with concentrations of C-reactive protein in the highest quintile was 1.6 ( 95 % confidence interval : 1.2-2.2 ) compared to subjects with C-reactive protein in the lowest quintile . This association was strongest in subjects who experienced venous thrombosis within a year after blood sampling with a three-fold increased risk of participants in the highest versus the lowest quintile . Having first degree relatives who had a myocardial infarction before the age of 60 years was positively associated with venous thrombosis compared to not having a positive family history [ odds ratio 1.3 ( 95 % confidence interval : 1.1-1.6 ) ] . Subjects with blood pressure in the highest quintile had half the risk of developing venous thrombosis compared to subjects whose blood pressure was in the lowest quintile . There were no associations between the risk of venous thrombosis and total cholesterol , low density lipoprotein-cholesterol , high density lipoprotein-cholesterol , triglycerides , glucose or smoking . We confirmed the positive association between obesity and venous thrombosis . CONCLUSIONS C-reactive protein and a family history of myocardial infarction were positively associated with subsequent venous thrombosis . Blood pressure was inversely correlated to venous thrombosis . These findings should be confirmed by further investigations .

patients with venous thrombosis


Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcome in unselected cases of mild male factor infertility : a prospective double-blind randomized crossover study . OBJECTIVES To evaluate the effect of sperm treatment with exogenous platelet-activating factor ( PAF ) on intrauterine insemination ( IUI ) clinical pregnancy rate in cases of mild male factor infertility . PAF is a phospholipid mediator , which is present in human sperm . METHODS The study was performed in the Assisted Reproduction Unit of the 2nd Department of Obstetrics and Gynecology , University of Athens , Aretaieion Hospital , Athens , Greece , and included 92 couples who presented with mild male factor infertility-all candidates for IUI . A maximum of 4 IUI cycles per couple with or without exogenous PAF treatment were performed and the main outcome measure was the clinical pregnancy rate ( pregnancies confirmed by ultrasonography per 100 cycles ) . RESULTS The overall clinical pregnancy rate after a maximum of 4 IUI cycles was comparable in cases with and without sperm treatment with PAF ( 12.24 % vs 11.11 % ) . Addition or exclusion of PAF sperm treatment in the same patients did not significantly alter the outcome . CONCLUSIONS The generalized use of exogenous PAF for the preparation of sperm in unselected cases of mild male infertility does not improve the clinical outcome of IUI .

platelet-activating factor

intrauterine insemination

intrauterine insemination ( IUI )

IUI

exogenous PAF treatment

IUI

sperm treatment with PAF

PAF sperm treatment

exogenous PAF

effect

clinical pregnancy rate

overall clinical pregnancy rate


A comparison of a spiritually based and non-spiritually based educational intervention for informed decision making for prostate cancer screening among church-attending African-American men . INTRODUCTION Health communication interventions have been modestly effective for increasing informed decision making for prostate cancer screening among African-American men ; however , knowledge and informed decision making is still questionable even with screening . Church-based programs may be more effective if they are spiritually based in nature . OBJECTIVE The aims of the present study were to implement and provide an initial evaluation of a spiritually based prostate cancer screening informed decision making intervention for African-American men who attend church , and determine its efficacy for increasing informed decision making . DESIGN AND METHOD Churches were randomized to receive either the spiritually based or the non-spiritual intervention . Trained community health advisors , who were African-American male church members , led an educational session and distributed educational print materials . Participants completed baseline and immediate follow-up surveys to assess the intervention impact on study outcomes . RESULTS The spiritually based intervention appeared to be more effective in areas such as knowledge , and men read more of their materials in the spiritually based group than in the non-spiritual group . CONCLUSIONS Further examination of the efficacy of the spiritually based approach to health communication is warranted .

Health communication interventions

educational session

materials

efficacy

men

men

men


Weekly docetaxel with or without gemcitabine as second-line chemotherapy in paclitaxel-pretreated patients with metastatic breast cancer : a randomized phase II study conducted by the Hellenic Co-Operative Oncology Group . OBJECTIVE A randomized phase II trial was conducted to test whether the addition of gemcitabine to weekly docetaxel could improve the objective response rate and survival outcomes as second-line chemotherapy in patients with metastatic breast cancer who have failed a paclitaxel-containing regimen . METHODS Patients were randomized to receive either weekly docetaxel 40 mg/m ( 2 ) ( group A , n = 34 ) or the combination of weekly docetaxel 35 mg/m ( 2 ) with gemcitabine 600 mg/m ( 2 ) ( group B , n = 41 ) . Three consecutive weekly infusions followed by a 1-week rest period represented 1 chemotherapy cycle . RESULTS The objective response rate was 18 % and 27.5 % in group A and B , respectively ( p = 0.413 ) . No statistically significant differences were demonstrated in terms of median overall survival and time to disease progression . The rate and grade 3 and 4 neutropenia were higher in group B ( 23 vs. 3 % ) . CONCLUSIONS The weekly administration of docetaxel and gemcitabine did not result in superior clinical outcomes over weekly docetaxel .

docetaxel

gemcitabine

second-line chemotherapy

paclitaxel-pretreated

gemcitabine

docetaxel

paclitaxel-containing

docetaxel 40 mg/m ( 2 )

chemotherapy

docetaxel

gemcitabine

objective response rate

survival outcomes

objective response rate

median overall survival

time to disease progression

rate and grade 3 and 4 neutropenia

clinical outcomes

paclitaxel-pretreated patients

metastatic breast cancer

metastatic breast cancer

failed a paclitaxel-containing regimen


Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo university ( ALPS-J ) . PURPOSE Many trials have shown that calcium channel blockers ( CCBs ) can reduce the cardiovascular ( CV ) events in patients with coronary artery disease ( CAD ) . The mechanisms of this effect could be associated with plaque regression due to the anti-atherosclerotic properties of CCBs . The goal of this study is to determine the effects of CCB on volumetric quantitative changes of coronary plaques accessed by intravascular ultrasound ( IVUS ) . To confirm this hypothesis , a multicenter randomized trial of CCBs treatment with azelnidipine or amlodipine will be conducted in hypertensive CAD patients undergoing elective percutaneous coronary intervention ( PCI ) . METHODS AND RESULTS Patients who have hypertension and are scheduled for PCI will be enrolled . Subjects will be randomized to azelnidipine or amlodipine and observed for 48 weeks . The primary endpoint will be the percent change of coronary plaque volume . The secondary endpoint will include inflammatory markers , antioxidant activity , and incidence of composite cardiovascular events . CONCLUSIONS In this study , we will investigate the improvement of coronary plaque with IVUS by treatment with two dihydropyridine CCBs in hypertensive patients undergoing elective PCI . This result will lead to the discovery of more effective drug therapy for inhibition of coronary events .

Azelnidipine

amlodipine

azelnidipine

amlodipine

azelnidipine

amlodipine

cardiovascular ( CV ) events

coronary plaque

coronary events


Nizatidine versus ranitidine in the treatment of peptic ulcer disease : report on the Dutch investigation as part of a European multicentre trial . The efficacy and safety of nizatidine was evaluated in comparison with ranitidine in 230 patients with endoscopically documented gastric ( 71 ) or duodenal ( 159 ) ulcers . Gastric ulcer patients who satisfied all criteria for inclusion and exclusion were randomly allocated to nizatidine 300 mg nocte , 150 mg b.d . or ranitidine 150 mg b.d. , duodenal ulcer patients to nizatidine 300 mg nocte or ranitidine 300 mg nocte . Endoscopic healing was defined as complete epithelialisation of all mucosal lesions . Endoscopy was performed at 4 and , if not healed , at 8 weeks . Healing rates were shown to be comparable for all treatment regimens . In both duodenal ulcer treatment groups , and with both drugs , healing was negatively influenced by ulcer size , ulcer number , smoking habits and a disease duration of 5 years or more . Few side effects were noted . Nizatidine , administered as a 300 mg nocte and as a 150 mg b.d . dose appeared to be a safe H2 antagonist and was as effective as ranitidine in the treatment of duodenal and gastric ulceration .

Nizatidine

ranitidine

nizatidine

ranitidine

Nizatidine

ranitidine

efficacy and safety

Endoscopic healing

Healing rates

healing

ulcer size

ulcer number

smoking habits

disease duration

Few side effects

effective

gastric

duodenal

ulcers

Gastric ulcer

duodenal and gastric ulceration .


Double-blind placebo-controlled trial of pentoxifylline added to risperidone : effects on aberrant behavior in children with autism . BACKGROUND There are several lines of evidence to indicate that the immune system plays an important role in the pathophysiology of autism . The objective of this study was to access the effects of pentoxifylline plus risperidone in the treatment of autistic disorder . METHODS Forty children between the ages 4 and 12 years with a DSM IV-TR clinical diagnosis of autism were recruited . The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder . Patients were randomly allocated to pentoxifylline+risperidone or placebo+risperidone for a 10-week , double-blind , placebo-controlled study . The dose of risperidone was titrated up to 3 mg/day , pentoxifylline was titrated to 600 mg/day . Patients were assessed at baseline and after 2 , 4 , 6 , 8 and 10 weeks of starting medication . The measure of the outcome was the Aberrant Behavior Checklist-Community ( ABC-C ) . RESULTS The difference between the two protocols was significant as the group that received pentoxifylline had greater reduction in ABC-C subscale scores for Irritability , Lethargy/Social Withdrawal , Stereotypic Behavior , Hyperactivity/Noncompliance and Inappropriate Speech . CONCLUSION The results suggest that combination of atypical antipsychotic medications and pentoxifylline might have synergistic effects in treatment of behavioral problems of children with autism .

pentoxifylline added to risperidone

pentoxifylline plus risperidone

pentoxifylline+risperidone

placebo+risperidone

risperidone

pentoxifylline

pentoxifylline

treatment of autistic disorder

children

autism

Forty

children

ages 4 and 12 years

autism

children

autistic disorder

children

autism


Cost-effectiveness of a telephone-delivered intervention for physical activity and diet . BACKGROUND Given escalating rates of chronic disease , broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed . The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet , targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined . METHODOLOGY/PRINCIPAL FINDINGS A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a " Usual Care " ( brief intervention ) alternative . Economic outcomes were assessed using a state-transition Markov model , which predicted the progress of participants through five health states relating to physical activity and dietary improvement , for ten years after recruitment . The costs and health benefits of Telephone Counselling , Usual Care and an existing practice ( Real Control ) group were compared . Telephone Counselling compared to Usual Care was not cost-effective ( $ 78,489 per quality adjusted life year gained ) . However , the Usual Care group did not represent existing practice and is not a useful comparator for decision making . Comparing Telephone Counselling outcomes to existing practice ( Real Control ) , the intervention was found to be cost-effective ( $ 29,375 per quality adjusted life year gained ) . Usual Care ( brief intervention ) compared to existing practice ( Real Control ) was also cost-effective ( $ 12,153 per quality adjusted life year gained ) . CONCLUSIONS/SIGNIFICANCE This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice ( Real Control ) is likely to be cost-effective . Choosing the 'Usual Care ' brief intervention over existing practice ( Real Control ) shows a lower cost per quality adjusted life year , but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers . The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile . TRIAL REGISTRATION This paper uses data collected in a previous clinical trial registered at the Australian Clinical Trials Registry , Australian New Zealand Clinical Trials Registry : Anzcrt.org.au ACTRN012607000195459 .

Telephone Counselling intervention

Telephone Counselling

, Usual Care and an

existing practice ( Real Control )

Telephone Counselling

Usual Care

Usual Care

Telephone Counselling

existing practice ( Real Control )

'Usual Care ' brief intervention

Cost-effectiveness

cost-effectiveness

Economic outcomes

costs and health benefits

Telephone Counselling

cost-effective

cost-effective

cost-effective

cost-effective

physical activity and diet .

adults

established chronic diseases


Phase III , randomised , multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer . This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer ( mRCC ) . Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1 , 3 and 5 , and then every 3 months until the first documented disease progression ( arm A , suspension ) , or the same regimen , with chronic maintenance of immunotherapy , regardless of tumour response , until death or intolerable toxicity ( arm B , maintenance ) . The primary endpoint was overall survival ( OS ) ; secondary endpoints were time from first progression to death ( TFPTD ) and tolerability . One hundred and eighty-three patients were enrolled between January 1998 and November 2003 . After a median follow-up of 53.9 months , response rate , median OS and median TFPTD were 14.7 % ( 6.3 % CR ) versus 11.3 % ( 5.5 % CR ) , 14 versus 14 months , 6 versus 5 months , in arms A and B , respectively with no significant differences between the groups . Cox regression analysis showed that the use of chemotherapy after first progression ( HR 0.54 ; 95 % CI 0.35-0.86 ; p = 0.008 ) , PS = 0 ( HR 0.53 ; 95 % CI 0.35-0.81 ; p = 0.001 ) and female gender ( HR 0.63 ; 95 % CI 0.41-0.98 ; p = 0.038 ) were significantly associated with a longer TFPTD ; treatment arm was not significant ( HR 0.88 ; 95 % CI 0.60-1.31 ; p = 0.54 ) . Toxicity was mainly limited to WHO grades 1 or 2 . Chronic maintenance immunotherapy after disease progression is feasible , but does not significantly increase OS or the TFPTD .

immunotherapy

interferon-alpha

subcutaneous low doses IL-2 + IFN

chemotherapy

Chronic maintenance immunotherapy

overall survival ( OS ) ;

tolerability

response rate

median OS

median TFPTD

TFPTD

Toxicity

OS

TFPTD

metastatic renal cell cancer

metastatic renal cell cancer


Prospective randomised multicentre trial with the birth trainer EPI-NO for the prevention of perineal trauma . BACKGROUND In several non-randomised trials training with EPI-NO increased the rate of intact perineum and decreased episiotomy rates , shortened the second stage of labour and lowered use of pain killers . AIMS To verify the preliminary results with EPI-NO in a prospective randomised trial . METHODS Randomised , single-blind multicentre trial in four university hospitals in Germany including 276 primigravidae . RESULTS After training with EPI-NO we observed a significant increase in the incidence of intact perineum ( 37.4 % vs 25.7 % ; P = 0.05 ) and a tendency towards lower episiotomy rates ( 41.9 % vs 50.5 % ; P = 0.11 ) . We found no significant differences between the two groups regarding incidence of perineal tears , duration of second stage of labour , use of pain relief and rate of vaginal infection . CONCLUSIONS Training with EPI-NO increases significantly the likelihood of having an intact perineum and reduces the episiotomy rate .

birth trainer EPI-NO

EPI-NO

EPI-NO

EPI-NO

EPI-NO

perineal trauma

incidence of intact perineum

lower episiotomy rates

incidence of perineal tears

duration of second stage of labour

use of pain relief

rate of vaginal infection

having an intact perineum

episiotomy rate

perineal trauma .

single-blind


Design of the DEFINE trial : determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib . BACKGROUND Residual cardiovascular ( CV ) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol ( LDL-C ) . New therapies to raise high-density lipoprotein cholesterol ( HDL-C ) are currently being investigated . Anacetrapib is a cholesteryl ester transfer protein ( CETP ) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin . Adverse effects on blood pressure , electrolytes , and aldosterone levels , seen with another drug in this class , have not been noted in studies of anacetrapib to date . METHODS Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib ( DEFINE ) is a randomized , double-blind , placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease ( CHD ) or CHD risk equivalents ( clinical trials.gov NCT00685776 ) . Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin , with or without other lipid-modifying medications , are treated with anacetrapib , 100 mg , or placebo for 18 months , followed by a 3-month , poststudy follow-up . The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib . Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points , including blood pressure and electrolytes . A preplanned Bayesian analysis will be performed to interpret the CV event distribution , given the limited number of events expected in this study . RESULTS A total of 2,757 patients were screened at 153 centers in 20 countries , and 1,623 patients were randomized into the trial . Lipid results , clinical CV events , and safety outcomes from this trial are anticipated in 2010 .

AnacEtrapib

Anacetrapib

anacetrapib

AnacEtrapib

placebo-controlled

anacetrapib

anacetrapib

placebo

anacetrapib

EFficacy and tolerability

LDL-C

efficacy and safety profile

LDL-C

baseline in LDL-C

safety and tolerability

blood pressure

electrolytes

Lipid results

clinical CV events

safety outcomes


A good response to oil with medium- and long-chain fatty acids in body fat and blood lipid profiles of male hypertriglyceridemic subjects . A double blind clinical trial was carried out to clarify the effects of oil with medium- and long-chain triglyceride ( MLCT ) on body fat and blood lipid profiles in hypertriglyceridemic subjects . One-hundred-and-twelve subjects were enrolled and divided into two groups ; those that consumed MLCT oil and those that consumed long-chain triglyceride ( LCT ) oil for 8 weeks . All subjects were requested to consume 25-30 g of the oils daily and maintain a fixed level of energy intake and exercise . Anthropometric and blood biochemical parameters were measured when the study was initiated and completed . The LCT group consisted of 50 subjects ( 34 men and 16 women ) , while the MLCT group consisted of 51 subjects ( 33 men and 18 women ) who completed the study . Larger decreases in body weight , body mass index , waist circumference , body fat , total fat area and subcutaneous fat area in the abdomen and serum triglycerides , low-density lipoprotein cholesterol , apolipoprotein B , C2 , C3 and E were observed in male subjects in the MLCT group than those in the LCT group . However , no significant differences in these parameters between the female subjects in the two groups were observed . Data from this study indicate that consumption of medium-and long-chain triglycerides can reduce body weight and body fat and improve blood lipid profiles in male hypertriglyceridemic subjects .

LCT

MLCT

MLCT

LCT

body fat

blood lipid profiles

body fat

blood lipid profiles

body weight

body fat

blood lipid

male

hypertriglyceridemic

hypertriglyceridemic

One-hundred-and-twelve

men

women

men

women

hypertriglyceridemic


The experience of pleasure before and after hearing rehabilitation . Hearing loss may lead to major changes in the social and emotional aspects of daily life . This follow-up study investigated the effect of hearing-aid use on emotional experience in adults with hearing impairment . Thirteen individuals with impaired hearing were tested before and after 6 months of hearing-aid use , and were compared with 19 individuals who had worn hearing aids for many years . The participants reported their daily emotional experiences , by completing questionnaires relating to sensory and social pleasure . After 6 months of hearing-aid use , individuals experienced more physical and social pleasure , whereas individuals using hearing aids for long periods of time reported similar levels of pleasure at the beginning and at the end of a 6-month interval . The participants also performed a visual task , in which they rated the intensity of pleasure they experienced in response to emotionally positive and neutral pictures differing in luminance contrast . In this task , pleasure typically decreases with decreasing contrast of the positive images displayed . Once they had been fitted with hearing aids , the participants reported lower levels of pleasure , especially at low contrast . These findings highlight that the anhedonia scales provide a measure sensitive to emotional improvements that accompany the partial restoration of hearing function , although these scales were not specifically designed for hearing-impaired populations . In contrast , the surprising decrease in pleasure ratings for pictures after the introduction of hearing-aid use may be because of the compensation of hearing loss by changes in visual attention functions .

hearing rehabilitation

hearing-aid

hearing-aid use

daily emotional experiences

physical and social pleasure

levels of pleasure

anhedonia scales

hearing rehabilitation

Hearing loss

adults

hearing impairment .

Thirteen

impaired hearing

6 months of hearing-aid use

worn hearing aids


A placebo-controlled , fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder . OBJECTIVE To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . METHOD Two hundred eighteen children and adolescents ( aged 6-17 years ) with a diagnosis of autistic disorder , and with behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these symptoms , were randomized 1:1:1:1 to aripiprazole ( 5 , 10 , or 15 mg/day ) or placebo in this 8-week double-blind , randomized , placebo-controlled , parallel-group study . Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale ( primary efficacy measure ) and the clinician-rated Clinical Global Impressions-Improvement score . Safety and tolerability were also assessed . RESULTS At week 8 , all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores ( 5 mg/day , -12.4 ; 10 mg/day , -13.2 ; 15 mg/day , -14.4 ; versus placebo , -8.4 ; all p < .05 ) . All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8 . Discontinuation rates due to adverse events were as follows : placebo 7.7 % , aripiprazole 5 mg/day 9.4 % , 10 mg/day 13.6 % , and 15 mg/day 7.4 % . The most common adverse event leading to discontinuation was sedation . There were two serious adverse events : presyncope ( 5 mg/day ) and aggression ( 10 mg/day ) . At week 8 , mean weight change ( last observation carried forward ) was as follows : placebo +0.3 kg , aripiprazole 5 mg/day +1.3 kg , 10 mg/day +1.3 kg , and 15 mg/day +1.5 kg ; all p < .05 versus placebo . CONCLUSIONS Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder .

placebo-controlled

aripiprazole

aripiprazole

aripiprazole

aripiprazole

aripiprazole

placebo

aripiprazole

placebo

Aripiprazole

efficacy

safety

Efficacy

Safety and tolerability

improvement

adverse events

adverse event

serious adverse events

presyncope

aggression

weight change

efficacious

safe

well tolerated

children

adolescents

irritability

autistic disorder

children

adolescents

autistic disorder

Two hundred eighteen

children

adolescents

6-17 years

autistic disorder

tantrums

aggression , self-injurious behavior ,

children

adolescents

irritability

autistic disorder .


Eye movements affirm : automatic overt gaze and arrow cueing for typical adults and adults with autism spectrum disorder . People with autism spectrum disorder ( ASD ) show reduced interest towards social aspects of the environment and a lesser tendency to follow other people 's gaze in the real world . However , most studies have shown that people with ASD do respond to eye-gaze cues in experimental paradigms , though it is possible that this behaviour is based on an atypical strategy . We tested this possibility in adults with ASD using a cueing task combined with eye-movement recording . Both eye gaze and arrow pointing distractors resulted in overt cueing effects , both in terms of increased saccadic reaction times , and in proportions of saccades executed to the cued direction instead of to the target , for both participant groups . Our results confirm previous reports that eye gaze cues as well as arrow cues result in automatic orienting of overt attention . Moreover , since there were no group differences between arrow and eye gaze cues , we conclude that overt attentional orienting in ASD , at least in response to centrally presented schematic directional distractors , is typical .

cueing task

combined with eye-movement recording

automatic overt gaze

and

arrow cueing

tendency

follow other people 's gaze

overt cueing effects

increased

saccadic reaction times

automatic orienting of overt attention

overt attentional orienting

adults and adults

people with ASD

adults

ASD