Anti-angiogenic effects of epigallocatechin-3-gallate in human skin . Epigallocatechin-3-gallate ( EGCG ) is the main polyphenol component of green tea . This compound exhibits antioxidant , immunomodulatory , photoprotective , anti-angiogenic , and anti-inflammatory properties . We conducted a small randomized , double blind , split face trial using a cream containing 2.5 % w/w of EGCG . Four healthy volunteers with significant erythema and telangiectasia on the face applied EGCG cream to one side of the face , and vehicle control cream to the other , twice daily for six weeks . After six weeks , biopsies were taken from EGCG and vehicle treated sites . Immunohistochemistry was used to measure VEGF and HIF-1 α. HIF-1 α expression was decreased in EGCG treated sites , such that 28.4 % of the epidermis showed positive staining in vehicle treated vs. 13.8 % in EGCG treated sites ( p < 0.001 ) . A similar decrease in VEGF expression was found ( 6.7 % in EGCG vs. 11.0 % in in vehicle-treated skin ( p < 0.005 ) . EGCG topical treatments influence HIF-1 α induction and VEGF expression and may serve as a potential agent in the prevention of telangiectasias .

Epigallocatechin-3-gallate ( EGCG )

cream containing 2.5 % w/w of EGCG .

EGCG cream

vehicle control cream

EGCG

vehicle treated

Anti-angiogenic effects

antioxidant

immunomodulatory

photoprotective

anti-angiogenic

anti-inflammatory properties

biopsies

Four

healthy


Green banana-supplemented diet in the home management of acute and prolonged diarrhoea in children : a community-based trial in rural Bangladesh . SUMMARY OBJECTIVE To determine the effectiveness of green banana in the home management of acute ( < 7 days ) or prolonged ( ≥ 7 days ) diarrhoea at the community level . METHODS A cluster randomized field trial was conducted among 2968 Bangladeshi rural children 6-36 months old . Wards ( villages ) were randomly assigned to either a standard care group or a standard care plus green banana group where mothers were instructed to add cooked green banana to the diets of diarrhoeal children . Through a village-based surveillance system , diarrhoeal morbidity data ( severity , duration , compliance ) were collected for 14 days . Treatment effects were determined by analysing cumulative probability of cure by testing Cox proportional hazards models and relative risk ( RR ) . RESULTS The cumulative probability of cure was significantly ( P < 0.001 ) different in children receiving GB for both acute [ hazard ratio ( HR ) = 0.63 ( 95 % CI : 0.56-0.67 ) ] and prolonged diarrhoea [ HR = 0.38 ( 95 % CI : 0.26-0.59 ) ] . The recovery rates of children with acute diarrhoea receiving GB ( vs. control ) were significantly more by day 3 : 79.9 % vs . 53.3 % [ ( RR ) = 0.47 , 95 % CI : 0.41-0.55 ] , ( P < 0.001 ) and day 7 : 96.6 % vs . 89.1 % ( RR = 0.32 ; 0.22-0.46 ) , ( P < 0.001 ) . Children with prolonged diarrhoea receiving green banana had significantly higher recovery rates by day 10 : 79.8 % vs . 51.9 % ( RR = 0.42 ; 0.23-0.73 ) , ( P < 0.001 ) and day 14 : 93.6 % vs . 67.2 % ( RR = 0.22 ; 0.08-0.54 ) , ( P < 0.001 ) . CONCLUSION A green banana-supplemented diet hastened recovery of acute and prolonged childhood diarrhoea managed at home in rural Bangladesh .

Green banana-supplemented diet

green banana

acute

prolonged

acute and prolonged diarrhoea

children

6-36 months old


A web-based patient activation intervention to improve hypertension care : study design and baseline characteristics in the web hypertension study . BACKGROUND Despite the known health risks of hypertension , many hypertensive patients still have uncontrolled blood pressure . Clinical inertia , the tendency of physicians not to intensify treatment , is a common barrier in controlling chronic diseases . This trial is aimed at determining the impact of activating patients to ask providers to make changes to their care through tailored feedback . METHODS Diagnosed hypertensive patients were enrolled in this RCT and randomized to one of two study groups : ( 1 ) the intervention condition -- Web-based hypertension feedback , based on the individual patient 's self-report of health variables and previous BP measurements , to prompt them to ask questions during their next physician 's visit about hypertension care ( 2 ) the control condition -- Web-based preventive health feedback , based on the individual 's self-report of receiving preventive care ( e.g. , pap testing ) , to prompt them to ask questions during their next physician 's visit about preventive care . The primary outcome of the study is change in blood pressure and change in the percentage of patients in each group with controlled blood pressure . CONCLUSION Five hundred participants were enrolled and baseline characteristics include a mean age of 60.0 years ; 57.6 % female ; and 77.6 % white . Overall 37.7 % participants had uncontrolled blood pressure ; the mean body mass index ( BMI ) was in the obese range ( 32.4 ) and 21.8 % had diabetes . By activating patients to become involved in their own care , we believe the addition of the web-based intervention will improve blood pressure control compared to a control group who receive web-based preventive messages unrelated to hypertension .

the control condition -- Web-based

preventive health feedback

preventive care

change in blood pressure

blood pressure control

hypertensive

hypertensive

Five hundred

60.0 years

female

uncontrolled blood pressure

diabetes


Effect of a synthetic appeasing pheromone on behavioral , neuroendocrine , immune , and acute-phase perioperative stress responses in dogs . OBJECTIVE To study the effects of a synthetic , dog-appeasing pheromone ( sDAP ) on the behavioral , neuroendocrine , immune , and acute-phase perioperative stress responses in dogs undergoing elective orchiectomy or ovariohysterectomy . DESIGN Randomized , controlled clinical trial . ANIMALS 46 dogs housed in animal shelters and undergoing elective orchiectomy or ovariohysterectomy . PROCEDURES Intensive care unit cages were sprayed with sDAP solution or sham treated with the carrier used in the solution 20 minutes prior to use . Dogs ( n = 24 and 22 in the sDAP and sham treatment exposure groups , respectively ) were placed in treated cages for 30 minutes before and after surgery . Indicators of stress ( ie , alterations in behavioral , neuroendocrine , immune , and acute-phase responses ) were evaluated perioperatively . Behavioral response variables , salivary cortisol concentration , WBC count , and serum concentrations of glucose , prolactin , haptoglobin , and C-reactive protein were analyzed . RESULTS Behavioral response variables and serum prolactin concentration were influenced by sDAP exposure . Dogs exposed to sDAP were more likely to have alertness and visual exploration behaviors after surgery than were dogs exposed to sham treatment . Decreases in serum prolactin concentrations in response to perioperative stress were significantly smaller in dogs exposed to sDAP , compared with findings in dogs exposed to the sham treatment . Variables examined to evaluate the hypothalamic-pituitary-adrenal axis , immune system , and acute-phase responses were unaffected by treatment . CONCLUSIONS AND CLINICAL RELEVANCE sDAP appeared to affect behavioral and neuroendocrine perioperative stress responses by modification of lactotropic axis activity . Use of sDAP in a clinical setting may improve the recovery and welfare of dogs undergoing surgery .

synthetic appeasing pheromone

sDAP solution

sham treated with the carrier

sDAP

sham treatment

sDAP

Behavioral response variables

serum prolactin concentration

serum prolactin concentrations

recovery

46 dogs


Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF . A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH ( rFSH ) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection . This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150μg corifollitropin alfa versus daily 200IU rFSH in 1509 patients . Comparative analyses were performed on serum concentrations of FSH immunoreactivity ( pharmacokinetics ) , and the number and size of growing follicles , and inhibin B and oestradiol concentrations as biomarkers of ovarian response ( pharmacodynamics ) . The rate of follicular development was similar in both treatment groups . By stimulation day 8 , 33 % of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin ( HCG ) injection . The number of follicles ⩾11mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 ( difference , 1.2 ; 95 % confidence interval ( CI ) 0.5-1.8 ; P < 0.01 ) and on the day of HCG injection ( difference , 2.1 ; 95 % CI 1.4-2.8 ; P < 0.01 ) . The rise of inhibin B and oestradiol concentrations was similar in both treatment groups . Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar . A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH ( rFSH ) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection . The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH . A total of 1509 patients were randomized in a double-blind , controlled trial to either a single injection of 150μg corifollitropin alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation . Serum levels of FSH immunoreactivity were analysed ( pharmacokinetic analysis ) , together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response ( pharmacodynamic analysis ) . Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards , when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached . Corifollitropin alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH . It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar .

corifollitropin alfa

recombinant FSH

corifollitropin alfa

recombinant FSH ( rFSH )

rate of follicular development

number of follicles ⩾11mm

rise of inhibin B

oestradiol concentrations

Serum FSH immunoreactivity levels

ovarian stimulation for IVF .


Maternal dietary counseling in the first year of life is associated with a higher healthy eating index in childhood . Food preferences are established in early childhood and track later in life . Therefore , it is important to promote healthy feeding practices as early as possible . A randomized field trial was conducted with 500 mother-child pairs from a low-income area of São Leopoldo , State of Rio Grande do Sul , Brazil , to evaluate the impact of a nutritional intervention in the first year of life on the dietary quality of 3- to 4-y-old children . Mother-child pairs were randomized either to intervention and control groups and dietary counseling was provided for mothers in the intervention group during 10 home visits in the course of the first year of life . These visits were carried out by fieldworkers who counseled the mothers about the Ten Steps for Healthy Feeding from Birth to Two Years of Age , based on the WHO guidelines . Dietary intake was assessed at 3-4 y of age for 345 children using two 24-h food recalls . Overall diet quality was determined by the Healthy Eating Index . The prevalence of poor diet in the intervention group was lower compared with the control group [ relative risk ( RR ) = 0.30 ; 95 % CI = 0.13-0.71 ) . The number of children who achieved the 75th percentile for the vegetable and fruit component score was higher in the intervention than in control group ( RR = 1.95 ; 95 % CI = 1.31-2.89 and RR = 1.49 ; 95 % CI = 1.07-2.07 , respectively ) . Such data provide evidence that dietary counseling for mothers during the first year of life improves the overall dietary quality of children in a low-income population .

Maternal dietary counseling

healthy eating index

childhood


Early treatment of cold sores with topical ME-609 decreases the frequency of ulcerative lesions : a randomized , double-blind , placebo-controlled , patient-initiated clinical trial . BACKGROUND Prior pilot studies support the use of antiviral medications with topical corticosteroids for herpes simplex labialis ( HSL ) . ME-609 ( Xerese , Xerclear ) is a combination of 5 % acyclovir and 1 % hydrocortisone developed for the topical treatment of HSL . OBJECTIVES The primary study end point was the prevention of ulcerative HSL lesions . METHODS In all , 2437 patients with a history of HSL were randomized to self-initiate treatment with ME-609 , 5 % acyclovir in ME-609 vehicle , or ME-609 vehicle ( placebo ) at the earliest sign of a cold sore recurrence . Cream was applied 5 times/d for 5 days . A total of 1443 patients experienced a recurrence and initiated treatment with ME-609 ( n = 601 ) , acyclovir ( n = 610 ) , or placebo ( n = 232 ) . RESULTS Of patients receiving ME-609 , 42 % did not develop an ulcerative lesion compared with 35 % of patients receiving acyclovir in ME-609 vehicle ( P = .014 ) and 26 % of patients receiving placebo ( P < .0001 ) . In patients with ulcerative lesions , healing times were reduced in the ME-609 and acyclovir groups compared with placebo ( P < .01 for both ) . The cumulative lesion area for all lesions was reduced 50 % in patients receiving ME-609 compared with the placebo group ( P < .0001 ) . There were no differences among groups in the number of patients with positive herpes simplex virus cultures . The side-effect profile was similar among treatments . LIMITATIONS The study did not contain a group treated with a topical corticosteroid alone . CONCLUSIONS ME-609 prevented progression of cold sores to ulcerative lesions and significantly reduced the cumulative lesion area compared with acyclovir and placebo . ME-609 treatment offers additional therapeutic benefit compared with therapy with topical acyclovir alone .

ME-609 ( Xerese , Xerclear )

acyclovir

hydrocortisone

5 % acyclovir in ME-609 vehicle

ME-609 vehicle ( placebo )

Cream was applied 5 times/d for 5 days

acyclovir

placebo

acyclovir in ME-609 vehicle

frequency of ulcerative lesions :

ulcerative HSL lesions .

a recurrence

ulcerative lesion

healing times

cumulative lesion area

side-effect profile

of cold sores to ulcerative lesions

cumulative lesion area

herpes simplex labialis

history of HSL


Acamprosate appears to decrease alcohol intake in weaned alcoholics . Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate ( calcium acetylhomotaurinate ( CA ) , 1.3 g/day ) on indicators of alcoholic relapse after withdrawal . One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study . The major efficacy criterion was plasma gamma-glutamyl transpeptidase ( GGT ) , as an indicator of recent alcohol ingestion . This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake . Patients in both groups were similar initially . After 3 months of treatment , the patients in the CA group had significantly lower GGT ( 1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal , P = 0.016 ) . All significant differences ( P less than 0.05 ) or trends ( 0.10 greater than P greater than 0.05 ) were in favor of a superior effect of CA over placebo . The major side-effect of CA was diarrhea ( present in 13 % of CA patients versus 7 % of placebo , P = 0.04 ) . CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months , in this large-scale multicenter study . It could be a new modality in the drug therapy of alcoholism , not involving an antabuse effect , an antidepressant action , or conditioning .

Acamprosate

placebo-controlled

Acamprosate

calcium acetylhomotaurinate ( CA )

CA

placebo

CA

CA

placebo

CA

placebo

CA

placebo

decrease alcohol intake

lower GGT

diarrhea

alcoholics

Five hundred and sixty-nine

alcoholics

One hundred and eighty-one

placebo group


Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo : a randomized controlled trial . BACKGROUND Previous epidemiological , animal and human data report that lycopene has a protective effect against ultraviolet radiation ( UVR ) -induced erythema . OBJECTIVES We examined whether tomato paste -- rich in lycopene , a powerful antioxidant -- can protect human skin against UVR-induced effects partially mediated by oxidative stress , i.e . erythema , matrix changes and mitochondrial DNA ( mtDNA ) damage . METHODS In a randomized controlled study , 20 healthy women ( median age 33 years , range 21-47 ; phototype I/II ) ingested 55 g tomato paste ( 16 mg lycopene ) in olive oil , or olive oil alone , daily for 12 weeks . Pre- and postsupplementation , UVR erythemal sensitivity was assessed visually as the minimal erythema dose ( MED ) and quantified with a reflectance instrument . Biopsies were taken from unexposed and UVR-exposed ( 3 × MED 24 h earlier ) buttock skin pre- and postsupplementation , and analysed immunohistochemically for procollagen ( pC ) I , fibrillin-1 and matrix metalloproteinase ( MMP ) -1 , and by quantitative polymerase chain reaction for mtDNA 3895-bp deletion . RESULTS Mean ± SD erythemal D ( 30 ) was significantly higher following tomato paste vs. control ( baseline , 26·5 ± 7·5 mJ cm ( -2 ) ; control , 23 ± 6·6 mJ cm ( -2 ) ; tomato paste , 36·6 ± 14·7 mJ cm ( -2 ) ; P = 0·03 ) , while the MED was not significantly different between groups ( baseline , 35·1 ± 9·9 mJ cm ( -2 ) ; control , 32·6 ± 9·6 mJ cm ( -2 ) ; tomato paste , 42·2 ± 11·3 mJ cm ( -2 ) ) . Presupplementation , UVR induced an increase in MMP-1 ( P = 0·01 ) and a reduction in fibrillin-1 ( P = 0·03 ) . Postsupplementation , UVR-induced MMP-1 was reduced in the tomato paste vs. control group ( P = 0·04 ) , while the UVR-induced reduction in fibrillin-1 was similarly abrogated in both groups , and an increase in pCI deposition was seen following tomato paste ( P = 0·05 ) . mtDNA 3895-bp deletion following 3 × MED UVR was significantly reduced postsupplementation with tomato paste ( P = 0·01 ) . CONCLUSIONS Tomato paste containing lycopene provides protection against acute and potentially longer-term aspects of photodamage .

Tomato paste rich in lycopene

tomato paste -- rich in lycopene

cutaneous photodamage

erythemal sensitivity

women

median age 33 years

range 21-47


A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer . PURPOSE/OBJECTIVE This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma . MATERIALS/METHODS Between May 2000 and May 2004 , 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m² Cisplatin ( group I ; 16 patients ) or 50 mg/m² paclitaxel ( group II ; 15 patients ) concurrently with radiotherapy . Median total dose to point A was 74 Gy ( range : 66-92 Gy ) for group I and 66 Gy ( range : 40-98 Gy ) for group II . Median follow-up time was 46 months . RESULTS Patient and tumor characteristics were similar in both groups . The mean number of chemotherapy cycles was also comparable with 87 % and 80 % of patients receiving at least 4 doses in groups I and II , respectively . Seven patients ( 44 % ) of group I and 8 patients ( 53 % ) of group II developed tumor recurrence . The Median Survival time was not reached for Group I and 53 months for group II . The proportion of patients surviving at 2 and 5 years was 78 % and 54 % for group I and 73 % and 43 % for group II respectively . CONCLUSIONS This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix .

radiotherapy

cisplatin

paclitaxel

cisplatin

paclitaxel

standard radiotherapy

advanced cervical cancer

advanced cervical carcinoma


The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction . BACKGROUND To evaluate the effect of the amino acids L-arginine and citrulline on endothelial function in patients in stable diastolic and right heart failure using photoplethysmography . METHODS Thirty patients from the Heart Failure Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición " Salvador Zubirán " underwent photoplethysmography using the hyperemia technique . Index finger flow was assessed at baseline and after ischemia every 30 s by maximum amplitude time ( MAT ) , total time of the curve ( TT ) and the index of the two ( MAT/TT < 30 = normal ) before and after the administration of L-arginine ( 8 g/day in two doses , n = 15 ) or citrulline ( 3 g/day in one dose , n = 15 ) for 60 days in addition to optimal pharmacological treatment . RESULTS There were no statistically significant differences between the two groups at baseline . After the intervention , the MAT/TT index of all patients normalized in each evaluation period with statistically significant differences . Basal L-arginine group = 38.75 ± 11.52 , final 23.32 ± 6.08 , p = 0.007 and basal citrulline group = 41.4 ± 13.47 , final 23.65 ± 6.74 , p = 0.007 at 60-90 s. Post-ischemia : basal L-arginine 36.60 ± 11.51 , final 18.81 ± 15.13 , p = 0.004 and basal citrulline = 49.51 ± 15.17 , final 27.13 ± 7.87 , p = 0.003 . CONCLUSIONS The administration of L-arginine and citrulline has a beneficial effect on endothelial function as shown by the normalized MAT/TT index . It probably improves systemic and pulmonary hemodynamics , which could help in the treatment of diastolic heart failure .

L-arginine and citrulline

amino acids L-arginine and citrulline

endothelial function

endothelial function

Thirty patients

treatment of diastolic heart


Influence of exercise training on leptin levels in patients with stable coronary artery disease : A pilot study . BACKGROUND This study was designed to examine the influence of exercise training on leptin levels in patients with stable coronary artery disease ( CAD ) . METHODS Sixty-four male patients , mean age 55.6 ± 6.0 years , were randomized either to six weeks of aerobic training , three times a week , at 60-80 % of maximal heart rate ( training group , Ex , n = 32 ) or to a control group ( n = 32 ) . Exercise stress test was performed and body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , waist circumference and plasma leptin levels were measured at the beginning and end of the study . RESULTS Physical capacity increased significantly only in Ex patients ( max workload in METs from 7.7 ± 1.4 to 8.2 ± 1.4 , p < 0.05 ) . There were no significant differences between initial and final results in either group in terms of BMI , WHR or waist circumference . Although , at the end of the study , leptin levels did not change in Ex patients ( 6.7 ± 3.2 vs 6.9 ± 3.6 ng/mL , NS ) , they did increase significantly in the control group ( 8.0 ± 4.0 vs 9.3 ± 5.2 ng/mL , p < 0.02 ) . CONCLUSIONS A short period of exercise training in CAD patients improved their physical capacity , but did not influence BMI , WHR and waist circumference . Exercise training prevented an increase in leptin levels during the study period .

exercise training

exercise training

leptin levels

coronary artery disease

Sixty-four

male

mean age 55.6 ± 6.0 years

CAD


Action observation treatment improves recovery of postsurgical orthopedic patients : evidence for a top-down effect ? OBJECTIVE To assess whether action observation treatment ( AOT ) may also improve motor recovery in postsurgical orthopedic patients , in addition to conventional physiotherapy . DESIGN Randomized controlled trial . SETTING Department of rehabilitation . PARTICIPANTS Patients ( N=60 ) admitted to our department postorthopedic surgery were randomly assigned to either a case ( n=30 ) or control ( n=30 ) group . Exclusion criteria were age 18 years or younger and 90 years or older , Mini-Mental State Examination score of 21 of 30 or lower , no ambulating order , advanced vision impairment , malignancy , pneumonia , or heart failure . INTERVENTIONS All participants underwent conventional physiotherapy . In addition , patients in the case group were asked to observe video clips showing daily actions and to imitate them afterward . Patients in the control group were asked to observe video clips with no motor content and to execute the same actions as patients in the case group afterward . Participants were scored on functional scales at baseline and after treatment by a physician blinded to group assignment . MAIN OUTCOMES MEASURES Changes in FIM and Tinetti scale scores , and dependence on walking aids . RESULTS At baseline , groups did not differ in clinical and functional scale scores . After treatment , patients in the case group scored better than patients in the control group ( FIM total score , P=.02 ; FIM motor subscore , P=.001 ; Tinetti scale score , P=.04 ) ; patients in the case group were assigned more frequently to 1 crutch ( P=.01 ) . CONCLUSIONS In addition to conventional physiotherapy , AOT is effective in the rehabilitation of postsurgical orthopedic patients . The present results strongly support top-down effects of this treatment in motor recovery , even in nonneurologic patients .

action observation treatment ( AOT )

control

Changes in

FIM

and

Tinetti scale scores

, and dependence on walking aids .

clinical and functional scale scores .

FIM total score

FIM motor subscore

Tinetti scale score

frequently to 1 crutch

postsurgical orthopedic patients

postsurgical orthopedic


[ Acute cardiovascular and metabolic changes in interval and endurance training in selected patients following aortocoronary bypass operation ] . UNLABELLED This study compared the acute changes of cardiovascular and metabolic reactions during interval and continuous training after coronary bypass surgery . Two groups of 9 male patients ( age : 59 +/- 4 and 56 +/- 6 years , resp . ) each trained on bicycle ergometer start on post-operative days 24 and 26 , resp . In both training groups training heart rate was set at 86 % of individual maximum heart rate . In the last week of training the exercise intensity in the group of patients who were trained by the continuous method was at 83 watts , and at 20:121 watts in the group of patients who were trained by interval method ( rest : work each 1:1 min ) . At this exercise training that lasted for 20 min the acute response of heart rate , blood pressure , rate-pressure product , glucose , lactate and catecholamines was measured . RESULTS In both methods there were no significant differences in systolic and diastolic pressure , rate-pressure product , in glucose or catecholamine levels . However , there was a significantly higher rate of lactate in the second 10 min of the interval training . And , in spite of higher peripheral exercise intensity by interval training , there was no higher cardiac work than by the continuous training . These findings suggest that interval training strains the oxidative capacity of the trained muscles in a more intensive and direct way than does continuous training .

endurance training

interval and continuous training

training heart rate

acute response of heart rate

blood pressure

rate-pressure product

glucose

lactate

catecholamines

systolic and diastolic pressure

rate-pressure product

glucose

catecholamine

rate of lactate

cardiac work

Two groups of 9

male


Multicenter , double-blind , placebo-controlled crossover study to assess the acute prokinetic efficacy of nizatidine-controlled release ( 150 and 300 mg ) in patients with gastroesophageal reflux disease . INTRODUCTION The aim of the study is to test whether nizatidine delivered via a unique bimodal pulsatile-controlled release system , nizatidine controlled release ( CR ) , accelerates gastric emptying in patients with gastroesophageal reflux disease ( GERD ) . METHODS Combined data were analyzed on 39 patients with delayed gastric emptying ( DGE ) from 2 studies ( n = 84 ) assessing the prokinetic effect of nizatidine CR . A single-blind placebo baseline was followed by double-blind nizatidine CR ( 150 and 300 mg ) in randomized sequence , 2 to 5 days apart . Each dose was followed 1 hour later by an egg-beater meal , labeled with Tc99m . Gamma camera images were obtained at meal completion , 1- , 2- , 3- and 4-hour postmeal . All the 84 patients were classified at baseline with DGE ( gastric retention > 6.3 % at 4 hours ) or normal gastric emptying . RESULTS In the 39 patients identified with DGE , change from placebo baseline ( CFB ) for percent gastric retention at 4-hour postmeal with nizatidine CR ( 150 and 300 mg ) was each improved and statistically significant ( P < 0.05 ) . In a subgroup of diabetic patients with DGE ( n = 10 ) , the CFB with nizatidine CR ( 300 mg ) was significant ( P < 0.05 ) at 3- and 4-hour postmeal . CONCLUSIONS Nizatidine CR ( 150 and 300 mg ) significantly enhanced gastric emptying of a standard meal in patients with GERD with DGE .

nizatidine-controlled release

nizatidine

nizatidine controlled release

nizatidine CR

single-blind placebo baseline

double-blind nizatidine CR

egg-beater meal

, labeled with Tc99m .

placebo

nizatidine CR

Nizatidine CR

acute prokinetic efficacy

gastric emptying

delayed gastric emptying

Gamma camera images

DGE

normal gastric emptying

CFB

percent gastric retention

gastric emptying

gastroesophageal reflux disease

delayed gastric emptying ( DGE )

n = 84

DGE

normal gastric emptying

diabetic

DGE

GERD

DGE


Hypoxic exercise training reduces senescent T-lymphocyte subsets in blood . The integration and control of systemic immune responses depends on the regulated trafficking of T-lymphocytes . This study elucidates how various exercises regimens with/without hypoxia affect phenotypic characteristics of T-lymphocyte subsets in blood . Fifty sedentary males were randomly divided into five groups . Each group ( n=10 ) received one of five interventions : normoxic ( 21 % O₂ ) resting ( N-C ) , hypoxic ( 15 % O₂ ) resting ( H-C ) , normoxic exercise ( 50 % W ( max ) under 21 % O₂ , N-T ) , hypoxic-relative exercise ( 50 % maximal heart rate reserve under 15 % O₂ , H-RT ) , or hypoxic-absolute exercise ( 50 % W ( max ) under 15 % O₂ , H-AT ) for 30 min/day , 5 days/week for 4 weeks . Before the intervention , strenuous exercise up to exhaustion increased the mobilization of CD3 , CD4 , CD8 , or CD8 ( bright ) lymphocytes expressing activated ( CD11a ) or senescent ( KLRG1 ) molecules into the peripheral blood compartment . The H-AT for 4 weeks up-regulated co-stimulatory molecule CD28 expression and was accompanied by depressed KLRG1 level on CD3 , CD4 , CD8 , or CD8 ( bright ) lymphocytes at rest or following exercise . Simultaneously , this intervention increased interferon-γ ( IFN-γ ) level and unchanged interleukin-4 level , as well as , decreased myeloperoxidase ( MPO ) and interleukin-6 levels in plasma . However , no significant changes in resting and exercise-induced mobilizations of various T-lymphocyte subsets and productions of cytokines and MPO occurred following the N-C , H-C , N-T , and H-RT interventions . Therefore , we conclude that 4-week H-AT intervention reduced senescent T-lymphocyte subsets with increasing IFN-γ level in blood , which responses are accompanied by depressed oxidative stress and pro-inflammatory cytokine production . These findings can help to determine an effective hypoxic exercise regimen to minimize immune dysfunction by retarding T-lymphocyte senescence .

Hypoxic exercise training

senescent T-lymphocyte subsets in blood

Fifty

sedentary

males


Tetracaine/adrenaline/cocaine for local anesthesia .

Tetracaine/adrenaline/cocaine

local anesthesia .


The effect of educational intervention on pain beliefs and postoperative pain relief among Chinese patients with fractured limbs .

educational intervention

fractured limbs


Late patient-reported toxicity after preoperative radiotherapy or chemoradiotherapy in nonresectable rectal cancer : results from a randomized Phase III study . PURPOSE Preoperative chemoradiotherapy ( CRT ) is superior to radiotherapy ( RT ) in locally advanced rectal cancer , but the survival gain is limited . Late toxicity is , therefore , important . The aim was to compare late bowel , urinary , and sexual functions after CRT or RT . METHODS AND MATERIALS Patients ( N = 207 ) with nonresectable rectal cancer were randomized to preoperative CRT or RT ( 2 Gy × 25 ± 5-fluorouracil/leucovorin ) . Extended surgery was often required . Self-reported late toxicity was scored according to the LENT SOMA criteria in a structured telephone interview and with questionnaires European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Questionnaire ( QLQ-C30 ) , International Index of Erectile Function ( IIEF ) , and sexual function-vaginal changes questionnaire ( SVQ ) . RESULTS Of the 105 patients alive in Norway and Sweden after 4 to 12 years of follow-up , 78 ( 74 % ) responded . More patients in the CRT group had received a stoma ( 73 % vs. 52 % , p = 0.09 ) . Most patients without a stoma ( 7 of 12 in CRT group and 9 of 16 in RT group ) had incontinence for liquid stools or gas . No stoma and good anal function were seen in 5 patients ( 11 % ) in the CRT group and in 11 ( 30 % ) in the RT group ( p = 0.046 ) . Of 44 patients in the CRT group , 12 ( 28 % ) had had bowel obstruction compared with 5 of 33 ( 15 % ) in the RT group ( p = 0.27 ) . One-quarter of the patients reported urinary incontinence . The majority of men had severe erectile dysfunction . Few women reported sexual activity during the previous month . However , the majority did not have concerns about their sex life . CONCLUSIONS Fecal incontinence and erectile dysfunction are frequent after combined treatment for locally advanced rectal cancer . There was a clear tendency for the problems to be more common after CRT than after RT .

radiotherapy

chemoradiotherapy

Preoperative chemoradiotherapy

radiotherapy

preoperative CRT

RT

survival gain

toxicity

late bowel , urinary

sexual functions

nonresectable rectal cancer

locally advanced rectal cancer

nonresectable rectal cancer


The maximal double step length test can evaluate more adequately the decrease of physical function with age , than the maximal single step length test . The maximal double step length ( MDSL ) test is a modified version of the maximal step length ( MSL ) test used to evaluate the dynamic balance related to falls in the elderly . Although this test can evaluate their physical function using movements similar to daily activities as compared to MSL , it has not been clarified whether it can adequately evaluate the activities of daily living ( ADL ) abilities of the elderly , as they decrease with age . This study aimed to examine the relationship between both MSL and MDSL on age and ADL in elderly subjects . Fifty-seven elderly females who live independently ( age 74.8±5.6 years ) were recruited . MSL and MDSL were conducted twice after completing an ADL questionnaire . Intra-class correlation coefficients ( ICCs ) of both tests were high ( for MSL : ICC=0.95 , for MDSL : ICC=0.81-0.82 ) . Age and ADL significantly correlated to MDSL ( age : r=-0.32-0.41 , ADL : r=0.28-0.48 ) , but not to MSL ( age : r=-0.19 , ADL : r=0.15 ) . MDSL has high reliability as it relates to age and ADL . It may be more useful to evaluate ADL required for independent living and prevent falls in the elderly better than MSL .

maximal double step length test

maximal double step length

maximal step length ( MSL ) test

MSL

MSL

MDSL

elderly subjects

Fifty-seven

elderly

females

( age 74.8±5.6 years


The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy : results of a randomized phase III clinical trial . BACKGROUND Chemotherapy-induced peripheral neuropathy ( CIPN ) continues to be a substantial problem for many cancer patients . Pursuant to promising appearing pilot data , the current study evaluated the use of vitamin E for the prevention of CIPN . METHODS A phase III , randomized , double-blind , placebo-controlled study was conducted in patients undergoing therapy with neurotoxic chemotherapy , utilizing twice daily dosing of vitamin E ( 400 mg ) /placebo . The primary endpoint was the incidence of grade 2+ sensory neuropathy ( SN ) toxicity ( CTCAE v 3.0 ) in each treatment arm , analyzed by chi-square testing . Planned sample size was 100 patients per arm to provide 80 % power to detect a difference in incidence of grade 2+ SN toxicity from 25 % in the placebo group to 10 % in the vitamin E group . RESULTS Two-hundred seven patients were enrolled between December 1 , 2006 and December 14 , 2007 , producing 189 evaluable cases for analysis . Cytotoxic agents included taxanes ( 109 ) , cisplatin ( 8 ) , carboplatin ( 2 ) , oxaliplatin ( 50 ) , or combination ( 20 ) . There was no difference in the incidence of grade 2+ SN between the two arms ( 34 % -vitamin E , 29 % -placebo ; P = 0.43 ) . There were no significant differences between treatment arms for time to onset of neuropathy ( P = 0.58 ) , for chemotherapy dose reductions due to neuropathy ( P = 0.21 ) , or for secondary endpoints derived from patient-reported neuropathy symptom assessments . The treatment was well tolerated overall . CONCLUSIONS Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy .

vitamin E

vitamin E

/placebo

-vitamin E

grade 2+ SN toxicity

grade 2+ SN

cancer

Two-hundred seven


Clinical trial : once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial . BACKGROUND Ulcerative colitis ( UC ) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder . AIM To evaluate once-daily mesalamine ( mesalazine ) granules ( MG ) for maintenance of remission of UC . METHODS Randomized , double-blind , placebo-controlled trial of patients ( n=209 MG , n=96 placebo ) with UC in remission [ revised Sutherland Disease Activity Index ( SDAI ) rectal bleeding=0 , mucosal appearance < 2 ] who took MG 1.5 g or placebo once-daily for up to 6 months . Primary efficacy endpoint : the percentage of patients who remained relapse-free at month 6/end of treatment . Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2 , a UC flare , or initiation of medication to treat a UC flare . RESULTS The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo ( 78.9 % vs. 58.3 % , P < 0.001 ) in the intent-to-treat analysis . Significant differences ( P ≤ 0.025 ) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding , physician 's disease activity rating , stool frequency , the SDAI at month 6/end of treatment , patients classified as a treatment success and relapse-free duration . The incidence of adverse events was similar between groups . CONCLUSIONS Once-daily mesalamine ( mesalazine ) was effective in maintaining remission of UC for 6 months .

mesalamine

mesalamine

mesalazine

or placebo


Patients appreciation for information on anesthesia and anxiolysis in dentistry . AIM The research regards information on anesthesia to patients undergoing oral surgery . Every patient evaluated the information received at the end of the preoperative visit and in the postoperative period . METHODS One hundred-fifty dental patients were asked about the most appreciated information received in the preoperative visit on the anxiolytic technique , local anesthesia and treatment of the perioperative pain . Afterwards the patients had to report on their reaction to the content of the preoperative visit and information quality . On a phone interview they had to evaluate their appreciation of the anxiolytic technique , their perception during loco-regional anesthesia and incidence of pain and edema . RESULTS The most appreciated details were those on the intervention , pharmacologic treatment , postoperative complicances , postoperative pain and operative competence ; less appreciated were those on loco-regional anesthesia , duration of the intervention , anxiolytic techniques , hospital reception and permanence in the hospital . Ninety-eight percent of the patients considered to have been adequately informed on a context judged to be extraordinary ( 99.3 % ) , 96.6 % indicated the information as necessary , 98.6 % appreciated the treatment of the intraoperative and postoperative ( 99.3 % ) pain and 99.3 % the anxiolytic treatment . On the telephone interview , 100 % of patients expressed satisfaction for the experienced intraoperative tranquillity , 91.3 % complained for not having received in the past a similar preoperative visit , 99.3 % wished a diffused application of the information . The loco-regional anesthesia was associated to psychological detachment in 84 % of the cases and the incidence of postoperative pain was of 36 % . CONCLUSION The information on the anxiolytic techniques , loco-regional anesthesia , treatment of perioperative pain and postoperative distress was enthusiastically accepted and albeit initially induced feelings of astonishment resulted to be appreciated and preferred in the whole of the patients .

anesthesia

anxiolysis

anesthesia

anxiolytic technique

treatment

intraoperative tranquillity

diffused application

postoperative pain

appreciated

preferred


Randomized comparative study of group versus individual cognitive behavioural therapy for obsessive compulsive disorder . OBJECTIVE The primary aim of the study was to compare the effectiveness of group and individual cognitive behaviour therapy ( CBT ) for obsessive compulsive disorder ( OCD ) . METHOD One hundred and ten out-patients with OCD were randomly assigned to 15 sessions of either group CBT or individual CBT . Outcome measures were administered before and after treatment , as well as at 6- and 12-month follow-ups . The study was supplemented by a meta-analysis of accomplished comparative studies of group vs. individual CBT for OCD . RESULTS Large and stable pre-post effect sizes were found for both treatment conditions in the study ( d = 1.06-1.24 on the Yale-Brown Obsessive Compulsive Scale ) . There were no significant between-group differences in outcome at any data point ( ds= -0.13 to 0.15 ) . The meta-analysis of four accomplished comparative studies ( including the present one ) found a between-group mean effect size of ( d= 0.15 favouring individual over group CBT at posttreatment ( 95 % confidence interval , -0.12 , 0.42 ) . CONCLUSION The results of this study suggest that OCD can be treated effectively with a group format of CBT , thus sparing some therapist resources , although the four accomplished comparative studies do not rule out the possibility of a small superiority of individually conducted CBT .

group CBT or individual CBT .

group vs. individual CBT

CBT

group format of CBT

CBT

effect sizes

Yale-Brown Obsessive Compulsive Scale

effectively


Clofarabine ± fludarabine with once daily i.v . busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS . Although a combination of i.v . busulfan ( Bu ) and fludarabine ( Flu ) is a safe , reduced-toxicity conditioning program for acute myelogenous leukemia/myelodysplastic syndromes ( AML/MDS ) , recurrent leukemia posttransplantation remains a problem . To enhance the conditioning regimen 's antileukemic effect , we decided to supplant Flu with clofarabine ( Clo ) , and assayed the interactions of these nucleoside analogs alone and in combination with Bu in Bu-resistant human cell lines in vitro . We found pronounced synergy between each nucleoside and the alkylator but even more enhanced cytotoxic synergy when the nucleoside analogs were combined prior to exposing the cells to Bu . We then designed a 4-arm clinical trial in patients with myeloid leukemia undergoing allogeneic stem cell transplantation ( allo-SCT ) . Patients were adaptively randomized as follows : Arm I-Clo : Flu 10:30 mg/m ( 2 ) , Arm II-20:20 mg/m ( 2 ) , Arm III-30:10 mg/m ( 2 ) , and Arm IV-single-agent Clo at 40 mg/m ( 2 ) . The nucleoside analog ( s ) were/was infused over 1 hour once daily for 4 days , followed on each day by Bu , infused over 3 hours to a pharmacokinetically targeted daily area under the curve ( AUC ) of 6000 μMol-min ± 10 % . Fifty-one patients have been enrolled with a minimum follow-up exceeding 100 days . There were 32 males and 19 females , with a median age of 45 years ( range : 6-59 ) . Nine patients had chronic myeloid leukemia ( CML ) ( BC : 2 , second AP : 3 , and tyrosine-kinase inhibitor refractory first chronic phase [ CP ] : 4 ) . Forty-two patients had AML : 14 were induction failures , 8 in first chemotherapy-refractory relapse , 7 in untreated relapse , 3 in second or subsequent relapse , 4 were in second complete remission ( CR ) , and 3 in second CR without platelet recovery ( CRp ) , 2 were in high-risk CR1 . Finally , 1 patient was in first CRp . Graft-versus-host disease ( GVHD ) prophylaxis was tacrolimus and mini-methorexate ( MTX ) , and those who had an unrelated or 1 antigen-mismatched donor received low-dose rabbit-ATG ( Thymoglobulin™ ) . All patients engrafted . Forty-one patients had active leukemia at the time of transplant , and 35 achieved CR ( 85 % ) . Twenty of the 42 AML patients and 5 of 9 CML patients are alive with a projected median overall survival ( OS ) of 23 months . Marrow and blood ( T cell ) chimerism studies at day +100 revealed that both in the lower-dose Clo groups ( groups 1+2 ) and the higher-dose Clo groups ( groups 3+4 ) , the patients had a median of 100 % donor ( T cell ) -derived DNA . There has been no secondary graft failure . In the first 100 days , 1 patient died of pneumonia , and 1 of liver GVHD . We conclude that ( 1 ) Clo ± Flu with i.v . Bu as pretransplant conditioning is safe in high-risk myeloid leukemia patients ; ( 2 ) clofarabine is sufficiently immunosuppressive to support allo-SCT in myeloid leukemia ; and ( 3 ) the median OS of 23 months in this high-risk patient population is encouraging . Additional studies to evaluate the antileukemic efficacy of Clo ± Flu with i.v . Bu as pretransplant conditioning therapy are warranted .

Clofarabine ± fludarabine

busulfan

i.v . busulfan ( Bu )

fludarabine ( Flu )

clofarabine ( Clo )

I-Clo : Flu

IV-single-agent Clo

Marrow and blood ( T cell )

secondary graft failure

evaluate the antileukemic efficacy


Cardiovascular safety of degarelix : results from a 12-month , comparative , randomized , open label , parallel group phase III trial in patients with prostate cancer . PURPOSE We assessed the cardiovascular safety profile of degarelix , a new gonadotropin-releasing hormone antagonist . MATERIALS AND METHODS This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix . Outcomes considered in these analyses included the QT interval by central reading and analysis , and cardiovascular adverse events . On multivariate analyses relationships between selected baseline factors and cardiovascular events were evaluated . RESULTS There were no significant differences between treatment groups for mean change in Fridericia 's correction of QT during the trial . Markedly abnormal Fridericia 's correction of QT values ( 500 milliseconds or greater ) were observed in only a small number of subjects by treatment group , that is 2 ( less than 1 % ) in the pooled degarelix group and 2 ( 1 % ) in the leuprolide group . Supraventricular arrhythmias were the most common type of arrhythmias , affecting 2 % of subjects in the pooled degarelix group and 4 % in the leuprolide group . Other arrhythmias occurred in 1 % or less of subjects by treatment group . The most frequently reported cardiac disorder was ischemic heart disease , which occurred in 4 % of subjects treated with degarelix and 10 % of those on leuprolide . Cox proportional hazard ratio estimates for selected baseline covariates showed a significantly increased risk of cardiovascular events by age ( p=0.0459 ) and systolic blood pressure ( p=0.0061 ) . CONCLUSIONS In men with prostate cancer degarelix and leuprolide have similar cardiovascular safety profiles . These observations suggest that the cardiovascular events associated with both agents result from hypogonadism rather than a direct drug effect .

degarelix

degarelix

leuprolide acetate

degarelix

degarelix

leuprolide

degarelix

leuprolide

degarelix

leuprolide

degarelix

leuprolide

cardiovascular adverse events

cardiovascular events

Supraventricular arrhythmias

Other arrhythmias

ischemic heart disease

patients with prostate cancer .

men

prostate cancer


A comparison of human papillomavirus testing of clinician-collected and self-collected samples during follow-up after screen-and-treat . Screen-and-treat cervical cancer prevention programs based on high-risk human papillomavirus ( HPV ) testing and cryotherapy have been shown to be effective in resource-limited settings . However , because cryotherapy is not 100 % effective , follow-up is needed after treatment to detect post-treatment failures . We compared the test performances of high-risk HPV testing ( Hybrid Capture 2 ) using self-collected and clinician-collected samples as well as cervical cytology for identifying cervical intraepithelial neoplasia grades 2 or 3 or invasive cervical cancer ( CIN2+ ) among women who did ( n=812 ) and did not ( n=1858 ) undergo cryotherapy in a South African screen-and-treat trial . At 6 months after enrolment ( and after cryotherapy , if performed ) , women were tested using all three screening methods and then underwent colposcopy/biopsy . A predefined subset of women ( n=1,455 ) had extended follow-up with colposcopy/biopsy at 12 months . A total of 33 and 91 cases of CIN2+ were detected among treated and untreated women , respectively . The sensitivity of HPV testing using clinician-collected samples and cervical cytology did not differ by treatment status . HPV testing of clinician-collected samples detected the most cases of CIN2+ among both treated ( 85 % ) and untreated ( 91 % ) women ( p=0.31 ) . Cytology ( at a cutoff of atypical squamous cells of undetermined significance or greater ) detected 76 % of cases among both treated and untreated women . However , the sensitivity of HPV testing using self-collected samples was significantly lower among treated versus untreated women ( 55 % vs. 78 % , p=0.01 ) . HPV testing using self-collected vaginal specimens may be useful in primary screening but performs poorly for detecting post-treatment failures .

cervical cytology

cryotherapy

colposcopy/biopsy

colposcopy/biopsy

clinician-collected samples

clinician-collected samples

self-collected samples

self-collected vaginal specimens

sensitivity of HPV testing

Cytology

sensitivity of HPV testing

post-treatment failures

women


Ipilimumab efficacy and safety in patients with advanced melanoma : a retrospective analysis of HLA subtype from four trials . Ipilimumab is a fully human , monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response . This agent improved overall survival in a phase III trial in previously treated patients with advanced melanoma . Because the mechanism of action for ipilimumab is thought to be HLA independent , most trials enrolled patients without regard to HLA subtype . However , enrollment in the phase III trial was restricted to class-I HLA-A*0201-positive patients because two of the three arms contained an HLA-A*0201-restricted gp100 vaccine . HLA typing was also performed prospectively in several phase II trials and was available for 93.5 % of patients . In this retrospective analysis , pooled efficacy and safety data are presented according to HLA-A*0201 status and dose from pretreated patients randomized to 0.3 , 3 , or 10 mg/kg ipilimumab in four phase II trials . Median overall survival ( OS ) was similar for the 187 HLA-A*0201-positive [ 9.3 months , 95 % CI ( confidence interval ) 7.4-11.5 ] and 266 HLA-A*0201-negative patients [ 11.4 months , 95 % CI 9.3-15.1 ] randomized to ipilimumab at all doses across the four phase II trials . These data are comparable to the OS for the 137 HLA-A*0201-positive patients randomized to ipilimumab in the phase III study [ 10.1 months , 95 % CI 8.0-13.8 ] . Ipilimumab-induced adverse events and immune-related adverse events ( skin , gastrointestinal , hepatic , other ) also occurred at similar frequencies among patients in the phase II and III trials , regardless of HLA-A*0201 status . These findings support the hypothesis that ipilimumab-treated patients with advanced melanoma have similar outcomes regardless of their HLA-A*0201 status .

Ipilimumab

Ipilimumab

ipilimumab

HLA-A*0201-restricted gp100 vaccine

Ipilimumab-induced

ipilimumab-treated

pooled efficacy and safety data

Median overall survival ( OS )

OS

advanced melanoma

previously treated

advanced melanoma

class-I HLA-A*0201-positive

pretreated

ipilimumab-treated


Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass - is retransfusion of pericardial blood harmful ? OBJECTIVES To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass ( CPB ) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion . METHODS Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases . Microparticles were isolated from systemic blood collected before anesthesia ( T1 ) and at the end of CPB ( T2 ) , and from pericardial blood . The microparticles were analyzed by flow cytometry for bound complement components C1q , C4 and C3 , and bound complement activator molecules C-reactive protein ( CRP ) , serum amyloid P-component ( SAP ) , immunoglobulin ( Ig ) M and IgG . Fluid-phase complement activation products ( C4b/c , C3b/c ) and activator molecules were determined by ELISA . RESULTS Compared with systemic T1 blood , pericardial blood contained increased C4b/c and C3b/c , and increased levels of microparticles with bound complement components . In systemic T1 samples , microparticle-bound CRP , whereas in pericardial blood , microparticle-bound SAP and IgM were associated with complement activation . At the end of CPB , increased C3b/c ( but not C4b/c ) was present in systemic T2 blood compared with T1 , while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar . Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood . CONCLUSIONS In pericardial blood of patients undergoing cardiac surgery with CPB , microparticles contribute to activation of the complement system via bound SAP and IgM . Retransfusion of pericardial blood , however , does not contribute to systemic complement activation .

cardiopulmonary bypass

blood collected before anesthesia

CPB

CPB

complement activation

systemic complement activation

C4b/c and C3b/c

levels of microparticles

C3b/c ( but not C4b/c )

activation of the complement system

systemic complement activation

cardiopulmonary bypass


Five-year outcome of surgical treatment of migraine headaches . BACKGROUND This study was designed to assess the long-term efficacy of surgical deactivation of migraine headache trigger sites . METHODS One hundred twenty-five volunteers were randomly assigned to the treatment ( n = 100 ) or control group ( n = 25 ) after examination by the team neurologist to ensure a diagnosis of migraine headache . Patients were asked to complete the Medical Outcomes Study 36-Item Short Form Health Survey , Migraine-Specific Quality of Life , and Migraine Disability Assessment questionnaires before treatment and at 12- and 60-month postoperative follow-up . The treatment group received botulinum toxin to confirm the trigger sites ; controls received saline injections . Treated patients underwent surgical deactivation of trigger site ( s ) . Results were analyzed at 1 year ( previously published ) and 5 years postoperatively ( the subject of this report ) . RESULTS Eighty-nine of 100 patients in the treatment group underwent surgery , and 79 were followed for 5 years . Ten patients underwent deactivation of additional ( different ) trigger sites during the follow-up period and were not included in the data analysis . The final outcome with or without inclusion of these 10 patients was not statistically different . Sixty-one ( 88 percent ) of 69 patients have experienced a positive response to the surgery after 5 years . Twenty ( 29 percent ) reported complete elimination of migraine headache , 41 ( 59 percent ) noticed a significant decrease , and eight ( 12 percent ) experienced no significant change . When compared with the baseline values , all measured variables at 60 months improved significantly ( p < 0.0001 ) . CONCLUSION Based on the 5-year follow-up data , there is strong evidence that surgical manipulation of one or more migraine trigger sites can successfully eliminate or reduce the frequency , duration , and intensity of migraine headache in a lasting manner .

botulinum toxin

saline injections .

surgical deactivation

deactivation

migraine headaches

migraine headache

Migraine-Specific Quality of Life

positive response

One hundred twenty-five

treatment ( n = 100 )

control group ( n = 25 )

migraine headache


High-calcium milk prevents overweight and obesity among postmenopausal women . BACKGROUND The Sixth National Nutrition Survey 2003 revealed that the highest prevalence of overweight and obesity among Filipino female adults ( 30.8 % ) was found in the age group from 40 to 59 years . Obesity is associated with a number of chronic diseases , including cardiovascular disease , hypertension , and diabetes . Low calcium intake has been identified as a potential contributing factor to overweight and obesity . OBJECTIVE To assess the effect of a high-calcium , fortified , low-fat milk drink with added vitamin D versus a low-calcium placebo drink on anthropometric measurements of postmenopausal women . METHODS Women who were at least 5 years postmenopausal were invited to participate in the study . Potential participants underwent three stages of screening : initial interview , dual-energy x-ray absorptiometry , and blood testing for biochemical screening . Anthropometric indices were measured at baseline and the end of the study . Sixty women were qualified to participate in the study . The women were randomly assigned to two groups , one of which received 400 ml of the high-calcium milk daily for 16 weeks while the other received the placebo drink . RESULTS No significant increases were observed in the anthropometric indices of the subjects receiving the high-calcium fortified milk at the end of the study . However , there were significant increases in the weight ( p = .008 ) , body mass index ( p = .007 ) , and waist ( p = .018 ) and hip ( p = .003 ) circumferences of the subjects receiving the placebo drink . CONCLUSIONS A change in dietary calcium intake may be a useful measure as part of an overall approach to prevent the occurrence of overweight and obesity among postmenopausal women .

High-calcium milk

added vitamin D

low-calcium placebo drink

high-calcium milk

placebo

high-calcium fortified milk

Anthropometric indices

anthropometric indices

weight

body mass index

waist

hip

circumferences

dietary calcium intake

postmenopausal women .


Line-item analysis of the Aberrant Behavior Checklist : results from two studies of aripiprazole in the treatment of irritability associated with autistic disorder . OBJECTIVES The aim of this study was to evaluate the efficacy of aripiprazole in the treatment of discrete symptoms of irritability associated with autistic disorder , as well as other symptoms captured on the Aberrant Behavior Checklist ( ABC ) . METHODS This was a post hoc analysis of data from two 8-week , randomized , double-blind , multicenter trials to evaluate the efficacy of aripiprazole dosed flexibly ( 2-15 mg/day , n=47 ) or fixed ( 5 , 10 , or 15 mg/day , n = 166 ) versus placebo ( flexibly dosed , n = 51 ; fixed dose , n = 52 ) . The effects of treatment on the 58 ABC items were evaluated . RESULTS Statistically significantly greater improvement was seen with aripiprazole versus placebo ( p < 0.05 ) for all arms in both trials on the ABC-Irritability total subscale score and on the following individual ABC-Irritability items : Mood changes quickly , cries/screams inappropriately , and stamps feet/bangs objects . Several additional items measuring tantrum-like behaviors improved in the flexibly dosed trial and at least one arm of the fixed-dose trial ( p < 0.05 ) . Measures of self-injurious behavior , which had low baseline values , demonstrated numerical , but not statistically significant , improvement in both trials . Statistically significantly greater improvement in ABC Stereotypic Behavior and Hyperactivity total subscale scores was also consistent across all arms in both trials . In particular , there was a cluster of items related to hyperkinesis that were consistently sensitive to treatment . CONCLUSIONS Aripiprazole is efficacious in the treatment of irritability in children and adolescents with autistic disorder , particularly with respect to symptoms associated with tantrum behavior .

aripiprazole

aripiprazole

aripiprazole dosed flexibly

placebo

aripiprazole

placebo

Aripiprazole

Mood changes quickly

cries/screams inappropriately

stamps feet/bangs objects

tantrum-like behaviors

Measures of self-injurious behavior

hyperkinesis

irritability

autistic disorder

autistic disorder


Theory of Mind training in children with autism : a randomized controlled trial . Many children with Autism Spectrum Disorders ( ASD ) participate in social skills or Theory of Mind ( ToM ) treatments . However , few studies have shown evidence for their effectiveness . The current study used a randomized controlled design to test the effectiveness of a 16-week ToM treatment in 8-13 year old children with ASD and normal IQs ( n = 40 ) . The results showed that , compared to controls , the treated children with ASD improved in their conceptual ToM skills , but their elementary understanding , self reported empathic skills or parent reported social behaviour did not improve . Despite the effects on conceptual understanding , the current study does not indicate strong evidence for the effectiveness of a ToM treatment on the daily life mindreading skills .

Mind training

Theory of Mind ( ToM ) treatments

ToM treatment

autism :

effectiveness

children

autism

children

Autism Spectrum Disorders ( ASD )

8-13 year old children


Gene expression of endothelin-1 and its receptors in the heart of broiler chickens with T ( 3 ) -induced pulmonary hypertension . To investigate the effect of T ( 3 ) -induced pulmonary hypertension on endothelin ( ET ) production and genes expression of ET-1 , ET ( A ) and ET ( B ) receptors ( ET ( A ) R and ET ( B ) R ) during rearing , semiquantitative RT-PCR and enzyme immunometric assay were performed in the heart ventricles and serum , respectively . The ET-1 and its receptor genes were expressed in the right and left ventricles of control and T ( 3 ) -treated broilers at 12 , 28 and 49 days of age . There were significant ( P < 0.05 ) reductions of the relative amounts of ET-1 ( in both ventricles ) and ET ( A ) R ( in the right ventricle ) mRNAs at 28 and 49 days of age , in T ( 3 ) -treated broilers compared to controls . The relative amounts of ET ( B ) R mRNA in the right and left ventricles did not significantly differ between control and T ( 3 ) -treated broilers at any age . The serum level of ET was significantly ( P < 0.05 ) increased in T ( 3 ) -treated chickens at 28 and 49 days of age when compared with that of the control . It is concluded that ET-1 , ET ( A ) R and ET ( B ) R genes are normally expressed in the heart ventricles of broilers . It is likely that increased serum level of ET and decreased ET-1/ET ( A ) R genes expression in the ventricles are involved in the heart dysfunction of broiler chickens with developmental pulmonary hypertension .

semiquantitative RT-PCR

enzyme immunometric assay

ET-1 and its receptor genes

relative amounts of ET ( B ) R mRNA

serum level of ET

ET-1 , ET ( A ) R and ET ( B ) R genes


Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis . BACKGROUND Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis , but its mechanism is not very clear . One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome . The present study aimed to observe effects of medical ozone therapy system on plasma renin activity ( PRA ) , angiotensin II ( AII ) , aldosterone ( ALD ) , renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis . METHODS Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group ( 43 cases ) and control group ( 42 cases ) . The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system . Basic autohemotherapy was used . One hundred milliliter venous blood was drawn from each patient , and was mixed with 100 ml ( 35 µg/ml ) medical ozone and then was returned the blood to the patient intravenously , once every other day for 20 days . Only the basic treatments were given to the control group . PRA , AII , ALD , renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared . Survival rates were also compared . RESULTS Twenty days after the treatment , in ozone therapy group , PRA was ( 1.31 ± 0.12 ) ng·ml⁻¹·h⁻¹ , AII ( 111.25 ± 17.35 ) pg/ml , ALD ( 251.31 ± 22.60 ) pg/ml , which decreased significantly compared with those before treatment ( PRA ( 2.23 ± 0.13 ) ng·ml⁻¹·h⁻¹ , AII ( 155.18 ± 19.13 ) pg/ml , ALD ( 405.31 ± 29.88 ) pg/ml , t = 4.67 - 14.23 , P < 0.01 ) , also lower than those of control group 20 days after the treatment ( PRA ( 2.02 ± 0.11 ) ng·ml⁻¹·h⁻¹ , AII ( 162.21 ± 15.32 ) pg/ml , ALD ( 401.20 ± 35.02 ) pg/ml , t = 4.97 - 15.61 , P < 0.01 ) ; renal blood flow was ( 175.15 ± 28.20 ) ml/min , which increased compared with that before the treatment ( ( 125.68 ± 21.25 ) ml/min ) and was higher than that of control group 20 days after the treatment ( ( 128.59 ± 23.15 ) ml/min , t = 4.78 , 4.61 , P < 0.01 ) . Renal damage occurred in 2 cases ( 5 % ) in ozone therapy group , less than that in control group ( 9 cases , 21 % ) ( χ² = 5.295 , P < 0.05 ) . Thirty-three cases ( 77 % ) in ozone therapy group vs. 16 cases ( 38 % ) in control group survived ( χ² = 12.993 , P < 0.01 ) . CONCLUSIONS Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA , AII and ALD levels significantly increase renal blood flow , prevent renal damage to certain extent and improve survival rate of the patients .

medical ozone therapy

Medical ozone therapy system

medical ozone therapy system

medical ozone therapy

ozone therapy group

control

ozone therapy

autohemotherapy

renal blood flow and renal function

complication of renal damage

hepatorenal syndrome .

Basic autohemotherapy

severe hepatitis

Eighty-five cases

severe hepatitis


Stepwise assessment tool of operative skills ( SATOS ) : validity testing on a porcine training model of open gastrectomy . BACKGROUND The aim of this prospective study was to evaluate and compare operative performance and technical improvement of surgical trainees learning open gastrectomy using an objective structured stepwise assessment tool of operative skills ( SATOS ) previously validated for open surgery . STUDY DESIGN Thirty residents in general surgery performed 2 open partial gastrectomy training events on a porcine model . Earlier instruction was provided for the critical operative steps , with additional intraoperative instruction when required . Performance was assessed by postgraduate year ( PGY ) according to operative time , technical skills using a 23-step objective structured tool , and error rate . RESULTS There were 11 PGY-3 , 11 PGY-4 , and 8 PGY-5 residents . At the initial assessment , performance significantly differentiated the 3 PGY grades according to technical skills and error rate . At the second assessment , all 3 PGY classes were still significantly differentiable by technical skills , with no difference in error rate . Comparing performances , residents improved operative time ( p < 0.001 ) , technical skills ( p < 0.001 ) , and error rate ( p = 0.019 ) over the 2 training events . CONCLUSIONS SATOS demonstrated relevant and accurate objective assessment of trainees ' operative skills and improvement for open gastrectomy in a porcine model . This tool may be useful to standardize instruction , to expose weaknesses of trainees , and to determine minimal technical standards in residency programs .

operative skills ( SATOS )

porcine training model

porcine model

postgraduate year ( PGY )

operative time

technical skills

technical skills and error rate .

operative time

technical skills

error rate

operative skills and improvement


PDE5 inhibition with sildenafil improves left ventricular diastolic function , cardiac geometry , and clinical status in patients with stable systolic heart failure : results of a 1-year , prospective , randomized , placebo-controlled study . BACKGROUND In heart failure ( HF ) , a defective nitric oxide signaling is involved in left ventricular ( LV ) diastolic abnormalities and remodeling . PDE5 inhibition , by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate , might be beneficial . In a cohort of systolic HF patients , we tested the effects of PDE5 inhibition ( sildenafil ) on LV ejection fraction , diastolic function , cardiac geometry , and clinical status . METHODS AND RESULTS Forty-five HF patients ( New York Heart Association class II-III ) were randomly assigned to placebo or sildenafil ( 50 mg three times per day ) for 1 year , with assessment ( 6 months and 1 year ) of LV ejection fraction , diastolic function , geometry , cardiopulmonary exercise performance , and quality of life . In the sildenafil group only , at 6 months and 1 year , LV ejection fraction , early diastolic tissue Doppler velocities ( E ' ) at the mitral lateral ( from 4.62 to 5.20 and 5.19 m/s ) and septal ( from 4.71 to 5.23 and 5.24 m/s ) annuli significantly increased , whereas the ratio of early transmitral ( E ) to E ' lateral decreased ( from 13.1 to 9.8 to 9.4 ) ( P < 0.01 ) . Changes were accompanied by a reverse remodeling of left atrial volume index ( from 32.0 to 29.0 and 29.1 mL/m ( 2 ) ; P < 0.01 ) and LV mass index ( from 148.0 to 130.0 and 128.0 g/m ( 2 ) ; P < 0.01 ) . Furthermore , sildenafil improved exercise performance ( peak Vo ( 2 ) ) , ventilation efficiency ( ventilation to CO ( 2 ) production slope ) , and quality of life ( P < 0.01 ) . Minor adverse effects were noted : flushing in 4 and headache in 2 treated patients . CONCLUSIONS Findings confirm that in HF , sildenafil improves functional capacity and clinical status and provide the first human evidence that LV diastolic function and cardiac geometry are additional targets of benefits related to chronic PDE5 inhibition .

sildenafil

placebo-controlled

sildenafil

placebo

sildenafil

sildenafil

sildenafil

septal

annuli significantly

LV mass index

flushing

headache

functional capacity and clinical status

LV diastolic function

cardiac geometry

stable systolic heart failure :

systolic HF

Forty-five

HF


[ Effect of treatment of non-nephrotic syndrome IgA nephropathy with Shenyanning ] . OBJECTIVE To observe the curative effect of Shenyanning ( SYN ) on non-nephrotic syndrome IgA nephropathy ( IgAN ) . METHODS Seventy primary IgAN patients were equally randomized into two groups , the treatment group and the control group , they were orally treated with SYN Decoction ( one dose per day ) and Losartan ( 50 mg per day ) respectively for 1 year . Efficacy of treatment , Chinese medicine syndrome scores , end-point events occurrence as well as changes of related laboratory indices were observed . RESULTS The total effective rate in the treatment group was obviously higher than that in the control group ( 77.1 % vs. 54.3 % , P < 0.05 ) . After treatment , the Chinese medicine syndrome scores , urinary protein and urinary red-cell count reduced significantly in the treatment group ( P < 0.05 or P < 0.01 ) and showed significant difference as compared with those in the control group ( P < 0.05 or P < 0.01 ) ; while the endogenous creatinine clearance was changed insignificantly in both groups . Beside , the occurrence of end-point events in the treatment group was slightly lower than that in the control group , though showed no statistical difference between them . CONCLUSION The curative effect of SYN in treating IgAN was obviously better than that of simple Western medicine .

Shenyanning

Shenyanning ( SYN )

SYN Decoction

Losartan

curative effect

Efficacy of treatment

Chinese medicine syndrome scores

end-point events occurrence

laboratory indices

total effective rate

Chinese medicine syndrome scores

urinary protein

urinary red-cell count

endogenous creatinine clearance

end-point events

non-nephrotic syndrome IgA nephropathy

Seventy

primary IgAN


Pre-transplant pharmacokinetic profiling and tacrolimus requirements post-transplant . AIM To determine the proportion of patients achieving tacrolimus whole-blood concentrations of ≥10 ng/mL within 3 days of kidney transplantation , after randomization either to standard dosing ( control group ) or post-transplantation dosing guided by a 2-hour ( C ( 2 ) ) level following a preoperative tacrolimus dose ( T2 group ) . METHODS The first postoperative tacrolimus dose was given either according to standard care ( control group ) or 0.15 mg/kg b.d . if the pre-transplant C ( 2 ) level was ≤20 ng/mL , 0.1 mg/kg b.d . if the C ( 2 ) level was 21-59 ng/mL or 0.05 mg/kg b.d . if the C ( 2 ) level was ≥60 ng/mL ( T2 group ) . Subsequent dosing in both groups was based upon tacrolimus trough level monitoring . Participants received concomitant mycophenolate mofetil and steroids . RESULTS Ninety patients were recruited , of which 84 were included in the analysis ( control group n=43 ; T2 group n=41 ) . There was no difference in the proportion of subjects achieving tacrolimus trough levels ≥10 ng/mL ( 82.9 % Control vs 93.0 % T2 ; P=0.19 ) or between 10 and 15 ng/mL ( 41.5 % Control vs 41.9 % T2 ; P=0.97 ) at day 3 post transplant . The T2 group achieved tacrolimus trough levels of ≥10 ng/mL significantly faster than the control group ( 100 % achievement in 14 days ( Control ) versus 4 days ( T2 ) ; P=0.01 ) . CONCLUSION Performing a pre-transplant tacrolimus C ( 2 ) does not significantly increase the high proportion of subjects achieving 10 ng/mL tacrolimus concentrations by day 3 using routine protocols . However , compared with standard care , performing a pre-transplant tacrolimus C ( 2 ) does lead to patients achieving a whole-blood concentration of ≥10 ng/mL sooner .

tacrolimus

tacrolimus requirements post-transplant

tacrolimus whole-blood concentrations

post-transplant

kidney transplantation


An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer . The value of early tumour marker changes during palliative chemotherapy in patients with upper gastrointestinal adenocarcinoma ( UGIA ) is unclear . Seventy-three patients with advanced UGIA were randomised to receive 45 mg/m2 docetaxel or 180 mg/m2 irinotecan with 5-FU/leucovorin . After every 2nd course the patients were crossed over to the other regimen . Serum was sampled before start of chemotherapy and every 2nd week during 8 weeks for CEA , TPA , TPS , CA72-4 , CA19-9 and CA242 measurements . Eighteen patients ( 25 % ) had partial response ( PR ) and 21 patients had stable disease for at least 4 months ( SD4 ) . All baseline marker levels , except CA72-4 , correlated with time to progression and survival . Patients with normal levels , except CA72-4 , also had more clinical responses ( PR+SD4 ) than patients with elevated values . Tumour marker changes early during treatment provided modest predictive information for tumour response and survival . A model combining baseline level , the change and the interaction between them gave the best prediction of outcome , however , insignificantly better than baseline level for all markers except CA242 . Baseline tumour marker levels provide prognostic information for patients with UGIA on palliative chemotherapy . Early changes generally failed to provide accurate information for tumour response and survival .

docetaxel

irinotecan with 5-FU/leucovorin

crossed over to the other regimen

Serum

time to progression

survival

Tumour marker changes

Baseline tumour marker

Seventy-three patients

advanced UGIA


Intensive case management before and after prison release is no more effective than comprehensive pre-release discharge planning in linking HIV-infected prisoners to care : a randomized trial . Imprisonment provides opportunities for the diagnosis and successful treatment of HIV , however , the benefits of antiretroviral therapy are frequently lost following release due to suboptimal access and utilization of health care and services . In response , some have advocated for development of intensive case-management interventions spanning incarceration and release to support treatment adherence and community re-entry for HIV-infected releasees . We conducted a randomized controlled trial of a motivational Strengths Model bridging case management intervention ( BCM ) beginning approximately 3 months prior to and continuing 6 months after release versus a standard of care prison-administered discharge planning program ( SOC ) for HIV-infected state prison inmates . The primary outcome variable was self-reported access to post-release medical care . Of the 104 inmates enrolled , 89 had at least 1 post-release study visit . Of these , 65.1 % of BCM and 54.4 % of SOC assigned participants attended a routine medical appointment within 4 weeks of release ( P > 0.3 ) . By week 12 post-release , 88.4 % of the BCM arm and 78.3 % of the SOC arm had at attended at least one medical appointment ( P = 0.2 ) , increasing in both arms at week 24-90.7 % with BCM and 89.1 % with SOC ( P > 0.5 ) . No participant without a routine medical visit by week 24 attended an appointment from weeks 24 to 48 . The mean number of clinic visits during the 48 weeks post release was 5.23 ( SD = 3.14 ) for BCM and 4.07 ( SD = 3.20 ) for SOC ( P > 0.5 ) . There were no significant differences between arms in social service utilization and re-incarceration rates were also similar . We found that a case management intervention bridging incarceration and release was no more effective than a less intensive pre-release discharge planning program in supporting health and social service utilization for HIV-infected individuals released from prison .

Intensive case management

antiretroviral therapy

routine medical appointment

least one medical appointment

HIV-infected prisoners

HIV-infected releasees .


[ Effects of computer-assisted practice on reading and spelling in children with learning disabilities ] . The main purpose of this study was to analyze the effects of computer-assisted practice on reading and spelling in children with learning disabilities ( LD ) . We compared three practice conditions , one with reading and two with spelling , in order to test whether computer-based reading and spelling practice has an influence on the development of reading and spelling ability in children with LD . A sample was selected of 85 children with LD , with age range between 8 years and 10 years ( age , M=111.02 , SD=9.6 ) , whose spelling performance was two years below grade level . The participants were randomly assigned to one of four groups : 1 ) Copy the target word from the computer screen ( n=22 ) , 2 ) Memorize the target word and write it from memory ( n=21 ) , 3 ) Word reading ( n=21 ) , and 4 ) the untrained control group ( n=21 ) . We administered measures of pseudoword reading , phonological awareness , phonological word decoding and orthographical word decoding tasks . We examined the learning effects and transfer effects on words classified as a function of length , consistency , and complexity of syllable structure . Overall , the results showed that reading training did not improve spelling ; however , the children who participated in the copy training condition improved their spelling skills .

computer-assisted practice

reading

spelling

reading and spelling


Detection rates of cancer , high grade PIN and atypical lesions suspicious for cancer in the European Randomized Study of Screening for Prostate Cancer . THE AIM OF THE STUDY This article presents the incidence of prostate cancer , isolated high grade prostatic intraepithelial neoplasia ( PIN ) and atypical lesions suspicious for prostate cancer ( LSPC ) during subsequent screening rounds in the centres of five of the countries participating in the European Randomized Study of Screening for Prostate Cancer ( ERSPC ) . The incidence and predictive value of high grade PIN and LSPC for prostate cancer in subsequent biopsy following these diagnoses were evaluated . PATIENTS AND METHODS Study group consisted of 56,653 screened men in the ERSPC centres of Finland , Italy , Netherlands , Sweden and Switzerland , who underwent 3-7 screening rounds at 2-4 year interval . Data for prostate cancer were obtained from the ERSPC central database . Data for high grade PIN and LSPC were gathered from each ERSPC centre . Detection rates of subsequent prostate cancer in the first re-biopsy after these diagnoses were determined . RESULTS The average cancer detection rate was 3.5 % , 3.2 % and 3.5 % for the completed rounds 1 , 2 and 3 , respectively , in all five centres . Incidence of high grade PIN increased from 1.5 % in the first round to 5.0 % in the third round , varying among centres in the first round between 0.8 % and 7.6 % . The cancer detection rate in the first re-biopsy after the diagnosis of high grade PIN was 12.9 % . Incidence of LSPC was 2.4 % , 2.7 % , 2.2 % and 2.6 % in the first , second , third and fourth round , respectively . The cancer detection rate at the first re-biopsy after the diagnosis of LSPC was in average 33.8 % . CONCLUSIONS Cancer detection rate was stable during the three screening rounds . The wide variation in frequency in particular of high grade PIN among the ERSPC centres suggests a considerable inter-observer variation . The average comparatively low detection rate of isolated high grade PIN in the first screening round may be screening-related , while its consistent increase during three screening rounds could be the consequence of a.o . previous screening and ageing of the population . The observed low risk of prostate cancer after isolated high grade PIN in this screening setting is in line with the current recommendation to abstain from early repeat biopsies after this diagnosis . The association of LSPC with high incidence of prostate cancer in re-biopsies confirms the need for early repeat biopsies and follow-up of these men . The low percentage of LSPC ( < 3 % of biopsies ) throughout all rounds is reassuring as it limits the biopsy burden in a screening setting .

high grade PIN and atypical lesions

screening rounds

biopsy

screened

screening rounds

screening

Detection rates

subsequent prostate cancer

average cancer detection rate

Incidence of high grade PIN

cancer detection rate

Incidence of LSPC

cancer detection rate

Cancer detection rate

detection rate

risk of prostate cancer

Screening for Prostate Cancer

men

PIN

LSPC


Lead-time in the European Randomised Study of Screening for Prostate Cancer . BACKGROUND Lead-time is defined as the time by which screening advances the diagnosis compared with absence of screening . A sufficiently long lead-time needs to be achieved so that cancer can be detected while still curable . A very short lead-time may indicate poor sensitivity of the screening test , while a very long lead-time suggests overdiagnosis . MATERIAL AND METHODS In the first screening round , a total of 56,294 men aged 55-74 years were screened with serum prostate specific antigen ( PSA ) in five countries of the European Randomised Study of Screening for Prostate Cancer ( ERSPC ) with an overall detection rate ( prevalence ) of 2.8 % ( 1972 prostate cancers ) . Prostate cancer incidence among 92,142 men randomly allocated to the control arm of the trial was also assessed . Lead-time was estimated as the time required to accumulate a similar cumulative risk of prostate cancer in the control arm to the detection rate in the intervention arm , i.e . from the ratio of detection rate ( prevalence of screen-detected cases ) and expected incidence ( cumulative risk ) . RESULTS Using a serum PSA cut-off of 4 ng/ml , the mean lead-time in the whole study population was estimated as 6.8 years ( 95 % confidence interval ( 95 % CI ) 7.9-8.4 ) . It was 8 years in The Netherlands , 6 in Sweden and Finland , 5 in Italy and 4 in Belgium . The mean lead-time was similar , 6-7 years , at ages 50-64 years , but close to 8 years among men aged 65-74 years . A lower PSA cut-off level of 3 ng/ml used in Sweden and The Netherlands prolonged the mean lead-time by approximately 1 year . Lead-time based on advanced prostate cancer only was slightly shorter , mean 5.3 years ( 95 % CI 4.6-6.0 ) . The lead-time for the second screening round was slightly shorter than that for the first ( 5.9 , 95 % CI 5.4-6.4 ) , reflecting a similar relation between detection rate and control group incidence . CONCLUSION The lead-time for prostate cancer found in ERSPC substantially exceeded that found for breast , cervical and colorectal cancer screening . One round of prostate cancer screening can advance clinical diagnosis by 4-8 years . Overdiagnosis or detection of non-progressive tumours may contribute substantially to the lead-time .

serum prostate specific antigen ( PSA )

Lead-time

mean lead-time

mean lead-time

PSA cut-off level

lead-time

Prostate Cancer .

men

aged 55-74 years

Prostate Cancer

Prostate cancer

men


Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer . BACKGROUND Pharmacogenetic markers related to drug metabolism and mechanisms of action could help to better select patients with metastatic colorectal cancer ( mCRC ) for treatment . Genetic interaction analysis is used as a rational tool to study the contribution of polygenic variation in relation to drug response . PATIENTS AND METHODS A selection of 17 polymorphisms in genes encoding drug targets , pathway molecules and detoxification enzymes was analyzed in 279 previously untreated mCRC patients treated with capecitabine , oxaliplatin and bevacizumab ( CAPOX-B ) . Multifactor dimensionality reduction analysis was used to identify a genetic interaction profile for progression-free survival ( PFS ) . RESULTS Median PFS was 10.9 [ 95 % confidence interval ( CI ) 9.4-12.4 ] months . A genetic interaction profile consisting of the TYMS enhancer region and VEGF +405G > C polymorphisms was significantly associated with PFS . Median PFS was 13.3 ( 95 % CI 11.4-15.3 ) and 9.7 ( 95 % CI 7.6-11.8 ) months for the beneficial and unfavorable genetic profiles , respectively , corresponding to a hazards ratio for PFS of 1.58 ( 95 % CI 1.14-2.19 ) . None of the studied polymorphisms were individually associated with PFS . CONCLUSIONS Our results support a genetic interaction between the TYMS enhancer region and VEGF +405G > C polymorphisms as a predictor of the efficacy of CAPOX-B in mCRC patients .

capecitabine

oxaliplatin

bevacizumab ( CAPOX-B )

pathway molecules

detoxification enzymes

PFS

genetic interaction profile

Median PFS

genetic profiles

PFS

genetic interaction

metastatic colorectal cancer .

metastatic colorectal cancer ( mCRC )

previously untreated mCRC

mCRC


Effect of total enteral nutrition on the short-term outcome of severely malnourished cirrhotics . A randomized controlled trial . Thirty-five severely malnourished cirrhotic patients were randomized to receive either enteral-tube feeding as the sole nutritional support ( n = 16 ) or an isocaloric , isonitrogenous , low-sodium standard oral diet ( n = 19 ) . Both groups were homogeneous regarding age , sex distribution , etiology of liver cirrhosis , history of previous complications , clinical status , liver and renal function , modified Child 's score , and nutritional status at admission . The enteral formula diet was energy dense , containing 40 mmol Na/day , whole protein plus branched-chain amino acids , medium- and long-chain triglycerides , and maltodextrin . It supplied 2115 kcal/day . The amount of vitamins and trace elements was at the upper limit of the recommended dietary allowances . The orally fed patients were encouraged to eat all meals served . Total enteral nutrition was well tolerated without major complications . Serum albumin and Child 's score improved in the enterally fed patients but not in controls . Mortality rate while in the hospital was lower in patients on enteral feeding than in controls ( 12 % vs 47 % ) . These results show that total enteral nutrition is safe and effective in improving the short-term clinical outcome in severely malnourished cirrhotics .

isocaloric

isonitrogenous

low-sodium standard oral diet

medium- and long-chain triglycerides

maltodextrin

It supplied 2115 kcal/day

severely malnourished cirrhotics .

Total enteral nutrition

tolerated

Serum albumin and Child 's score

Mortality rate while in the hospital

short-term clinical outcome

malnourished cirrhotics

Thirty-five

malnourished cirrhotic

malnourished cirrhotics


Antimigraine efficacy of telcagepant based on patient 's historical triptan response . OBJECTIVE To evaluate whether the same or different patients respond to triptans and telcagepant . BACKGROUND Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans . It is currently unknown whether migraine patients who can not be adequately helped with triptans might benefit from treatment with telcagepant . METHODS Post-hoc analysis of data from a randomized , controlled trial of telcagepant ( 150 mg , 300 mg ) zolmitriptan 5 mg , or placebo for a moderate/severe migraine . Responder rates were analyzed according to patients ' self-reported historical triptan response ( HTR ) : ( 1 ) good HTR ( N = 660 ) : response in 75-100 % of attacks ; ( 2 ) intermediate HTR ( N = 248 ) : response in 25-74 % of attacks ; ( 3 ) poor HTR/no use ( N = 407 ) : response in < 25 % of attacks , or patient did not take triptans . A limitation of the analysis is that the last subgroup comprised mainly ( 91 % ) patients who reported that they did not take triptans , but it was not known whether these patients were triptan-naïve or had previously used triptans and stopped taking them . RESULTS For zolmitriptan , 2-hour pain relief rates were higher in the good HTR subgroup ( 116/162 , 72 % ) than in the intermediate ( 29/62 , 47 % ) and poor/no use ( 44/111 , 40 % ) HTR subgroups . The 2-hour pain relief rates were similar across HTR subgroups for telcagepant 150 mg ( 48-58 % ) , 300 mg ( 52-58 % ) , and placebo ( 26-31 % ) . In the poor/no use HTR subgroup , more patients receiving telcagepant 300 mg ( 56/98 , 57.1 % ) had 2-hour pain relief than those receiving zolmitriptan ( 44/111 , 39.6 % ; odds ratio = 2.11 [ 95 % CI : 1.20,3.71 ] , P = .009 ) ; the percentage for telcagepant 150 mg ( 57/119 , 47.9 % ) was not significantly different from zolmitriptan ( odds ratio = 1.41 [ 95 % CI : 0.82 , 2.40 ] , P = .211 ) . CONCLUSIONS This suggests that different patients may respond to triptans or telcagepant 300 mg . Caution should be exercised in interpreting the results because of the post-hoc nature of the analysis ( clinical trial registry : NCT00442936 ) .

telcagepant

triptan

triptans

telcagepant

Telcagepant

oral triptans .

triptans

telcagepant

triptan

Antimigraine efficacy

respond to triptans

antimigraine efficacy


[ Management of the perineal wounds after abdominoperineal resection : simple drainage only or with continuous irrigation ? ] . OBJECTIVE To compare the effects of presacral irrigation and simple drainage on the perineal wound healing in patients after abdominoperineal resection ( APR ) . METHODS From October 2004 to August 2009 , patients with rectal cancer , ulcerative colitis or rectal gastrointestinal stromal tumor , who underwent APR or proctocolectomy , were randomized into two arms : simple drainage group ( n = 37 ) and continuous irrigation ( n = 37 ) . Patients randomized to arm B received simple drainage only to presacral space ; while those patients in arm A received continuous irrigation in addition to simple drainage . Perineal wound healing was taken as endpoint of this study . Major complication was defined as wound dehiscence or wound infection that the perineal wound should be reopened for drainage . Minor complication was defined as delayed healing wound with seroma or hematoma . RESULTS A total of 74 patients were enrolled in present study , with 37 patients in each arm , and there were 12 cases and 10 cases who received preoperative radiation therapy , respectively . In the arm A , 2 patients developed major complications , 3 patients incurred with minor complications and 32 patients got primary healing of the perineal wounds . In arm B , 8 patients suffered major complications , 3 patients incurred with minor complications and 26 patients got primary healing of the perineal wounds . The incidence of major complication was significantly lower in arm A ( 5.4 % vs.21.6 % , P = 0.042 ) . Patients received preoperative radiation therapy had significantly higher rate of minor complications than patients underwent surgery only ( 18.2 % vs. 3.9 % , P = 0.039 ) . CONCLUSIONS Simple drainage with continuous irrigation of the presacral space , in patients with abdominoperineal resection or proctocolectomy , could significantly lower the incidence of major complication and improve wound healing for perineal wound when compared with simple drainage only . Preoperative radiation therapy tends to increase the incidence of minor complications .

simple drainage

continuous irrigation

presacral irrigation

simple drainage

abdominoperineal resection ( APR )

APR

proctocolectomy

simple drainage

continuous irrigation

simple drainage

continuous irrigation

of the presacral space

wound dehiscence

wound infection

healing

incidence of major complication

rate of minor complications

abdominoperineal resection ( APR )

rectal cancer

ulcerative colitis

rectal gastrointestinal stromal tumor


Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer : a randomized , double-blind study . PURPOSE This randomized study compared denosumab , a fully human monoclonal antibody against receptor activator of nuclear factor κ B ( RANK ) ligand , with zoledronic acid in delaying or preventing skeletal-related events ( SREs ) in patients with breast cancer with bone metastases . PATIENTS AND METHODS Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo ( n = 1,026 ) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo ( n = 1,020 ) every 4 weeks . All patients were strongly recommended to take daily calcium and vitamin D supplements . The primary end point was time to first on-study SRE ( defined as pathologic fracture , radiation or surgery to bone , or spinal cord compression ) . RESULTS Denosumab was superior to zoledronic acid in delaying time to first on-study SRE ( hazard ratio , 0.82 ; 95 % CI , 0.71 to 0.95 ; P = .01 superiority ) and time to first and subsequent ( multiple ) on-study SREs ( rate ratio , 0.77 ; 95 % CI , 0.66 to 0.89 ; P = .001 ) . Reduction in bone turnover markers was greater with denosumab . Overall survival , disease progression , and rates of adverse events ( AEs ) and serious AEs were similar between groups . An excess of renal AEs and acute-phase reactions occurred with zoledronic acid ; hypocalcemia occurred more frequently with denosumab . Osteonecrosis of the jaw occurred infrequently ( 2.0 % , denosumab ; 1.4 % , zoledronic acid ; P = .39 ) . CONCLUSION Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated . With the convenience of a subcutaneous injection and no requirement for renal monitoring , denosumab represents a potential treatment option for patients with bone metastases .

Denosumab

zoledronic acid

denosumab

delaying time to first on-study SRE

Reduction in bone turnover markers

Overall survival

disease progression

excess of renal AEs

Osteonecrosis of the jaw

advanced breast cancer

breast cancer with bone metastases