A double-blind , placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome . PURPOSE The chronic fatigue syndrome ( CFS ) is characterized by profound fatigue , neuropsychiatric dysfunction , and frequent abnormalities in cell-mediated immunity . No effective therapy is known . PATIENTS AND METHODS Forty-nine patients ( 40 with abnormal cell-mediated immunity ) participated in a randomized , double-blind , placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month . Assessment of the severity of symptoms and associated disability , both before and after treatment , was completed at detailed interviews by a physician and psychiatrist , who were unaware of the treatment status . In addition , any change in physical symptoms and functional capacity was recorded using visual analogue scales , while changes in psychologic morbidity were assessed using patient-rated indices of depression . Cell-mediated immunity was evaluated by T-cell subset analysis , delayed-type hypersensitivity skin testing , and lymphocyte transformation with phytohemagglutinin . RESULTS At the interview conducted by the physician 3 months after the final infusion , 10 of 23 ( 43 % ) immunoglobulin recipients and three of the 26 ( 12 % ) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work , leisure , and social activities . The patients designated as having responded had improvement in physical , psychologic , and immunologic measures ( p less than 0.01 for each ) . CONCLUSION Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS , a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder .

placebo-controlled

intravenous immunoglobulin therapy

placebo-controlled

placebo solution

immunoglobulin

Immunomodulatory treatment

immunoglobulin

substantial reduction in their symptoms

recommencement of work

leisure

, and

social activities

effective

chronic fatigue syndrome

Forty-nine

abnormal cell-mediated immunity


Influence of two different flap designs on the sequelae of mandibular third molar surgery . PURPOSE The aim of this study was to compare the influence of triangular and envelope flaps on trismus , pain , and facial swelling after mandibular third molar surgery . METHODS Twenty healthy patients with bilateral , symmetrically impacted mandibular third molars were included in this double-blinded , prospective , cross-over , randomized study . The patients were operated with envelope flap on one side and triangular flap on the other side . Trismus was determined by measuring maximum interincisal opening , and facial swelling was evaluated using a tape measuring method . Pain was determined using visual analog scale ( VAS ) and recording the number of pain pills taken . RESULTS The facial swelling measurements and VAS scores were lower in the envelope flap group compared to the triangular flap group . There was no significant difference between the two flap designs in operation time , maximum interincisal opening , and the number of analgesics taken . CONCLUSION Envelope flap yields to less facial swelling and reduced VAS scores in comparison to triangular flap . There is no clinical difference in trismus between the two flap designs . Despite the higher VAS scores with triangular flap , no additional doses of analgesics were required in triangular flap .

trismus

pain

facial swelling

Trismus

facial swelling

Pain

facial swelling measurements

VAS scores

operation time

maximum interincisal opening

the number of analgesics taken

facial swelling

VAS scores

mandibular third molar surgery

mandibular third molar surgery

Twenty


The effects of face expertise training on the behavioral performance and brain activity of adults with high functioning autism spectrum disorders . The effect of expertise training with faces was studied in adults with ASD who showed initial impairment in face recognition . Participants were randomly assigned to a computerized training program involving either faces or houses . Pre- and post-testing included standardized and experimental measures of behavior and event-related brain potentials ( ERPs ) , as well as interviews after training . After training , all participants met behavioral criteria for expertise with the specific stimuli on which they received training . Scores on standardized measures improved after training for both groups , but only the face training group showed an increased face inversion effect behaviorally and electrophysiological changes to faces in the P100 component . These findings suggest that individuals with ASD can gain expertise in face processing through training .

face expertise training

expertise training with faces

training

the behavioral performance

brain activity

interviews

behavioral criteria

Scores on standardized measures

face processing


Effect of propranolol on word fluency in autism . OBJECTIVE AND BACKGROUND Autism is characterized by repetitive behaviors and impaired socialization and communication . Preliminary evidence showed possible language benefits in autism from the β-adrenergic antagonist propranolol . Earlier studies in other populations suggested propranolol might benefit performance on tasks involving a search of semantic and associative networks under certain conditions . Therefore , we wished to determine whether this benefit of propranolol includes an effect on semantic fluency in autism . METHODS A sample of 14 high-functioning adolescent and adult participants with autism and 14 matched controls were given letter and category word fluency tasks on 2 separate testing sessions ; 1 test was given 60 minutes after the administration of 40 mg propranolol orally , and 1 test was given after placebo , administered in a double-blinded , counterbalanced manner . RESULTS Participants with autism were significantly impaired compared with controls on both fluency tasks . Propranolol significantly improved performance on category fluency , but not letter fluency among autism participants . No drug effect was observed among controls . Expected drug effects on heart rate and blood pressure were observed in both the groups . CONCLUSIONS Results are consistent with a selective beneficial effect of propranolol on flexibility of access to semantic and associative networks in autism , with no observed effect on phonological networks . Further study will be necessary to understand potential clinical implications of this finding .

propranolol

on heart rate and blood pressure

autism


A randomized study on hormone-resistant prostatic cancer : estramustine phosphate versus low dose epirubicin with or without medroxyprogesterone acetate . A Norwegian multicenter study . A prospective randomized study has been carried out in order to compare three different treatment modalities for symptomatic metastatic hormone-resistant prostatic cancer . A total of 79 patients were included . One group was treated with estramustine phosphate , another with Epirubicin plus Medroxyprogesterone acetate ( MPA ) , while the third arm consisted of Epirubicin plus placebo . Best palliation was obtained by the combination of Epirubicin and MPA . This combination also seemed to be associated with the longest response duration .

estramustine phosphate

estramustine phosphate

Epirubicin

placebo

Epirubicin and MPA

Best palliation

total of 79 patients were included .


Brief report : mediation of treatment effect in a communication intervention for pre-school children with autism . Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development . We conducted a mediation analysis of a previously published randomised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care , with 28 children aged 2-5 years ( Aldred et al . in J Child Psychol Psychiatr 45:1-11 , 2004 ) . The hypothesised mediating process , targeted by the intervention , was an increase in parental synchronous response within parent-child interaction . The results showed partial mediation , with change in synchrony accounting for 34 % of the positive intervention effect on autism symptomatology ( Autism Diagnostic Observation Schedule communication and social domain algorithm ) ; the result was confirmed by bootstrap estimation . Improved parental synchronous response to child communication can alter short-term autism symptom outcome with targeted therapy .

pre-school children with autism .


Theory-driven intervention improves calcium intake , osteoporosis knowledge , and self-efficacy in community-dwelling older Black adults . OBJECTIVE To assess the effectiveness of an osteoporosis education program to improve calcium intake , knowledge , and self-efficacy in community-dwelling older Black adults . DESIGN Randomized repeated measures experimental design . SETTING Churches and community-based organizations . PARTICIPANTS Men and women ( n = 110 ) 50 years old and older from 3 south Florida counties . INTERVENTION Participants randomly assigned to either of 2 groups : Group 1 ( experimental group ) or Group 2 ( wait-list control group ) . Group 1 participated in 6 weekly education program sessions immediately following baseline assessment , and Group 2 started the program following Group 1 's program completion . A tested curriculum was adapted to meet the needs of the target population . MAIN OUTCOME MEASURES Dietary calcium intake , osteoporosis knowledge , health beliefs , and self-efficacy . ANALYSIS Descriptive and summary statistics , repeated measures analysis of variance , and regression analysis . RESULTS Of the total participants , 84.6 % completed the study ( mean age = 70.2 years ) . Overall , an educational program developed with a theoretical background was associated with improvement in calcium intake , knowledge , and self-efficacy , with no effect on most health belief subscales . Assigned group was the major predictor of change in calcium intake . CONCLUSIONS AND IMPLICATIONS A theory-driven approach is valuable in improving behavior to promote bone health in this population . Health professionals should consider using more theory-driven approaches in intervention studies .

Theory-driven intervention

osteoporosis education program

wait-list control group

6 weekly education program sessions

baseline assessment

educational program

calcium intake

osteoporosis knowledge

self-efficacy

effectiveness

calcium intake

knowledge

self-efficacy

Dietary calcium intake

osteoporosis knowledge

health beliefs

self-efficacy

calcium intake

knowledge

self-efficacy

health belief subscales

calcium intake

community-dwelling

older

Black

adults

community-dwelling

older

Black

adults

Men

women

50 years old and older

from 3 south Florida counties


Predictors of smoking cessation among cancer patients enrolled in a smoking cessation program . UNLABELLED Many cancer patients continue to smoke postdiagnosis , which is associated with poorer clinical outcomes . Identifying prospective predictors of smoking cessation among patients currently receiving smoking cessation treatment can help guide the development and implementation of smoking cessation programs with this population . MATERIAL AND METHODS Data from 246 cancer patients participating in a randomized placebo-controlled smoking cessation clinical trial were used to examine baseline predictors of end-of-treatment and six-month postbaseline smoking cessation outcomes . Baseline demographic , smoking-related , disease-related , and psychological variables were examined as predictors of biochemically-confirmed point-prevalence abstinence . RESULTS Multivariate analysis indicated that , for end-of-treatment abstinence , patients were significantly more likely to have quit smoking if they were older ( OR = 1.06 , 95 % CI : 1.03-1.10 , p < 0.05 ) and were diagnosed with a non-tobacco related cancer ( OR = 2.54 , 95 % CI : 1.24-5.20 , p < 0.05 ) . Likewise , for six-month abstinence , patients were significantly more likely to have quit smoking if they were older ( OR = 1.04 , 95 % CI : 1.01-1.08 , p < 0.05 ) and were significantly less likely to have quit smoking if they were female ( OR = 0.47 , 95 % CI : 0.22-0.97 , p < 0.05 ) . Patients with tobacco-related cancers and female patients reported significantly higher levels of depression symptoms ( p < 0.05 ) , which proved predictive of smoking relapse . CONCLUSIONS Patient age , gender , and cancer-type may be important factors to consider when developing and implementing smoking cessation interventions for cancer patients .

smoking cessation

smoking cessation

smoking cessation programs

placebo-controlled

smoking cessation

smoking cessation interventions

Multivariate

end-of-treatment abstinence

quit smoking

six-month abstinence

quit smoking

levels of depression symptoms

predictive of smoking relapse .

smoking cessation

cancer

cancer patients

cancer

female patients


A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis . Evidence supporting aspirin and resistant starch ( RS ) for colorectal cancer prevention comes from epidemiologic and laboratory studies ( aspirin and RS ) and randomized controlled clinical trials ( aspirin ) . Familial adenomatous polyposis ( FAP ) strikes young people and , untreated , confers virtually a 100 % risk of colorectal cancer and early death . We conducted an international , multicenter , randomized , placebo-controlled trial of aspirin ( 600 mg/d ) and/or RS ( 30 g/d ) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age . In a 2 × 2 factorial design , patients were randomly assigned to the following four study arms : aspirin plus RS placebo ; RS plus aspirin placebo ; aspirin plus RS ; RS placebo plus aspirin placebo ; they were followed with standard annual clinical examinations including endoscopy . The primary endpoint was polyp number in the rectum and sigmoid colon ( at the end of intervention ) , and the major secondary endpoint was size of the largest polyp . A total of 206 randomized FAP patients commenced intervention , of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis . Neither intervention significantly reduced polyp count in the rectum and sigmoid colon : aspirin relative risk = 0.77 ( 95 % CI , 0.54-1.10 ; versus nonaspirin arms ) ; RS relative risk = 1.05 ( 95 % CI , 0.73-1.49 ; versus non-RS arms ) . There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin -- mean 3.8 mm versus 5.5 mm for patients treated 1 or more years ( adjusted P = 0.09 ) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year ( P = 0.02 ) ; there were similar weaker trends with RS versus non-RS . Exploratory translational endpoints included crypt length ( which was significantly shorter in normal-appearing mucosa in the RS group over time ) and laboratory measures of proliferation ( including Ki67 ) . This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load ( number and size ) with 600 mg of aspirin daily . RS had no clinical effect on adenomas .

placebo-controlled

aspirin

resistant starch

aspirin

resistant starch ( RS )

aspirin

RS

aspirin

placebo-controlled

aspirin

RS

young

familial adenomatous polyposis

colorectal cancer

10 to 21 years


Physical activity for patients undergoing an allogeneic hematopoietic stem cell transplantation : benefits of a moderate exercise intervention . UNLABELLED An allogeneic hematopoietic stem cell transplantation ( HSCT ) can have profound and lasting adverse effects on a patient 's physical and psychological well-being . So far , only few studies have investigated the effectiveness of physical activity over the entire inpatient phase of an allogeneic HSCT . PURPOSE We performed a randomized controlled study to examine the influence of a controlled moderate exercise program starting parallel to chemotherapeutic conditioning and total body irradiation on the patient 's physical and psychological constitution . PATIENTS AND METHODS Forty-seven patients undergoing an allogeneic HSCT were randomly assigned to an exercise group ( EG ) or a control group ( CG ) . While the EG took part in an endurance and activity of daily living-training twice a day , the CG received the clinic 's standard physiotherapy program once a day . RESULTS Significant differences and/or trends in favor of the EG were observed regarding the primary endpoint endurance performance ( P=0.002 ) , muscular strength ( P=0.022 ) , fatigue ( P=0.046 ) , and emotional state ( P=0.028 ) without posing an additional risk for the individual . CONCLUSION The results show that the training program is feasible and seems to have positive influences on physical performance and quality of life in patients undergoing an allogeneic HSCT . However , further studies are necessary to confirm these results .

moderate exercise intervention

moderate exercise program

exercise group ( EG )

control group ( CG )

effectiveness

endurance performance

muscular strength

fatigue

emotional state

Forty-seven

allogeneic HSCT

patients undergoing an allogeneic HSCT


Immediate effects of a tibiofibular joint manipulation on lower extremity H-reflex measurements in individuals with chronic ankle instability . Persistent muscle inhibition of the fibularis longus and soleus muscles and altered joint arthrokinematics may play a role in chronic ankle instability ( CAI ) . Joint mobilization has been shown to improve ankle joint motion , but effects on surrounding musculature is unknown . The purpose of this study was to determine the change in fibularis longus and soleus activation following tibiofibular joint manipulation in individuals with CAI . Forty-three subjects were randomized to one of three groups ( proximal tibiofibular manipulation , distal tibiofibular manipulation , or control ) . A two-way mixed model ANOVA was used to compare changes in the ratio of the maximum H-reflex and maximum M-wave measurements ( H/M ratio ) of the fibularis longus and soleus between groups over time ( pre , post 0 , 10 , 20 , 30 min ) . The distal tibiofibular joint manipulation group demonstrated a significant increase ( P < .05 ) in soleus H/M ratio at all post-intervention time periods except 20 min post-intervention ( P=.48 ) . The proximal tibiofibular joint manipulation and control groups did not demonstrate a change in soleus H/M ratios . All groups demonstrated a decrease ( P < .05 ) from baseline values in fibularis longus ( 10-30 min post-intervention ) and soleus ( 30 min post-intervention ) H/M ratios . Interventions directed at the distal tibiofibular joint acutely increase soleus muscle activation .

tibiofibular joint manipulation

tibiofibular joint manipulation

proximal tibiofibular manipulation

distal tibiofibular manipulation

control

tibiofibular joint manipulation

tibiofibular joint manipulation

control

H-reflex measurements

maximum H-reflex

maximum M-wave measurements

soleus H/M ratio

soleus H/M ratios

fibularis longus

soleus

H/M ratios

soleus muscle activation

chronic ankle instability

chronic ankle instability ( CAI )

CAI

Forty-three


Pulsed azithromycin treatment is as effective and safe as 2-week-longer daily doxycycline treatment of acne vulgaris : a randomized , double-blind , noninferiority study . Efficacy and safety of azithromycin and doxycycline for the treatment of moderate acne vulgaris were evaluated ( 240 patients ) in both intention-to-treat and per-protocol populations . The evaluation of clinical efficacy was based on the change in the number of facial inflammatory lesions from baseline to the end of treatment , and noninferiority was defined by the upper 95 % confidence limit of the difference between two treatments being less than 9 . Reduction in the number of lesions was similar with both azithromycin and doxycycline treatments ( 27 +/- 12 and 30 +/- 12 , respectively ) in both groups . Also , the upper 95 % confidence limit of 5 inflammatory lesions has satisfied the noninferiority criterion . The incidence of adverse events did not differ between the two treatment groups . The shorter and simpler treatment schedule of azithromycin had similar efficacy and safety as doxycycline in the treatment of moderate acne vulgaris , confirming noninferiority of azithromycin as compared with doxycycline .

Pulsed azithromycin treatment

azithromycin and doxycycline

azithromycin

doxycycline

azithromycin

doxycycline

azithromycin

doxycycline

number of facial inflammatory lesions

number of lesions

efficacy and safety

acne vulgaris

moderate acne vulgaris

moderate acne vulgaris


The effects of aerobic exercise on academic engagement in young children with autism spectrum disorder . PURPOSE To determine whether participation in aerobic exercise before classroom activities improves academic engagement and reduces stereotypic behaviors in young children with autism spectrum disorder . METHODS This study employed a within-subjects crossover design , using a treatment condition ( aerobic exercise ) and a control condition , across 4 classrooms . The treatment condition included 15 minutes of running/jogging followed by a classroom task . The control condition included a classroom task not preceded by exercise . The number of stereotypic behaviors , percentage of on-task behavior , and correct/incorrect responses were measured . The Wilcoxon signed rank test was used to compare differences between conditions . RESULTS Statistically significant improvements were found in correct responding following exercise ( P < .05 ) . No significant differences were found for on-task behavior or stereotypic behaviors . CONCLUSIONS Consistent with findings in older children , these results indicate that aerobic exercise prior to classroom activities may improve academic responding in young children with autism spectrum disorder .

aerobic exercise

aerobic exercise

aerobic exercise

control condition

control

classroom task not preceded by exercise

aerobic exercise

on-task behavior

stereotypic behaviors

young children

autism spectrum disorder

young children

autism spectrum disorder

young children

autism spectrum disorder


Comparison of the evolutional process of children with autism spectrum disorders in different language therapeutic interventions . PURPOSE To analyze and compare the extension and the speed of the evolutional process of children with Autism Spectrum Disorders in direct and indirect interventions as opposed to only indirect intervention . METHODS The design of this study is a clinical trial . The sample was composed of 11 children diagnosed with Autism ( n=6 ) and Asperger syndrome ( n=5 ) by a multidisciplinary team , that attended specialized speech-language pathology therapy at the institution were the study was carried out . These children were randomly divided into two groups : Therapy Group ( TG ) - composed by six subjects receiving both direct and indirect intervention ; and Orientation Group ( OG ) - constituted by five subjects receiving exclusively indirect intervention . It was used the Autism Behavior Checklist ( ABC ) to interview the mothers , and the Sample of Vocal Behavior ( SVB ) , in three occasions : at the beginning of the intervention process ( time 0 ) , six months later ( time 1 ) and 12 months later ( time 2 ) . RESULTS It was observed greater speed and extension in the evolutional process of the TG Group , both in the analysis of the Autism Behavior Checklist ( total and partial scores ) and the Sample of Vocal Behavior , especially in the item Full Language . The performance of children with Asperger syndrome was considered more positive when compared to that of children with autism . There was greater evolution in younger children and with normal , mild , and moderate adaptive functioning . CONCLUSION The tendency towards better performance of the children attending direct and indirect intervention showed that this association is fundamental in the therapeutic process of children with Autism Spectrum Disorders .

language therapeutic interventions

direct and indirect interventions

direct and indirect intervention

evolutional process

Autism Behavior Checklist ( ABC )

Sample of Vocal Behavior ( SVB )

Sample of Vocal Behavior

evolution

adaptive functioning

performance


On the benign qualities of behavioral disinhibition : because of the prosocial nature of people , behavioral disinhibition can weaken pleasure with getting more than you deserve . This article focuses on social situations in which people are surprised about what is happening and inhibited about how to respond to the situation at hand . We study these situations by examining a classic topic in social psychology : how people respond to receiving better outcomes than are deserved . In these situations , the actions of an authority or a coworker push in the direction of accepting and enjoying the unfair outcome , whereas personal values for most people push in the direction of rejecting or being displeased with the outcome . This conflict may inhibit people 's response to the advantageous but unfair outcomes . If people are indeed inhibited about how to respond to these kinds of outcomes , then lowering behavioral inhibition by reminding people of having acted in the past without inhibitions ( in a manner that is unrelated to the outcomes participants subsequently receive ) should affect reactions to the outcomes . Specifically , we hypothesize that because many people are prosocial and want to adhere to principles of fairness , reminders of behavioral disinhibition will lead to less pleasure with the unfairly obtained outcomes . The results of 8 experiments ( conducted both inside and outside the psychology laboratory ) revealed evidence for this benign disinhibition effect on various reactions to outcomes that are better than deserved . In further accordance with our line of reasoning , the effect is particularly pronounced among those who adhere to a prosocial orientation or who have adopted a prosocial mindset and is not observed among those with proself orientations or mindsets .

behavioral disinhibition

behavioral disinhibition

experiments

behavioral disinhibition

prosocial nature of people


Literacy skills in primary school-aged children with pragmatic language impairment : a comparison with children with specific language impairment . BACKGROUND Children with pragmatic language impairment ( CwPLI ) are characterized by difficulties with the interpersonal use of language in social contexts and they possess a range of language difficulties that affect their educational attainment . Since literacy skills are central to this attainment , one way of identifying appropriate support needs for CwPLI would be to profile their reading and writing skills as a group . AIMS To investigate the word reading , non-word reading , reading comprehension , and written expression skills of CwPLI and a comparison group of children with specific language impairment ( CwSLI ) . CwSLI were recruited in order to examine any overlaps in literacy impairments for the two groups . METHODS & PROCEDURES Primary school-aged CwPLI ( n= 59 ) and CwSLI ( n= 12 ) were recruited from speech and language therapists . Children completed standardized assessments of literacy skills . The level of impairment for each component literacy skill was examined for CwPLI and CwSLI . OUTCOMES & RESULTS For the CwPLI , group mean scores on each of the literacy skills were at the lower end of the normal range compared with population norms . The range of individual scores was large , with some children scoring near floor level and others scoring up to 2 SDs ( standard deviations ) above the mean , illustrating the heterogeneity of literacy skills within the group . For the CwSLI , group mean scores on each of the literacy skills were between 1 SD and 2 SDs below the population mean . CwSLI were significantly more impaired on all of the literacy measures compared with CwPLI . This difference remained even when receptive language ability and non-verbal intelligence were controlled for . CONCLUSIONS & IMPLICATIONS The results demonstrate that there is a high level of literacy impairment within CwPLI and CwSLI , providing evidence that individualized literacy skill intervention is important for the long-term academic outcome of these children .

standardized assessments

literacy skills

individual scores

literacy measures

language ability

non-verbal intelligence

level of literacy impairment

primary school-aged children

with pragmatic language impairment

children

with specific language impairment

Children

pragmatic language impairment ( CwPLI )

CwPLI

children

specific language impairment ( CwSLI )

( n= 59 )

( n= 12 )


Safety and pharmacokinetics of a glycoPEGylated recombinant activated factor VII derivative : a randomized first human dose trial in healthy subjects . BACKGROUND Extensive research is currently ongoing to prolong the half-life of coagulation factors . One of these techniques is glycoPEGylation , which has also been applied to recombinant activated factor VII ( rFVIIa ) , resulting in a rFVIIa derivative ( N7-GP ) with a prolonged terminal half-life ( t ( 1/2 ) ) . The main clinical purpose of N7-GP is to provide safe and effective prophylaxis to patients with hemophilia and inhibitors . The prolonged t ( 1/2 ) of N7-GP can potentially reduce the dosing frequency and thereby facilitate convenience and compliance , which are two significant barriers to effective prophylaxis . OBJECTIVES To determine the safety and pharmacokinetics of single doses of N7-GP in healthy men . METHODS A randomized , placebo-controlled , dose-escalation trial with five cohorts ( N7-GP dose of 12.5-100 μg kg ( -1 ) ) was performed . In each cohort , eight subjects were randomized to receive N7-GP ( n = 6 ) or placebo ( n = 2 ) . RESULTS The mean FVIIa activity was measurable for up to at least 72 h after dosing , and the overall mean t ( 1/2 ) for FVIIa activity was 15 h. The pharmacokinetics of N7-GP appeared to be dose-proportional in the dose range investigated . No serious adverse events ( including thromboembolic events ) were reported . The frequency of adverse events was similar in both the placebo and N7-GP groups . No neutralizing antibodies against N7-GP were detected . A pharmacologic effect was apparent from a dose-dependent statistically significant decrease in the mean prothrombin time in all N7-GP groups as compared with placebo . CONCLUSIONS N7-GP had a plasma half-life of 15 h and a profile that makes it a potential candidate for prophylaxis in patients with hemophilia and inhibitors .

Safety

pharmacokinetics


Impact of dronedarone on hospitalization burden in patients with atrial fibrillation : results from the ATHENA study . AIMS Cardiovascular ( CV ) hospitalization is a predictor of CV mortality and has a negative impact on patients ' quality of life . The primary endpoint of A placebo-controlled , double-blind , parallel-arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENTs with Atrial fibrillation/atrial flutter ( ATHENA ) , a composite of first CV hospitalization or death from any cause , was significantly reduced by dronedarone . This post hoc analysis evaluated the secondary endpoint of CV hospitalization and the clinical benefit of dronedarone on the number and duration of CV hospitalizations in patients with atrial fibrillation ( AF ) . METHODS AND RESULTS ATHENA was a double-blind , parallel group study in 4628 patients with a history of paroxysmal/persistent AF and additional risk factors , treated with placebo or dronedarone . Dronedarone treatment significantly reduced the risk of first CV hospitalization ( P < 0.0001 vs. placebo ) , while the risk of first non-CV hospitalization was similar in both groups ( P = 0.77 ) . About half of the CV hospitalizations were AF-related , with a median duration of hospital stay of four nights . The risk of any hospitalization for AF [ hazard ratio ( 95 % confidence interval ) 0.626 ( 0.546-0.719 ) ] and duration of hospital stay were significantly reduced by dronedarone ( P < 0.0001 vs. placebo ) . Dronedarone treatment reduced total hospitalizations for acute coronary syndrome ( P = 0.0105 ) and the time between the first AF/atrial flutter recurrence and CV hospitalization/death ( P = 0.0048 ) . Hospitalization burden was significantly reduced across all levels of care ( P < 0.05 ) . Cumulative incidence data indicated that the effects of dronedarone persisted for at least 24 months . CONCLUSION Dronedarone reduced the risk for CV hospitalization and the total hospitalization burden in this patient group . The trial is registered under ClinicalTrials.gov # NCT 00174785 .

dronedarone

dronedarone

dronedarone

dronedarone

placebo

dronedarone

Dronedarone

placebo

dronedarone

placebo

Dronedarone

dronedarone

Dronedarone

hospitalization burden

CV mortality

quality of life .

efficacy

cardiovascular Hospitalization

death

CV hospitalization

clinical benefit

CV hospitalizations

non-CV hospitalization

CV hospitalizations

AF-related

hospital stay

hospital stay

reduced total hospitalizations

first AF/atrial flutter recurrence and

CV hospitalization/death

Hospitalization burden

CV hospitalization

hospitalization burden

patients with atrial fibrillation :


Effect of a multi-faceted intervention on gingival health among adults with systemic sclerosis . OBJECTIVES To evaluate the effect of adaptive oral hygiene devices and orofacial exercise to improve gingival health among adults with systemic sclerosis ( SSc ) . METHODS Forty-eight patients with SSc were assigned randomly to the multifaceted oral health intervention or usual dental care control group . Participants in the intervention group received a rechargeable , powered Oral-B® oscillating-rotating-pulsating toothbrush and a Reach® Access™ Flosser that has a toothbrush-like handle . For those with an oral aperture of less than 40 mm , orofacial exercises were taught . Participants in the control group were each given a manual toothbrush and dental floss . Participants in both groups received instructions and demonstration on the use of the devices , and were requested to perform the respective intervention twice a day for 6 months . Evaluations were at baseline , 3- , and 6-months . The main outcome was gingival index ( GI ) , an indicator of gingival inflammation . RESULTS Both groups showed significant reduction in GI scores at 6 months ( ps < 0.005 ) . Reduction in GI scores of the intervention group at 6 months was 20.8 % which is considered to be clinically significant . Compared to the control group , the intervention group showed a significant and larger reduction in GI score by 8 % at 6 months ( p=0.0007 ) . CONCLUSIONS Results support the use of adaptive devices and orofacial exercise to improve gingival health in adults with SSc when compared to use of manual toothbrushing and finger-held flossing . Recommending and educating patients with SSc to use adaptive devices to clean the tooth surfaces looks promising for long-term oral health improvement .

multi-faceted intervention

adaptive oral hygiene devices

orofacial exercise

multifaceted oral health intervention

usual dental care

Effect

gingival health

evaluate the effect

gingival health

adults

systemic sclerosis

adults

systemic sclerosis

SSc

Forty-eight

SSc


Effects of vitamin A or beta carotene supplementation on pregnancy-related mortality and infant mortality in rural Bangladesh : a cluster randomized trial . CONTEXT Maternal vitamin A deficiency is a public health concern in the developing world . Its prevention may improve maternal and infant survival . OBJECTIVE To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality . DESIGN , SETTING , AND PARTICIPANTS Cluster randomized , double-masked , placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks ( 84 days ) postpartum in rural northern Bangladesh between 2001 and 2007 . Interventions Five hundred ninety-six community clusters ( study sectors ) were randomized for pregnant women to receive weekly , from the first trimester through 12 weeks postpartum , 7000 μg of retinol equivalents as retinyl palmitate , 42 mg of all-trans beta carotene , or placebo . Married women ( n = 125,257 ) underwent 5-week surveillance for pregnancy , ascertained by a history of amenorrhea and confirmed by urine test . Blood samples were obtained from participants in 32 sectors ( 5 % ) for biochemical studies . MAIN OUTCOME MEASURES All-cause mortality of women related to pregnancy , stillbirth , and infant mortality to 12 weeks ( 84 days ) following pregnancy outcome . RESULTS Groups were comparable across risk factors . For the mortality outcomes , neither of the supplement group outcomes was significantly different from the placebo group outcomes . The numbers of deaths and all-cause , pregnancy-related mortality rates ( per 100,000 pregnancies ) were 41 and 206 ( 95 % confidence interval [ CI ] , 140-273 ) in the placebo group , 47 and 237 ( 95 % CI , 166-309 ) in the vitamin A group , and 50 and 250 ( 95 % CI , 177-323 ) in the beta carotene group . Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 ( 95 % CI , 0.75-1.76 ) and 1.21 ( 95 % CI , 0.81-1.81 ) , respectively . In the placebo , vitamin A , and beta carotene groups the rates of stillbirth and infant mortality were 47.9 ( 95 % CI , 44.3-51.5 ) , 45.6 ( 95 % CI , 42.1-49.2 ) , and 51.8 ( 95 % CI , 48.0-55.6 ) per 1000 births and 68.1 ( 95 % CI , 63.7-72.5 ) , 65.0 ( 95 % CI , 60.7-69.4 ) , and 69.8 ( 95 % CI , 65.4-72.3 ) per 1000 live births , respectively . Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study ( 1.46 [ 95 % CI , 1.42-1.50 ] μmol/L vs 1.13 [ 95 % CI , 1.09-1.17 ] μmol/L and 1.18 [ 95 % CI , 1.14-1.22 ] μmol/L , respectively ; P < .001 ) and reduced , but did not eliminate , gestational night blindness ( 7.1 % for vitamin A vs 9.2 % for placebo and 8.9 % for beta carotene [ P < .001 for both ] ) . CONCLUSION Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh , compared with placebo , did not reduce all-cause maternal , fetal , or infant mortality . TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT00198822 .

vitamin A

beta carotene

placebo-controlled


Effects of alcohol on the pharmacokinetics of morphine sulfate and naltrexone hydrochloride extended release capsules . Although contraindicated , coingestion of alcohol and opioids by patients or drug abusers is a major health concern because of dangerous additive and potentially life-threatening sedative and respiratory effects . In addition , alcohol has been shown to disrupt the extended-release characteristics of certain extended-release opioid formulations , releasing a hazardous amount of opioid over a short time period . Morphine sulfate and naltrexone hydrochloride extended release capsules ( MS-sNT ) , which contain naltrexone sequestered in each pellet core , are indicated for management of chronic , moderate to severe pain . Sequestered naltrexone is designed for release upon product tampering ( crushing ) to potentially mitigate morphine-induced subjective effects . This open-label , single-dose , 4-way crossover , pharmacokinetic drug interaction study compared the relative bioavailability of morphine and naltrexone when MS-sNT is administered ( under fasting conditions ) with increasing doses of alcohol . Thirty-two healthy , opioid-naive adults were randomized to MS-sNT administered with 240 mL of 4 % , 20 % , or 40 % alcohol or water . No drug interaction was found between morphine in MS-sNT and 4 % or 20 % alcohol . Administration with 40 % alcohol did not affect overall morphine exposure but was associated with a 2-fold increase in C ( max ) and reduction of t ( max ) from 9 to 4 hours versus MS-sNT taken with water . Naltrexone sequestering was successful in all treatment arms and not affected by coadministration with alcohol over the dose range tested .

alcohol

morphine sulfate

naltrexone hydrochloride

opioids

MS-sNT

alcohol

Naltrexone

pharmacokinetics

relative bioavailability

of morphine and naltrexone

doses of alcohol

drug interaction

overall morphine exposure

C ( max )

t ( max )

Naltrexone sequestering was successful


Tailored , iterative , printed dietary feedback is as effective as group education in improving dietary behaviours : results from a randomised control trial in middle-aged adults with cardiovascular risk factors . BACKGROUND Tailored nutrition interventions have been shown to be more effective than non-tailored materials in changing dietary behaviours , particularly fat intake and fruit and vegetable intake . But further research examining efficacy of tailored nutrition education in comparison to other nutrition education methods and across a wider range of dietary behaviours is needed . The Stages to Healthy Eating Patterns Study ( STEPs ) was an intervention study , in middle-aged adults with cardiovascular risk factors , to examine the effectiveness of printed , tailored , iterative dietary feedback delivered by mail in improving short-term dietary behaviour in the areas of saturated fat , fruit , vegetable and grain and cereal intake . METHODS STEPs was a 3-month randomised controlled trial with a pre and post-test design . There were three experimental conditions : 1 ) tailored , iterative , printed dietary feedback ( TF ) with three instalments mail-delivered over a 3-month period that were re-tailored to most recent assessment of dietary intake , intention to change and assessment of self-adequacy of dietary intake . Tailoring for dietary intake was performed on data from a validated 63-item combination FFQ designed for the purpose 2 ) small group nutrition education sessions ( GE ) : consisting of two 90-minute dietitian-led small group nutrition education sessions and 3 ) and a wait-listed control ( C ) group who completed the dietary measures and socio-demographic questionnaires at baseline and 3-months later . Dietary outcome measures in the areas of saturated fat intake ( g ) , and the intake of fruit ( serves ) , vegetables ( serves ) , grain and cereals as total and wholegrain ( serves ) were collected using 7-day estimated dietary records . Descriptive statistics , paired t-tests and general linear models adjusted for baseline dietary intake , age and gender were used to examine the effectiveness of different nutrition interventions . RESULTS The TF group reported a significantly greater increase in fruit intake ( 0.3 serves/d P = 0.031 ) in comparison to GE and the C group . All three intervention groups showed a reduction in total saturated fat intake . GE also had a within-group increase in mean vegetable intake after 3 months , but this increase was not different from changes in the other groups . CONCLUSIONS In this study , printed , tailored , iterative dietary feedback was more effective than small group nutrition education in improving the short-term fruit intake behaviour , and as effective in improving saturated fat intake of middle-aged adults with cardiovascular risk factors . This showed that a low-level dietary intervention could achieve modest dietary behaviour changes that are of public health significance .

nutrition education sessions

TF

saturated fat intake ( g )

total and wholegrain ( serves )

fruit intake

total saturated fat intake

mean vegetable intake

middle-aged adults

cardiovascular risk factors

middle-aged adults

cardiovascular risk factors

middle-aged adults

cardiovascular risk factors


Poor self-rated health is not associated with a high total allostatic load in type 2 diabetic patients -- but high blood pressure is . OBJECTIVE Allostatic load has been linked to self-rated health ( SRH ) , cardiovascular disease and mortality in non-diabetic individuals . The aim of this study was to construct an allostatic load score and to find any correlations with SRH . METHODS The subjects included in the study came from a randomized , controlled trial of type 2 diabetes . Blood samples were drawn , urine was collected for 24h , and questionnaires , including SRH , were filled out on three occasions : at baseline ; after the 10-week intervention ; and at a follow-up 3 months after the intervention . Allostatic load was estimated using a wide range of variables , including systolic and diastolic blood pressure , pulse pressure , cortisol , catecholamines , HbA ( 1c ) , insulin , plasma glucose and waist circumference . RESULTS There was no association between SRH and allostatic load . However , three other components were significantly correlated with allostatic load at the baseline investigation and the two follow-up investigations - namely , systolic blood pressure , diastolic blood pressure and HbA ( 1c ) . CONCLUSION The absence of an association between allostatic load and SRH in diabetic individuals contrasts with previous findings in non-diabetic women , and shows that it is hazardous to apply findings in one population to another , especially diabetic and non-diabetic populations .

SRH


The effects of encoding in hypnosis and post-hypnotic suggestion on academic performance . This study examined the relationship between proactive learning in hypnosis , post-hypnotic suggestion , and academic performance . Participants ( N = 56 ) were randomly assigned to a control group or a treatment group . The treatment group was hypnotized and read a passage while in hypnosis . Concurrently , they were given a post-hypnotic suggestion , which attempted to aid recognition and performance on a test immediately following the hypnosis session . Both groups completed a multiple-choice test based on the aforementioned passage . An analysis of covariance discerned the effect of proactive learning and post-hypnotic suggestion on test performance , while controlling for the variance introduced by scholastic aptitude as measured by the ACT . Results indicated that the hypnosis sessions predicted significantly impaired test performance .

hypnosis , post-hypnotic suggestion

control

treatment

hypnotized

hypnosis

post-hypnotic suggestion

hypnosis

effect of proactive learning

post-hypnotic suggestion

test performance

scholastic aptitude

impaired test performance


Study protocol : Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease . BACKGROUND Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals . The Breathlessness Intervention Service ( BIS ) seeks to improve the care of breathless patients with advanced disease ( regardless of cause ) through the use of evidence-based practice and working with other healthcare providers . BIS delivers a complex intervention ( of non-pharmacological and pharmacological treatments ) via a multi-professional team . BIS is being continuously developed and its impact evaluated using the MRC 's framework for complex interventions ( PreClinical , Phase I and Phase II completed ) . This paper presents the protocol for Phase III . METHODS/DESIGN Phase III comprises a pragmatic , fast-track , single-blind randomised controlled trial of BIS versus standard care . Due to differing disease trajectories , the service uses two broad service models : one for patients with malignant disease ( intervention delivered over two weeks ) and one for patients with non-malignant disease ( intervention delivered over four weeks ) . The Phase III trial therefore consists of two sub-protocols : one for patients with malignant conditions ( four week protocol ) and one for patients with non-malignant conditions ( eight week protocol ) . Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol . Qualitative interviews are conducted with referring and non-referring health care professionals ( malignant disease protocol only ) . The primary outcome measure is 'patient distress due to breathlessness ' measured on a numerical rating scale ( 0-10 ) . The trial includes economic evaluation . Analysis will be on an intention to treat basis . DISCUSSION This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast track methodology and single-blinding . The results will provide evidence of the clinical and cost-effectiveness of the service , informing its longer term development and implementation of the model in other centres nationally and internationally . It adds to methodological developments in palliative care research where complex interventions are common but evidence sparse . TRIAL REGISTRATION ClinicalTrials.gov : NCT00678405ISRCTN : ISRCTN04119516 .

complex intervention

non-pharmacological

standard care

two broad service models

Mixed method interviews

palliative care

breathlessness in advanced disease

distress to patients

care of breathless patients

economic evaluation

breathlessness in advanced disease

malignant disease

non-malignant disease

malignant conditions

non-malignant conditions


Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery : results from a randomized trial . OBJECTIVE A heightened inflammatory response occurs after cardiac surgery . The perioperative use of glucocorticoids has been advocated as a method to improve postoperative outcomes . Randomized prospective studies to quantify the effect of methylprednisolone on perioperative outcomes in neonatal cardiac surgery have not been performed . We sought to determine whether preoperative methylprednisolone would improve postoperative recovery in neonates requiring cardiac surgery . METHODS Neonates scheduled for cardiac surgery were randomly assigned to receive either 2-dose ( 8 hours preoperatively and operatively , n = 39 ) or single-dose ( operatively , n = 37 ) methylprednisolone ( 30 mg/kg per dose ) in a prospective double-blind trial . The primary outcome was the incidence of low cardiac output syndrome ( standardized score ) or death 36 hours postoperatively . Secondary outcomes were death at 30 days , interleukin-6 levels , inotropic score , fluid balance , serum creatinine , and intensive care unit and hospital stay . RESULTS Preoperative plasma levels of the inflammatory cytokine interleukin-6 were reduced by 2-fold ( P < .001 ) in the 2-dose methylprednisolone group , consistent with the anti-inflammatory effects of methylprednisolone . However , the incidence of low cardiac output syndrome was 46 % ( 17/37 ) in the single-dose and 38 % ( 15/39 ) in the 2-dose methylprednisolone groups ( P = .51 ) . Two-dose methylprednisolone was associated with a higher serum creatinine ( 0.61 ± 0.18 mg/dL vs 0.53 ± 0.12 mg/dL , P = .03 ) and poorer postoperative diuresis ( -96 ± 49 mL , P = .05 ) . Inotropic requirement , duration of mechanical ventilation , intensive care unit , and hospital stay did not differ between the 2 groups . CONCLUSIONS Combined preoperative and intraoperative use of glucocorticoids in neonatal cardiac surgery does not favorably affect early clinical outcomes and may exacerbate perioperative renal dysfunction .

corticosteroid

methylprednisolone

death at 30 days

intensive care unit and hospital stay

Preoperative plasma levels

the inflammatory cytokine interleukin-6

serum creatinine

postoperative

neonates undergoing cardiac surgery :


Do sheltered workshops enhance employment outcomes for adults with autism spectrum disorder ? This study investigated whether sheltered workshops help prepare individuals with autism spectrum disorder ( ASD ) for competitive employment within the community . Two groups of individuals were compared : ( a ) 215 supported employees who were in sheltered workshops prior to entering supported employment and ( b ) 215 supported employees who were not in sheltered workshops . Individuals from both groups were matched based on their primary diagnosis , secondary diagnosis ( if present ) , and gender . Results showed that there were no differences in rates of employment between these two groups . However , individuals who participated in sheltered workshops earned significantly less ( US $ 129.36 versus US $ 191.42 per week ) , and cost significantly more to serve ( US $ 6,065.08 versus US $ 2,440.60 ) , than their non-sheltered workshop peers . Results presented here suggest that individuals with ASD achieve better vocational outcomes if they do not participate in sheltered workshops prior to enrolling in supported employment .

sheltered workshops

sheltered workshops

sheltered workshops

not in sheltered workshops

sheltered workshops

non-sheltered workshop

employment outcomes

competitive employment

rates of employment

earned significantly less

cost significantly more

better vocational outcomes

adults with autism spectrum disorder


Effectiveness of a short-term treatment with progesterone injections on synchrony of lambing and fertility in tropical hair sheep . The efficacy of using a low cost system for delivering progesterone as part of an estrous synchronization protocol in sheep was evaluated . In experiment 1 , Barbados Black Belly ewes ( n=34 ) and ewe lambs ( n=35 ; 37.5±0.9 kg ) were assigned to be untreated , control animals ( C ) , or to receive PGF ( 2α ) on d0 ( PG ) , or receive two injections of progesterone ( 200mg , i.m . each ) on D -5 and on D -2.5 , prior to PGF ( 2α ) , on D 0 ( 2PPG ) . Treatment with 2PPG increased the proportion of animals lambing to the first service ( P < 0.05 ) , an effect that was greater in ewe lambs than ewes ( treatment × parity ; P < 0.05 ) . The interval from ram introduction to lambing and the mean lambing day was less ( P=0.04 ) in the 2PPG-treated animals compared to control animals . In Experiment 2 , lactating ewes from experiment 1 ( n=61 ) 60-85 days postpartum were assigned within parity and number of lambs reared to remain nursing ( S ; n=29 ) or weaned ( W ; n=32 ) 3 weeks prior to treatment with the 2PPG protocol . There was no effect of treatment on the proportion of animals lambing to the first service or overall , interval from ram introduction to lambing and lambing interval . An 8-month lambing interval was observed in ewes in which estrus was synchronized regardless of physiological state . In conclusion , the two-progesterone injection synchronization protocol may be used as a practical low cost and efficient method of synchronizing estrus to reduce the lambing interval and maximize productivity in tropical breeds of sheep .

progesterone

progesterone


Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial . Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies . Using logistic regression , we estimated odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) to prospectively evaluate the association between lignan and proanthocyanidin intake , estimated from databases linked to a food frequency questionnaire , and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial . Overall , individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence . However , in sex-specific analyses , total lignan intake was positively associated with any adenoma recurrence in women ( highest vs. lowest lignan intake quartile OR = 2.07 , 95 % CI : 1.22-3.52 , p trend = 0.004 ) but not in men ( p interaction = 0.04 ) . To conclude , dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence ; however , high lignan intake may increase the risk of adenoma recurrence in women .

Dietary lignan

proanthocyanidin

polyphenols

lignan

proanthocyanidin intake

colorectal adenoma recurrence

colorectal neoplasms

adenoma recurrence

colorectal adenoma recurrence

adenoma recurrence

colorectal adenoma recurrence

risk of adenoma recurrence

colorectal adenoma recurrence

colorectal neoplasms

women .


Lung function and respiratory symptoms in a 1-year randomized smoking cessation trial of varenicline in COPD patients . UNLABELLED There are few data concerning changes in lung function and respiratory symptoms in smokers with chronic obstructive pulmonary disease ( COPD ) weeks to months after quitting smoking . We examined serial changes in spirometry and Clinical COPD Questionnaire ( CCQ ) scores ( measuring respiratory symptoms and health-related quality of life ) in COPD participants by smoking status during a smoking cessation trial . In this randomized , double-blind trial , smokers with mild-to-moderate COPD were treated with varenicline 1 mg b.i.d . or placebo for 12 weeks and followed to Week 52 . Primary endpoints of abstinence were previously reported . Secondary endpoints were mean changes from baseline in post-bronchodilator forced expired volume in 1 s ( FEV ( 1 ) ) and CCQ scores . Change from baseline in post-bronchodilator FEV ( 1 ) was significantly improved in continuous abstainers ( 121.8 mL ) vs. continuous smokers ( 37.9 mL ) at Week 12 ( P = 0.0069 ) , but not at Weeks 24 or 52 . Mean change from baseline at Week 12 in CCQ Total Score was significantly better in continuous abstainers ( -1.04 ) vs. continuous smokers ( -0.53 ; P < 0.0001 ) : this improvement was sustained at Weeks 24 and 52 . In a 1-year cessation trial of smokers with COPD , continuous abstinence compared with continuous smoking significantly improved post-bronchodilator FEV ( 1 ) at Week 12 ( although the difference narrowed subsequently ) and CCQ Total Scores at Week 12 , with sustained improvement thereafter . ( TRIAL REGISTRY http : //www.clinicaltrials.gov ; trial identifier : NCT00285012 ) .

varenicline

varenicline 1 mg b.i.d .

placebo

abstinence

CCQ scores

FEV ( 1

CCQ Total Score

continuous abstinence

post-bronchodilator

CCQ Total Scores

COPD patients

COPD

COPD

smokers with COPD


Enalapril and lisinopril in the treatment of mild to moderate essential hypertension . Hypertensive patients were randomly assigned to receive 5 mg of enalapril ( n = 50 ) or 10 mg of lisinopril ( n = 47 ) daily . During a four-week titration period , the doses were increased weekly to a maximum of 40 mg once daily until the treatment goal of diastolic blood pressure ( BP ) of less than 90 mmHg was reached ; treatment was then continued for four weeks . Systolic and diastolic BP declined significantly in the two treatment groups , from 147/98 mmHg in both the enalapril and lisinopril groups to 126/82 and 122/81 mmHg , respectively , at the end of treatment . During the first week of treatment , the goal of diastolic BP of less than 90 mmHg was reached by 40 % of the enalapril group and 62 % of the lisinopril group ; by the end of the titration period , 98 % and 96 % , respectively , had achieved the BP goal . Few side effects were reported and there were no abnormal laboratory findings during treatment . It is concluded that once-daily administration of enalapril or lisinopril was generally effective and well-tolerated in the management of mild to moderate uncomplicated essential hypertension .

Enalapril

lisinopril

5 mg of enalapril

10 mg of lisinopril

enalapril

lisinopril

enalapril

lisinopril

enalapril

lisinopril

Systolic and diastolic BP

diastolic BP

BP

side effects

two

hypertension


A prospective double-blind , randomized clinical trial of levocarnitine to treat autism spectrum disorders . BACKGROUND L-carnitine was proposed as a potential treatment for patients diagnosed with an autism spectrum disorder to improve mitochondrial dysfunction , but no prior randomized controlled trials have been conducted . MATERIAL/METHODS Thirty subjects diagnosed with an ASD were randomly assigned to receive a standardized regimen ( 50 mg L-carnitine/kg bodyweight/day ) of liquid L-carnitine ( n=19 ) or placebo ( n=11 ) for 3-months . Measures included changes in professionally completed Childhood Autism Rating Scale ( CARS ) , hand muscle testing , and modified clinical global impression ( CGI ) forms ; parent completed Autism Treatment Evaluation Checklist ( ATEC ) , treatment adherence measurement ( TAM ) , frequency and intensity of side effect rating ( FISER ) /global rating of side effect burden ( GRSEB ) /patient report of incidence of side effects ( PRISE ) forms ; and lab testing . RESULTS Significant improvements were observed in CARS ( -2.03 , 95 % CI=-3.7 to -0.31 ) , CGI ( -0.69 , 95 % CI=-1.1 to -0.06 ) , and ATEC scores . Significant correlations between changes in serum free-carnitine levels and positive clinical changes were observed for hand muscle strength ( R2=0.23 , P=0.046 ) , cognitive scores ( R2=0.27 , P=0.019 ) , and CARS scores ( R2=0.20 , P=0.047 ) . Study subjects were protocol-compliant ( average adherence was > 85 % ) and generally well-tolerated the L-carnitine therapy given . CONCLUSIONS L-carnitine therapy ( 50 mg/kilogram-bodyweight/day ) administered for 3-months significantly improved several clinical measurements of ASD severity , but subsequent studies are recommended .

levocarnitine

L-carnitine

placebo ( n=11 ) for 3-months

Childhood Autism Rating Scale ( CARS )

treatment adherence measurement ( TAM )

CARS

CGI

ATEC scores

hand muscle strength

cognitive scores

CARS scores

autism spectrum disorders .

Thirty subjects diagnosed with an ASD


Effect of intensive insulin therapy on the somatotropic axis of critically ill children . CONTEXT Intensive insulin therapy ( IIT ) improved outcome in the adult and pediatric intensive care unit ( PICU ) compared with conventional insulin therapy ( CIT ) . IIT did not increase the anabolic hormone IGF-I in critically ill adults , but feeding in critically ill children and pediatric hormonal responses may differ . Twenty-five percent of the children with IIT experienced hypoglycemia , which may have evoked counterregulatory responses . OBJECTIVE We hypothesized that IIT reactivates the somatotropic axis and anabolism in PICU patients . DESIGN This was a preplanned subanalysis of a randomized controlled trial on IIT . PATIENTS We studied 369 patients who stayed in PICU for at least 3 d ( study 1 ) and 126 patients in a nested case-control study ( study 2 ) . MAIN OUTCOME MEASURES Circulating insulin , C-peptide , GH , IGF-I , bioavailable IGF-I , IGF-binding protein ( IGFBP ) -1 , IGFBP-3 , and acid-labile subunit were analyzed upon admission and d 3 . In the nested case-control study , the somatotropic axis , cortisol , and glucagon were analyzed before and after hypoglycemia . RESULTS On d 3 , C-peptide was more than 10-fold lower ( P < 0.0001 ) in the IIT group than in the CIT group . IIT increased circulating GH ( P = 0.04 ) and lowered bioavailable IGF-I ( P = 0.002 ) . IIT also decreased IGFBP-3 ( P = 0.0005 ) and acid-labile subunit ( P = 0.007 ) , while increasing IGFBP-1 ( P = 0.04 ) and the urea/creatinine ratio , a marker of catabolism ( P = 0.03 ) . In the nested case-control study , IGFBP-1 was increased after hypoglycemia , whereas the somatotropic axis and the counterregulatory hormones cortisol and glucagon did not change . CONCLUSIONS Despite improved PICU outcome , IIT did not counteract the catabolic state of critical illness . Suppression of portal insulin may have resulted in lower bioavailable IGF-I .

intensive insulin therapy

Intensive insulin therapy ( IIT )

conventional insulin therapy ( CIT )

IIT

IIT

IIT

IIT

CIT

IIT

IIT

IIT

anabolism

insulin

C-peptide

GH

IGF-I

bioavailable IGF-I

IGF-binding protein ( IGFBP ) -1

acid-labile subunit

cortisol

glucagon

C-peptide

circulating GH

bioavailable IGF-I

acid-labile subunit

urea/creatinine ratio

cortisol and glucagon

catabolic state of critical illness

critically ill

children

children

hypoglycemia


Short-term metabolic effects of prednisone administration in healthy subjects . AIMS Supraphysiologic glucocorticoid activity is well established to cause impaired glucose tolerance and insulin resistance , yet no study has evaluated dose-dependent effects of low-dose prednisone during short-term oral administration . METHODS The objective of this study was to quantify the effects of daily 10 or 25 mg prednisone administration for one week on insulin sensitivity by employing a two-step hyperinsulinemic euglycemic glucose clamp ( Step 1 : insulin infusion = 20 mU/m²/min ; Step 2 : insulin infusion = 80 mU/m²/min ) in healthy , lean males . The amount of glucose infused at steady-state to maintain stable blood glucose [ 90 mg/dl ( 4.95 mmol/l ) ] was used to calculate several indices of insulin sensitivity . RESULTS During Step 1 of the clamp , whole body glucose disposal ( M ) was reduced by 35 % ( p = 0.003 ) and M/I was reduced by 29 % ( p = 0.025 ) for 25 mg prednisone compared to placebo . No appreciable effect of 10 mg prednisone was observed . During Step 2 , M was reduced by 33 % ( p = 0.001 ) and 15 % ( p = 0.006 ) for 25 and 10 mg prednisone compared to placebo ; and M/I ratio was reduced by 31 % ( p < 0.001 ) and 13 % ( p = 0.026 ) , respectively . The insulin sensitivity index , Si , calculated as the quotient of augmentation of M/I between Step 1 and 2 , was reduced by 35.3 % ( p < 0.01 ) and 23.5 % ( p < 0.05 ) for 25 and 10 mg prednisone , respectively . CONCLUSION Administration of relatively low pharmacological doses of prednisone for one week impaired insulin sensitivity in a dose-dependent manner in healthy males . These observed changes in insulin sensitivity are likely to be clinically relevant , especially in individuals predisposed to develop glucose intolerance .

prednisone

prednisone

10 or 25 mg prednisone

effects

glucose tolerance

insulin resistance

healthy


Short-term effect of pitavastatin on the reactive hyperemic index in post-menopausal women with high levels in serum LDL-cholesterol .

pitavastatin

reactive hyperemic index

post-menopausal

women

high levels in serum LDL-cholesterol


Exemestane for breast-cancer prevention in postmenopausal women . BACKGROUND Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer . Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer . METHODS In a randomized , placebo-controlled , double-blind trial of exemestane designed to detect a 65 % relative reduction in invasive breast cancer , eligible postmenopausal women 35 years of age or older had at least one of the following risk factors : 60 years of age or older ; Gail 5-year risk score greater than 1.66 % ( chances in 100 of invasive breast cancer developing within 5 years ) ; prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ ; or ductal carcinoma in situ with mastectomy . Toxic effects and health-related and menopause-specific qualities of life were measured . RESULTS A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3 % were randomly assigned to either exemestane or placebo . At a median follow-up of 35 months , 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo , with a 65 % relative reduction in the annual incidence of invasive breast cancer ( 0.19 % vs. 0.55 % ; hazard ratio , 0.35 ; 95 % confidence interval [ CI ] , 0.18 to 0.70 ; P=0.002 ) . The annual incidence of invasive plus noninvasive ( ductal carcinoma in situ ) breast cancers was 0.35 % on exemestane and 0.77 % on placebo ( hazard ratio , 0.47 ; 95 % CI , 0.27 to 0.79 ; P=0.004 ) . Adverse events occurred in 88 % of the exemestane group and 85 % of the placebo group ( P=0.003 ) , with no significant differences between the two groups in terms of skeletal fractures , cardiovascular events , other cancers , or treatment-related deaths . Minimal quality-of-life differences were observed . CONCLUSIONS Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer . During a median follow-up period of 3 years , exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life . ( Funded by Pfizer and others ; NCIC CTG MAP.3 ClinicalTrials.gov number , NCT00083174 . ) .

Exemestane

placebo-controlled

exemestane

exemestane

placebo

exemestane

placebo

placebo

Exemestane

Toxic effects and

median Gail risk score

Adverse events

skeletal fractures

cardiovascular events

other

cancers

treatment-related deaths

quality-of-life


Infliximab in ankylosing spondylitis : alone or in combination with methotrexate ? A pharmacokinetic comparative study . INTRODUCTION Methotrexate ( MTX ) has been shown to modify infliximab pharmacokinetics in rheumatoid arthritis . However , its combination with infliximab in the treatment of ankylosing spondylitis ( AS ) is not recommended . The objective of this study was to examine the influence of MTX on infliximab exposure in patients with AS . METHODS Patients with AS patients who had predominantly axial symptoms were randomised to receive infliximab alone ( infusions of 5 mg/kg at weeks 0 , 2 , 6 , 12 and 18 ) or infliximab combined with MTX ( 10 mg/week ) . Infliximab concentrations were measured before and 2 hours after each infusion and at 1 , 3 , 4 , 5 , 8 , 10 , 14 and 18 weeks . We estimated individual cumulative area under the concentration versus time curves ( AUC ) for infliximab concentration between baseline and week 18 ( AUC ( 0-18 ) ) . Clinical and laboratory evaluations were performed at each visit . The Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score was the primary end point for clinical response . RESULTS Twenty-six patients were included ( infliximab group : n = 12 , infliximab + MTX group : n = 14 ) , and 507 serum samples were available for measurement of infliximab concentration . The two groups did not differ with regard to AUC ( 0-18 ) or evolution of BASDAI scores and biomarkers of inflammation . CONCLUSIONS The combination of MTX and infliximab does not increase the exposure to infliximab over infliximab alone in patients with AS . TRIAL REGISTRATION ClinicalTrials.gov : NCT00507403 .

Infliximab

methotrexate

Methotrexate

infliximab

infliximab

MTX on infliximab

infliximab alone

or infliximab combined with MTX

Infliximab

infliximab

infliximab + MTX

infliximab

Infliximab concentrations

infliximab concentration

infliximab concentration

AUC

( 0-18 )

BASDAI scores


β-Blockers in patients with intermittent claudication and arterial hypertension : results from the nebivolol or metoprolol in arterial occlusive disease trial . The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone . The β-blocker nebivolol possesses vasodilating , endothelium-dependent , NO-releasing properties that might be beneficial in peripheral arterial disease . The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients . A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol ( N=65 ) or 95 mg of metoprolol ( N=63 ) once daily . End points were changes in ankle-brachial index , initial and absolute claudication distance , endothelial function assessed by flow-mediated dilatation of the brachial artery , blood pressure , and quality of life using the claudication scale questionnaire . End point analysis was possible in 109 patients ( 85.2 % ) . After the 48-week treatment period , ankle-brachial index and absolute claudication distance improved significantly in both patient groups ( P < 0.05 for both ) , with no difference across treatments . A significant increase of initial claudication distance was found in the nebivolol group . Adjusted mean change of initial claudication distance was 33.9 % after nebivolol ( P=0.003 ) and 16.6 % after metoprolol ( P=0.12 ) treatment . Quality of life was not influenced by either treatment , and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol ( P=0.16 ) . Both drugs were equally effective in lowering blood pressure . In conclusion , β-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year . In the direct comparison , there was no significant difference between nebivolol and metoprolol .

effects and tolerability

blood pressure

lowering blood pressure


Low-dose clonidine administration in the treatment of mild or moderate essential hypertension : results from a double-blind placebo-controlled study ( Clobass ) . The Clobass Study Group . Five hundred and fifty-nine hypertensive outpatients with diastolic blood pressure between 95 and 110 mmHg participated in this double-blind , placebo-controlled , multicenter study . Eligible subjects were randomly allocated to receive either clonidine ( 75 micrograms twice daily ) or a placebo . After 4 weeks , 'responders ' to treatment ( diastolic blood pressure reduced to less than or equal to 90 mmHg or by greater than or equal to 10 mmHg ) were kept on monotherapy and checked at 4-weekly intervals for another 3 months . Non-responders were given 15 mg chlorthalidone and were also checked for a further 3 months . At the end of the first month , 54.2 % of the subjects were responders to clonidine and 41.5 % were responders to the placebo ( P less than 0.05 for both groups ) . Of the remaining patients , 69.0 % became responders to clonidine plus chlorthalidone , whereas only 34.7 % were responders to placebo plus chlorthalidone ( P less than 0.01 for both groups ) . Withdrawals from the study because of excessive diastolic blood pressure levels were about eight times less frequent among the subjects treated with clonidine , either alone or with chlorthalidone . Dry mouth was twice as frequent in the clonidine-treated patients , but there was no significant difference in the incidence of all side effects or the number of withdrawals from the study because of side effects between the two groups . We conclude that low-dose clonidine is effective in the treatment of mild or moderate hypertension . Clonidine-related side effects are still evident , but the overall tolerance profile for this reduced dosage of the drug appears to be favorable .

clonidine

placebo-controlled

placebo-controlled

clonidine

placebo .

monotherapy

chlorthalidone

clonidine

placebo

clonidine

chlorthalidone

placebo

chlorthalidone

clonidine

chlorthalidone .

clonidine-treated

clonidine

Clonidine-related

diastolic blood pressure

Dry mouth

side effects

number of withdrawals

mild or moderate essential hypertension

Five hundred and fifty-nine


An allopurinol-controlled , randomized , double-dummy , double-blind , parallel between-group , comparative study of febuxostat ( TMX-67 ) , a non-purine-selective inhibitor of xanthine oxidase , in patients with hyperuricemia including those with gout in Japan : phase 3 clinical study . BACKGROUND Allopurinol has been widely used for treatment of hyperuricemia , however , it may be associated with various adverse effects . Febuxostat is potentially a safe and efficacious alternative . OBJECTIVES Febuxostat or allopurinol was administered to patients with hyperuricemia including gout for 8 weeks to compare the efficacy and safety of these drugs . METHODS Doses of febuxostat and allopurinol were 10 and 100 mg/d , respectively , during a 12-day introduction period and were increased to 40 and 200 mg/d for the subsequent treatment period of 44 days . RESULTS : The percent changes in serum uric acid levels after 8 weeks were -40.75 % for the febuxostat group and -34.41 % for the allopurinol group ( P < 0.001 , analysis of variance , closing testing procedure ) . The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 82.0 % for the febuxostat group and 70.0 % for the allopurinol group ( P = 0.019 , logistic regression analysis ) . Regarding safety , 213 adverse events were observed in the febuxostat group and 220 events in the allopurinol group . For 10 patients ( 8.2 % ) in the febuxostat group and 14 patients ( 11.6 % ) in the allopurinol group , association with the study drugs could not be ruled out . There were no severe adverse drug reactions in the febuxostat group other than a high frequency of gout attacks induced by the sudden reduction in blood uric acid levels during the early treatment period . CONCLUSIONS Febuxostat at 40 mg/d demonstrated more potent hypouricemic effects than allopurinol at 200 mg/d , was efficacious regardless of medical history of gout , and is considered safe for treatment of hyperuricemia .

allopurinol-controlled

febuxostat ( TMX-67 )

Allopurinol

Febuxostat

allopurinol

febuxostat

allopurinol

febuxostat

allopurinol

allopurinol

febuxostat

febuxostat

allopurinol

febuxostat

Febuxostat

allopurinol

efficacy

safety

changes in serum uric acid levels

serum uric acid levels

safety

adverse events

severe adverse drug reactions

gout attacks

potent hypouricemic effects

hyperuricemia

hyperuricemia

hyperuricemia

gout


Effects of cognitive-behavioral therapy on anxiety in children with autism spectrum disorders : a randomized controlled trial . We compared the effects of a 16-week Cognitive-Behavioral Therapy ( CBT ) program and a Social Recreational ( SR ) program on anxiety in children with Autism Spectrum Disorders ( ASD ) . Seventy children ( 9-16 years old ) were randomly assigned to either of the programs ( n ( CBT ) = 36 ; n ( SR ) = 34 ) . Measures on child 's anxiety using the Spence Child Anxiety Scale -- Child ( SCAS-C ) and the Clinical Global Impression-Severity scale ( CGI -- S ) were administered at pre- , post-treatment , and follow-ups ( 3- and 6-month ) . Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as " Normal " and " Borderline " for both programs . Findings from the present study suggest factors such as regular sessions in a structured setting , consistent therapists , social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD .

cognitive-behavioral therapy

Cognitive-Behavioral Therapy ( CBT )

program

Social Recreational ( SR ) program

CBT

autism-friendly strategies

CGI-S


[ Diabetic retinopathy candesartan trial ] .

Diabetic retinopathy

candesartan

[ Diabetic retinopathy


The benefits of including clinical factors in rectal normal tissue complication probability modeling after radiotherapy for prostate cancer . PURPOSE To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial . METHODS AND MATERIALS Toxicity data of 512 patients ( conformally treated to 68 Gy [ n = 284 ] and 78 Gy [ n = 228 ] ) with complete follow-up at 3 years after radiotherapy were studied . Scored end points were rectal bleeding , high stool frequency , and fecal incontinence . Two traditional dose-based models ( Lyman-Kutcher-Burman ( LKB ) and Relative Seriality ( RS ) and a logistic model were fitted using a maximum likelihood approach . Furthermore , these model fits were improved by including the most significant clinical factors . The area under the receiver operating characteristic curve ( AUC ) was used to compare the discriminating ability of all fits . RESULTS Including clinical factors significantly increased the predictive power of the models for all end points . In the optimal LKB , RS , and logistic models for rectal bleeding and fecal incontinence , the first significant ( p = 0.011-0.013 ) clinical factor was " previous abdominal surgery . " As second significant ( p = 0.012-0.016 ) factor , " cardiac history " was included in all three rectal bleeding fits , whereas including " diabetes " was significant ( p = 0.039-0.048 ) in fecal incontinence modeling but only in the LKB and logistic models . High stool frequency fits only benefitted significantly ( p = 0.003-0.006 ) from the inclusion of the baseline toxicity score . For all models rectal bleeding fits had the highest AUC ( 0.77 ) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence , respectively . LKB and logistic model fits resulted in similar values for the volume parameter . The steepness parameter was somewhat higher in the logistic model , also resulting in a slightly lower D ( 50 ) . Anal wall DVHs were used for fecal incontinence , whereas anorectal wall dose best described the other two endpoints . CONCLUSIONS Comparable prediction models were obtained with LKB , RS , and logistic NTCP models . Including clinical factors improved the predictive power of all models significantly .

complication probability modeling

radiotherapy

High stool frequency

after radiotherapy

prostate cancer


Positive impact of crisis resource management training on no-flow time and team member verbalisations during simulated cardiopulmonary resuscitation : a randomised controlled trial . OBJECTIVES To evaluate the impact of video-based interactive crisis resource management ( CRM ) training on no-flow time ( NFT ) and on proportions of team member verbalisations ( TMV ) during simulated cardiopulmonary resuscitation ( CPR ) . Further , to investigate the link between team leader verbalisation accuracy and NFT . METHODS The randomised controlled study was embedded in the obligatory advanced life support ( ALS ) course for final-year medical students . Students ( 176 ; 25.35±1.03 years , 63 % female ) were alphabetically assigned to 44 four-person teams that were then randomly ( computer-generated ) assigned to either CRM intervention ( n=26 ) , receiving interactive video-based CRM-training , or to control intervention ( n=18 ) , receiving an additional ALS-training . Primary outcomes were NFT and proportions of TMV , which were subdivided into eight categories : four team leader verbalisations ( TLV ) with different accuracy levels and four follower verbalisation categories ( FV ) . Measurements were made of all groups administering simulated adult CPR . RESULTS NFT rates were significantly lower in the CRM-training group ( 31.4±6.1 % vs. 36.3±6.6 % , p=0.014 ) . Proportions of all TLV categories were higher in the CRM-training group ( p < 0.001 ) . Differences in FV were only found for one category ( unsolicited information ) ( p=0.012 ) . The highest correlation with NFT was found for high accuracy TLV ( direct orders ) ( p=0.06 ) . CONCLUSIONS The inclusion of CRM training in undergraduate medical education reduces NFT in simulated CPR and improves TLV proportions during simulated CPR . Further research will test how these results translate into clinical performance and patient outcome .

crisis resource management training

simulated cardiopulmonary resuscitation

CRM intervention

interactive video-based CRM-training

control intervention

CRM training

simulated CPR

no-flow time ( NFT )

team member verbalisations ( TMV )

Students (

; 25.35±1.03 years , 63 %

female

44 four-person teams


Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer ; results of a randomised phase II study ( DaVINCI ) and meta-analysis [ corrected ] . BACKGROUND Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival . It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine . We compared toxicity ( particularly diarrhoea ) , quality of life , and efficacy of combination chemotherapy and irinotecan in these patients . METHODS In DaVINCI , a randomised phase II trial , patients with advanced colorectal cancer were randomly allocated to : Combination therapy ( FOLFIRI ) , irinotecan ( 180 mg/m ( 2 ) IV over 90 min , day 1 ) , 5-fluorouracil ( 400mg/m ( 2 ) IV bolus and 2400 mg/m ( 2 ) by 46-hour infusion from day 1 ) and folinic acid ( 20mg/m ( 2 ) IV bolus , day 1 ) , 2-weekly ; or Single-agent , irinotecan ( 350 mg/m ( 2 ) IV over 90 min ) , 3-weekly . Toxicity was evaluated every treatment cycle ; QOL and response 6-weekly . Analysis was by intention to treat . The trial , amended from a larger factorial design , was terminated early due to slow recruitment . Results were also combined with other second-line irinotecan trials . FINDINGS We randomised 44 patients to combination and 45 to single agent . Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea ( P=0.24 ) . Treatment groups did not differ significantly in overall QOL changes , response rate or progression free or overall-survival . In a systematic review of 29 trials of second-line irinotecan-based treatment , single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar . INTERPRETATION Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes . Both regimens remain as reasonable treatment options . FUNDING Research grant ( Pfizer ) .

irinotecan

FOLFIRI

chemotherapy

irinotecan

irinotecan

fluoropyrimidine

chemotherapy

irinotecan

FOLFIRI

irinotecan

folinic acid

irinotecan

irinotecan

irinotecan-based

irinotecan

Combination treatment

irinotecan

advanced colorectal cancer

survival .

Toxicity

grade 3/4 diarrhoea

overall QOL changes

response rate

progression free

or overall-survival

diarrhoea

alopecia

alopecia and diarrhoea

efficacy on clinical outcomes


Design and subject characteristics in the federally-funded citalopram trial in children with pervasive developmental disorders . The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders ( PDDs ) . We present the rationale , design and sample characteristics of the citalopram trial . Subjects ( 128 boys , 21 girls ) had a mean age of 9.3 ( ±3.12 ) years ; 132 ( 88.6 % ) were diagnosed with autistic disorder ( 4.7 % with Asperger 's Disorder ; 6.7 % with PDD-not otherwise specified ) . Less than half of the subjects were intellectually disabled ; 117 ( 78.5 % ) were rated Moderate or Marked on the Clinical Global Impression for Severity . Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials . Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials .

citalopram

citalopram

citalopram

were

intellectually disabled

repetitive behavior

children

pervasive developmental disorders


A simple meal plan of 'eating vegetables before carbohydrate ' was more effective for achieving glycemic control than an exchange-based meal plan in Japanese patients with type 2 diabetes . This study aimed to determine whether educating diabetic patients to 'eat vegetables before carbohydrate ' was as effective on long-term glycemic control as a traditional exchange-based meal plan . To test this hypothesis , we carried out a randomized , controlled trial in patients with type 2 diabetes that compared changes in HbA1c as the primary outcome . A total of 101 patients were stratified according to sex , age , BMI , duration of diabetes , and HbA1c , and then randomized to receive instructions to eat either vegetables before carbohydrate ( VBC , n=69 ) or an exchange-based meal plan ( EXB , n=32 ) . The impact of the two plans on glycemic control was compared over 24 months of follow-up . Significant improvements in HbA1c over 24 months were observed in both groups ( VBC , 8.3 to 6.8 % vs EXB , 8.2 to 7.3 % ) . HbA1c levels were significantly lower in the VBC group than in the EXB group after 6 , 9 , 12 and 24 months of the study . Both groups exhibited similar improvements in dietary practices with respect to intake of carbohydrate , fats and sweets , while the VBC group had a significant increase in consumption of green vegetables and a significant decrease in fruit consumption . A simple meal plan of 'eating vegetables before carbohydrate ' achieved better glycemic control than an exchange-based meal plan in Japanese patients with type 2 diabetes over a 24-month period .

exchange-based meal plan

'eat vegetables before carbohydrate

vegetables before carbohydrate

exchange-based meal plan

glycemic control

long-term glycemic control

changes in HbA1c

HbA1c levels

dietary practices

consumption of green vegetables

decrease in fruit consumption

better glycemic control


A randomized crossover study comparing patient preference for tamsulosin and silodosin in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia . Patient preference for benign prostatic hyperplasia ( BPH ) treatment with the α ( 1 ) -blockers , tamsulosin or silodosin , was compared using patient-reported outcomes . Japanese patients with lower urinary tract symptoms associated with BPH were randomly allocated to either the T-S group ( tamsulosin 0.2 mg orally once daily for 4 weeks then silodosin 4 mg orally twice daily for 4 weeks ) or the S-T group ( silodosin 4 mg orally twice daily for 4 weeks then tamsulosin 0.2 mg orally once daily for 4 weeks ) . The primary endpoint was the preferred drug for treatment continuation at 8 weeks , determined by a patient-reported questionnaire . In total , 102 patients ( mean age 70.3 years ) were enrolled and 84 ( n = 42 per group ) completed the study . A significant difference was observed between the proportion of patients who preferred tamsulosin ( 59/84 patients ; 70.2 % ) and those who preferred silodosin ( 18/84 patients ; 21.4 % ) . A major reason for preference of either drug was 'good efficacy ' . Incidence of adverse effects was significantly lower with tamsulosin ( 3/91 patients ; 3.3 % ) than with silodosin ( 25/88 patients ; 28.4 % ) . These findings indicate that tamsulosin is very effective for BPH , has few adverse effects and that patients want to continue to use it .

tamsulosin

silodosin

lower urinary tract symptoms

benign prostatic hyperplasia

lower urinary tract symptoms

BPH

mean age 70.3 years


Alternating chemotherapy in small cell lung cancer . Based on the hypothesis of Goldie and Coldman , rapid cyclic alternating chemotherapy has been supposed to be a favorable treatment modality in small cell lung cancer . This approach has been tested in a large series of trials since the late 70 's . A few trials performed randomization between alternating and continuous treatment after a period of initial common continuous therapy . The results of these studies are controversial and their interpretation is complicated by the effects of the continuous pretreatment . Recently , most trials were designed as 2-arm approaches with a comparison of continuous standard therapy based on the CAV- or CMC-protocol with an alternating schedule often consisting of the CAV- or CMC-derived combinations and a second regimen including cisplatinum and/or etoposide . In these trials the addition of the second regimen in the alternating treatment arms has improved the treatment results . However , these trials could not clarify whether this advantage was due to the concept of alternating treatment or to the high activity of new drugs given early in the course of therapy in the alternating treatment arms . To ameliorate this weakness , 3 studies were designed as 3-arms approaches using both alternating protocols as continuous control arms . Whereas one investigation noticed an advantage of the alternating schedule , the two others observed no difference . These studies did not report their criteria for shifting non-responding patients from continuous treatment to second line therapy . The longer these patients stayed on the continuous protocol the more the study design favoured the alternating therapy . ( ABSTRACT TRUNCATED AT 250 WORDS )

Alternating chemotherapy

rapid cyclic alternating chemotherapy

initial common continuous therapy

CAV-

or

second regimen including

cisplatinum

and/or etoposide

small cell lung cancer .

small cell lung cancer


A pilot randomized controlled trial of DIR/Floortime™ parent training intervention for pre-school children with autistic spectrum disorders . This pilot study was designed to test the efficacy of adding home-based Developmental , Individual-Difference , Relationship-Based ( DIR ) /Floortime™ intervention to the routine care of preschool children with autistic spectrum disorder . Measures of functional emotional development and symptom severity were taken . It was found that after the parents added home-based DIR/Floortime™ intervention at an average of 15.2 hours/week for three months , the intervention group made significantly greater gains in all three measures employed in the study : Functional Emotional Assessment Scale ( FEAS ) ( F = 5.1 , p = .031 ) , Childhood Autism Rating Scale ( F = 2.1 , p = .002 ) , and the Functional Emotional Questionnaires ( F = 6.8 , p = .006 ) . This study confirms the positive results obtained by a previous DIR pilot study ( Solomon et al. , 2007 ) .

parent training intervention

Functional Emotional Assessment Scale

Childhood Autism Rating

Functional Emotional Questionnaires

pre-school children

autistic spectrum disorders

autistic spectrum disorder


Effects of dietary pyridoxine on haemato-immunological responses of Labeo rohita fingerlings reared at higher water temperature . A sixty-day feeding trial was carried out to elucidate the effect of dietary pyridoxine ( PN ) on hemato-immunological parameters in Labeo rohita fingerlings exposed to an elevated temperature ( ET ) of 33 °C . Two hundred and seventy fingerlings ( 6.71 ± 0.32 g ) were randomly distributed into six treatments in triplicates ( 15 fish/tank ) . Five iso-nitrogenous ( 356.3 ± 2.7 g/kg crude protein ) purified diets were prepared with graded levels ( 0 , 10 , 50 , 100 and 200 mg/kg diet ) of PN . Six treatment groups were P10T26 ( 10 mg PN + ambient temperature ( 26 °C ) , P0T33 ( 0 mg PN + ET ) , P10T33 ( 10 mg PN + ET ) , P50T33 ( 50 mg PN + ET ) , P100T33 ( 100 mg PN + ET ) and P200T33 ( 200 mg PN + ET ) . The responses of L. rohita fingerlings to dietary PN were assessed in terms of growth and by analysing some hemato-immunological parameters . When PN supplementation increased from 10 to 200 mg/kg diet , a significant improvement in weight gain percentage was observed . Erythrocyte ( RBC ) count , leucocyte ( WBC ) count , haemoglobin content and respiratory burst activity were significantly ( p < 0.05 ) higher in 100 mg PN/kg diet-fed group than their non-PN-fed counterpart . Also , serum albumin , globulin and lysozyme activity were found significantly ( p < 0.05 ) higher in PN-fed groups . The overall results indicated that dietary PN supplementation at 100 mg/kg diet may reverse the negative effects caused by ET and may protect the haemato-immunological status of L. rohita fingerlings reared at higher water temperature .

dietary pyridoxine

dietary pyridoxine ( PN )

haemato-immunological responses

hemato-immunological parameters


A pilot study to improve venipuncture compliance in children and adolescents with autism spectrum disorders . OBJECTIVE Medical procedures , particularly venipuncture ( the puncture of a vein especially for the withdrawal of blood ) , can cause serious distress and behavior disturbance for many children . Noncompliance to blood draws can have significant ramifications in both research and clinical settings . The negative reactions may be exacerbated in individuals with autism spectrum disorders . Even so , there has been little research into the prevalence of the problem or effective intervention procedures . In response to these concerns , we developed and evaluated the Blood Draw Intervention Program . The program was designed to be easy to use , require little provider or family time , effectively reduce negative behaviors , and increase blood draw compliance . METHOD In a quasi-randomized trial over the course of ∼ 18 months , 58 of 210 families with children with autism spectrum disorders participating in a larger study of phenotypic and genotypic factors reported significant concerns about blood draws and elected to use the Blood Draw Intervention Program . RESULTS Completion of the program increased blood draw compliance rates from 85.4 % to 96.6 % ( odds ratio = 4.80 ; 95 % confidence interval = 1.12 , 20.59 ; p = .03 ) . CONCLUSION Results indicate the efficacy of the program in a research setting and suggest a potential clinical application . The current intervention , unlike many others for the same or similar difficulties proposed in the past , was successful without requiring extensive time , training , or effort on the part of providers and parents or their children , nor did it require large-scale institutional changes .

Blood Draw Intervention Program .

venipuncture compliance

serious distress

behavior disturbance

negative behaviors

increase blood draw compliance

blood draw compliance rates

autism spectrum disorders

210 families

children

autism spectrum disorders