BNP-guided vs symptom-guided heart failure therapy : the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure ( TIME-CHF ) randomized trial . CONTEXT It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide ( BNP ) is superior to symptom-guided therapy . OBJECTIVE To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy . DESIGN , SETTING , AND PATIENTS Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure ( TIME-CHF ) of 499 patients aged 60 years or older with systolic heart failure ( ejection fraction < or = 45 % ) , New York Heart Association ( NYHA ) class of II or greater , prior hospitalization for heart failure within 1 year , and N-terminal BNP level of 2 or more times the upper limit of normal . The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008 . INTERVENTION Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less ( symptom-guided therapy ) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less ( BNP-guided therapy ) . MAIN OUTCOME MEASURES Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires . RESULTS Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations ( 41 % vs 40 % , respectively ; hazard ratio [ HR ] , 0.91 [ 95 % CI , 0.72-1.14 ] ; P = .39 ) . Patients ' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies . Compared with the symptom-guided group , survival free of hospitalization for heart failure , a secondary end point , was higher among those in the N-terminal BNP-guided group ( 72 % vs 62 % , respectively ; HR , 0.68 [ 95 % CI , 0.50-0.92 ] ; P = .01 ) . Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older ( P < .02 for interaction ) CONCLUSION Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment . TRIAL REGISTRATION isrctn.org Identifier : ISRCTN43596477 .

Intensified vs Standard Medical Therapy

symptom-guided therapy

BNP-guided therapy

Patients ' quality-of-life metrics

quality of life


MF101 , a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes : a phase II clinical trial . OBJECTIVE To determine the optimal dose , safety , and efficacy of an estrogen receptor beta selective Chinese herbal extract , menopausal formula 101 ( MF101 ) , for treating hot flushes . METHODS A randomized , blinded trial in 217 postmenopausal women with hot flushes randomized to 5 or 10 g/day of MF101 or placebo for 12 weeks . RESULTS The effects of 5 g/day of MF101 did not differ from those of placebo . After 12 weeks , the mean percent decrease in frequency of hot flushes in the 10 g/day group was 12.9 % greater than that in the placebo group ( P = 0.15 ) , the median percent decrease was 11.7 % greater than that in the placebo group ( P = 0.05 ) , and the proportion of women with at least a 50 % reduction in hot flushes was 16.2 % greater than that in the placebo group ( P = 0.03 ) . CONCLUSIONS Treatment with 10 g/day of MF101 reduces the frequency of hot flushes . Trials with higher doses are planned .

MF101 , a selective estrogen receptor

menopausal formula 101

placebo

placebo

placebo

postmenopausal

women

hot flushes


A randomized , phase II trial of two dose schedules of carboplatin/paclitaxel/cetuximab in stage IIIB/IV non-small-cell lung cancer ( NSCLC ) . BACKGROUND This trial investigated the efficacy and safety of weekly cetuximab combined with two different schedules of paclitaxel/carboplatin for stage IIIB/IV non-small-cell lung cancer ( NSCLC ) . METHODS A total of 168 patients with previously untreated stage IIIB/IV NSCLC were randomized to arm A , cetuximab ( 400 mg/m ( 2 ) day 1 followed by weekly 250 mg/m ( 2 ) ) + paclitaxel ( Taxol ) ( 225 mg/m ( 2 ) ) /carboplatin ( AUC6 ) day 1 every 3 weeks or arm B , same cetuximab regimen plus paclitaxel ( 100 mg/m ( 2 ) ) days 1 , 8 , and 15 every 3 weeks and carboplatin ( AUC6 ) day 1 every 4 weeks . Treatment continued for a four-cycle maximum . Patients with a complete response , partial response , or stable disease after four cycles could receive cetuximab 250 mg/m ( 2 ) /week until disease progression or unacceptable toxicity . The primary end point was to evaluate progression-free survival ( PFS ) . RESULTS Median PFS was 4.7 and 4.3 months for arms A and B , respectively ( 6-month PFS , 27.3 % versus 30.9 % ) . Median overall survival was 11.4 versus 9.8 months for arms A and B , respectively ; estimated 1-year survival , 47.7 % versus 39.3 % ; and objective response rate , 29.6 % versus 25 % . The regimen was well tolerated with rash and hematologic toxicity being most common . CONCLUSIONS This study did not meet the prespecified benchmark of 35 % 6-month PFS rate ; both combination schedules of cetuximab plus paclitaxel/carboplatin were feasible and equivalent for treating advanced NSCLC .

carboplatin/paclitaxel/cetuximab

cetuximab

paclitaxel

mg/m ( 2 ) ) /carboplatin ( AUC6 )

cetuximab regimen plus paclitaxel

and carboplatin

cetuximab

cetuximab plus paclitaxel/carboplatin

efficacy and safety

progression-free survival ( PFS )

PFS

Median overall survival

tolerated

rash and hematologic toxicity

non-small-cell lung cancer

168 patients

advanced NSCLC


Evaluation of mood profiles during malaria chemoprophylaxis : a randomized , double-blind , four-arm study . BACKGROUND To objectively compare the mood profiles of users of malaria chemoprophylaxis regimens ( atovaquone-proguanil , chloroquine-proguanil , doxycycline , or mefloquine ) in a group of nonimmune tourists to sub-Saharan Africa . METHODS In a randomized , double-blind , four-arm study with placebo run-in phase conducted at travel clinics in Switzerland , Germany , and Israel , we compared moods and feelings in chemoprophylaxis users ( n= 547 ) by administering the standardized " Profile of Mood States " ( POMS ) questionnaire . This is designed to provide data on six categories of feelings : tension , depression , anger , vigor , fatigue , and confusion . The questionnaire was administered at four time points : recruitment ( T1 ) , 13 to 11 days before departure ( T2 ) , 6 to 4 days before departure ( T3 ) , and 7 to 14 days after return from Africa ( T4 ) . RESULTS There were no significant differences with respect to overall mood impact between the medication arms . All scores were in the normal range , and no means were more than 1 SD from the norm . The POMS data were reanalyzed with respect to sex , age , medication group , and control time points ( T1-T4 ) . There were significant interaction effects between sex and medication group -- women in the mefloquine group showed more " fatigue " ( p= .011 ) and " confusion " ( p= .011 ) than men . Significant effects of age group ( below median age 34 y vs median age and above ) were noted on the " tension " and " fatigue " scales in that less " tension " ( p= .045 ) and less " fatigue " ( p= .000 ) were noted in those aged 34 years and older . Younger participants , aged < 34 years , reported more " confusion " ( p= .013 ) at T2 than at T1 and T4 . CONCLUSIONS Although the overall mood profiles were similar for the users of any of the standard malaria chemoprophylaxis regimens , we found that women using mefloquine showed more fatigue and confusion than men and that younger persons aged less than 34 years , regardless of chemoprophylaxis used , reported more tension and fatigue than their older counterparts .

malaria chemoprophylaxis

malaria chemoprophylaxis

mood

fatigue

confusion

tension " and " fatigue

tension

fatigue

confusion

malaria

malaria

Younger

malaria

younger

older


Approval summary : imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors . The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate ( Gleevec ; Novartis Pharmaceuticals , East Hanover , NJ ) in patients with CD117 ( + ) unresectable and/or metastatic malignant gastrointestinal stromal tumors ( GISTs ) . In addition , this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose . Two open-label , controlled , multicenter , intergroup , international , randomized phase III studies were submitted -- one conducted by the European Organization for Research and Treatment of Cancer ( n = 946 ) and the other by the Southwest Oncology Group ( n = 746 ) . These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib . A combined analysis of the two studies was prospectively defined and agreed to by both groups . Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression . Objective responses were achieved in > 50 % of patients receiving either imatinib dose . The median progression-free survival time was approximately 20 months and the median overall survival ( OS ) time was approximately 49 months . In the combined analysis , 347 patients crossed over to 800 mg/day imatinib at the time of progression . The median OS time after crossover was 14.3 months . The most common adverse events ( AEs ) were fluid retention , nausea , fatigue , skin rash , gastrointestinal complaints , and myalgia . The most common laboratory abnormality was anemia . Most often the AEs were of mild-to-moderate severity . Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients .

imatinib mesylate

imatinib mesylate

imatinib

imatinib

imatinib

imatinib

imatinib

imatinib

imatinib

imatinib mesylate

imatinib

progression-free survival time

median OS

adverse events ( AEs )

abnormality was anemia .

AEs

GISTs


Effects of propranolol on bone metabolism in the rat . Propranolol , a nonspecific beta-blocker has many physiologic effects . Its effects on bone in vivo are unknown , although beta receptor sites have been found on osteoblasts . In this study , the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation . In a group of nonsurgical rats , propranolol treatment increased femoral torsional strength on biomechanical testing . In the rat surgical model used , right femora were fixed to a polyethylene plate and then defects were created mid-diaphysis and subsequently filled with demineralized bone matrix . These rats ( defect rats ) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days . In the defect rats , increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol-treated groups . Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol-treated rats revealed increased callus and bone union . The results of this study indicate that propranolol treatment can significantly affect bone properties .

propranolol

Propranolol

propranolol

propranolol

propranolol

saline

propranolol

bone metabolism

bone

bone properties

femoral torsional strength

callus and bone union .

bone properties

rat

nonsurgical rats

rat surgical model


Development of a telehealth intervention for head and neck cancer patients . Treatment for head and neck cancer precipitates a myriad of distressing symptoms . Patients may be isolated both physically and socially and may lack the self-efficacy to report problems and participate as partners in their care . The goal of this project was to design a telehealth intervention to address such isolation , develop patient self-efficacy , and improve symptom management during the treatment experience . Participatory action research and a review of the literature were used to develop electronically administered symptom management algorithms addressing all major symptoms experienced by patients undergoing treatment for head and neck cancers . Daily questions and related messages were then programmed into an easy-to-use telehealth messaging device , the Health Buddy ( R ) . Clinician and patient acceptance , feasibility , and technology issues were measured . Using participatory action research is an effective means for developing electronic algorithms acceptable to both clinicians and patients . The use of a simple tele-messaging device as an adjunct to symptom management is feasible , affordable , and acceptable to patients . This telehealth intervention provides support and education to patients undergoing treatment for head and neck cancers .

telehealth intervention

Health Buddy ( R )

telehealth intervention

Clinician and patient acceptance

feasibility

technology issues

feasible

affordable

acceptable

head and neck cancer

head and neck cancer

head and neck cancers

head and neck cancers


Effect of light-cured filled sealant on shear bond strength of metal and ceramic brackets bonded with a resin-modified glass ionomer cement . INTRODUCTION Our objective was to evaluate the effects of a highly filled light-cured sealant ( HFLCS ) on the shear bond strength and bond failure site of metal and ceramic brackets bonded with resin-modified glass ionomer cement ( RMGIC ) . METHODS Eighty freshly extracted maxillary premolars were randomly divided into 4 groups ( 20 in each group ) . In all groups , the teeth were etched with 37 % phosphoric acid for 20 seconds , and RMGIC ( Fuji Ortho LC , GC Europe , Leuven , Belgium ) was used for bracket bonding . In groups 1 and 3 , the brackets were bonded directly to etched enamel surfaces ; in groups 2 and 4 , the etched enamel was covered with HFLCS ( Pro Seal , Reliance Orthodontic Products , Itasca , Ill ) . Groups 1 and 2 received metal brackets , and groups 3 and 4 had ceramic brackets . The specimens were stored in distilled water at room temperature for 24 hours and subsequently tested in shear mode with a universal testing machine . After debonding , the teeth and the brackets were examined under a stereomicroscope ( model SMZ-1B , Nikon , Osaka , Japan ) at 20-times magnification to assess the residual adhesive on the tooth surfaces . RESULTS Interaction between HFLCS and bracket type was not statistically significant ( P = 0.15 ) . Pretreatment with HFLCS did not cause a statistically significant change in the shear bond values of either metal or ceramic brackets ( P = 0.38 ) . Shear bond values of the ceramic brackets were higher than those of the metal brackets independent of HFLCS application ( P < 0.001 ) . No significant differences were found in bond failure modes in the 4 groups . CONCLUSIONS HFLCS application on enamel etched with 37 % phosphoric acid did not affect the bond strength values and the bond failure modes of metal and ceramic brackets bonded with RMGIC . RESULTS Interaction between HFLCS and bracket type was not statistically significant ( P = 0.15 ) . Pretreatment with HFLCS did not cause a statistically significant change in the shear bond values of either metal or ceramic brackets ( P = 0.38 ) . Shear bond values of the ceramic brackets were higher than those of the metal brackets independent of HFLCS application ( P < 0.001 ) . No significant differences were found in bond failure modes in the 4 groups . CONCLUSIONS HFLCS application on enamel etched with 37 % phosphoric acid did not affect the bond strength values and the bond failure modes of metal and ceramic brackets bonded with RMGIC .

light-cured sealant ( HFLCS )

37 % phosphoric acid for 20 seconds

metal brackets

ceramic brackets

bond failure modes

bond strength values

bond failure modes


Cardiac failure : symptoms and functional status . The associations between exercise capacity , symptoms and specific aspects of quality of life were examined in subjects participating in a trial of the treatment of heart failure . Patients were assessed on entry and after three months treatment . The principle symptoms were fatigue , breathlessness and chest pain . These limited the extent and speed of physical activities , restricted social , leisure and family life and were associated with emotional distress . There were associations between baseline exercise capacity and measures of quality of life . Change in exercise capacity during three months treatment was correlated with changes in measures of symptoms , limitation of activity and quality of life . The findings confirm the value of change in exercise capacity as a measure of functional status and suggest that it should be supported by a limited number of specific measures of quality of life .

treatment of heart failure

baseline exercise capacity

measures of quality of life

measures of symptoms

exercise capacity

quality of life


Comparison of injection comfort of a new category of cohesive hyaluronic acid filler with preincorporated lidocaine and a hyaluronic acid filler alone . BACKGROUND A smooth , cohesive , 24-mg/mL hyaluronic acid ( HA ) gel with uniform consistency , even flow characteristics , and extended duration was designed for injection into the mid to deep dermis . OBJECTIVE To compare injection pain of a HA gel with preincorporated lidocaine with that with a non-lidocaine formulation . METHODS & MATERIALS This double-blind study at three centers enrolled 60 subjects , injected with both products , randomly assigned to left or right nasolabial fold . The injecting physician assessed severity of pain and ease of injection . Subjects used a visual analog scale ( 0-10 ) for pain assessment . Adverse events were recorded . RESULTS Physician assessment of injection pain was none or mild in 81 % of HA gel injections with preincorporated lidocaine and 36 % of HA-alone injections ( p < .001 ) . Mean pain assessment by subjects was 3.6 for HA+lidocaine and 5.8 for HA alone ( p < .001 ) . Ninety-five percent of the injections were considered easy or very easy ; a greater percentage of HA+lidocaine injections were rated very easy . Mild to moderate adverse events were reported for both products . CONCLUSION The smooth , cohesive HA gel with preincorporated lidocaine increased subject comfort during treatment and improved the injection experience .

hyaluronic acid filler

lidocaine

hyaluronic acid filler alone

hyaluronic acid ( HA ) gel

HA gel with preincorporated lidocaine

lidocaine

lidocaine

injection comfort

pain

ease of injection

injection pain

Mean pain assessment

subject comfort

injection experience

injection comfort

cohesive hyaluronic acid filler

pain assessment


Esophageal damage during radiofrequency ablation of atrial fibrillation : impact of energy settings , lesion sets , and esophageal visualization . INTRODUCTION Atrioesophageal fistula is an uncommon but often lethal complication of atrial fibrillation ( AF ) ablation . The purpose of our study was to prospectively investigate the incidence of esophageal ulcerations ( ESUL ) as well as the impact of energy settings , radiofrequency lesion sets , and direct visualization of the esophagus on esophageal wall injury . METHODS AND RESULTS One hundred seventy-five patients , 57.1 % paroxysmal AF , 78.5 % male , underwent AF ablation and esophagoscopy 24 hours thereafter . We performed a 2:1:1-randomization as follows : CONTROL GROUP Ablation without visualization of the esophagus using 25 Watt ( W ) power limit on the posterior wall , n = 70 . Visualization and 15 W maximum : Ablation guided by barium visualization of the esophageal course using a limit of 15 W , n = 35 . Visualization and 25 W " short burns " : Ablation guided by barium visualization using 25 W and " short burns " ( max . 5 sec ) , n = 35 . Patients performed under general anesthesia ( n = 35 ) were separated as a nasogastric tube for visualization of the esophagus was used . In total , we found 2.9 % of patients ( 5/175 ) presenting ESUL . Parameters discriminating the development of ESUL in a specific patient were type of AF , maximum energy delivered , usage of a nasogastric tube , and additional left atrial lines . Visualization of the esophageal course by barium contrast was not able to prevent ESUL . CONCLUSION ESUL is a rare finding when using a reasonable energy maximum of 25 W with open-irrigated tip catheters at the posterior wall . Lower energy settings may increase safety without losing efficacy . Additional linear radiofrequency lesions increase the risk of ESUL development .

radiofrequency ablation

AF ablation

esophagoscopy

Ablation guided by barium visualization

esophageal ulcerations ( ESUL )

ESUL

ESUL

ESUL

atrial fibrillation ( AF ) ablation

One hundred seventy-five patients

male

AF ablation and esophagoscopy


Using a laryngeal tube suction-device ( LTS-D ) reduces the " no flow time " in a single rescuer manikin study . BACKGROUND In 2005 , the European Resuscitation Council and the American Heart Association published new guidelines for Advanced Life Support . One of the points was to reduce the time without chest compressions in the first phase of cardiac arrest . OBJECTIVE We evaluated in a manikin model whether using the single-use laryngeal tube with suction option ( LTS-D ) instead of endotracheal intubation ( ET ) and bag-mask-valve ventilation ( BMV ) for emergency airway management could reduce the " no-flow time " ( NFT ) . The NFT is defined as the time during resuscitation when no chest compressions take place . METHODS A randomized , prospective study was undertaken with 150 volunteers who performed management of a standardized simulated cardiac arrest in a manikin . Every participant was randomized to one of three different airway management groups ( LTS-D vs . ET vs. BMV ) . RESULTS The LTS-D was inserted significantly faster than the ET tube ( 15 s vs. 44 s , respectively , p < 0.01 ) . During the cardiac arrest simulation , establishing and performing ventilation took an average of 57 s with the LTS-D compared to 116 s with ET and 111 s with the BMV . Using the LTS-D significantly reduced NFT compared to ET and the BMV ( 125 s vs. 207 s vs. 160 s ; p < 0.01 ) . CONCLUSIONS In our manikin study , NFT was reduced significantly when the LTS-D was used when compared to ET and BMV . The results of our manikin study suggest that for personnel not experienced in tracheal intubation , the LTS-D offers a good alternative to ET and BMV to manage the airway during resuscitation , and to avoid the failure to achieve tracheal intubation with the ET , and the failure to achieve adequate ventilation with the BMV .

laryngeal tube suction-device ( LTS-D )

instead

LTS-D

LTS-D

ET

BMV

LTS-D

ET

BMV

LTS-D

ET

BMV

LTS-D

ET

BMV

ET

BMV

" no flow time "

time without chest compressions

no-flow time " ( NFT )

establishing and performing ventilation

NFT

NFT


A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea . The Gonorrhea Treatment Study Group . BACKGROUND Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline , ceftriaxone is now recommended for the treatment of gonorrhea . There is , however , a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone , which requires intramuscular administration . Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration . METHODS AND RESULTS In a randomized , unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea , we compared three single-dose treatment regimens : 400 mg or 800 mg of cefixime , administered orally , and 250 mg of ceftriaxone administered intramuscularly . The overall cure rates were 96 percent for the 400-mg dose of cefixime ( 89 of 93 patients ) ( 95 percent confidence interval , 93.5 percent to 97.8 percent ) ; 98 percent for the 800-mg dose of cefixime ( 86 of 88 patients ) ( 95 percent confidence interval , 94.6 percent to 100 percent ) ; and 98 percent for ceftriaxone ( 92 of 94 patients ) ( 95 percent confidence interval , 94.9 to 100 percent ) . The cure rates were similar in men and women , and pharyngeal infection was eradicated in 20 of 22 patients ( 91 percent ) . Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance ; the efficacy of all three regimens was independent of the resistance pattern . Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group . All three regimens were well tolerated . CONCLUSIONS In the treatment of uncomplicated gonorrhea , a single dose of cefixime ( 400 or 800 mg ) given orally appears to be as effective as the currently recommended regimen of ceftriaxone ( 250 mg given intramuscularly ) .

cefixime

ceftriaxone

ceftriaxone

400 mg or 800 mg of cefixime

administered orally

250 mg of ceftriaxone

cefixime

cefixime

ceftriaxone

cefixime

ceftriaxone

uncomplicated gonorrhea

gonorrhea

overall cure rates

cure rates

pharyngeal infection

efficacy

Chlamydia trachomatis infection

tolerated

uncomplicated gonorrhea

effective

gonorrhea

gonorrhea


Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial ( The MEDAL study ) . OBJECTIVE To compare cardiovascular ( CV ) and other safety and efficacy parameters of etoricoxib 60 and 90 mg , and diclofenac 150 mg. METHODS This double-blind study randomized OA patients to etoricoxib 90 mg , then to 60 mg once daily vs diclofenac 75 mg twice daily ; RA patients were randomized to etoricoxib 90 mg once daily or diclofenac 75 mg twice daily . The primary endpoint was non-inferiority of etoricoxib vs diclofenac for thrombotic CV events ( 95 % CI upper bound of hazard ratio < 1.30 ) . Other safety and efficacy parameters were evaluated in cohorts of patients based on etoricoxib dose and disease . RESULTS A total of 23 504 patients were randomized with mean treatment duration from 19.4 to 20.8 months . The thrombotic CV risk hazard ratio ( HR ) ( etoricoxib to diclofenac ) was 0.96 ( 95 % CI 0.81 , 1.15 ) , consistent with non-inferiority of etoricoxib to diclofenac . The cumulative gastrointestinal ( GI ) /liver adverse events ( AEs ) discontinuation rate was significantly lower for etoricoxib than diclofenac in each patient cohort ; HR ( 95 % CI ) of 0.46 ( 0.39 , 0.54 ) , 0.52 ( 0.42 , 0.63 ) and 0.49 ( 0.39 , 0.62 ) for the 60 mg OA , 90 mg OA and RA cohorts . The maximum average change in systolic blood pressure ( BP ) with etoricoxib was 3.4-3.6 mmHg ( diastolic BP : 1.0-1.5 mmHg ) , while diclofenac produced a maximum average change of 0.9-1.9 mmHg ( diastolic BP : 0.0-0.5 mmHg ) . Both agents resulted in similar efficacy regardless of etoricoxib dose . CONCLUSION Long-term etoricoxib use is associated with a risk of thrombotic CV events comparable with that of diclofenac . Compared with diclofenac , etoricoxib demonstrated a greater risk of renovascular AEs , but a more favourable GI/liver tolerability profile .

etoricoxib

diclofenac

etoricoxib

diclofenac

etoricoxib

diclofenac

etoricoxib

diclofenac

etoricoxib

etoricoxib

etoricoxib

diclofenac

etoricoxib

diclofenac

etoricoxib

etoricoxib

diclofenac

diclofenac

etoricoxib

Cardiovascular safety

gastrointestinal tolerability

Other safety and efficacy parameters

thrombotic CV risk hazard ratio

systolic blood pressure

efficacy

thrombotic CV events

renovascular AEs

GI/liver tolerability profile

OA patients

RA patients

23 504


[ Efficacy of immunomodulating treatment in patients with different degrees of immunosuppression ] . Immunodepression is a common condition in patients undergoing elective operations and it constitutes a high risk for the onset of postoperative infective complications . The use of immunomodulatory drugs has proved useful in the prophylaxis of these complications , although the precise indications for each drug have not yet been clearly codified . The present study aimed to assess the effects of thymostimulin in patients with different degrees of immunodepression , by evaluating both the incidence of postoperative infections and the changes induced in various immunological parameters . The results obtained indicated that those subjects with the highest degree of immunodepression ( hypo-anergic ) benefited most from drug therapy in comparison to those with a lesser degree of immunodepression ( relatively hypo-ergic ) . The advantages were evident in hypo-anergic subjects both with regard to the frequency of early postoperative infections , and with regard to immunological parameters . On the other hand , in relatively hypo-ergic subjects , benefits were limited to the improvement of some immunological parameters . In our opinion , the use of thymostimulin is of particular use only in those subjects with marked immunodepression since the incidence of post-operative sepsis is highest in this group .

immunomodulatory drugs

thymostimulin

drug therapy

thymostimulin

incidence of postoperative infections

immunological parameters

immunological parameters

immunological parameters

post-operative sepsis

immunosuppression

immunodepression


Intensive insulin therapy on infection rate , days in NICU , in-hospital mortality and neurological outcome in severe traumatic brain injury patients : a randomized controlled trial . OBJECTIVES Evaluate the impact of an intensive insulin therapy and conventional glucose control protocol during staying in neurological intensive care unit ( NICU ) on infection rate , days in NICU , in-hospital mortality and long-term neurological outcome in severe traumatic brain injury ( TBI ) patients . METHODS A total of 240 patients with severe TBI ( GCS score 3-8 ) admitted to NICU were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy . Patients in intensive glucose control group ( n=121 ) received continuous insulin infusion to maintain glucose levels between 4.4 m mol/l ( 80 mg/dl ) and 6.1 m mol/l ( 110 mg/dl ) . Patients in the conventional treatment group ( n=119 ) were not given insulin unless glucose levels were greater than 11.1 m mol/l ( 200mg/dl ) . Both groups were treated with insulin infusion to maintain normoglycemia after leaving NICU . Comparison was made against conventional insulin therapy using a randomized trial design . The primary outcomes is the mortality rate at 6 months follow-up . The second outcomes including ICU infection rate , duration of ICU stay , in-hospital mortality rate and neurologic outcome at 6 months follow-up . RESULTS There was no significant difference in gender ( 66 % vs. 67 % male ) , age ( 46+/-11 years vs. 45+/-10 years ) , APACHE II score ( 30 vs. 29 ) , TISS-28 score ( 47 vs. 46 ) , and Glasgow Coma Score ( GCS , 5.3 vs. 5.3 ) between the two groups . Overall mortality rates at 6 months follow-up were similar in the 2 groups ( 61 of 117 , 52.1 % vs. 62 of 116 , 53.4 % ; P=0.8 ) . The infection rate during the study was significantly higher in patients who received conventional insulin therapy than that in patients who received intensive insulin therapy ( 46.2 % vs. 31.4 % ; P < 0.05 ) . The days stay in NICU was shorter in intensive insulin control group than that in conventional therapy group [ 4.2 days vs. 5.6 days ( medians ) P < 0.05 ] . The in-hospital mortality during the study was similar in conventional and intensive therapy groups ( 34 of 119 , 28.6 % vs. 35 of 121 , 28.9 % in the conventional and intensive insulin therapy groups ; P=0.85 ) . The neurologic outcome according to Glasgow Outcome Score ( GOS ) at 6 months ( GOS 5 and 4 ) was better in the intensive insulin therapy group ( 34 of 117 , 29.1 % ) than that in the conventional therapy group ( 26 of 116 , 22.4 % , P < 0.05 ) . CONCLUSIONS Mortality rates at 6 months follow-up are not affected by intensive glucose control in patients with severe TBI . Intensive insulin therapy decreases infection rate and days in NICU and improves the neurological outcome at 6 months follow-up , while has no obvious influence on in-hospital mortality of severe TBI patients .

Intensive insulin therapy

intensive insulin therapy

conventional glucose control protocol

conventional insulin therapy

intensive insulin therapy

intensive glucose control group

continuous insulin infusion

conventional treatment group

insulin

insulin

conventional insulin therapy

conventional insulin therapy

intensive insulin therapy

intensive insulin

conventional therapy

conventional

intensive therapy

conventional

intensive insulin therapy

conventional therapy

Intensive insulin therapy

in-hospital mortality

neurological outcome

infection rate

days in NICU

in-hospital mortality

long-term neurological outcome

glucose levels

mortality rate

ICU infection rate

duration of ICU stay

in-hospital mortality rate

neurologic outcome

TISS-28 score

Glasgow Coma Score

Overall mortality rates

infection rate

days stay in NICU

in-hospital mortality

Glasgow Outcome Score ( GOS )

Mortality rates

infection rate

days in NICU

neurological outcome

in-hospital mortality


Effect of broccoli intake on markers related to oxidative stress and cancer risk in healthy smokers and nonsmokers . Cruciferous vegetables ( CVs ) have been widely studied for their anticarcinogenic properties . The aim of the present study was to evaluate the protective effect of broccoli intake in smokers and nonsmokers . Twenty young healthy males ( 10 smokers and 10 nonsmokers ) were randomized in a cross-over design and received a portion of broccoli ( 200 g ) or maintained a controlled diet for 10 days each . The two periods were separated by a wash-out period ( 20 days ) . Blood samples were collected at 0 , 10 , 30 , and 40 days and used for the evaluation of DNA damage , insulin-like growth factor-I ( IGF-I ) and histone deacetylase ( HDAC ) . Ex vivo protection from H ( 2 ) O ( 2 ) -induced DNA damage and endogenous DNA damage were evaluated in lymphocytes by means of the comet assay . Strand breaks decreased significantly after the broccoli diet in smokers as well as in nonsmokers ( -22.2 % ; P < 0.0001 ) , whereas oxidized purines decreased significantly only in smokers ( -51.0 % ; P < 0.0001 ) . Broccoli intake did not modify HDAC activity and IGF-I serum levels . Our results strengthen the importance of consuming CVs to increase cell protection against DNA damage . Future investigation , with different amount of broccoli and/or different time of exposure , is needed to understand the lack of effect on HDAC activity and IGF-I levels .

broccoli intake

broccoli

maintained a controlled diet

Strand breaks

oxidized purines

HDAC activity and IGF-I serum levels .

HDAC activity and IGF-I levels .


Pharmacokinetics and pharmacodynamics of six epoetin alfa dosing regimens in anemic critically ill patients without acute blood loss . OBJECTIVE To describe the pharmacokinetic profiles of six different dosing regimens for epoetin alfa , and whether more rapid and robust reticulocytosis can be elicited with more frequent administration of epoetin alfa in anemic critically ill patients . DESIGN Randomized , open-label , multicenter , 28-day clinical trial . SETTING Ten centers in the United States . PATIENTS Adult ( age > or=18 years ) critically ill patients with hemoglobin < or=12 g/dL , expected hospitalization of > or=7 days , with no ongoing acute blood loss . INTERVENTIONS One of six dosing epoetin alfa regimens for 15 days , as follows : 40,000 IU once weekly , subcutaneously ( group A ) or intravenously ( IV ) ( group B ) ; 15,000 IU every other day , subcutaneously ( group C ) or IV ( group D ) ; or 40,000 IU day 1 and 3 , subcutaneously ( group E ) or IV ( group F ) , followed by 15,000 IU once every other day on [ corrected ] days 5-15 [ corrected ] MEASUREMENTS Serum erythropoietin concentration , absolute reticulocyte count , and adverse events . MAIN RESULTS Of the 60 patients who were enrolled ( 60 % men , mean age 53 years , mean Acute Physiology and Chronic Health Evaluation II score , 19.5 ) , 30 were evaluable for both pharmacokinetics and pharmacodynamics ( 50 % ) . Erythropoietin exposure was approximately ten times greater for IV dosing than for subcutaneous dosing . Mean absolute reticulocyte count peaked at day 11 or 15 in each group and appeared to be greater for subcutaneous dosing ( mean peak response 149-169 x 10 ( 9 ) /L ) compared with IV dosing ( mean peak response 138-147 x 10 ( 9 ) /L ) at most visits . The most frequently reported adverse events were pyrexia ( 18 % ) , hypokalemia ( 15 % ) , and hypophosphatemia ( 15 % ) . CONCLUSIONS In this study of anemic critically ill patients treated with epoetin alfa , all dosing regimens were well tolerated and appeared to effect reticulocytosis , with a peak at day 11 or 15 in most patients . The pharmacokinetics of epoetin alfa did not predict pharmacodynamic response in anemic critically ill patients .

epoetin alfa

epoetin alfa

epoetin alfa

six dosing epoetin alfa regimens

40,000 IU once weekly

40,000 IU day

subcutaneously

Erythropoietin exposure

subcutaneous dosing

dosing

epoetin alfa

epoetin alfa

Serum erythropoietin concentration

absolute reticulocyte count

adverse events

Erythropoietin exposure

Mean absolute reticulocyte count

adverse events

pyrexia

hypokalemia

hypophosphatemia

reticulocytosis

pharmacodynamic response


Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I ( 131 ) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma . BACKGROUND Advanced pancreatic cancer has a poor prognosis , and the current standard of care ( gemcitabine based chemotherapy ) provides a small survival advantage . However the drawback is the accompanying systemic toxicity , which targeted treatments may overcome . This study aimed to evaluate the safety and tolerability of KAb201 , an anti-carcinoembryonic antigen monoclonal antibody , labelled with I ( 131 ) in pancreatic cancer ( ISRCTN 16857581 ) . METHODS Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route . The dose limiting toxicities within each group were determined . Patients were assessed for safety and efficacy and followed up until death . RESULTS Between February 2003 and July 2005 , 25 patients were enrolled . Nineteen patients were randomised , 9 to the intravenous and 10 to the intra-arterial arms . In the intra-arterial arm , dose limiting toxicity was seen in 2/6 ( 33 % ) patients at 50 mCi whereas in the intravenous arm , dose limiting toxicity was noted in 1/6 patients at 50 mCi , but did not occur at 75 mCi ( 0/3 ) .The overall response rate was 6 % ( 1/18 ) . Median overall survival was 5.2 months ( 95 % confidence interval = 3.3 to 9 months ) , with no significant difference between the intravenous and intra-arterial arms ( log rank test p = 0.79 ) . One patient was still alive at the time of this analysis . CONCLUSION Dose limiting toxicity for KAb201 with I ( 131 ) by the intra-arterial route was 50 mCi , while dose limiting toxicity was not reached in the intravenous arm .

gemcitabine based chemotherapy

KAb 201

safety

efficacy

safety

tolerability

dose limiting toxicities

safety and efficacy

toxicity

toxicity

response rate

Median overall survival

Dose limiting toxicity

dose limiting toxicity

Advanced pancreatic cancer


Using a novel wound model to investigate the healing properties of products for superficial wounds . OBJECTIVE To establish a new wound model that can induce uniform abrasions and use it to assess the healing properties of a range of products commonly applied to these wounds . METHOD Ten healthy volunteers were enrolled into an open-label , randomised , intra-individual comparison pilot study . Five standardised , superficial abrasions were induced on their forearms by repeatedly scrubbing the skin with a surgical brush until the first signs of uniform glistening and punctuate bleeding were observed . Three products that promote a moist wound environment ( polyurethane , hydrocolloid , hydrogel ) and two standard plasters were randomly allocated to the test areas . RESULTS Evaluation of wound healing on days 2 , 5 , 8 and 14 +/- 1 showed best results for the polyurethane and hydrocolloid plasters . Visible re-epithelialisation was recorded on days 5 and 8 . More than 50 % of the wound area had closed . Video microscope images support these findings . The investigator and volunteers assessed cosmetic outcomes on day 31 +/- 2 . Best results were obtained for the polyurethane and hydrocolloid products , which had high mean scores close to the maximum of 10 . Histological examination of biopsies taken from the abrasions of two volunteers showed the dermis remained intact , making the model highly suitable for the study of superficial wounds . CONCLUSION Uniform and identical standardised wounds created using an abrasive brush technique can be used to reliably detect differences in the performance of plasters intended for superficial wounds . In general , products that promote a moist wound environment produced better results than those that promote a dry wound environment , with an earlier onset of healing and better healing outcomes . Superficial cutaneous wounds treated with polyurethane or hydrocolloid products demonstrated superior rates of re-epithelialisation and overall cosmetic outcomes . DECLARATION OF INTEREST This study was funded by Beiersdorf AG . Neither author has any interest in the sponsor 's commercial activities .

polyurethane

hydrocolloid

hydrogel

two standard plasters

polyurethane

hydrocolloid

polyurethane

hydrocolloid

healing properties

healing properties

Evaluation of wound healing

Visible re-epithelialisation

wound area had closed

cosmetic outcomes

Histological examination of biopsies

dermis remained intact

performance of plasters

healing

healing outcomes

Ten

superficial wounds .


Acute and short-term effects of secondhand smoke on lung function and cytokine production . RATIONALE The acute effect of secondhand smoke ( SHS ) on lung function and the duration of system disruption remain unknown . OBJECTIVES To assess the SHS effects and their duration on lung function and inflammatory markers . METHODS In a randomized single-blind crossover experiment data were obtained from 16 ( 8 women ) nonsmoking adults at baseline and at 0 , 1 , and 3 hours after a 1-hour SHS exposure set at bar/restaurant SHS levels . MEASUREMENTS AND MAIN RESULTS Serum and urine cotinine , lung function , and cytokines IL-4 , IL-5 , IL-6 , tumor necrosis factor ( TNF ) -alpha , and IFN-gamma . At 0 hours most lung function parameters were significantly reduced ( indicative : FEV ( 1 ) , 4.3 +/- 0.4 vs. 3.8 +/- 0.3 L ; FEV ( 1 ) /FVC , 0.9 +/- 0.1 vs. 0.8 +/- 0.1 ; P < 0.05 ) but at 3 hours they were at baseline levels . In contrast , cotinine ( serum , 8.9 +/- 3.2 vs. 35.5 +/- 10.2 ng x ml ( -1 ) ) , IL-4 ( 41.3 +/- 5.8 vs. 44.2 +/- 4.5 pg x ml ( -1 ) ) , IL-5 ( 36.1 +/- 3.2 vs. 60.1 +/- 7.0 pg x ml ( -1 ) ) , IL-6 ( 2.5 +/- 0.3 vs. 7.6 +/- 1.4 pg x ml ( -1 ) ) and IFN-gamma ( 0.3 +/- 0.2 vs. 0.6 +/- 0.2 IU x ml ( -1 ) ) at 3 hours were higher than at baseline ( P < 0.05 ) . IL-4 and TNF-alpha increased only in men , whereas IL-5 , IL-6 , and IFN-gamma were different between sexes after exposure ( P < 0.05 ) . Regression analyses revealed inverse associations of FEV ( 1 ) and FEV ( 1 ) /FVC ratio with IL-5 ( P < 0.05 ) in men and with IL-5 ( P = 0.01 ) , IL-6 ( P < 0.001 ) , IFN-gamma ( P = 0.034 ) and serum cotinine ( P < 0.001 ) in women . CONCLUSIONS We conclude that 1 hour of SHS exposure at bar/restaurant levels is accompanied by significant decrements on lung function and marked increases in inflammatory cytokines , particularly in men . More importantly , whereas most smoke-induced effects on lung function appear to recede within 60 minutes , inflammatory cytokines remain elevated for at least 3 hours after exposure to SHS .

cytokines IL-4 , IL-5 , IL-6

tumor necrosis factor ( TNF ) -alpha

IFN-gamma

lung function

cytokine production

lung function

system disruption

lung function

inflammatory markers

Serum and urine cotinine

lung function

cytokines IL-4 , IL-5 , IL-6

tumor necrosis factor ( TNF ) -alpha

IFN-gamma

lung function parameters

cotinine

IFN-gamma

IL-4 and TNF-alpha

IL-5 , IL-6 , and IFN-gamma

FEV ( 1 )

FEV ( 1 ) /FVC ratio

IFN-gamma

serum cotinine

decrements on lung function

inflammatory cytokines

effects on lung function

inflammatory cytokines

women

adults


Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone . OBJECTIVE To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone . DESIGN Multicenter , randomized , prospective , double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol ( 2mg ) +trimegestone ( 0.5mg ) ( T-group ) or estradiol ( 2mg ) +dydrogesterone ( 10mg ) ( DYDR group ) . Cardiovascular risk markers were measured before , after cycle 1 , 3 and 6 and at 4 weeks post-treatment . RESULTS Fibrinogen was reduced in both groups but more markedly in the DYDR group . Factor VIIc activity levels decreased in both groups with a greater change in the T-group . Factor VII antigen was increased in both groups with a greater increase in the DYDR group . Factor VIIa was increased in the DYDR group only . Plasminogen levels were also increased in both groups with a greater increase in the T-group . There were no statistically significant changes in lipid variables between the different regimens . Changes in total cholesterol and LDL cholesterol were correlated positively with changes in factor VIIc in the DYDR group and negatively with changes in factor VIIc in the T-group . Trigemestone was associated with a better bleeding pattern . CONCLUSIONS Trimegestone was associated with less procoagulant changes in factor VIIa and factor VIIc activity and larger decrease in PAI-1 activity compared with the dydrogesterone preparation . These results reflect less androgenic properties of the trimegestone preparation . The fibrinogen level and Lp ( a ) were more decreased during dydrogesterone treatment . Further investigation is required to clarify the relative importance of beneficial effects with respect to cardiovascular risk .

estradiol

trimegestone

dydrogesterone

Cardiovascular risk markers

Cardiovascular risk markers

cardiovascular risk markers

Cardiovascular risk markers

Factor VII antigen

lipid variables

total cholesterol and LDL cholesterol

factor VIIc

factor VIIc

women

healthy post-menopausal

women


Prospective comparison of the value of brushings before and after biopsy in the endoscopic diagnosis of gastroesophageal malignancy . The hypothesis that the cytodiagnostic results on endoscopic brushings obtained before biopsy may be superior to those brushings obtained after biopsy , but with the accuracy of the subsequent biopsy reduced , was examined for 300 consecutive patients , including 256 with esophageal or gastric carcinomas . Following stratification by site and endoscopic appearance of their lesions , the patients were randomized to undergo brushing either before or after forceps biopsy . The accuracy of brushing cytology in patients with carcinoma was significantly higher when the brushing was performed before biopsy than after biopsy ( 93.5 % versus 82.6 % ; P less than .01 ) . The diagnostic yield of the biopsy was not significantly different whether the lesions were brushed before or after the biopsy ( 92.7 % versus 93.2 % ; P less than .5 ) . The diagnostic superiority of brushings obtained before biopsy did not relate to the site or endoscopic appearance of the tumor . There were no false-positive cytologic or histologic reports . For all 256 carcinomas , the cumulative accuracy ( brushing cytology plus biopsy ) reached 98.8 % and was significantly better ( P less than .001 ) than that of biopsy alone ( 93.9 % ) or cytology alone ( 87.9 % ) . Apart from reinforcing the belief that the combined application of brushing and biopsy is mandatory for achieving optimal results , this study indicated that the brushing should be performed before the biopsy .

brushings before and after biopsy

endoscopic brushings

brushings

brushing cytology

brushings obtained before biopsy

( brushing cytology plus biopsy )

biopsy alone

cytology alone

accuracy

brushing cytology

diagnostic yield

cumulative accuracy

gastroesophageal malignancy .

esophageal or gastric carcinomas

carcinoma


A randomized , controlled study on the influence of acetaminophen , diclofenac , or naproxen on aspirin-induced inhibition of platelet aggregation . Nonsteroidal anti-inflammatory drugs ( NSAID ) may interfere with aspirin ( acetylsalicylic acid ) and increase the risk for cardiovascular events . The clinical relevance is uncertain . The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation . In a randomized , placebo controlled trial , eleven healthy volunteers were studied during 4 separate study periods of 4 days each . Individuals were treated on each occasion with 100 mg aspirin daily in combination with either 3 x 1 g acetaminophen , 3 x 50 mg diclofenac , 3 x 250 mg naproxen , or 3 x 1 placebo . Primary hemostasis was assessed with a platelet function analyser ( PFA-100 ) , which measures the closure time ( CT ) of a collagen- and epinephrine-coated pore by aggregating platelets in flowing blood . Naproxen enhanced the anti-aggregatory action of aspirin after 24 h ( CT rising from 104+/-16 s at baseline to 212+/-69 s at 24 h , P < 0.001 ) , which was not seen with any other drug combination . Diclofenac reduced the anti-aggregatory action of aspirin in the first two days , since the CT did not rise significantly ( 109+/-19 s , 148+/-56 s , and 168+/-66 s at 0 h , 24 h , 48 h , respectively , P > 0.05 ) . Acetaminophen had no effect compared with placebo . After 4 days of treatment platelet aggregation was similarly inhibited by all combinations . We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac . This effect is lost after 4 days , suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin .

acetaminophen

diclofenac

naproxen

aspirin ( acetylsalicylic acid )

aspirin

NSAID

aspirin

placebo

Naproxen

aspirin

Diclofenac

aspirin

Acetaminophen

placebo

NSAID

aspirin

naproxen

diclofenac

NSAID

aspirin

platelet aggregation

cardiovascular events

platelet aggregation

Primary hemostasis

the

closure time ( CT )

anti-aggregatory action

CT

anti-aggregatory action

CT

platelet aggregation

platelet inhibition

platelet inhibition

eleven healthy volunteers


Stability , tipping and relapse of bone-borne versus tooth-borne surgically assisted rapid maxillary expansion ; a prospective randomized patient trial . This study evaluated stability , tipping and relapse after surgically assisted rapid maxillary expansion ( SARME ) , comparing bone-borne and tooth-borne devices , in skeletally matured non-syndromal patients with transverse maxillary hypoplasia . The study is a randomized , open-label , clinical trial . Patients were randomized to bone-borne ( n=25 ) and tooth-borne ( n=21 ) groups . The surgical technique for corticotomy was the same in both groups . Expansion was performed using a bone-borne or tooth-borne device . Dental study casts , lateral and postero-anterior cephalograms were taken before treatment , after the distraction phase and at 12-month follow up . Stability , segmental maxillary tipping and relapse were studied . 23 bone-borne and 19 tooth-borne patients were analyzed . There were no significant differences between the two groups . Widening was comparable at canine , premolar and molar level . Relapse was not significant and at follow up the significant increase in distance was sustained . A significant increase in palatal width , at premolar and molar level , occurred in both groups . The maxilla moves slightly downward in SARME . Segmental maxillary tipping occurred in both groups and did not affect relapse . There is no significant difference between the two groups . In SARME , the widening achieved at dental level is stable after 12 months . Over-correction is not necessary . Tipping of the maxillary segments and increases in the retention period are equal in both groups .

bone-borne

and

tooth-borne devices

SARME

Widening

Relapse

Segmental maxillary tipping

relapse

retention period


Neuromuscular excitability changes in the vastus medialis following anterior cruciate ligament reconstruction . PURPOSE Quadriceps weakness following anterior cruciate ligament reconstruction ( ACLR ) is prevalent despite intensive rehabilitation . Diminished neuromuscular excitability is one potential factor that may limit muscular recovery following injury or surgery . The H-reflex provides a measure of alpha motorneuron ( neuromuscular ) excitability in the sensory-motor pathway of the respective muscle and nerve . To date the vastus medialis ( VM ) and soleus ( SOL ) H-reflexes have been examined primarily in control subjects with induced knee joint effusion . This prospective , randomized clinical trial evaluated the affect of ACLR , utilizing hamsting ( HS ) or bone-patellar tendon-bone ( BTB ) autograft , on VM and SOL H-reflex latency and amplitude in twenty subjects . METHODS Preoperatively bilateral VM and SOL H-reflex tests were conducted . VM and SOL H-reflexes were subsequently conducted on the involved lower extremity at 1 and 3 months post surgery . At each test session subjects completed visual analog scales and knee girth was measured . RESULTS The VM H-reflex amplitude increased in the HS group at 3 months compared to 1-month post surgery ( p < .05 ) . Significant changes over time were also noted in the visual analog pain and functional scales and the mid-patella girth . CONCLUSIONS The increased VM H-reflex amplitude at 3 months following HS autograft ACLR demonstrates an increase in VM neuromuscular excitability . Increased VM neuromuscular excitability was not evident in patients following BTB reconstruction . The increased neuromuscular excitability , observed only in the HS group , warrants consideration when selecting graft type for patients with extensive preoperative quadriceps dysfunction .

ACLR

ACLR

H-reflex

hamsting ( HS )

VM and SOL H-reflexes

visual analog scales

knee girth

VM H-reflex amplitude

visual analog pain

VM H-reflex amplitude

VM neuromuscular excitability

VM neuromuscular excitability

neuromuscular excitability


FDA review of a panitumumab ( Vectibix ) clinical trial for first-line treatment of metastatic colorectal cancer . On September 27 , 2006 , the U.S. Food and Drug Administration granted accelerated approval to panitumumab ( Vectibix ; Amgen , Inc. , Thousand Oaks , CA ) for the treatment of patients with epidermal growth factor receptor-expressing , metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine- , oxaliplatin- , and irinotecan-containing chemotherapy regimens . Accelerated approval was based on demonstration of a beneficial effect on progression-free survival ( PFS ) . The present submission summarizes a second clinical trial , to be included in the panitumumab package insert in June 2008 , of chemotherapy and bevacizumab with and without panitumumab in the first-line treatment of patients with metastatic colorectal cancer . The study was closed when inferior PFS and greater toxicity were demonstrated at the time of the planned interim efficacy analysis . Patients receiving panitumumab in combination with bevacizumab and chemotherapy experienced a higher incidence of death ( 9 % versus 4 % ) and a higher risk for grade 3 and 4 toxicities than patients receiving bevacizumab and chemotherapy alone . The incidences of any Common Terminology Criteria for Adverse Events grade 3 and 4 adverse events ( AEs ) were 87 % and 72 % in the panitumumab and control groups , respectively . Grade 3 and 4 AEs occurring more commonly in panitumumab-treated patients included rash/acneiform dermatitis , diarrhea , dehydration , primarily resulting from diarrhea , hypokalemia , stomatitis/mucositis , and pulmonary embolism . The addition of panitumumab to bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer was harmful when compared with bevacizumab and chemotherapy alone . The use of panitumumab in this setting can not be recommended .

panitumumab ( Vectibix )

panitumumab ( Vectibix ;

fluoropyrimidine-

panitumumab

chemotherapy

panitumumab

bevacizumab and chemotherapy

bevacizumab

chemotherapy

panitumumab

panitumumab-treated

bevacizumab and chemotherapy alone

panitumumab

death

grade 3 and 4 toxicities

Grade 3 and 4 AEs

rash/acneiform dermatitis

diarrhea

dehydration

diarrhea

hypokalemia

stomatitis/mucositis

pulmonary embolism

colorectal cancer

metastatic colorectal cancer

colorectal cancer


Hyperbaric treatment for children with autism : a multicenter , randomized , double-blind , controlled trial . BACKGROUND Several uncontrolled studies of hyperbaric treatment in children with autism have reported clinical improvements ; however , this treatment has not been evaluated to date with a controlled study . We performed a multicenter , randomized , double-blind , controlled trial to assess the efficacy of hyperbaric treatment in children with autism . METHODS 62 children with autism recruited from 6 centers , ages 2-7 years ( mean 4.92 +/- 1.21 ) , were randomly assigned to 40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere ( atm ) and 24 % oxygen ( " treatment group " , n = 33 ) or slightly pressurized room air at 1.03 atm and 21 % oxygen ( " control group " , n = 29 ) . Outcome measures included Clinical Global Impression ( CGI ) scale , Aberrant Behavior Checklist ( ABC ) , and Autism Treatment Evaluation Checklist ( ATEC ) . RESULTS After 40 sessions , mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning ( p = 0.0008 ) , receptive language ( p < 0.0001 ) , social interaction ( p = 0.0473 ) , and eye contact ( p = 0.0102 ) ; 9/30 children ( 30 % ) in the treatment group were rated as " very much improved " or " much improved " compared to 2/26 ( 8 % ) of controls ( p = 0.0471 ) ; 24/30 ( 80 % ) in the treatment group improved compared to 10/26 ( 38 % ) of controls ( p = 0.0024 ) . Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning ( p = 0.0336 ) , receptive language ( p = 0.0168 ) , and eye contact ( p = 0.0322 ) . On the ABC , significant improvements were observed in the treatment group in total score , irritability , stereotypy , hyperactivity , and speech ( p < 0.03 for each ) , but not in the control group . In the treatment group compared to the control group , mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability ( p = 0.0311 ) . On the ATEC , sensory/cognitive awareness significantly improved ( p = 0.0367 ) in the treatment group compared to the control group . Post-hoc analysis indicated that children over age 5 and children with lower initial autism severity had the most robust improvements . Hyperbaric treatment was safe and well-tolerated . CONCLUSION Children with autism who received hyperbaric treatment at 1.3 atm and 24 % oxygen for 40 hourly sessions had significant improvements in overall functioning , receptive language , social interaction , eye contact , and sensory/cognitive awareness compared to children who received slightly pressurized room air . TRIAL REGISTRATION clinicaltrials.gov NCT00335790 .

hyperbaric treatment

slightly pressurized room air

efficacy

Aberrant Behavior Checklist ( ABC )

CGI

overall functioning

receptive language

social interaction

eye contact

parental CGI scores

overall functioning

receptive language

eye contact

ABC

ABC total score and subscales

ATEC , sensory/cognitive awareness

children

autism

children

autism

ages 2-7 years ( mean 4.92 +/- 1.21 )

Children

autism


A prospective , randomized , comparative trial of a COX-2 selective nonsteroidal anti-inflammatory drug versus placebo in inguinal herniorrhaphy patients . OBJECTIVE The standard opioid treatment for postoperative pain can be associated with nausea , vomiting , and constipation . In addition , opioids often provide insufficient pain relief . The purpose of this study was to compare postoperative pain and functional outcomes in patients undergoing inguinal herniorrhaphy who receive a COX-2 selective nonsteroidal anti-inflammatory drug ( COX-2 ) or placebo preoperatively and for 4 days postoperatively . METHODS A prospective , randomized , blinded , placebo-controlled trial was conducted in adults undergoing elective , outpatient , unilateral inguinal herniorrhaphy . Patients received rofecoxib ( 50 mg , 1 h prior to incision ) or placebo . Doses were re-administered once daily on postoperative days 1-4 . Patients were also given hydrocodone bitartrate for use as needed in the postoperative period . Pain outcomes were assessed , including pain intensity ( 1-10 visual-analogue scale ) and the use of hydrocodone bitartrate . In addition , functional outcomes such as activity and return of bowel function were examined for 5 postoperative days . Incidence and severity of side effects were examined . Statistics are mean +/- standard deviation . RESULTS Fifty-five subjects completed the study . Twenty-six patients received rofecoxib and 29 patients received placebo . Patients who received COX-2 demonstrated improved bowel function as reflected by more bowel movements on postoperative day 2 and postoperative day 3 . COX-2-treated patients also reported better oral intake on these same days . In addition , COX-2-treated patients had less difficulty coughing on postoperative day 1 . Overall satisfaction with pain management was better in COX-2-treated patients ( very satisfied vs. satisfied ) . There were no statistically significant differences between groups in the amount of hydrocodone bitartrate consumption . There were no complications during the study period . CONCLUSIONS Administration of a COX-2 selective nonsteroidal anti-inflammatory drug prior to and following outpatient inguinal herniorrhaphy improves functional outcomes when compared with placebo and increases patient satisfaction . These results suggest that multimodal pain therapy with COX-2 inhibitors may have a role in outpatient inguinal hernia repair .

placebo

placebo-controlled

rofecoxib

placebo

hydrocodone bitartrate

Pain

pain intensity

activity and return of bowel function

side effects

bowel function

oral intake

coughing

pain management

complications

inguinal herniorrhaphy

inguinal herniorrhaphy

adults

unilateral inguinal herniorrhaphy

Fifty-five

outpatient inguinal hernia


The effect of risedronate treatment on serum cytokines in postmenopausal osteoporosis : a 6-month randomized and controlled study . There is much evidence suggesting that the decline in ovarian function after menopause is associated with spontaneous increases in proinflammatory cytokines . Treatment with risedronate is accompanied by significant changes in bone turnover and bone mineral density . The objective of this study was to determine the effects of risedronate treatment on the level of serum cytokines including receptor activator of nuclear factor-kappaB ligand ( RANKL ) and osteoprotegerin among postmenopausal women with osteoporosis . The study group consisted of 61 postmenopausal women with osteoporosis . Patients were randomly divided in two groups : In group 1 ( n = 41 ) postmenopausal women received oral risedronate ( 35 mg/week ) , calcium ( 1,000 mg/day ) , and vitamin D ( 400 IU/day ) for 12 months . In group 2 ( control group ; n = 20 ) patients received only oral calcium ( 1,000 mg/day ) and vitamin D ( 400 IU/day ) . Bone mineral density ( BMD ) of lumbar spine ( L1-L4 ) and proximal femur were determined using dual X-ray absorptiometry at baseline and after one year . Venous blood samples were obtained for determination of serum cytokines including interleukin-1beta ( IL-1beta ) , tumor necrosis factor-alpha ( TNF-alpha ) , RANKL , osteoprotegerin , and markers of bone formation and resorption . Levels of serum cytokines were measured before therapy and after three and 6 months . Markers of bone metabolism were studied before therapy and after 6 months . In group 1 ( risedronate plus calcium/vitamin D-treated patients ) , serum levels of RANKL and IL-1beta significantly decreased and the level of osteoprotegerin significantly increased after three and 6 months , but no significant difference was found in TNF-alpha level . In group 2 , however , the level of serum cytokines did not change after three and 6 months . In cases of bone turnover , both markers of bone resorption and formation significantly decreased after 6 months in group 1 . In conclusion risedronate could improve osteoporosis by increasing osteoprotegerin and reducing RANKL and IL-1beta .

risedronate

risedronate

risedronate

oral risedronate

calcium

vitamin D

oral calcium

vitamin D

Venous blood

serum cytokines

serum cytokines

Markers of bone metabolism

serum levels of RANKL and IL-1beta

level of osteoprotegerin

TNF-alpha level

serum cytokines

bone turnover

postmenopausal osteoporosis :


Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial ( ONTARGET ) : implications for reduced cardiovascular risk . The recently published Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial ( ONTARGET ) in patients with vascular disease or high-risk diabetes , as the largest published comparative trial of these agent classes , provides further evidence concerning the comparison between the angiotensin-receptor blockers ( ARBs ) and the angiotensin-converting enzyme inhibitors ( ACEIs ) . In this trial , telmisartan ( an ARB ) was non-inferior to ramipril ( an ACEI ) in reducing fatal and nonfatal cardiovascular events . Moreover , ONTARGET is an example of a high-quality noninferiority trial . However , the combination of the 2 agents was associated with more adverse effects without an increase in benefit . The study differed from several other comparative studies in which the dose and choice of ACEI was left to individual physicians . Further , in ONTARGET , the ACEI was not titrated to the maximum dose and patients with heart failure were excluded .

angiotensin-receptor blockers ( ARBs )

telmisartan ( an ARB )

ramipril ( an ACEI )

ONTARGET

ACEI

ONTARGET

ACEI

cardiovascular risk

adverse effects


Mastication and late mandibular fracture after surgery of impacted third molars associated with no gross pathology . PURPOSE This study was undertaken with the null hypothesis that in patients , fully denate or with 1 or 2 teeth missing and older than 25 years , mastication does not affect late mandibular fracture after surgical removal of impacted third molars ( M3s ) associated with no gross pathology . MATERIALS AND METHODS Five hundred sixty patients , fully dentate or with 1 or 2 teeth missing and older than 25 years who had no gross pathology associated with their impacted lower M3s , were recruited in this study . They were operated on under local anesthesia using a standard technique and randomly assigned into 2 groups for nonroutine ( NR group ) and routine ( R group ) postoperative instructions . In the NR group , patients were postoperatively educated in the possibility of mandibular fracture and were given an emphasis on the necessity of limiting mastication to a soft diet for 4 weeks . In the R group , patients were given no such education or emphasis . Patients were followed up for 2 months , and data concerning patients ' age and gender ; tooth position , angulation , and depth ; date and site of surgery ; and occurrence of late mandibular fracture were recorded and statistically analyzed . A value of P less than .05 was considered statistically significant . RESULTS In no patient group was there a late mandibular fracture recorded . All patients completed the follow-up period , and most of the R group patients had normal eating habits 10 to 14 days after surgery . In no patient group was there a statistically significant difference in relation to gender ( P = .735 ) , site of surgery ( P = .552 ) , class horizontal space available ( P = .427 ) , class highest portion of the M3 crown ( P = .424 ) , angulations of the teeth ( P = .925 ) , and severity of impaction ( P = .445 ) . CONCLUSIONS In patients , fully dentate or with 1 or 2 teeth missing and older than 25 years who have no jawbone atrophy and no systemic problems that may impair bone strength , mastication seems not to affect late mandibular fracture after surgical removal of impacted M3s associated with no gross pathology . The remote possible risk of the late fracture shown in our patients indicates the need for no special precautions .

surgery

surgical removal

operated

local anesthesia

surgery

mandibular fracture

mandibular fracture

limiting mastication

late mandibular fracture

severity of impaction

impair bone strength

late mandibular fracture

late fracture


Cognitive behavioral therapy for anxiety in children with autism spectrum disorders : a randomized , controlled trial . BACKGROUND Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment . This study tested a modular cognitive behavioral therapy ( CBT ) program for children with this profile . A standard CBT program was augmented with multiple treatment components designed to accommodate or remediate the social and adaptive skill deficits of children with ASD that could pose barriers to anxiety reduction . METHOD Forty children ( 7-11 years old ) were randomly assigned to 16 sessions of CBT or a 3-month waitlist ( 36 completed treatment or waitlist ) . Therapists worked with individual families . The CBT model emphasized behavioral experimentation , parent-training , and school consultation . Independent evaluators blind to treatment condition conducted structured diagnostic interviews and parents and children completed anxiety symptom checklists at baseline and posttreatment/postwaitlist . RESULTS In intent-to-treat analyses , 78.5 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 8.7 % of the waitlist group . CBT also outperformed the waitlist on diagnostic outcomes and parent reports of child anxiety , but not children 's self-reports . Treatment gains were maintained at 3-month follow-up . CONCLUSIONS The CBT manual employed in this study is one of the first adaptations of an evidence-based treatment for children with autism spectrum disorders . Remission of anxiety disorders appears to be an achievable goal among high-functioning children with autism .

Cognitive behavioral therapy

cognitive behavioral therapy ( CBT )

CBT

CBT

3-month waitlist

CBT

CBT

waitlist

CBT

waitlist

CBT

anxiety

functional impairment

anxiety reduction

anxiety symptom checklists

parent reports of child anxiety

anxiety

Children with autism spectrum disorders

children with ASD


Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance . OBJECTIVE Coffee consumption has been associated with lower risk of type 2 diabetes . We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance . RESEARCH DESIGN AND METHODS We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee , 1 g chlorogenic acid , 500 mg trigonelline , and placebo ( 1 g mannitol ) on glucose and insulin concentrations during a 2-h oral glucose tolerance test ( OGTT ) in 15 overweight men . RESULTS Chlorogenic acid and trigonelline ingestion significantly reduced glucose ( -0.7 mmol/l , P = 0.007 , and -0.5 mmol/l , P = 0.024 , respectively ) and insulin ( -73 pmol/l , P = 0.038 , and -117 pmol/l , P = 0.007 ) concentrations 15 min following an OGTT compared with placebo . None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo . CONCLUSIONS Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT .

decaffeinated coffee

chlorogenic

trigonelline

Coffee

decaffeinated coffee

decaffeinated coffee

chlorogenic acid

trigonelline

placebo

mannitol

placebo

glucose tolerance .

glucose

insulin

glucose and insulin responses

glucose tolerance

type 2 diabetes .

overweight

men


Fixed-dose manidipine/delapril versus losartan/hydrochlorothiazide in hypertensive patients with type 2 diabetes and microalbuminuria . INTRODUCTION Patients with diabetes complicated by hypertension and microalbuminuria have elevated cardiovascular risk , and controlling blood pressure in these patients is an urgent clinical priority . The present study aimed to examine the effects of a fixed-dose combination of antihypertensives on blood pressure and microalbuminuria . METHODS Patients with type 2 diabetes , mild-to-moderate hypertension ( diastolic blood pressure 85-105 mmHg , systolic blood pressure < 160 mmHg , and 24-hour mean systolic blood pressure > 130 mmHg ) , and microalbuminuria were randomized to 1 year of doubleblind treatment with fixed-dose manidipine/delapril ( n=54 ) or losartan/hydrochlorothiazide ( HCTZ ) ( n=56 ) . RESULTS Blood pressure was significantly reduced at 1 year in both groups ( -22.2/-14.6 mmHg and -19.5/-14.3 mmHg , for systolic and diastolic blood pressure respectively , P < 0.001 for each ) , with no significant between-group difference . Reductions in microalbuminuria occurred in both groups , with mean changes at 1 year of -3.9 mg/mmol creatinine ( 95 % CI -5.3 , -2.5 ) for manidipine/delapril ( P < 0.001 vs. baseline ) and -2.7 mg/mmol creatinine ( 95 % CI -4.0 , -1.3 ) for losartan/HCTZ ( P < 0.001 vs. baseline and P=0.199 between groups ) . Glycemia over the 1-year study was largely unaffected ; the blood glucose concentration was reduced from baseline with manidipine/delapril , although not statistically significant ( mean change -0.2 mmol/L , P=0.064 ) . Both treatments were well tolerated , with discontinuation for adverse events for one ( 1.9 % ) patient in the manidipine/delapril group and two ( 3.6 % ) in the losartan/HCTZ group . CONCLUSIONS A fixed-dose manidipine/delapril combination represents a useful addition to the treatment options available to control hypertension complicated by diabetes and microalbuminuria .

manidipine/delapril

losartan/hydrochlorothiazide

fixed-dose manidipine/delapril

losartan/hydrochlorothiazide ( HCTZ )

manidipine/delapril

losartan/HCTZ

manidipine/delapril

manidipine/delapril

losartan/HCTZ

manidipine/delapril

blood pressure

microalbuminuria

Blood pressure

systolic and diastolic blood pressure

microalbuminuria

Glycemia

blood glucose concentration

adverse events

hypertensive

type 2 diabetes

microalbuminuria

diabetes

hypertension

microalbuminuria

type 2 diabetes

hypertension

microalbuminuria


The SNRI venlafaxine improves emotional unawareness in patients with post-stroke depression . OBJECTIVE Patients with stroke have a high prevalence of depression and unawareness of emotions or alexithymia . Here we investigated the effects of the serotoninergic and noradrenergic reuptake inhibitor ( SNRI ) venlafaxine in comparison with the SSRI fluoxetine on alexithymia severity in patients with DSM-IV post-stroke major depressive-like episode ( PSD ) . METHODS Fifty inpatients with first-ever stroke and PSD were consecutively enrolled in this randomized open-label study . Twenty-five were treated with the SNRI venlafaxine SR ( 75-150 mg/die ) , and 25 with the SSRI fluoxetine ( 20-40 mg/die ) . All patients were assessed at day 0 , and after 1 , 2 , 4 , 6 , and 8 weeks , using the Mini-Mental State Examination , the Hamilton Depression Rating Scale , and the Toronto Alexithymia Scale ( TAS-20 ) . RESULTS Patients treated with fluoxetine and those treated with venlafaxine showed similar improvement in depressive symptoms . However , patients treated with venlafaxine had a greater improvement on alexithymia severity than those treated with fluoxetine . The effect of venlafaxine on unawareness of emotions was evident in patients with alexithymia ( TAS-20 > or= 61 ) at the baseline and in those without alexithymia ( TAS-20 < 61 ) . CONCLUSIONS Antidepressants acting on both the serotoninergic and noradrenergic systems might represent a valid resource not only for the treatment of depression but also for improving emotional unawareness in stroke patients .

SNRI venlafaxine

SSRI fluoxetine

SNRI venlafaxine

SSRI fluoxetine

emotional unawareness

alexithymia .

alexithymia

depressive symptoms .

alexithymia severity

unawareness of emotions

emotional unawareness


Diverting stoma after low anterior resection : more arguments in favor . PURPOSE The necessity of a protective stoma in patients undergoing low anterior resection with total mesorectal excision for primary rectal cancer is discussed controversially . We conducted a randomized , controlled , pilot-study to evaluate the need for diverting ileostomy in patients undergoing low anterior resection [ NCT00457327 ] . METHODS Forty patients after elective sphincter-saving low anterior resection were eligible for intraoperative randomization . The primary objective of this trial was to demonstrate similar risks after the resection with both techniques . A priori stopping rules were defined for early termination of the trial . RESULTS Between July 4 , 2006 and March 12 , 2007 , a total of 41 patients were screened and 34 patients were randomized . Eighteen patients were randomized to the stoma group and 16 patients to the nonstoma group The symptomatic anastomotic leakage rate was significantly higher in the nonstoma group ( 37.5 percent ) than in the stoma group ( 5.5 percent , P = 0.02 ) . In all six cases in the nonstoma group , reoperations were necessary . The study was stopped after 34 patients were included . A meta-analysis of the available data confirmed the value of a protective ostomy for patients undergoing low anterior resection . CONCLUSIONS The data demonstrate a high risk for patients undergoing low anterior resection without diverting ileostomy .

protective stoma

low anterior resection

stoma group

nonstoma group

Diverting stoma

diverting ileostomy

similar risks

reoperations

primary rectal cancer

Forty

Eighteen

anterior resection


Pregabalin versus naltrexone in alcohol dependence : a randomised , double-blind , comparison trial . Pregabalin ( PRE ) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the alpha ( 2 ) -delta subunit of voltage-gated calcium channels . In this randomised , double-blind comparison trial with naltrexone ( NAL ) , we aimed to investigate the efficacy of PRE on alcohol drinking indices . Craving reduction and improvement of psychiatric symptoms were the secondary endpoints . Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups , receiving 50 mg of NAL or 150-450 mg of PRE . Craving ( VAS ; OCDS ) , withdrawal ( CIWA-Ar ) and psychiatric symptoms ( SCL-90-R ) rating scales were applied . Alcohol drinking indices and craving scores were not significantly different between groups . Compared with NAL , PRE resulted in greater improvement of specific symptoms in the areas of anxiety , hostility and psychoticism , and survival function ( duration of abstinence from alcohol ) . PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder . Results from this study globally place PRE within the same range of efficacy as that of NAL . The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology .

Pregabalin

naltrexone

Pregabalin ( PRE )

naltrexone ( NAL )

NAL , PRE

NAL .

PRE

alcohol drinking indices

Craving reduction

improvement of psychiatric symptoms

Craving ( VAS ; OCDS )

withdrawal ( CIWA-Ar )

Alcohol drinking indices

craving scores

anxiety

hostility

psychoticism

survival function

duration of abstinence from alcohol

alcohol craving

alcohol dependence

Seventy-one

comorbid psychiatric disorder


Bridge plate osteosynthesis using dynamic condylar screw ( DCS ) or retrograde intramedullary supracondylar nail ( RIMSN ) in the treatment of distal femoral fractures : comparison of two methods in a prospective randomized study . BACKGROUND The treatment of distal femoral fractures remains a significant surgical challenge . With the rigid fixation of the distal femoral fractures , bone grafting is frequently needed . Biological osteosynthesis using dynamic condylar screw ( DCS ) and retrograde intramedullary supracondylar nail ( RIMSN ) preserve the blood supply and limit the need for bone grafting . METHODS From September 2002 to December 2004 , 68 closed fractures of the distal femur were treated by bridge plate osteosynthesis using DCS in 31 and RIMSN in 37 . The patients were allocated to one of the two groups randomly and followed for 24-36 months ( average : 30 months ) . RESULTS With respect to operation time , the DCS group presented significantly better results than the RIMSN group ( p=0.000 ) . However , the blood loss was significantly more in the DCS group ( p=0.000 ) . There were no significant differences in terms of cumulative rate of union ( p=0.855 ) , range of motion of the knee ( p=0.727 ) , overall results ( p=0.925 ) and complications ( p=0.927 ) between the two groups . CONCLUSION No implant or surgical technique is superior to any other under all circumstances for distal femoral fracture . RIMSN is standard care , yet the biological osteosynthesis using DCS is a very good alternative for the treatment of distal femoral fractures .

Bridge plate osteosynthesis

dynamic condylar screw ( DCS )

bridge plate osteosynthesis

DCS

RIMSN

blood loss

cumulative rate of union

range of motion of the knee

overall results

complications

distal femoral fractures

distal femoral fractures

fractures of the distal femur

distal femoral fractures


Feasibility of a telephone-based intervention for support persons to help smokers quit : a pilot study . BACKGROUND Nonsmokers have a potentially supportive role in tobacco cessation efforts . The present study examined the feasibility , acceptability , and potential efficacy of a telephone-based intervention for nonsmoking support persons . METHODS A total of 59 support persons ( mean age = 36 years , 92 % female , 95 % White ) were randomly assigned to a control condition ( N = 30 ; written materials only ) or to a social cognitive theory-based intervention ( N = 29 ; written materials and 5 weekly , 20- to 30-min telephone counseling sessions ) . Both support persons and smokers completed assessments separately by mail at baseline and at weeks 6 ( end of treatment ) and 26 . RESULTS Two thirds of the smokers reported low-moderate levels of motivation to quit at baseline as assessed by the contemplation ladder . Study retention rates were excellent , with 95 % of both support persons and smokers completing the week 26 assessment . Moreover , 86 % of support persons in the intervention group completed all five telephone sessions . Treatment acceptability was high for both support persons and smokers . Compared with the control condition , the intervention was associated with a significant increase in support person self-efficacy to help their smoker ( p = .034 ) and outcome expectancies ( p = .025 ) from baseline to week 6 . However , the intervention was not associated with higher smoking abstinence rates or quit attempts . DISCUSSION The program was successful in reaching smokers with lower levels of readiness to quit . The intervention was feasible and acceptable to both support persons and smokers . Although support persons and smokers can be engaged in this type of outreach program , refinements in the intervention approach are needed to improve the smoking outcomes .

telephone-based intervention

telephone-based intervention

written materials only )

written materials and

telephone counseling sessions )

smokers

levels of motivation to quit

Study retention rates

Treatment acceptability

support person self-efficacy

smoker

outcome expectancies

lower levels of readiness to quit

feasible and acceptable

smoking outcomes

smokers quit :

nonsmoking support persons

mean age = 36 years

female

smokers


Deep vein thrombosis in acute spinal cord injury . STUDY DESIGN Randomized study . OBJECTIVES To find out the incidence of deep vein thrombosis ( DVT ) in acute spinal cord injury ( SCI ) patients with and without therapeutic prophylaxis . SETTING Patients admitted in the department of Physical Medicine & Rehabilitation , SMS Medical College , Jaipur , India . METHODS All 297 patients received physical therapy measures and were randomly divided into two groups . 166 patients received prophylactic heparin , whereas 131 patients did not . RESULTS A total of three cases ( 1.8 % ) in study group and four cases ( 3 % ) in control group developed DVT . This difference was statistically insignificant ( P > 0.05 ) . CONCLUSION Incidence of DVT in SCI is low in our study .

therapeutic prophylaxis

physical therapy measures

prophylactic heparin

Deep vein thrombosis

Incidence of DVT

low

acute spinal cord injury .

received physical therapy measures


Social competence and social skills training and intervention for children with Autism Spectrum Disorders . This study examined the effectiveness of a 30 week social competence and social skills group intervention program with children , ages 7-11 , diagnosed with Autism Spectrum Disorders ( ASD ) . Eighteen children with ASD were assessed with pretreatment and posttreatment measures on the Walker-McConnell Scale ( WMS ) and the MGH YouthCare Social Competence Development Scale . Each received the 30-week intervention program . For comparison , a matched sample of ten non-ASD children was also assessed , but received no treatment . The findings indicated that each ASD intervention group demonstrated significant gains on the WMS and significant improvement in the areas of anxiety management , joint attention , and flexibility/transitions . Results suggest that this approach can be effective in improving core social deficits in individuals with ASD .

WMS

anxiety management

joint attention

flexibility/transitions

social deficits

children

Autism Spectrum Disorders

children , ages 7-11

ASD


What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders ? OBJECTIVE To find out the optimum maximal dosage of recombinant follicle stimulating hormone ( rFSH ) in microdose gonadotropin-releasing hormone analog ( GnRH-a ) flare cycles in poor responders . DESIGN Prospective randomized study . SETTING Private infertility clinic . PATIENT ( S ) A total of 119 women were taken into the study . INTERVENTION ( S ) The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration . On the third day of GnRH-a administration , 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH ( group A , n = 38 ) , or 450 IU of rFSH ( group B , n = 39 ) , or 600 IU of rFSH ( group C , n = 42 ) . MAIN OUTCOME MEASURE ( S ) Peak E ( 2 ) levels , days of stimulation with rFSH , total rFSH dosage , total number of oocytes retrieved , M2 oocytes retrieved , total number of embryos , number of embryos transferred , number of Grade-1 embryos transferred , clinical pregnancy rate ( positive fetal cardiac activity ) , and cancellation rates of stimulation and embryo transfer . RESULT ( S ) Clinical pregnancy rates were 13.1 % , 15.3 % , and 16.1 % for group A , group B , and group C , respectively . There were no significant differences in the age , peak serum E ( 2 ) concentration , days of stimulation with rFSH , total number of M2 oocytes retrieved , number of embryos transferred , clinical pregnancy rates , and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage . CONCLUSION ( S ) There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles . In addition , because the duration of stimulation does not differ between the groups , the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages , and this would obviously cost less money to the patients .

gonadotropin

GnRH-agonist

rFSH administration

GnRH-a

rFSH

rFSH

rFSH

rFSH

rFSH

rFSH

rFSH

rFSH

rFSH

rFSH

Clinical pregnancy rates


[ Randomized clinical trial between nutritional counselling and commercial hypocaloric diet in weight loss in obese patients with chronic arthropathy ] . BACKGROUND AND OBJECTIVE The aim of our work was to evaluate in obese patients with an indication of replacement surgery for degenerative osteoarthritis , the utility of a hypocaloric diet with Optisource vs nutritional counseling . MATERIAL AND METHOD Thirty six patients were randomized in both branches : diet I with lunch and dinner substituted by two Optisource ( 1109,3 kcal/day , 166,4g of carbohydrates ( 60 % ) , 63g of proteins ( 23 % ) , 21,3g of lipids 17 % ) and diet II with nutritional counselling with a decrease of 500 cal/day from the previous dietary intake . Before and 3 months after treatment , a nutritional and biochemical study was performed . RESULTS Nineteen patients were randomized in group I and 17 patients in group II . 19 patients finished the study in group I and 14 in group II . Weight loss was higher in group I than II ( 7,7 [ 4,7 ] vs 3,92 [ 3,32 ] kg ; P=.05 ) , with a significant decrease of HOMA and diastolic blood pressure in group I. Decreases of body mass index ( -2,9 [ 1,8 ] vs -1,4 [ 0,9 ] ; P=.05 ) , fat mass ( -3,8 [ 3,4 ] vs -2,3 [ 1,7 ] kg ; P=.0,05 ) and HOMA ( -2,0 [ 2,2 ] vs -0,4 [ 1,82 ] ; P=.05 ) were higher in group I than II . CONCLUSIONS Obese patients with chronic osteoarthritis treated with a mixed diet supplemented with a commercial hypocaloric formula improved weight , fat mass and HOMA in a better way than patients treated with a dietary counselling alone .

hypocaloric diet

Optisource

commercial hypocaloric formula

dietary counselling

Weight loss

HOMA

diastolic blood pressure

body mass index

fat mass

HOMA

weight

fat mass

HOMA

obese patients

chronic arthropathy

obese patients

Thirty six

Obese patients

chronic osteoarthritis


Evaluation of electrofunctional data following argon-laser trabeculoplasty in primary open-angle glaucoma . To establish whether or not glaucomatous damage is reversible , we obtained pattern-reversal electroretinograms ( PERGs ) and visual evoked potentials ( VEPs ) in 25 eyes of 25 patients suffering from bilateral primary open-angle glaucoma ( POAG ) before and after argon-laser trabeculoplasty . The laser treatment was carried out in only one eye chosen at random , and the fellow eye was used as a control . In the present study we intended to verify the possibility of using electrofunctional techniques to determine the two distinct and , probably , consecutive glaucomatous alterations occurring in ganglion cells : functional ( reversible ) and anatomical ( irreversible ) . The results obtained indicate that glaucomatous damage is irreversible . We propose that such alterations differ very slightly and that the current electrofunctional techniques may not be sufficiently sophisticated to distinguish between them .

argon-laser trabeculoplasty

argon-laser trabeculoplasty

glaucomatous damage

visual evoked potentials ( VEPs )

glaucomatous damage


Randomized evaluation of octreotide vs prochlorperazine for ED treatment of migraine headache . UNLABELLED Patients with headaches account for approximately 2 % of all ED visits , with migraines being the most common defined primary headache syndrome . Our goals were to evaluate the efficacy of intravenous octreotide ( OC ) for the treatment of migraines , when compared to standard therapy with prochlorperazine . METHODS The study was conducted as a double-blinded , randomized controlled trial . Each subject received either 100 microg of octreotide or 10 mg of prochlorperazine intravenously for a 2-minute period . RESULTS Comparison of the change in median visual analog scale scores for 60 minutes demonstrated that octreotide was less effective at reducing pain ( P = .03 ) and producing clinical success ( P < .01 ) . Restlessness consistent with akathisia was noted by 35 % of the PC group and 8 % of the OC group ( P < .01 ) . At 60 minutes , rescue medication was required by 48 % of the patients in the OC group , whereas 10 % of the PC group required such therapy ( P < .01 ) . All 44 patients were contacted for follow-up at 48 to 72 hours after enrollment . At that time , 10 % of the prochlorperazine and 25 % of the octreotide patients had experienced some headache recurrence ( P = .1 ) . CONCLUSION Prochlorperazine was statistically superior to octreotide in clinical success rate and decrease in pain in migraine patients but caused more restlessness and sedation .

octreotide

prochlorperazine

octreotide ( OC )

prochlorperazine .

octreotide

prochlorperazine

octreotide

prochlorperazine

octreotide

migraine headache

median visual analog scale scores

pain

Restlessness consistent with akathisia

rescue medication

headache recurrence

clinical success rate

pain

restlessness

sedation


Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia : pooled results of 2 phase 3 studies . PURPOSE We evaluated the efficacy and safety of silodosin for treatment of benign prostatic hyperplasia symptoms in 2 randomized , placebo controlled , phase 3 studies . MATERIALS AND METHODS Men 50 years or older with an International Prostate Symptom Score of 13 or greater and peak urinary flow rate of 4 to 15 ml per second received placebo or 8 mg silodosin daily with breakfast for 12 weeks . The primary end point was International Prostate Symptom Score change from baseline to last observation . Change in peak urinary flow rate was a secondary end point . Differences in treatment efficacy were assessed by ANCOVA . RESULTS Of 923 patients ( mean age 65 years ) 466 received silodosin and 457 placebo . After 0.5 week ( range 3 to 4 days ) of treatment patients receiving silodosin vs placebo achieved significant improvement in total International Prostate Symptom Score ( difference -1.9 , p < 0.0001 ) and irritative ( -0.5 , p = 0.0002 ) and obstructive ( -1.4 , p < 0.0001 ) subscores . The mean +/- SD change from baseline in total International Prostate Symptom Score was -4.2 +/- 5.3 for silodosin vs -2.3 +/- 4.4 for placebo . Differences ( silodosin vs placebo ) in International Prostate Symptom Score and subscores increased by week 12 ( p < 0.0001 ) . Mean change from baseline in peak urinary flow rate ( ml per second ) 2 to 6 hours after initial dose was greater ( p < 0.0001 ) with silodosin ( 2.8 +/- 3.4 ) than placebo ( 1.5 +/- 3.8 ) . Differences remained significant ( p < 0.001 ) through week 12 . The most common treatment emergent adverse event was ( mostly mild ) retrograde ejaculation ( silodosin 28.1 % of patients , placebo 0.9 % ) . Few patients receiving silodosin ( 2.8 % ) discontinued because of retrograde ejaculation . Proportions of patients with treatment emergent orthostatic hypotension were similar for silodosin ( 2.6 % ) and placebo ( 1.5 % ) . CONCLUSIONS Treatment with silodosin produced rapid improvement in urinary symptoms that was sustained for 12 weeks . Silodosin was well tolerated with a low incidence of orthostatic hypotension .

silodosin

silodosin

placebo controlled

placebo

silodosin

silodosin

silodosin

efficacy and safety

International Prostate Symptom Score

peak urinary flow rate

Differences in treatment efficacy

irritative

obstructive

International Prostate Symptom Score

International Prostate Symptom Score

peak urinary flow rate

adverse event

retrograde ejaculation

retrograde ejaculation

orthostatic hypotension

urinary symptoms

orthostatic hypotension

men

benign prostatic hyperplasia

Men

50 years or older

Prostate