# Datasets: allenai /ms2_sparse_oracle

Languages: English
Multilinguality: monolingual
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review_id (string)pmid (sequence)title (sequence)abstract (sequence)target (string)background (string)
"30760312"
[ "22776744", "25271670", "3493740", "1863023", "16291984", "23984728", "23996433", "18466198", "12151469", "27400308", "16053970", "22922316", "11897647", "11597664", "4230647" ]
[ "Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension", "Adipose-derived stem cells attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling in monocrotaline-induced pulmonary hypertensive rats", "Effect of bone marrow mesenchymal stem cells on experimental pulmonary arterial hypertension", "Survival in patients with primary pulmonary hypertension. Results from a national prospective registry.", "Sildenafil citrate therapy for pulmonary arterial hypertension.", "Macitentan and morbidity and mortality in pulmonary arterial hypertension.", "Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension", "Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study.", "Inhaled iloprost for severe pulmonary hypertension.", "Sildenafil reduces pulmonary vascular resistance in single ventricular physiology.", "Ambrisentan therapy for pulmonary arterial hypertension.", "Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism.", "Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.", "Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebocontrolled study", "SYRCLE’s risk of bias tool for animal studies" ]
"Conclusions SC therapy is effective for PAH in pre clinical studies . These results may help to st and ardise pre clinical animal studies and provide a theoretical basis for clinical trial design in the future ."
"Background Despite significant progress in drug treatment , the prognosis of patients with advanced pulmonary arterial hypertension ( PAH ) remains extremely poor . Many pre clinical studies have reported the efficacy of stem cell ( SC ) therapy for PAH ; however , this approach remains controversial . The aim of this systematic review and meta- analysis is to assess the potential efficacy of SC therapy for PAH ."
"19588356"
[ "8532025", "10790348", "17504794", "16793845", "10733441" ]
[ "A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.", "Improvement in exercise capacity with nitric oxide inhalation in patients with precapillary pulmonary hypertension.", "Results of European post-marketing surveillance of bosentan in pulmonary hypertension", "Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions", "Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease" ]
"There was a trend for endothelin receptor antagonists to reduce mortality ( OR 0.48 ; 95 % CI 0.21 to 1.09 ) , and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients . Hepatic toxicity was not common , and endothelin receptor antagonists were well tolerated in this population . Endothelin receptor antagonists can increase exercise capacity , improve WHO/NYHA functional class , prevent WHO/NYHA functional class deterioration , reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III . However , there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension . Efficacy data are strongest in those with idiopathic pulmonary hypertension"
"BACKGROUND Pulmonary arterial hypertension is a devastating disease , which leads to right heart failure and premature death . Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension . OBJECTIVES To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension ."
"23893797"
[ "10637197", "14967718", "17599437", "22419603", "15170709", "20298994", "3305080", "22137076", "17213001", "18178395" ]
[ "Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs.", "Impact of Microvascular Dysfunction on Left Ventricular Remodeling and Long-Term Clinical Outcome After Primary Coronary Angioplasty for Acute Myocardial Infarction", "Relation between neutrophil counts on admission, microvascular injury, and left ventricular functional recovery in patients with an anterior wall first acute myocardial infarction treated with primary coronary angioplasty.", "Early statin treatment prior to primary PCI for acute myocardial infarction: REPERATOR, a randomized placebo‐controlled pilot trial", "Use of statins prior to percutaneous coronary intervention reduces myonecrosis and improves clinical outcome", "Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial.", "Impact of chronic statin-pretreatment on myocardial damage as assessed by Cardiac Magnetic Resonance findings in patients with acute ST-elevation myocardial infarction", "Effects of atorvastatin pretreatment on infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.", "Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention.", "Effect of statin therapy before Q-wave myocardial infarction on myocardial perfusion." ]
"This present meta- analysis suggests that statin pretreatment might be effective in improving myocardial perfusion in STEMI patients"
"BACKGROUND To achieve sufficient myocardial perfusion in ST-segment elevation myocardial infa rct ion ( STEMI ) patients receiving primary percutaneous coronary intervention ( PPCI ) , many adjunctive therapies have been proposed . Previous trials have reported variances in myocardial perfusion improvement for statin pretreatment , which made it inconvincible to confirm the beneficial effects of statins . Therefore , we performed a systematic review and meta- analysis to determine whether statin pretreatment was effective in improving myocardial perfusion . HYPOTHESIS Statin pretreatment could improve myocardial perfusion in STEMI patients undergoing PPCI ."
"27167891"
[ "24376277", "23328881", "21247734", "22140149", "4254406", "4376148", "2963881", "24629480", "18052855", "25957438" ]
[ "Effect of cessation interventions on hookah smoking: post-hoc analysis of a cluster-randomized controlled trial.", "A randomized, controlled community-wide intervention to reduce environmental tobacco smoke exposure.", "GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias).", "Patterns of water-pipe and cigarette smoking initiation in schoolchildren: Irbid longitudinal smoking study.", "Challenges to obtaining parental permission for child participation in a school-based waterpipe tobacco smoking prevention intervention in Qatar", "A Web-Based Program to Increase Knowledge and Reduce Cigarette and Nargila Smoking Among Arab University Students in Israel: Mixed-Methods Study to Test Acceptability", "Study of Secondhand Smoke Levels Pre and Post Implementation of the Comprehensive Smoking Ban in Mumbai", "Behavioral cessation treatment of waterpipe smoking: The first pilot randomized controlled trial.", "Outcomes and adherence in Syria's first smoking cessation trial.", "Waterpipe Tobacco Smoking Prevalence and Correlates in 25 Eastern Mediterranean and Eastern European Countries: Cross-Sectional Analysis of the Global Youth Tobacco Survey." ]
"In conclusion , there is a lack of evidence of effectiveness for most waterpipe interventions ."
"Waterpipe tobacco smoking is growing in popularity despite adverse health effects among users . We systematic ally review ed the literature , search ing MEDLINE , EMBASE and Web of Science , for interventions targeting prevention and cessation of waterpipe tobacco smoking ."
"28753768"
[ "24322061", "24216616", "23632798", "8831469", "18176739" ]
[ "The Arizona Sexual Experiences Scale: a validity and reliability assessment of the Thai translation (ASEX-Thai) in Parkinson's disease.", "Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury", "A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)", "Sexual adjustment and quality of relationship in spinal paraplegia: a controlled study.", "Sexuality and sexual life in women with spinal cord injury: a controlled study." ]
[ "INTRODUCTION Cultural sensitivities tend to limit assessment s of sexual dysfunction ( SD ) in Parkinson 's disease ( PD ) . OBJECTIVE To assess the validity and reliability of the Thai translation ( ASEX-Thai ) of the Arizona Sexual Experiences Scale ( ASEX ) . METHOD The validity and reliability of ASEX-Thai were assessed with a r and om sample of 40 PD patients . Back translation and cross-cultural modifications assured content validity . Criterion validity used DSM-IV-TR criteria and receiver operating characteristics ( ROC ) analysis was calculated for cutoff points plus sensitivity and specificity . Internal consistency was assessed with Cronbach 's alpha coefficient . Test-retest reliability was assessed by Pearson 's correlation at baseline and at a 2-month follow-up . RESULT Criterion validity was conducted with a positive correlation between the clinical diagnosis of SD and DSM-IV-TR ( r = 0.601 ; p < 0.001 ) . The ROC analysis differentiated between SD and non-SD patients ( p < 0.001 ) . The cutoff point of ASEX-Thai at ≥16 points effectively screened for SD ( sensitivity 96.2 % , specificity 92.9 % ) . Reliability was documented with the Cronbach 's alpha of all items at baseline and at a 2-month follow-up with values of 0.948 and 0.962 respectively . The Pearson 's correlation also showed highly significant test-retest reliability [ Item 1 ( r = 0.959 , p < 0.001 ) , Item 2 ( r = 0.914 , p < 0.001 ) , Item 3 ( r = 0.944 , p < 0.001 ) , Item 4 ( r = 0.992 , p < 0.001 ) , Item 5 ( r = 0.930 , p < 0.001 ) , and total ASEX-Thai score ( r = 0.883 , p < 0.001 ) ] . CONCLUSION ASEX-Thai is a valid and reliable instrument for the assessment of sexual dysfunction in Thai PD patients", "Study design : Two r and omized , double-blind , placebo-controlled trials . Objective : To evaluate the efficacy and safety of fampridine sustained-release tablets ( fampridine-SR ) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury ( SCI ) . Setting : United States and Canada . Methods : Patients with incomplete chronic SCI were r and omized to twice daily fampridine-SR 25 mg or placebo , with a 2-week single-blind placebo run-in , a 2-week titration , 12 weeks of stable dosing , 2 weeks of downward titration and 2 weeks of untreated follow-up . Co- primary end points were the change from baseline , averaged over the double-blind treatment period , for Ashworth score ( bilateral knee flexors and extensors ) and a 7-point Subject Global Impression of treatment ( SGI ; 1 , terrible ; 7 , delighted ) . Secondary end points were : Penn Spasm Frequency Scale ; the motor/sensory score from the International St and ards for Neurological Classification of SCI ; Clinician ’s Global Impression of Change of neurological status ; and the International Index of Erectile Function ( men ) or the Female Sexual Function Index ( women ) . Results : The population s were 212 and 203 patients in the two studies , respectively . Changes from baseline in Ashworth score were −0.15 ( placebo ) and −0.19 ( fampridine-SR ) in the first study , and −0.16 ( placebo ) and −0.28 ( fampridine-SR ) in the second study . The between-treatment difference was not significant for either the Ashworth score or the SGI and , with few exceptions , neither were the secondary end points . Fampridine-SR was generally well tolerated ; treatment-emergent adverse events ( TEAEs ) and serious TEAEs were reported with similar frequency between treatments . Conclusion : Fampridine-SR was well tolerated . No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI", "Introduction and hypothesisThe objective of this study was to create a valid , reliable , and responsive sexual function measure in women with pelvic floor disorders ( PFDs ) for both sexually active ( SA ) and inactive ( NSA ) women . Methods Expert review identified concept gaps and generated items evaluated with cognitive interviews . Women underwent Pelvic Organ Prolapse Quantification ( POPQ ) exams and completed the Incontinence Severity Index ( ISI ) , a prolapse question from the Epidemiology of Prolapse and Incontinence Question naire ( ISI scores ) , the Pelvic Floor Distress Inventory-20 ( PFDI-20 ) , and the Female Sexual Function Index ( FSFI ) . Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping . Cronbach ’s alpha measured internal consistency . Factor correlations evaluated criterion validation . Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery . Results A total of 589 women gave baseline data , 200 returned surveys after treatment , and 147 provided test-retest data . For SA women , 3 subscales each in 2 domains ( 21 items ) and for NSA women 2 subscales in each of 2 domains ( 12 items ) emerged with robust psychometric properties . Cronbach ’s alpha ranged from .63 to .91 . For SA women , correlations were in the anticipated direction with PFDI-20 , ISI , and FSFI scores , POPQ , and EPIQ question # 35 ( all p < .05 ) . PFDI-20 , ISI , and FSFI subscale change scores correlated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Question naire International Urogynecological Association-revised ( PISQ-IR ) factor change scores and with mean change scores in women who underwent surgery ( all p < .05 ) . For NSA women , PISQ-IR scores correlated with PFDI-20 , ISI scores , and with EPIQ question # 35 ( all p < .05 ) . No items demonstrated differences between test and retest ( all p ≥ .05 ) , indicating stability over time . Conclusions The PISQ-IR is a valid , reliable , and responsive measure of sexual function", "OBJECTIVE To identify determinants of sexual adjustment by persons with spinal cord injury ( SCI ) and quality of the relationship compared with persons in the general population . DESIGN Controlled survey . SETTING Postdischarge community setting . PARTICIPANTS A consecutive series of 252 persons admitted to our spinal unit between November 1982 and July 1991 with traumatic SCI were contacted , 85 of whom persons were excluded : 36 were dead , 37 had recovered , 5 could not be located , 4 were younger than 18 years , 2 had language difficulties , and 1 had a psychiatric illness . Of the remaining 167 persons with SCI , 85 had a stable partner relationship , 75 of whom ( 88 % ) completed and returned the question naires ( median age , 33 years ; range 19 to 76 ) . An age- and sex-matched control group was r and omly selected from the general population . Of the 264 respondents , 155 ( 59 % ) had a stable partner relationship . MAIN OUTCOME MEASURES The 80-item question naire addressed experiences concerning sexual functioning , desire , and activity , sexual behavior , satisfaction with sex life , and aspects of the emotional quality of the relationship . RESULTS Sexual activity and satisfaction was lower among persons with SCI compared with the controls ; the emotional quality of the relationship did not differ . The most important correlates for sexual fulfillment in both groups were found to be the use of a varied repertoire of sexual behaviors and the perception that the partner enjoys and is satisfied with the sexual part of the relationship . CONCLUSION Psychosocial rather than physical factors were important for a satisfying sexual life and relationship . A qualitative study should be undertaken to further explore the complexity of sexual adjustment after SCI", "OBJECTIVE To describe sexual life in women with spinal cord injury . DESIGN Controlled cross-sectional , question naire . PARTICIPANTS AND METHODS Women , 18 - 65 years , treated at spinal cord centres in Sweden , Denmark , Norway , Finl and and Icel and . 545 women ( 57 % ) completed the question naires . The age-matched control group consisted of 507 women . The 104-item Spinal Cord Injury Women Question naire , was design ed to assess different dimensions of sexuality . RESULTS 80 % of the women with spinal cord injury had engaged in sex after the injury . Reasons for not wanting or not having the courage to be intimate and sexual were physical problems , low sexual desire , low self-esteem and feelings of being unattractive . The motivations of both the women with spinal cord injury and controls to engage in sexual activity were intimacy-based rather than primarily sexual . Being in the right mood both before and during sex to become receptive to sexual stimulation was important . CONCLUSION For women who are able to overcome the physical restrictions and mental obstacles due to injury , it is possible to regain an active and positive sexual life together with a partner . Sexual information and counselling should be available both during initial rehabilitation and later when the women have returned to their homes" ]
"Several PROMs have been identified to evaluate sexual function in neurologic patients . Strong evidence was found only for the Multiple Sclerosis Intimacy and Sexuality Question naire-15 and Multiple Sclerosis Intimacy and Sexuality Question naire-19 for patients with MS , although evidence was lacking for certain measurement properties as well ."
"CONTEXT Impaired sexual function has a significant effect on quality of life . Various patient-reported outcome measures ( PROMs ) are available to evaluate sexual function . The quality of the PROMs to be used for neurologic patients remains unknown . OBJECTIVE To systematic ally review which vali date d PROMs are available to evaluate sexual function in neurologic patients and to critically assess the quality of the validation studies and measurement properties for each identified PROM ."
"24417824"
[ "2403851", "8936492", "2914336", "18331374", "15979768", "19363695", "10197653", "19399583", "19142085", "15681099", "10459075", "11682427", "15301325", "15739210", "14760661", "20205227", "12631049", "17902094" ]
[ "Large volumes of apple juice preoperatively do not affect gastric pH and volume in children", "The effect of preoperative carbohydrate loading on hormonal changes, hepatic glycogen, and glucoregulatory enzymes during abdominal surgery.", "The effect of preoperative apple juice on gastric contents, thirst, and hunger in children", "Pre‐operative carbohydrate loading may be used in type 2 diabetes patients", "Effect of \"preoperative\" oral carbohydrate treatment on insulin action--a randomised cross-over unblinded study in healthy subjects.", "Preoperative Fasting of 2 Hours Minimizes Insulin Resistance and Organic Response to Trauma After Video-Cholecystectomy: A Randomized, Controlled, Clinical Trial", "Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures.", "Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas", "Effect of preoperative intravenous carbohydrate loading on preoperative discomfort in elective surgery patients", "The administration of an oral carbohydrate-containing fluid prior to major elective upper-gastrointestinal surgery preserves skeletal muscle mass postoperatively--a randomised clinical trial.", "Preoperative oral carbohydrates and postoperative insulin resistance.", "A Carbohydrate-Rich Drink Reduces Preoperative Discomfort in Elective Surgery Patients", "Effect of an intensive glucose management protocol on the mortality of critically ill adult patients.", "Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy", "Randomized clinical trial comparing an oral carbohydrate beverage with placebo before laparoscopic cholecystectomy", "Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery", "Effects of preoperative oral carbohydrates and peptides on postoperative endocrine response, mobilization, nutrition and muscle function in abdominal surgery", "Randomized clinical trial of the effect of preoperative oral carbohydrate treatment on postoperative whole‐body protein and glucose kinetics" ]
"Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery , especially hunger , thirst , malaise , anxiety and nausea . No definite conclusions could be made regarding preservation of muscle mass . Following ingestion of carbohydrate drinks , no adverse events such as apparent or proven aspiration during or after surgery were reported . Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome ."
"INTRODUCTION Surgical stress in the presence of fasting worsens the catabolic state , causes insulin resistance and may delay recovery . Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects . A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance , gastric emptying , gastric acidity , patient wellbeing , immunity and nutrition following surgery ."
"28416626"
[ "23920426", "22153256", "24032706", "16018519", "25710659" ]
[ "Long-Term Outcome after Anticoagulation-Associated Intracerebral Haemorrhage with or without Restarting Antithrombotic Therapy", "Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: the Best Practice for Reinitiating Anticoagulation Therapy After Intracranial Bleeding (BRAIN) study.", "Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment.", "Risk Analysis of Thrombo-Embolic and Recurrent Bleeding Events in the Management Of Intracranial Haemorrhage Due to Oral Anticoagulation", "Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage." ]
[ "Background : For patients who survive intracerebral haemorrhage ( ICH ) during treatment with oral anticoagulation ( OAC ) , the balance between the benefits and risks of restarting OAC is unclear . The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved . We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH . Methods : We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period . Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through question naires and patient files . The primary outcome was recurrent fatal or non-fatal stroke . Secondary outcomes were the occurrence of other haemorrhagic , thrombotic or thromboembolic events . With patients without antithrombotic treatment as reference , we calculated incidence ratios with corresponding 95 % confidence intervals ( CI ) for treatment with OAC and for treatment with antiplatelet therapy . Results : We included 38 patients , of whom 21 ( 55 % ) died during a mean follow-up of 3.5 years . The medication regime changed frequently during follow-up , illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time . Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication , 7 during 63.8 patient-years on antiplatelet medication ( incidence ratio 1.9 ; 95 % CI , 0.4 - 9.4 ) , and 3 during 19.5 patient-years on OAC ( incidence ratio 2.7 ; 95 % CI , 0.5 - 16.3 ) . There was only 1 recurrent ICH , which occurred during treatment with OAC . Conclusion : In this observational study , no significant difference in the primary outcome measure was found between the treatment groups , but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy . However , based on these results it is difficult to draw any concrete conclusions or make any strong recommendations . A r and omized trial to assess the optimal long-term strategy after OAC-related ICH is warranted . Based on the point estimates of our study , such a trial should involve at least 300 patient-years of follow-up", "BACKGROUND While warfarin-related intracranial hemorrhage ( ICH ) occurs in 0.25%-1.1 % patients per year , little is known about the practice and outcomes of anticoagulant reinitiation . METHODS We studied a cohort of consecutive patients with warfarin-related ICH ( intracerebral or subarachnoid ) admitted to 13 stroke centres in the Registry of the Canadian Stroke Network between July 2003 and March 2008 . We examined patterns of warfarin reinitiation and variables associated with 30-day and 1-year outcomes . RESULTS Among the 284 patients studied ( mean age 74 ± 12 years ) , warfarin was restarted in-hospital in 91 patients ( 32 % ) . Factors associated with restarting warfarin were lower stroke severity ( adjusted odds ratio [ aOR ] 2.07 , 95 % confidence interval [ CI ] ; 1.20 - 3.57 , P = 0.009 ) or presence of valve prosthesis ( aOR 3.07 , 95 % CI ; 1.29 - 7.27 , P = 0.011 ) . Mortality rates were not higher in those who restarted warfarin in-hospital : 31.9 % vs 54.4 % ( 30-day , P < 0.001 ) and 48 % vs 61 % ( 1-year , P = 0.04 ) , and bleeding was not increased . Multivariable predictors of mortality included initial international normalized ratio > 3.0 ( aOR , 3.28 [ 30-day , P < 0.001 ] and 3.32 [ 1-year , P = 0.003 ] ) , greater stroke severity ( aOR , 6.04 [ 30-day ] and 4.22 [ 1-year ] ; both P < 0.001 ) , and intraventricular hemorrhage ( aOR , 2.19 [ 30-day ; P = 0.03 ] and 2.04 [ 1-year ; P = 0.04 ] ) . In selected patients who reinitiated warfarin , there was no increase in 30-day ( aOR , 0.49 ; P = 0.03 ) or 1-year mortality ( aOR , 0.79 ; P = 0.43 ) . CONCLUSIONS In selected patients at high thrombosis risk , reinitiation of warfarin after ICH did not confer increased mortality or bleeding events", "OBJECT Aneurysmal subarachnoid hemorrhage ( aSAH ) predisposes to delayed neurological deficits , including stroke and cognitive and neuropsychological abnormalities . Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH . METHODS The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus . Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion ( Maryl and low-dose intravenous heparin infusion protocol : 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr ) beginning 12 hours after surgery and continuing until Day 14 after the ictus . Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis . RESULTS Patients in the 2 groups were balanced in terms of baseline characteristics . In the heparin group , activated partial thromboplastin times were normal to mildly elevated ; no clinical ly significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered . In the control group , the incidence of clinical vasospasm requiring rescue therapy ( induced hypertension , selective intraarterial verapamil , and angioplasty ) was 20 ( 47 % ) of 43 patients , and 9 ( 21 % ) of 43 patients experienced a delayed infa rct on CT scanning . In the heparin group , the incidence of clinical vasospasm requiring rescue therapy was 9 % ( 4 of 43 , p = 0.0002 ) , and no patient suffered a delayed infa rct ( p = 0.003 ) . CONCLUSIONS In patients with Fisher Grade 3 aSAH whose aneurysm is secured , postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial", "Abstract Purpose s : Intracranial haemorrhage ( ICH ) is a rare but potentially devastating complication of oral anticoagulants ( OAC ) . This raises the difficult clinical choice between either permanent cessation of OAC , or continuing OAC and if so , when to restart . To make this choice , one needs to balance the thrombo-embolic risk after cessation of OAC against the risk of recurrent intracranial haemorrhage when OAC are restarted . There are few published data to base this difficult clinical decision on . Methods : We present an observational study of a consecutive series of 108 patients , collected prospect ively and admitted to our department , with an OAC-related intracranial haemorrhage , in whom we assessed the thrombotic event rate and the recurrent intracranial bleeding rate during follow-up . Results : In the 25 patients in whom OAC were reinstituted no new thrombo-embolic events occurred ( 0/506 unprotected patient-days ) . In the group of patients in whom OAC were not restarted ( n = 81 ) , the thrombo-embolic event rate was 8/11590 unprotected patient-days , of which only 2 were cerebrovascular thrombo-embolisms . The overall risk of a thrombo-embolic complication can be estimated to be 0.66 events/1000 patient-days at risk ( 95 % exact confidence limits of 0.3 to 1.3 events/1000 patient-days at risk ) . In three patients the thrombo-embolic event was fatal . We saw recurrent intracranial bleeding in eight patients , 2 of which were fatal . Seven of these occurred before the restarting of the OAC . Conclusions : In OAC-related intracranial haemorrhages , OAC can be stopped safely for a considerable period , with a very low overall thrombotic event rate . The recurrent bleeding risk after restarting OAC is low . Recurrent bleeding mostly occurred before restarting OAC and is probably caused by insufficient or unsustained correction of the initial coagulation deficit . Immediate reversal of anticoagulation provides the patient with the best possible treatment options including surgery . OAC-related intracranial haemorrhages can therefore be actively treated", "IMPORTANCE Although use of oral anticoagulants ( OACs ) is increasing , there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage ( ICH ) . OBJECTIVE To assess the association of anticoagulation reversal and blood pressure ( BP ) with hematoma enlargement and the effects of OAC resumption . DESIGN , SETTING , AND PARTICIPANTS Retrospective cohort study at 19 German tertiary care centers ( 2006 - 2012 ) including 1176 individuals for analysis of long-term functional outcome , 853 for analysis of hematoma enlargement , and 719 for analysis of OAC resumption . EXPOSURES Reversal of anticoagulation during acute phase , systolic BP at 4 hours , and reinitiation of OAC for long-term treatment . MAIN OUTCOMES AND MEASURES Frequency of hematoma enlargement in relation to international normalized ratio ( INR ) and BP . Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption . Factors associated with favorable ( modified Rankin Scale score , 0 - 3 ) vs unfavorable functional outcome . RESULTS Hemorrhage enlargement occurred in 307 of 853 patients ( 36.0 % ) . Reduced rates of hematoma enlargement were associated with reversal of INR levels < 1.3 within 4 hours after admission ( 43/217 [ 19.8 % ] ) vs INR of ≥1.3 ( 264/636 [ 41.5 % ] ; P < .001 ) and systolic BP < 160 mm Hg at 4 hours ( 167/504 [ 33.1 % ] ) vs ≥160 mm Hg ( 98/187 [ 52.4 % ] ; P < .001 ) . The combination of INR reversal < 1.3 within 4 hours and systolic BP of < 160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement ( 35/193 [ 18.1 % ] vs 220/498 [ 44.2 % ] not achieving these values ; OR , 0.28 ; 95 % CI , 0.19 - 0.42 ; P < .001 ) and lower rates of in-hospital mortality ( 26/193 [ 13.5 % ] vs 103/498 [ 20.7 % ] ; OR , 0.60 ; 95 % CI , 0.37 - 0.95 ; P = .03 ) . OAC was resumed in 172 of 719 survivors ( 23.9 % ) . OAC resumption showed fewer ischemic complications ( OAC : 9/172 [ 5.2 % ] vs no OAC : 82/547 [ 15.0 % ] ; P < .001 ) and not significantly different hemorrhagic complications ( OAC : 14/172 [ 8.1 % ] vs no OAC : 36/547 [ 6.6 % ] ; P = .48 ) . Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 ( 95 % CI , 0.125 - 0.534 ; P < .001 ) for long-term mortality . Functional long-term outcome was unfavorable in 786 of 1083 patients ( 72.6 % ) . CONCLUSIONS AND RELEVANCE Among patients with OAC-associated ICH , reversal of INR < 1.3 within 4 hours and systolic BP < 160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement , and resumption of OAC therapy was associated with lower risk of ischemic events . These findings require replication and assessment in prospect i ve studies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01829581" ]
"Conclusions — In observational studies , reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence ."
"Background and Purpose — The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage ( ICH ) remain unclear . We performed a systematic review and meta- analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism ."
"25767129"
[ "23422399", "19243716", "20048210", "16908788", "22323747", "16908789", "23024246", "25006684", "22890119", "22048460", "23536105", "3438402", "2997603", "3281242", "23916324", "24030388", "21635992", "22697191", "21810630", "16820548", "21504885", "4151018", "23072834", "23953658", "3805476", "17407636", "19192221", "23728065", "20716302", "17692720", "18513462", "21835552", "20864613", "17692719", "21295286", "10800427", "22573730", "10873129", "24042367", "24399553", "21652735", "20466870" ]
[ "Varenicline Treatment of Concurrent Alcohol and Nicotine Dependence in Schizophrenia: A Randomized, Placebo-Controlled Pilot Trial", "Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent smokers: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study.", "Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease: A Randomized Trial", "Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.", "A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3", "Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation.", "Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial.", "Varenicline for smoking cessation in bipolar disorder: a randomized, double-blind, placebo-controlled study.", "A Perioperative Smoking Cessation Intervention with Varenicline: A Double-blind, Randomized, Placebo-controlled Trial", "Adjunctive Varenicline Treatment with Antipsychotic Medications for Cognitive Impairments in People with Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial", "Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal.", "Varenicline decreases alcohol consumption in heavy-drinking smokers", "Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial", "A Randomized Placebo-Controlled Trial of Varenicline for Smoking Cessation Allowing Flexible Quit Dates", "Results from a pilot clinical trial of varenicline for the treatment of alcohol dependence.", "Varenicline, smoking cessation, and neuropsychiatric adverse events.", "Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study.", "A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder.", "Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder.", "Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial.", "A pilot study of the efficacy of varenicline for the treatment of smokeless tobacco users in Midwestern United States.", "Retreatment With Varenicline for Smoking Cessation in Smokers Who Have Previously Taken Varenicline: A Randomized, Placebo-Controlled Trial", "Effects of Short-Term Varenicline Administration on Emotional and Cognitive Processing in Healthy, Non-Smoking Adults: A Randomized, Double-Blind, Study", "Varenicline for smoking cessation among methadone-maintained smokers: a randomized clinical trial.", "Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study", "Comment and Reply: A double-blind study evaluating the long-term safety of varenicline for smoking cessation", "Varenicline for smoking cessation: a placebo-controlled, randomized study.", "A Double-Blind, Placebo-Controlled Trial Assessing the Efficacy of Varenicline Tartrate for Alcohol Dependence", "The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study.", "Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers.", "The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial.", "Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline.", "Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial.", "A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.", "A Double-Blind Randomized Placebo-Controlled Pilot Study of Neuropsychiatric Adverse Events in Abstinent Smokers Treated with Varenicline or Placebo", "Cigarettes and suicide: a prospective study of 50,000 men.", "Effects of varenicline on abstinence and smoking reward following a programmed lapse.", "Cigarette smoking and suicide: a prospective study of 300,000 male active-duty Army soldiers.", "Effects of Varenicline on Smoking Cessation in Adults With Stably Treated Current or Past Major Depression", "Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial.", "Efficacy of varenicline to prompt quit attempts in smokers not currently trying to quit: a randomized placebo-controlled trial.", "Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers." ]
"This meta- analysis found no evidence of an increased risk of suicide or attempted suicide , suicidal ideation , depression , or death with varenicline . These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline . There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams ."
"OBJECTIVE To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in r and omised controlled trials ."
"26949760"
[ "21198773", "22392163", "17695870", "17580452", "15705433", "19744264", "23476914", "22574689", "18792702", "20691334", "18006051", "21519566", "19523678", "17695869", "16594356", "24264638", "20095200", "22383203", "21667056", "18548960", "25010879", "22141229", "15732546", "23342329", "19058686", "19477570" ]
[ "Five-year clinical evaluation of In-Ceram crowns fabricated using GN-I (CAD/CAM) system.", "Clinical results of lithium-disilicate crowns after up to 9 years of service", "An up to 16-year prospective study of 304 porcelain veneers.", "Clinical evaluation of Procera AllCeram crowns in the anterior and posterior regions.", "Clinical performance of bonded leucite-reinforced glass ceramic inlays and onlays after eight years.", "Clinical evaluation of Procera AllCeram crowns in Japanese patients: results after 5 years.", "Survival rates of a lithium disilicate-based core ceramic for three-unit esthetic fixed partial dentures: a 10-year prospective study.", "Clinical performance of long-span zirconia frameworks for fixed dental prostheses: 5-year results.", "Totally bonded ceramic inlays and onlays after eight years.", "A prospective 15-year evaluation of extensive dentin-enamel-bonded pressed ceramic coverages.", "Midterm results of a 5-year prospective clinical investigation of extended ceramic veneers.", "Six-year clinical performance of lithium disilicate fixed partial dentures.", "Clinical outcome of three-unit lithium-disilicate glass-ceramic fixed dental prostheses: up to 8 years results.", "Five-year clinical results of zirconia frameworks for posterior fixed partial dentures.", "Survival rates of IPS empress 2 all-ceramic crowns and fixed partial dentures: results of a 5-year prospective clinical study.", "Long-term performance of posterior InCeram Alumina crowns cemented with different luting agents: a prospective, randomized clinical split-mouth study over 5 years", "Clinical evaluation of all-ceramic posterior three-unit FDPs made of In-Ceram Zirconia.", "Ten-year outcome of three-unit fixed dental prostheses made from monolithic lithium disilicate ceramic.", "Five-year prospective clinical study of posterior three-unit zirconia-based fixed dental prostheses", "Five-year clinical prospective evaluation of zirconia-based Denzir 3-unit FPDs.", "Prospective clinical study of press-ceramic overlap and full veneer restorations: 7-year results.", "10-year clinical outcomes of fixed dental prostheses with zirconia frameworks.", "Five-year follow-up with Procera all-ceramic crowns.", "Prospective clinical split-mouth study of pressed and CAD/CAM all-ceramic partial-coverage restorations: 7-year results.", "Leucite-reinforced glass ceramic inlays and onlays after 12 years.", "All-ceramic partial coverage restorations--midterm results of a 5-year prospective clinical splitmouth study." ]
"Overall , the 5-year complication rates were low . The most frequent complications were secondary caries , endodontic problems , ceramic fractures , ceramic chipping , and loss of retention . CONCLUSION This systematic review showed that all-ceramic restorations fabricated using the correct clinical protocol have an adequate clinical survival for at least 5 years of clinical service with very low complication rates . Minor ceramic chipping and debonding did not affect the longevity of the restorations . CLINICAL RELEVANCE Long-term clinical performance of all-ceramic restorations manufactured using various ceramic systems provides clinical evidence of complications and long-term management of these restorations . Available evidence indicates the effectiveness of many ceramic systems for numerous clinical applications . Correct planning and a rigorous technical execution protocol increase clinical success . Studies of ceramic prostheses indicate more problems with ceramic failure and debonding"
"OBJECTIVE The purpose of this systematic review was to compare the survival and complication rates of all-ceramic restorations after a minimum follow-up time of 5 years ."
"21474812"
[ "11739989", "16549855", "8505635", "11830217", "17446421", "16931787", "12750536", "1527534", "10657421", "3174926", "8869395", "17761925", "18434640", "1636182", "18556582", "12140674", "1987664", "17642023", "18195138", "10408548", "17766429", "17060137", "7872877", "8831472", "18602106", "16568808", "7733845", "15258232", "9779680", "14981174", "20555154" ]
[ "A New Method for Predicting Recovery After Stroke", "Evaluation of the Quality of Prognosis Studies in Systematic Reviews", "Selection of acute stroke patients for treatment of visual neglect.", "Cohort studies: marching towards outcomes", "Validation of an Acute Ischemic Stroke Model: Does Diffusion-Weighted Imaging Lesion Volume Offer a Clinically Significant Improvement in Prediction of Outcome?", "Impact of Time on Improvement of Outcome After Stroke", "Poor nutritional status on admission predicts poor outcomes after stroke: observational data from the FOOD trial.", "Prognostic factors in patients with intracerebral haematoma.", "A predictive risk model for outcomes of ischemic stroke.", "Prognostic indices in stroke.", "A study of prognostic predictors of supratentorial haematomas", "The Increase of Circulating Endothelial Progenitor Cells After Acute Ischemic Stroke Is Associated With Good Outcome", "Baseline NIH Stroke Scale Score predicting outcome in anterior and posterior circulation strokes", "Measurement of Motor Recovery After Stroke: Outcome Assessment and Sample Size Requirements", "Prediction of Functional Outcome in Patients With Primary Intracerebral Hemorrhage: The FUNC Score", "Predicting functional outcome and survival after acute ischemic stroke", "Death and functional outcome after spontaneous intracerebral hemorrhage. A prospective study of 166 cases using multivariate analysis.", "Depressive symptoms and independence in BADL and IADL.", "Undernutrition as a predictor of poor clinical outcomes in acute ischemic stroke patients.", "Baseline NIH Stroke Scale score strongly predicts outcome after stroke", "Predicting outcome in hyper-acute stroke: validation of a prognostic model in the Third International Stroke Trial (IST3)", "Early prediction of functional outcome after stroke", "Prediction of long-term outcome in the early hours following acute ischemic stroke. Italian Acute Stroke Study Group.", "Prestroke physical function predicts stroke outcomes in the elderly.", "Prediction of long-term functional outcome in patients with acute ischemic non-embolic stroke.", "Variables Explaining Functional Recovery Following Motor Stroke", "Prediction of functional outcome and tissue loss in acute cortical infarction.", "Is the common carotid artery intima–media thickness associated with functional outcome after acute ischaemic stroke?", "Ischemic stroke: relation of age, lesion location, and initial neurologic deficit to functional outcome.", "Predicting outcome after acute ischemic stroke", "Early detection of non-ambulatory survivors six months after stroke." ]
"Because of insufficient method ological quality of most prognostic studies , the predictive value of many clinical determinants for outcome of ADL remains unclear ."
"BACKGROUND AND PURPOSE Knowledge about robust and unbiased factors that predict outcome of activities of daily living ( ADL ) is paramount in stroke management . This review investigates the method ological quality of prognostic studies in the early poststroke phase for final ADL to identify variables that are predictive or not predictive for outcome of ADL after stroke ."
"25299481"
[ "18564350", "17361851", "20214120", "3011370", "12376442", "2763005", "23166195", "16735334", "2811172", "19496420", "18291003", "11127233", "2519687", "12749496", "7548945" ]
[ "Vector control by insecticide-treated nets in the fight against visceral leishmaniasis in the Indian subcontinent, what is the evidence?", "A multifaceted intervention to prevent American cutaneous leishmaniasis in Colombia: results of a group-randomized trial.", "Efficacy of Olyset long-lasting bednets to control transmission of cutaneous leishmaniasis in Iran.", "Longlasting insecticidal nets for prevention of Leishmania donovani infection in India and Nepal: paired cluster randomised trial", "Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial", "Chemical and environmental vector control as a contribution to the elimination of visceral leishmaniasis on the Indian subcontinent: cluster randomized controlled trials in Bangladesh, India and Nepal", "A cluster-randomized trial of insecticide-treated curtains for dengue vector control in Thailand.", "Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trials", "Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial", "Importance of Eaves to House Entry by Anopheline, But Not Culicine, Mosquitoes", "Insecticide-treated bednets to control dengue vectors: preliminary evidence from a controlled trial in Haiti.", "A randomized controlled trial of insecticide-treated bednets and chaddars or top sheets, and residual spraying of interior rooms for the prevention of cutaneous leishmaniasis in Kabul, Afghanistan.", "Permethrin-impregnated bednets reduce nuisance arthropods in Gambian houses.", "Community reactions to the introduction of permethrin-treated bed nets for malaria control during a randomized controlled trial in western Kenya.", "Evaluation of deltamethrin-impregnated bednets and curtains against phlebotomine sandflies in Valle del Cauca, Colombia." ]
"There are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria . Nonetheless , it is clear that insecticide-treated material s such as ITNs have the potential to reduce pathogen transmission and morbidity from VBDs where vectors enter houses"
"INTRODUCTION Insecticide-treated nets ( ITNs ) are one of the main interventions used for malaria control . However , these nets may also be effective against other vector borne diseases ( VBDs ) . We conducted a systematic review and meta- analysis to estimate the efficacy of ITNs , insecticide-treated curtains ( ITCs ) and insecticide-treated house screening ( ITS ) against Chagas disease , cutaneous and visceral leishmaniasis , dengue , human African trypanosomiasis , Japanese encephalitis , lymphatic filariasis and onchocerciasis ."
"25506813"
[ "521079", "3995264", "21768318", "22428572", "20720454", "2315072", "9775842", "21999476", "17767120", "16952598", "1865372", "9811284", "12019051", "10578803", "17273373", "8826172", "12903698", "9017547", "12449049", "7488804", "11800243", "8176527", "10578788", "16127520", "15953322", "9511686", "11903211", "16216739" ]
[ "A failed RCT to determine if antibiotics prevent mastitis: Cracked nipples colonized with Staphylococcus aureus: A randomized treatment trial [ISRCTN65289389]", "Randomised controlled trial of early frenotomy in breastfed infants with mild–moderate tongue-tie", "Efficacy of Neonatal Release of Ankyloglossia: A Randomized Trial", "An all-purpose nipple ointment versus lanolin in treating painful damaged nipples in breastfeeding women: a randomized controlled trial.", "Positive Effect of HPA Lanolin versus Expressed Breastmilk on Painful and Damaged Nipples during Lactation", "Breast‐Feeding Problems In the First Week Postpartum", "Risk Factors for Lactation Mastitis", "A double-blind, randomized, controlled trial of tongue-tie division and its immediate effect on breastfeeding.", "A randomized trial of peppermint gel, lanolin ointment, and placebo gel to prevent nipple crack in primiparous breastfeeding women.", "Immediate nipple pain relief after frenotomy in breast-fed infants with ankyloglossia: a randomized, prospective study.", "Effect of peppermint water on prevention of nipple cracks in lactating primiparous women: a randomized controlled trial", "Sore nipples in breast-feeding women: a clinical trial of wound dressings vs conventional care.", "Factors associated with weaning in the first 3 months postpartum.", "The Treatment of Staphyloccocus Aureus Infected Sore Nipples: A Randomized Comparative Study", "Pain reduction and treatment of sore nipples in nursing mothers.", "A comparison of topical agents to relieve nipple pain and enhance breastfeeding.", "Comparing the use of hydrogel dressings to lanolin ointment with lactating mothers.", "Does application of tea bags to sore nipples while breastfeeding provide effective relief?", "Factors Influencing Continuation of Breastfeeding in a Cohort of Women", "Effect of the method of breast feeding on breast engorgement, mastitis and infantile colic", "The effect of peer support on breast-feeding duration among primiparous women: a randomized controlled trial.", "Comfort measures in breastfeeding, primiparous women.", "Nipple Care, Sore Nipples, and Breastfeeding: A Randomized Trial", "The effect of breast milk and lanolin on sore nipples.", "Randomized, controlled trial of division of tongue-tie in infants with feeding problems.", "Positive effects of an antenatal group teaching session on postnatal nipple pain, nipple trauma and breast feeding rates.", "Postpartum positioning and attachment education for increasing breastfeeding: a randomized trial.", "Management of lactational breast abscesses." ]
"We did not pool data for other outcomes due to either heterogeneity in outcome measures or differing interventions .There was no evidence that glycerine gel dressings or breast shells with lanolin significantly improved nipple pain . However , this beneficial effect was not maintained after six to seven days of treatment . There were no group differences in nipple pain perceptions at any assessment between women who applied expressed breast milk and women who applied nothing . Women who applied an " all- purpose nipple ointment " , in comparison to women who applied lanolin , had no improvement in nipple pain after seven days of treatment . There was insufficient evidence that glycerine gel dressings , lanolin with breast shells , lanolin alone , expressed breast milk , or all- purpose nipple ointment improved maternal perceptions of nipple pain . Overall , there was insufficient evidence to recommend any intervention for the treatment of nipple pain . However , one important finding was that regardless of the treatment used , for most women nipple pain reduced to mild levels after approximately seven to 10 days ' postpartum . The provision of anticipatory guidance regarding usual time to pain reduction may be a useful strategy in assisting women to continue to breastfeed and to do so exclusively . There was insufficient evidence that glycerine gel dressings , breast shells with lanolin , lanolin alone , or the all- purpose nipple ointment significantly improved maternal perceptions of nipple pain . The results from these four trials of good method ological quality suggested that applying nothing or just expressed breast milk may be equally or more beneficial in the short-term experience of nipple pain than the application of an ointment such as lanolin ."
"BACKGROUND Leading health authorities all recommend exclusive breastfeeding to six months ' postpartum . While most women initiate breastfeeding , many discontinue due to difficulties encountered rather than maternal choice . One common breastfeeding difficulty is painful nipples . Research has identified poor infant positioning or latch as a common cause of painful nipples . While many different interventions design ed to reduce nipple pain in breastfeeding women have been evaluated , it is unclear which intervention is the most effective treatment . An underst and ing of nipple pain and treatment options are needed to improve breastfeeding duration and exclusivity rates and to address systematic ally one of the most frequent difficulties encountered by breastfeeding women . OBJECTIVES To assess the effects of all interventions in the resolution or reduction of nipple pain and the impact of the interventions on other outcomes such as nipple trauma , nipple infections , breast mastitis , breastfeeding duration , breastfeeding exclusivity , and maternal satisfaction . Nipple pain in women who are feeding with expressed breast milk ( i.e. women of infants in neonatal units ) is associated with other methods of removing milk from the mother 's breast such as manual expression and various types of breast pumps . Nipple pain and subsequent treatment is different in this unique maternal population and thus we excluded women solely feeding with expressed breast milk from this review ."
"25947646"
[ "23958375", "22276821", "23932548", "10086815", "21569994", "21707383", "22565005", "22276820" ]
[ "Randomized phase II study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer.", "Bevacizumab added to neoadjuvant chemotherapy for breast cancer.", "Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial.", "The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus.", "Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial.", "Reputation and precedent in the bevacizumab decision.", "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial.", "Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer." ]
"VEGF-A level is a reasonable c and i date biomarker for bevacizumab in the treatment of breast cancer ."
"Abstract Bevacizumab may improve outcomes of patients with breast cancer , but the absence of an established biomarker hampers patient selection and research ers ´ ability to demonstrate a clear survival benefit . Its putative target , circulating VEGF-A , emerged as the main c and i date and we sought to identify the relationship between VEGF-A levels and outcomes through systematic review ."
"24895945"
[ "8155437", "3394771", "8606715", "3964515", "12505947", "7726398", "21157359", "19380337", "15942580", "1642946", "17923980", "10442959", "21967909", "7946366", "7917732", "10479837", "7877221", "11567703", "8499506", "9014635", "9278836", "9496210", "12538121", "8251019", "9416715", "16810141", "3630598", "7191674", "23404220" ]
[ "Pre-emptive use of the space blanket reduces shivering after general anaesthesia.", "Methods of Patient Warming during Abdominal Surgery", "Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group.", "Effect of heat conservation during and after major abdominal surgery on muscle protein breakdown in elderly patients.", "A comparative study of three warming interventions to determine the most effective in maintaining perioperative normothermia.", "Mild Hypothermia Alters Propofol Pharmacokinetics and Increases the Duration of Action of Atracurium", "Thermal suits as an alternative way to keep patients warm peri-operatively: a randomised trial", "A randomised controlled trial comparing Mediwrap heat retention and forced air warming for maintaining normothermia in thoracic surgery.", "Thermo-wrap technology preserves normothermia better than routine thermal care in patients undergoing off-pump coronary artery bypass and is associated with lower immune response and lesser myocardial damage.", "Reflective blankets used for reduction of heat loss during regional anaesthesia.", "Hypothermia control in elderly surgical patients in the intraoperative period: evaluation of two nursing interventions.", "Covering the head and face maintains intraoperative core temperature", "The effectiveness and cost of passive warming in adult ambulatory surgery patients.", "Bair hugger forced-air warming maintains normothermia more effectively than thermo-lite insulation.", "Prevention of hypothermia during hip surgery: effect of passive compared with active skin surface warming.", "Shortening the discharging time after total hip replacement under combined spinal/epidural anesthesia by actively warming the patient during surgery.", "Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity.", "Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial", "Comparison of the effect of insulated and noninsulated head covers on heat loss during abdominal surgery.", "Use of a pneumatic tourniquet induces changes in central temperature.", "Active warming, not passive heat retention, maintains normothermia during combined epidural-general anesthesia for hip and knee arthroplasty.", "Heat retention using passive systems during anaesthesia: comparison of two plastic wraps, one with reflective properties.", "A new thermoregulation system for maintaining perioperative normothermia and attenuating myocardial injury in off-pump coronary artery bypass surgery.", "Prevention of Intraoperative Hypothermia by Preoperative Skin-Surface Warming", "Mild Intraoperative Hypothermia Prolongs Postanesthetic Recovery", "Evaluating a new method for maintaining body temperature during OPCAB and robotic procedures.", "Peroperative hypothermia prevention", "Operating Room Temperature Prior to Surgical Draping: Effect on Patient Temperature in Recovery Room", "[Efficacy of a novel warming blanket: prospective randomized trial]." ]
"There were no clear effects on bleeding , shivering or length of stay in post-anaesthetic care for either comparison . No other adverse effects were reported . There is no clear benefit of extra thermal insulation compared with st and ard care . Forced air warming does seem to maintain core temperature better than extra thermal insulation , by between 0.5 ºC and 1 ºC , but the clinical importance of this difference is unclear"
"BACKGROUND Inadvertent perioperative hypothermia occurs because of interference with normal temperature regulation by anaesthetic drugs and exposure of skin for prolonged periods . A number of different interventions have been proposed to maintain body temperature by reducing heat loss . Thermal insulation , such as extra layers of insulating material or reflective blankets , should reduce heat loss through convection and radiation and potentially help avoid hypothermia . OBJECTIVES To assess the effects of pre- or intraoperative thermal insulation , or both , in preventing perioperative hypothermia and its complications during surgery in adults ."
"22513917"
[ "23956241" ]
[ "Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial." ]
[ "BACKGROUND To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy ( WBRT ) . METHODS Adult patients with brain metastases received WBRT and were r and omized to receive placebo or memantine ( 20 mg/d ) , within 3 days of initiating radiotherapy for 24 weeks . Serial st and ardized tests of cognitive function were performed . RESULTS Of 554 patients who were accrued , 508 were eligible . Grade 3 or 4 toxicities and study compliance were similar in the 2 arms . There was less decline in delayed recall in the memantine arm at 24 weeks ( P = .059 ) , but the difference was not statistically significant , possibly because there were only 149 analyzable patients at 24 weeks , result ing in only 35 % statistical power . The memantine arm had significantly longer time to cognitive decline ( hazard ratio 0.78 , 95 % confidence interval 0.62 - 0.99 , P = .01 ) ; the probability of cognitive function failure at 24 weeks was 53.8 % in the memantine arm and 64.9 % in the placebo arm . Superior results were seen in the memantine arm for executive function at 8 ( P = .008 ) and 16 weeks ( P = .0041 ) and for processing speed ( P = .0137 ) and delayed recognition ( P = .0149 ) at 24 weeks . CONCLUSIONS Memantine was well tolerated and had a toxicity profile very similar to placebo . Although there was less decline in the primary endpoint of delayed recall at 24 weeks , this lacked statistical significance possibly due to significant patient loss . Overall , patients treated with memantine had better cognitive function over time ; specifically , memantine delayed time to cognitive decline and reduced the rate of decline in memory , executive function , and processing speed in patients receiving WBRT . RTOG 0614 , Clinical Trials.gov number CT00566852" ]
"None of the RCTs with altered WBRT dose-fractionation schemes as compared to st and ard ( 3000 cGy in 10 daily fractions or 2000 cGy in 4 or 5 daily fractions ) found a benefit in terms of overall survival , neurologic function , or symptom control . Radiosurgery boost with WBRT may improve local disease control in selected participants as compared to WBRT alone , although survival remains unchanged for participants with multiple brain metastases . The addition of WBRT to radiosurgery improves local and distant brain control but there is no difference in overall survival . It may be that supportive care alone , without WBRT , is appropriate for some participants , particularly those with advanced disease and poor performance status"
"BACKGROUND Brain metastases represent a significant healthcare problem . It is estimated that 20 % to 40 % of patients with cancer will develop metastatic cancer to the brain during the course of their illness . The burden of brain metastases impacts on quality and length of survival . Presenting symptoms include headache ( 49 % ) , focal weakness ( 30 % ) , mental disturbances ( 32 % ) , gait ataxia ( 21 % ) , seizures ( 18 % ) , speech difficulty ( 12 % ) , visual disturbance ( 6 % ) , sensory disturbance ( 6 % ) and limb ataxia (6%).Brain metastases may spread from any primary site . The most common primary site is the lung , followed by the breast then gastrointestinal sites . Eighty-five per cent of brain metastases are found in the cerebral hemispheres , 10 % to 15 % in the cerebellum and 1 % to 3 % in the brainstem . Brain radiotherapy is used to treat cancer participants who have brain metastases from various primary malignancies . This is an up date to the original review published in Issue 3 , 2006 . OBJECTIVES To assess the effectiveness and adverse effects of whole brain radiotherapy ( WBRT ) in adult participants with multiple metastases to the brain ."
"26901389"
[ "17574858", "12883404", "22222469", "16884976", "12883398", "11899189", "15277911", "12131102", "17156509", "16797430", "15513312", "20573633", "2291320", "20580572", "19233758", "19686479", "15728039", "3987406", "24643920", "1560125", "12766638", "15179345", "16931656", "25686857", "22103571", "19953916", "25440807", "14508313", "21291422", "19726290", "22965457", "17905272", "21466991", "15144293", "21675061", "22379906", "21544683", "19464461", "15232804", "23886454", "17905274", "17905275", "15220766", "20656748", "23302012", "23287079", "16507192", "21872490", "4589874", "18627368", "19105250", "10514958", "20865880", "16884979", "17707752", "17913754", "22415082", "17894911", "16861404", "18662628" ]
[ "Desflurane preconditioning in coronary artery bypass graft surgery: a double-blinded, randomised and placebo-controlled study.", "Effects of Propofol, Desflurane, and Sevoflurane on Recovery of Myocardial Function after Coronary Surgery in Elderly High-risk Patients", "Remote Ischemic Preconditioning Applied during Isoflurane Inhalation Provides No Benefit to the Myocardium of Patients Undergoing On-pump Coronary Artery Bypass Graft Surgery: Lack of Synergy or Evidence of Antagonism in Cardioprotection?", "Myocardial damage prevented by volatile anesthetics: a multicenter randomized controlled study.", "Short- and Long-term Prognostic Value of Postoperative Cardiac Troponin I Concentration in Patients Undergoing Coronary Artery Bypass Grafting", "Is there a place for preconditioning during cardiac operations in humans?", "Cardioprotective Properties of Sevoflurane in Patients Undergoing Coronary Surgery with Cardiopulmonary Bypass Are Related to the Modalities of Its Administration", "Sevoflurane but Not Propofol Preserves Myocardial Function in Coronary Surgery Patients", "Cardiac protection by volatile anaesthetics: a multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass", "Early increases in cardiac troponin levels after major vascular surgery is associated with an increased frequency of delayed cardiac complications.", "Isoflurane produces only minor preconditioning in coronary artery bypass grafting", "Influence of propofol-opioid vs isoflurane-opioid anaesthesia on postoperative troponin release in patients undergoing coronary artery bypass grafting.", "Is general anesthesia a risk for myocardium? Effect of anesthesia on myocardial function as assessed by cardiac troponin-i in two different groups (isofluran+N2O inhalation and propofol+fentanyl iv anesthesia)", "Myocardial protection with isoflurane during off-pump coronary artery bypass grafting: a randomized trial.", "Cardioprotective effects of sevoflurane, isoflurane, and propofol in coronary surgery patients: a randomized controlled study.", "A comparison of volatile and non volatile agents for cardioprotection during on‐pump coronary surgery", "Sevoflurane but Not Propofol Preserves Myocardial Function During Minimally Invasive Direct Coronary Artery Bypass Surgery", "A Comparative Study of Cardioprotective Effect of Three Anesthetic Agents by Measuring Serum Level of Troponin-T after Coronary Artery Bypass Grafting", "Comparison of haemodynamics and myocardial injury markers under desflurane vs. propofol anaesthesia for off-pump coronary surgery. A prospective randomised trial.", "Intermediate and high peri-operative cardiac enzyme release following isolated coronary artery bypass surgery are independently associated with higher one-year mortality", "Preconditioning by Sevoflurane Decreases Biochemical Markers for Myocardial and Renal Dysfunction in Coronary Artery Bypass Graft Surgery: A Double-blinded, Placebo-controlled, Multicenter Study", "Preoperative shift from glibenclamide to insulin is cardioprotective in diabetic patients undergoing coronary artery bypass surgery.", "Large-Dose Propofol During Cardiopulmonary Bypass Decreases Biochemical Markers of Myocardial Injury in Coronary Surgery Patients: A Comparison with Isoflurane", "Effects of sevoflurane vs. propofol on mitochondrial functional activity after ischemia-reperfusion injury and the influence on clinical parameters in patients undergoing CABG surgery with cardiopulmonary bypass", "Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study", "[Effect of long-term sevoflurane anesthesia on markers of myocardial damage].", "Sevoflurane in acute myocardial infarction: a pilot randomized study.", "Sevoflurane Provides Greater Protection of the Myocardium than Propofol in Patients Undergoing Off-pump Coronary Artery Bypass Surgery", "Synergy of isoflurane preconditioning and propofol postconditioning reduces myocardial reperfusion injury in patients.", "[Remifentanil preconditioning lowers cardiac troponin I levels in patients undergoing off-pump coronary artery bypass graft surgery].", "Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study", "Desflurane versus propofol in patients undergoing mitral valve surgery.", "Comparison of the effects of sevoflurane and isoflurane on myocardial protection in coronary bypass surgery.", "A prospective, randomised, single‐blind pilot study to determine the effect of anaesthetic technique on troponin T release after off‐pump coronary artery surgery", "Myocardial Injury in Remifentanil-Based Anaesthesia for off-Pump Coronary Artery Bypass Surgery: An Equipotent Dose of Sevoflurane versus Propofol", "[Cardioprotective properties of sevoflurane in coronary bypass surgery with extracorporeal circulation].", "Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation?", "Impact of preconditioning protocol on anesthetic-induced cardioprotection in patients having coronary artery bypass surgery.", "Anesthetic myocardial protection with sevoflurane.", "Prolonged sevoflurane administration in the off-pump coronary artery bypass graft surgery: beneficial effects.", "Isoflurane, 0.5 minimum alveolar concentration administered through the precardiopulmonary bypass period, reduces postoperative dobutamine requirements of cardiac surgery patients: a randomized study.", "Sevoflurane provides earlier tracheal extubation and assessment of cognitive recovery than isoflurane in patients undergoing off-pump coronary artery bypass surgery.", "Choice of Primary Anesthetic Regimen Can Influence Intensive Care Unit Length of Stay after Coronary Surgery with Cardiopulmonary Bypass", "Cardiac Protection During On-Pump Coronary Artery Bypass Grafting: Ischemic Versus Isoflurane Preconditioning", "Sevoflurane at 1 MAC provides optimal myocardial protection during off-pump CABG", "Myocardial protection during off pump coronary artery bypass surgery: a comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia.", "Isoflurane preconditioning‐induced cardio‐protection in patients undergoing coronary artery bypass grafting", "Volatile agents for cardiac protection in noncardiac surgery: a randomized controlled study.", "Statistics: the problem of examining accumulating data more than once.", "The effects of interrupted or continuous administration of sevoflurane on preconditioning before cardio‐pulmonary bypass in coronary artery surgery: comparison with continuous propofol", "[Method of pharmacological myocardial preconditioning with halogen-containing anesthetics in cardiosurgical patients].", "Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.", "The Effect of Remote Ischaemic Preconditioning on Myocardial Injury in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery", "Effects of sevoflurane on cytokine balance in patients undergoing coronary artery bypass graft surgery.", "Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial", "Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial.", "Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass", "Myocardial protection by isoflurane vs. sevoflurane in ultra‐fast‐track anaesthesia for off‐pump aortocoronary bypass grafting", "Cardioprotective Properties of Sevoflurane in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass", "Cardiac protection with volatile anesthetics in stenting procedures." ]
"This is not yet the case for off-pump surgery"
"BACKGROUND Reports from animal studies indicate that volatile anaesthetics protect the myocardium against the effects of acute ischaemia – reperfusion injury by reducing infa rct size . This cardioprotective effect in the clinical setting of coronary artery bypass graft ( CABG ) surgery , where the heart is subjected to global ischaemia – reperfusion injury , remains controversial . OBJECTIVE The objective was to demonstrate that clinical studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in CABG are no longer warranted . We also investigated the effect of volatile anaesthetics on cardiac enzymes in off-pump cardiac surgery ."
"31688792"
[ "25620436", "24022324", "25716128", "20510295", "26686309", "3196245", "26658126", "3885801", "26000508", "26850200", "18261965", "27050402", "18004632", "11775562", "23271087", "28918992", "18005758", "26350667", "23958275", "29404935", "30713119", "25223871" ]
[ "The EFFORT trial: Preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial.", "Incidence of Venous Thromboembolism After Bariatric Surgery: A Population-Based Cohort Study", "Use of Enoxaparin in Obese Adolescents During Bariatric Surgery—a Pilot Study", "Extended thromboprophylaxis reduces incidence of postoperative venous thromboembolism in laparoscopic bariatric surgery.", "Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study.", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "A randomized controlled trial of differing doses of postcesarean enoxaparin thromboprophylaxis in obese women", "Prophylaxis of Venous Thromboembolism with Low Molecular Weight Heparin in Bariatric Surgery: a Prospective, Randomised Pilot Study Evaluating Two Doses of Parnaparin (BAFLUX Study)", "Enoxaparin Dosing After Cesarean Delivery in Morbidly Obese Women", "Non-weight-based enoxaparin dosing subtherapeutic in trauma patients.", "Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity.", "Retrospective analysis of 3 different antithrombotic prophylaxis regimens in bariatric surgery.", "Prophylaxis of Thromboembolism in Bariatric Surgery with Parnaparin", "Prophylaxis of Venous Thromboembolism Using Two Different Doses of Low-Molecular-Weight Heparin (Nadroparin) in Bariatric Surgery: A Prospective Randomized Trial", "Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients", "Anti-factor Xa levels in patients undergoing laparoscopic sleeve gastrectomy: 2 different dosing regimens of enoxaparin.", "Best Poster Award. A comparison of thromboembolic and bleeding events following laparoscopic gastric bypass in patients treated with prophylactic regimens of unfractionated heparin or enoxaparin.", "Standard Dosing of Enoxaparin for Venous Thromboembolism Prophylaxis is Not Sufficient for Most Patients within a Trauma Intensive Care Unit", "Peak plasma anti-Xa levels after first and third doses of enoxaparin in women receiving weight-based thromboprophylaxis following caesarean section: a prospective cohort study.", "The Effect of Obesity on Anti-Xa Concentrations in Bariatric Patients", "Anticoagulant activity of enoxaparin and unfractionated heparin for venous thromboembolism prophylaxis in obese patients undergoing sleeve gastrectomy.", "Fixed-Dose Enoxaparin After Bariatric Surgery: The Influence of Body Weight on Peak Anti-Xa Levels" ]
"Weight-based and high fixed-dose chemoprophylaxis regimens achieved target anti-Xa concentrations more frequently than st and ard fixed-dose regimens but were not associated with a reduction in VTE . Additionally , high fixed-dose approaches are associated with increased bleeding complications ."
"BACKGROUND Venous thromboembolism ( VTE ) continues to be a devastating source of morbidity and mortality in obese patients who suffer traumatic injuries or obese surgery patients . High incidence rates in VTE despite adherence to prevention protocol s have stirred interest in new dosing regimens . The purpose of this study was to systematic ally review the literature and present the existing VTE chemoprophylaxis regimens for obese trauma and surgical patients in terms of efficacy and safety as measured by the incidence of VTE , anti-factor Xa levels , and the occurrence of bleeding events ."
"32140829"
[ "29558208", "28293966", "28878834", "28917520" ]
[ "Anterolateral Knee Extra-articular Stabilizers: A Robotic Sectioning Study of the Anterolateral Ligament and Distal Iliotibial Band Kaplan Fibers", "Anatomic Reconstruction of the Anterior Cruciate Ligament of the Knee With or Without Reconstruction of the Anterolateral Ligament: A Randomized Clinical Trial", "Combined Anatomic Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction.", "Short-term complications in intra- and extra-articular anterior cruciate ligament reconstruction. Comparison with the literature on isolated intra-articular reconstruction. A multicenter study by the French Arthroscopy Society." ]
[ "Background : The individual kinematic roles of the anterolateral ligament ( ALL ) and the distal iliotibial b and Kaplan fibers in the setting of anterior cruciate ligament ( ACL ) deficiency require further clarification . This will improve underst and ing of their potential contribution to residual anterolateral rotational laxity after ACL reconstruction and may influence selection of an anterolateral extra-articular reconstruction technique , which is currently a matter of debate . Hypothesis/ Purpose : To compare the role of the ALL and the Kaplan fibers in stabilizing the knee against tibial internal rotation , anterior tibial translation , and the pivot shift in ACL-deficient knees . We hypothesized that the Kaplan fibers would provide greater tibial internal rotation restraint than the ALL in ACL-deficient knees and that both structures would provide restraint against internal rotation during a simulated pivot-shift test . Study Design : Controlled laboratory study . Methods : Ten paired fresh-frozen cadaveric knees ( n = 20 ) were used to investigate the effect of sectioning the ALL and the Kaplan fibers in ACL-deficient knees with a 6 degrees of freedom robotic testing system . After ACL sectioning , sectioning was r and omly performed for the ALL and the Kaplan fibers . An established robotic testing protocol was utilized to assess knee kinematics when the specimens were subjected to a 5-N·m internal rotation torque ( 0 ° -90 ° at 15 ° increments ) , a simulated pivot shift with 10-N·m valgus and 5-N·m internal rotation torque ( 15 ° and 30 ° ) , and an 88-N anterior tibial load ( 30 ° and 90 ° ) . Results : Sectioning of the ACL led to significantly increased tibial internal rotation ( from 0 ° to 90 ° ) and anterior tibial translation ( 30 ° and 90 ° ) as compared with the intact state . Significantly increased internal rotation occurred with further sectioning of the ALL ( 15 ° -90 ° ) and Kaplan fibers ( 15 ° , 60 ° -90 ° ) . At higher flexion angles ( 60 ° -90 ° ) , sectioning the Kaplan fibers led to significantly greater internal rotation when compared with ALL sectioning . On simulated pivot-shift testing , ALL sectioning led to significantly increased internal rotation and anterior translation at 15 ° and 30 ° ; sectioning of the Kaplan fibers led to significantly increased tibial internal rotation at 15 ° and 30 ° and anterior translation at 15 ° . No significant difference was found when anterior tibial translation was compared between the ACL/ALL- and ACL/Kaplan fiber – deficient states on simulated pivot-shift testing or isolated anterior tibial load . Conclusion : The ALL and Kaplan fibers restrain internal rotation in the ACL-deficient knee . Sectioning the Kaplan fibers led to greater tibial internal rotation at higher flexion angles ( 60 ° -90 ° ) as compared with ALL sectioning . Additionally , the ALL and Kaplan fibers contribute to restraint of the pivot shift and anterior tibial translation in the ACL-deficient knee . Clinical Relevance : This study reports that the ALL and distal iliotibial b and Kaplan fibers restrain anterior tibial translation , internal rotation , and pivot shift in the ACL-deficient knee . Furthermore , sectioning the Kaplan fibers led to significantly greater tibial internal rotation when compared with ALL sectioning at high flexion angles . These results demonstrate increased rotational knee laxity with combined ACL and anterolateral extra-articular knee injuries and may allow surgeons to optimize the care of patients with this injury pattern", "Background : Rotational instability of the knee remains an issue after anterior cruciate ligament ( ACL ) reconstruction . Hypothesis/ Purpose : The purpose was to evaluate the subjective and objective outcomes of combined reconstruction of the ACL and anterolateral ligament ( ALL ) of the knee . The hypothesis was that favorable outcomes can be achieved with this surgical procedure compared with isolated anatomic reconstruction of the ACL . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : One hundred ten patients with a unilateral ACL injury and high- grade pivot shift were r and omly assigned to undergo either combined ACL and ALL reconstruction ( group A ) or isolated ACL reconstruction ( group B ) . Preoperative and postoperative evaluations of the patients were conducted by obtaining history details , recording physical examination findings , measuring knee laxity using the KT-1000 arthrometer , and using vali date d outcome scores for the knee . P < .05 was considered as the cut-off level of statistical significance . The Fisher exact and Mann-Whitney U tests were used to assess statistical significance . Results : At a mean follow-up of 27 months , 53 and 50 patients in groups A and B , respectively , were available for analysis . No statistically different outcomes were found between the 2 groups except for the KT-1000 arthrometer values . The median KT-1000 arthrometer result for combined ACL and ALL reconstruction was 1.3 mm , while the median result for isolated ACL reconstruction was 1.8 mm ( P < .001 ) . None of the patients ( n = 0 ; 0.0 % ) who underwent combined ACL and ALL reconstruction had anterior translation of greater than 5 mm at maximum pulling strength compared with their normal knees at final follow-up . On the other h and , 3 ( 6.0 % ) patients who underwent isolated ACL reconstruction had anterior translation of more than 5 mm . No serious complications were found in both groups . Conclusion : Combined ACL and ALL reconstruction was found to be effective in improving subjective and objective outcomes . Nevertheless , these findings were not significantly superior to isolated ACL reconstruction except for the instrumented knee laxity testing results . This might indicate that ALL reconstruction should not be performed routinely for patients undergoing ACL reconstruction", "PURPOSE The purpose of the current paper was to report the surgical technique of combined anatomic anterior cruciate ligament ( ACL ) and anterolateral ligament ( ALL ) reconstruction as well as the short term clinical results after this surgical procedure . MATERIAL AND METHODS The current prospect i ve study included 32 patients ( 5 females and 27 males ) with combined ACL and ALL reconstruction performed between December 2015 and July 2016 . The patients were included in the study taking into consideration the following criteria : chronic ACL lesion , high grade rotational instability ( pivot shift grade II and III ) and participation in high grade pivoting sports . Patient evaluation followed an established clinical and imaging protocol both preoperatively and at 6 and 12 weeks postoperatively . This included clinical knee stability testing ( Lachman test , Pivot shift test ) , Rolimeter differential laxity testing , subjective and objective IKDC scores and Lysholm score and Tegner score . RESULTS Postoperative stability at 6 weeks and 12 weeks as tested with Lachman test ( p=0.02 and 0.01 , respectively ) , pivot shift test ( p=0.03 and 0.01 , respectively ) and the Rolimeter arthrometer ( p=0.008 and 0.006 , respectively ) showed a statistically significant difference as compared to preoperative values . Postoperative scores at 6 weeks and 12 weeks as measured using objective IKDC form ( p=0.008 and 0.006 , respectively ) , subjective IKDC form ( p=0.04 and 0.03 , respectively ) and Lysholm form ( p=0.02 and 0.01 , respectively ) were statistically significant improved as compared to preoperative values . All patients had a negative Lachman test at 6 and 12 weeks postoperatively . One patient had a positive grade I pivot shift test at 6 weeks postoperatively and two patients had a positive grade I pivot shift test at 12 weeks postoperatively . Differential anteroposterior laxity as measured with the Rolimeter arthrometer improved from 7.19±1.96 mm preoperatively to 0.28±0.45 mm and 0.13±0.34 mm , at 6 weeks and 12 weeks postoperatively , respectively . According to the objective IKDC form , 29 patients were normal or nearly normal ( grade A and B ) at 6 weeks postoperatively and 31 patients were normal or nearly normal at 12 weeks postoperatively . Subjective IKDC score improved from 47.72±17.18 preoperatively to 56.52±11.74 and 73.38±14.28 at 6 and 12 weeks postoperatively , respectively . Lysholm score improved from 63.44±23.01 preoperatively to 80.41±11.94 and 90.47±8.22 at 6 and 12 weeks postoperatively , respectively . Improved Tegner activity scores were present at 12 weeks postoperatively as compared with 6 weeks postoperatively , but still lower as compared to pre-traumatic scores . No significant complications were present in the current study group . CONCLUSIONS Combined ACL and ALL reconstruction is an effective surgical procedure , with improved postoperative clinical results and no significant short term complications . Longer follow-up is necessary in order to better evaluate the results of this procedure", "INTRODUCTION Lateral tenodesis ( LT ) is performed to limit the risk of iterative tear following anterior cruciate ligament ( ACL ) reconstruction in at-risk patients . By adding an extra procedure to isolated ACL graft , LT reconstruction increases operating time and may complicate postoperative course . The objective of the present study was to evaluate the rate of early complications . The study hypothesis was that associating ALL reconstruction to ACL reconstruction does not increase the complications rate found with isolated ACL reconstruction . MATERIAL AND METHODS A prospect i ve multicenter study included 392 patients : 70 % male ; mean age , 29.9 years ; treated by associated ACL and LT reconstruction . All adverse events were inventoried . RESULTS Mean hospital stay was 2 days , with 46 % day-surgery . Walking was resumed at a mean 27 days , with an advantage for patients treated by the hamstring technique . The early postoperative complications rate was 12 % , with 1.7 % specifically implicating LT reconstruction : pain , hematoma , stiffness in flexion and extension , and infection . There was a 5 % rate of surgical revision during the first year , predominantly comprising arthrolysis for extension deficit . The 1-year recurrence rate was 2.8 % . DISCUSSION The complications rate for combined intra- and extra-articular reconstruction was no higher than for isolated intra-articular ACL reconstruction , with no increase in infection or stiffness rates . The rate of complications specific to ALL reconstruction was low , at 1.7 % , and mainly involved fixation error causing lateral soft-tissue impingement . LEVEL OF EVIDENCE IV , prospect i ve multicenter study" ]
"LET could lead to worse anterior instability than with ALL reconstruction when these two approaches were combined with single-bundle ACL reconstruction . However , rotational stability and patient-reported outcomes were similar between the techniques"
"Anterolateral augmentation procedures can be divided into traditional lateral extra-articular tenodesis ( LET ) and modern anterolateral ligament ( ALL ) reconstruction . Nevertheless , no studies have compared the clinical results between LET and ALL reconstruction , when combined with intra-articular ACL reconstruction . This study was therefore design ed to compare the clinical results , including the anterior translation , rotational laxity , and patient-reported outcomes , in a group of patients who underwent ACL reconstruction combined with LET or ALL reconstruction ."
"15836553"
[ "9467701", "9353681", "9481346", "10517717", "9431286", "7361799", "8279598", "2441013", "1419592", "8973920", "9683116", "7599672", "11508020", "7513587", "15476993", "11683310", "10570675", "9565385" ]
[ "A hypertension control program tailored to unskilled and minority workers.", "Results of a Community-Based Low-Literacy Nutrition Education Program", "A polio immunization pamphlet with increased appeal and simplified language does not improve comprehension to an acceptable level.", "Use of a low-literacy patient education tool to enhance pneumococcal vaccination rates. A randomized controlled trial.", "The Stanford Nutrition Action Program: a dietary fat intervention for low-literacy adults.", "Patient comprehension of written drug information.", "Educating patients with limited literacy skills: the effectiveness of printed and videotaped materials about colon cancer.", "Evaluation of an audiovisual diabetes education program", "The use of illustrations and narrative text style to improve readability of a health education brochure.", "Involving parents in cancer risk reduction: a program for Hispanic American families.", "Randomized trial of geragogy-based medication instruction in the emergency department.", "Evaluation of a smoking cessation program for pregnant minority women.", "Two-Year Comparison of Income, Education, and Depression among Parents Participating in Regular Head Start or Supplementary Family Service Center Services", "Minimizing Effects of Low Literacy on Medication Knowledge and Compliance among the Elderly", "Development and pilot testing of a disease management program for low literacy patients with heart failure.", "The effectiveness of a self-care management interactive multimedia module.", "Outcomes of a cardiovascular nutrition counseling program in African-Americans with elevated blood pressure or cholesterol level.", "Intervention to increase mammography utilization in a public hospital" ]
[ "PURPOSE A comprehensive worksite health promotion program design ed to reduce risk factors for cardiovascular disease among 4000 city of Birmingham employees was used to develop and implement a tailored antihypertensive educational intervention . The mean age of the underlying population was 36 years , 89 % were blue-collar or unskilled workers , 50 % were African Americans and 20 % were female . METHODS First , we identified barriers to hypertension control : low literacy , difficulty underst and ing the need for treatment of asymptomatic disease , and wide variability of health beliefs and priorities . We then tailored an educational program , which offered employees health education sessions on a variety of different topics , including heart disease , cancer , sleep disorders and back injury . All program material s focused on lifestyle changes and the need to seek medical care . This program was offered to all hypertensive workers ; 130 chose to enroll , and 81 completed the program . These 81 participants were matched by age , sex , race and baseline BP with nonparticipating hypertensive workers ( controls ) . Changes in SBP and DBP from before to after the educational program were used to evaluate the program . RESULTS Overall , intervention participants had a decrease of 4.5 mm Hg in mean SBP ( different from zero , [ p = 0.03 ] ) . African American participants showed a significant decrease ( 7.4 mm Hg , [ p = 0.004 ] ) , as did unskilled intervention participants ( SBP changes = 7.7 mm Hg , [ p = 0.004 ] ) . Although not statistically significant , controls showed decreases in BP in the same direction . CONCLUSION An educational intervention tailored to the specific health perceptions and working conditions of a low literacy population is feasible , and may have a significant effect on hypertension control", "A nutrition intervention focused on low-fat eating pattern changes was conducted among low-literacy participants in a Twin Cities Metropolitan area Exp and ed Food and Nutrition Education Program ( EFNEP ) . A total of 134 EFNEP participants who participated in the intervention were compared to 70 comparison participants who received EFNEP nutrition education material s. Associations between changes in outcome variables specific to the intervention were evaluated using mixed-model regression analyses . The principal effects seen for this program were related to changes in eating pattern scales . More modest effects were seen in scales related to attitudes of low-fat eating , and although changes in dietary fat intake as measured by 24-hour dietary interviews suggested a positive intervention effect , this did not approach statistical significance", "We used a r and omized trial to compare two polio vaccine pamphlets written on a sixth grade level -- the vaccine information statement prepared by the Centers for Disease Control ( CDC ) and an easy-to-read pamphlet we developed (LSU)--for reading ability , comprehension and preference among 610 parents with a broad range of demographic characteristics . Parents at all reading levels and incomes preferred LSU ( 76 % vs. 21 % , P < 0.001 ) . Although readers of LSU achieved significantly higher comprehension ( 65 % vs. 60 % , P < 0.05 ) this difference may not be clinical ly significant . The information items presented with instructional graphics were the only items on which differences in comprehension levels achieved both clinical and statistical significance . Comprehension was lowest for the CDC m and ated information on risks and the National Injury Compensation . Our findings demonstrate that simplifying written immunization material and making it more suitable will increase appeal , but such modification may not raise comprehension to an acceptable level without use of instructional graphics . Health education material s intended for general parent population s , which are written on a sixth grade reading level , may not adequately educate parents or prepare them for a discussion with their physicians", "CONTEXT Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60 % established by the US Public Health Service . Limited or marginal literacy , which affects nearly 100 million Americans , especially the elderly , may contribute to these low rates of immunization . OBJECTIVE To determine whether the use of a simple , low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization . DESIGN A r and omized controlled trial conducted between May and June of 1998 . SETTING Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent , low-literate , African American , inner-city population . PARTICIPANTS Of 433 patients who presented for routine primary care , had vaccine indications ( age > or = 65 years or chronic disease ) , and had not been previously vaccinated , 221 were r and omly assigned to the intervention group and 212 to the control group . Of the total patient population ( mean age , 63 years ) , 280 ( 64.7 % ) had less than a high school education , 401 ( 92.6 % ) were African American , and 300 ( 69.3 % ) were female . INTERVENTION One-page , low-literacy ( below fifth- grade level ) educational h and out encouraging patients to \" ask your doctor about the pneumonia shot \" vs a control group ( 1 -page , low-literacy educational h and out conveying information about nutrition ) . MAIN OUTCOME MEASURES Vaccination rates ( documented by chart audit ) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians . RESULTS Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group ( 87/221 [ 39.4 % ] vs 21/212 [ 9.9 % ] ; relative risk [ RR ] , 3.97 [ 95 % confidence interval [ CI ] , 2.71 - 5.83 ] ) , and were more than 5 times as likely to have received the pneumococcal vaccine than the control group ( 44/221 [ 19.9 % ] vs 8/212 [ 3.8 % ] ; RR , 5.28 [ 95 % CI , 2.80 - 9.93 ] ) . In a multivariate analysis controlling for race , sex , education , insurance status , age , level of physician training , health status , and vaccine indication , only assignment to the intervention group was statistically significantly related to the probability of being immunized or discussing the issue with their physicians ( P<.001 for both trends ) . CONCLUSIONS A simple , low-literacy educational tool increased pneumococcal vaccination rates and patient-physician discussion s about the vaccine in an elderly , low-literate , indigent , minority population", "OBJECTIVES This study was undertaken to test the effectiveness of the Stanford Nutrition Action Program , an experimental trial to reduce dietary fat intake among low-literacy , low-income adults . METHODS Twenty-four paired adult education classes ( 351 participants , 85 % women , mean age = 31 years ) were r and omly assigned to receive a newly developed dietary fat curriculum ( the Stanford Nutrition Action Program ) or an existing general nutrition curriculum . Food frequency and nutrition-related data , body mass index , and capillary blood cholesterol were collected at baseline and at two postintervention follow-ups . RESULTS The Stanford Nutrition Action Program classes showed significantly greater net improvements in nutrition knowledge ( + 7.7 ) , attitudes ( /0.2 ) , and self-efficacy ( -0.2 ) than the general nutrition classes ; they also showed significantly greater reductions in the percentage of calories from total ( -2.3 % ) and saturated ( -0.9 % ) fat . There were no significant differences in body mass index or blood cholesterol . All positive intervention effects were maintained for 3 months postintervention . CONCLUSIONS The Stanford Nutrition Action Program curriculum , tailored to the cultural , economic , and learning needs of low-literacy , low-income adults , was significantly more effective in achieving fat-related nutritional changes than the general nutrition curriculum", "The effect of the readability level of patient drug information material s on patient comprehension of and attitude toward the information was studied . The reading level of 108 out patients at a Veterans Administration hospital who could read English , read type of normal size , and who were not receiving warfarin sodium was measured . Patients then were given , on a r and om basis , a warfarin drug monograph written on either the 5th- or 10th- grade level . To test comprehension , all subjects took a true-false test of recall written at the 5th- grade level . A significant relationship was found between comprehension and reading ability ( p less than 0.001 ) . Patients receiving the 5th- grade level monograph exhibited significantly better comprehension than those receiving the 10th- grade level material ( p less than 0.001 ) . As compared with those getting 10th- grade material , the group receiving the 5th- grade material had a more favorable perception of the level of difficulty , underst and ability , and clarity of the material . The study indicates that comprehension of written patient drug information can be improved by adjusting the readability of informational material s to the reading level of the patients", "We investigated whether printed or videotaped information is more effective in enhancing colon cancer knowledge . Subjects ( n = 1100 ) were r and omized into three groups : to receive a booklet , view a videotape , or receive no intervention . Subjects receiving the intervention showed increased knowledge compared with control subjects ( booklet = 23 % and videotape = 26 % vs no intervention = 3 % ) . Findings suggest that personalized educational material s are effective in enhancing colon cancer knowledge", "A r and omized controlled trial was conducted to determine whether an education program specifically design ed for patients with non-insulin-dependent diabetes and limited literacy could improve and sustain glucose and weight control . From a referral clinic , 120 obese ( > 130 per cent of ideal body weight ) diabetic patients who were not taking insulin were recruited . Of these , 55 per cent were female and 49 per cent were black ; the mean age was 53 years . Mean glycosylated hemoglobin ( HbA1 % ) was 10.2 per cent . Each subject was assigned to one of three groups : 1 ) monthly group sessions with videotapes for diabetic persons with low literacy skills ; 2 ) monthly group sessions without videotapes ; or 3 ) no monthly sessions . After seven months , there had been 16 dropouts ( 13 per cent ) . Differences in weight changes between groups were significant ( p<0.05 ) ; group 1 lost a median of 1 kg of weight ( p<0.05 ) compared with a 0.1-kg loss and no change in groups 2 and 3 , respectively . This weight loss was not sustained at 11 months . There was no significant change in HbA1 % . Age , education , and compliance beliefs did not predict outcome . The authors conclude that the patient education programs did not result in sustained glucose or weight control", "Research suggests that much of the available health education literature requires a level of reading ability that makes it inaccessible to a large proportion of the population in greatest need of health information . The present study tested the value of illustrations and a narrative text style as means of improving the readability of a brochure design ed to provide information on cervical cancer and condyloma . Two versions of the brochure were design ed , one that had only text presented as simple sentences in bullet-type format ( SMOG reading level score of 7.7 ) , and a second version that had somewhat more difficult text formatted in a narrative style ( SMOG grade level score of 8.4 ) together with drawings design ed to complement the text . A r and omized study design was used to test for comprehension , perceived ease of underst and ing , and overall rating of the two brochures . Women selected from one private and three public health primary -care clinics were r and omly assigned to read one of the two brochures . The brochure with illustrations and narrative text was given a significantly higher overall rating than the one with bullet-type text and no illustrations , while no difference was found in perceived ease of reading . Among poor readers , comprehension was significantly greater for women who read the brochure with illustrations and narrative text , with no difference in comprehension of the two brochures for better readers . The results suggest that the use of aids such as illustrations and text style can make health education literature more accessible to high-risk population s , while remaining interesting enough to appeal to individuals at all levels of reading ability", "The authors explored changes in dietary behavior , nutrition knowledge , and parental support among inner-city , low-income , Hispanic American families . Thirty-eight families were r and omly assigned to receive a 12-week , culture-specific dietary intervention or be in a control group . Results showed that parental support was related to changes in diet , nutrition knowledge , and attendance for both mothers and children . Dietary behavior changes ( e.g. , reduction in dietary fat ) were seen only in the treatment group . Distribution of health-related pamphlets to the control group may have promoted cognitive changes ( e.g. , increased nutrition knowledge ) seen in this low-literacy sample . Further research is needed to document behavioral changes after ethnic-specific interventions and the maintenance of those changes over time", "BACKGROUND Medication adherence by older adults who are discharged from the emergency department ( ED ) is an essential attribute of effective treatment . Research ers have demonstrated that delivery of well-structured instructions increases the knowledge of discharge regimens and increases adherence among ED population s. OBJECTIVES This study compared the level of medication knowledge of elderly ED patients receiving instruction by one of two teaching methods : the usual preprinted discharge instructions with h and written medication information and individualized computer-generated discharge instructions design ed within a geragogy framework . METHOD The geragogy intervention included large-print , easily readable , specific information ordered within the elderly memory schema . This schema consists of purpose , administration , and emergency information in that order . The Knowledge of Medication Subtest by Horn and Swain ( 1977 ) was administered by telephone 48 to 72 hours after discharge . Sixty patients ( 38 women , 22 men ) with a mean age of 76 years were r and omly assigned to groups and completed the study at three rural ED sites . RESULTS Subjects in the geragogy-based intervention group demonstrated significantly more knowledge of medications than did subjects experiencing the usual discharge teaching method ( t = 2.19 , p = .016 ) . CONCLUSIONS These findings suggest that a medication teaching intervention geared to the special needs of the elderly can be effective in increasing medication knowledge", "The purpose of this project was to develop and test culturally appropriate , low literacy , smoking cessation intervention material s design ed to increase quit rates and prevent relapse postpartum for low-income African American and Hispanic women . A quasi-experimental , pretest-posttest design was used . Four Women , Infants , and Children ( WIC ) clinic sites in south and central Los Angeles were identified , pair-matched based on ethnic mix , and r and omized to intervention ( 2 sites ) or control status ( 2 sites ) . Participants were 18 years of age or older and either current or exsmokers ( stopped smoking in the past year ) . The intervention group received the \" Time for a Change : A Program for Healthy Moms and Babies \" program including a 15-minute one-to-one counseling session and self-help guide , incorporating behavior-change strategies , booster postcard , and incentive contest . All material s were design ed to match the cultural , language , and literacy needs of the target population . The smoking cessation intervention had a positive impact on both quit-smoking behavior during pregnancy and relapse prevention postpartum . Almost twice as many smokers in the intervention group ( 43 % ) reported quitting smoking at 9 months , compared to the control group ( 25 % ) ( P < 0.01 ) . At 6 weeks postpartum , 25 % of the intervention baseline smokers were abstinent , compared to 12 % of the control group ( P < 0.01 ) . Although no significant differences were observed for relapse during pregnancy among exsmokers at 6 weeks postpartum , a significantly higher proportion of intervention exsmokers were still abstinent ( 79 % ) , compared to control exsmokers ( 62 % ) ( P < 0.01 ) . For the exsmokers , relapse prevention rates remained significant when adjusted for cotinine vali date d abstinence . ( ABSTRACT TRUNCATED AT 250 WORDS", "Changes after 2 years in a Head Start Family Service Center Demonstration Project were assessed through pre-implementation and postimplementation interviews with 80 parents of Head Start children to evaluate changes during the project noted for the children 's parents . Compared with parents in regular Head Start , parents in the supplementary Family Service Center project reported more contact with staff , increased their functional literacy scores , and increased their family incomes . The percentage of these parents with high depression scores decreased . These changes encourage implementation of more intensive social services within Head Start programs as a means of effectively assisting Head Start parents", "Medication knowledge and compliance among the elderly was examined using a color-coded method , which was design ed to tailor the medication regimen to the person 's daily schedule . Data were collected from 80 elderly , predominantly indigent , and individuals of low literacy . Group 1 of the study received verbal teaching only , whereas Group 2 received verbal teaching and a color-coded medication schedule . Knowledge increased significantly among both groups . Compliance to the medication schedule increased in Group 2 , among those subjects whose pretest compliance scores were low . These results suggest that a method that considers the characteristics of the individual can significantly increase knowledge and compliance", "UNLABELLED Development and pilot testing of a disease management program for low literacy patients with heart failure . BACKGROUND R and omized trials have shown that disease management programs can reduce hospitalizations and improve symptoms for patients with congestive heart failure . We sought to create and pilot test such a program for patients with low literacy skills . METHODS We used focus groups and individual cognitive response interviews ( CRIs ) to develop an educational booklet for low literacy patients with heart failure . We incorporated the booklet into a disease management intervention that also included an initial individualized 1-h educational session and scheduled supportive phone calls that were tapered over 6 weeks . We then conducted a 3-month before-after study on patients with low literacy skills ( < 9th grade literacy level ) in a university internal medicine clinic to test the acceptability and efficacy of our program . Outcomes of interest included heart failure-related knowledge , self-care behavior and heart failure-related symptoms measured on the Minnesota Living with Heart Failure ( MLwHF ) scale . RESULTS Twenty-five patients were enrolled and 23 ( 92 % ) completed 3-month follow-up . Mean age was 60 years ( range 35 - 74 ) , 60 % were men , 60 % were African-American , and 74 % had household income under 15,000 per year . The median reading level was fifth grade with 32 % reading at or below the third grade level . Mean knowledge score at baseline was 67 % and did not improve after the intervention . The proportion of patients reporting weighing themselves daily increased from 32 % at baseline to 100 % at 12 weeks . Mean improvement on the MLwHF scale was 9.9 points over the 3-month trial ( 95 % CI : 0.5 , 19.2 ) , which corresponds to an improvement in one class on the New York Heart Association heart failure scale . CONCLUSION A heart failure disease management program design ed specifically for patients with low literacy skills is acceptable and is associated with improvement in self-care behavior and heart failure related symptoms", "PURPOSE / OBJECTIVES To develop and test an interactive multimedia module prototype design ed to accommo date adults with limited literacy and without computer skills . DESIGN Experimental , r and omized , controlled , pretest , post-test . SETTING Cancer treatment centers in California , Louisiana ( pilot ) . New Hampshire , Pennsylvania , and Texas . SAMPLE Out patients who were at least 18 years old with a minimum fifth- grade reading level ; 86 experimental treatment , 88 control . METHODS Experimental treatment involved use of the interactive multimedia module ; the control group received customary Instruction . FINDINGS As compared to the control group , subjects in the experimental group had significant improvement ( p = 0.0001 ; 257 % gain ) in self-care ability regardless of age , sex race , education , geographic location , reading ability , computer experience , or preferred learning style ; a 6.515 % increase in fatigue content covered and 16.775 % Increase in instructional duration ; and significantly greater benefit from sleep-related activities and a consistent , positive pattern of self-care behavior . CONCLUSIONS The program is instructionally effective , appropriate for a wide and geographically diverse audience , and feasible for use in the ambulatory setting . IMPLICATION S FOR NURSING PRACTICE The interactive multimedia module is an effective , self-directed re source for individualized patient fatigue education", "OBJECTIVE To evaluate a cardiovascular nutrition education package design ed for African-American adults with a wide range of literacy skills . DESIGN Comparison of a self-help group and a full-instruction group ; each group received nutrition counseling and clinical monitoring every 4 months . SUBJECTS Three hundred thirty African-American adults , aged 40 to 70 years , with elevated cholesterol level or high blood pressure were r and omly assigned to the self-help or full-instruction group ; 255 completed the 12-month follow-up . INTERVENTIONS Counseling to reduce intake of dietary fat , cholesterol , and sodium was based on Cardiovascular Dietary Education System ( CARDES ) material s , which included food-picture cards , a nutrition guide ( self-help and full-instruction group ) , a video and audiotape series , and 4 classes ( full-instruction group only ) . MAIN OUTCOME MEASURES Changes in lipid levels and blood pressure after 12 months . STATISTICAL ANALYSES PERFORMED Primary analyses consisted of repeated- measures analysis of variance to examine effects of time and r and omization group on outcomes . RESULTS Total cholesterol and low-density lipoprotein cholesterol level decreased by 7 % to 8 % in the self-help and full-instruction groups of men and women ( P < .01 ) . The ratio of total cholesterol to high-density lipoprotein cholesterol ( HDL-C ) decreased in both groups of women and in the men in the full-instruction group ( P < .01 ) . In full-instruction and self-help participants with elevated blood pressure at baseline , systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg ( P < .01 ) . Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES material s. APPLICATIONS/ CONCLUSIONS These results suggest that periodic nutrition counseling based on CARDES material s used for home study can enhance management of lipid levels and blood pressure in African-American out patients", "Abstract OBJECTIVE : To study the effects of three approaches to increasing utilization of screening mammography in a public hospital setting in Northwest Louisiana . DESIGN : R and omized intervention study . POPULATION : Four hundred forty-five women aged 40 years and over , predominantly low-income and with low literacy skills , who had not had a mammogram in the preceding year . INTERVENTION : All interventions were chosen to motivate women to get a mammogram . Group 1 received a personal recommendation from one of the investigators . Group 2 received the recommendation plus an easy-to-read National Cancer Institute ( NCI ) brochure . Group 3 received the recommendation , the brochure , and a 12-minute interactive educational and motivational program , including a soap-operastyle video , developed in collaboration with women from the target population . MEASUREMENTS AND MAIN RESULTS : Mammography utilization was determined at 6 months and 2 years after intervention . A significant increase ( p=.05 ) in mammography utilization was observed after the intervention design ed in collaboration with patients ( 29 % ) as compared with recommendation alone ( 21 % ) or recommendation with brochure ( 18 % ) at 6 months . However , at 2 years the difference favoring the custom-made intervention was no longer significant . CONCLUSIONS : At 6 months there was at least a 30 % increase in the mammography utilization rate in the group receiving the intervention design ed in collaboration with patients as compared with those receiving the recommendation alone or recommendation with brochure . Giving patients an easy-to-read NCI brochure and a personal recommendation was no more effective than giving them a recommendation alone , suggesting that simply providing women in a public hospital with a low-literacy-level , culturally appropriate brochure is not sufficient to increase screening mammography rates . In a multivariate analysis , the only significant predictor of mammography use at 6 months was the custom-made intervention" ] ": Several interventions have been developed to improve health for people with low literacy ." "Abstract OBJECTIVE : To perform a systematic review of interventions design ed to improve health outcomes for persons with low literacy skills ." "28176333" [ "8276683", "5402639", "23974453", "25092356", "15603570", "4459625", "24112747", "7664230", "6428627", "23901667", "18221925", "8092203", "3119022", "6432201", "8066836", "25056465", "27179374", "24972557" ] [ "[Does episiotomy prevent perineal trauma and pelvic floor relaxation?].", "Selective episiotomy vs. implementation of a non-episiotomy protocol: a randomized clinical trial", "A randomized control trial evaluating the prevalence of obstetrical anal sphincter injuries in primigravida in routine versus selective mediolateral episiotomy.", "Clinical evaluation of early postpartum pain and healing outcomes after mediolateral versus lateral episiotomy.", "Episiotomy and perineal tears presumed to be imminent: the influence on the urethral pressure profile, analmanometric and other pelvic floor findings – follow‐up study of a randomized controlled trial", "Randomized trial comparing episiotomies with Braun-Stadler episiotomy scissors and EPISCISSORS-60®", "Clinical evaluation of peripartum outcomes of mediolateral versus lateral episiotomy.", "Physicians' beliefs and behaviour during a randomized controlled trial of episiotomy: consequences for women in their care.", "Is routine episiotomy necessary?", "Morbidity from episiotomy.", "Selective vs routine midline episiotomy for the prevention of third- or fourth-degree lacerations in nulliparous women.", "Relationship of episiotomy to perineal trauma and morbidity, sexual dysfunction, and pelvic floor relaxation.", "West Berkshire perineal management trial: three year follow up.", "West Berkshire perineal management trial.", "[Episiotomy and perineal lesions in spontaneous vaginal delivery].", "Comparison between two incision angles of mediolateral episiotomy in primiparous women: a randomized controlled trial.", "Mediolateral versus lateral episiotomy and their effect on postpartum coital activity and dyspareunia rate 3 and 6 months postpartum.", "Curved versus straight scissors to avoid 3rd and 4th degree perineal tears: a randomised feasibility study." ] [ "OBJECTIVE : To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation ( control group ) to a policy of restricting episiotomy use to specific fetal and maternal indications ( experimental group ) . DESIGN : A r and omized controlled trial ( RCT ) . SETTING : Three university hospitals in Montreal . SUBJECTS : Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were r and omized late in labor to the design ated trial arm , by parity , and followed up to 3 months postpartum . MAIN OUTCOME MEASURES : Antepartum and postpartum information on perineal trauma and pain , pelvic floor symptoms ( urinary incontinence ) , and sexual activity was collected through the use of st and ard question naires ; pelvic floor function was measured by electromyographic ( EMG ) perineometry . RESULTS : Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach . Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum ( 31 % compared with 19 % , odds ratio ( OR ) = 1.85 , 95 % confidence interval ( CI ) = 1.09 to 3.16 ) . All but one 3rd/4th-degree perineal tear was associated with median episiotomy ( 46 of 47 in primiparous women and 6 of 6 among multiparous women ) . No difference between trial groups was found in postpartum perineal pain , antepartum and 3-month postpartum EMG perineometry , and urinary and pelvic floor symptoms . CONCLUSIONS : We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation . Virtually all severe perineal trauma was associated with median episiotomy . Restriction of episiotomy use among multiparous women result ed in significantly more intact perineums and less perineal suturing", "Background Despite all the evidence corroborating the selective use of episiotomy and although routine use of the procedure is contraindicated , there are no evidence s corroborating if episiotomy is necessary in any circumstance . The present clinical r and omized trial was performed to compare maternal and perinatal outcomes in women su bmi tted to a non-episiotomy protocol versus one of selective episiotomy . Methods An open-labelled , r and omized clinical trial was carried out in a tertiary teaching hospital in Recife , Northeastern Brazil . Women in labor with a full-term live foetus , dilatation of 6 to 8 cm and cephalic presentation ( vertex position ) were included . Exclusion criteria consisted of bleeding disorders and an indication for a caesarean section . After signing the consent form , 241 women were r and omized to a non-episiotomy protocol ( the experimental group ) or to a selective episiotomy group ( the control group ) . No episiotomies were to be performed in the experimental group except under exceptional circumstances . In the control group , selective episiotomies were to be performed in accordance with the healthcare professionals ’ clinical judgement . Maternal and perinatal outcomes were evaluated . Ratio Risk ( RR ) and the 95 % confidence interval ( 95 % CI ) were calculated for our outcomes . Results The analysis include 115 women assigned to a non-episiotomy protocol and 122 to selective episiotomy . There was no difference between the two groups with respect to maternal or perinatal outcomes . The episiotomy rate was similar ( two cases in each group , about 1.7 % ) , as was the duration of the second stage of labor , the frequency of perineal tears , severe perineal trauma , need for perineal suturing and blood loss at delivery . Conclusions A non-episiotomy protocol appears to be safe for mother and child , and highlights the need to investigate whether there is , in fact , any indication for this procedure . Trial registration This trial was registered at Clinical Trials.gov under reference number ( NCT02178111 )", "OBJECTIVE To evaluate the prevalence of obstetrical anal sphincter injuries ( OASIS ) , which include third and fourth degree perineal tears in primigravida in routine versus selective mediolateral episiotomy . Secondly , to determine the rate of episiotomy in local setting s. METHODS This r and omized control trial was carried out in the labor ward of a tertiary hospital of the Universiti Kebangsaan Malaysia Medical Center , Kuala Lumpur , Malaysia between May and October 2009 . The trial included 171 primigravida beyond 38 weeks gestation who achieved vaginal delivery , and r and omly assigned to selective and routine episiotomy groups . The type of perineal injuries following childbirth among 171 women were evaluated . RESULTS The overall episiotomy rate from both groups was 76.6 % . The prevalence of third degree perineal tears was 3.7 % in the routine compared with selective mediolateral episiotomy at 1.1 % . There was no occurrence of fourth degree tears in both groups . However , selective mediolateral episiotomy was associated with an increased risk of periurethral and labial injury compared with the routine group ( 4.5 % versus 0 % ) . CONCLUSION Routine mediolateral episiotomy in primigravida is associated with a higher prevalence of obstetrical anal sphincter injuries . As anal sphincter injuries are known to have morbidities , selective mediolateral episiotomy in primigravida is therefore recommended in the implementation of new delivery practice , and in an attempt to reduce our high episiotomy rate", "OBJECTIVE To evaluate short-term perineal pain among primiparous women after mediolateral episiotomy ( MLE ) and lateral episiotomy ( LE ) . METHODS The prospect i ve r and omized study was conducted in the Czech Republic during 2010 - 2012 . Consecutive primiparous women who gave birth at or after 37 weeks of pregnancy and had indications for an episiotomy were enrolled and r and omly assigned to undergo MLE or LE . Patients were unaware of the episiotomy type performed . The primary outcomes were pain at 24 hours , 72 hours , and 10 days post partum , measured by a visual analog scale , verbal rating scale , interference with activities of daily living , and amount of analgesic use . RESULTS The analysis included 266 women who underwent MLE and 297 women who underwent LE . Complete relief of pain was observed in 6 ( 2.3 % ) of 266 women after 24 hours , 21 ( 8.0 % ) of 264 after 72 hours , and 77 ( 29.1 % ) of 265 after 10 days in the MLE group , and in 11 ( 3.9 % ) of 285 , 23 ( 7.7 % ) of 297 , and 78 ( 26.4 % ) of 295 in the LE group , respectively ( P=0.36 ) . There were no significant differences in overall pain scores from any rating system or in the amount of analgesics used . CONCLUSION Incidence and extent of pain in the first 10 days after LE correspond to those after adequately performed MLE", "Background . The influence of the restrictive use of episiotomy at perineal tears judged to be imminent on the urethral pressure profile , analmanometric , and other pelvic floor findings is unknown", "Introduction Episiotomy angle is a crucial factor in causation of obstetric anal sphincter injuries ( OASIS ) , which are the major cause of female bowel incontinence . Sutured episiotomies angled too close to the midline ( < 30 degree ) or too far away from the midline ( > 60 degree ) fail to unload the perineum sufficiently and predispose to OASIS . A 25-degree post-delivery episiotomy suture angle has a 10 % risk of OASIS while 45-degree episiotomy is associated with 0.5 % risk . To account for perineal distension at crowning , a 60-degree episiotomy incision is required to achieve 43–50 degree suture angles . We compared episiotomy suture angles with commonly used Braun-Stadler episiotomy scissors with the new fixed angle EPISCISSORS-60 ® . Methods Ethical approval was obtained . A prospect i ve cluster r and omization design was chosen . Thirty-one patients were required in each group for a 12-degree difference with power at 90 % and 5 % significance . Sutured episiotomy angles and post-delivery linear distance from caudal end of the sutured episiotomy to the anus were measured with protractors and rulers . Two-tailed t-tests were used to compare the two groups . Results Thirty-one nulliparae had episiotomies with EPISCISSORS-60 ® , 32 with Braun-Stadler . Mean age ( 25 versus 24.8 years ) was similar . EPISCISSORS-60 ® episiotomies were angled 12 degrees more laterally away from the anus compared to Braun-Stadler ( 40.6 degrees , 95 % confidence interval [ CI ] ±2 , interquartile range [ IQR ] 35–45 versus 28.3 degrees , 95 % CI ±2 , IQR 25–30 , P<0.0001 ) . The post-delivery linear distance from caudal end of the sutured episiotomy to the anus was 15 mm more with the EPISCISSORS-60 ® compared to Braun-Stadler ( 35 mm , 95 % CI ±2.2 , IQR = 30–39 versus 19.5 ; 95 % CI ±1.3 , IQR = 14.75–22.25 P<0.0001 ) . EPISCISSORS-60 ® episiotomies measured longer ( 47 mm versus 40 mm , P<0.0001 ) . There were no OASIS cases in the EPISCISSORS-60 ® group versus one in the Braun-Stadler group . Conclusion The EPISCISSORS-60 ® sutured episiotomies are much further away from the midline in angular and distance measures , hence at lower OASIS risk", "OBJECTIVE To evaluate the incidence and extent of vaginal and perineal trauma among primiparous women after mediolateral and lateral episiotomy . METHODS In a prospect i ve r and omized study at University Hospital Pilsen , Czech Republic , 790 consecutive primiparous women were enrolled between April 2010 and April 2012 . Mediolateral episiotomy ( MLE ) followed an angle of at least 60 ° from the midline . Lateral episiotomy ( LE ) started 1 - 2 cm laterally from the midline and was directed toward the ischial tuberosity . A rectal examination was performed before episiotomy repair . RESULTS MLE was performed for 390 women , and LE for 400 . The groups did not differ in maternal or neonatal characteristics . No difference was found in incidence or extent of vaginal and perineal trauma ; or in additional perineal ( 1.8 % vs 1.5 % , P=0.6 ) or vaginal ( 8.5 % vs 10.6 % , P=0.2 ) trauma continuing along the episiotomy incision . The incidence of anal sphincter injury did not differ between MLE and LE ( 1.5 % vs 1.3 % , P=0.7 ) . MLE was associated with shorter repair times ( P<0.05 ) , less suturing material ( P<0.05 ) , and shorter distances from the anus ( P<0.001 ) . CONCLUSION Risk of additional vaginal and perineal trauma , and anal sphincter injury after adequately performed mediolateral episiotomy is relatively low and corresponds to that of lateral episiotomy", "OBJECTIVE To evaluate whether physicians ' beliefs concerning episiotomy are related to their use of procedures and to differential outcomes in childbirth . DESIGN Post-hoc cohort analysis of physicians and patients involved in a r and omized controlled trial of episiotomy . SETTING Two tertiary care hospitals and one community hospital in Montreal . PARTICIPANTS Of the 703 women at low risk of medical or obstetric problems enrolled in the trial we studied 447 women ( 226 primiparous and 221 multiparous ) attended by 43 physicians . Subjects attended by residents or nurses were excluded . MAIN OUTCOME MEASURES PATIENTS intact perineum v. perineal trauma , length of labour , procedures used ( instrumental delivery , oxytocin augmentation of labour , cesarean section and episiotomy ) , position for birth , rate of and reasons for not assigning women to a study arm , postpartum perineal pain and satisfaction with the birth experience , physicians : beliefs concerning episiotomy . RESULTS Women attended by physicians who viewed episiotomy very unfavorably were more likely than women attended by the other physicians to have an intact perineum ( 23 % v. 11 % to 13 % , p < 0.05 ) and to experience less perineal trauma . The first stage of labour was 2.3 to 3.5 hours shorter for women attended by physicians who viewed episiotomy favourably than for women attended by physicians who viewed episiotomy very unfavorably ( p < 0.05 to < 0.01 ) , and the former physicians were more likely to use oxytocin augmentation of labour . Physicians who viewed episiotomy more favourably failed more often than those who viewed the procedure very unfavourably to assign patients to a study arm late in labour ( odds ratio [ OR ] 1.88 , p < 0.05 ) , both overall and because they felt that \" fetal distress \" or cesarean section necessitated exclusion of the subject . They used the lithotomy position for birth more often ( OR 3.94 to 4.55 , p < 0.001 ) , had difficulty limiting episiotomy in the restricted-use arm of the trial and diagnosed fetal distress and perineal inadequacy more often than the comparison groups . The patients of physicians who viewed episiotomy very favourably experienced more perineal pain ( p < 0.01 ) , and of those who viewed episiotomy favourably and very favourably experienced less satisfaction with the birth experience ( p < 0.01 ) than the patients of physicians who viewed the procedure very unfavourably . CONCLUSIONS Physicians with favourably views of episiotomy were more likely to use techniques to expedite labour , and their patients were more likely to have perineal trauma and to be less satisfied with the birth experience . This evidence that physician beliefs can influence patient outcomes has both clinical and research implication", "One hundred and eighty one primigravid women delivering vaginally in July and August 1982 in the Rotunda Hospital , Dublin , were r and omly allocated to one of two groups . Patients in one group were to undergo episiotomy . Those in the other group were not to undergo episiotomy unless it was considered to be essential . The outcome was compared with that of the clinical practice over the previous six months at the hospital . Of the 92 patients allocated not to undergo episiotomy , seven ( 8 % ) had one done for medical reasons compared with 507 ( 89 % ) in the previous six months . First degree tears occurred in 23 ( 25 % ) and second degree tears in 43 ( 47 % ) . Nineteen ( 21 % ) , however , retained an intact perineum compared with only 35 ( 6 % ) of the women who had delivered in the preceding six months . Assessment s of perineal pain , bruising , swelling , and healing and records of ingestion of analgesics were made for the first four days after delivery , and again at a check up six weeks after delivery , in patients who had had spontaneous vertex deliveries . Forty patients who underwent episiotomy and 37 who sustained a second degree tear formed two comparable groups . There was no difference in outcome between them . Data were also evaluated for 19 women who retained an intact perineum , 22 who sustained a first degree tear , and 11 who underwent episiotomy and epidural anaesthesia ; all 52 of these women had spontaneous vertex deliveries . Despite severe soft tissue injury in two patients those who fared best were those who retained an intact perineum . First degree tears were associated with symptoms similar to those associated with second degree tears . Those who fared worst were women who underwent episiotomy after epidural anaesthesia . The value of routine episiotomy in primigravid patients is question ed , but the final decision can be made only by the accoucheur at the time of imminent delivery", "OBJECTIVE To assess the morbidity from episiotomy . METHODS The prospect i ve r and omised control study was conducted at the Military Hospital Rawalpindi 's Gynaecology & Obstetrics Department from January 2006 to April 2008 . It comprised 100 patients who were given a mediolateral episiotomy at the crowning of the foetal head ( group 1 ) . Another group of 100 patients were delivered without an episiotomy ( group 2 ) . Postpartum morbidity was compared in the two groups . Morbidity included perineal damage by tears , subjective assessment of pain at perineum , dyspareunia after puerperium , feeling of pressure puerperium , incontinence and objective assessment of prolapse after puerperium . RESULTS Morbidity including perineal damage by tears , pain at perineum and dyspareunia , was much more in group I as compared to the group II . There was no significant difference in feeling of pressure perineum , subjective feeling of urinary and flatus incontinence or objective assessment of prolapse of vagina and uterus . CONCLUSION There are no significant advantages of episiotomy . In fact , it leads to morbidity which is otherwise avoidable in deliveries that are episiotomy-free", "OBJECTIVE The purpose of this study was to determine whether selective midline episiotomy contributes to the prevention of third- or fourth-degree perineal lacerations . STUDY DESIGN A r and omized controlled clinical trial was performed with 446 nulliparous women with deliveries after 28 weeks of pregnancy . Patients were r and omized to undergo either routine episiotomy or selective episiotomy . In the selective episiotomy group , episiotomies were performed only in cases of imminent lacerations , fetal distress , or forceps delivery . RESULTS In the group of 223 patients who underwent routine episiotomy , 32 ( 14.3 % ) had third- or fourth-degree perineal lacerations , as compared to 15 ( 6.8 % ) in the group of 222 patients undergoing selective episiotomy ( relative risk , 2.12 ; 95 % confidence interval , 1.18 - 3.81 ) . Only reduction in third-degree lacerations was significant when analyzed separately . Moreover , periurethral , labia minora , and superficial vaginal lacerations were significantly more frequent in the selective episiotomy group . CONCLUSION The policy of performing selective midline episiotomy in nulliparous patients results in a reduction in the risk of third-degree perineal lacerations", "OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications", "Women who had participated in a r and omised controlled trial of policies of restricted ( 10 % ) versus liberal ( 51 % ) episiotomy during spontaneous vaginal delivery were recontacted by postal question naire three years after delivery . Altogether 674 out of 1000 responded , and there was no evidence of a differential response rate between the two trial groups . Similar numbers of women in the two groups reported further deliveries , almost all of which had been vaginal and spontaneous . Fewer women allocated to restrictive use of episiotomy required perineal suturing after subsequent delivery , but this difference was not significant . Pain during sexual intercourse and incontinence of urine were equally reported in the two groups . The similarity in incontinence rates persisted when severity , type of incontinence , and subsequent deliveries were taken into account . Liberal use of episiotomy does not seem to prevent urinary incontinence or increase long term dyspareunia", "One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity", "The purpose of the study was to evaluate the influence of mediolateral episiotomy on the perineal state after spontaneous , singleton vaginal deliveries with the foetus in the occiput anterior position . The design was that of a population based , observational study . Two approaches were used in the analyses : Initially , we considered the parturients as quasi-r and omised to one of three equally sized groups of midwives with different attitudes towards episiotomy . Secondly , we studied the effect of episiotomy on the state of the anal sphincter , controlling for birth weight , parity , and duration of second stage of labour . The subjects were 2188 pregnant women delivering consecutively , and the main outcome measures were perineal lacerations and tearing of the anal sphincter . Women allocated to the group of midwives with the lowest rate of episiotomy were more likely to have an intact perineum after delivery ( OR = 1.8 ( 1.4 - 2.2 ) ) , had a slight tendency towards more perineal lacerations ( OR = 1.3 ( 1.0 - 1.5 ) ) , but no increased risk of tearing of the anal sphincter , compared with the women allocated to the two groups of midwives with higher frequencies of episiotomy . The second approach showed that episiotomy was related to an increased risk of tearing of the anal sphincter ( OR = 2.3 ( 1.2 - 4.6 ) ) . However , this relation was not found among the group of parturients delivered by the midwives with the lowest rate of episiotomy ( 22 % ) . Our results encourage a conservative approach to the use of mediolateral episiotomy , and in the light of previous findings , it seems reasonable to suggest that episiotomy should ideally be used in about one in five spontaneous vaginal deliveries", "AIM To compare two incision angles ( 60 ° vs 40 ° ) of mediolateral episiotomy in primiparous Egyptian women , regarding the incidence of anal sphincter injury as well as episiotomy-related pain and dyspareunia . METHODS The current prospect i ve r and omized controlled trial ( Clinical Trials.gov , NCT01930721 ) was conducted at Ain Shams University Maternity Hospital . Eligible women were r and omized into two groups : group 1 included women who had the episiotomy incision made at an angle of 60 ° to the midline ; and group 2 included women who had the episiotomy incision made at an angle of 40 ° to the midline . Primary outcome measures were differences in short-term related pain and rate of third/fourth degree perineal tears . RESULTS A total of 330 primiparous women were recruited . The shortest distance to the outer edge of the anal epithelium was significantly shorter in women of group 2 when compared to that in women of group 1 . Out of the included 330 women , 13 ( 4 % ) had third/fourth-degree perineal tears ( 4 [ 2.4 % ] in group 1 in contrast to nine [ 5.5 % ] in group 2 ) . This difference was not significant A 60 ° -angled mediolateral episiotomy was associated with significantly higher rates of moderate/severe episiotomy-related pain post-partum . The rates of moderate/severe episiotomy-related pain and dyspareunia assessed 6 months post-partum were also higher among women of group 1 , when compared to group 2 ; the latter two differences did not reach statistical significance , however . CONCLUSION When compared to the 40 ° -angled mediolateral episiotomies , 60 ° -angled ones were associated with significantly higher short-term-related pain . Although they were also associated with lower rate of third/fourth-degree perineal tears and higher rate of long-term related pain and dyspareunia , these differences did not reach a statistically significant level", "OBJECTIVES Comparison of the effects of two episiotomy types on sexual activity , dyspareunia and overall satisfaction after childbirth . STUDY DESIGN A prospect i ve follow-up study of a r and omized comparative trial evaluating peripartum outcome of a vaginal delivery after mediolateral ( MLE ) or lateral ( LE ) episiotomy . MAIN OUTCOME MEASURES The participants completed question naires regarding sexual activity , dyspareunia , perineal pain , aesthetic appearance and overall satisfaction 3 ( 3 M ) and 6 months ( 6 M ) postpartum . RESULTS A total of 648 women were available for the analyses ( 306 MLE , 342 LE ) . The groups showed no difference regarding resumption and regularity of sex , timing of resumption , frequency and intensity of dyspareunia , perineal pain , aesthetic appearance or overall satisfaction 3 M or 6 M postpartum . 98.0 % of women after MLE and 97.7 % after LE resumed sexual intercourse within 6 M after delivery ( p = 0.74 ) . In the same period 15.6 % of women after MLE and 16.1 % after LE suffered from considerable dyspareunia ( p = 0.86 ) . CONCLUSIONS Quality of sexual life and perception of perineal pain after MLE is equivalent to LE", "BACKGROUND Severe perineal tears sustained during childbirth cause significant distress and morbidity amongst women . The objective of this study was to compare the use of straight scissors for cutting an episiotomy with the use of curved scissors , which are design ed to curve away from the anal sphincter . METHODS We used a single-centre , r and omised feasibility trial . The intervention was the use of curved scissors . Women were recruited during a prenatal visit and r and omised in the delivery suite , when it became clear that an episiotomy was required . The feasibility outcomes were the proportion of women able to be recruited , r and omised and followed up . We also calculated the incidence of obstetric anal sphincter injury when either straight or curved scissors were used to cut an episiotomy . Other outcomes assessed were pain , length of hospital stay , perineal infection and perineal dehiscence . RESULTS Of the 155 patients recruited in the prenatal period , only 20 ( 12.9 % ) were eventually r and omised at birth . The main reasons for the high loss were that women either did not have a vaginal delivery ( 38 , 24.5 % ) , or they did not need an episiotomy ( 72 , 46.5 % ) . Rates of obstetric anal sphincter injury and other outcomes were similar between groups . DISCUSSION Anal sphincter injury during childbirth remains an important problem . Although the use of curved scissors provides a theoretical solution , we found that the high attrition rate made feasibility of conducting a suitably powered , r and omised trial using the current design untenable . Alternative strategies have been suggested to make any future study more viable" ] "Subgroup analyses by parity ( primiparae versus multiparae ) and by surgical method ( midline versus mediolateral episiotomy ) did not identify any modifying effects . One trial examined selective episiotomy compared with routine episiotomy in women where an operative vaginal delivery was intended in 175 women , and did not show clear difference on severe perineal trauma between the restrictive and routine use of episiotomy , but the analysis was underpowered . Authors ' conclusions In women where no instrumental delivery is intended , selective episiotomy policies result in fewer women with severe perineal/vaginal trauma . Other findings , both in the short or long term , provide no clear evidence that selective episiotomy policies results in harm to mother or baby . The review thus demonstrates that believing that routine episiotomy reduces perineal/vaginal trauma is not justified by current evidence ." "Background Some clinicians believe that routine episiotomy , a surgical cut of the vagina and perineum , will prevent serious tears during childbirth . On the other h and , an episiotomy guarantees perineal trauma and sutures . Objectives To assess the effects on mother and baby of a policy of selective episiotomy ( ' only if needed ' ) compared with a policy of routine episiotomy ( ' part of routine management ' ) for vaginal births ." "29245998" [ "27705084", "18268152", "3219978", "4861009", "25315937", "15135713", "9164421", "21855289", "23740284", "27483065" ] [ "Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis.", "Effects of Levosimendan on Left Ventricular Relaxation and Early Filling at Maintained Preload and Afterload Conditions After Aortic Valve Replacement for Aortic Stenosis", "Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study", "Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial", "[Effects of levosimendan on hemodynamics and cardiac function in patients with septic shock].", "Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure.", "Myocardial efficiency during calcium sensitization with levosimendan: A noninvasive study with positron emission tomography and echocardiography in healthy volunteers", "The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock.", "Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study", "Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial." ] [ "BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis . METHODS We conducted a double-blind , r and omized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis . Patients were r and omly assigned to receive a blinded infusion of levosimendan ( at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute ) for 24 hours or placebo in addition to st and ard care . The primary outcome was the mean daily Sequential Organ Failure Assessment ( SOFA ) score in the intensive care unit up to day 28 ( scores for each of five systems range from 0 to 4 , with higher scores indicating more severe dysfunction ; maximum score , 20 ) . Secondary outcomes included 28-day mortality , time to weaning from mechanical ventilation , and adverse events . RESULTS The trial recruited 516 patients ; 259 were assigned to receive levosimendan and 257 to receive placebo . There was no significant difference in the mean ( ±SD ) SOFA score between the levosimendan group and the placebo group ( 6.68±3.96 vs. 6.06±3.89 ; mean difference , 0.61 ; 95 % confidence interval [ CI ] , -0.07 to 1.29 ; P=0.053 ) . Mortality at 28 days was 34.5 % in the levosimendan group and 30.9 % in the placebo group ( absolute difference , 3.6 percentage points ; 95 % CI , -4.5 to 11.7 ; P=0.43 ) . Among patients requiring ventilation at baseline , those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days ( hazard ratio , 0.77 ; 95 % CI , 0.60 to 0.97 ; P=0.03 ) . More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia ( 3.1 % vs. 0.4 % ; absolute difference , 2.7 percentage points ; 95 % CI , 0.1 to 5.3 ; P=0.04 ) . CONCLUSIONS The addition of levosimendan to st and ard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality . Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia . ( Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others ; LeoPARDS Current Controlled Trials number , IS RCT N12776039 . )", "Background — We determined the effects of levosimendan , a calcium sensitizer , on left ventricular ( LV ) diastolic function in patients with LV hypertrophy . Methods and Results — In this prospect i ve , r and omized , blinded study , 23 patients received either levosimendan ( 0.1 and 0.2 & mgr;g · kg−1 · min−1 ; n=12 ) or placebo ( n=11 ) after aortic valve replacement for aortic stenosis . The effects on LV performance , dimensions , filling patterns , and isovolumic relaxation time , as well as systemic hemodynamics , were assessed by pulmonary artery thermodilution catheterization and transesophageal 2-dimensional Doppler echocardiography . To circumvent the confounding effects of the levosimendan-induced hemodynamic changes on Doppler echocardiographic indexes of LV early relaxation , heart rate and mean arterial and central venous pressures were kept constant during levosimendan/placebo infusion by atrial pacing , vasopressor , and colloid infusions . In the levosimendan group , dose-dependent increases in cardiac output ( 28 % ; P<0.001 ) and stroke volume ( 26 % ; P<0.001 ) and a decrease in systemic vascular resistance ( −22 % ; P<0.001 ) were observed . There was a trend for an increase in LV ejection fraction ( 12 % ; P=0.058 ) with levosimendan . There were no significant differences in systolic , diastolic arterial , or LV filling pressures or LV end-diastolic area between the 2 groups . Isovolumic relaxation time decreased ( −23 % ; P<0.001 ) , as did the deceleration slope of early diastolic filling ( −45 % ; P<0.01 ) , whereas peak early diastolic filling velocity ( 16 % , P<0.01 ) and peak late diastolic filling velocity ( 15 % ; P<0.001 ) increased after levosimendan compared with placebo . Conclusion — Levosimendan , in addition to its inotropic effects , exerts a direct positive lusitropic effect in patients with LV hypertrophy as it shortens isovolumic relaxation time and improves LV filling", "Introduction The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug ( i.e. dobutamine ) . The primary end point was a difference of ≥ 20 % in the microvascular flow index of small vessels ( MFIs ) among groups . Methods The study was design ed as a prospect i ve , r and omized , double-blind clinical trial and performed in a multidisciplinary intensive care unit . After achieving normovolemia and a mean arterial pressure of at least 65 mmHg , 40 septic shock patients were r and omized to receive either levosimendan 0.2 μg·kg-1·min-1 ( n = 20 ) or an active comparator ( dobutamine 5 μg·kg-1·min-1 ; control ; n = 20 ) for 24 hours . Sublingual microcirculatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging . Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after r and omization . Baseline and demographic data were compared by means of Mann-Whitney rank sum test or chi-square test , as appropriate . Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test . Results Microcirculatory flow indices of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group ( 24 hrs : MFIm 3.0 ( 3.0 ; 3.0 ) vs. 2.9 ( 2.8 ; 3.0 ) ; P = .02 ; MFIs 2.9 ( 2.9 ; 3.0 ) vs. 2.7 ( 2.3 ; 2.8 ) ; P < .001 ) . The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group ( dMFIm 10 ( 3 ; 23)% vs. 0 ( -1 ; 9)% ; P = .007 ; dMFIs 47 ( 26 ; 83)% vs. 10 ( -3 ; 27 ) ; P < .001 ) . In addition , the heterogeneity index decreased only in the levosimendan group ( dHI -93 ( -100 ; -84)% vs. 0 ( -78 ; 57)% ; P < .001 ) . There was no statistically significant correlation between systemic and microcirculatory flow variables within each group ( each P > .05 ) . Conclusions Compared to a st and ard dose of 5 μg·kg-1·min-1 of dobutamine , levosimendan at 0.2 μg·kg-1·min-1 improved sublingual microcirculatory blood flow in patients with septic shock , as reflected by changes in microcirculatory flow indices of small and medium vessels . Trial registration NCT00800306", "Background We aim ed to investigate the effect of levosimendan on biomarkers of myocardial injury and systemic hemodynamics in patients with septic shock . Material / Methods After achieving normovolemia and a mean arterial pressure of at least 65 mmHg , 38 septic shock patients with low cardiac output ( left ventricular ejective fraction ) , LEVF ≤45 % ) were r and omly divided into two groups : levosimendan dobutamine . Patients in the levosimendan and dobutamine groups were maintained with intravenous infusion of levosimendan ( 0.2 μg/kg/minute ) and dobutamine ( 5 μg/kg/minute ) for 24 hours respectively . During treatment we monitored hemodynamics and LVEF , and measured levels of heart-type fatty acid binding protein ( HFABP ) , troponin I ( TNI ) , and brain natriuretic peptide(BNP ) . In addition , the length of mechanical ventilation , intensive care unit ( ICU ) stay , hospital stay , and 28-day mortality were compared between the two groups . Results The levosimendan group and the dobutamine group were well matched with respect to age ( years , 55.4±1 7.5 versus 50.2±13.6 ) and gender ( males , 68.4 % versus 57.9 % ) . Levosimendan-treated patients had higher stroke volume index ( SVI ) , cardiac index ( CI ) , LVEF , and left ventricular stroke work index ( LVSWI ) , and lower extravascular lung water index ( EVLWI ) compared to dobutamine-treated patients ( p<0.05 ) . HFABP , TNI , and BNP in the levosimendan group were less than in the dobutamine group ( p<0.05 ) . There was no difference in the mechanical ventilation time , length of stay in ICU and hospital , and 28-day mortality between the two groups . Conclusions Compared with dobutamine , levosimendan reduces biomarkers of myocardial injury and improves systemic hemodynamics in patients with septic shock . However , it does not reduce the days on mechanical ventilation , length of stay in ICU and hospital , or 28-day mortality", "OBJECTIVE To evaluate the effects of levosimendan on hemodynamics and cardiac function in patients with septic shock . METHODS A prospect i ve single-center r and omized controlled trial was conducted . The patients with septic shock admitted to the Department of Critical Care Medicine of the Third Hospital of Hebei Medical University from June 2011 to October 2013 were enrolled . The patients with septic shock received the conventional treatment according to international guidelines for management of severe sepsis and septic shock . Thirty-six patients received the examination of echocardiography and left ventricular ejection fraction (LVEF)≤ 0.45 after fluid resuscitation were enrolled the study , who were divided into two groups according to r and om number table , with 18 cases in each group . After the conventional treatment , the patients in dobutamine group received intravenous injection of 5 μg × kg⁻¹ min⁻¹ dobutamine for 48 hours immediately after fluid resuscitation , and those in levosimendan group received a 24-hour infusion of 5 μg × kg⁻¹ min⁻¹ dobutamine followed by a 24-hour infusion of 0.2 μg × kg⁻¹ × min⁻¹ levosimendan . The hemodynamics and cardiac function were evaluated by pulse indicator continuous cardiac output ( PiCCO ) and ultrasound during treatment . RESULTS Compared with dobutamine group , after the treatment in the levosimendan group , stroke volume index ( SVI ) , cardiac index ( CI ) and left ventricular stroke work index ( LVSWI ) were significantly increased [ SVI ( mL/m² ) : 39.8 ± 5.4 vs. 37.5 ± 4.5 , t=-2.762 , P=0.020 ; CI ( L × min⁻¹ × m⁻² ) : 4.6 ± 0.7 vs. 3.6 ± 0.7 , t=-9.829 , P=0.000 ; LVSWI ( kg ×min⁻ ¹ m⁻² ) : 33.7 ± 2.4 vs. 28.2 ± 1.2 , t=-6.307 , P=0.000 ] , and central venous pressure ( CVP ) , intrathoracic blood volume index ( ITBVI ) and extravascular lung water index ( EVLWI ) were significantly decreased [ CVP ( mmHg , 1 mmHg=0.133 kPa ) : 8.2 ± 0.9 vs. 12.1 ± 0.8 , t=3.928 , P=0.002 ; ITBVI ( mL/m² ) : 820 ± 42 vs. 978 ± 69 , t=9.472 , P=0.000 ; EVLWI ( mL/kg ) : 6.1 ± 1.6 vs. 8.9 ± 1.7 , t=4.467 , P=0.001 ] . Cardiac ultrasound showed that compared with dobutamine group , in the levosimendan group , left ventricular end-systolic volume ( LVESI ) and end-diastolic volume ( LVEDI ) were significantly lowered [ LVESI ( mL/m² ) : 32.7 ± 9.2 vs. 48.2 ± 13.4 , t=0.882 , P=0.000 ; LVEDI ( mL/m² ) : 61.7 ± 11.4 vs. 78.6 ± 13.6 , t=2.453 , P=0.032 ] , and the LVEF was significantly increased ( 0.463 ± 0.068 vs. 0.383 ± .085 , t=-2.439 , P=0.035 ) . Levosimendan also could decrease the lactic acid ( mmol/L : 3.4 ± 1.1 vs. 5.2 ± 1.2 , t=3.346 , P=0.007 ) , and increase the lactate clearance rate ( mL/min : 73.2 ± 13.5 vs. 47.6 ± 11.8 , t=-4.079 , P=0.002 ) , 24-hour urinary output ( mL : 2 213.4 ± 354.0 vs. 1 533.8 ± 402.0 , t=6.342 , P=0.000 ) and 24-hour cumulative intake ( mL : 5 746.6 ± 420.0 vs. 4 156.7 ± 215.0 , t=7.126 , P=0.000 ) . There were no significant differences in total volume of norepinephrine , mortality in intensive care unit ( ICU ) and 28-day mortality between two groups . CONCLUSIONS Levosimendan can increase cardiac ejection function , reduce the heart blood and vascular preload , intrathoracic lung water , improve heart function and systemic hemodynamic indexes of patients with septic shock", "This r and omized , placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators , such as soluble Fas and Fas lig and in patients with decompensated heart failure . These immunomodulatory effects may lead to improvement of symptoms and echocardiographic markers of cardiac contractile performance in these patients", "Dynamic positron emission tomography ( PET ) with [11C]acetate allows noninvasive assessment of myocardial oxygen consumption . In combination with echocardiography , PET enables determination of cardiac efficiency ( defined as useful cardiac work per unit of oxygen consumption ) . We used this approach to compare the effects of levosimendan , a Ca2+‐dependent calcium sensitizer , with dobutamine and sodium nitroprusside in healthy male volunteers . The effects of levosimendan on kmono , an index of oxygen consumption , and cardiac efficiency were neutral , whereas the hemodynamic profile was consistent with balanced inotropism and vasodilatation . Dobutamine enhanced cardiac efficiency at the expense of increased oxygen requirement , but the effects of nitroprusside on kmono and cardiac efficiency were neutral . This study shows the feasibility of PET in phase 1 pharmacodynamic studies and suggests potential energetical advantages of calcium sensitization with levosimendan", "BACKGROUND Septic shock is the leading causes of death in intensive care units . In addition to generous fluid administration , inotropic agents are commonly used to improve cardiac output . The effects of inotropic agents on regional blood flow remains unknown . OBJECTIVE The aim of this study was to assess the effects of levosimendan vs dobutamine added to dopamine on liver functions assessed using noninvasive liver function monitoring ( LiMON ) in patients with septic shock . DESIGN Prospect i ve analysis . MEASUREMENTS AND RESULTS We analyzed 30 patients with septic shock who were treated in an intensive care unit . Indocyanine green plasma disappearance rate ( ICG-PDR ) was conducted concurrently using the LiMON system . A dose of 0.3 mg/kg ICG was given through a cubital fossa vein as a bolus . RESULTS Statistical analysis showed that the variation of hemodynamic variables was different between groups . In our results , the increase in systolic blood pressure , diastolic blood pressure , and mean arterial pressure was significantly higher in levosimendan group than in dobutamine group ( P < .05 ) . There was a decrease in before- and after-infusion ICG-PDR values in dobutamine group ( 20.38 ± 4.83 vs 20.34 ± 5.30 ) , and no statistical difference was detected ( P = .649 ) . There was an increase in before- and after-infusion ICG-PDR values in levosimendan group ( 18.70 ± 2.59 vs 21.65 ± 3.20 ) , and a statistical difference was detected ( P = .001 ) . There was statistical difference between groups ( P = .000 ) . CONCLUSION These results suggest that levosimendan added to dopamine improves systemic hemodynamics and increases splanchnic perfusion assessed using the user-friendly noninvasive bedside system LiMON in patients with septic shock compared with dobutamine", "Purpose The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion . Our objective was to determine the potential benefits of dobutamine on hemodynamic , metabolic , peripheral , hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation . Methods We design ed a r and omized , controlled , double-blind , crossover study comparing the effects of 2.5-h infusion of dobutamine ( 5 mcg/kg/min fixed-dose ) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m2 and hyperlactatemia . Primary outcome was sublingual perfused microvascular density . Results Despite an increasing cardiac index , heart rate and left ventricular ejection fraction , dobutamine had no effect on sublingual perfused vessel density [ 9.0 ( 7.9–10.1 ) vs. 9.1 n/mm ( 7.9–9.9 ) ; p = 0.24 ] or microvascular flow index [ 2.1 ( 1.8–2.5 ) vs. 2.1 ( 1.9–2.5 ) ; p = 0.73 ] compared to placebo . No differences between dobutamine and placebo were found for the lactate levels , mixed venous-arterial pCO2 gradient , thenar muscle oxygen saturation , capillary refill time or gastric-to-arterial pCO2 gradient . The indocyanine green plasma disappearance rate [ 14.4 ( 9.5–25.6 ) vs. 18.8 % /min ( 11.7–24.6 ) ; p = 0.03 ] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [ 2.1 ( 1.1–3.1 ) vs. 2.5 % /s ( 1.2–3.4 ) ; p = 0.01 ] were worse with dobutamine compared to placebo . Conclusions Dobutamine failed to improve sublingual microcirculatory , metabolic , hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion", "IMPORTANCE Norepinephrine is currently recommended as the first-line vasopressor in septic shock ; however , early vasopressin use has been proposed as an alternative . OBJECTIVE To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock . DESIGN , SETTING , AND PARTICIPANTS A factorial ( 2 × 2 ) , double-blind , r and omized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015 , enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock . INTERVENTIONS Patients were r and omly allocated to vasopressin ( titrated up to 0.06 U/min ) and hydrocortisone ( n = 101 ) , vasopressin and placebo ( n = 104 ) , norepinephrine and hydrocortisone ( n = 101 ) , or norepinephrine and placebo ( n = 103 ) . MAIN OUTCOMES AND MEASURES The primary outcome was kidney failure-free days during the 28-day period after r and omization , measured as ( 1 ) the proportion of patients who never developed kidney failure and ( 2 ) median number of days alive and free of kidney failure for patients who did not survive , who experienced kidney failure , or both . Rates of renal replacement therapy , mortality , and serious adverse events were secondary outcomes . RESULTS A total of 409 patients ( median age , 66 years ; men , 58.2 % ) were included in the study , with a median time to study drug administration of 3.5 hours after diagnosis of shock . The number of survivors who never developed kidney failure was 94 of 165 patients ( 57.0 % ) in the vasopressin group and 93 of 157 patients ( 59.2 % ) in the norepinephrine group ( difference , -2.3 % [ 95 % CI , -13.0 % to 8.5 % ] ) . The median number of kidney failure-free days for patients who did not survive , who experienced kidney failure , or both was 9 days ( interquartile range [ IQR ] , 1 to -24 ) in the vasopressin group and 13 days ( IQR , 1 to -25 ) in the norepinephrine group ( difference , -4 days [ 95 % CI , -11 to 5 ] ) . There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group ( 25.4 % for vasopressin vs 35.3 % for norepinephrine ; difference , -9.9 % [ 95 % CI , -19.3 % to -0.6 % ] ) . There was no significant difference in mortality rates between groups . In total , 22 of 205 patients ( 10.7 % ) had a serious adverse event in the vasopressin group vs 17 of 204 patients ( 8.3 % ) in the norepinephrine group ( difference , 2.5 % [ 95 % CI , -3.3 % to 8.2 % ] ) . CONCLUSIONS AND RELEVANCE Among adults with septic shock , the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days . Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation , the confidence interval included a potential clinical ly important benefit for vasopressin , and larger trials may be warranted to assess this further . TRIAL REGISTRATION clinical trials.gov Identifier : IS RCT N 20769191" ] "Blood lactate was significantly reduced in the levosimendan group while there was no difference in MAP , CI , norepinephrine dose and length of ICU stay . Conclusions Findings from this meta- analysis demonstrated that levosimendan treatment may not reduce mortality in patients with septic shock ." "Object Several studies have investigated a survival benefit for levosimendan treatment in patients with septic shock . However , data are conflicting . We conducted a meta- analysis to evaluate the effect of levosimendan treatment on mortality in patients with septic shock ." "27861583" [ "19580356", "3161305", "4526947", "21406018", "5003734", "5066661", "4753582", "4529491", "4275495", "26199275", "23844570", "19246607", "19538239", "18473689", "24876589", "27417302", "19364893" ] [ "Telemedicine influence on the follow-up of type 2 diabetes patients.", "Cluster-Randomized Trial of a Mobile Phone Personalized Behavioral Intervention for Blood Glucose Control", "Telemonitoring and Mobile Phone-Based Health Coaching Among Finnish Diabetic and Heart Disease Patients: Randomized Controlled Trial", "Qualitative evaluation of a mobile phone and web-based collaborative care intervention for patients with type 2 diabetes.", "Effects of a Multicomponent Life-Style Intervention on Weight, Glycemic Control, Depressive Symptoms, and Renal Function in Low-Income, Minority Patients With Type 2 Diabetes: Results of the Community Approach to Lifestyle Modification for Diabetes Randomized Controlled Trial", "Apparent subadditivity of the efficacy of initial combination treatments for type 2 diabetes is largely explained by the impact of baseline HbA1c on efficacy", "Utilization of a Cloud-Based Diabetes Management Program for Insulin Initiation and Titration Enables Collaborative Decision Making Between Healthcare Providers and Patients", "It's LiFe! Mobile and Web-Based Monitoring and Feedback Tool Embedded in Primary Care Increases Physical Activity: A Cluster Randomized Controlled Trial", "A Mobile Health Intervention for Self-Management and Lifestyle Change for Persons With Type 2 Diabetes, Part 2: One-Year Results From the Norwegian Randomized Controlled Trial RENEWING HEALTH", "Participant experiences in a smartphone-based health coaching intervention for type 2 diabetes: A qualitative inquiry", "Active assistance technology reduces glycosylated hemoglobin and weight in individuals with type 2 diabetes: results of a theory-based randomized trial.", "Mobile communication using a mobile phone with a glucometer for glucose control in Type 2 patients with diabetes: as effective as an Internet-based glucose monitoring system", "A Ubiquitous Chronic Disease Care system using cellular phones and the internet.", "WellDoc mobile diabetes management randomized controlled trial: change in clinical and behavioral outcomes and patient and physician satisfaction.", "Mobile Diabetes Intervention for Glycemic Control", "A nurse‐led interdisciplinary approach to promote self‐management of type 2 diabetes: a process evaluation of post‐intervention experiences", "Evaluation of a mobile phone telemonitoring system for glycaemic control in patients with diabetes" ] [ "OBJECTIVE This study was design ed to evaluate the impact of a teleassistance system on the metabolic control of type 2 diabetes patients . RESEARCH DESIGN AND METHODS We conducted a 1-year controlled parallel-group trial comparing patients r and omized ( 1 ) to an intervention group , assigned to a teleassistance system using real-time transmission of blood glucose results , with immediate reply when necessary , and telephone consultations , or ( 2 ) to a control group , being regularly followed-up at their healthcare center . Study subjects were type 2 diabetes patients > 30 years of age followed in the primary care setting . RESULTS A total of 328 type 2 diabetes patients were recruited from 35 family practice s in the province of Málaga , Spain . There was a reduction in hemoglobin A1c after 12 months from 7.62 + /- 1.60 % to 7.40 + /- 1.43 % ( P = 0.027 ) in the intervention group and from 7.44 + /- 1.31 % to 7.35 + /- 1.38 % ( P = 0.303 ) in the control group . The difference in the change between groups was not statistically significant . There was also a significant decrease in systolic and diastolic blood pressure , total cholesterol , low-density lipoprotein cholesterol , and body mass index in the intervention group . In the control group , the only significant decline was in low-density lipoprotein cholesterol . CONCLUSIONS A teleassistance system using real-time transmission of blood glucose results with an option to make telephone consultations is feasible in the primary care setting as a support tool for family physicians in their follow-up of type 2 diabetes patients", "OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year", "Background There is a strong will and need to find alternative models of health care delivery driven by the ever-increasing burden of chronic diseases . Objective The purpose of this 1-year trial was to study whether a structured mobile phone-based health coaching program , which was supported by a remote monitoring system , could be used to improve the health-related quality of life ( HRQL ) and /or the clinical measures of type 2 diabetes and heart disease patients . Methods A r and omized controlled trial was conducted among type 2 diabetes patients and heart disease patients of the South Karelia Social and Health Care District . Patients were recruited by sending invitations to r and omly selected patients using the electronic health records system . Health coaches called patients every 4 to 6 weeks and patients were encouraged to self-monitor their weight , blood pressure , blood glucose ( diabetics ) , and steps ( heart disease patients ) once per week . The primary outcome was HRQL measured by the Short Form ( 36 ) Health Survey ( SF-36 ) and glycosylated hemoglobin ( HbA1c ) among diabetic patients . The clinical measures assessed were blood pressure , weight , waist circumference , and lipid levels . Results A total of 267 heart patients and 250 diabetes patients started in the trial , of which 246 and 225 patients concluded the end-point assessment s , respectively . Withdrawal from the study was associated with the patients ’ unfamiliarity with mobile phones — of the 41 dropouts , 85 % ( 11/13 ) of the heart disease patients and 88 % ( 14/16 ) of the diabetes patients were familiar with mobile phones , whereas the corresponding percentages were 97.1 % ( 231/238 ) and 98.6 % ( 208/211 ) , respectively , among the rest of the patients ( P=.02 and P=.004 ) . Withdrawal was also associated with heart disease patients ’ comorbidities—40 % ( 8/20 ) of the dropouts had at least one comorbidity , whereas the corresponding percentage was 18.9 % ( 47/249 ) among the rest of the patients ( P=.02 ) . The intervention showed no statistically significant benefits over the current practice with regard to health-related quality of life — heart disease patients : beta=0.730 ( P=.36 ) for the physical component score and beta=-0.608 ( P=.62 ) for the mental component score ; diabetes patients : beta=0.875 ( P=.85 ) for the physical component score and beta=-0.770 ( P=.52 ) for the mental component score . There was a significant difference in waist circumference in the type 2 diabetes group ( beta=-1.711 , P=.01 ) . There were no differences in any other outcome variables . Conclusions A health coaching program supported with telemonitoring did not improve heart disease patients ' or diabetes patients ' quality of life or their clinical condition . There were indications that the intervention had a differential effect on heart patients and diabetes patients . Diabetes patients may be more prone to benefit from this kind of intervention . This should not be neglected when developing new ways for self-management of chronic diseases . Trial Registration Clinical Trials.gov NCT01310491 ; http:// clinical trials.gov/ct2/show/NCT01310491 ( Archived by WebCite at http://www.webcitation.org/6Z8l5FwAM )", "BACKGROUND Drawing on previous web-based diabetes management programs based on the Chronic Care Model , we exp and ed an intervention to include care management through mobile phones and a game console web browser . METHODS The pilot intervention enrolled eight diabetes patients from the University of Washington in Seattle into a collaborative care program : connecting them to a care provider specializing in diabetes , providing access to their full electronic medical record , allowing wireless glucose uploads and e-mail with providers , and connecting them to the program 's web services through a game system . To evaluate the study , we conducted qualitative thematic analysis of semistructured interviews . RESULTS Participants expressed frustrations with using the cell phones and the game system in their everyday lives , but liked the wireless system for collaborating with a provider on uploaded glucoses and receiving automatic feedback on their blood sugar trends . A majority of participants also expressed that their participation in the trial increased their health awareness . DISCUSSION Mobile communication technologies showed promise within a web-based collaborative care program for type 2 diabetes . Future intervention design should focus on integrating easy-to-use applications within mobile technologies already familiar to patients and ensure the system allows for sufficient collaboration with a care provider", "Objective Few interventions have combined life-style and psychosocial approaches in the context of Type 2 diabetes management . The purpose of this study was to determine the effect of a multicomponent behavioral intervention on weight , glycemic control , renal function , and depressive symptoms in a sample of overweight/obese adults with Type 2 diabetes and marked depressive symptoms . Methods A sample of 111 adults with Type 2 diabetes were r and omly assigned to a 1-year intervention ( n = 57 ) or usual care ( n = 54 ) in a parallel groups design . Primary outcomes included weight , glycosylated hemoglobin , and Beck Depression Inventory II score . Estimated glomerular filtration rate served as a secondary outcome . All measures were assessed at baseline and 6 and 12 months after r and omization by assessors blind to r and omization . Latent growth modeling was used to examine intervention effects on each outcome . Results The intervention result ed in decreased weight ( mean [ M ] = 0.322 kg , st and ard error [ SE ] = 0.124 kg , p = .010 ) and glycosylated hemoglobin ( M = 0.066 % , SE = 0.028 % , p = .017 ) , and Beck Depression Inventory II scores ( M = 1.009 , SE = 0.226 , p < .001 ) , and improved estimated glomerular filtration rate ( M = 0.742 ml·min−1·1.73 m−2 , SE = 0.318 ml·min−1·1.73 m−2 , p = .020 ) each month during the first 6 months relative to usual care . Conclusions Multicomponent behavioral interventions targeting weight loss and depressive symptoms as well as diet and physical activity are efficacious in the management of Type 2 diabetes . Trial Registration : This study is registered at Clinical trials.gov ID : NCT01739205", "Aim To explain the subadditive efficacy typically observed with initial combination treatments for type 2 diabetes . Methods Individual subject data from 1186 patients with type 2 diabetes [ mean glycated haemoglobin ( HbA1c ) = 8.8 % ] treated with metformin , canagliflozin or canagliflozin + metformin were used . The baseline HbA1c versus ΔHbA1c relationships for monotherapy arms were determined using analysis of covariance and then used to predict efficacy in the combination arms by modelling how applying one treatment lowers the ‘ effective baseline HbA1c ’ for a second treatment . The model was further tested using data from several published combination studies . Results The mean ΔHbA1c levels were −1.25 , −1.33 , −1.37 , −1.77 and −1.81 % with metformin , canagliflozin 100 mg , canagliflozin 300 mg , canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin , respectively . Using the monotherapy results , the predicted efficacy for the canagliflozin/metformin arms was within 10 % of the observed values using the new model , whereas assuming simple additivity overpredicted efficacy in the combination arms by nearly 50 % . For 10 other published initial combination studies , predictions from the new model [ mean ( st and ard error ) predicted ΔHbA1c = 1.67 % ( 0.14 ) ] were much more consistent with observed values [ ΔHbA1c = 1.72 % ( 0.12 ) ] than predictions based on assuming additivity [ predicted ΔHbA1c = 2.19 % ( 0.21 ) ] . Conclusions The less‐than‐additive efficacy commonly seen with initial combination treatments for type 2 diabetes can be largely explained by the impact of baseline HbA1c on the efficacy of individual treatments . Novel formulas have been developed for predicting the efficacy of combination treatments based on the efficacy of individual treatments and the baseline HbA1c of the target patients", "Abstract Background : Overseeing proper insulin initiation and titration remains a challenging task in diabetes care . Recent advances in mobile technology have enabled new models of collaborative care between patients and healthcare providers ( HCPs ) . We hypothesized that the adoption of such technology could help individuals starting basal insulin achieve better glycemic control compared with st and ard clinical practice . Material s and Methods : This was a 12 ± 2-week r and omized controlled study with 40 individuals with type 2 diabetes who were starting basal insulin due to poor glycemic control . The control group ( n = 20 ) received st and ard face-to-face care and phone follow-up as needed in a tertiary center , whereas the intervention group ( n = 20 ) received care through the cloud-based diabetes management program where regular communications about glycemic control and insulin doses were conducted via patient self-tracking tools , shared decision-making interfaces , secure text messages , and virtual visits ( audio , video , and shared screen control ) instead of office visits . Results : By intention-to-treat analysis , the intervention group achieved a greater hemoglobin A1c decline compared with the control group ( 3.2 ± 1.5 % vs. 2.0 % ± 2.0 % ; P = 0.048 ) . The Diabetes Treatment Satisfaction Question naire showed a significant improvement in the intervention group compared with the control group ( an increase of 10.1 ± 11.7 vs. 2.1 ± 6.5 points ; P = 0.01 ) . HCPs spent less time with patients in the intervention group compared with those in the control group ( 65.9 min per subject vs. 81.6 min per subject ) . However , the intervention group required additional training time to use the mobile device . Conclusions : Mobile health technology could be an effective tool in sharing data , enhancing communication , and improving glycemic control while enabling collaborative decision making in diabetes care", "Background Physical inactivity is a major public health problem . The It ’s LiFe ! monitoring and feedback tool embedded in the Self-Management Support Program ( SSP ) is an attempt to stimulate physical activity in people with chronic obstructive pulmonary disease or type 2 diabetes treated in primary care . Objective Our aim was to evaluate whether the SSP combined with the use of the monitoring and feedback tool leads to more physical activity compared to usual care and to evaluate the additional effect of using this tool on top of the SSP . Methods This was a three-armed cluster r and omised controlled trial . Twenty four family practice s were r and omly assigned to one of three groups in which participants received the tool + SSP ( group 1 ) , the SSP ( group 2 ) , or care as usual ( group 3 ) . The primary outcome measure was minutes of physical activity per day . The secondary outcomes were general and exercise self-efficacy and quality of life . Outcomes were measured at baseline after the intervention ( 4 - 6 months ) , and 3 months thereafter . Results The group that received the entire intervention ( tool + SSP ) showed more physical activity directly after the intervention than Group 3 ( mean difference 11.73 , 95 % CI 6.21 - 17.25 ; P<.001 ) , and Group 2 ( mean difference 7.86 , 95 % CI 2.18 - 13.54 ; P=.003 ) . Three months after the intervention , this effect was still present and significant ( compared to Group 3 : mean difference 10.59 , 95 % CI 4.94 - 16.25 ; P<.001 ; compared to Group 2 : mean difference 9.41 , 95 % CI 3.70 - 15.11 ; P<.001 ) . There was no significant difference in effect between Groups 2 and 3 on both time points . There was no interaction effect for disease type . Conclusions The combination of counseling with the tool proved an effective way to stimulate physical activity . Counseling without the tool was not effective . Future research about the cost-effectiveness and application under more tailored conditions and in other target groups is recommended . Trial Registration Clinical Trials.gov : NCT01867970 , https:// clinical trials.gov/ct2/show/NCT01867970 ( archived by WebCite at http://www.webcitation.org/6a2qR5BSr )", "Background Self-management is crucial in the daily management of type 2 diabetes . It has been suggested that mHealth may be an important method for enhancing self-management when delivered in combination with health counseling . Objective The objective of this study was to test whether the use of a mobile phone – based self-management system used for 1 year , with or without telephone health counseling by a diabetes specialist nurse for the first 4 months , could improve glycated hemoglobin A1c ( HbA1c ) level , self-management , and health-related quality of life compared with usual care . Methods We conducted a 3-arm prospect i ve r and omized controlled trial involving 2 intervention groups and 1 control group . Eligible participants were persons with type 2 diabetes with an HbA1c level ≥7.1 % ( ≥54.1 mmol/mol ) and aged ≥18 years . Both intervention groups received the mobile phone – based self-management system Few Touch Application ( FTA ) . The FTA consisted of a blood glucose – measuring system with automatic wireless data transfer , diet manual , physical activity registration , and management of personal goals , all recorded and operated using a diabetes diary app on the mobile phone . In addition , one intervention group received health counseling based on behavior change theory and delivered by a diabetes specialist nurse for the first 4 months after r and omization . All groups received usual care by their general practitioner . The primary outcome was HbA1c level . Secondary outcomes were self-management ( heiQ ) , health-related quality of life ( SF-36 ) , depressive symptoms ( CES-D ) , and lifestyle changes ( dietary habits and physical activity ) . Data were analyzed using univariate methods ( t test , ANOVA ) and multivariate linear and logistic regression . Results A total of 151 participants were r and omized : 51 to the FTA group , 50 to the FTA-health counseling ( FTA-HC ) group , and 50 to the control group . Follow-up data after 1 year were available for 120 participants ( 79 % ) . HbA1c level decreased in all groups , but did not differ between groups after 1 year . The mean change in the heiQ domain skills and technique acquisition was significantly greater in the FTA-HC group after adjusting for age , gender , and education ( P=.04 ) . Other secondary outcomes did not differ between groups after 1 year . In the FTA group , 39 % were substantial users of the app ; 34 % of the FTA-HC group were substantial users . Those aged ≥63 years used the app more than their younger counterparts did ( OR 2.7 ; 95 % CI 1.02 - 7.12 ; P=.045 ) . Conclusions The change in HbA1c level did not differ between groups after the 1-year intervention . Secondary outcomes did not differ between groups except for an increase in the self-management domain of skill and technique acquisition in the FTA-HC group . Older participants used the app more than the younger participants did", "Introduction We investigated the experience of individuals diagnosed with type 2 diabetes mellitus ( T2DM ) who participated in an intervention in which the key elements were the provision of a smartphone and self-monitoring software . The interviews focused on use of a smartphone and the effects on motivation for health behavior change . Methods This was a qualitative evaluation of participants in a larger T2DM self-management r and omized controlled trial ( RCT ) conducted at the Black Creek Community Health Centre ( BCCHC ) in Toronto , Canada ( Clinical Trials.gov Identifier : NCT02036892 ) . The study is based on semi-structured interviews ( n = 11 ) that were audio taped and analyzed with a thematic analytic approach . The RCT compared the effectiveness of six months of smartphone-based self-monitoring and health coaching with a control group who received health coaching without internet or smartphone-based assistance . Results Qualitative data analyses result ed in derivation of four major themes that describe participant experience : ( a ) ‘ smartphone and software ’ , describes smartphone use in relation to health behavior change ; ( b ) ‘ health coach ’ describes how client/health coach relationships were assisted by smartphone use ; ( c ) ‘ overall experience ’ describes perceptions of the overall intervention ; and ( d ) ‘ frustrations in managing chronic conditions ’ describes difficulties with the complexities of T2DM management from a patient perspective . Discussion Findings suggest that interventions with T2DM assisted by smartphone software and health coaches actively engage individuals in improved hemoglobin A1c ( HbA1c ) control", "BACKGROUND Type 2 diabetes is an individual health challenge requiring ongoing self-management . Remote patient reporting of relevant health parameters and linked automated feedback via mobile telephone have potential to strengthen self-management and improve outcomes . This research involved development and evaluation of a mobile telephone-based remote patient reporting and automated telephone feedback system , guided by health behavior change theory , aim ed at improving self-management and health status in individuals with type 2 diabetes . SUBJECTS AND METHODS This research comprised a r and omized controlled trial . Inclusion criteria were diagnosis of type 2 diabetes , elevated glycosylated hemoglobin ( HbA1c ) levels ( range , 6.5 - 11 % ) or use of oral diabetes medication , and 30 - 70 years of age . Intervention subjects ( n=24 ) participated in remote patient reporting of health status parameters and linked health behavior change feedback . Control participants ( n=24 ) received st and ard of care including diabetes education and healthcare provider counseling . Patients were followed for approximately 10 months . RESULTS Intervention participants achieved , compared with controls and controlling for baseline , a significantly greater mean reduction in HbA1c of -0.40 % ( 95 % confidence interval [ CI ] -0.67 % to -0.14 % ) versus 0.036 % ( 95 % CI -0.23 % to 0.30 % ) ( P<0.03 ) and significantly greater weight reduction of -2.1 kg ( 95 % CI -3.6 to -0.6 kg ) versus 0.4 kg ( 95 % CI -1.1 to 1.9 kg ) . Nonsignificant trends for greater intervention compared with control improvement in systolic and diastolic blood pressure were observed . CONCLUSIONS Sophisticated information technology platforms for remote patient reporting linked with theory-based health behavior change automated feedback have potential to improve patient outcomes in type 2 diabetes and merit scaled-up research efforts", "A mobile phone with a glucometer integrated into the battery pack ( the ‘ Diabetes Phone ’ ) was launched in Korea in 2003 . We compared its effect on management of type 2 diabetes to the Internet-based glucose monitoring system ( IBGMS ) , which had been studied previously . We conducted a r and omized trial involving 69 patients for three months . Participants were assigned to an Internet group or a phone group . The phone group communicated with medical staff through the mobile phone only . Their glucose-monitoring data were automatically transferred to individual , web-based charts and they received medical recommendations by short message service . The Internet group used the IBGMS . There were no significant differences between the groups at baseline . After three months ' intervention , HbA1c levels of both groups had decreased significantly , from 7.6 % to 6.9 % for the Internet group and from 8.3 % to 7.1 % for the phone group ( P < 0.01 ) . Levels of patient satisfaction and adherence to medical advice were similar . Mobile , bidirectional communication between doctors and patients using the diabetes phone was as effective for glucose control as the previously-studied Internet-based monitoring system and it was good for patient satisfaction and adherence", "AIMS The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide . To improve the quality and efficiency of chronic disease care , we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care ( UCDC ) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension . METHODS We conducted a r and omized , controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre . RESULTS After 12 weeks , there were significant improvements in HbA(1c ) in the intervention group ( 7.6 + /- 0.9 % to 7.1 + /- 0.8 % , P < 0.001 ) compared with the control group ( 7.4 + /- 0.9 % to 7.6 + /- 1.0 % , P = 0.03 ) . Furthermore , we observed a significant reduction in systolic and diastolic blood pressure , as well as improvements in total cholesterol , low-density lipoprotein-cholesterol and triglyceride levels in the intervention group . Furthermore , there was a significant increase in adiponectin levels in the intervention group compared with the control group , although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group . CONCLUSIONS The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension", "BACKGROUND Less than 63 % of individuals with diabetes meet professional guidelines target of hemoglobin A1c < 7.0 % , and only 7 % meet combined glycemic , lipid , and blood pressure goals . The primary study aim was to assess the impact on A1c of a cell phone-based diabetes management software system used with web-based data analytics and therapy optimization tools . Secondary aims examined health care provider ( HCP ) adherence to prescribing guidelines and assessed HCPs ' adoption of the technology . METHODS Thirty patients with type 2 diabetes were recruited from three community physician practice s for a 3-month study and evenly r and omized . The intervention group received cell phone-based software design ed by endocrinologists and CDEs ( WellDoc Communications , Inc. , Baltimore , MD ) . The software provided real-time feedback on patients ' blood glucose levels , displayed patients ' medication regimens , incorporated hypo- and hyperglycemia treatment algorithms , and requested additional data needed to evaluate diabetes management . Patient data captured and transferred to secure servers were analyzed by proprietary statistical algorithms . The system sent computer-generated logbooks ( with suggested treatment plans ) to intervention patients ' HCPs . RESULTS The average decrease in A1c for intervention patients was 2.03 % , compared to 0.68 % ( P < 0.02 , one-tailed ) for control patients . Of the intervention patients , 84 % had medications titrated or changed by their HCP compared to controls ( 23 % , P = 0.002 ) . Intervention patients ' HCPs reported the system facilitated treatment decisions , provided organized data , and reduced logbook review time . CONCLUSIONS Adults with type 2 diabetes using WellDoc 's software achieved statistically significant improvements in A1c . HCP and patient satisfaction with the system was clinical ly and statistically significant", "Background : Of adults with type 2 diabetes , 84 % take antihyperglycemic medication . Successful treatment requires active monitoring and medication dose adjustment by health providers . The objective of this study was to determine how a mobile-phone-based coaching system for diabetes management influences physician prescribing behavior . Method : This secondary data analysis is based on a cluster r and omized clinical trial that reported patients provided with mobile self-management had reduction in glycated hemoglobin ( HbA1c ) of 1.9 % over 1 year , compared to 0.7 % in control patients ( P < .001 ) . Participants were primary care patients with type 2 diabetes r and omized at physician practice level into a control group ( n = 55 ) and intervention group ( n = 62 ) . Main study measures were patients ’ medication records ( medication , dose , frequency , start and end date ) abstract ed at baseline and study end . Antihyperglycemic medications , including sulfonylureas or thiazolidinediones , and antihypertensive and antilipemic medications were analyzed . Results : A higher percentage of patients in the intervention group had modification and intensification of incretin mimetics during the 1-year study period ( 9.7 % vs 0.0 % and 8.1 % vs 0.0 % , both P = .008 ) . A higher percentage of patients in the intervention group had modification and intensification of metformin ( 24.2 % vs 7.3 % , P = .033 ) . The overall difference in physician prescribing of oral antihyperglycemic medications was not statistically significant . Conclusions : Our results suggest mobile diabetes interventions can encourage physicians to modify and intensify antihyperglycemic medications in patients with type 2 diabetes . Differences in physician prescribing behavior were modest , and do not appear to be large enough to explain a 1.2 % decrease in HbA1c", "RATIONALE , AIMS AND OBJECTIVES Self-management of type 2 diabetes through diet , exercise and for many medications , are vital in achieving and maintaining glycaemic control in type 2 diabetes . A number of interventions have been design ed to improve self-management , but the outcomes of these are rarely explored from a qualitative angle and even fewer through a process evaluation . METHOD A process evaluation was conducted using a qualitative design with participants r and omized to an intervention . Seventy-three people living with type 2 diabetes and hyperglycaemia for a minimum of 1 year , r and omized to one of two interventions ( n = 34 to an education intervention and n = 39 to an education and acceptance and commitment therapy intervention ) completed stage one of the process evaluation , immediately following the intervention through written feedback guided by open-ended questions . A purposive sample of 27 participants completed semi-structured interviews at 3 and 6 months post intervention . Interview data were transcribed and data analysed using a thematic analysis . RESULTS The majority of participants described an increase in knowledge around diabetes self-management and an increased sense of personal responsibility . Participants also described changes in self-management activities and reflected on the challenges in instigating and maintaining change to improve diabetes management . CONCLUSION The complexities of implementing change in daily life to improve glycaemic control indicate the need for ongoing support post intervention , which may increase and maintain the effectiveness of the intervention", "We conducted a r and omized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes . Patients in the intervention group ( n = 72 ) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link . Clinicians were then able to examine and respond to the readings which were viewed with a web-based application . Patients in the control arm of the study ( n = 65 ) did not transmit their readings and received care with their usual doctor in the outpatient and /or primary care setting . The mean follow-up period was 9 months in each group . The default rate was higher in the patients in the intervention arm due to technical problems . In an intention-to-treat analysis there were no differences in HbA1c between the intervention and control groups . In a sub-group analysis of the patients who completed the study , the telemonitoring group had a lower HbA1c than those in the control group : 7.76 % and 8.40 % , respectively ( P = 0.06 )" ] "No effects of mHealth app interventions were found on blood pressure , serum lipids , or weight . Smartphone apps offered moderate benefits for T2DM self-management ." "BACKGROUND Mobile health interventions ( mHealth ) based on smartphone applications ( apps ) are promising tools to help improve diabetes care and self-management ; however , more evidence on the efficacy of mHealth in diabetes care is needed . The objective of this study was to conduct a systematic review and meta- analysis of r and omized controlled trials ( RCTs ) assessing the effect of mHealth apps on changes in hemoglobin A1c ( HbA1c ) , blood glucose , blood pressure , serum lipids , and body weight in type 2 diabetes mellitus ( T2DM ) patients ." "28835875" [ "2599891", "15472162", "22385446", "7327728", "12956787", "2670950", "23678838", "20630527" ] [ "Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale", "Old or frail: what tells us more?", "Outcomes of elderly patients with proximal femoral fractures according to positive criteria for surgical treatment.", "The treatment of unstable intertrochanteric fractures of the hip: a prospective trial of 150 cases.", "Methodological index for non‐randomized studies (MINORS): development and validation of a new instrument", "Operative or conservative treatment for trochanteric fractures of the femur. A randomised epidemiological trial in elderly patients.", "Mortality among third age patients with hip fracture and high cardiac risk.", "One-year outcome for elderly patients with displaced intracapsular fractures of the femoral neck managed non-operatively." ] [ "Background Research ers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values . However , the assumptions of r and om utility theory , which underpin the statistical models used to provide these estimates , have received insufficient attention . In particular , the assumptions made about the decisions between living states and the death state are not satisfied , at least for some people . Estimated values are likely to be incorrectly anchored with respect to death ( zero ) in such circumstances . Methods Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument ( ICECAP ) valuation exercise were analysed . The values ( previously anchored to the worst possible state ) were rescaled using an ordinal model proposed previously to estimate QALY-like values . Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional r and om utility model underpinning the analyses . Results Only 26 % of respondents conformed unequivocally to the assumptions of conventional r and om utility theory . At least 14 % of respondents unequivocally violated the assumptions . Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values , particularly for lower-valued states . As a result these values could be either positive ( considered to be better than death ) or negative ( considered to be worse than death ) . Conclusion Use of a statistical model such as conditional ( multinomial ) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional r and om utility theory . This is clearest when estimating values for that group of respondents observed in valuation sample s who refuse to consider any living state to be worse than death : in such circumstances the model can not be estimated . Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents", "BACKGROUND Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics . Chronological age , although often used , does not seem to be the best selection criterion . Instead , the concept of frailty , which indicates several concurrent losses in re sources , can be used . METHODS The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older , r and omly drawn from the register of six municipalities in the northern regions of the Netherl and s ( 45 % of the original addressees ) . The participants ' generative capacity to sustain well-being ( i.e. , self-management abilities ) was used as the main outcome measure . RESULTS When using chronological age instead of frailty , both too many and too few persons were selected . Furthermore , frailty related more strongly ( with beta values ranging from -.25 to -.39 ) to a decline in the participants ' self-management abilities than did chronological age ( with beta values ranging from -.06 to -.14 ) . Chronological age added very little to the explained variances of all outcomes once frailty was included . CONCLUSIONS Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age", "Proximal femoral fractures in elderly patients are a serious problem in the aging society . Recently , surgical indications have changed due to advancements in medical technology . The purpose of this study was to investigate the outcome of elderly patients with displaced proximal hip fractures according to our positive criteria for surgical treatment . Exclusion criteria included ( 1 ) terminal-stage malignancy ; ( 2 ) a combination of an inability to walk , a severe mental disorder , and caregiver refusal of surgery ; and ( 3 ) nonapproval of the anesthesiologist for surgery . The study group comprised 666 elderly patients . They were categorized into surgically and nonsurgically treated groups , and their treatment outcomes were retrospectively analyzed . The majority of patients were treated surgically ( 97.0 % vs 3.0 % ) . One-year survival rate was higher among surgically treated patients ( 82.2%-91.8 % ) than non-surgically treated patients ( 55 % ) . The major cause of death in nonsurgically treated patients was deterioration of comorbidities ( 66.7 % ) , whereas this was the cause of death in 18.9 % of surgically treated patients . One-year survival rates were worse in both groups with a lower American Society of Anesthesiologists grade . The 1-year survival rate of our patients suggests that our surgical criteria offer a reasonable outcome in surgically and nonsurgically treated patients . American Society of Anesthesiologists grade and preexisting comorbidities were strongly correlated with patient outcome", "We report a prospect i ve clinical trial of 150 cases for the treatment of unstable intertrochanteric fracture of the neck of the femur . Three methods were tested in our series -- skeletal traction with a tibial pin , medial displacement osteotomy and valgus osteotomy -- with 50 patients in each group . Our results showed no significant difference between those treated with the Dimon and Hughston osteotomy and those treated by the Sarmiento osteotomy . Conservative treatment of skeletal traction for unstable fracture was found to be well tolerated by the Chinese patient . A low mortality and morbidity rate was found in this series with an overall infection rate of 4 per cent", "Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument", "All elderly patients with extracapsular hip fractures seen in hospitals in Newcastle upon Tyne over a 12-month period were studied and followed up for six months . At one of the hospitals , patients were r and omised to treatment by AO dynamic hip-screw or by traction . Complications specific to the two treatments were low , and general complications , six-month mortality and prevalence of pain , leg swelling and unhealed sores , showed no difference between the two modes of treatment . Operative treatment gave better anatomical results and a shorter hospital stay , but significantly more of the patients treated by traction showed loss of independence six months after injury", "INTRODUCTION Mortality after hip fracture remains high in spite of the progress of medicine . Due to the trend toward longer life , the problem of hip fracture is getting more significant . The aim of this study is to determine the effects of surgical treatment in patients with high risk of hip fracture on mortality reduction . METHODS In the retrospective- prospect i ve study , 66 patients aged 65 - 92 with a hip fracture and a high cardiac risk have been analyzed . The risk estimation was based on the Lee index . The patients with three or more risk factors were considered high-risk . The first group consisted of surgically treated patients with a hip fracture and at high cardiac risk , and in the second group were conservatively treated patients with a hip fracture and high cardiac risk . RESULTS In the group of conservatively treated patients , 75 % were women and in operatively treated group 67.6 % . Patient in both group are similar in relation to the participation of risk factor . A difference has been noticed in terms of renal insufficiency ( RI ) . There was 18.8 % conservatively treated patient with RI and 2.9 % in operatively treated group . CONCLUSION Patients with hip fracture and at high cardiac risk have lower mortality when treated surgically", "The outcome of patients with a displaced intracapsular femoral neck fracture treated non-operatively was assessed at 1 year and compared with patients managed operatively over the same time period . Data were collected prospect ively for 102 consecutive patients . 80 patients underwent hemiarthroplasty and 22 were managed non-operatively . Patients were managed non-operatively if they were felt to have an unacceptably high risk of death within the perioperative period despite medical optimisation . Non-operative management entailed active early mobilisation without bed rest or traction . Patients managed non-operatively had a greater 30-day mortality compared with operatively managed patients . Deaths were due to pre-existing medical conditions or events , which had occurred at the time of hip fracture . No patient in the non-operative treatment group developed pneumonia , pressure sores or thrombo-embolic events . Patients treated non-operatively , who survived 30 days after fracture , had a mortality rate over the following year comparable with those who had undergone surgery . At 1 year , all non-operatively managed patients were able to transfer without pain and 6 of the 11 surviving patients were able to mobilise with walking aids . At 1 year , the majority of surviving non-operatively managed patients were living in their own homes . Surgical intervention is the treatment of choice for the majority of elderly patients with a displaced intracapsular femoral neck fracture . However , in patients with life-threatening medical co-morbidity , non-operative treatment with early mobilisation can yield acceptable results" ] "A significantly higher 30-day and 1-year mortality was revealed in nonoperatively treated hip fracture patients . No data were found examining (HR)QOL and costs ." "Introduction : Increasing numbers of patients with hip fractures also have advanced comorbidities . A majority are treated surgically . However , a significantly increasing percentage of medically unfit patients with unacceptably high risk of perioperative death are treated nonoperatively . Important questions about patients ’ prefracture quality of life ( QOL ) and future perspectives should be asked before considering different treatment options to assess what kind of treatment is advisable in frail elderly high-risk patients with a hip fracture . Objective : The aim of this review was to provide an overview of differences in mortality , health-related QOL [ (HR)QOL ] , functional outcome , and costs between nonoperative management ( NOM ) and operative management ( OM ) of hip fractures in patients above 65 years ." "22133697" [ "9469675", "19595578", "18824954", "9860108", "18374841", "19542525", "16585435", "19011428", "10192829", "7871035", "20099987", "15641867", "18803070", "16172203", "16633144", "9659858", "8935809", "18007569", "8981383", "15121646", "19890230", "15465981", "15650846", "19375893", "12088164", "9690695", "12177583", "10771448", "19026256", "16199834" ] [ "The effect of timing of a standard meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic agent ziprasidone.", "Factors influencing the choice of new generation antipsychotic medication in the treatment of patients with schizophrenia", "Therapeutic Drug Monitoring of Ziprasidone in a Clinical Treatment Setting", "Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial", "Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial", "Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial.", "Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic.", "Striatal and Extrastriatal D2/D3-Receptor-Binding Properties of Ziprasidone: A Positron Emission Tomography Study With [18F]Fallypride and [11C]Raclopride (D2/D3-Receptor Occupancy of Ziprasidone)", "Ziprasidone 80 mg/day and 160 mg/day in the Acute Exacerbation of Schizophrenia and Schizoaffective Disorder: A 6-Week Placebo-Controlled Trial", "Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride", "Effects of Oral Ziprasidone and Oral Haloperidol on QTc interval in patients with Schizophrenia or Schizoaffective disorder.", "Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial.", "Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic schizophrenia: A 12-week open-label, multicentre clinical trial", "Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.", "A 24-Week Randomized Study of Olanzapine Versus Ziprasidone in the Treatment of Schizophrenia or Schizoaffective Disorder in Patients with Prominent Depressive Symptoms", "5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation.", "The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography", "The effect of food on the absorption of oral ziprasidone.", "A PET Study of 5-HT2 and D2 Dopamine Receptor Occupancy Induced by Olanzapine in Healthy Subjects", "A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone.", "Ziprasidone in Black patients with schizophrenia: analysis of four short-term, double-blind studies.", "Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.", "Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study", "Effect of ziprasidone dose on all-cause discontinuation rates in acute schizophrenia and schizoaffective disorder: A post-hoc analysis of 4 fixed-dose randomized clinical trials", "A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia", "An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder.", "A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study", "Single- and multiple-dose pharmacokinetics of ziprasidone under non-fasting conditions in healthy male volunteers.", "The impact of calories and fat content of meals on oral ziprasidone absorption: a randomized, open-label, crossover trial.", "Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia." ] [ "STUDY OBJECTIVE To evaluate the influence of a high-fat meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic drug ziprasidone . DESIGN Open , r and omized , three-way crossover study . SETTING University-based research facility . SUBJECTS Eight healthy male volunteers . INTERVENTIONS Ziprasidone 20 mg was administered under fasting conditions ( treatment A ) , and directly after ( treatment B ) and 2 hours after ( treatment C ) a st and ard high-fat breakfast . MEASUREMENTS AND MAIN RESULTS Serial blood sample s were obtained over 36 hours . Three objective psychometric tests were employed to evaluate daytime vigilance at baseline and 2 hours after each dose . Ziprasidone had a significant effect on area under the curve ( AUC0-infinity ) , maximum serum concentration , and half-life ( analysis of variance all p<0.05 ) , with the mean AUC0-infinity being significantly greater ( 627.2 + /- 206.4 vs 371.0 + /- 126.5 ng x hr/ml , ANOVA with Bonferroni 's criteria p<0.016 ) and half-life significantly shorter ( 4.7 + /- 0.8 vs 6.6 + /- 1.3 hrs , ANOVA with Bonferroni 's criteria p<0.016 ) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A , the differences did not reach statistical significance when Bonferroni 's correction criteria were applied ( p>0.016 ) . CONCLUSION These data suggest an increase in systemic exposure to the highly lipophilic compound ziprasidone when taken after fatty foods , possibly due to improved drug dissolution and solubilization . The drug 's longer half-life under fasting conditions may reflect dissolution-limited absorption , although this could not be directly assessed . Despite postpr and ial increases in ziprasidone AUC0-infinity and maximum concentration , daytime vigilance was not affected", "OBJECTIVE This prospect i ve , naturalistic study investigated the factors influencing physicians ' choice of antipsychotic drug therapy in the treatment of patients with schizophrenia . METHOD 108 in- and out patients treated at the Department of Psychiatry of the Medical University Innsbruck who started treatment with a new generation antipsychotic ( except clozapine ) were included . The following factors were investigated : sociodemographic and illness-related variables , pretreatment , the reasons for change of treatment ( lack of efficacy , side effects , non-compliance ) , side effects of pretreatment and body-mass-index ( BMI ) . RESULTS Sociodemographic and most illness-related variables did not have an influence on the physicians ' choice of medication . Risperidone was more frequently prescribed in patients with severe positive symptoms than amisulpride or quetiapine . Rigidity , orthostatic dizziness and gynecomastia during pretreatment were frequently associated with starting patients on ziprasidone . In patients with diminished sexual desire ziprasidone was preferred over olanzapine . Amisulpride was used more commonly than olanzapine if patients had experienced weight gain during pretreatment . Moreover , patients who were prescribed amisulpride had a significantly higher BMI in comparison to patients who were prescribed olanzapine . The reasons for current change of treatment , as well as the drug history ( total number of antipsychotic drugs prescribed during the course of the illness ) did not have an influence on the physicians ' choice of antipsychotic . CONCLUSION In summary , the data suggest that side effects have a larger influence on the choice of antipsychotic than demographic or illness-related variables , except the severity of positive symptoms", "There is limited information on the pharmacokinetics of ziprasidone ( ZIP ) in naturalistic clinical setting s. The objective of this study was to investigate the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone ( SMDZ ) , and the dose-normalized concentrations , using routine therapeutic drug monitoring ( TDM ) data . A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linköping , Sweden . This analytical service was available to all physicians in Sweden . Between January 2001 and December 2004 , 545 analyses , representing sample s from 370 patients , were performed . The median daily ZIP dose was 120 mg ( range 20 -320 mg ) . In all , 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation . The median ( 25th to 75th percentile ) serum concentration of ZIP was 125 nmol/L ( 82 - 188 nmol/L ) . The SMDZ : ZIP ratio decreased with increasing serum concentration of ZIP . The median ( 25th to 75th percentile ) dose-normalized concentrations ( nmol L−1 mg−1 d−1 ) for ZIP and SMDZ were 1.13 ( 0.74 - 1.77 ) and 0.62 ( 0.45 - 0.86 ) , respectively , with SMDZ : ZIP ratio of 0.57 ( 0.42 - 0.79 ) . The overall coefficients of variation for dose-normalized serum concentrations of ZIP , SMDZ , and SMDZ : ZIP ratio were 62 % , 56 % , and 57 % , respectively ( n = 121 ) . Smoking women had lower normalized ZIP concentrations than nonsmoking women . Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time . In summary , great interindividual and intraindividual differences in ZIP concentrations were observed . TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence", "Abstract A double-blind , placebo-controlled , multicenter study , was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder . Patients were r and omized to receive ziprasidone 40 mg/day , 120 mg/day or placebo for 28 days . Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total , CGI-S , BPRS depression cluster and BPRS anergia cluster scores ( all P < 0.05 ) . Similarly , the percentages of patients classified as responders on the BPRS ( ≥30 % reduction ) and the CGI improvement ( score ≤2 ) were significantly greater with ziprasidone 120 mg/day compared with placebo ( P < 0.05 ) . The number of patients who experienced an adverse event was similar in all three treatment groups , and discontinuation due to adverse events was rare ( five of 91 ziprasidone-treated patients ) . The most frequently reported adverse events , that were more common in either ziprasidone group than in the placebo group , were dyspepsia , constipation , nausea and abdominal pain . There was a notably low incidence extrapyramidal side-effects ( including akathisia ) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain . Ziprasidone-treated patients were not clinical ly different from placebo-treated patients on the Simpson-Angus Rating scale , Barnes Akathisia scale and AIMS assessment s. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive , negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden", "BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement", "INTRODUCTION Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions . The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia . METHODS The study was an 8-week , double-blind , parallel-group , r and omized , controlled multicenter trial ( NCT00145444 ) . Seventy-six patients with schizophreniform disorder , schizophrenia or schizoaffective disorder ( diagnosis < 5 y ) , and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study . Efficacy of ziprasidone ( 80 - 160 mg/d ) and olanzapine 10 - 20 mg was measured using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression ( CGI ) Scale , the Calgary Depression Scale for Schizophrenia ( CDSS ) , and the Heinrich Quality of Life Scale ( HQLS ) ; tolerability assessment s included laboratory assessment s , body weight , and electroencephalogram . RESULTS Olanzapine ( n = 34 ) and ziprasidone ( n = 39 ) showed equal efficacy as measured by the PANSS , CDSS , CGI , and HQLS . However , mean weight gain was significantly higher in the olanzapine group ( 6.8 vs 0.1 kg , P < .001 ) . Ziprasidone was associated with decreasing levels of triglycerides , cholesterol , and transaminases , while these parameters increased in the olanzapine group ( all P values < .05 ) . There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects . Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently ( P < .05 ) . DISCUSSION The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile . However , there is a risk of a type II error with this sample size . Clinical ly significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine , while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms", "BACKGROUND In the treatment of schizophrenia , changing antipsychotics is common when one treatment is suboptimally effective , but the relative effectiveness of drugs used in this strategy is unknown . This r and omized , double-blind study compared olanzapine , quetiapine , risperidone , and ziprasidone in patients who had just discontinued a different atypical antipsychotic . METHOD Subjects with schizophrenia ( N=444 ) who had discontinued the atypical antipsychotic r and omly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) investigation were r and omly reassigned to double-blind treatment with a different antipsychotic ( olanzapine , 7.5 - 30 mg/day [ N=66 ] ; quetiapine , 200 - 800 mg/day [ N=63 ] ; risperidone , 1.5 - 6.0 mg/day [ N=69 ] ; or ziprasidone , 40 - 160 mg/day [ N=135 ] ) . The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason . RESULTS The time to treatment discontinuation was longer for patients treated with risperidone ( median : 7.0 months ) and olanzapine ( 6.3 months ) than with quetiapine ( 4.0 months ) and ziprasidone ( 2.8 months ) . Among patients who discontinued their previous antipsychotic because of inefficacy ( N=184 ) , olanzapine was more effective than quetiapine and ziprasidone , and risperidone was more effective than quetiapine . There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability ( N=168 ) . CONCLUSIONS Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic , risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason", "To eluci date the \" atypicality \" of ziprasidone , its striatal and extrastriatal D2/D3-receptor binding was characterized in patients with schizophrenia under steady-state conditions . These data were compared with striatal receptor occupancy values after single-dose ziprasidone ingestion in healthy controls . [18F]fallypride positron emission tomography ( PET ) recordings were obtained in 15 patients under steady-state ziprasidone treatment at varying time points after the last dose . Binding potentials were calculated for striatal and extrastriatal regions . D2/D3-receptor occupancies were expressed relative to binding potentials in 8 unmedicated patients . In a parallel [11C]raclopride-PET study , striatal D2/D3-receptor occupancy was measured in healthy subjects after single oral doses of 40 mg ziprasidone or 7.5 mg haloperidol . Ziprasidone plasma concentrations correlated significantly with D2/D3-receptor occupancies in all volumes of interests . Occupancy in extrastriatal regions was approximately 10 % higher than in striatal regions . Half maximal effective concentration values were consistently higher in striatal than in extrastriatal regions ( temporal cortex : 39 ng/mL ; putamen : 64 ng/mL ) , irrespective of the time between last dosing and scan . Single ziprasidone doses result ed in higher occupancies exceeding the 95 % prediction limits of the occupancy versus plasma concentrations for chronic dosing . Ziprasidone shares moderate preferential extrastriatal D2/D3-receptor binding with some other atypicals . D2/D3-receptor occupancy is rapidly attuning to the daily course of ziprasidone plasma levels , suggesting relatively high intraday variations of D2/D3-receptor binding . The discrepancies between single-dose and steady-state results are important for the future design of dose-finding PET occupancy studies of novel antipsychotics . Single-dose studies may not be totally relied on for final dose selection", "In this double-blind study , patients with an acute exacerbation of schizophrenia or schizoaffective disorder were r and omized to receive either ziprasidone 80 mg/day ( n = 106 ) or 160 mg/day ( n = 104 ) or placebo ( n = 92 ) , for 6 weeks . Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total , BPRS total , BPRS core items , CGI-S , and PANSS negative subscale scores ( p < .05 ) . Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinical ly significant depression at baseline ( MADRS ≥ 14 , over-all mean 23.5 ) ( p < .05 ) as compared with placebo . The percentage of patients experiencing adverse events was similar in each treatment group , and result ant discontinuation was rare . The most frequent adverse events associated with ziprasidone were generally mild dyspepsia , nausea , dizziness , and transient somnolence . Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain . The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive , negative , and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder", "Positron emission tomography ( PET ) and 11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic , CP-88,059 - 1 . In a double blind dose escalation study , seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059 - 1 , 5 h before PET scanning . One additional subject was assigned to placebo predose . Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied . Binding of11C-raclopride decreased in a dose dependent manner , and 85 % dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059 - 1 . The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059 - 1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg . The study highlights the potential of positron emission tomography in the pre clinical evaluation of new drugs", "STUDY OBJECTIVE To characterize the effect of oral ziprasidone and haloperidol on the corrected QT ( QTc ) interval under steady-state conditions . Design . Prospect i ve , r and omized , open-label , parallel-group study . SETTING Inpatient clinical research facility . Patients Fifty-nine adults ( age range 25 - 59 yrs ) with schizophrenia or schizoaffective disorder who had no clinical ly significant abnormality on electrocardiogram ( ECG ) at screening . Intervention . During period 1 ( days -10 to -4 ) , antipsychotic and anticholinergic drugs were tapered . On the first day ( day -3 ) of period 2 , the drugs were discontinued , and placebo was given for the next 3 days ( days -2 to 0 ) . On the last day ( day 0 ) of period 2 , serial baseline ECGs were collected . During period 3 ( days 1 - 16 ) , patients received escalating oral doses of ziprasidone and haloperidol to reach steady state . Period 4 ( days 17 - 19 ) allowed for study drug washout and initiation of outpatient antipsychotic therapy ; safety assessment s were also performed during this period . MEASUREMENTS AND RESULTS At each steady-state dose level , three ECGs and a serum or plasma sample were collected at the predicted time of peak exposure to the administered drug . Point estimates and 95 % confidence intervals ( CIs ) were determined for the mean QTc interval at baseline and for the mean change from baseline in QTc at each steady-state dose level . Mean changes from baseline in the QTc interval ( msec ) for ziprasidone were 4.5 ( 95 % CI 1.9 - 7.1 ) , 19.5 ( 95 % CI 15.5 - 23.4 ) , and 22.5 ( 95 % CI 15.7- 29.4 ) for steady-state doses of 40 , 160 , and 320 mg/day , respectively ; for haloperidol , -1.2 ( 95 % CI -4.1 - 1.7 ) , 6.6 ( 95 % CI 1.6 - 11.7 ) , and 7.2 ( 95 % CI 1.4 - 13.1 ) for steady-state doses of 2.5 , 15 , and 30 mg/day . Although no patient in either treatment group experienced a QTc interval of 450 msec or greater , the QTc interval increased 30 msec or more in 11 and 17 ziprasidone-treated patients at 160 and 320 mg/day , respectively , and in 3 and 5 haloperidol-treated patients at 15 and 30 mg/day , respectively . Most treatment-emergent adverse drug reactions were mild in intensity , and none were severe . CONCLUSION The QTc interval in ziprasidone- and haloperidol-treated patients increased with dose . Treatment with high doses of ziprasidone or haloperidol did not result in any patient experiencing a QTc interval of 450 msec or greater", "BACKGROUND More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds . Thus , we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder . METHOD Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were r and omly assigned to double-blind ziprasidone 40 to 80 mg b.i.d . ( N = 149 ) or risperidone 3 to 5 mg b.i.d ( N = 147 ) for 8 weeks . Primary efficacy measures included Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score ; secondary measures included scores on the PANSS negative sub-scale , CGI-Improvement scale ( CGI-I ) , and PANSS-derived Brief Psychiatric Rating Scale ( BPRSd ) total and core items . Safety assessment s included movement disorder evaluations , laboratory tests , electrocardiography , vital signs , and body weight . Efficacy analyses employed a prospect ively defined Evaluable Patients cohort . Treatment equivalence was conferred if the lower limit of the 95 % confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60 . Data were gathered from August 1995 to January 1997 . RESULTS Equivalence was demonstrated in PANSS total scores , CGI-S scores , PANSS negative subscale scores , BPRSd total and core item scores , and PANSS total and CGI-I responder rates . Both agents were well tolerated . Risperidone exhibited a significantly higher Movement Disorder Burden ( MDB ) score ( p < .05 ) and higher incidences of prolactin elevation and clinical ly relevant weight gain . However , compared with current recommendations , study dosing may have been high for some risperidone-treated patients ( mean dose = 7.4 mg/day ) and low for some ziprasidone-treated patients ( mean dose = 114.2 mg/day ) . CONCLUSION Both agents equally improved psychotic symptoms , and both were generally well tolerated , with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone", "The efficacy , safety and tolerability of ziprasidone versus the comparators olanzapine , risperidone or quetiapine were investigated in adult patients with chronic schizophrenia , schizoaffective and schizophreniform disorders , with lack of efficacy or intolerance to their previous antipsychotic treatment based on clinical judgement of the investigator . A total of 293 patients were r and omized to 12 weeks treatment with either ziprasidone 80–160 mg/day ( n=147 ) or with one of the comparator drugs ( n=146 ) . In the latter group the investigator could choose between olanzapine 10–20 mg/day ( n=24 ) , risperidone 4–8 mg/day ( n=22 ) or quetiapine 300–750 mg/day ( n=97 ) . The study comprised four visits including a baseline examination prior to r and omization and further examinations at the end of weeks 1 , 4 and 12 . Ziprasidone was non-inferior ( defined as a difference of = 7 units or less on the PANSS scale to the disadvantage of ziprasidone . ) to the composite group ( olanzapine , risperidone or quetiapine ) on the total PANSS score as well as on all subscores ( P<0.0001 ) ; there were no significant between-group differences in the CGI-S and I and UKU scores . Ziprasidone-treated patients lost an average of 2.1 kg in the 12 weeks of the study , the mean weight for risperidone and quetiapine remained unchanged , and patients receiving olanzapine gained 3.1 kg on average", "BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism", "Objective : The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms . Methods : This r and omized , double-blind , 24-week , fixed-dose study compared olanzapine ( n = 202 ) and ziprasidone ( n = 192 ) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms . Outcome measures included change in Calgary Depression Scale for Schizophrenia ( CDSS ) score from baseline to 8 weeks ( primary outcome ) and changes in CDSS , Montgomery-Åsberg Depression Rating Scales , Positive and Negative Syndrome Scale , and Global Assessment of Functioning ( GAF ) scores for 24 weeks . Statistical analyses included mixed-effects model repeated measures ( primary analysis ) and change from baseline to last observation carried forward ( LOCF ) . Results : At baseline , patients had moderate depressive symptoms ( mean Montgomery-Åsberg Depression Rating Scales total score , 27.3 ) . For 8 weeks , patients treated with olanzapine or ziprasidone had significant improvements on CDSS . Treatment group differences were not statistically significant ( P = 0.493 , mixed-effects model repeated measures ; P = 0.497 , LOCF ) . For 24 weeks , olanzapine-treated patients showed significantly greater improvements in depressive symptoms ( results varied by depression measure and statistical approach ) and GAF ( P < 0.017 , LOCF ) . A significantly higher proportion of olanzapine-treated patients completed the study ( 44.6 % vs 29.7 % ; P = 0.003 ) and remained longer on medication ( median , 163 vs 73 days , P < 0.001 ) , compared with ziprasidone-treated patients . Olanzapine-treated patients experienced significantly ( P < 0.05 ) greater increases in triglycerides , HgbA1c , and weight . Conclusions : For 24 weeks , olanzapine-treated patients had greater and more sustained participation in treatment , during which time significantly greater improvements were observed in depressive symptoms and GAF scores , along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients", "OBJECTIVE Olanzapine is a new atypical antipsychotic recently introduced for the treatment of schizophrenia . The purpose of this study was to investigate olanzapine 's binding to the serotonin 5-HT2 and dopamine D2 receptors in schizophrenic patients being treated with clinical ly relevant doses . METHOD Twelve patients with schizophrenia were r and omly assigned to 5 , 10 , 15 , or 20 mg/day of olanzapine in a prospect i ve fashion . Three other subjects taking 30 - 40 mg/day were also included . Once steady-state plasma levels were achieved , dopamine D2 and serotonin 5-HT2 receptors were assessed by using [11C]raclopride and [18F]setoperone positron emission tomography imaging , respectively . Ratings of clinical status , extrapyramidal side effects , and prolactin levels were also obtained . RESULTS Olanzapine induced near saturation of the 5-HT2 receptors , even at 5 mg/day . Its D2 occupancy increased with dose : patients taking 5 - 20 mg/day showed 43%-80 % D2 occupancy , while patients taking 30 - 40 mg/day showed 83%-88 % . CONCLUSIONS Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses . However , its D2 occupancy is higher than that of clozapine and similar to that of risperidone . In the usual clinical dose range of 10 - 20 mg/day , its occupancy varies from 71 % to 80 % , and this restricted range may explain its freedom from extrapyramidal side effects and prolactin elevation . However , doses of 30 mg/day and higher are associated with more than 80 % D2 occupancy and may have a higher likelihood of prolactin elevation and extrapyramidal side effects", "Positron emission tomography ( PET ) and 11C-raclopride were used to assess the time course of binding to central dopamine D2 receptors by the novel neuroleptic ziprasidone . In a third party blind study , six healthy male control subjects received a predose of 40 mg ziprasidone and were scanned at an interval of between 4 and 36 h post-dose . One additional subject was assigned to placebo predose and was scanned at 4 h post-dose . Binding potential ( BP ) was compared with that seen in the subject predosed with placebo and with that seen in nine unmedicated normal volunteers . Subjects studied up to 12 h post-dose had BPs that were greater than 2 SD less than the mean BP , indicative of extensive D2 receptor binding by ziprasidone . With increasing time between dosing and PET scanning there was a curvilinear increase in BP , so that all studies performed at or after 18 h post-dose gave BPs in the normal range ( mean±2 SD ) . Elevated prolactin levels returned to within the normal range by 18 h post-dose . PET measures of binding potential correlated significantly with serum levels of ziprasidone at the time of scanning and less significantly with absolute prolactin levels at the same time", "Oral ziprasidone bioavailability is increased when taken with food . Here we describe two pharmacokinetic studies to quantify the impact of food on ziprasidone absorption in healthy volunteers . The first , an open-label , six-way crossover study , investigated ziprasidone absorption in eight healthy men . Subjects received oral ziprasidone ( 20 , 40 , and 80 mg ) after an 8-hour fast or immediately following a US Food and Drug Administration st and ard meal ( 50 % fat ) . In this study , area under the serum concentration- time curve ( AUC ) was greater in fed than in fasting states at each dose ( 20 mg , + 48 % ; 40 mg , + 87 % ; 80 mg , + 101 % ) . Under fasting conditions , increases in AUC and maximum drug concentration ( Cmax ) were less than dose-proportional ; under fed conditions , they were dose-proportional . The second , an open-label , r and omized , three-way crossover study , explored the impact of dietary fat on ziprasidone absorption in 14 healthy subjects . Subjects received ziprasidone ( 40 mg ) under three conditions : fasting , with a high-fat meal ( 60 % fat ) , and with a moderate-fat ( 30 % fat ) meal . AUC and Cmax under fed conditions increased by 104 % and 84 % ( 60%-fat meal ) and 79 % and 98 % ( 30%-fat meal ) , respectively , relative to the fasting state . There was no clear difference in ziprasidone bioavailability between the fed groups , suggesting that meal fat content is not a major determinant of bioavailability . Less pharmacokinetic variability was observed in the fed state , suggesting more consistent absorption of ziprasidone . These results demonstrate that administration of ziprasidone with food is crucial to ensure optimal , reliable dose-dependent bioavailability and thus predictable symptom control and tolerability", "Olanzapine is a new antipsychotic drug with affinity for 5-HT2 , D2 , D1 , and muscarinic receptors . Positron emission tomography and the radiolig and s [11C]raclopride and [11C]NMSP were used to measure D2 and 5-HT2 receptor occupancy in three healthy subjects after 10 mg olanzapine orally . After seven hours D2 receptor occupancy was 63 % , 62 % and 59 % , respectively . After 9.5 hours 5-HT2 receptor occupancy was 74 % , 86 % and 92 % . D2 and 5-HT2 receptor occupancy was comparable to that found in patients continuously treated with clozapine . Clinical efficacy has been demonstrated for olanzapine in the dose range 5 to 15 mg per day . Extrapolation from our present observations after a 10 mg single-dose suggest , that at the lower end of the clinical ly examined dose range the D2 and 5-HT2 receptor occupancy should be similar to that induced by st and ard doses of clozapine . Detailed evaluation of the dose-response characteristics of olanzapine and direct clinical comparison to clozapine will thus provide valuable leads to the clarification of atypical antipsychotic action", "OBJECTIVE Ziprasidone is an atypical antipsychotic drug that shows a higher affinity for serotonin 5-HT(2 ) receptors compared with dopamine D(2 ) receptors in vitro . The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography ( PET ) study . METHOD The authors conducted a PET study to evaluate D(2 ) occupancy ( using [(11)C]raclopride ) and 5-HT(2 ) occupancy ( using [(18)F]setoperone ) in brain regions of interest in 16 patients with schizophrenia or schizoaffective disorder r and omly assigned to receive 40 , 80 , 120 , or 160 mg/day of ziprasidone , which reflected the recommended dose range . PET scanning was done after 3 weeks of administration and at trough plasma levels , i.e. , 12 - 16 hours after the last dose . RESULTS The mean 5-HT(2 ) receptor occupancy was significantly higher than the mean D(2 ) receptor occupancy ( mean=76 % , SD=15 % , and mean=56 % , SD=18 % , respectively ) . The estimated plasma ziprasidone concentration associated with 50 % maximal 5-HT(2 ) receptor occupancy was almost four times lower than that for D(2 ) receptor occupancy . CONCLUSIONS These data affirm that ziprasidone is similar to other novel antipsychotics in having greater 5-HT(2 ) than D(2 ) receptor occupancy at therapeutic doses and suggest that the optimal effective dose of ziprasidone is closer to 120 mg/day than to the lower doses suggested by previous PET studies . The relatively high D(2 ) receptor occupancy , even at trough plasma levels , suggests that ziprasidone is more similar to risperidone and olanzapine in receptor occupancy profile than to clozapine and quetiapine . Since ziprasidone plasma levels show significant ( more than twofold ) variation within a single dose cycle , studies that are aim ed at peak plasma levels ( 6 hours after the last dose ) and that examine extrastriatal regions are required to fully characterize the in vivo occupancy profile of ziprasidone", "OBJECTIVE To better underst and the efficacy and tolerability of atypical antipsychotics among racial groups , we review ed data from four short-term ( 4 - 6 weeks ) , fixed-dose , placebo-controlled trials of ziprasidone for black , white , and overall population s of patients with schizophrenia . METHODS Efficacy of ziprasidone in the black , white , and overall schizophrenic population s was compared to placebo using st and ard efficacy measures ( Positive and Negative Syndrome Scale [ PANSS ] total , PANSS negative , Brief Psychiatric Rating Scale [ BPRS ] , Clinical Global Impression-Severity [ CGI-S ] , CGI-Improvement [ CGI-I ] ) . RESULTS Black patients receiving ziprasidone demonstrated statistically significant improvements from baseline in PANSS total , PANSS negative , and BPRS , and improvements in CGI-S and CGI-I ( n=99 - 149 ) compared with placebo ( n=41 - 66 ) ; improvements were comparable to those observed in the overall population ( n=451 - 639 ) and the white population ( n=310 - 430 ) . Interaction effect ( treatment by race ) was not significant for any efficacy variables . Ziprasidone was well-tolerated among black patients ( n=175 ) . Adjusted mean ( least squares mean ) overall weight gain in black patients receiving ziprasidone ( n=124 ) was 1.8 kg . There were no increases in total cholesterol , triglycerides , or r and om glucose in the black population . CONCLUSION Ziprasidone has similar efficacy and safety in black patients with schizophrenia compared with patients in the white and overall population", "OBJECTIVE Limited r and omized , controlled trial data exist on possible differences between atypical antipsychotics in efficacy , overall tolerability , and important indices of health status . The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill in patients with schizophrenia or schizoaffective disorder . METHOD In this 6-week , multicenter , double-blind , parallel- design , flexible-dose trial , patients were r and omly assigned to receive ziprasidone ( N=136 ) or olanzapine ( N=133 ) . Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression ( CGI ) severity scale scores ; secondary measures were scores on the CGI improvement scale , Positive and Negative Syndrome Scale , and Calgary Depression Scale for Schizophrenia . Tolerability assessment s included fasting lipid profiles , fasting glucose and insulin measurements , electrocardiography , and monitoring of vital signs and body weight . RESULTS The overall mean daily doses were 129.9 mg ( SD=27.3 ) for ziprasidone and 11.3 mg ( SD=2.8 ) for olanzapine . Both antipsychotics were efficacious in improving symptoms and global illness severity . The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis . Both agents were well tolerated . Body weight , total cholesterol , triglycerides , and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone ; all between-group comparisons of these variables were significant and favored ziprasidone . Olanzapine , but not ziprasidone , was associated with significant increases in fasting insulin level . No patient in either group exhibited a corrected QT interval > /=500 msec . CONCLUSIONS During 6 weeks ' treatment , ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy . Differences favoring ziprasidone were observed in metabolic parameters", "Rationale Conventional intramuscular ( IM ) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia . Objectives To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder . Methods In a 6-week , multicenter , parallel-group , flexibly dosed study , patients were r and omized to ziprasidone ( IM up to 3 days , then oral 40–80 mg , b.i.d . ) or haloperidol ( IM up to 3 days , then oral 5–20 mg/day ) . Assessment s were rater-blinded . Results At the end of IM treatment , patients receiving ziprasidone ( n=427 ) showed significantly improved Brief Psychiatric Rating Scale Total ( BPRS total ) scores compared with those receiving haloperidol ( n=138 ) [ least-squares ( LS ) mean change −6.14 for ziprasidone versus −4.13 for haloperidol , P<0.0018 ] . At endpoint , there were no significant between-group differences in BPRS total scores . There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients , both at the end of IM treatment ( LS mean change −1.15 for ziprasidone and −0.28 for haloperidol , P<0.0001 ) and at study endpoint ( LS mean change −2.94 for ziprasidone and −2.24 for haloperidol , P<0.0001 ) . Haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint ( P<0.0001 ) . They also had significantly higher ratings on the Barnes Akathisia Scale ( P<0.0001 ) and the Movement Disorder Burden Score ( P<0.005 ) , as well as higher incidences of movement disorder-related adverse events . Conclusions Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia", "BACKGROUND Higher dose ziprasidone has been associated with improved treatment outcomes in patients with schizophrenia or schizoaffective disorder . This study examines the relationship of ziprasidone dose and all-cause discontinuation in r and omized clinical trials in patients with an acute exacerbation of schizophrenia or schizoaffective disorder . METHOD Data were analyzed for the first 28 days from 4 pivotal , r and omized , double-blind , fixed-dose ziprasidone trials . Patients in these trials had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder where ziprasidone was administered twice daily with food . Data were analyzed to examine the association between ziprasidone dose and all-cause discontinuation due to lack of efficacy , adverse events , or because of other reasons , relative to placebo . Differences in discontinuation were evaluated using Cox proportional hazard models and number needed to treat ( NNT ) . RESULTS All-cause discontinuation for ziprasidone ranged from a low of 26.9 % for the 160 mg/d dose group , to 40.9 % for the 40 mg/d and 45.5 % for the 80 mg/d groups , compared with 49.5 % for placebo . The NNTs for avoiding 1 additional all-cause discontinuation compared with placebo were 12 ( 40 mg/d ; n=186 ) , 25 ( 80 mg/d ; n=154 ) , 9 ( 120 mg/d ; n=125 ) , and 4 ( 160 mg/d ; n=104 ) . The 120 mg/d and 160 mg/d groups were the only ziprasidone regimens associated with significantly lower all-cause discontinuation rates versus placebo in both the survival analysis ( p=0.031 and < 0.0001 , respectively ) and in examination of the NNT . The 160 mg/d group was associated with lower all-cause discontinuation rates versus lower-dose ziprasidone regimens ( p=0.0158 for versus 40 mg/d , p=0.002 for versus 80 mg/d ) . Efficacy accounted for 51 % of all medication discontinuations across ziprasidone groups , compared with 62 % for placebo . Findings for overall discontinuation due to lack of efficacy are consistent with results for all-cause discontinuation . CONCLUSIONS Consistent with previous reports , higher doses of ziprasidone ( 120 - 160 mg/d , dosed twice daily with meals ) are associated with significantly lower all-cause discontinuation rates and more favorable NNTs versus placebo . This was primarily driven by lower rates of discontinuation due to lack of efficacy", "BACKGROUND Ziprasidone is a novel antipsychotic with a unique pharmacologic profile . This study compared ziprasidone with the conventional antipsychotic haloperidol in out patients with stable schizophrenia . METHOD Three hundred one out patients with stable chronic or subchronic schizophrenia ( DSM-III-R ) were r and omized and participated in this double-blind , multicenter , parallel-group clinical study comparing flexible-dose oral ziprasidone , 80 - 160 mg/day ( N = 148 ) , with haloperidol , 5 - 15 mg/day ( N = 153 ) , over 28 weeks . Patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Severity of Illness scale , the Montgomery-Asberg Depression Rating Scale , the Simpson-Angus Scale , the Barnes Akathisia Scale , and the Abnormal Involuntary Movement Scale . RESULTS Modal doses at endpoint were 80 mg/day for ziprasidone and 5 mg/day for haloperidol . Improvements in all mean efficacy variables with both ziprasidone and haloperidol were observed . Significantly more patients were categorized as negative symptom responders ( > or = 20 % reduction in PANSS negative subscale score ) in the ziprasidone group ( 48 % ) compared with the haloperidol group ( 33 % ) ( p < .05 ) . Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders . Changes in body weight were negligible with both treatments . No pattern of laboratory or cardiovascular changes was observed . CONCLUSION Ziprasidone and haloperidol were both effective in reducing overall psychopathology ; ziprasidone demonstrated effective treatment of negative symptoms and was better tolerated than haloperidol . Ziprasidone appears to offer an effective alternative to haloperidol in the long-term treatment of stable out patients with schizophrenia", "Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind , exploratory , dose-ranging trial . After a single-blind washout period of 4 to 7 days , patients were r and omly assigned to receive one of four fixed doses of the new antipsychotic , ziprasidone 4 ( N = 19 ) , 10 ( N = 17 ) , 40 ( N = 17 ) , or 160 ( N = 20 ) mg/day or haloperidol 15 mg/day ( N = 17 ) for 4 weeks . A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity ( CGI-S ) score ( p = 0.002 ) but not in Brief Psychiatric Rating Scale ( BPRS ) total score ( p = 0.08 ) . The intent-to-treat analysis of mean changes from baseline in the BPRS total , BPRS Psychosis core , and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day . Despite the small sample size and short duration of the trial , the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day ( p = 0.001 and p = 0.005 , respectively ) . The percentage of patients classified as responders on both the BPRS total ( > or = 30 % improvement ) and CGI-Improvement ( score of 1 or 2 ) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group . On all assessment s of clinical efficacy , the improvements associated with ziprasidone 4 mg/day , 10 mg/day , and 40 mg/day were similar . Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day ( 15 % ) than with haloperidol ( 53 % ) . Haloperidol was associated with a sustained hyperprolactinemia , unlike ziprasidone , where only transient elevations in prolactin that returned to normal within the dosing interval were observed . Ziprasidone was well tolerated , and the incidence of adverse events was similar in all groups . The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms", "We evaluated relapse in patients with stable , chronic schizophrenia over a 1-year period ; in patients were r and omized to ziprasidone 40 mg/day ( n = 72 ) , 80 mg/day ( n = 68 ) , 160 mg/day ( n = 67 ) or placebo ( n = 71 ) . The probability of relapse ( Kaplan – Meier ) at 1 year was significantly lower in the ziprasidone 40 , 80 , and 160 mg/day groups ( 43 % , 35 % and 36 % , respectively ) compared to placebo ( 77%;P = 0.002 , P < 0.001 and P < 0.001 , respectively ) . In those patients who remained on treatment for at least 6 months , only 9 % subsequently relapsed on ziprasidone compared to 42 % on placebo ( P = 0.001 ) . All three doses of ziprasidone were significantly superior to placebo on Positive and Negative Syndrome Scale ( PANSS ) efficacy variables ( all P < 0.05 ) . Ziprasidone was associated with a significantly greater mean improvement in the PANSS negative symptom subscale compared to placebo ( P < 0.05 ) . Discontinuation due to adverse events was similar with ziprasidone and placebo . Ziprasidone treatment was indistinguishable from placebo in assessment s of movement disorders and was not associated with weight gain or cardiovascular abnormalities . These results demonstrate that ziprasidone was effective in reducing the frequency of relapse and was associated with long-term improvement in negative symptoms . Ziprasidone was well tolerated in this population of patients with chronic , stable schizophrenia", "AIMS To evaluate the pharmacokinetics and tolerability of single and multiple oral doses of ziprasidone in healthy male volunteers , and to determine the influence of ziprasidone on serum prolactin levels . METHODS Single and multiple doses of ziprasidone were given orally ( as two divided daily doses ) , at fixed dosages of 10 and 40 mg day(-1 ) , and using titrated regimens of 40 - 80 and 40 - 120 mg day(-1 ) , for 14 days . All dosages were taken immediately after food . The study adopted a r and omized , double-blind , placebo-controlled design . Prolactin response , sedative properties , tolerability , and extrapyramidal symptoms were also investigated . RESULTS Steady-state exposure to ziprasidone was attained after 1 day of dosing . Mean Cmax and AUC(0,12 h ) increased with increasing dose , with apparent dose-proportionality between the 20 and 60 mg dose levels . Trough-to-peak ratios at steady state ranged from 2 to 5 . Accumulation ratios for the fixed-dose regimens were 1.49 and 1.48 at the 5 and 20 mg dose levels , respectively . Ziprasidone was associated with transient prolactin elevation but levels of prolactin returned to baseline within the dosing interval at steady state . There was a marginal , transient increase in serum prolactin levels which was not dose-related at the 80 and 120 mg day(-1 ) doses , and which was noted to attenuate with chronic dosing . Ziprasidone was generally well tolerated . The most frequent side-effect was mild or moderate headache . A minority of patients suffered first-dose postural hypotension . Ziprasidone was also associated with a mild sedative effect that became less pronounced as treatment continued . There were no drug-related changes in electrocardiogram or clinical laboratory variables that were of clinical importance . CONCLUSIONS Ziprasidone is characterized by a predictable pharmacokinetic profile result ing in symptoms that reflect its pharmacological action", "BACKGROUND Food is known to increase the bioavailability of ziprasidone . Therefore , we evaluated the effects of meals of differing caloric and fat content on steady-state ziprasidone exposure in a stable , treated group of subjects with DSM-IV diagnoses of schizophrenia , schizoaffective disorder , bipolar disorder , or psychotic disorder ( not otherwise specified ) who were already receiving oral ziprasidone as their st and ard therapy . METHOD Patients took ziprasidone under 6 meal conditions in r and omized sequences ( fasted , low calorie/low fat , low calorie/high fat , medium calorie/high fat , high calorie/low fat , and high calorie/high fat ) ; each crossover period was separated by at least 3 days for washout of the previous meal condition . Serial blood sample s were obtained over the 12 hours postdose . The study was conducted from July 27 to September 28 of 2006 . RESULTS Maximum ziprasidone exposures in this study were observed with high-calorie meals ( 1000 kcal ) , which were nearly twice those observed under fasting conditions . The medium-calorie meal ( 500 kcal ) was associated with exposures similar to the high-calorie meals . Low-calorie meals ( 250 kcal ) were associated with exposures that were approximately 60 % to 90 % lower than those of medium- and high-calorie meals , and approached exposures seen under fasting conditions . Fat content of the meal had no significant effect on ziprasidone absorption . The ziprasidone exposures observed with medium- and high-calorie meals had less variability than those with low-calorie meals and under fasting conditions . CONCLUSIONS These results confirm that ziprasidone should be taken with food and that a meal equal to or greater than 500 kcal , irrespective of fat content , is required for optimal and reproducible bioavailability of the administered dose", "OBJECTIVE The efficacy and safety of olanzapine were compared with those of ziprasidone . METHOD This was a multicenter r and omized , double-blind , parallel-group , 28-week study of patients with schizophrenia . Patients were r and omly assigned to treatment with 10 - 20 mg/day of olanzapine or 80 - 160 mg/day of ziprasidone . The primary efficacy measure was the Positive and Negative Syndrome Scale total score . Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood , quality of life , and extrapyramidal symptom scales . Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight . RESULTS The study was completed by significantly more olanzapine-treated patients ( 165 of 277 , 59.6 % ) than ziprasidone-treated patients ( 115 of 271 , 42.4 % ) . At 28 weeks , the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement . The responder rate was higher for olanzapine than for ziprasidone . Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses , but results favored olanzapine on baseline-to-maximum changes . Weight change was significantly greater with olanzapine ( mean=3.06 kg , SD=6.87 ) than with ziprasidone ( mean=-1.12 kg , SD=4.70 ) . Fasting lipid profiles were significantly superior in the ziprasidone group ; there was no significant difference in fasting glucose level . CONCLUSIONS Olanzapine treatment result ed in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment , while ziprasidone was superior for weight change and lipid profile" ] "Ziprasidone exposure was increased when the medication was administered with food , irrespective of fat content . The findings from this meta- analysis and review suggest that ziprasidone 120 - 160 mg/d is a less effective treatment for psychotic disorders compared with olanzapine and risperidone , but that the low levels of hyperprolactinemia and weight gain/metabolic adverse events associated with ziprasidone may make it a useful option in patients in whom antipsychotics are poorly tolerated for these reasons" "BACKGROUND Among atypical antipsychotics , ziprasidone exhibits a unique clinical profile . However , prescription rates for this medication remain among the lowest of all atypical antipsychotics . OBJECTIVE The present meta- analysis examined premature study discontinuation ( PSD ) and dose-response associated with ziprasidone . Furthermore , a systematic review of the clinical pharmacokinetic and pharmacodynamic properties and tolerability of ziprasidone was conducted to explain the meta-analytic findings ." "16628439" [ "7593073", "8895640", "11322998", "11724040", "16075212", "11790060", "2404315", "8325117", "8851402", "3336713", "8819396", "8517292" ] [ "Magnetic resonance venography to evaluate the deep venous system of the pelvis in patients who have an acetabular fracture.", "Magnetic Resonance Venography Versus Contrast Venography to Diagnose Thrombosis After Joint Surgery", "Accuracy of magnetic resonance imaging in the diagnosis of deep vein thrombosis in asymptomatic patients with injuries of the lower extremity. A pilot study.", "Isolated calf vein thrombosis: comparison of MR venography and conventional venography after initial sonography in symptomatic patients.", "Optimized image reconstruction for detection of deep venous thrombosis at multidetector-row CT venography", "Diagnosis of Lower-Limb Deep Venous Thrombosis: A Prospective Blinded Study of Magnetic Resonance Direct Thrombus Imaging", "Deep venous thrombosis of extremities: role of MR imaging in the diagnosis.", "Detection of deep venous thrombosis by magnetic resonance imaging.", "Detection of deep venous thrombosis: prospective comparison of MR imaging and sonography.", "Deep venous thrombosis evaluation with limited-flip-angle, gradient-refocused MR imaging: preliminary experience.", "Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography.", "1992 ARRS Executive Council Award. Detection of deep venous thrombosis: prospective comparison of MR imaging with contrast venography." ] [ "We performed a prospect i ve , blinded study to assess and compare the values of preoperative contrast venography and magnetic resonance venography in the detection of deep venous thrombosis in the thigh and pelvis of forty-five consecutive patients who had a displaced acetabular fracture . The magnetic resonance venography and contrast venography were performed an average of seven days ( range , one to twenty-nine days ) after the injury . Twenty-four asymptomatic thrombi were identified with magnetic resonance venography in fifteen ( 33 percent ) of the patients . Four of the thrombi were in the superficial femoral vein , nine were in the common femoral vein , one was in the external iliac vein , seven were in the internal iliac vein , and three were in the common iliac vein . Ten ( 42 percent ) of the twenty-four thrombi were confirmed with contrast venography ; nine of them were located in the thigh . The remaining fourteen thrombi ( 58 percent ) that had been noted on magnetic resonance venography could not be seen with contrast venography because they were located either in the deep pelvic veins or in the uninjured extremity . The thrombi in the internal iliac vein were identified only with magnetic resonance venography . Twelve of the fifteen patients who had thrombi had a filter placed in the inferior vena cava preoperatively . In eight of these patients , the filter was placed because of the findings of magnetic resonance venography alone . Magnetic resonance venography result ed in a change in the therapeutic management of ten ( 22 per cent ) of the forty-five patients . There were no pulmonary emboli . We concluded that magnetic resonance venography is superior to contrast venography for the preoperative evaluation of proximal deep venous thrombosis in patients who have an acetabular fracture . Magnetic resonance venography is non-invasive , does not require the use of contrast medium , images the proximal aspects of both lower extremities simultaneously , and , most importantly , allows for the identification of deep venous thrombosis in the pelvis", "Magnetic resonance venography is a recently developed , noninvasive means of visualizing the proximal veins of the lower extremity and pelvis . Magnetic resonance venography is compared with st and ard contrast venography in the diagnosis of proximal deep vein thrombosis after total joint arthroplasty . Two hundred seven extremities were evaluated in a blinded study 5 to 7 days after surgery . St and ard contrast venography identified 11 proximal deep vein thromboses . Initial interpretations of the magnetic resonance venographies by staff radiologists identified 5 of the proximal vein thromboses ( sensitivity 45 % ) . Two patients with negative st and ard contrast venographies were identified as positive ( specificity 99 % ) . A retrospective review of all magnetic resonance venographies by a dedicated magnetic resonance angiographer identified 10 of 11 deep vein thromboses seen on st and ard contrast venography ( sensitivity 91 % ) . Both false negatives were identified as positives . St and ard contrast venography remains the gold st and ard for identifying proximal vein thromboses . Emerging magnetic resonance imaging techniques have created a potential alternative modality by which to identify deep vein thrombosis . The present study suggests that st and ard contrast venography continues to be the most accurate modality currently available . Although magnetic resonance venography seems to be accurate , its interpretation requires experience . As costs diminish and experience increases , magnetic resonance venography will have increased importance in the clinical recognition of deep vein thrombosis", "This is a prospect i ve comparative study of magnetic resonance imaging ( MRI ) of the deep veins versus contrast venography in consecutive patients treated for various injuries to their lower extremities , showing no clinical symptoms of deep vein thrombosis . The majority of examinations referred to in this study were performed according to the following methodology : First , the patient was subjected to MRI . Subsequently , within a 24-h interval , he/she was subjected to contrast venography . The acquired results were compared in a blinded manner . The diagnostic indices for MRI were calculated on the assumption that the results of contrast venography were sure to give an accurate indication of either presence or absence of thrombosis . Thirty-six patients were included in the study , of which 27 ( 15 males ) completed it . The overall incidence of distal deep venous thrombosis ( DVT ) was 22 % ( 6/27 ) . One patient showed extension of a crural thrombus into the popliteal vein . MRI did not detect any of the thrombi . This lack of result was ascribed to failure to fully demonstrate all segments of the crural veins . However , MRI did show three proximal thrombi in the superficial femoral vein , which were not shown by the venograms . Thus , both the sensitivity and specificity of MRI were 0 % , so MRI proved to be of no value in the diagnosis of asymptomatic deep venous thrombosis in this study", "RATIONALE AND OBJECTIVES The authors performed this study to compare magnetic resonance ( MR ) venography and conventional venography in the diagnosis of deep venous thrombosis ( DVT ) in the calf after sonography . MATERIAL S AND METHODS Sonography was performed in 595 patients who were suspected of having lower-extremity DVT . Patients with positive above-knee duplex sonograms , allergy to iodinated contrast material , renal insufficiency , or cardiac pacemakers and patients who were obese were excluded . The remaining 73 patients were asked to undergo MR venography and conventional venography . All studies were to be performed within 48 hours of the clinical diagnosis and according to st and ard clinical practice . Images were interpreted by radiologists who were blinded to the results of other modalities . Two separate analyses were performed : one in which conventional venography was used as the st and ard of reference , and one in which the presence of at least two positive studies for thrombus was considered diagnostic . RESULTS Although 36 patients agreed to participate in the study , only 14 underwent MR venography and conventional venography within 48 hours of the clinical diagnosis . With use of any two positive studies for confirmation , acute DVT was diagnosed in three patients . Conventional venography depicted two of the three cases , whereas sonography and MR venography each depicted all three . The findings were concordant in only five of the 14 patients . CONCLUSION Moderate discrepancy among modalities was demonstrated . This suggests radiologists should undertake comparisons among these three modalities for the detection of calf DVT . In patients with a high clinical suspicion , a second modality may be useful if the initial study is negative", "The aims of this study were to optimize image quality for indirect CT venography ( sequential versus spiral ) , and to evaluate different image reconstruction parameters for patients with suspected deep venous thrombosis ( DVT ) . Fifty-one patients ( 26/25 with/without DVT ) were prospect ively evaluated for pulmonary embolism ( PE ) with st and ard multidetector-row computed tomography ( MDCT ) protocol s. Retrospective image reconstruction was done with different slice thicknesses and reconstruction increments in sequential and spiral modes . All reconstructions were read for depiction of DVT and to evaluate best reconstruction parameters in comparison with the thinnest reconstruction ( “ gold st and ard ” ) . Image noise and venous enhancement were measured as objective criteria for image quality . Subjective image quality was rated on a four-point scale . Effective dose was estimated for all reconstructions . In sequential 10/50 reconstruction DVT was completely detected in 13/26 cases , partially in 10/26 cases and was not detected at all in 3/26 cases , and 15/26 , 9/26 and 2/26 cases for the 10/20 reconstruction , respectively . DVT was completely detected in all spiral reconstructions . Image noise ranged between 14.8 - 29.1 HU . Median image quality was 2 . Estimated effective dose ranged between 2.3 mSv and 11.8 mSv . Gaps in sequential protocol s may lead to false negative results . Therefore , spiral scanning protocol s for complete depiction of DVT are m and atory", "Despite considerable recent advances in diagnostic techniques for lower-limb deep venous thrombosis ( DVT ) , current methods have disadvantages . Ultrasonography , the most accurate noninvasive test , is widely available and cheap . As such , it has largely replaced venography as the test of first choice for symptomatic DVT . In a recent meta- analysis , the sensitivity of ultrasonography was 89 % overall for symptomatic DVT and 97 % for above-knee thrombosis ( 1 ) . Large outcome studies have shown that patients may be safely left untreated after a negative result on ultrasonography if they have a low clinical risk score , a low d-dimer level , or a negative result on repeated ultrasonography at 1 week ( 2 - 4 ) . However , these strategies may be complex and still require 3 % to 34 % of out patients and most in patients to undergo repeated ultrasonography at 1 week ( 2 - 4 ) . In practice , retesting after 1 week is inconvenient , and physicians often rely on a single test or request immediate venography ( 5 ) . Other problems with ultrasonography include poor sensitivity for asymptomatic disease , difficulties in diagnosing DVT recurrence , and limited visualization in the pelvis ( 1 , 6 , 7 ) . Impedance plethysmography is also commonly used ; however , it has a lower diagnostic accuracy than ultrasonography and has similar weaknesses in the setting of recurrent thrombosis , asymptomatic DVT , and DVT below the knee or in the pelvis ( 1 , 4 , 6 ) . Computed tomography and magnetic resonance imaging techniques can visualize DVT above the knee and in the pelvis but in general are unsuccessful below the knee ( 8 - 10 ) . The ability of these techniques to diagnose DVT recurrence and asymptomatic disease has not been tested . Venography is the reference st and ard diagnostic test , but it has in large part been replaced by noninvasive tests . In clinical practice , it is the most reliable test for the diagnosis of asymptomatic thrombosis and thrombosis isolated within the calf or pelvis . However , imaging in the pelvis is inadequate in up to 24 % of normal studies , and the proximal extent of thrombosis is frequently not delineated in patients with above-knee DVT ( 11 ) . Underfilling of vessels and vessels overlying one another also create problems with venography below the knee . Studies have shown that interobserver variability for venography is high ( 10 % to 16 % ) , especially below the knee ( = 0.46 to 0.73 below the knee and 0.46 to 0.84 above the knee ) ( 12 , 13 ) . In addition , a high proportion of studies are nondiagnostic for possible DVT recurrence ( 1 , 6 ) . A noninvasive test is needed that accurately diagnoses above-knee DVT and thrombus below the knee , in the pelvis , and in asymptomatic limbs . Unlike most imaging techniques , which identify thrombus as filling defects , magnetic resonance direct thrombus imaging ( MRDTI ) visualizes thrombus against a suppressed background ( 14 ) . In an unblinded comparison with venography , we previously showed that MRDTI precisely visualizes acute deep venous thrombus ( 14 , 15 ) . In the current study , we sought to assess prospect ively whether MRDTI is a reliable diagnostic test for suspected acute symptomatic DVT . Methods The ethics committee at our institution granted approval for the study , and all participants gave written informed consent . With the exceptions of pregnant women , patients with known contrast allergy , and those with renal failure , all patients with DVT suspected on the basis of lower limb symptoms are investigated by using venography at our institution . Participants were recruited after routine venography was done between May 1998 and September 1999 . During this time , 338 consecutive patients underwent routine contrast venography . Consecutive patients with positive venograms were selected , along with one quarter of those with negative venograms , according to a predetermined r and om sequence . This protocol was chosen to equalize the numbers of positive and negative cases and was based on a 6-month audit of venograms in our institution that found that 22 % of venograms were positive . Clinical diagnostic criteria were not used , and the decision to request investigation for suspected DVT had been made by the attending clinician ; however , patients who did not have leg symptoms were not recruited . Other exclusion criteria were failed or inconclusive venography , failed or inconclusive MRDTI , contraindications to MRI , and claustrophobia ( Figure 1 ) . Individual venous segments that were nondiagnostic at venography were also excluded from analysis . Figure 1 . Outline of the study . Magnetic resonance direct thrombus imaging was performed on all patients recruited within 48 hours of venography . The scans were interpreted by an experienced radiologist ( review er A ) and by a nonradiologist ( review er B ) trained to read MRDTI scans . For venograms and MRDTI scans , the review ers noted the presence or absence of DVT ; the diagnostic classification of DVT , divided into isolated calf DVT , femoropopliteal DVT , and ileofemoral DVT ; and the presence of thrombus in the calf , femoropopliteal , and iliac venous segments . Venograms were obtained and initially reported by the radiologists on duty . This initial report was used to make recruitment decisions ; if the results were discordant with those of MRDTI , ultrasonography was also performed . However , ultrasonography was not used in the calculations of the accuracy of MRDTI . After completion of the study , venograms were interpreted by an independent radiologist , and these results were used as the gold st and ard against which MRDTI was compared . Results of MRDTI and venography were reported without knowledge of the results of other tests and the other readings . The d-dimer level was measured in all patients at the time of the MRDTI scan by using the Nycocard ( Nycomed Pharma AS , Asker , Norway ) technique ( normal level < 0.3 mg/L ) . Venography Venography was performed by cannulating a dorsal pedal vein with a 21-gauge needle and rapidly injecting 50 to 100 mL of iodinated contrast medium ( I2 , 300 mg/mL ) , with the patient supine and tilted 30 degrees with his or her feet downward . A tourniquet was applied above the ankle . Anteroposterior and two oblique views of the deep calf and popliteal veins were obtained . Views of the femoral and iliac veins were then obtained . The study result was considered positive if intraluminal filling defects were seen or persistent nonfilling of veins with a sharp cut-off was detected . Magnetic Resonance Imaging Magnetic resonance imaging was performed by using a 1.5-Tesla unit ( Siemens Vision , Erlangen , Germany ) with a T1-weighted magnetization-prepared three-dimensional gradient-echo sequence . The sequence included a water-only excitation radiofrequency pulse to abolish the fat signal , and the effective inversion time was chosen to nullify the blood signal . Imaging was performed from the ankle to the inferior vena cava in two imaging blocks with a total acquisition time of 12 minutes by using a 55-cm body coil . Both legs were imaged simultaneously . Scanning was performed by radiographers in all cases . Image assessment involved reading of coronal source data and st and ard image reconstruction techniques . Acute thrombus was diagnosed on the basis of its high signal against the suppressed background ( Figure 2 ) . Figure 2 . Magnetic resonance direct thrombus imaging in three patients . A. arrows B. arrows C. single arrows double arrow Ultrasonography Color flow and compression ultrasonographic images of the symptomatic limb from the common femoral vein distally were obtained by using a 5-MHz linear array transducer . As much of the superficial femoral vein as possible was imaged , together with the popliteal vein and the calf veins . Augmentation of flow was used to verify patency . Examinations were performed by senior radiologists , and DVT was confirmed in all cases by noncompressibility on gray-scale images . The sonographer was unaware of the other test results , but in cases of possible isolated calf thrombosis , he or she was told to concentrate the examination below the knee to maximize accuracy in this region . Statistical Analysis Sensitivity and specificity were calculated for the overall diagnosis of DVT ; diagnosis of isolated calf DVT , femoropopliteal DVT , and ileofemoral DVT ; and presence of thrombus in the calf , femoropopliteal vein , and iliac vein . Exact CIs were calculated . Interobserver error was calculated for these observations by using the weighted statistic with equally spaced weights for positive , nondiagnostic , and negative studies . Confidence intervals for the statistic were calculated from asymptotic estimations of the st and ard error . Calculations were performed by using SPSS software ( SPSS , Inc. , Chicago , Illinois ) . Results One hundred four patients were recruited according to our protocol ( Figure 1 ) . The time between venography and MRDTI was less than 8 hours in 28 patients , 8 to 24 hours in 44 patients , and 24 to 48 hours in 32 patients . Age ranged from 20 to 95 years , and symptom onset varied from 1 to 35 days . Ninety-five patients were referred from medical specialties and 9 from surgical specialties ; 47 were in patients and 57 were out patients . Both review ers reported that 3 of 5 patients with ipsilateral total hip replacements had nondiagnostic MRDTI scans . Venography diagnosed femoropopliteal DVT in 1 of these patients and was negative in 2 patients . These 3 patients were excluded from further analysis , leaving 101 patients in the study . One patient could tolerate only the first scanning block from ankle to thigh level owing to claustrophobia ; however , femoropopliteal DVT could still be diagnosed . All other patients tolerated MRI . Eighteen of 148 patients ( 12 % ) were excluded from the study . Fifteen patients could not undergo MRI because of contraindications ( 9 patients ) or claustrophobia ( 6 patients ) , and 3 patients had inconclusive results on MRDTI . Venography failed ( 29 patients ) or was inconclusive ( 11 patients ) in 12 % of patients ( 40 of 338 ) . Venography was", "Current noninvasive imaging techniques for diagnosis of deep venous thrombosis ( DVT ) of extremities are limited in their ability to demonstrate central vein involvement and to distinguish acute from chronic changes . The utility of spin-echo magnetic resonance ( MR ) imaging for DVT was evaluated in 100 patients suspected of having either upper- ( n = 25 ) or lower-extremity ( n = 75 ) DVT . Ninety-seven patients were imaged successfully . In a subset of 36 patients , prospect i ve comparison of MR imaging with contrast venography revealed a sensitivity of 90 % , specificity of 100 % , and Kappa level of agreement of .752 ( P less than .0001 ) . MR imaging showed more central extent of thrombus than did venography in all five patients with upper-extremity DVT and in 13 of 25 patients ( 52 % ) with lower-extremity DVT . Although all patients in the study were evaluated for acute symptoms , 13 of 59 ( 22 % ) MR imaging studies positive for DVT demonstrated chronic disease . MR images demonstrated ancillary abnormalities in 18 of 41 ( 44 % ) patients who did not have DVT . Thus , MR imaging has a role as the definitive examination when the results of initial screening studies are unsatisfactory , or as a first-line examination if ( a ) there is suspicion of upper-extremity or pelvic vein thrombosis , ( b ) there is a history of prior DVT that necessitates distinction of acute from chronic changes , or ( c ) other tests are unavailable", "OBJECTIVE To determine the accuracy of gradient recalled echo magnetic resonance imaging in assessing deep venous thrombosis . DESIGN This is a retrospective review of a prospect i ve clinical experience in 216 consecutive patients studied using gradient recalled echo magnetic resonance imaging . Sixteen patients were unavailable for follow-up and 1 study was technically suboptimal , leaving 199 studies as the basis of this report . RESULTS In 79 cases with confirmatory venography ( n = 54 ) , ultrasound ( n = 16 , thigh veins only ) , or computed tomography ( n = 9 , pelvic veins only ) , magnetic resonance imaging was 97 percent sensitive , 95 percent specific , and 96 percent accurate . Including cases that were normal by magnetic resonance imaging , not anticoagulated , and with uneventful follow-up as true normal cases , the corresponding sensitivity , specificity , and accuracy of magnetic resonance imaging were as follows : 97 percent , 98 percent , and 97 percent . CONCLUSION Magnetic resonance imaging , using gradient recalled echo acquisitions , is capable of accurately diagnosing acute deep venous thrombosis", "Seventy-five patients ( 41 women and 34 men , 20 - 85 years old ) with clinical ly suspected deep venous thrombosis ( DVT ) were examined with MR imaging and sonography . In 26 patients , the final diagnosis was acute femoropopliteal DVT . The sensitivity of MR imaging for detecting this disease was 100 % with a 95 % confidence interval ( CI ) of 87 - 100 % ; the specificity was 100 % with a CI of 92 - 100 % ; and the accuracy was 96 % with a CI of 89 - 99 % . The correspond-ing sensitivity of sonography was 77 % with a CI of 53 - 92 % ; the specificity was 98 % with a CI of 89 - 100 % ; and the accuracy was 83 % with a CI of 72 - 90 % . In four of the 75 patients , MR images revealed thrombus of the pelvis ( n = 1 ) or calf ( n = 3 ) without femoropopliteal involvement . The estimated prevalence of isolated calf and /or pelvic DVT was 5 % with a CI of 1 - 13 % . MR imaging is significantly more sensitive ( P = .02 ) and accurate ( P < .01 ) than sonography in the detection of lower extremity DVT , but there was no difference in the specificity of MR imaging and that of sonography ( P = .31 )", "Sixteen patients ( 17 lower extremities ) were prospect ively examined with venography and limited-flip-angle , gradient-refocused magnetic resonance ( MR ) imaging for the presence or absence of deep venous thrombosis . Thrombosed vessels showed decreased-to-absent signal intensity , while patent vessels had high signal intensity . In 16 of 17 extremities , MR images allowed accurate detection and localization of the thrombi found with venography . In the remaining extremity , MR imaging allowed correct identification of thrombus in the iliac and femoral veins but incorrectly demonstrated clot in the calf and popliteal veins . MR imaging with limited-flip-angle , gradient-refocused pulse sequences appears to be a sensitive , noninvasive means of detecting deep venous thrombosis", "OBJECTIVE This study was design ed to compare the diagnostic value of MR venography and color Doppler sonography in the assessment of deep venous thrombosis . SUBJECTS AND METHODS MR venograms and color Doppler examinations were obtained in 37 patients either with suspected deep venous thrombosis of the lower limbs or pelvis or with pulmonary embolism . Two-dimensional time-of-flight venography was used for all studies . MR and color Doppler data were collected prospect ively and analyzed in a blinded manner . In a subset of 21 patients , MR venography and color Doppler sonography were prospect ively compared with contrast-enhanced venography . RESULTS When compared with contrast-enhanced venography , MR venography was 100 % sensitive and 100 % specific in the diagnosis of deep venous thrombosis above the knee . Color Doppler imaging depicted 13 of 15 cases of deep venous thrombosis and 5 of 6 venous examinations that had normal results , yielding a sensitivity and a specificity of 87 % and 83 % , respectively . The differences in sensitivity and specificity between MR venography and color Doppler sonography were not statistically significant . MR venography was 95 % sensitive and 99 % specific in detecting the extension of deep venous thrombosis , compared with the 46 % sensitivity and 100 % specificity of color Doppler sonography ( differences in sensitivity , p < .01 ) . MR images showed 29 collateral vessels , whereas only 21 were detected by contrast-enhanced venography ( p < .04 ) . CONCLUSION MR venography seems to be more accurate than color Doppler sonography in detecting the extension of deep venous thrombosis . The positive diagnosis and extent of deep venous thrombosis can be easily detected and monitored by a noninvasive technique such as MR venography", "OBJECTIVE Preliminary reports have described the use of MR imaging for the detection of deep venous thrombosis . However , no prospect i ve study comparing MR imaging with contrast venography ( the gold st and ard ) has been reported . Accordingly , we performed a prospect i ve , blinded study of the efficacy of MR imaging in 61 consecutive patients with clinical ly suspected deep venous thrombosis . In cases of disagreement , additional testing was performed to determine the diagnosis . SUBJECTS AND METHODS From June 1991 to February 1992 , 61 patients with clinical ly suspected deep venous thrombosis were examined with venography and MR imaging . The average time between studies was 3 hr . In 21 of the 61 patients , the final diagnosis was deep venous thrombosis . RESULTS For detection of deep venous thrombosis in the pelvis , the sensitivity of MR imaging was 100 % ( 9/9 ) with a 95 % confidence interval of 72 - 100 % and the specificity was 95 % ( 52/55 ) with a 95 % confidence interval of 85 - 99 % . In the thigh , the sensitivity ( 16/16 ) and specificity ( 43/43 ) were both 100 % with 95 % confidence intervals of 83 - 100 % and 93 - 100 % , respectively . In the calf , the sensitivity was 87 % ( 13/15 ) with a 95 % confidence interval of 60 - 98 % and the specificity was 97 % ( 36/37 ) with a 95 % confidence interval of 86 - 100 % . CONCLUSION We found no statistically significant difference between MR imaging and contrast venography in the detection of deep venous thrombosis . This result suggests that MR imaging is at least as sensitive and specific as contrast venography in the detection of deep venous thrombosis" ] "MRI has equivalent sensitivity and specificity to ultrasound for diagnosis of DVT , but has been evaluated in many fewer studies , using a variety of different techniques" "Magnetic resonance imaging ( MRI ) may be used to diagnose deep vein thrombosis ( DVT ) in patients for whom ultrasound examination is inappropriate or unfeasible . We undertook a systematic review of the literature and meta- analysis to estimate the diagnostic accuracy of MRI for DVT ." "16279145" [ "11568067", "9412880", "7522906", "11323066", "7519132", "10509988", "9308747", "7580360", "7536481", "9270645", "7515193", "7574046", "11547294", "9169364", "1385010", "10645113", "7527112", "7539874", "7545448", "7529464", "11139109", "9806378", "7524460", "7475139", "10468248", "8873736", "7554207", "10719945", "8698787", "8884859", "7535064", "9676682", "8773637", "11216738", "12038916", "8957369", "12078788", "8633944", "7541637", "8751522", "1280411", "7531423", "8993243", "9845139" ] [ "Aprotinin But Not &egr;-Aminocaproic Acid Decreases Interleukin-10 After Cardiac Surgery With Extracorporeal Circulation: Randomized, Double-Blind, Placebo-Controlled Study in Patients Receiving Aprotinin and &egr;-Aminocaproic Acid", "A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.", "Randomized placebo‐controlled double‐blind study of three aprotinin regimens in primary cardiac surgery", "The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials", "Randomized Study of Aprotinin and DDAVP to Reduce Postoperative Bleeding After Cardiopulmonary Bypass Surgery", "Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass.", "Aprotinin reduces blood loss after cardiopulmonary bypass by direct inhibition of plasmin.", "Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs.", "The use of ultra-low-dose aprotinin to reduce blood loss in cardiac surgery.", "Effects of minimal-dose aprotinin on coronary artery bypass grafting.", "Effect of reduced aprotinin dosage on blood loss and use of blood products in patients undergoing cardiopulmonary bypass.", "Influence of High-dose Aprotinin on Anticoagulation, Heparin Requirement, and Celite- and Kaolin-Activated Clotting Time in Heparin-pretreated Patients Undergoing Open-Heart Surgery: A Double-blind, Placebo-controlled Study", "Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial.", "Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin regimen in reoperative and/or complex cardiac operations.", "Aprotinin Prevents Cardiopulmonary Bypass‐Induced Platelet Dysfunction: A Scanning Electron Microscope Study", "Technologies to minimize blood transfusion in cardiac and orthopedic surgery. Results of a practice variation survey in nine countries. International Study of Peri-operative Transfusion (ISPOT) Investigators.", "Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass.", "Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.", "A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery.", "High-dose Aprotinin in Cardiac Surgery—A Prospective, Randomized Study", "High-dose aprotinin modulates the balance between proinflammatory and anti-inflammatory responses during coronary artery bypass graft surgery.", "Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial.", "Aprotinin preserves hemostasis in aspirin-treated patients undergoing cardiopulmonary bypass.", "Aprotinin versus desmopressin for patients undergoing operations with cardiopulmonary bypass. A double-blind placebo-controlled study.", "Platelet function during cardiac surgery and cardiopulmonary bypass with low-dose aprotinin.", "Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial.", "A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting.", "Comparison of Blood-conservation Strategies in Cardiac Surgery Patients at High Risk for Bleeding", "Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs tranexamic acid vs epsilon aminocaproic acid.", "Efficacy and safety of aprotinin in aortocoronary bypass and valve replacement operations: a placebo-controlled randomized double-blind study", "Influence of aprotinin on early graft thrombosis in patients undergoing myocardial revascularization.", "Discussion sections in reports of controlled trials published in general medical journals: islands in search of continents?", "Improving the quality of reporting of randomized controlled trials. The CONSORT statement.", "Ultra-low dose aprotinin decreases transfusion requirements and is cost effective in coronary operations.", "Discussion sections in reports of controlled trials published in general medical journals.", "Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens.", "Aprotinin in coronary operation with cardiopulmonary bypass: does \"low-dose\" aprotinin inhibit the inflammatory response?", "Postoperative aprotinin: effect on blood loss and transfusion requirements in cardiac operations.", "Aprotinin in elective primary bypass surgery. Graft patency and clinical efficacy.", "Low-dose and high-dose aprotinin improve hemostasis in coronary operations.", "Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study.", "Hemostatic efficacy of dipyridamole, tranexamic acid, and aprotinin in coronary bypass grafting.", "\"Low-dose\" aprotinin modifies hemostasis but not proinflammatory cytokine release.", "Aprotinin counterbalances an increased risk of peri-operative hemorrhage in CABG patients pre-treated with Aspirin." ] [ "Background —Extracorporeal circulation induces a systemic inflammatory response , which may adversely affect organ function . One manifestation of this response is increased fibrinolysis . Antifibrinolytic drugs such as aprotinin and & egr;-aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation ; however , the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known . This study examined the effects of aprotinin and & egr;-aminocaproic acid on plasma levels of proinflammatory [ interleukin-6 ( IL-6 ) ] and anti-inflammatory [ interleukin-10 ( IL-10 ) ] cytokines during and after extracorporeal circulation . Methods and Results —Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were r and omly assigned in a double-blind study to receive high-dose aprotinin , & egr;-aminocaproic acid , or saline placebo . Plasma levels of IL-6 and IL-10 were measured at 5 time points before , during , and after extracorporeal circulation . In all 3 groups , both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day . Compared with saline , aprotinin significantly reduced IL-10 ( P = 0.02 ) and peak IL-6 ( P = 0.02 ) after extracorporeal circulation . In contrast , none of the reductions in IL-6 and IL-10 by & egr;-aminocaproic acid achieved statistical significance . Both aprotinin and & egr;-aminocaproic acid decreased blood loss compared with saline , but there was no significant difference in the number of patients receiving blood products among the treatment groups . Conclusions —These data suggest that aprotinin and & egr;-aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation . Aprotinin but not & egr;-aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10 . Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes", "OBJECTIVES To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization . DESIGN A prospect i ve r and omized study . SETTING A university hospital . PARTICIPANTS Forty-three patients were r and omly assigned to either group A , 21 patients treated with 2 x 10(6 ) kallikrein inhibitor units ( KIU ) of aprotinin in the cardiopulmonary bypass ( CPB ) prime , or group B , 22 patients , untreated . INTERVENTIONS Patients , scheduled for elective coronary surgery , were treated with 2 x 10(6 ) KIU of aprotinin in the CPB prime . Markers of coagulation and fibrinolysis were evaluated . MEASUREMENTS AND MAIN RESULTS Surgical times , number of reopenings , and allogeneic blood requirements were collected for each patient . Blood sample s were obtained before and after surgery for assessing coagulation ( prothrombin time [ PT ] , activated partial thromboplastin time [ aPTT ] , ethanol test , factor VII , antithrombin III [ AT III ] , thrombin-antithrombin III complex [ TAT ] , fragment 1.2 of prothrombin [ F1.2 ] ) and fibrinolysis ( fibrin degradation products [ FOP ] , plasmin-antiplasmin complexes [ PAP ] , D-dimers ) markers variations . In group A surgical times were faster , there were fewer reopenings ( 0 v 3 ) , and fewer blood transfusions ( 1 patient v 4 patients ) . The two groups did not differ for PT , aPTT , and fibrinogen measurements . Postoperative FDP ( measurable in more patients of group B at the end of the operation ) , PAP , and D-dimers postoperatory levels ( less increased in aprotinin group ) show the antifibrinolytic properties of the drug . Regarding the coagulation markers , factor VII decreased , whereas TAT and F1.2 increased , all to a lesser extent in the aprotinin group compared with the untreated patients , at the end of operation . CONCLUSION Pump-prime aprotinin minimized , even if not completely inhibited , the activation of coagulation and fibrinolysis during CPB , possibly ensuring a less complicated and safer postoperative recovery . It seemed to allow the maintenance of a correct balance of hemostatic systems , avoiding the risk of thrombotic phenomena", "The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass . This study compared two low‐dose regimens with administration of high‐dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery . Some 100 patients were r and omly assigned to one of four groups : control group ( 0·9 per cent saline placebo , n = 25 ) ; high‐dose group ( aprotinin 2 × 106 kallikrein inactivator ( KI ) units intravenous patient bolus and 0·5 × 106 KI units h−1 plus 2 × 106 KI units into pump prime , n = 25 ) ; prime group ( aprotinin 2 × 106 KI units added to the pump prime , n = 24 ) ; and patient group ( aprotinin 106 KI units intravenous patient bolus plus 106 KI units added to the pump prime , n = 26 ) . Only patients from the high‐dose and patient groups had reduced intraoperative blood loss , but patients from all three aprotinin‐treated groups demonstrated a significant decrease in median postoperative blood loss compared with the control group ( high‐dose 350 ml , prime 420 ml , patient 340 ml versus control 780 ml ; P < 0·001 ) . There was an even greater reduction in measured median postoperative haemoglobin loss within the chest drains in the treated compared with the control patients ( high‐dose 15 g , prime 24 g , patient 14 g versus control 47 g ; P < 0·001 ) . These decreases were statistically the same for all the treated groups ; it is possible to lower the dose of aprotinin to approximately one‐third of the currently recommended dosage and still obtain significantly reduced postoperative blood loss in primary cardiac surgery", "To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results", "Background Patients on cardiopulmonary bypass ( CPB ) have an increased susceptibility to postoperative bleeding . Previous reports using desmopressin acetate ( DDAVP ) for the prevention of postoperative bleeding have given contradictory results , whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery . This r and omized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB . Methods and Results One hundred nine of 122 eligible patients were r and omized to four different groups : Group A ( n=28 ) received aprotinin starting with a bolus of 2 × 106 KIU followed by a continuous infusion of 0.5 × 106 KIU/h until the end of surgery ; group B ( n=25 ) received of DDAVP 0.3 μ/kg IV on completion of CPB ; group C ( n=28 ) received two doses of DDAVP , the first as in group B and an additional dose 6 hours after surgery ; group D ( n=28 ) received no treatment . There was a marked reduction of postoperative blood loss either at 12 hours ( P<.01 ) or 72 hours ( P<.02 ) in the aprotinin group compared with all other groups , whereas no significant effect was observed in either of the two DDAVP regimens . A significant reduction in the amount of blood used was observed only in the aprotinin group ( P<.01 ) . Of the plasma fibrinolytic components assayed , there was a significant reduction of the fibrin degradation product generation in the aprotinin group ( P<.001 ) , whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group . No side effects related to the study drugs were observed in any patient . Conclusions Aprotinin inhibited fibrinolysis ; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB . Neither one nor two doses of DDAVP had a beneficial effect . Aprotinin offers better alternative than DDAVP in the prevention of bleeding after CPB", "BACKGROUND Aprotinin therapy is now widely used during cardiac surgery . This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo . METHODS In a double blind , r and omized study , three groups of 50 patients received high-dose aprotinin costing AUS614 per patient ( AUS$= Australian dollars ) , low-dose aprotinin costing AUS$220 per patient or placebo . Re source use influenced by aprotinin therapy was measured . RESULTS Both doses were effective in reducing chest drainage and postoperative transfusion requirements , high-dose being more effective than low-dose . Both doses reduced the rate of reoperations for hemostasis . A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient , respectively . If the demonstrated less significant reductions in operating room and ward stay are included , these savings become AUS$463 and AUS$715 , respectively . Alternately , if cross-matches are replaced by group- and -hold and cell savers are not used , the savings per patient would be AUS$196 and AUS$467 , respectively . CONCLUSIONS While high-dose aprotinin is clinical ly more effective than low-dose aprotinin , low-dose therapy demonstrates greater cost savings", "The effectiveness and mechanism of aprotinin reduced bleeding after cardiopulmonary bypass surgery was studied in a double blind r and omised study of 106 patients undergoing valve replacement surgery . Aprotinin therapy was associated with significant reduction in perioperative bleeding and postoperative blood transfusion requirements . Although initially tissue plasminogen activator ( t-PA ) activity was lower in the aprotinin than placebo group , as surgery proceeded this difference was reversed due to less plasminogen activator inhibitor-1 release in the aprotinin group . This indicates that aprotinin-mediated suppression of fibrinolysis as demonstrated by reduced D-dimer concentration was not related to t-PA . Furthermore , similar perioperative reduction of plasminogen levels in aprotinin and placebo groups indicated a similar degree of conversion of plasminogen to plasmin . However , less plasmin bound with alpha 2-antiplasmin in the plasma in the aprotinin group as it was already complexed with aprotinin where it remained protected from the natural inhibitor on the intact fibrin surface . The reduced fibrinolytic activity of the aprotinin group was thus brought about by the complexing of aprotinin with the plasmin which was bound to the fibrin surface", "Sixty consecutive patients undergoing elective open-heart surgery were prospect ively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion . The patients were r and omized to 1 of 4 intraoperative treatment regimens : 1 ) control ( no antifibrinolytic therapy ) ; 2 ) epsilon-aminocaproic acid ( 10 g IV at induction of anesthesia , followed by infusion of 2 g/h for 5 hours ) ; 3 ) tranexamic acid ( 10 mg/kg IV within 30 minutes after induction of anesthesia , followed by infusion of 1 mg/kg per hour for 10 hours ) ; or 4 ) high-dose aprotinin ( 2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit , followed by infusion of 500 thous and KIU/h during surgery ) . Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients . Indications for blood transfusion were hypotension , tachycardia , or both , with hemoglobin values < 8.5 g/dL ; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group , patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour ( control , 128 + /- 94 mL ; aprotinin , 54 + /- 47 mL , p = 0.01 ; and epsilon-aminocaproic acid , 69 + /- 35 mL , p = 0.03 ) ; this trend continued at 24 hours after operation ( control , 724 + /- 280 mL ; aprotinin , 344 + /- 106 mL , p < 0.0001 ; and epsilon-aminocaproic acid , 509 + /- 148 mL , p = 0.01 ) . Aprotinin was significantly more efficient than epsilon-aminocaproic acid ( p=0.002 ) . Tranexamic acid did not have a statistically significant effect on blood loss . Homologous blood requirements were not significantly different among the groups ; postoperative hematologic values and coagulation times were also comparable . Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study , the blood requirements were not significantly different from those that are found when transfusions are restricted , autotransfusions are used , and blood from the operative field and extracorporeal circuit is concentrated and reinfused . Therefore , intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted", "One hundred patients due to undergo primary cardiac surgery were prospect ively r and omized to receive aprotinin or placebo . In the aprotinin group , 250,000 kallikrein inhibitory units ( KIU ) of aprotinin were added to the cardiopulmonary bypass prime solution . A further 250,000 KIU of aprotinin were infused intravenously over 30 minutes immediately before the start of cardiopulmonary bypass . The control group received 0.9 % saline in equal volumes at identical times . The study was design ed to have a 90 % chance of demonstrating a 30 % reduction in blood loss . No significant differences were found between the two groups . The median blood loss in the aprotinin group was 750 mL ( interquartile range 556 to 1025 mL , 95 % confidence interval 600 to 800 mL ) . In the control group , the median blood loss was also 750 mL ( interquartile range 500 to 988 mL , 95 % confidence interval 625 to 925 mL ) . In the aprotinin group , 12 patients received postoperative autotransfusion of shed mediastinal blood of median volume of 665 mL ( interquartile range 500 to 925 mL , 95 % confidence interval 450 to 1000 mL ) . In the control group , 14 patients received postoperative autotransfusion of mediastinal blood of median volume of 663 mL ( interquartile range 600 to 800 mL , 95 % confidence interval 600 to 700 mL ) . Five patients in the aprotinin group and seven patients in the control group required postoperative homologous blood transfusion . Re assessment of inclusion criteria showed a 19 % reduction in blood loss in patients undergoing only aortocoronary bypass receiving aprotinin compared with controls . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE To evaluate the effects of minimal-dose aprotinin in patients undergoing coronary artery bypass grafting , we conducted a prospect i ve r and omized study . METHODS A total of 167 patients were r and omized to receive no aprotinin treatment ( control , n = 57 ) , minimal-dose aprotinin ( 1.0 x 10(6 ) KIU ; n = 55 ) , or low-dose aprotinin ( 2.7 + /- 0.5 x 10(6 ) KIU ; n = 55 ) . Blood loss and transfusion requirements , parameters of clotting and fibrinolysis , renal function , and early graft patency rates were assessed . RESULTS Postoperative blood loss and transfusion requirements were significantly ( p = 0.01 ) lower in both the minimal-dose and low-dose groups than in the control group . The increase in D-dimer level after cardiopulmonary bypass was significantly ( p < 0.05 ) less marked in the low-dose group than in the control group . The alpha 2-plasmin inhibitor and plasminogen activator inhibitor-1 levels were significantly ( p < 0.05 ) greater in the minimal-dose and low-dose groups than in the control group after bypass , suggesting the prevention of fibrinolysis by both aprotinin doses . No statistically significant differences in postoperative renal function and early vein graft patency rates were noted ( control group , 93.8 % ; minimal-dose group , 95.5 % ; low-dose group , 92.3 % ; p = 0.25 ) . CONCLUSIONS Aprotinin was not associated with a significant increase in the prevalence of renal dysfunction or early vein graft occlusion . Minimal-dose aprotinin inhibited enhanced fibrinolytic activity and reduced blood loss and transfusion requirements after bypass equivalently to low-dose aprotinin . The dose of 1 x 10(6 ) KIU added to the pump prime may be acceptably effective in reducing blood loss in patients undergoing primary coronary operations", "High-dose aprotinin reduces bleeding after cardiac surgery , but has also evoked concern with regard to potential side effects and hospital costs . To evaluate the effects of reduced-dose aprotinin on blood loss and need for blood transfusion , 40 patients undergoing myocardial revascularization were studied ( double-blind , placebo-controlled ) . Postoperative bleeding was reduced by 40 % and erythrocyte infusion by 85 % in the group given 3 x 10(6 ) KIU aprotinin ( 1 x 10(6 ) as a loading dose before cardiopulmonary bypass , 1 x 10(6 ) in the priming volume and 2.5 x 10(5)/hour intraoperatively ) Aprotinin concentrations during the operation were monitored and maintained above the required level . There were no adverse effects of the drug . Hospital expenditure on blood products was reduced by 51 % when aprotinin was used . Our study suggests that aprotinin in reduced dosage diminishes bleeding and requirements for blood products , and that it should be given before , during and after cardiopulmonary bypass", "Background Aprotinin causes a prolongation of the celite-activated clotting time ( CACT ) , but not of the kaolin-activated clotting time ( KACT ) . Therefore , concern has been raised regarding the reliability of CACT to monitor anticoagulation in the presence of aprotinin . The current study was design ed to test the efficacy of aprotinin to improve anticoagulation , and to investigate whether the prolongation of CACT reflects true anticoagulation or is an in vitro artifact . To eluci date this antithrombotic effect of aprotinin , this study was done in patients prone to reduced intraoperative heparin sensitivity", "BACKGROUND Although low-dose aprotinin administered after cardiopulmonary bypass has been reported to reduce mediastinal blood loss and blood product requirements in patients not taking aspirin , it is unknown whether low-dose postoperative aprotinin has any beneficial effects in patients undergoing coronary artery bypass operations who are at high risk of excessive postoperative bleeding and increased transfusion requirements because of aspirin use until just before the operation . METHODS Fifty-five patients undergoing primary coronary artery operations with cardiopulmonary bypass who continued taking aspirin ( 150 mg/d ) until the day before the operation were enrolled in a prospect i ve , r and omized , double-blind trial to receive a single dose of either placebo ( n = 29 ) or 2 x 10(6 ) kallikrein inhibiting units of aprotinin ( n = 26 ) at the time of sternal skin closure . RESULTS Patients in the aprotinin group had a lower rate ( 28 + /- 18 vs 43 + /- 21 mL/h [ mean + /- st and ard deviation ] , P < .005 ) and total volume of mediastinal drainage ( 955 + /- 615 vs 1570 + /- 955 mL , P < .007 ) , as well as a shorter duration of mediastinal drain tube insertion ( 24.4 + /- 13.8 vs 31.3 + /- 16.5 hours , P < .05 ) . In addition , a smaller proportion of patients receiving aprotinin required a blood product ( 31 % vs 62 % , P = .03 ) , result ing in a reduction in the use of packed cells by 47 % ( P = .05 ) , platelets by 77 % ( P = .01 ) , fresh frozen plasma by 88 % ( P = .03 ) , and total blood products by 68 % ( P = .01 ) in this group . CONCLUSIONS These results suggest that postoperative administration of low-dose aprotinin in patients taking aspirin until just before primary coronary artery operations with cardiopulmonary bypass not only reduces the rate and total amount of postoperative mediastinal blood loss but also lowers postoperative blood product use", "BACKGROUND AND AIM OF THE STUDY High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass ( CPB ) . Very low doses of aprotinin have been shown to be effective in primary cardiac surgery , but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB . We evaluated the efficacy of ultra-low-dose aprotinin in this patient population . METHODS Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and /or a complex surgical procedure . Dryness of operative field , hemoglobin concentrations , coagulation parameters , chest drainage , and transfusion requirements were compared . RESULTS Total chest drainage was not different between groups , but fewer patients in the aprotinin group required additional protamine postoperatively ( 35 % vs 69 % for controls , p = 0.03 ) and fewer received fresh frozen plasma ( FFP ; 19 % vs 46 % for controls , p = 0.04 ) . Red cell transfusion was smaller in the aprotinin group compared to placebo ( median 4 and 2 units , respectively , p = 0.04 ) . Transfusion of FFP , platelets , cryoprecipitates was not different between groups . Total number of units transfused tended to be reduced in the aprotinin group compared to control ( median 2 and 7 units , respectively , p = 0.06 ) . CONCLUSIONS Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures . Aprotinin could be used in a more economical manner , even in this patient population at high-risk of receiving allogeneic blood products", "Background Administration of aprotinin during extracorporeal circulation reduces blood loss and improves platelet function . Methods and Results To evaluate the protective effect of aprotinin on platelets , 50 patients undergoing cardiopulmonary bypass were r and omized before surgery to one of three groups . Seventeen patients ( group A ) received continuous high-dose aprotinin ( 7X106 KIU ) during cardiopulmonary bypass , 17 ( group B ) received a single bolus of aprotinin in the pump prime ( 2x106 KIU ) , and 16 ( group C ) received placebo . Scanning electron microscopy was used to evaluate platelet aggregation on extracellular matrix . The platelet function was grade d from 1 to 4 , with grade 4 being normal aggregation . Immediately after cardiopulmonary bypass , 16 patients in group A ( 94 % ) reached preoperative aggregation grade ( mean grade , 3.4±0.7 ) compared with nine of 17 in group B ( 52 % ) ( mean grade , 2.9±1.2 ) , and none in group C ( 0 % ) ( mean grade , 1.4±0.5 ; p<0.001 ) . Postoperative platelet count did not differ significantly among the three groups . After surgery , group A bled less than groups B and C ( 395±120 versus 488±135 and 780±408 ml , respectively ; p<0.01 ) . Patients in the aprotinin groups received fewer red blood cell units ( 0.9±1.2 and 1.9±1.2 versus 3.4±1.9 , respectively ; p<0.01 ) and were exposed to less homologous blood products ( 1.3±1.7 and 2.1±1.1 versus 6.1±5 , respectively ; p<0.001 ) . Conclusions By preserving platelet function , aprotinin improves postoperative hemostasis in all patients who receive high dose and in most who receive low dose", "OBJECTIVES Due to the discovery in the 1980s that blood transfusion can transmit HIV , there has been increased interest in technologies that reduce the amount of allogeneic blood used during and after surgery . These technologies include drugs ( aprotinin , tranexamic acid , epsilon-aminocaproic acid , erythropoietin ) , devices ( cell salvage ) , and techniques ( acute hemodilution , predeposited autologous donation ) . The purpose of this study was to ascertain the degree of practice variation , if any , that exists for eight technologies in nine countries in orthopedic and cardiac surgery . METHODS In each country , either all hospitals or a r and om sample of hospitals with medical/surgical beds were surveyed between 1995 and 1997 . Two instruments were used . The first instrument was a postcard that asked recipients whether the technologies were currently being used in their hospital for orthopedic and /or cardiac surgery to reduce perioperative allogeneic transfusion . The second question naire elicited information regarding the degree of use both in qualitative and quantitative terms . Data were collected , entered , and analyzed in each country , with summary results su bmi tted to the Canadian coordinating center on a st and ardized data collection form . RESULTS Pharmaceuticals were generally used in a much smaller proportion of hospitals in orthopedic than in cardiac surgery . Aprotinin and tranexamic acid were the drugs most frequently used in cardiac surgery . Nonpharmacological technologies were used to a greater degree than drugs in orthopedic surgery , although there was wide variation among technologies and countries . Acute hemodilution and cell salvage were used in a greater proportion of hospitals for cardiac surgery than orthopedic surgery . CONCLUSIONS The results of this survey indicate that there is considerable practice variation in the use of technologies to minimize exposure to perioperative allogeneic transfusion within and between countries", "Aprotinin reduces blood loss after cardiopulmonary bypass , but may sensitize recipients and is expensive . Tranexamic acid , a synthetic antifibrinolytic , has less disadvantages , but opinions differ regarding its efficacy . We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease : recipients of aprotinin ( total dose 4.2 x 10(6 ) kallikrein inhibiting units , n = 14 ) , recipients of tranexamic acid ( total dose 20 mg/kg body weight , n = 15 ) , and nonmedicated controls ( n = 14 ) during 24 hours after cardiopulmonary bypass . Compared with controls , aprotinin reduced blood loss , the number of patients requiring transfusions , and the mean number of transfused red cell units ( all with p < 0.05 ) , whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls . Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls ( p < 0.05 ) . Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation , without any intergroup differences . The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis , without differences between the groups . The concentrations of D-dimer , a breakdown product of cross-linked fibrin , remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls ( p < 0.05 ) . By contrast , the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin ( p < 0.05 ) . This discrepancy may reflect the different modes of action of the two agents , which may make aprotinin more efficacious than tranexamic acid in the \" nonfibrinolytic \" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass", "Nowadays in many European heart centers the activation of the fibrinolytic system , always occurring during cardiopulmonary bypass , is routinely reduced by high-dose application of the proteinase inhibitor aprotinin ( total of > 4 million KIU ) . In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin , particularly the protection of the myocardium during the ischemic period of aortic crossclamping . Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were r and omly and in a double-blind fashion divided into two groups , one that received high-dose aprotinin therapy and one that received only saline solution . Markers such as troponin T , with high specificity for detection of myocardial ischemia and infa rct ion , and markers with more general specificity such as creatine kinase , its isoenzyme , and lactate dehydrogenase showed significantly increased values after ischemia in both groups . In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group . Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury", "OBJECTIVES To assess the relative efficacy of a \" low-dose \" aprotinin regimen and tranexamic acid on blood loss and homologous blood usage in patients undergoing primary cardiac surgery . DESIGN The trial was prospect i ve , r and omized , and controlled . SETTING A single center study in a regional cardiothoracic unit in the UK . PARTICIPANTS 75 Patients , age 18 years or over , who were scheduled for routine primary cardiac surgery . INTERVENTIONS The patients were r and omly allocated to receive neither drug nor placebo , a total of 5 g of tranexamic acid , or a total of 2 x 10(6 ) kallikrein inhibitory units of aprotinin in the perioperative period . MEASUREMENTS AND MAIN RESULTS The volume of blood loss and blood replacement were measured in the operative and postoperative periods . Hemoglobin concentration , platelet count , and white cell counts were determined preoperatively and at 24 hours postoperatively . Patients receiving tranexamic acid or aprotinin showed a significant reduction in postoperative blood loss ( median[interquartile range ] 375 mL [ 252 to 542 ] and 230 mL [ 137 to 547 ] ) , respectively , compared with the control group ( 615 mL [ 430 to 861 ] ) . Blood usage was also reduced in patients in both the tranexamic acid group ( 600 mL [ 415 to 800 ] ) and the aprotinin-treated group ( 420 mL [ 350 to 887 ] ) compared with the control group ( 1,050 mL [ 0 to 1,337 ] ) . There was no significant difference in blood loss or homologous blood use between patients treated with tranexamic acid or aprotinin . CONCLUSIONS Tranexamic acid is as effective as low-dose aprotinin in the reduction of postoperative blood loss and homologous blood transfusion in patients undergoing primary cardiac surgery", "Fifty patients undergoing primary coronary artery bypass surgery and 50 patients undergoing valve surgery received either high-dose aprotinin ( 2 million units loading dose , 2 million units added to the CPB prime , and 500,000 units/hr maintenance infusion ) or placebo . Mean postoperative blood loss in the first six hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin group ( 95 % confidence interval ( CI ) for difference = 95 to 189 ml ) . Seven patients in the placebo group and 16 patients in the aprotinin group did not require transfusion with homologous blood . This study adds to the growing body of evidence that the administration of high-dose aprotinin reduces blood loss and blood transfusion requirements associated with primary cardiac surgery", "OBJECTIVE To rule out the effect of high-dose aprotinin in respect to the balance of proinflammatory and anti-inflammatory mediators induced by cardiopulmonary bypass ( CPB ) . DESIGN R and omized , double-blind , placebo-controlled study . SETTING University-affiliated cardiac center . PARTICIPANTS Twenty patients scheduled for coronary artery bypass graft surgery . INTERVENTIONS In group A patients ( n = 10 ) , high-dose aprotinin was administered ( 2 x 106 KIU pre-CPB , 2 x 10(6 ) KIU in prime , 500,000 KIU/hr during CPB ) . In group C patients ( n = 10 ) , placebo was used instead . Proinflammatory interleukin (IL)-6 , anti-inflammatory IL-1-receptor antagonist , and clinical parameters were measured 8 times perioperatively . The values are presented as mean + /- SEM . MEASUREMENTS AND MAIN RESULTS Four hours after CPB , IL-6 concentration reached the maximum value , being significantly lower in group A patients as compared with group C patients ( 615 + /- 62 pg/mL v 1,409 + /- 253 pg/mL ; p = 0.019 ) . On the first postoperative day , the concentration of IL-6 in group A patients remained lower ( 219 + /- 24 pg/mL v 526 + /- 123 pg/mL ; p = 0.015 ) . In contrast , IL-1-receptor antagonist concentration was higher in group A patients as compared with group C patients after CPB ( 13,857 + /- 4,264 pg/mL v 5,675 + /- 1,832 pg/mL ; p = 0.03 ) . Total postoperative blood loss was lower in group A patients as compared with group C patients ( 648 + /- 64 mL v 1,284 + /- 183 mL ; p = 0.002 ) . CONCLUSIONS High-dose aprotinin treatment reduced the inflammatory reaction and postoperative blood loss . The anti-inflammatory reaction was significantly enhanced in these patients , which suggests that the physiologic reaction of the organism to reduce the deleterious effects from CPB is more pronounced by using high-dose aprotinin", "OBJECTIVE We examined the effects of aprotinin on graft patency , prevalence of myocardial infa rct ion , and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass . METHODS Patients from 13 international sites were r and omized to receive intraoperative aprotinin ( n = 436 ) or placebo ( n = 434 ) . Graft angiography was obtained a mean of 10.8 days after the operation . Electrocardiograms , cardiac enzymes , and blood loss and replacement were evaluated . RESULTS In 796 assessable patients , aprotinin reduced thoracic drainage volume by 43 % ( P < .0001 ) and requirement for red blood cell administration by 49 % ( P < .0001 ) . Among 703 patients with assessable saphenous vein grafts , occlusions occurred in 15.4 % of aprotinin-treated patients and 10.9 % of patients receiving placebo ( P = .03 ) . After we had adjusted for risk factors associated with vein graft occlusion , the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 ( 90 % confidence interval , 0.6 to 1.8 ) . These factors included female gender , lack of prior aspirin therapy , small and poor distal vessel quality , and possibly use of aprotinin-treated blood as excised vein perfusate . At United States sites , patients had characteristics more favorable for graft patency , and occlusions occurred in 9.4 % of the aprotinin group and 9.5 % of the placebo group ( P = .72 ) . At Danish and Israeli sites , where patients had more adverse characteristics , occlusions occurred in 23.0 % of aprotinin- and 12.4 % of placebo-treated patients ( P = .01 ) . Aprotinin did not affect the occurrence of myocardial infa rct ion ( aprotinin : 2.9 % ; placebo : 3.8 % ) or mortality ( aprotinin : 1.4 % ; placebo : 1.6 % ) . CONCLUSIONS In this study , the probability of early vein graft occlusion was increased by aprotinin , but this outcome was promoted by multiple risk factors for graft occlusion", "Various clinical trials have shown that hemostasis is improved by the administration of aprotinin during cardiopulmonary bypass . However , this effect has not been proved for those patients treated preoperatively with aspirin . Therefore , a double-blind , placebo-controlled study was conducted to test the efficacy of low-dose aprotinin ( 2 x 10(6 ) KIU in the pump prime solution ) in preserving hemostasis in 40 aspirin-treated ( 325 mg ) patients undergoing coronary artery bypass grafting . Aprotinin brought about a decrease in the postoperative blood loss ( p < 0.05 ) . The in vitro bleeding test ( Thrombostat ) demonstrated that aprotinin preserved the platelet hemostatic function in aspirin-treated patients during cardiopulmonary bypass ( p < 0.05 ) . The inhibitory effects of aspirin on collagen-induced platelet aggregation and thromboxane production were not influenced by aprotinin treatment . The findings from the present study indicate that aprotinin preserves hemostasis in aspirin-treated patients during cardiopulmonary bypass , but aspirin 's effect on platelets is maintained . Therefore , aprotinin seems to be a useful adjunct treatment in aspirin-treated patients undergoing coronary artery bypass grafting", "BACKGROUND Aprotinin reduces blood loss in operations done with cardiopulmonary bypass , whereas the use of desmopressin remains controversial . We compared aprotinin , desmopressin , and placebo in a double-blind , r and omized trial to evaluate bleeding and transfusion requirements . METHODS AND RESULTS One hundred forty-nine patients ( 48 received aprotinin , 50 desmopressin , 51 placebo ) were included . Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity , von Willebr and 's factor , thrombin-antithrombin complexes , and D-dimer were measured . Overall blood loss was 195 + /- 146 ml/m2 in the aprotinin group , 400 + /- 192 ml/m2 in the desmopressin group , and 489 + /- 361 ml/m2 in the placebo group ( 95 % confidence intervals : difference between desmopressin and aprotinin 98 to 312 ml/m2 , p < 0.001 ; difference between placebo and aprotinin 190 to 398 ml/m2 , p < 0.001 ) . Twenty-six percent of patients treated with aprotinin , 66 % of those treated with desmopressin , and 56 % of those treated with placebo were given transfusion ( 95 % confidence intervals : difference between aprotinin versus placebo plus desmopressin 51 % to 71 % , p < 0.001 ) . Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration . D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo , but not in those receiving aprotinin . CONCLUSION Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass . This benefit may be explained by a lower activation of fibrinolysis", "OBJECTIVE To determine whether two low-dose regimens of aprotinin influence platelet function . DESIGN Prospect i ve , r and omized , single-blinded trial . SETTING University teaching hospital performing 600 cardiac operations per year . PARTICIPANTS Fifty-nine patients scheduled for cardiac surgery undergoing cardiopulmonary bypass ( CPB ) of expected duration of 60 minutes or more . INTERVENTIONS Patients were r and omized into three groups . Group C ( control ) included 21 patients who did not receive aprotinin . In group A2 , 17 patients received 14,286 kallikrein inhibitor units (KIU)/kg ( 2 mg/kg ) of aprotinin before surgery , followed by a continuous infusion of 7,143 KIU/kg/h ( 1 mg/kg/h ) until the end of surgery . In group A4 , 19 patients received 28,572 KIU/kg ( 4 mg/kg ) of aprotinin before surgery , followed by the same infusion . MEASUREMENTS AND MAIN RESULTS Postoperative bleeding and transfusion requirements were significantly less in group A4 . Changes in platelet number and function were similar in the three groups . Platelet aggregation was assessed in four periods : before CPB ( T1 ) , post-CPB ( T2 ) , and 2 hours ( T3 ) and 4 hours ( T4 ) after CPB . Platelet aggregation induced by adenosine diphosphate , 1 and 2 micromol/L ; ristocetin , 1 mg/mL ; and arachadonic acid ( AA ) , 1.4 mmol/L , decreased at T2 ( p < 0.001 ) in all groups , and for the ristocetin and AA groups , remained at less than baseline values at T3 and T4 . In five patients from each group , platelet receptors for glycoprotein IIb-IIIa ( GPIIb-IIIa ) and expression of platelet activation markers , guanosine monophosphate 140 ( GMP-140 ) and lysosomal protein , were measured by flow cytometry before and after CPB . Modifications in the expression of GPIIb-IIIa were always modest and without statistical significance . Platelet activation markers , GMP-140 or lysosomal protein , nearly doubled from baseline to post-CPB only in the A4 group , whereas they remained stable in both other groups ( statistically not significant ) . CONCLUSION The two regimens of aprotinin , both considered low dosage , did not exert a protective effect on platelet function . Neither dose produced changes in platelet GPIIb-IIIa or platelet activation markers . However , bleeding and transfusion needs were decreased", "BACKGROUND Patients having cardiac operations often require blood transfusions . Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations . To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage , we studied 212 patients undergoing primary sternotomy for valve replacement or repair . METHODS This study was multicenter , r and omized , prospect i ve , double-blind , and placebo-controlled . Patients received high-dose aprotinin ( n = 71 ) , low-dose aprotinin ( n = 70 ) , or placebo ( n = 71 ) . The study medication was given as a loading dose followed by a continuous infusion and pump prime dose . Heparin administration was st and ardized . Transfusions , postoperative mediastinal shed blood , and adverse events were tracked . RESULTS Demographic profiles were similar among the treatment groups . Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo ( high-dose aprotinin , 63 % , p = 0.092 ; low-dose aprotinin , 52 % , p = 0.592 ; placebo , 48 % ) . Aprotinin was associated with a reduction in the volume of mediastinal shed blood ( high-dose aprotinin vs placebo , p = 0.002 ; low-dose aprotinin vs placebo , p = 0.017 ) . Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction ( high-dose aprotinin , 11 % ; low-dose aprotinin , 7 % ; placebo , 0 % ; p = 0.01 ) . A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus . CONCLUSIONS Aprotinin treatment in this population did not reduce allogeneic blood use , although there were significant reductions in the volume of mediastinal shed blood", "BACKGROUND Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients . To examine the safety and dose-related efficacy of aprotinin , a prospect i ve , multicenter , placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft ( CABG ) surgery . METHODS AND RESULTS Two hundred eighty-seven patients were r and omly assigned to receive either high-dose aprotinin , low-dose aprotinin , pump-prime-only aprotinin , or placebo . Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume . The percentage of patients requiring donor-red-blood-cell ( RBC ) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups ( high-dose aprotinin , 54 % ; low-dose aprotinin , 46 % ; pump-prime only , 72 % ; and placebo , 75 % ; overall P = .001 ) . The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo ( high-dose aprotinin , 1.6 + /- 0.2 U ; low-dose aprotinin , 1.6 + /- 0.3 U ; pump-prime-only , 2.5 + /- 0.3 U ; and placebo , 3.4 + /- 0.5 U ; P = .0001 ) . There was also a significant difference in total blood-product exposures among treatment groups ( high-dose aprotinin , 2.2 + /- 0.4 U ; low-dose aprotinin , 3.4 + /- 0.9 U ; pump-prime-only , 5.1 + /- 0.9 U ; placebo , 10.3 + /- 1.4 U ) . There were no differences among treatment groups for the incidence of perioperative myocardial infa rct ion ( MI ) . CONCLUSIONS This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI", "Background : Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery . There is a large difference in agent price and perhaps in efficacy . Methods : In a prospect i ve , r and omized , partially blinded study , 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion , tranexamic acid ( 10-mg/kg load , 1-mg · kg−1 · h−1 infusion ) , tranexamic acid with pre – cardiopulmonary bypass autologous whole-blood collection ( 12.5 % blood volume ) and reinfusion after cardiopulmonary bypass ( combined therapy ) , or saline infusion ( placebo group ) . Results : There were complete data in 160 patients . The aprotinin ( n = 40 ) and combined therapy ( n = 32 ) groups ( data are median [ range ] ) had similar reductions in blood loss in the first 4 h in the intensive care unit ( 225 [ 40–761 ] and 163 [ 25–760 ] ml , respectively;P = 0.014 ) , erythrocyte transfusion requirements in the first 24 h in the intensive care unit ( 0 [ 0–3 ] and 0 [ 0–3 ] U , respectively;P = 0.004 ) , and duration s of time from end of cardiopulmonary bypass to discharge from the operating room ( 92 [ 57–215 ] and 94 [ 37 , 186 ] min , respectively;P = 0.01 ) compared with the placebo group ( n = 43 ) . Ten patients in the combined therapy group ( 30.3 % ) required transfusion of the autologous blood during cardiopulmonary bypass for anemia . Conclusions : The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin . Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies", "Cardiopulmonary bypass ( CPB ) increases risk of postoperative bleeding and need for transfusion . The aim of this study was to evaluate the effects of aprotinin , epsilon aminocaproic acid and tranexamic acid on coagulation patterns and need for banked blood transfusion . Ninety-six consecutive patients who underwent coronary artery bypass surgery were r and omly assigned to 4 groups ( 24 patients each ) . The following parameters were monitored before , during and after CPB : activated lotting time , hemoglobin , prothrombin time , activated prothromboplastin time , fibrinogen , antithrombin III , xDP , Factor VIII , Thrombin-Antithrombin Complex and plasminogen . Analysis of postoperative bleeding and need for transfusion showed that the aprotinin group had significantly lower mediastinal bleeding . Transfused patients were 2 , 4 , 12 and 18 respectively in the aprotinin , epsilon aminocaproic acid , tranexamic acid and placebo treated group . In conclusion the use of protease inhibitors significantly reduces postoperative bleeding and transfusion . The aprotinin-treated group had the lower need for transfusion", "To assess the efficacy and safety of the use of a high-dose regimen of aprotinin in routine cardiac operations , a placebo-controlled r and omized double- blind study was conducted in 93 adult patients undergoing cardiopulmonary bypass . Aprotinin-treated patients ( group A , n = 46 ) received 2 × 106 Kallikrein Inactivating Units ( KIU ) of aprotinin before incision , 2 × 106 KIU in the priming solution and 5 x 105 KIU/h during CPB . Control patients ( group B , n = 47 ) received the same volume of normal saline . Mean postoperative blood loss in ml after six hours and in total until removal of thoracic drains decreased significantly from 752 and 1933 in controls , to 358 and 1051 in treated patients ( p < 0.001 ) . Mean total transfusion needs were 2.6 ( A ) and 4.8 ( B ) units per patient . Adverse events were evenly distributed between both groups and could not be attributed to aprotinin use . We , therefore , recommend the use of a high-dose regimen of aprotinin for routine cardiac operations despite its cost", "One hundred sixty-five patients undergoing primary myocardial revascularization were prospect ively entered into a r and omized , double-blind , placebo-controlled study , in a single institution , in order to determine the influence of high- and low-dose aprotinin application on early coronary artery bypass graft patency . All patients were operated on by the same team and the three treatment groups were comparable in all demographic data and surgical variables . Postoperative chest tube drainage and transfusion requirements were significantly reduced in patients receiving high or low doses of aprotinin . In all patients vein and internal mammary artery graft patency was assessed by control coronary angiograms 4 to 15 days ( median 8.2 days ) postoperatively . In the high-dose aprotinin group , 140 of 142 vein grafts and in the low-dose aprotinin group all of the 128 vein grafts were patent compared with 138 of 139 in the placebo group . The difference was not statistically significant ( P > 0.05 ) . All pedicled internal mammary artery grafts were patent in the three treatment groups . The prevalence of perioperative myocardial infa rct ion was evaluated by serial creatine kinase-myocardial b and ( CK-MB ) isoenzyme measurements and by electrocardiographic recordings . No additional changes that could be attributed to aprotinin were observed . In conclusion , these results suggest that perioperative myocardial infraction secondary to aprotinin-induced native coronary artery or conduit thrombosis is not increased by aprotinin in patients undergoing primary myocardial revascularization", "CONTEXT Several journals have adopted the Consoli date d St and ards of Reporting Trials ( CONSORT ) recommendations to make assessment of the quality of r and omized controlled trials ( RCTs ) easier . One of these recommendations is that the trial 's results be discussed in light of the totality of the available evidence . OBJECTIVE To assess the extent to which reports of RCTs published in 5 general medical journals have discussed new results in light of all available evidence . DESIGN Assessment of the discussion sections in all 26 reports of RCTs published during May 1997 in Annals of Internal Medicine , BMJ , JAMA , The Lancet , and The New Engl and Journal of Medicine . MAIN OUTCOME MEASURE The inclusion or mention of a systematic review in the discussion section of each article . RESULTS In only 2 articles were the RCT 's results discussed in the context of an up date d systematic review of earlier trials . In a further 4 articles , references were made to relevant systematic review s , but no attempts were made to integrate the results of the new trials in up date d versions of these review s. One article was probably the first published trial to address the question studied . The remaining 19 articles included no evidence that any systematic attempt had been made to set the reported trial 's results in the context of previous trials . CONCLUSION There is little evidence that journals have adequately implemented the CONSORT recommendation that results of an RCT be discussed in light of the totality of the available evidence", "THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard", "BACKGROUND The recommended dose of aprotinin has been shown to reduce blood loss and need for blood transfusions , but the cost precludes its routine use . This study was design ed to determine whether a less expensive , ultra-low dose of aprotinin is effective when used in coronary artery bypass grafting with left internal mammary artery . METHODS Patients ( n = 202 ) were r and omized to receive either placebo or aprotinin , 0.5 million KIU before incision and 0.5 million KIU during initiation of cardiopulmonary bypass . Differences in quantity of blood transfused were analyzed . Further groups were analyzed to account for the effect of aspirin . Multivariable analysis was performed to determine risk factors for transfusion . Direct costs of blood products and aprotinin were tabulated for each group . RESULTS There was an important reduction in the proportion of patients transfused , and number of blood units transfused when aprotinin was given before coronary artery bypass grafting . These differences were even more important in patients on aspirin preoperatively . Independent predictors for increased number of transfusions were aspirin continued before operation , smaller body surface area , and the use of placebo instead of ultra-low dose aprotinin . There was no difference in morbidity between treatment groups . There was a reduction in direct costs associated with the use of aprotinin . CONCLUSIONS These data support the routine use of aprotinin 1 million KIU in coronary artery bypass grafting with left internal mammary artery to reduce cost and transfusion requirements", "CONTEXT Reliable interpretation of the results of a controlled trial entails setting its results in the context of similar research . A previous study showed that most reports of controlled trials published in 5 general medical journals in May 1997 were deficient in this respect . We assessed the extent to which reports of controlled trials published in the same 5 journals discussed new results in light of the totality of evidence from other controlled trials . METHODS Assessment of the discussion sections in all 33 reports of r and omized trials published during May 2001 in Annals of Internal Medicine , BMJ , JAMA , The Lancet , and The New Engl and Journal of Medicine . RESULTS Three reports appeared to have been the first published trials to address the questions studied . In none of the remaining 30 reports were the results of the new trial discussed in the context of an up date d systematic review of other trials . Although reference was made to relevant systematic review s in 3 of these 30 reports , there was no integration , quantitative or qualitative , of the results of the new trials in an up date of these review s. In the remaining 27 reports , there was no evidence that any systematic attempt had been made to set the new results in the context of previous trials . CONCLUSIONS Between 1997 and 2001 , there was no evidence of progress in the proportion of reports of trials published in general medical journals that discussed the new results within the context of , or with reference to , up-to- date systematic review s of relevant evidence from other controlled trials", "BACKGROUND High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting , but the safety and effectiveness of smaller doses is unclear . Furthermore , patient selection criteria for optimal use of the drug are not well defined . METHODS Seven hundred and four first-time coronary artery bypass grafting patients were r and omized to receive one of three doses of aprotinin ( high , low , and pump-prime-only ) or placebo . The patients were stratified as to risk of excessive bleeding . RESULTS All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements . Consistent efficacy was not , however , demonstrated in the subgroup of patients at low risk for bleeding . There were no differences in mortality or the incidences of renal failure , strokes , or definite myocardial infa rct ions between the groups , although the pump-prime-only dose was associated with a small increase in definite , probable , or possible myocardial infa rct ions ( p = 0.045 ) . CONCLUSIONS Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens . Although safe , aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding . The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infa rct ions", "BACKGROUND Cardiopulmonary bypass induces a systemic inflammatory response . Aprotinin , a nonspecific proteinase inhibitor is known to improve postoperative hemostasis and may modify the inflammatory reaction . This study evaluates the effects of low-dose aprotinin on inflammatory markers in patients scheduled for elective coronary artery bypass grafting . METHODS Patients were prospect ively r and omized into two groups : the control group ( C ) ( n = 14 ) and the low-dose aprotinin group ( A ) ( n = 15 ) with ( 2 x 10(6 ) KIU = 280 mg ) aprotinin added to the pump prime . Cytokine response ( interleukin-6 , soluble TNF II receptor ) , terminal complement production ( SC5b-9 ) , and neutrophil activation ( lactoferrin ) were assessed up to 6 hours postoperatively . Clinical data and hemostatic factors including fibrinopeptide A , thrombin-antithrombin complex , D-dimer , and plasmin/alpha2-antiplasmin were investigated . RESULTS In both study groups , a significant increase of all inflammatory markers was seen ( IL-6 , sTNF-IIR , SC5b-9 , lactoferrin ) , p less than 0.001 . Peak levels of complement production occurred after protamine administration , whereas cytokine increases were more pronounced postoperatively with marked elevation up to 6 hours . The markers did not differ significantly between groups throughout the study period ( p > 0.05 at each time of determination ) . However , after protamine administration reduced fibrinolysis ( D-dimer , plasmin/alpha2-antiplasmin ) was detected in group A. Measurements for coagulation ( fibrinopeptide A , thrombin-antithrombin complex ) were not significantly influenced by aprotinin . The total amount of blood loss during the first 24 hours was significantly reduced in group A ( p < 0.02 ) . CONCLUSIONS Low-dose aprotinin added to the pump prime does not inhibit the inflammatory response caused by cardiopulmonary bypass , but improves postoperative hemostasis . A potential effect of high-dose aprotinin on inflammatory markers remains to be eluci date", "BACKGROUND Aprotinin has been used increasingly to reduce postoperative blood loss in open heart operations . Although it was reported as safe in earlier studies , the overall safety of prophylactic use has been question ed recently . Because of the potential for complications and the high cost , it will be reasonable to use aprotinin more selectively in the postoperative period . METHODS We prospect ively studied the effect of postoperative low-dose aprotinin ( 2 million kallikrein inactivator units [ 280 mg ] ) on blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass . Seventy-five patients were r and omly assigned to three groups : prophylactic high-dose aprotinin ( group 1 ) , postoperative aprotinin ( group 2 ) , or a nonmedicated control group ( group 3 ) . RESULTS The three groups were comparable in all demographic and operative variables . Postoperative chest tube drainage was significantly decreased in both aprotinin groups compared with that in the control group ( 295 mL in group 1 and 325 mL in group 2 versus 411 mL in group 3 ; p < 0.05 ) . No significant difference was seen between the two aprotinin groups . The use of homologous blood products was significantly less in group 1 and group 2 than in group 3 ( 1.15 + /- 1.13 U and 1.35 + /- 1.30 U versus 2.55 + /- 1.09 U ; p < 0.05 ) . CONCLUSIONS Our results suggest that postoperative aprotinin reduces blood loss and transfusion requirements comparably with prophylactic high-dose aprotinin . Thus , one can restrict its use to patients with excessive postoperative bleeding", "The proteinase inhibitor aprotinin is used in open heart surgery to reduce intraoperative and postoperative blood loss and transfusion requirements . To investigate a possible influence on graft patency , a r and omized double-blind group comparison study was carried out in male patients elected for primary bypass surgery . One hundred ten ( 55/55 ) patients received either placebo treatment or aprotinin according to the Hammersmith scheme ( 2 Mio KIU as loading dose before sternotomy , followed by an infusion of 0.5 Mio KIU/h until the end of surgery ; 2 Mio KIU added to the priming volume additionally ) . Graft patency was evaluated by angiography in 44 aprotinin and 35 placebo patients between the 18th and 35th days postoperatively . There was no difference in the overall graft occlusion : in the aprotinin group 89.5 % ( 111/124 ) grafts were found patent compared to 87.2 % ( 89/102 ) in the placebo group . Of the aprotinin patients 72.7 % ( 32/44 ) and 71.4 % ( 25/35 ) of the placebo patients had all grafts patent . Venous grafts were occluded in 16 % ( 7/44 ) of aprotinin patients and in 29 % ( 10/35 ) of placebo patients . On the other h and 5/27 patients in the aprotinin group vs 0/27 in the placebo group had occluded internal mammary artery ( IMA ) grafts ( P = 0.0511 % ) . Graft occlusions were not accompanied by signs of myocardial infa rct ion in any case . Fifty-one patients in the aprotinin group and 47 patients in the placebo group were valid for parameters of clinical efficacy : blood loss within 6 h postoperatively was reduced by 58.5 % in the aprotinin group ( P < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Prophylactic aprotinin therapy has become a popular method to reduce bleeding associated with cardiac operations . Today essentially two dose regimens are used , a high-dose regimen with administration throughout the complete operative procedure and a low-dose regimen with administration only during bypass . In unblinded studies both regimens were found to be equally effective . This double-blind placebo-controlled study in 115 patients undergoing elective coronary artery bypass grafting was done to confirm these results without potential investigator bias . Intraoperative hemoglobin loss was significantly reduced ( p < 0.01 ) by 42 % in the high-dose group and by 17 % in the low-dose group compared with loss in control subjects . Blood loss 6 hours after operation was 377 ml in the low-dose and 266 ml in the high-dose group compared with 630 ml in the placebo group ( p < 0.05 and p < 0.001 , respectively ) . The average number of transfusions with packed red blood cells was reduced 31 % in the low-dose group and 45 % in the high-dose group , but the reductions were not significant . In a subgroup of patients , markers for coagulation and fibrinolysis were studied to investigate whether a different extent of activation existed . Fibrinolysis as measured by D-dimer levels was completely inhibited by the high-dose regimen , but was only partly suppressed in the low-dose group as compared with findings in the placebo group . Thrombin generation during cardiopulmonary bypass as reflected by F1 + 2 levels was lower in patients treated with aprotinin , but the difference was not significant . Concentrations of thrombin inactivated by antithrombin III were not different between the groups . The observation that low-dose aprotinin significantly improved hemostasis but did not inhibit hyperfibrinolysis supports our previous finding that low-dose aprotinin mainly protects platelet adhesive function . The better result obtained with high-dose aprotinin may indicate the contribution of hyperfibrinolysis to bleeding after cardiopulmonary bypass . Because high-dose aprotinin is administered outside the period of full heparinization and might therefore increase the risk of thromboembolic complications , we propose a modification of the low-dose schedule to increase aprotinin levels sufficient for plasmin inhibition before release of the aortic crossclamp", "We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization . Patients were r and omly assigned to high-dose aprotinin , low-dose aprotinin , or placebo treatment groups in a double-blind , placebo-controlled study . Treatment groups did not differ significantly with respect to age , sex , red cell mass , number of grafts , use of internal thoracic artery , or incidence of preoperative aspirin therapy . Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage ( 720 + /- 753 , 866 + /- 1,636 , and 1,121 + /- 683 mL , respectively , for high-dose aprotinin , low-dose aprotinin , and placebo ; p < 0.001 ) . Transfusion requirements were reduced in aprotinin-treated patients ( 2.1 + /- 4.2 , 4.8 + /- 11.8 , and 4.1 + /- 6.2 units for high-dose , low-dose , and placebo , respectively ; p < 0.001 ) . A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively . Q-wave myocardial infa rct ions were increased in the aprotinin subgroups ( 17.5 % , 14.3 % , and 8.9 % for high-dose , low-dose , and placebo groups ; not significant ) . Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo . We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis", "Sixty patients ( four groups of 15 patients ) were entered in a r and omized , controlled study to compare the efficacy of prophylactic treatment with dipyridamole , tranexamic acid , and aprotinin to reduce bleeding after elective coronary artery bypass grafting . Only patients with a preoperative platelet count of less than 246 x 10(9)/L were selected because a previous study showed that these individuals are at risk for increased postoperative bleeding . Compared to control subjects , postoperative blood loss 6 hours after operation was significantly reduced by tranexamic acid ( 674 + /- 411 versus 352 + /- 150 mL ; p < 0.05 ) and by aprotinin ( 270 + /- 174 mL ; p < 0.01 ) . Dipyridamole did not reduce postoperative blood loss and was associated with complications in 3 patients . We conclude that hemostasis after cardiac operations can be improved with tranexamic acid and aprotinin . Dipyridamole appeared to be ineffective", "BACKGROUND Cytokines are implicated in the pathogenesis of the \" whole-body inflammatory response \" that may complicate the period after cardiopulmonary bypass ( CPB ) . Low-Dose aprotinin in the pump during CPB has been shown to improve postoperative hemostasis and platelet preservation . We tested the hypothesis that low-dose aprotinin influences the inflammatory reaction ( in terms of cytokine release ) after CPB . METHODS In a prospect i ve , r and omized study , 36 patients undergoing elective coronary artery bypass grafting were investigated . Nineteen patients received low-dose aprotinin ( 2 x 10(6 ) KIU ( 280 mg ] in the pump ) , and a control group of 19 did not . Complement activation , cytokine production , leukocyte elastase release . D-dimer level , full blood count , postoperative blood loss , and transfusion requirements were analyzed before , during , and after after CPB . RESULTS Interleukin-1 beta was not detected in either group , whereas traces of tumor necrosis factor-alpha were infrequently observed . Plasma elastase , interleukin-6 , interleukin-8 , and neutrophil count increased ( p < 0.001 ) during and after CPB compared with the baseline levels , reaching a peak at 2 hours after protamine administration in both groups before returning toward baseline at 24 hours . Proinflammatory cytokine markers did not differ significantly ( p > 0.1 ) between the groups throughout the study period . The C5b-9 level increased ( p < 0.001 ) in both groups perioperatively , reaching its peak 15 minutes after protamine . Twenty-four-hour postoperative blood loss was significantly ( p < 0.001 ) reduced in the aprotinin group in association with markedly reduced D-dimer levels ( p < 0.001 ) . Patients in the aprotinin group also received significantly less banked blood postoperatively than the control group ( p < 0.01 ) . CONCLUSIONS Low-dose aprotinin fails to modify proinflammatory cytokine release , yet confers hemostatic improvement through reduced fibrinolysis in patients undergoing routine coronary artery bypass grafting", "OBJECTIVE As Aspirin ( ASA ) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases , most patients scheduled for CABG are treated with ASA therapy . Consequently , impaired hemostasis is a problem in the management of CABG patients . Clinical studies have shown that Aprotinin can reduce bleeding and the use of blood products by 50 % in patients both with and without pre-operative ASA therapy . Concerning the combined effect of peri-operative low-dose ASA therapy and intra-operative high-dose Aprotinin therapy , the gathering of additional and prospect i ve data seemed to be necessary . METHODS We conducted a double-blind two-centre r and omised three-arm study in patients with elective primary CABG surgery . Three groups have been tested , comprising 119 patients in total ( group A : ASA + Aprotinin , group B : placebo + Aprotinin , group C : placebo + placebo ) to investigate a possible reduction of bleeding in Aprotinin treated patients . For all patients , thromboxane levels were used to identify ASA or placebo treatment . RESULTS The post-operative blood loss is significantly reduced by 21 % after Trasylol administration ( B vs. C ; P = 0.009 ) . The unexpected result of this study has been that the pre-treatment with ASA led to a further reduction of 18 % ( A vs. C ; P < 0.0001 ) . The difference between the two Aprotinin groups ( A and B ) is significant ( P = 0 . 01 ) in favour of ASA pre-treatment . Myocardial infa rct ion ( MI ) had been diagnosed at levels of 1.8 % in total ( 2/113 ) , 2.6 % ( 1/38 ) in group B and 3.2 % ( 1/31 ) in group C. An additional blinded evaluation of ECG , enzyme levels and clinical status revealed ' definite , probable and possible ' MIs of 5 % in group A , compared to 16 % in group B and 13 % in group C , thus providing no evidence for a higher risk of infa rct ion by Aprotinin treatment . When comparing the ASA group to non-ASA pre-treatment , a strong trend towards a reduction in MI rate becomes obvious , from 15 % to 5 % in favour of the ASA pre-treatment ( P = 0.08 ) . Concerning other peri-operative complications , no statistical difference between the groups could be detected . CONCLUSIONS A reduction in post-operative blood loss in primary elective CABG surgery with intra-operative Aprotinin treatment could be confirmed . A low-dose ASA treatment combined with a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding , but did in fact reduce the post-operative blood loss . The protective effect of ASA on peri-operative MI has been evident through a reduction of MI rate in ASA treated patients" ]