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"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" ]
[ "Although transplantation of adult bone marrow mesenchymal stem cells ( BM-MSCs ) holds promise in the treatment for pulmonary arterial hypertension ( PAH ) , the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency . Here , we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs ( hESC-MSCs ) with adult BM-MSCs for the treatment of PAH in an animal model . One week following monocrotaline (MCT)-induced PAH , mice were r and omly assigned to receive phosphate-buffered saline ( MCT group ) ; 3.0 × 106 human BM-derived MSCs ( BM-MSCs group ) or 3.0 × 106 hESC-derived MSCs ( hESC-MSCs group ) via tail vein injection . At 3 weeks posttransplantation , the right ventricular systolic pressure ( RVSP ) , degree of RV hypertrophy , and medial wall thickening of pulmonary arteries were lower= , and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups ( all p < 0.05 ) . At 1 week posttransplantation , the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group ( all p < 0.01 ) . At 3 weeks posttransplantation , implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation . In addition , protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity . Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation , especially blood vessel morphogenesis . We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH", "Abstract We investigated the effect of adipose-derived stem cells ( ADSCs ) transplantation effects on structural remodeling and pulmonary artery pressure in monocrotaline (MCT)-induced pulmonary hypertensive rats . In the first experiment , 32 male Sprague-Dawley ( SD ) rats were r and omly divided into four groups ( n = 8/group ) : 3 ADSCs treated groups and normal control ( Ctrl ) . ADSCs were administered through the left jugular vein at 105 , 106 and 107 cells , respectively , and a cell density of 106cells/ml was shown to be optimal . The GFP-tagged ADSCs were identified in the lungs and differentiated into endothelial-like cells . In the second experiment , 96 male SD rats were r and omly divided into three groups ( n = 32/group ) : Ctrl , MCT-induced pulmonary arterial hypertension ( PAH ) , and PAH treated with ADSCs ( ADSCs ) . Two weeks post-MCT administration , the ADSCs group received 1 × 106 ADSCs via the external jugular vein . Compared to PAH rats , mean pulmonary arterial pressure was decreased in rats at 1 , 2 , and 3 weeks after ADSCs-treatment ( 18.63 ± 2.15 mmHg versus 24.53 ± 2.90 mmHg ; 23.07 ± 2.84 mmHg versus 33.18 ± 2.30 mmHg ; 22.98 ± 2.34 mmHg versus 36.38 ± 3.28 mmHg , p < 0.05 ) . Meanwhile , the right heart hypertrophy index ( 36.2 1 ± 4.27 % versus 41.01 ± 1.29 % ; 39.47 ± 4.02 % versus 48.75 ± 2 .13 % ; 41.02 ± 0.9 % versus 50.52 ± 1.49 % , p < 0.05 , respectively ) , ratio of wall/lumen thickness , as well as the wall/lumen area were significantly reduced in PAH rats at these time points following ADSCs-treatment , as compared with untreated PAH rats . In summary , ADSCs may colonize the pulmonary arteries , attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling", "The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell ( BMSC ) transp1antation on lung and heart damage in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension ( PAH ) . The animals were r and omly divided into 3 groups : control , PAH and BMSC implantation groups . Structural changes in the pulmonary vascular wall , such as the pulmonary artery lumen area ( VA ) and vascular area ( TAA ) were measured by hematoxylin and eosin ( H&E ) staining , and the hemodynamics were detected by echocardiography . Two weeks post-operation , our results demonstrated that sublingual vein injection of BMSCs significantly attenuated the pulmonary vascular structural and hemodynamic changes caused by pulmonary arterial hypertension . The mechanism may be executed via paracrine effects", "OBJECTIVE To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival . DESIGN Registry with prospect i ve follow-up . SETTING Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart , Lung , and Blood Institute . PATIENTS Patients ( 194 ) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988 . MEASUREMENTS At diagnosis , measurements of hemodynamic variables , pulmonary function , and gas exchange variables were taken in addition to information on demographic variables , medical history , and life-style . Patients were followed for survival at 6-month intervals . MAIN RESULTS The estimated median survival of these patients was 2.8 years ( 95 % Cl , 1.9 to 3.7 years ) . Estimated single-year survival rates were as follows : at 1 year , 68 % ( Cl , 61 % to 75 % ) ; at 3 years , 48 % ( Cl , 41 % to 55 % ) ; and at 5 years , 34 % ( Cl , 24 % to 44 % ) . Variables associated with poor survival included a New York Heart Association ( NYHA ) functional class of III or IV , presence of Raynaud phenomenon , elevated mean right atrial pressure , elevated mean pulmonary artery pressure , decreased cardiac index , and decreased diffusing capacity for carbon monoxide ( DLCO ) . Drug therapy at entry or discharge was not associated with survival duration . CONCLUSIONS Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables : mean pulmonary artery pressure , mean right atrial pressure , and cardiac index . Such an equation , once vali date d prospect ively , could be used as an adjunct in planning treatment strategies and allocating medical re sources", "BACKGROUND Sildenafil inhibits phosphodiesterase type 5 , an enzyme that metabolizes cyclic guanosine monophosphate , thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells , including those in the lung . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 278 patients with symptomatic pulmonary arterial hypertension ( either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts ) to placebo or sildenafil ( 20 , 40 , or 80 mg ) orally three times daily for 12 weeks . The primary end point was the change from baseline to week 12 in the distance walked in six minutes . The change in mean pulmonary-artery pressure and World Health Organization ( WHO ) functional class and the incidence of clinical worsening were also assessed , but the study was not powered to assess mortality . Patients completing the 12-week r and omized study could enter a long-term extension study . RESULTS The distance walked in six minutes increased from baseline in all sildenafil groups ; the mean placebo-corrected treatment effects were 45 m ( + 13.0 percent ) , 46 m ( + 13.3 percent ) , and 50 m ( + 14.7 percent ) for 20 , 40 , and 80 mg of sildenafil , respectively ( P<0.001 for all comparisons ) . All sildenafil doses reduced the mean pulmonary-artery pressure ( P=0.04 , P=0.01 , and P<0.001 , respectively ) , improved the WHO functional class ( P=0.003 , P<0.001 , and P<0.001 , respectively ) , and were associated with side effects such as flushing , dyspepsia , and diarrhea . The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo . Among the 222 patients completing one year of treatment with sildenafil monotherapy , the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS Sildenafil improves exercise capacity , WHO functional class , and hemodynamics in patients with symptomatic pulmonary arterial hypertension", "BACKGROUND Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point . We assessed the efficacy of macitentan , a new dual endothelin-receptor antagonist , using a primary end point of morbidity and mortality in a long-term trial . METHODS We r and omly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily , macitentan at a once-daily dose of 3 mg , or macitentan at a once-daily dose of 10 mg . Stable use of oral or inhaled therapy for pulmonary arterial hypertension , other than endothelin-receptor antagonists , was allowed at study entry . The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death , atrial septostomy , lung transplantation , initiation of treatment with intravenous or subcutaneous prostanoids , or worsening of pulmonary arterial hypertension . RESULTS A total of 250 patients were r and omly assigned to placebo , 250 to the 3-mg macitentan dose , and 242 to the 10-mg macitentan dose . The primary end point occurred in 46.4 % , 38.0 % , and 31.4 % of the patients in these groups , respectively . The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 ( 97.5 % confidence interval [ CI ] , 0.52 to 0.96 ; P=0.01 ) , and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 ( 97.5 % CI , 0.39 to 0.76 ; P<0.001 ) . Worsening of pulmonary arterial hypertension was the most frequent primary end-point event . The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline . Adverse events more frequently associated with macitentan than with placebo were headache , nasopharyngitis , and anemia . CONCLUSIONS Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study . ( Funded by Actelion Pharmaceuticals ; SERAPHIN Clinical Trials.gov number , NCT00660179 . )", "Our previous studies have shown that bone marrow mesenchymal stem cells ( BMSCs ) can inhibit the progression of pulmonary artery hypertension ( PAH ) in the monocrotaline ( MCT ) model in the short term . The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation . PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study . Postoperatively , the animals were r and omly divided into three groups ( n = 10 in each group ) : control , PAH group , and BMSCs implantation group . Six months after injection , immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced ( P < 0.05 ) ; the area of collagen fibers in lung tissue was lower ( P < 0.05 ) , and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased ( P < 0.05 ) . Immunofluorescence showed that the cells have the ability to differentiate between von Willebr and factor and vascular endothelial growth factor . Six months after intravenous injection , BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation", "Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs . In addition , our previous studies suggested that autologous EPC transplantation was feasible , safe , and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH . Thus , we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH . Thirteen children with IPAH received intravenous infusion of autologous EPCs . The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion . At the time of 12 wk , mPAP decreased by 6.4 mmHg from 70.3 + /- 19.0 to 63.9 + /- 19.3 mmHg ( p = 0.015 ) . PVR decreased by approximately 19 % from 1118 + /- 537 to 906 + /- 377 dyn s/cm(5 ) ( p = 0.047 ) . CO increased from 3.39 + /- 0.79 to 3.85 + /- 0.42 L/min ( p = 0.048 ) . The 6-MWD increased by 39 m from 359 + /- 82 to 399 + /- 74 m ( p = 0.012 ) . NYHA functional class also improved . There were no severe adverse events with cell infusion . The small pilot study suggested that intravenous infusion of autologous EPCs was feasible , safe , and associated with significant improvements in exercise capacity , NYHA functional class , and pulmonary hemodynamics in children with IPAH . Confirmation of these results in a r and omized controlled trial are essential", "BACKGROUND Uncontrolled studies suggested that aerosolized iloprost , a stable analogue of prostacyclin , causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension . METHODS We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost ( six or nine times per day ; median inhaled dose , 30 microg per day ) with inhalation of placebo . A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension ( New York Heart Association [ NYHA ] functional class III or IV ) were included . The primary end point was met if , after week 12 , the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent , respectively , in the absence of clinical deterioration according to predefined criteria and death . RESULTS The combined clinical end point was met by 16.8 percent of the patients receiving iloprost , as compared with 4.9 percent of the patients receiving placebo ( P=0.007 ) . There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole ( P=0.004 ) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension . Overall , 4.0 percent of patients in the iloprost group ( including one who died ) and 13.7 percent of those in the placebo group ( including four who died ) did not complete the study ( P=0.024 ) ; the most common reason for withdrawal was clinical deterioration . As compared with base-line values , hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation ( P<0.001 ) , were largely unchanged when measured before iloprost inhalation , and were significantly worse in the placebo group . Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class ( P=0.03 ) , dyspnea ( P=0.015 ) , and quality of life ( P=0.026 ) . Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group , although this adverse effect was not associated with clinical deterioration . CONCLUSIONS Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension", "BACKGROUND High pulmonary vascular resistance ( PVR ) may be a risk factor for early and late mortality in both Glen shunt and Fontan operation patients . Furthermore , PVR may increase long after the Fontan operation . Whether pulmonary vasodilators such as phosphodiesterase 5 inhibitors can decrease PVR in patients with single ventricular physiology remains undetermined . METHODS AND RESULTS This was a prospect i ve , multicenter study . Patients with single ventricular physiology who have a PVR index higher than 2.5 Wood units · ㎡ ( WU ) were enrolled . Cardiac catheterization was performed before and after administration of sildenafil in all patients . After the Fontan operation , a six minute walk test ( 6MWT ) was also performed . A total of 42 patients were enrolled . PVR was significantly decreased in each stage of single ventricular physiology after sildenafil administration : from 4.3±1.5WU to 2.1±0.6WU ( p<0.01 ) in patients before a Glenn shunt , from 3.2±0.5WU to 1.6±0.6WU ( p<0.001 ) in patients after a Glenn shunt , and from 3.9±1.7WU to 2.3±0.8WU ( p<0.001 ) in patients after Fontan . In patients after Fontan , the 6MWT increased from 416±74 m to 485±72 m ( p<0.01 ) , and NYHA functional class improved significantly ( p<0.05 ) after sildenafil administration . No major side effects were observed in any patients . CONCLUSIONS Sildenafil reduced PVR in patients with single ventricle physiology . Sildenafil increased exercise capacity and improved NYHA functional class in patients after a Fontan operation . This implies that pulmonary vasodilation is a potential therapeutic target in selected patients with elevated PVR with single ventricle physiology . Long-term clinical significance warrants further study", "OBJECTIVES The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan , an oral endothelin type A receptor-selective antagonist , in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options . Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH . METHODS In this double-blind , dose-ranging study , 64 patients with idiopathic PAH or PAH associated with collagen vascular disease , anorexigen use , or human immunodeficiency virus infection were r and omized to receive 1 , 2.5 , 5 , or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan . The primary end point was an improvement from baseline in 6-min walk distance ( 6MWD ) ; secondary end points included Borg dyspnea index , World Health Organization ( WHO ) functional class , a subject global assessment , and cardiopulmonary hemodynamics . RESULTS At 12 weeks , ambrisentan increased 6MWD ( + 36.1 m , p < 0.0001 ) with similar and statistically significant increases for each dose group ( range , + 33.9 to + 38.1 m ) . Improvements were also observed in Borg dyspnea index , WHO functional class , subject global assessment , mean pulmonary arterial pressure ( -5.2 mm Hg , p < 0.0001 ) , and cardiac index ( + 0.33 l/min/m2 , p < 0.0008 ) . Adverse events were mild and unrelated to dose , including the incidence of elevated serum aminotransferase concentrations > 3 times the upper limit of normal ( 3.1 % ) . CONCLUSIONS Ambrisentan appears to improve exercise capacity , symptoms , and hemodynamics in patients with PAH . The incidence and severity of liver enzyme abnormalities appear to be low", "UNLABELLED Pulmonary arterial hypertension ( PAH ) is characterized by functional and structural changes in the pulmonary vasculature , and despite the drug treatment that made significant progress , the prognosis of patients with advanced PH remains extremely poor . In the present study , we investigated the early effect of bone marrow mesenchymal stem cells ( BMSCs ) on experimental high blood flow-induced PAH model rats and discussed the mechanism . BMSCs were isolated , cultured from bone marrow of Sprague-Dawley ( SD ) rat . The animal model of PAH was created by surgical methods to produce a left-to-right shunt . Following the successful establishment of the PAH model , rats were r and omly assigned to three groups ( n=20 in each group ) : sham group ( control ) , PAH group , and BMSC group ( received a sublingual vein injection of 1 - 5 × 10(6 ) BMSCs ) . Two weeks after the administration , BMSCs significantly reduced the vascular remodeling , improved the hemodynamic data , and deceased the right ventricle weight ratio to left ventricular plus septal weight ( RV/LV+S ) ( P<0.05 ) . Real-time reverse transcription-polymerase chain reaction ( RT-PCR ) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1β ( IL-1β ) , IL-6 , and tumor necrosis factor-α ( TNF-α ) were reduced ( P<0.05 ) ; the expression of matrix metallo proteinase-9 ( MMP-9 ) was lower ( P<0.05 ) ; vascular endothelial growth factor ( VEGF ) was higher in BMSC group than those in PAH group ( P<0.05 ) . CONCLUSION Sublingual vein injection of BMSCs for 2 weeks , significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH ; decreased pulmonary vascular remodeling and inflammation ; and enhanced angiogenesis", "Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective . However , this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis , thromboembolism , or syncope . Treprostinil , a stable prostacyclin analogue , can be administered by a continuous subcutaneous infusion , avoiding these risks . We conducted a 12-week , double-blind , placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension , either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts . Exercise capacity improved with treprostinil and was unchanged with placebo ; the between treatment group difference in median six-minute walking distance was 16 m ( p = 0.006 ) . Improvement in exercise capacity was greater in the sicker patients and was dose-related , but independent of disease etiology . Concomitantly , treprostinil significantly improved indices of dyspnea , signs and symptoms of pulmonary hypertension , and hemodynamics . The most common side effect attributed to treprostinil was infusion site pain ( 85 % ) leading to premature discontinuation from the study in 8 % of patients . Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage . We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension", "BACKGROUND Endothelin 1 , a powerful endogenous vasoconstrictor and mitogen , might be a cause of pulmonary hypertension . We describe the efficacy and safety of bosentan , a dual endothelin-receptor antagonist that can be taken orally , in patients with severe pulmonary hypertension . METHODS In this double-blind , placebo-controlled study , 32 patients with pulmonary hypertension ( primary or associated with scleroderma ) were r and omly assigned to bosentan ( 62.5 mg taken twice daily for 4 weeks then 125 mg twice daily ) or placebo for a minimum of 12 weeks . The primary endpoint was change in exercise capacity . Secondary endpoints included changes in cardiopulmonary haemodynamics , Borg dyspnoea index , WHO functional class , and withdrawal due to clinical worsening . Analysis was by intention to treat . FINDINGS In patients given bosentan , the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline , whereas it worsened by 6 m in those on placebo ( difference 76 m [ 95 % CI 12 - 139 ] , p=0.021 ) . The improvement was maintained for at least 20 weeks . The cardiac index was 1.0 L min(-1 ) m(-2 ) ( 95 % CI 0.6 - 1.4 , p<0.0001 ) greater in patients given bosentan than in those given placebo . Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5 ) with bosentan , but increased by 191 dyn s cm(-5 ) with placebo ( difference -415 [ -608 to -221 ] , p=0.0002 ) . Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class . All three withdrawals from clinical worsening were in the placebo group ( p=0.033 ) . The number and nature of adverse events did not differ between the two groups . INTERPRETATION Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension , suggesting that endothelin has an important role in pulmonary hypertension", "Background Systematic Review s ( SRs ) of experimental animal studies are not yet common practice , but awareness of the merits of conducting such SRs is steadily increasing . As animal intervention studies differ from r and omized clinical trials ( RCT ) in many aspects , the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies . The Cochrane Collaboration developed a Risk of Bias ( RoB ) tool to establish consistency and avoid discrepancies in assessing the method ological quality of RCTs . A similar initiative is warranted in the field of animal experimentation . Methods We provide an RoB tool for animal intervention studies ( SYRCLE ’s RoB tool ) . This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies . To enhance transparency and applicability , we formulated signalling questions to facilitate judgment . Results The result ing RoB tool for animal studies contains 10 entries . These entries are related to selection bias , performance bias , detection bias , attrition bias , reporting bias and other biases . Half these items are in agreement with the items in the Cochrane RoB tool . Most of the variations between the two tools are due to differences in design between RCTs and animal studies . Shortcomings in , or unfamiliarity with , specific aspects of experimental design of animal studies compared to clinical studies also play a role . Conclusions SYRCLE ’s RoB tool is an adapted version of the Cochrane RoB tool . Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies . This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the method ological quality of 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" ]
[ "BACKGROUND Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospect i ve , r and omized trial to improve survival . METHODS We conducted a 12-week prospect i ve , r and omized , multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol ( formerly called prostacyclin ) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension ( New York Heart Association functional class III or IV ) . RESULTS Exercise capacity was improved in the 41 patients treated with epoprostenol ( median distance walked in six minutes , 362 m at 12 weeks vs. 315 m at base line ) , but it decreased in the 40 patients treated with conventional therapy alone ( 204 m at 12 weeks vs. 270 m at base line ; P < 0.002 for the comparison of the treatment groups ) . Indexes of the quality of life were improved only in the epoprostenol group ( P < 0.01 ) . Hemodynamics improved at 12 weeks in the epoprostenol-treated patients . The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and + 3 percent , respectively ( difference in mean change , -6.7 mm Hg ; 95 percent confidence interval , -10.7 to -2.6 mm Hg ; P < 0.002 ) , and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and + 9 percent , respectively ( difference in mean change , -4.9 mm Hg/liter/min ; 95 percent confidence interval , -7.6 to -2.3 mm Hg/liter/min ; P < 0.001 ) . Eight patients died during the study , all of whom had been r and omly assigned to conventional therapy ( P = 0.003 ) . Serious complications included four episodes of catheter-related sepsis and one thrombotic event . CONCLUSIONS As compared with conventional therapy , the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement , as well as improved survival in patients with severe primary pulmonary hypertension", "BACKGROUND Patients with precapillary pulmonary hypertension ( PH ) exhibit a poor exercise capacity due to an impaired vasodilatory response of their pulmonary arteries . By causing the pulmonary artery to dilate , inhaled nitric oxide ( NO ) may allow an increase in exercise capacity in patients with PH . METHODS AND RESULTS On 2 separate days , 3 days apart , 14 patients with precapillary PH ( 10 primary PH , 4 residual PH after correction of an intracardiac shunt ; age , 40+/-12 years ; mean pulmonary artery pressure , 60+/-23 mm Hg ) performed exercise , with and without inhalation of 20 ppm NO , on a cycle ergometer . The work rate was increased 15 W/min until their symptom-limited maximum , with breath-by-breath gas analysis . Patients were r and omly and blindly selected to inhale NO on either their first or second test . Peak exercise load and anaerobic threshold tended to increase , but not significantly . Peak oxygen consumption ( f1.gif \" BORDER=\"0\" > O(2 ) ) and Deltaf1.gif \" BORDER=\"0\" > O(2)/DeltaW ratio increased significantly , by 18 % and 22 % , respectively ( peak f1.gif \" BORDER=\"0\" > O(2 ) , 13.6+/-3.6 to 16.0+/-4 . 1 mL. kg(-1 ) . min(-1 ) ; Deltaf1.gif \" BORDER=\"0\" > O(2)/DeltaW ratio , 5 . 8+/-2.4 to 7.1+/-2.3 mL. kg(-1 ) . min(-1 ) . W(-1 ) ; both P<0.01 ) . Peak f1.gif \" BORDER=\"0\" > O(2 ) increased > 10 % in 12 of the 14 patients . However , respiratory quotient at peak exercise decreased from 1 . 22+/-0.15 to 1.09+/-0.15 ( P<0.01 ) . CONCLUSIONS Inhaled NO substantially increases oxygen consumption at the same workload during exercise . This finding supports the possibility of ambulatory NO inhalation therapy in patients with precapillary PH", "After the approval of bosentan for the treatment of pulmonary arterial hypertension ( PAH ) , European authorities required the introduction of a post-marketing surveillance system ( PMS ) to obtain further data on its safety profile . A novel , prospect i ve , internet-based PMS was design ed , which solicited reports on elevated aminotransferases , medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation . Data captured included demographics , PAH aetiology , baseline functional status and concomitant PAH-specific medications . Safety signals captured included death , hospitalisation , serious adverse events , unexpected adverse events and elevated aminotransferases . Within 30 months , 4,994 patients were included , representing 79 % of patients receiving bosentan in Europe . In total , 4,623 patients were naïve to treatment ; of these , 352 had elevated aminotransferases , corresponding to a crude incidence of 7.6 % and an annual rate of 10.1 % . Bosentan was discontinued due to elevated aminotransferases in 150 ( 3.2 % ) bosentan-naïve patients . Safety results were consistent across subgroups and aetiologies . The novel post-marketing surveillance captured targeted safety data ( “ potential safety signals ” ) from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials . These data complement those from r and omised controlled clinical trials and provide important additional information on the safety profile of bosentan", "Background : Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases ( CTDs ) such as systemic sclerosis ( SSc ) , leading to vasoconstriction , fibrosis , hypertrophy and inflammation . A frequent complication of CTD is pulmonary arterial hypertension ( PAH ) , which has a major effect on functioning and quality of life , and is associated with a particularly poor prognosis . Objective : To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD , mostly SSc and lupus erythematosus . Methods : 66 patients with PAH secondary to CTD , in World Health Organization functional class III or IV , were r and omised to two double-blind , placebo-controlled studies and followed up for 12 and 16 weeks , respectively . The primary end point was change in exercise capacity , assessed using the 6-min walk test . In both studies and their extensions , survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan – Meier estimates . Results : 44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study ( + 19.5 m , 95 % confidence interval ( CI ) −3.2 to 42.2 ) , whereas patients treated with placebo deteriorated ( −2.6 m , 95 % CI −54.0 to 48.7 ) . 64 patients subsequently received bosentan in an open-label long-term extension study . Mean ( st and ard deviation ( SD ) ) exposure to bosentan was 1.6 ( 0.9 ) years , and duration of observation was 1.8 ( 0.8 ) years . 8 ( 16 % ) patients received epoprostenol as add-on treatment and 7 ( 14 % ) after discontinuation of bosentan . Survival in those receiving bosentan was 85.9 % after 1 year and 73.4 % after 2 years . Conclusion : Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo . The long-term follow-up of these patients suggests that first-line bosentan , with the subsequent addition of other PAH treatments if required , is safe for long-term treatment and may have a positive effect on outcome", "Pulmonary hypertension is characterized by progressive elevation of pulmonary artery pressure and vascular resistance , often leading to right ventricular failure and death ( 1 - 3 ) . Continuous intravenous infusion of epoprostenol improves prognosis and symptoms in patients with primary ( idiopathic ) pulmonary hypertension ( 4 - 8 ) . R and omized , controlled clinical trials of epoprostenol for secondary pulmonary hypertension have not been conducted . Pulmonary hypertension frequently complicates the scleroderma spectrum of disease , which includes diffuse scleroderma , limited scleroderma ( the CREST syndrome [ calcinosis cutis , the Raynaud phenomenon , esophageal dysfunction , sclerodactyly , and telangectasia ] ) , and the overlap syndrome . These multisystem diseases are characterized by connective tissue and vascular abnormalities ; vascular lesions are prominent in all affected tissues ( 9 ) . Pulmonary hypertension occurs in up to 33 % of patients with diffuse scleroderma and 10 % to 50 % of those with the CREST syndrome ( 10 , 11 ) , in which it is one of the leading causes of death ( 12 , 13 ) . Pulmonary hypertension in the scleroderma spectrum of disease may be associated with interstitial pulmonary fibrosis or may consist of a direct involvement of small and medium-sized pulmonary arteries and arterioles with smooth-muscle hyperplasia , medial hypertrophy , and intimal proliferation ( 10 , 13 , 14 ) . Principal involvement of the pulmonary vasculature is more common in the CREST syndrome , whereas patients with pulmonary hypertension and diffuse scleroderma more often have interstitial lung disease ( 13 ) . No therapies have been proven effective for pulmonary hypertension secondary to the scleroderma spectrum of disease . Small numbers of patients have responded to captopril ( 15 ) , nifedipine ( 16 - 20 ) , and prazosin . In a short-term study of intravenous epoprostenol in seven patients with scleroderma ( two with diffuse scleroderma and five with limited scleroderma ) , six had a decrease in mean pulmonary artery pressure and pulmonary vascular resistance ( 21 ) . In a small study of pulmonary hypertension secondary to connective tissue disease , long-term infusion therapy with a prostacyclin analogue , iloprost , result ed in improvement in New York Heart Association ( NYHA ) functional class and quality of life but a variable hemodynamic response ( 22 ) . Results from a single-center , uncontrolled study suggest that long-term , continuously infused epoprostenol therapy can produce hemodynamic and symptomatic responses in patients with connective tissue disease who have severe pulmonary hypertension that is refractory to conventional medical therapy ( 23 ) . The rationale for using continuous epoprostenol infusion to treat pulmonary hypertension secondary to the scleroderma spectrum of disease was based on the efficacy of this therapy for primary pulmonary hypertension ( 4 - 8 ) and recognition that scleroderma is a disease characterized by vasospasm and structural changes in the walls of blood vessels . Prostacyclin is a naturally occurring substance produced by vascular endothelium that has vasodilating , antiplatelet aggregation , and cytoprotective effects ( 24 - 33 ) . Endogenous production of prostacyclin is decreased in an animal model of neonatal pulmonary hypertension ( 34 ) and in adult humans with pulmonary hypertension ( 35 ) . Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in patients with primary pulmonary hypertension ( 36 ) . Endothelial dysfunction also plays an important role in the vascular manifestations of the scleroderma spectrum of disease ( 37 , 38 ) , including the Raynaud phenomenon and digital ischemia , which cause considerable morbidity . Calcium-channel blockers ( 39 - 45 ) , enalapril ( 46 ) , and intermittent intravenous infusions of prostacyclin ( 47 - 49 ) and iloprost ( 50 - 54 ) improve the Raynaud phenomenon in some patients . Mixed results have been obtained with oral prostacyclin analogues ( 55 , 56 ) , and a recent multicenter trial of oral iloprost showed no benefit ( 57 ) . The effect of long-term , continuously infused epoprostenol on the severity of the Raynaud phenomenon and on digital ulcer counts has not been previously evaluated . Our 12-week multicenter , open-label , r and omized study was design ed to determine whether the beneficial effect of epoprostenol seen in patients with primary pulmonary hypertension could be extended to patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . Our objective was to evaluate the effects of continuous infusion of epoprostenol on exercise capacity in patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . A secondary objective was assessment of the effects of long-term continuous epoprostenol infusion on cardiopulmonary hemodynamics , Borg Dyspnea Score , Dyspnea-Fatigue Rating , NYHA functional class , survival , and safety . Vasospastic manifestations , such as the Raynaud phenomenon and digital ulcerations , were also followed . Methods Patient Selection Eligible patients had pulmonary hypertension secondary to the scleroderma spectrum of disease in accordance with the inclusion and exclusion criteria summarized in Table 1 . For the purpose s of this study , the scleroderma spectrum of disease was defined as systemic sclerosis with diffuse or limited scleroderma ( 58 ) ; systemic sclerosis that overlapped with another connective tissue disease ; or the presence of definite features of systemic sclerosis , including the Raynaud phenomenon and positive test result for antinuclear antibody , plus positive test results for anticentromere antibody , anti-Scl 70 antibody , or nailfold capillary abnormalities . Systemic sclerosis with limited cutaneous involvement ( the CREST syndrome ) was defined as the presence of any three of the following conditions : subcutaneous calcinosis , the Raynaud phenomenon , esophageal dysfunction ( defined clinical ly ) , sclerodactyly , or telangectasia . Patients with interstitial lung disease of a more than mild degree were not included in the study because such patients were thought to be less likely to show benefit . Table 1 . Key Inclusion and Exclusion Criteria On the basis of a previous 12-week study of the effects of epoprostenol infusion in patients with severe primary pulmonary hypertension ( 6 ) and using the 6-minute walk test as the primary outcome measure , we calculated that 50 patients per treatment group would provide 80 % power to detect a difference of 50 meters in the average change from baseline , at an level of 0.05 ( two-tailed t-test ) . R and omization and Treatment The protocol was approved by the institutional review boards of the 17 participating centers . After giving informed consent , 111 eligible patients were r and omly assigned ( 1:1 ) to receive continuous epoprostenol infusion ( Flolan , Glaxo Wellcome , Inc. , Research Triangle Park , North Carolina ) plus conventional therapy or to receive conventional therapy alone . Investigators contacted a central r and omization center to obtain treatment assignment , which was based on a stratified r and omized block design . Assignments were stratified on the basis of vasodilator use at baseline ( yes or no ) and exercise capacity at baseline ( 50 to<200 m or 200 m ) and were r and omized within blocks . Fifty-six patients were assigned to receive epoprostenol plus conventional therapy , and 55 patients were assigned to receive conventional therapy alone . Investigators were not blinded to treatment group assignment ; however , independent blinded observers assessed the primary efficacy measure , exercise capacity . Patients taking calcium-channel blockers at study entry continued to take them during the study period . Adjustments in concomitant medications were allowed during the study on the basis of clinical judgment . Patients in both groups were to receive oral anticoagulants during the study ; 94 of the 111 enrolled patients took warfarin . Venous access for epoprostenol infusion ( in the epoprostenol group only ) was obtained by insertion of a permanent indwelling central venous catheter . Epoprostenol was infused continuously by a portable infusion pump ( CADD-1 Model 5100 HF , SIMS Deltec , St. Paul , Minnesota ) . Patients were instructed in sterile technique , catheter care , and drug preparation and administration . Epoprostenol therapy was initiated at a low dose ( usually 2 ng/kg of body weight per minute ) . During the 12-week study , doses were adjusted on the basis of signs or symptoms consistent with persistent pulmonary hypertension in the absence of intolerable adverse effects ( Figure 1 ) . Figure 1 . Epoprostenol dosing . Outcome Measures The primary measure of efficacy was exercise capacity , as defined by the distance a patient could walk in 6 minutes . Trained observers at each site who were not otherwise involved in patient care administered the 6-minute walk test . All patients wore an ambulatory infusion pump and a hospital gown over their clothes to mask the presence or absence of a long-term indwelling catheter , thereby blinding testers to the patients ' treatment groups . Each patient performed one practice walk test . A st and ardized , unencouraged 6-minute walk test was performed as described elsewhere ( 59 ) at baseline and at 1 , 6 , and 12 weeks . The 6-minute walk test has been shown to provide meaningful outcome data in assessing potential therapy for patients with pulmonary hypertension ( 6 ) . Secondary measures of efficacy were cardiopulmonary hemodynamics measured by performing right-heart catheterization using st and ard techniques at baseline and week 12 ; the Borg Dyspnea Score ( 60 ) , obtained immediately after completion of the 6-minute walk test at baseline and 1 , 6 , and 12 weeks ( 6 , 59 ) ; the Dyspnea-Fatigue Rating , obtained before the 6-minute walk test at baseline and weeks 1 , 6 , and 12 ( 61 ) ; NYHA functional class ( 62 ) , measured at baseline and weeks 1 , 6 , and 12 ; digital ulcer counts , done at baseline and weeks 6 and 12 ; and the severity of the Raynaud phenomenon ," ]
"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." ]
[ "BACKGROUND Although improved epicardial blood flow ( as assessed with either TIMI flow grade s or TIMI frame count ) has been related to reduced mortality after administration of thrombolytic drugs , the relationship of myocardial perfusion ( as assessed on the coronary arteriogram ) to mortality has not been examined . METHODS AND RESULTS A new , simple angiographic method , the TIMI myocardial perfusion ( TMP ) grade , was used to assess the filling and clearance of contrast in the myocardium in 762 patients in the TIMI ( Thrombolysis In Myocardial Infa rct ion ) 10B trial , and its relationship to mortality was examined . TMP grade 0 was defined as no apparent tissue-level perfusion ( no ground-glass appearance of blush or opacification of the myocardium ) in the distribution of the culprit artery ; TMP grade 1 indicates presence of myocardial blush but no clearance from the microvasculature ( blush or a stain was present on the next injection ) ; TMP grade 2 blush clears slowly ( blush is strongly persistent and diminishes minimally or not at all during 3 cardiac cycles of the washout phase ) ; and TMP grade 3 indicates that blush begins to clear during washout ( blush is minimally persistent after 3 cardiac cycles of washout ) . There was a mortality gradient across the TMP grade s , with mortality lowest in those patients with TMP grade 3 ( 2.0 % ) , intermediate in TMP grade 2 ( 4.4 % ) , and highest in TMP grade s 0 and 1 ( 6.0 % ; 3-way P=0.05 ) . Even among patients with TIMI grade 3 flow in the epicardial artery , the TMP grade s allowed further risk stratification of 30-day mortality : 0.73 % for TMP grade 3 ; 2.9 % for TMP grade 2 ; 5.0 % for TMP grade 0 or 1 ( P=0.03 for TMP grade 3 versus grade s 0 , 1 , and 2 ; 3-way P=0.066 ) . TMP grade 3 flow was a multivariate correlate of 30-day mortality ( OR 0.35 , 95 % CI 0.12 to 1.02 , P=0.054 ) in a multivariate model that adjusted for the presence of TIMI 3 flow ( P = NS ) , the corrected TIMI frame count ( OR 1.02 , P=0.06 ) , the presence of an anterior myocardial infa rct ion ( OR 2.3 , P=0.03 ) , pulse rate on admission ( P = NS ) , female sex ( P = NS ) , and age ( OR 1.1 , P<0.001 ) . CONCLUSIONS Impaired perfusion of the myocardium on coronary arteriography by use of the TMP grade is related to a higher risk of mortality after administration of thrombolytic drugs that is independent of flow in the epicardial artery . Patients with both normal epicardial flow ( TIMI grade 3 flow ) and normal tissue level perfusion ( TMP grade 3 ) have an extremely low risk of mortality", "Background —We hypothesized that preserved microvascular integrity in the area at risk would favorably influence left ventricular ( LV ) remodeling and long-term outcome after acute myocardial infa rct ion . Methods and Results —Before and after successful primary angioplasty ( percutaneous transluminal coronary angioplasty [ PTCA ] ) , 124 patients with acute myocardial infa rct ion underwent intracoronary myocardial contrast echo ( MCE ) . An MCE score index ( MCESI ) was derived by averaging the single-segment score ( 0=not visible , 1=patchy , 2=homogeneous contrast effect ) within the area at risk . An MCESI ≥1 was considered adequate reperfusion . Mean follow-up was 46±32 months . After PTCA , 100 patients showed adequate reperfusion ( no microvascular dysfunction , NoMD ) , whereas 24 did not ( MD ) . MD patients had a higher mean creatine kinase ( 4153±2422 versus 2743±1774 U/L ; P = 0.002 ) and baseline wall-motion score index ( 2.61±0.31 versus 2.25±0.42 ; P < 0.001 ) and a lower baseline ejection fraction ( 33±8 % versus 40±7 % ; P < 0.001 ) . From day 1 on , LV volumes progressively increased in the MD patients ( n=19 ) and were larger than those of NoMD patients ( n=85 ) at 6 months ( end-diastolic volume 170±55 versus 115±29 mL ; P < 0.001 ) . MCESI was the most important independent predictor of LV dilation ( OR 0.61 , 95 % CI 0.52 to 0.71 , P < 0.000001 ) . By Cox analysis , MD represented the only predictor of cardiac death ( OR 0.26 , 95 % CI 0.09 to 0.72 , P = 0.010 ) and combined events ( cardiac death , reinfa rct ion , and heart failure ; OR 0.44 , 95 % CI 0.23 to 0.85 , P = 0.014 ) . MD patients showed worse survival in terms of cardiac death ( P < 0.0001 ) and combined events ( P < 0.0001 ) . Conclusions —In reperfused acute myocardial infa rct ion , MD within the risk area is an important predictor of both LV remodeling and unfavorable long-term outcome", "Increased neutrophil counts have been associated with an increased risk of adverse clinical events after acute myocardial infa rct ion ( AMI ) . We examined the association of neutrophil counts on admission with degree of microvascular injury and left ventricular functional recovery after primary coronary angioplasty in AMI . We studied 116 patients with a first anterior wall AMI who underwent primary coronary angioplasty within 12 hours of onset . Patients were categorized into 3 groups based on initial neutrophil count : low ( < 5,000/mm(3 ) ) , intermediate ( 5,000 to 10,000/mm(3 ) ) , and high ( > 10,000/mm(3 ) ) . Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire . We defined severe microvascular injury as the presence of systolic flow reversal and a diastolic deceleration time < 600 ms . Echocardiographic wall motion was analyzed before revascularization and 4 weeks after revascularization . In patients with a high neutrophil count , systolic flow reversal was more frequently observed , diastolic deceleration time was shorter , and coronary flow reserve was lower . By regression analysis , neutrophil count significantly correlated with diastolic deceleration time ( r = -0.38 , p < 0.0001 ) , coronary flow reserve ( r = -0.33 , p = 0.0004 ) , and score for change in wall motion ( r = -0.36 , p = 0.0004 ) . Multivariate analysis showed that neutrophil count on admission was an independent predictor of severe microvascular injury ( odds ratio 2.94 , p = 0.02 ) . In conclusion , neutrophilia on admission is associated with impaired microvascular reperfusion and poor functional recovery after primary coronary angioplasty", "Objective : The aim of this pilot study was to determine whether early atorvastatin treatment will reduce left ventricle ( LV ) remodeling , infa rct size , and improve microvascular perfusion . Background : In animal studies , early statin therapy reduces reperfusion injury after a percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( AMI ) . Methods : Forty‐two consecutive patients ( 82 % male , mean age 61.2 ± 9.8 ) who underwent a primary PCI for a first ST‐elevated AMI were r and omized for pretreatment with atorvastatin 80 mg ( n = 20 ) or placebo ( n = 22 ) and continued with the same dosage daily for 1 week . All patients received atorvastatin 80 mg once daily 7 days after primary PCI . The LV function and infa rct size were measured by magnetic resonance imaging within 1 day , at 1 week , and 3 months follow up . The primary endpoint was the end‐systolic volume index ( ESVI ) at 3 months . Secondary endpoints were global LV function measurements , myocardial infa rct size , biochemical cardiac markers , TIMI flow , and ST‐T elevation resolution . Results : ESVI 3 months after AMI was 25.1 mL/m2 in the atorvastatin arm and 25.0 mL/m2 in the placebo arm ( P = 0.74 ) . The differences in change from baseline to 3 months follow up in global LV function and myocardial infa rct size did not differ between both treatment arms . Furthermore , biochemical markers , TIMI flow , and ST‐T elevation resolution did not differ between atorvastatin and placebo arm . Conclusions : In this pilot study , pretreatment with atorvastatin in an acute myocardial infa rct ion does not result in an improved cardiac function , microvascular perfusion , or decreased myocardial infa rct size . © 2012 Wiley Periodicals", "Primary and secondary prevention with statins reduce major cardiac events in patients with coronary artery disease . The impact of pretreatment with statins prior to percutaneous coronary intervention ( PCI ) is not well established . The objective of this study was to determine if pretreatment with statins prior to PCI reduce myonecrosis and improve clinical outcome . One hundred nineteen consecutive patients with acute coronary syndrome who underwent PCI were identified . We compared the incidence of myonecrosis defined as peak elevation of CK‐MB or CK three time above upper limit of normal within 24 hr and the 6‐month cardiovascular event rate ( death , nonfatal myocardial infa rct ion unrelated to PCI , target vessels revascularization , and unstable angina requiring hospitalization ) among patients who received statins prior to PCI ( n = 63 ) to those who did not ( n = 56 ) . Pretreated patients were more likely to have history of myocardial infa rct ion or revascularization ( 63 % vs. 43 % ; P = 0.015 ) , hyperlipidemia ( 80 % vs. 48 % ; P = 0.001 ) , hypertension ( 83 % vs. 49 % ; P = 0.02 ) , and use of angiotensin‐converting enzyme inhibitor ( 62 % vs. 38 % ; P = 0.008 ) . The rest of baseline characteristics were similar between the two groups , including use of glycoprotein IIb/IIIa inhibitors , number of diseased vessels , and type of lesions . Patients pretreated with statins had a significantly lower incidence of myonecrosis ( 2 % vs. 10 % ; P = 0.04 ) at 24 hr and a significantly lower clinical event ( CE ) rate at 6 months ( 17 % vs. 21 % ; P = 0.015 ) . Of patients not pretreated with statins , 72 % were taking statins at 6 months as compared to 98 % of pretreated patients . After adjusting for all baseline characteristics , use of statins prior to PCI was associated with a marked decrease in risk of all CEs ( OR = 0.2 ; CI = 0.06–0.63 ; P = 0.006 ) . Statin therapy prior to PCI may reduces peri‐PCI myonecrosis and late cardiac events . These results need to be confirmed in large prospect i ve r and omized trials . Catheter Cardiovasc Interv 2004;62:193–197 . © 2004 Wiley‐Liss ,", "OBJECTIVES This study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( PCI ) . BACKGROUND Previous r and omized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events ( MACEs ) in patients with stable angina pectoris and acute coronary syndrome . However , no r and omized studies have been carried out with STEMI patients in a primary PCI setting . METHODS A total 171 patients with STEMI were r and omized to 80-mg atorvastatin ( n = 86 ) or 10-mg atorvastatin ( n = 85 ) arms for pre-treatment before PCI . All patients were prescribed clopidogrel ( 600 mg ) before PCI . After PCI , both groups were treated with atorvastatin ( 10 mg ) . The primary end point was 30-day incidence of MACE including death , nonfatal MI , and target vessel revascularization . Secondary end points included corrected thrombolysis in myocardial infa rct ion frame count , myocardial blush grade , and ST-segment resolution at 90 min after PCI . RESULTS MACE occurred in 5 ( 5.8 % ) and 9 ( 10.6 % ) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms , respectively ( p = 0.26 ) . Corrected thrombolysis in myocardial infa rct ion frame count was lower in the 80-mg atorvastatin arm ( 26.9 + /- 12.3 vs. 34.1 + /- 19.0 , p = 0.01 ) . Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm ( 2.2 + /- 0.8 vs. 1.9 + /- 0.8 , p = 0.02 and 61.8 + /- 26.2 vs. 50.6 + /- 25.8 % , p = 0.01 ) . CONCLUSIONS High-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI . High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion . ( Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infa rct ion [ STATIN STEMI ] ; NCT00808717 )", "Background Recent data have demonstrated a lower mortality in acute ST-elevation myocardial infa rct ion ( STEMI ) patients with previous treatment with statins , especially in patients with high risk profiles . Moreover , a significant reduction in enzymatic infa rct size in non-STEMI patients could be observed . However , systematic data of the impact of chronic statin pre-treatment on myocardial damage and reperfusion injury assessed with the gold st and ard cardiac magnetic resonance imaging ( CMR ) are lacking . The aim of our prospect i ve study was therefore to assess the effects of a chronic statin pre-treatment on myocardial damage as assessed by CMR in patients with acute reperfused STEMI .", "BACKGROUND Atorvastatin pretreatment has been reported to reduce myocardial damage in patients undergoing percutaneous coronary intervention ( PCI ) . We sought to investigate the effect of atorvastatin pretreatment on infa rct size in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . METHODS Patients undergoing primary PCI for ST-segment elevation myocardial infa rct ion within 12 hours after symptom onset were r and omized to an atorvastatin group ( 80 mg before PCI and for 5 days after PCI [ n = 89 ] ) or a control group ( 10 mg daily after PCI [ n = 84 ] ) . The primary end point was infa rct size measured by technetium Tc 99 m tetrofosmin single-photon emission computed tomography between days 5 and 14 . RESULTS Baseline clinical , angiographic , and procedural characteristics were not significantly different between groups except for age and current smoking status . There was no significant difference in infa rct size ( as a percentage of the left ventricle ) between groups ( 22.2 % ± 15.5 % in the atorvastatin group vs 21.6 % ± 15.4 % in the control group , P = .79 ) . The median infa rct size was 19.0 % ( interquartile range 9.0 - 32.0 ) in the atorvastatin group and 18.0 % ( 9.3 - 32.5 ) in the control group ( P = .76 ) . Achievement of myocardial blush grade 2/3 and complete ST-segment resolution at 60 minutes after PCI occurred with similar frequency ( 72.8 % vs 81.9 % , P = .33 and 43.2 % vs 47.5 % , P = .57 , respectively ) . CONCLUSIONS Pretreatment with high-dose atorvastatin followed by further treatment for 5 days did not reduce infa rct size measured by single-photon emission computed tomography in patients undergoing primary PCI", "BACKGROUND Studies have reported an association between receipt of statin therapy and a reduction in complications after elective percutaneous coronary intervention ( PCI ) . However , there are limited data on the effects of chronic statin therapy before the occurrence of an acute myocardial infa rct ion ( AMI ) . OBJECTIVE This study investigated whether administration of chronic statin therapy before AMI was associated with a reduction in reperfusion injury in AMI patients undergoing PCI . METHODS This was a retrospective study of consecutive patients with a first AMI who underwent successful reperfusion therapy with PCI within 24 hours after the onset of AMI between April 1998 and October 2003 . Patients were stratified according to whether they had or had not been receiving chronic statin therapy for > or = 1 month before the onset of AMI . The following end points were compared after PCI : electrocardiographic resolution of ST segment elevation , defined as a reduction of > or = 50 % from the initial value ; achievement of Thrombolysis in Myocardial Infa rct ion ( TIMI ) grade 3 flow ; corrected TIMI frame count ( cTFC ) ; maximum serum creatine kinase ( CK ) level ; and the type and frequency of ventricular arrhythmias . RESULTS The study enrolled 386 patients , 40 of whom had been receiving statin therapy before the onset of AMI . The clinical characteristics of the 2 groups were similar at baseline , with the exceptions of a significantly higher rate of hyperlipidemia in the statin group compared with the nonstatin group ( P < 0.001 ) , significantly greater chronic use of aspirin therapy ( P < 0.001 ) , and significantly greater chronic use of antihypertensive medications ( beta-blockers : P = 0.004 ; angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers : P = 0.007 ; calcium channel blockers : P = 0.006 ) . Electrocardiographic ST segment resolution after PCI was observed in 87.5 % and 69.9 % of the statin and nonstatin groups , respectively ( hazard ratio [ HR ] : 3.01 ; 95 % CI , 1.15 - 7.90 ; P = 0.025 ) . Achievement of TIMI grade 3 flow after PCI was seen in 95.0 % of the statin group and 83.5 % of the nonstatin group ( HR : 3.75 ; 95 % CI , 0.88 - 16.0 ; P = NS ) . Patients treated with a statin had a significantly lower mean ( SD ) maximum CK level compared with the nonstatin group ( 2300 [ 1449 ] vs 3538 [ 3170 ] IU/mL , respectively ; P = 0.015 ) and a lower cTFC after PCI ( 18.8 [ 4.0 ] vs 24.2 [ 14.2 ] ; P = 0.017 ) . The difference in reperfusion arrhythmias between groups was not statistically significant . After adjustment for baseline covariates , pretreatment with a statin was found to be an independent predictor of ST segment resolution after PCI ( HR : 2.95 ; 95 % CI , 1.08 - 8.09 ; P = 0.035 ) and prevention of impaired coronary flow ( HR : 3.00 ; 95 % CI , 1.63 - 5.55 ; P < 0.001 ) . CONCLUSION In this study , receipt of chronic statin therapy before the onset of AMI was associated with improvement in epicardial perfusion and a reduction in myocardial necrosis after PCI", "Recent studies emphasized the non-lipid-lowering effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on endothelial function , inflammation , and platelet activation in patients with stable atherosclerosis . This study sought to evaluate the impact of statin pretreatment in patients with acute myocardial infa rct ion ( AMI ) on level of systemic inflammation and myocardial perfusion . A total of 253 consecutive patients undergoing primary angioplasty on a native vessel within 12 hours of AMI were divided into a group with statin pretreatment ( n = 86 ) and control patients ( n = 167 ) . Angiographic myocardial blush grade ( MBG ) after revascularization of the infa rct -related artery was determined to evaluate myocardial perfusion . Statin pretreatment was associated with a lower frequency of increased C-reactive protein ( > or=5 mg/L ) on admission compared with the control group ( 48 % vs 64 % ; p = 0.019 ) . The frequency of normal perfusion ( MBG 3 ) was higher in the statin-pretreatment group than the control group ( 45 % vs 26 % , respectively ; p < 0.001 ) . Statin pretreatment was an independent predictor of normal myocardial perfusion ( MBG 3 ; odds ratio 2.53 , 95 % confidence interval 1.15 to 9.53 , p = 0.022 ) in addition to age < or=70 years and C-reactive protein < 5 mg/L. In conclusion , statin pretreatment in patients with AMI was associated with decreased systemic inflammation and better perfusion after primary angioplasty of the infa rct -related artery" ]
"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." ]
[ "INTRODUCTION We explored the differential effect of cessation interventions ( behavioral support sessions with [ BSS+ ] and without [ BSS ] bupropion ) between hookah and cigarette smokers . METHODS We reanalyzed the data from a major cluster-r and omized controlled trial , ASSIST ( Action to Stop Smoking In Suspected Tuberculosis ) , which consisted of 3 conditions : ( a ) behavioral support sessions ( BSS ) , ( b ) behavioral support sessions plus 7 weeks of bupropion therapy ( BSS+ ) , and ( c ) controls receiving usual care . The trial originally recruited 1,955 adult smokers with suspected tuberculosis from 33 health centers in the Jhang and Sargodha districts of Pakistan between 2010 and 2011 . The primary endpoint was continuous 6-month smoking abstinence , which was determined by carbon monoxide levels . Subgroup-specific relative risks ( RRs ) of smoking abstinence were computed and tested for differential intervention effect using log binomial regression ( generalized linear model ) between 3 subgroups ( cigarette-only : 1,255 ; mixed : 485 ; and hookah-only : 215 ) . RESULTS The test result for homogeneity of intervention effects between the smoking forms was statistically significant ( p-value for BSS+ : .04 and for BSS : .02 ) . Compared to the control , both interventions appeared to be effective among hookah smokers ( RR = 2.5 ; 95 % CI = 1.3 - 4.7 and RR = 2.2 ; 95 % CI = 1.3 - 3.8 , respectively ) but less effective among cigarette smokers ( RR = 6.6 ; 95 % CI = 4.6 - 9.6 and RR = 5.8 ; 95 % CI = 4.0 - 8.5 ) , respectively . CONCLUSIONS The differential intervention effects on hookah and cigarette smokers were seen ( a ) because the behavioral support intervention was design ed primarily for cigarette smokers ; ( b ) because of differences in demographic characteristics , behavioral , and sociocultural determinants ; or ( c ) because of differences in nicotine dependency levels between the 2 groups", "INTRODUCTION Tobacco use in low- to middle-income countries is a major public health concern for both smokers and those exposed to environmental tobacco smoke ( ETS ) . Egypt has made important strides in controlling tobacco use , but smoking and ETS remain highly prevalent . This r and omized intervention sought to improve the target population 's knowledge regarding the hazards of smoking and ETS and to change attitudes and smoking behaviors within the community and the household . METHODS In this 2005 - 2006 study in Egypt 's Qalyubia governorate , trained professionals visited schools , households , mosques , and health care centers in rural villages r and omly selected for the intervention to discuss the adverse effects of smoking and ETS exposure and ways to reduce one 's ETS exposure . Data collected in interviewer-facilitated surveys before and after the intervention period were analyzed in pairwise comparisons with data from control villages to assess the effectiveness of the intervention in achieving its aims . RESULTS The intervention group showed a greater increase in underst and ing the dangers associated with smoking cigarettes and waterpipes and became more proactive in limiting ETS exposure by asking smokers to stop , avoiding areas with ETS , and enacting smoking bans in the home . However , the intervention had little to no impact on the number of smokers and the amount of tobacco smoked . CONCLUSIONS Results are consistent with previous studies showing that changing smokers ' behavior can be difficult , but community-wide efforts to reduce ETS exposure through smoking bans , education , and empowering people to ask smokers to stop are effective . The method can be generalized to other setting", "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias", "INTRODUCTION Tobacco use remains a major public health problem worldwide . Water-pipe smoking is spreading rapidly and threatening to undermine the successes achieved in tobacco control . METHODS A school-based longitudinal study in the city of Irbid , Jordan , was performed from 2008 to 2010 . All seventh- grade students in 19 r and omly selected schools , out of a total of 60 schools in the city , were enrolled at baseline and surveyed annually . RESULTS Of the 1781 students enrolled at baseline 1,701 ( 95.5 % ) were still in the study at the end of the second year of follow-up ( 869 boys , median age at baseline 13 years ) . Ever and current water-pipe smoking were higher than those of cigarette smoking at baseline ( ever smoking : 25.9 % vs. 17.6 % and current smoking : 13.3 % vs. 5.3 % for water-pipe and cigarette smoking , respectively ; p < .01 for both ) but cigarette smoking caught up by the second year of follow-up ( ever smoking : 46.4 % vs. 44.7 % ; p = .32 and current smoking : 18.9 % vs. 14.9 % ; p < .01 ) . Water pipe-only smokers at baseline were twice as likely to become current cigarette smokers after 2 years compared with never smokers ( relative risk ( RR ) = 2.1 ; 95 % CI = 1.2 , 3.4 ) . A similar pattern was observed for cigarette-only smokers at baseline ( RR = 2.0 ; 95 % CI = 0.9 , 4.8 ) . CONCLUSIONS Prevalence of water-pipe and cigarette smoking increased dramatically over the 2-year follow-up period with similar patterns in boys and girls , although girls had lower prevalence in all categories . Water-pipe smoking at baseline predicted the progress to cigarette smoking in the future and vice versa", "Background Involving children in research studies requires obtaining parental permission . A school-based intervention to delay/prevent waterpipe use for 7th and 8th grade rs in Qatar was developed , and parental permission requested . Fifty three percent ( 2308/4314 ) of the parents returned permission forms ; of those 19.5 % of the total ( 840/4314 ) granted permission . This paper describes the challenges to obtaining parental permission . No research to date has described such challenges in the Arab world . Methods A r and om sample of 40 schools in Doha , Qatar was selected for inclusion in the original intervention . Permission forms were distributed to parents for approval of their child ’s participation . The permission forms requested that parents indicate their reasons for non-permission if they declined . These were categorized into themes . In order to underst and reasons for non-permission , interviews with parents were conducted . Phone numbers of parents were requested from the school administration ; 12 of the 40 schools ( 30 % ) agreed to provide the contact information . A r and om sample of 28 parents from 12 schools was interviewed to reach data saturation . Thematic analysis was used to analyze their responses . Results Reasons for non-permission documented in both the forms and interviews included : poor timing ; lack of interest ; the child not wanting to participate ; and the child living in a smoke-free environment . Interviews provided information on important topics to include in the consent forms , parents ’ decision-making processes regarding their child ’s participation , and considerations for communicating with parents . Many parents also indicated that this was the first time they had been asked to give an informed consent for their child ’s participation in a study . Conclusions Results indicate that more attention needs to be given to the informed parental consent process . Research ers should consider enhancing both the methods of communicating information as well the specific information provided . Before embarking on recruitment of children for studies , formative research on the parental consent process is suggested", "Background Among Arab citizens in Israel , cigarette and nargila ( hookah , waterpipe ) smoking is a serious public health problem , particularly among the young adult population . With the dramatic increase of Internet and computer use among Arab college and university students , a Web-based program may provide an easy , accessible tool to reduce smoking rates without heavy re source dem and s required by traditional methods . Objective The purpose of this research was to examine the acceptability and feasibility of a pilot Web-based program that provides tailored feedback to increase smoking knowledge and reduce cigarette and nargila smoking behaviors among Arab college/university students in Israel . Methods A pilot Web-based program was developed , consisting of a self-administered question naire and feedback system on cigarette and nargila smoking . Arab university students were recruited to participate in a mixed- methods study , using both quantitative ( pre-/posttest study design ) and qualitative tools . A posttest was implemented at 1 month following participation in the intervention to assess any changes in smoking knowledge and behaviors . Focus group sessions were implemented to assess acceptability and preferences related to the Web-based program . Results A total of 225 participants —response rate of 63.2 % (225/356)—completed the intervention at baseline and at 1-month post study , and were used for the comparative analysis . Statistically significant reductions in nargila smoking among participants ( P=.001 ) were found . The intervention did not result in reductions in cigarette smoking . However , the tailored Web intervention result ed in statistically significant increases in the intention to quit smoking ( P=.021 ) . No statistically significant increases in knowledge were seen at 1-month post study . Participants expressed high satisfaction with the intervention and 93.8 % ( 211/225 ) of those who completed the intervention at both time intervals reported that they would recommend the program to their friends , indicating excellent acceptability and feasibility of the intervention . This was further emphasized in the focus group sessions . Conclusions A tailored Web-based program may be a promising tool to reduce nargila smoking among Arab university students in Israel . The tailored Web intervention was not successful at significantly reducing cigarette smoking or increasing knowledge . However , the intervention did increase participants ’ intention to quit smoking . Participants considered the Web-based tool to be an interesting , feasible , and highly acceptable strategy . Trial Registration Trial Registration : IS RCT N registry IS RCT N59207794 ; http://www.is rct n.com/IS RCT N59207794 ( Archived by WebCite at http://www.webcitation.org/6VkYOBNOJ )", "Objectives : This research was undertaken with the aim of assessing the indoor air quality in popular hospitality venues , as also to evaluate the effectiveness of the nationwide comprehensive public smoking ban . The analysis was split into two halves – baseline study taken up prior to implementation of the said ban on 2nd October 2008 , and the follow-up study after it came into effect . Material s and Methods : Twenty-five venues including five restaurants , fourteen resto-bars , two hookah ( smoking water-pipe ) cafes and four pubs were selected using a mix of r and om , convenience and purpose ful sampling . Particulate matter ( PM2.5 ) measurements at these venues were made using TSI SidePak AM510 Personal Aerosol Monitor . Results : The average PM2.5 level in venues where smoking was permitted prior to implementation of ban was found to be 669.95 μg/m3 in the baseline study . Post ban , the average PM2.5 level in same test venues reduced to 240.8 μg/m3 . The hookah cafes were an exception as the average PM2.5 levels exceeded the permissible limits before as well as post ban . Conclusion : The baseline study showed that the hospitality venues had hazardous levels of PM2.5 particles arising from second-h and smoke prior to smoking ban . These decreased by a maximum of 64 % after the law took effect . A substantial improvement in air quality at these venues post implementation of the smoking ban indicated the effectiveness of the law", "BACKGROUND Waterpipe use has increased dramatically in the Middle East and other parts of the world . Many users exhibit signs of dependence , including withdrawal and difficulty quitting , but there is no evidence base to guide cessation efforts . METHODS We developed a behavioral cessation program for willing-to-quit waterpipe users , and evaluated its feasibility and efficacy in a pilot , two arm , parallel group , r and omized , open label trial in Aleppo , Syria . Fifty adults who smoked waterpipe ≥3 times per week in the last year , did not smoke cigarettes , and were interested in quitting were r and omized to receive either brief ( 1 in-person session and 3 phone calls ) or intensive ( 3 in-person sessions and 5 phone calls ) behavioral cessation treatment delivered by a trained physician in a clinical setting . The primary efficacy end point of the developed interventions was prolonged abstinence at three months post-quit day , assessed by self-report and exhaled carbon monoxide levels of < 10 ppm . Secondary end points were 7 day point-prevalent abstinence and adherence to treatment . RESULTS Thirty percent of participants were fully adherent to treatment , which did not vary by treatment group . The proportions of participants in the brief and intensive interventions with prolonged abstinence at the 3-month assessment were 30.4 % and 44.4 % , respectively . Previous success in quitting ( OR=3.57 ; 95 % CI=1.03 - 12.43 ) predicted cessation . Higher baseline readiness to quit , more confidence in quitting , and being unemployed predicted a better adherence to treatment ( all p-values < 0.05 ) . CONCLUSIONS Brief behavioral cessation treatment for waterpipe users appears to be feasible and effective", "OBJECTIVE To determine the feasibility of implementing cessation interventions in Syria . METHODS We r and omized 50 smokers to either a brief or intensive behavioral cessation intervention . Adherence to treatment and cessation through 3 months postcessation were calculated . RESULTS Adherence in the intensive group was only moderate and was associated with smoking for more years and higher self-efficacy . Cessation rates in the brief and intensive intervention groups were 16 % and 4 % , respectively . Nicotine dependence predicted abstinence at 3 months . CONCLUSION Important barriers to cessation included perceived dependence , lack of access to pharmacotherapy , poor social support , and water pipe smoking", "INTRODUCTION Waterpipe tobacco smoking is highly prevalent among young people in some setting s. There is an absence of nationally representative prevalence studies of waterpipe tobacco use and dual use with other tobacco products in young people . METHODS We conducted a secondary analysis of the Global Youth Tobacco Survey , a nationally representative cross-sectional study of students aged 13 - 15 years . Of 180 participating countries , 25 included optional waterpipe tobacco smoking questions : 15 Eastern Mediterranean and 10 Eastern European countries . We calculated the prevalence of current ( past 30-day ) waterpipe tobacco use , including dual waterpipe and other tobacco use , and used logistic regression models to identify sociodemographic correlates of waterpipe tobacco smoking . Individual country results were combined in a r and om effects meta- analysis . RESULTS Waterpipe tobacco smoking prevalence was highest in Lebanon ( 36.9 % ) , the West Bank ( 32.7 % ) and parts of Eastern Europe ( Latvia 22.7 % , the Czech Republic 22.1 % , Estonia 21.9 % ) . These countries also recorded greater than 10 % prevalence of dual waterpipe and cigarette use . In a meta- analysis , higher odds of waterpipe tobacco smoking were found among males ( Adjusted odds ratio [ AOR ] = 1.37 , 95 % confidence interval [ CI ] = 1.18 % to 1.59 % ) , cigarette users ( AOR = 6.95 , 95 % CI = 5.74 % to 8.42 % ) , those whose parents ( AOR = 1.54 , 95 % CI = 1.31 % to 1.82 % ) or peers smoked ( AOR = 3.53 , 95 % CI = 2.97 % to 4.20 % ) and those whose parents had higher educational attainment ( Father , AOR = 1.47 , 95 % CI = 1.14 % to 1.89 % ; Mother , AOR = 1.62 , 95 % CI = 1.07 % to 2.46 % ) . We report on regional- and country income-level differences . CONCLUSIONS Waterpipe tobacco smoking , including dual waterpipe and cigarette use , is alarmingly high in several Eastern Mediterranean and Eastern European countries . Ongoing waterpipe tobacco smoking surveillance is warranted" ]
"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" ]
[ "The effect on gastric pH and volume of 0 , 6 and 10 ml · kg−1 , of apple juice given 2.5 hours before surgery to children aged five to ten years was investigated in this prospect i ve , r and omized , single-blind study . Gastric contents were aspirated after induction of anaesthesia , and the volume measured . The pH of the gastric aspirate was then assessed using pH paper . Neither gastric volume nor pH immediately following the induction of general anaesthesia were significantly different among the three groups . Gastric volumes after 0 , 6 and 10 ml · kg−1 , of juice averaged ( mean ±SD ) 0.45 ±0.31 , 0.66 ±0.79 and 0.71 ±0.76 ml · kg−1 , respectively ; gastric pH averaged 1.7 ±0.6 , 1.7 ±0.6 and 1.8 ±0.8 , respectively . On the basis of questions asked immediately before induction of anaesthiesia , patients who drank 6 ml · kg−1 of apple juice had decreased thirst and were less irritable and upset before anaesthesia than those who had not ( P < 0.05 ) . It is concluded that drinking large volumes of clear apple juice 2.5 hours before scheduled surgery does not have a measurable effect on gastric volume and pH and may offer benefits such as improved patient comfort . RésuméL’effet sur le volume et le pH gastrique de 0,6 et 10 ml · kg−1 de jus de pomme donné 2.5 heures avant la chirurgie aux enfants âgés de cinq à dix ans a été investigué dans cette étude prospect i ve r and omisée et a simple insu . Le contenu gastrique fut aspiré après induction de l’anesthésie et le volume mesuré . Le pH du sue gastrique aspiré a par la suite été évalué par un papier à pH. Ni le volume gastrique ni son pH n’était significativement différent pour les trois groupes après l’induction de l’anesthesie générale . Le volume gastrique après 0,6 et 10 ml · kg−1 de jus de pomme était en moyenne ( moyenne ±SD ) respectivement 0,45 ±0,31 , 0,66 ±0,79 et 0,71 ±0,76 ml · kg−1 , en moyenne le pH gastrique était de 1,7 ±0,6 , 1,7 ±0,6 et 1,8 ±0,8 . Pour les avoir question né immédiatement avant l’induction de l’anesthésie les patients ayant bu 6 ml · kg−1 de jus de pomme avaient moins soif et étaient moins irritables avant l’anesthésie que ceux qui n’en ont pas eu ( P < 0.05 ) . On conclut que l’ingestion dun large volume de jus de pomme 2.5 heures avant la chirurgie n’a pas d’effet mesurable sur le volume et le pH gastrique et peut offrir des bénéfices tel que l’amélioration du confort du patient", "The effect of preoperative glucose infusion on preoperative alterations in hepatic glycogen content , the activity of key hepatic glucoregulatory enzymes ( fructose 1,6-diphosphatase [ FDPase ] ) , pyruvate kinase ( PK ) , hormonal developments , and plasma levels of free fatty acids ( FFA ) were investigated in 16 patients undergoing open cholecystectomy . Patients were r and omized to receive ( group G ) or not receive ( group C ) overnight glucose infusion ( 5 mg.kg-1.d-1 ) preoperatively . Infusion of glucose overnight result ed in preoperative elevations of insulin and c-peptide ( P < 0.05 ) and lower plasma levels of FFA , while the same glucose levels were found in both groups , 4.6 mmol/L. During and after surgery , only minor changes in the plasma levels of insulin , c-peptide , catecholamines , glucagon , cortisol , growth hormone , and FFA were found , with minimal differences between groups . The hepatic glycogen content was 65 % higher in group G and a significant reduction was confirmed only in this group of patients during surgery . The higher glycogen content was associated with a higher FDPase activity ratio ( P < 0.05 ) , which remained unchanged during surgery . In contrast , a significant ( P < 0.05 ) increase in the activity of this enzyme was found in group C. The PK activity ratio did not differ between groups and remained unchanged during surgery . The finding of enhanced FDPase activity suggests that the indirect route ( via gluconeogenesis ) represents an important contributor to the increased glycogen formation during glucose infusion . Additionally , surgery in the overnight fasted patient induces enzymatic changes favoring gluconeogenesis . Lastly , preoperative high-dose glucose infusion has only minor effects on the endocrine response , plasma levels of FFA , and glycogen depletion during elective open cholecystectomy", "The effect of 3 ml·kg-1 of apple juice given 2.6 ± 0.4 hours preoperatively was investigated in 80 healthy children of ages five to ten years in this prospect i ve , r and omized , single blind study . The children who drank apple juice preoperatively had decreased gastric volume , thirst , and hunger ( p < 0.05 ) . The gastric volume in the control group was 0.43 ± 0.46 ml·kg-1 and in the patients who received apple juice the gastric volume was 0.24 ± 0.31 ml·kg-1 . The gastric pH was not significantly different , with the control group ’s gastric pH being 1.7 ± 0.6 and the treated group ’s pH was 2.2 ± 1.2 . Further studies of the effects of different volumes and timing of preoperative clear fluids are indicated in paediatric patients .RésuméNous avons entrepris une étude prospect i ve , r and omisée et à ľaveugle pour déterminer ľeffet de 3 ml · kg-1 de jus de pomme donné 2.6 ± 0.4 h. avant ľopération à 80 enfants agés de 5 à 10 ans . Les enfants qui avaient bu du jus avant ľopération avaient moins f aim et soif et leurs volumes gastriques étaient moindres ( p < 0.05 ) . Le volume gastrique était de 0.43 ± 0.46 ml · kg-1 chez le groupe contrôle , et de 0.24 ± 0.31 ml · kg-1 chez le groupe “ jus de pomm ” . Le pH du liquide se chiffrait à 1.7 ± 0.6 pour les contrôles et à 2.2 ± 1.2 pour les buveurs de jus , écart non significatif . On aura besoin ďautres études pour préciser ľimpact du volume et de ľintervalle ďadministration des liquides clairs chez les enfants", "Background : Post‐operative insulin resistance and hyperglycaemia are associated with an impaired outcome after surgery . Pre‐operative oral carbohydrate loading ( CHO ) reduces post‐operative insulin resistance with a reduced risk of hyperglycaemia during post‐operative nutrition . Insulin‐resistant diabetic patients have not been given CHO because the effects on pre‐operative glycaemia and gastric emptying are unknown", "BACKGROUND AND AIMS Preoperative intake of a clear carbohydrate-rich drink reduces insulin resistance after surgery . In this study , we evaluated whether this could be related to increased insulin sensitivity at the onset of surgery . Furthermore , we aim ed to establish the optimal dose-regimen . METHODS Six healthy volunteers underwent hyperinsulinaemic ( 0.8 mU/kg/min ) , normoglycaemic ( 4.5 mmol/l ) clamps and indirect calorimetry on four occasions in a crossover-r and omised order ; after overnight fasting ( CC ) , after a single evening dose ( 800 ml ) of the drink ( LC ) , after a single morning dose ( 400 ml , CL ) and after intake of the drink in the evening and in the morning before the clamp ( LL ) . Data are presented as mean+/-SD . Statistical analysis was performed using the Student 's t-test and ANOVA . RESULTS Insulin sensitivity was higher in CL and LL ( 9.2+/-1.5 and 9.3+/-1.9 mg/kg/min , respectively ) compared to CC and LC ( 6.1+/-1.6 and 6.6+/-1.9 mg/kg/min , P<0.01 vs. CL and LL ) . CONCLUSIONS A carbohydrate-rich drink enhances insulin action 3 h later by approximately 50 % . Enhanced insulin action to normal postpr and ial day-time level at the time of onset of anaesthesia or surgery is likely to , at least partly , explain the effects on postoperative insulin resistance", "Background Studies showing the improvement of insulin sensitivity by reducing the term of preoperative fasting are mostly done in patients undergoing major operations . More information about the role of shortened preoperative fasting in perioperative metabolism is needed for such elective minor/moderate abdominal procedures as laparoscopic cholecystectomy . We investigated the influence of a carbohydrate-rich drink given 2 h before laparoscopic cholecystectomy on insulin resistance and the metabolic response to trauma . Methods A group of 21 female c and i date s ( 18–65 years old ) for elective laparoscopic cholecystectomy were r and omized to either an 8 h fasting group ( control group : n = 10 ) or to a group receiving 200 ml of a carbohydrate beverage containing 12.5 % ( 25 g , 50 kcal per 100 ml and approximately 285 mOsm ) of maltodextrine 2 h before operation ( CHO group : n = 11 ) . Blood sample s for various biochemical assays were collected both at induction of anesthesia and after the 10th postoperative hour . Insulin resistance was assessed by the HOMA-IR equation ( Insulin ( μU/ml ) × blood glucose (mg/dl)/405 ) . Results There were no postoperative complications . Seventy percent ( 7/10 ) of the controls and 27.3 % ( 3/11 ) of the CHO group experienced at least one episode of vomiting ( RR = 2.42 , 95 % Confidence Interval [ CI ] = 0.88–6.68 ; P = 0.08 ) . Biochemical analysis showed that serum glucose ( P < 0.01 ) , insulin ( P < 0.01 ) , lactate/pyruvate ratio ( P = 0.03 ) , and triglycerides ( P < 0.01 ) for the control group were higher than for the CHO group . The value of HOMA-IR was significantly greater ( P = 0.03 ) in the conventionally fasted patients than in the CHO group . Conclusions Abbreviation of the period of preoperative fasting and administration of a carbohydrate beverage diminishes insulin resistance and the organic response to trauma", "BACKGROUND Diabetes mellitus is a risk factor for deep sternal wound infection after open heart surgical procedures . We previously showed that elevated postoperative blood glucose levels are a predictor of deep sternal wound infection in diabetic patients . Therefore , we hypothesized that aggressive intravenous pharmacologic control of postoperative blood glucose levels would reduce the incidence of deep sternal wound infection . METHODS In a prospect i ve study of 2,467 consecutive diabetic patients who underwent open heart surgical procedures between 1987 and 1997 , perioperative blood glucose levels were recorded every 1 to 2 hours . Patients were classified into two sequential groups : the control group included 968 patients treated with sliding-scale-guided intermittent subcutaneous insulin injections ( SQI ) ; the study group included 1,499 patients treated with a continuous intravenous insulin infusion in an attempt to maintain a blood glucose level of less than 200 mg/dL. There were no differences between these groups with respect to age , sex , procedure , bypass time , antibiotic prophylaxis , or skin preparation methods . RESULTS Compared with subcutaneous insulin injections , continuous intravenous insulin infusion induced a significant reduction in perioperative blood glucose levels , which led to a significant reduction in the incidence of deep sternal wound infection in the continuous intravenous insulin infusion group ( 0.8 % [ 12 of 1,499 ] ) versus the intermittent subcutaneous insulin injection group ( 2.0 % [ 19 of 968 ] , p = 0.01 by the chi2 test ) . Multivariate logistic regression revealed that continuous intravenous insulin infusion induced a significant decrease in the risk of deep sternal wound infection ( p = 0.005 ; relative risk , 0.34 ) , whereas obesity ( p < 0.03 ; relative risk , 1.06 ) and use of an internal thoracic artery pedicle ( p = 0.1 ; relative risk , 2.0 ) increased the risk of deep sternal wound infection . CONCLUSIONS Use of perioperative continuous intravenous insulin infusion in diabetic patients undergoing open heart surgical procedures significantly reduces major infectious morbidity and its associated socioeconomic costs", "Glucose metabolism is adversely affected in patients following major surgery . Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance . A r and omized trial was conducted to eluci date the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection . A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were r and omly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not . The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22 . Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group ( P = 0.039 ) . There was no incidence of hypoglycemia ( < 40 mg/dL ) observed in patients , including those with diabetes mellitus , when the STG-22 was used to control blood glucose levels . STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance . The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection", "Background and objective We studied the effect of three different fasting protocol s on preoperative discomfort and glucose and insulin levels . Methods Two hundred and ten ASA I – III patients undergoing general or gastrointestinal surgery were r and omly assigned to three groups : overnight intravenous 5 % glucose infusion ( 1000 ml ) , carbohydrate-rich drink ( 400 ml ) at 6–7 a.m. , or overnight fasting . The subjective feelings of thirst , hunger , mouth dryness , weakness , tiredness , anxiety , headache and pain of each patient were question ed preoperatively using a visual analogue scale . Serum glucose and insulin levels were measured at predetermined time points preoperatively . Results During the waiting period before surgery , the carbohydrate-rich drink group was less hungry than the fasting group ( P = 0.011 ) . No other differences were seen in visual analogue scale scores among the study groups . Trend analysis showed increasing thirst , mouth dryness and anxiety in the intravenous glucose group ( P < 0.05 ) . The carbohydrate-rich drink group experienced decreasing thirst but increasing hunger and mouth dryness ( P < 0.05 ) . In the fasting group , thirst , hunger , mouth dryness , weakness , tiredness and anxiety increased ( P < 0.05 ) . Both intravenous and oral carbohydrate caused a significant increase in glucose and insulin levels . Conclusion Intravenous glucose infusion does not decrease the sense of thirst and hunger as effectively as a carbohydrate-rich drink but does alleviate the feelings of weakness and tiredness compared with fasting", "AIM Recent evidence suggests that the provision of energy-containing fluids is safe and may impact positively on markers of recovery . The aims of this study were to assess the tolerance of preoperative carbohydrate fluid administration and to determine its effect on postoperative metabolic and clinical responses . METHODS Patients admitted to the Royal Infirmary of Edinburgh for major , elective abdominal surgery were recruited to this double-blind , r and omised study and received either a placebo drink or carbohydrate ( 12.6g/100ml ) drink ( CHOD ) . Patients consumed 800 ml of their drink on the evening before surgery and 400 ml on the day of surgery 2 - 3 h before the induction of anaesthesia . Nutritional status was determined using body mass index ( BMI ) and upper arm anthropometry ; all measurements were taken preoperatively , postoperatively and at discharge . Blood glucose and insulin concentrations were also measured preoperatively and on the first post operative day . Length of hospital stay ( LOS ) and postoperative complications were recorded . RESULTS Seventy-two patients were recruited and 65 ( 34 male:31 female ) completed this study . Thirty-four patients were r and omised to receive the placebo drink ( control group ) and 31 patients to receive the carbohydrate drink ( CHOD group ) . Groups were well-matched in terms of gender and age . There were no differences between the two groups at baseline for BMI ( control : -25.1+/-1.7 kg/m2 ; CHOD -25.2+/-1.2 kg/m2 ) , upper arm anthropometry or surgical procedure . At discharge loss of muscle mass ( arm muscle circumference ) was significantly greater in the control group when compared with the CHOD group ( control : -1.1+/-0.15 cm ; CHOD : -0.5+/-0.16 cm ; P<0.05 ) . Baseline insulin ( control : 20.7+/-4.9 mU/l ; CHOD : 24.6+/-6.2 mU/l ) and glucose ( control : 6.0+/-1.4 mmol/l ; CHOD 5.7+/-1.4 mmol/l ) were comparable in the two groups and did not differ postoperatively . No complications were recorded as a result of preoperative fluid consumption . Postoperative morbidity occurred in six patients from each group . Median LOS in the control group was 10 days ( IQR=6 ) , and 8 days ( IQR=4 ) in the CHOD group . CONCLUSION Preoperative consumption of carbohydrate-containing fluids is safe . Provision of a carbohydrate energy source prior to surgery may attenuate depletion of muscle mass after surgery . Further studies are required to determine if this preservation of muscle mass is reflected in improved function and reduced rehabilitation time", "UNLABELLED Infusions of carbohydrates before surgery have been shown to reduce postoperative insulin resistance . Presently , we investigated the effects of a carbohydrate drink , given shortly before surgery , on postoperative insulin sensitivity . METHODS Insulin sensitivity and glucose turnover ( [ 6 , 6,(2)H(2)]-D-glucose ) were measured using hyper-insulinemic , normoglycemic clamps before and after elective surgery . Sixteen patients undergoing total hip replacement were r and omly assigned to preoperative oral carbohydrate administration ( CHO-H , n = 8) or the same amount of a placebo drink ( placebo , n = 8) before surgery . Insulin sensitivity was measured before and immediately after surgery . Patients undergoing elective colorectal surgery were studied before surgery and 24 h postoperatively ( CHO-C ( n = 7 ) , and fasted ( n = 7 ) , groups ) . The fasted group underwent surgery after an overnight fast . In both studies , the CHO groups received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation ( 100 g carbohydrates ) , as well as another 400 ml ( 50 g carbohydrates ) 2 h before the initiation of anesthesia . RESULTS Immediately after surgery , insulin sensitivity was reduced 37 % in the placebo group ( P < 0.05 vs. preoperatively ) while no significant change was found in the CHO-H group ( -16 % , p = NS ) . During clamps performed 24h postoperatively , insulin sensitivity and whole-body glucose disposal was reduced in both groups , but the reduction was greater compared to that in the CHO-C group ( -49 + /- 6 % vs. -26 + /- 8 % , P > > 0.05 fasted vs. CHO-C ) . CONCLUSIONS Patients given a carbohydrate drink shortly before elective surgery displayed less reduced insulin sensitivity after surgery as compared to patients undergoing surgery after an overnight fast", "We studied the effects of different preoperative oral fluid protocol s on preoperative discomfort , residual gastric fluid volumes , and gastric acidity . Two-hundred-fifty-two elective abdominal surgery patients ( ASA physical status I – II ) were r and omized to preparation with a 12.5 % carbohydrate drink ( CHO ) , placebo ( flavored water ) , or overnight fasting . The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery . Visual analog scales were used to score 11 different discomfort variables . CHO did not increase gastric fluid volumes or affect acidity , and there were no adverse events . The visual analog scale scores in a control situation were not different between groups . During the waiting period before surgery , the CHO-treated group was less hungry and less anxious than both the other groups ( P ≤ 0.05 ) . CHO reduced thirst as effectively as placebo ( P < 0.0001 versus Fasted ) . Trend analysis showed consistently decreasing thirst , hunger , anxiety , malaise , and unfitness in the CHO group ( P < 0.05 ) . The Placebo group experienced decreasing unfitness and malaise , whereas nausea , tiredness , and inability to concentrate increased ( P < 0.05 ) . In the Fasted group , hunger , thirst , tiredness , weakness , and inability to concentrate increased ( P < 0.05 ) . In conclusion , CHO significantly reduces preoperative discomfort without adversely affecting gastric contents", "OBJECTIVE To assess the effect of an intensive glucose management protocol in a heterogeneous population of critically ill adult patients . PATIENTS AND METHODS This study consisted of 800 consecutive patients admitted after institution of the protocol ( treatment group , between February 1 , 2003 , and January 10 , 2004 ) and 800 patients admitted immediately preceding institution of the protocol ( baseline group , between February 23 , 2002 , and January 31 , 2003 ) . The setting was a 14-bed medical-surgical intensive care unit ( ICU ) in a university-affiliated community teaching hospital . The protocol involved intensive monitoring and treatment to maintain plasma glucose values lower than 140 mg/dL. Continuous intravenous insulin was used if glucose values exceeded 200 mg/dL on 2 successive occasions . RESULTS The 2 groups of patients were well matched , with similar age , sex , race , prevalence of diabetes mellitus , Acute Physiology and Chronic Health Evaluation II scores , and distribution of diagnoses . After institution of the protocol , the mean glucose value decreased from 152.3 to 130.7 mg/dL ( P<.001 ) , marked by a 56.3 % reduction in the percentage of glucose values of 200 mg/dL or higher , without a significant change in hypoglycemia . The development of new renal insufficiency decreased 75 % ( P=-.03 ) , and the number of patients undergoing transfusion of packed red blood cells decreased 18.7 % ( P=.04 ) . Hospital mortality decreased 29.3 % ( P=.002 ) , and length of stay in the ICU decreased 10.8 % ( P=.01 ) . CONCLUSION The protocol result ed in significantly improved glycemic control and was associated with decreased mortality , organ dysfunction , and length of stay in the ICU in a heterogeneous population of critically ill adult patients . These results support the adoption of this low-cost intervention as a st and ard of care for critically ill patients", "A carbohydrate‐rich drink ( CHO ) has been shown to reduce preoperative discomfort . It was hypothesized that it may also reduce postoperative nausea and vomiting ( PONV )", "Preoperative oral carbohydrate can attenuate postoperative insulin resistance and catabolism , and may have the potential to improve postoperative recovery . There are no data from r and omized studies on postoperative clinical outcome after specific surgical procedures . This study evaluated the clinical effects of a preoperative carbohydrate beverage in patients undergoing laparoscopic cholecystectomy", "Major surgery is associated with postoperative insulin resistance which is attenuated by preoperative carbohydrate ( CHO ) treatment . The effect of this treatment on clinical outcome after major abdominal surgery has not been assessed in a double‐blind r and omized trial", "Background : Surgery is succeeded by long‐lasting state of relative peripheral insulin resistance , which is reduced by giving glucose infusion or oral carbohydrate‐rich drinks immediate before operating instead of fasting . The aim of the present study was to investigate whether oral carbohydrate or carbohydrate with peptide drinks preoperatively instead of fasting would improve postoperative voluntary muscle strength , nutritional intake and ambulation , decrease postoperative fatigue , anxiety and discomfort , and reduce the endocrine response to surgery", "Preoperative oral carbohydrate ( CHO ) reduces postoperative insulin resistance . In this r and omized trial , the effect of CHO on postoperative whole‐body protein turnover was studied" ]
"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." ]
[ "Abstract Alcohol and nicotine dependence are common in schizophrenia . Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers . The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia . Out patients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week , double-blind , r and omized , placebo-controlled trial . Alcohol use and smoking were assessed using self-report ( Timeline Follow-Back ) and biological measures . Adverse events were recorded . Changes in the number of st and ard drinks per week and cigarettes per week were compared in the 2 groups . Because of safety concerns or loss to follow-up , of 55 patients enrolled , only 10 started study medication , 5 each on varenicline and placebo . Gastrointestinal adverse effects , such as severe abdominal pain , limited study completion to only 4 subjects . Number of st and ard alcoholic drinks consumed per week decreased by [ mean ( SD ) ] 16.6 ( 20.1 ) in the varenicline group and by 2.4 ( 27.4 ) in the placebo group . Mean ( SD ) number of cigarettes smoked per week decreased by 66 ( 65 ) in the varenicline group and by 47 ( 77 ) in the placebo group . Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability ( gastrointestinal adverse effects ) limiting retention . There was no increased number of serious neuropsychiatric adverse events in the varenicline group . Based on this small sample , concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline", "BACKGROUND Varenicline is approved as an aid to smoking cessation in adults aged > or = 18 years . OBJECTIVE The goal of this study was to characterize the multiple-dose pharmacokinetics , safety , and tolerability of varenicline in adolescent smokers . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study enrolled healthy 12- to 16-year-old smokers ( > or =3 cigarettes daily ) into high-body-weight ( > 55 kg ) and low-body-weight ( < or = 55 kg ) groups . Subjects were r and omized to receive 14 days of treatment with a high dose of varenicline , a low dose of varenicline , or placebo . The varenicline doses in the high-body-weight group were 1 mg BID and 0.5 mg BID ; the varenicline doses in the low-body-weight group were 0.5 mg BID and 0.5 mg once daily . The apparent renal clearance ( CL/F ) and volume of distribution ( V/F ) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling . RESULTS The high-body-weight group consisted of 35 subjects ( 65.7 % male ; 77.1 % white ; mean age , 15.2 years ) . The low-body-weight group consisted of 37 subjects ( 37.8 % male ; 48.6 % white ; mean age , 14.3 years ) . The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d . The CL/F for a 70-kg adolescent was 10.4 L/h , comparable to that in a 70-kg adult . The estimated varenicline V/F was decreased in individuals of small body size , thus predicting a varenicline C(max ) approximately 30 % greater in low-body-weight subjects than in high-body-weight subjects . In high-body-weight subjects , steady-state varenicline exposure , as represented by the AUC(0 - 24 ) , was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID , consistent with values reported previously in adult smokers at the equivalent doses . In low-body-weight subjects , varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily , values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID , respectively . Among high-body-weight subjects , adverse events ( AEs ) were reported by 57.1 % of subjects in both the high- and low-dose varenicline groups and by 14.3 % of subjects in the placebo group ; among low-body-weight subjects , AEs were reported by 64.3 % , 73.3 % , and 12.5 % of subjects in the high-dose varenicline , low-dose varenicline , and placebo groups , respectively . The most common AEs were nausea , headache , vomiting , and dizziness . Psychiatric AEs that were considered treatment related included abnormal dreams in 2 subjects and mild , transient anger in 1 subject . Of the AEs reported by > or = 1 subject in any treatment group , > or = 92 % were mild in intensity . No subject discontinued the study because of an AE . CONCLUSIONS Varenicline steady-state exposure in study subjects weighing > 55 kg was similar to that observed previously in adults . The body-weight effect on varenicline pharmacokinetics , which result ed in higher exposure in individuals of smaller body size ( < or = 55 kg ) , was adequately offset by administration of half the varenicline dose recommended in adults . Varenicline was generally well tolerated during the 14-day treatment period . Clinical Trials Identification Number : NCT00463918", "Background — Smoking cessation is a key component of secondary cardiovascular disease prevention . Varenicline , a partial & agr;4&bgr;2 nicotinic acetylcholine receptor agonist , is effective for smoking cessation in healthy smokers , but its efficacy and safety in smokers with cardiovascular disease are unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease . Participants received varenicline ( 1 mg twice daily ) or placebo , along with smoking-cessation counseling , for 12 weeks . Follow-up lasted 52 weeks . The primary end point was carbon monoxide – confirmed continuous abstinence rate for weeks 9 through 12 ( last 4 weeks of treatment ) . The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 ( 47.0 % versus 13.9 % ; odds ratio , 6.11 ; 95 % confidence interval [ CI ] , 4.18 to 8.93 ) and weeks 9 through 52 ( 19.2 % versus 7.2 % ; odds ratio , 3.14 ; 95 % CI , 1.93 to 5.11 ) . The varenicline and placebo groups did not differ significantly in cardiovascular mortality ( 0.3 % versus 0.6 % ; difference , −0.3 % ; 95 % CI , −1.3 to 0.7 ) , all-cause mortality ( 0.6 % versus 1.4 % ; difference , −0.8 % ; 95 % CI , −2.3 to 0.6 ) , cardiovascular events ( 7.1 % versus 5.7 % ; difference , 1.4 % ; 95 % CI , −2.3 to 5.0 ) , or serious adverse events ( 6.5 % and 6.0 % ; difference , 0.5 % ; 95 % CI , −3.1 to 4.1 ) . As a result of adverse events , 9.6 % of varenicline and 4.3 % of placebo participants discontinued study drug . Conclusions — Varenicline is effective for smoking cessation in smokers with cardiovascular disease . It was well tolerated and did not increase cardiovascular events or mortality ; however , trial size and duration limit definitive conclusions about safety . Clinical Trial Registration Information— URL : http://www . clinical trials.gov/ct2/show/NCT00282984 . Unique identifier : NCT00282984", "BACKGROUND Currently available smoking cessation therapies have limited success rates . Varenicline tartrate is a novel , selective nicotinic receptor partial agonist developed specifically for smoking cessation . This study evaluated the efficacy , tolerability , and safety of 3 varenicline doses for smoking cessation . Bupropion hydrochloride was included as an active control . METHODS A phase 2 , multicenter , r and omized , double-blind , placebo-controlled study of healthy smokers ( 18 - 65 years old ) . Subjects were r and omized to varenicline tartrate , 0.3 mg once daily ( n = 128 ) , 1.0 mg once daily ( n = 128 ) , or 1.0 mg twice daily ( n = 127 ) , for 6 weeks plus placebo for 1 week ; to 150-mg sustained-release bupropion hydrochloride twice daily ( n = 128 ) for 7 weeks ; or to placebo ( n = 127 ) for 7 weeks . RESULTS During the treatment phase , the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate , 1.0 mg twice daily ( 48.0 % ; P<.001 ) and 1.0 mg once daily ( 37.3 % ; P<.001 ) , than for placebo ( 17.1 % ) . The bupropion rate was 33.3 % ( P = .002 vs placebo ) . The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate , 1.0 mg twice daily , group compared with the placebo group ( 14.4 % vs 4.9 % ; P = .002 ) . The bupropion rate was 6.3 % ( P = .60 vs placebo ) . Discontinuation owing to treatment-emergent adverse events was 15.9 % for bupropion , 11.2 % to 14.3 % for varenicline , and 9.8 % for placebo . No dose-related increases occurred in adverse events for varenicline . CONCLUSIONS Varenicline tartrate demonstrated both short-term ( 1 mg twice daily and 1 mg once daily ) and long-term efficacy ( 1 mg twice daily ) vs placebo . Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation", "Objective : The objective of this double-blind , placebo-controlled , r and omized study was to evaluate the efficacy of varenicline ( Chantix ) , a partial agonist at α4β2 neuronal nicotinic acetylcholine receptors used for smoking cessation , in patients with spinocerebellar ataxia ( SCA ) 3 . Methods : Patients with genetically confirmed SCA3 were r and omly assigned to receive either varenicline ( 4 weeks for titration and 4 weeks at a dose of 1 mg twice daily ) or placebo . Outcome measures included changes in the Scale for the Rating and Assessment of Ataxia ( SARA ) scores at endpoint ( 8 weeks ) compared with baseline , a timed 25-foot walk and 9-hole peg test , measurements of mood and anxiety , and adverse events . Results : Twenty patients with SCA3 ( mean age = 51 ± 10.98 years ; mean disease duration = 14 ± 9.82 years ; mean SARA score = 16.13 ± 4.67 ) were enrolled in the study , and data on 18 patients were analyzed in period I. The most common side effect associated with varenicline was nausea . Improvements were noted in the SARA subsections for gait ( p = 0.04 ) , stance ( p = 0.03 ) , rapid alternating movements ( p = 0.003 ) , and timed 25-foot walk ( p = 0.05 ) and Beck Depression Inventory scores ( p = 0.03 ) in patients taking varenicline compared with those taking placebo at endpoint , with a trend toward improvement in the SARA total score ( p = 0.06 ) in the varenicline group . Conclusions : In this controlled study , varenicline significantly improved axial symptoms and rapid alternating movements in patients with SCA3 as measured by SARA subscores and was fairly well tolerated . Classification of evidence : This study provides Class II evidence that varenicline improved the axial functions of gait , stance , and timed 25-foot walk but did not improve appendicular function , except for rapid alternating movements , in adult patients with genetically confirmed SCA3", "BACKGROUND The selective nicotinic acetylcholine receptor partial agonist , varenicline tartrate , represents a novel type of therapy for smoking cessation . This study evaluated the efficacy , safety , and tolerability of 4 varenicline dose regimens , 2 with progressive dosing over the first week ( eg , titrated ) and 2 with a fixed dosing schedule ( eg , non-titrated ) , for promoting smoking cessation . METHODS This multicenter , double-blind , placebo-controlled study r and omized healthy smokers ( aged 18 - 65 years ) to varenicline tartrate , 0.5 mg twice daily nontitrated ( n = 129 ) , 0.5 mg twice daily titrated ( n = 130 ) , 1.0 mg twice daily nontitrated ( n = 129 ) , 1.0 mg twice daily titrated ( n = 130 ) , or placebo ( n = 129 ) for 12 weeks to aid in smoking cessation . A 40-week follow-up period assessed long-term efficacy . The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52 . RESULTS Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group ( 49.4 % ) and the 0.5-mg group ( 44.0 % ) vs placebo ( 11.6 % ; P<.001 vs both doses ) . Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group ( 22.4 % ; P<.001 ) and the 0.5-mg group ( 18.5 % ; P<.001 ) vs placebo ( 3.9 % ) . Varenicline was generally well tolerated , with nausea occurring in 16 % to 42 % of varenicline-treated subjects . Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation . CONCLUSION Varenicline tartrate , 0.5 mg and 1.0 mg twice daily , is efficacious for smoking cessation", "INTRODUCTION This study evaluated the effect of varenicline in combination with counseling to assist long-term nicotine replacement therapy ( NRT ) users to quit NRT . METHODS This was a double-blind , placebo-controlled , r and omized trial of varenicline or placebo for 12 weeks , with 52-week follow-up , performed in 1 hospital-based smoking cessation specialist clinic . At the first visit , 139 ex-smokers and long-term NRT users were allocated to treatment according to a computer-generated list with r and om numbers . Visits were scheduled at Weeks 0 , 2 , 4 , 6 , 9 , 12 , and 52 . At each visit , nurse-led counseling was delivered , carbon monoxide in expired air , plasma cotinine , and body weight were assessed , and subjects were asked about craving , nausea , and dreams . The primary outcome was 12-week point prevalence quit rate ( PPR ) of nicotine replacement therapy use . RESULTS At all time points , the PPR was superior for varenicline versus placebo , although the difference was only statistically significant at 12 and 36 weeks . The PPR was 64.3 % ( varenicline ) versus 40.6 % ( placebo ) at 12 weeks ( p = .006 ) , and 42.9 % ( varenicline ) versus 36.2 % ( placebo ) at 52 weeks ( NS ) . The continuous abstinence rate from Week 9 to Week 12 was 48.6 % ( varenicline ) versus 30.4 % ( placebo ) ( p = .03 ) . Withdrawal symptoms were statistically significantly lower in the varenicline group than the placebo group . CONCLUSION Varenicline for 12 weeks combined with supportive visits was superior to placebo to get long-term NRT users to quit NRT . A larger study is needed to evaluate long-term efficacy", "OBJECTIVE Virtually no clinical trials for smoking cessation have been undertaken in bipolar disorder . Varenicline has shown efficacy for smoking cessation , but warnings about neuropsychiatric adverse events have been issued . We assessed the efficacy and safety of varenicline in euthymic bipolar subjects motivated to quit smoking . METHOD Clinical ly stable adult patients with DSM-IV bipolar disorder ( n = 60 ) who smoked ≥ 10 cigarettes per day were r and omized to a 3-month , double-blind , placebo-controlled varenicline trial and a 3-month follow-up . Study enrollment was completed from February 2010 through March 2013 . Varenicline was dosed using st and ard titration , and smoking cessation counseling was provided to all patients . The primary outcome was defined as a 7-day point prevalence of self-reported no smoking verified by expired carbon monoxide level < 10 ppm at 12 weeks . Psychopathology and side-effects were assessed at each visit . RESULTS At 3 months ( end of treatment ) , significantly more subjects quit smoking with varenicline ( n/n = 15/31 , 48.4 % ) than with placebo ( n/n = 3/29 , 10.3 % ) ( OR = 8.1 ; 95 % CI , 2.03 - 32.5 ; P < .002 ) . At 6 months , 6 of 31 varenicline-treated subjects ( 19.4 % ) remained abstinent compared to 2 of 29 ( 6.90 % ) assigned to placebo ( OR = 3.2 ; 95 % CI , 0.60 - 17.6 ; P = .17 ) . Psychopathology scores remained stable . Ten serious adverse events occurred ( n = 6 , varenicline ; n = 4 , placebo ) . Abnormal dreams occurred significantly more often in varenicline-treated subjects ( n/n = 18/31 , 61.3 % ) than in those receiving placebo ( n/n = 9/29 , 31 % ; Fisher exact test , P = .04 ) . Eight varenicline-treated and 5 placebo-assigned subjects expressed fleeting suicidal ideation , a nonsignificant difference . CONCLUSIONS Varenicline shows efficacy for initiating smoking cessation in bipolar patients , but medication trials of longer duration are warranted for maintaining abstinence . Vigilance for neuropsychiatric adverse events is prudent when initiating varenicline for smoking cessation in this patient population . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01010204", "Background : The efficacy of perioperative tobacco interventions on long-term abstinence and the safety of smoking cessation less than 4 weeks before surgery is unclear . Our objective was to determine the efficacy and safety of a perioperative smoking cessation intervention with varenicline to reduce smoking in elective surgical patients . Methods : In a prospect i ve , multicenter , double-blind , placebo-controlled trial , 286 patients were r and omized to receive varenicline or placebo . Both groups received in-hospital and telephone counseling during 12 months . The primary outcome was the 7-day point prevalence abstinence rate 12 months after surgery . Secondary outcomes included abstinence at 3 and 6 months after surgery . Multivariable logistic regression was used to identify independent variables related to abstinence . Results : The 7-day point prevalence abstinence at 12 months for varenicline versus placebo was 36.4 % versus 25.2 % ( relative risk : 1.45 ; 95 % : CI : 1.01–2.07 ; P = 0.04 ) . At 3 and 6 months , the 7-day point prevalence abstinence was 43.7 % versus 31.9 % ( relative risk : 1.37 ; 95 % CI : 1.01 to 1.86 ; P = 0.04 ) , and 35.8 % versus 25.9 % ( relative risk : 1.43 ; 95 % : CI 1.01–2.04 ; P = 0.04 ) for varenicline versus placebo , respectively . Treatment with varenicline ( odds ratio : 1.76 ; 95 % CI : 1.03–3.01 ; P = 0.04 ) , and preoperative nicotine dependence ( odds ratio : 0.82 , 95 % CI : 0.68 to 0.98 ; P = 0.03 ) predicted abstinence at 12 months . The adverse events profile in both groups was similar except for nausea , which occurred more frequently for varenicline versus placebo ( 13.3 % vs. 3.7 % , P = 0.004 ) . Conclusions : A perioperative smoking cessation intervention with varenicline increased abstinence from smoking 3 , 6 , and 12 months after elective noncardiac surgery with no increase in serious adverse events", "The aim of this study is to examine the effects of treatment with varenicline , a partial agonist at the α4β2 and full agonist at the α7 nicotine acetylcholine receptor , on cognitive impairments in people with schizophrenia . In all , 120 clinical ly stable people with schizophrenia participated in r and omized , double-blind , placebo-controlled 8-week trial . Antipsychotic and concomitant medication doses remained fixed throughout the study . Varenicline was titrated up to 1 mg twice daily for weeks 2–8 . Neuropsychological , clinical , and safety assessment s were administered at baseline and weeks 1 , 2 , 4 , and 8 . In the primary analyses of neurocognitive differences at week 8 , no varenicline – placebo differences were significant . In secondary longitudinal analyses , varenicline improved compared with placebo on the Digital Symbol Substitution Test ( p=0.013 ) and the Wisconsin Card Sorting Test non-perseverative errors ( p=0.043 ) . Some treatment effects were different between smokers and non-smokers . In smokers , Continuous Performance Test hit reaction time ( p=0.008 ) and Stroop Interference ( p=0.004 ) were reduced for varenicline compared with placebo , while there were no treatment differences in non-smokers . No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms . Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia . In some cases , effects of treatment varied between smokers and non-smokers . Further study is required to assess the functional significance of these changes", "IMPORTANCE Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release ( SR ) on neurobiological targets related to affect and reward , it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness . OBJECTIVE To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning . DESIGN AND SETTING Placebo-controlled r and omized clinical trial at a university medical center . PARTICIPANTS In total , 294 community volunteers who wanted to quit smoking . INTERVENTIONS Twelve weeks of varenicline , bupropion SR , or placebo plus intensive smoking cessation counseling ( 10 sessions , for a total of approximately 240 minutes of counseling ) . MAIN OUTCOME MEASURES Prolonged abstinence from smoking and weekly measures of depression , negative affect , and other symptoms of nicotine withdrawal . RESULTS Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit , favoring both active medications compared with placebo . At the 6-month postquit follow-up visit , only the varenicline vs placebo comparison remained significant . Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments , while both active medications improved concentration , reduced craving , and decreased negative affect and sadness compared with placebo , while having little effect ( increase or decrease ) on anxiety and anger . No differences were noted in self-reported rates of neuropsychiatric adverse events . CONCLUSIONS AND RELEVANCE In a community sample , varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable ( suppressive ) effect on symptoms of depression and other affective measures , with no clear unfavorable effect on neuropsychiatric adverse events . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00507728", "Rationale Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor ( nAChR ) modulates the rewarding effects of alcohol . The nAChR α4β2 subunit partial agonist varenicline ( Chantix ™ ) , which is approved by the Food and Drug Administration for smoking cessation , also decreases ethanol consumption in rodents ( Steensl and et al. , Proc Natl Acad Sci U S A 104:12518–12523 , 2007 ) and in human laboratory and open-label studies ( Fucito et al. , Psychopharmacology ( Berl ) 215:655–663 , 2011 ; McKee et al. , Biol Psychiatry 66:185–190 2009 ) . Objectives We present a r and omized , double-blind , 16-week study in heavy-drinking smokers ( n = 64 r and omized to treatment ) who were seeking treatment for their smoking . The study was design ed to determine the effects of varenicline on alcohol craving and consumption . Outcome measures included number of alcoholic drinks per week , cigarettes per week , amount of alcohol craving per week , cumulative cigarettes and alcoholic drinks consumed during the treatment period , number of abstinent days , and weekly percentage of positive ethyl glucuronide and cotinine screens . Results Varenicline significantly decreases alcohol consumption ( χ2 = 35.32 , p < 0.0001 ) in smokers . Although varenicline has previously been associated with suicidality and depression , side effects were low in this study and declined over time in the varenicline treatment group . Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke . Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking", "Objective To assess the efficacy and safety of varenicline ( a licensed cigarette smoking cessation aid ) in helping users of smokeless tobacco to quit . Design Double blind , placebo controlled , parallel group , multicentre , r and omised controlled trial . Setting Medical clinics ( mostly primary care ) in Norway and Sweden . Participants Men and women aged ≥18 who used smokeless tobacco at least eight times a day , with no abstinence period over three months within one year before screening , who wanted to quit all tobacco use . Participants were excluded if they used any other form of tobacco ( except smokeless tobacco ) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition . Interventions Varenicline 1 mg twice daily ( titrated during the first week ) or placebo for 12 weeks , with 14 weeks ’ follow-up after treatment . Main outcome measures The primary end point was the four week continuous abstinence rate at the end of treatment ( weeks 9 - 12 ) confirmed with cotinine concentration . A secondary end point was continuous abstinence rate for weeks 9 - 26 . Safety and tolerability were also evaluated . Results 431 participants ( 213 varenicline ; 218 placebo ) were r and omised and received at least one dose of study drug . Participants ’ demographics and baseline use of smokeless tobacco were similar ( 89 % ( 189 ) and 90 % ( 196 ) , respectively , were men ; mean age in both groups was 43.9 ; participants used smokeless tobacco products about 15 times a day , and about 80 % first used smokeless tobacco within 30 minutes after awakening ) . Continuous abstinence rate at week 9 - 12 was higher in the varenicline group than the placebo group ( 59 % ( 125 ) v 39 % ( 85 ) ; relative risk 1.60 , 95 % confidence interval 1.32 to 1.87 , P<0.001 ; risk difference 20 % ; number needed to treat 5 ) . The advantage of varenicline over placebo persisted through 14 weeks of follow-up ( continuous abstinence rate at week 9 - 26 was 45 % ( 95 ) v 34 % ( 73 ) ; relative risk 1.42 , 1.08 to 1.79 , P=0.012 ; risk difference 11 % ; number needed to treat 9 ) . The most common adverse events in the varenicline group compared with the placebo group were nausea ( 35 % ( 74 ) v 6 % ( 14 ) ) , fatigue ( 10 % ( 22 ) v 7 % ( 15 ) ) , headache ( 10 % ( 22 ) v 9 % ( 20 ) ) , and sleep disorder ( 10 % ( 22 ) v 7 % ( 15 ) ) . Few adverse events led to discontinuation of treatment ( 9 % ( 19 ) and 4 % ( 9 ) , respectively ) , and serious adverse events occurred in two ( 1 % ) and three ( 1 % ) participants , respectively . Conclusion Varenicline can help people to give up smokeless tobacco and has an acceptable safety profile . The response rate in the placebo group in this study was high , suggesting a population less resistant to treatment than smokers . Trial Registration NCT00717093", "Introduction : Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy . However , providing flexibility in the date of quitting may be more acceptable to some smokers . The objective of this study was to compare varenicline 1 mg twice daily ( b.i.d . ) with placebo in subjects using a flexible quit date paradigm after starting medication . Methods : In this double-blind , r and omized , placebo-controlled international study , smokers of ≥10 cigarettes/day , aged 18–75 years , and who were motivated to quit were r and omized ( 3:1 ) to receive varenicline 1 mg b.i.d . or placebo for 12 weeks . Subjects were followed up through Week 24 . Subjects were instructed to quit between Days 8 and 35 after starting medication . The primary endpoint was carbon monoxide – confirmed continuous abstinence during Weeks 9–12 , and a key secondary endpoint was continuous abstinence during Weeks 9–24 . Results : Overall , 493 subjects were r and omized to varenicline and 166 to placebo . Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment ( Weeks 9–12 : 53.1 % vs. 19.3 % ; odds ratio [ OR ] 5.9 ; 95 % CI , 3.7–9.4 ; p < .0001 ) and through 24 weeks follow-up ( Weeks 9–24 : 34.7 % vs. 12.7 % ; OR 4.4 ; 95 % CI , 2.6–7.5 ; p < .0001 ) . Serious adverse events occurred in 1.2 % varenicline ( none were psychiatric ) and 0.6 % placebo subjects . Fewer varenicline than placebo subjects reported depression-related adverse events ( 2.3 % vs. 6.7 % , respectively ) . Conclusions : Varenicline 1 mg b.i.d . using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies", "BACKGROUND Alcohol use , abuse and dependence remain a pressing public health problem . Based on its mechanism of action , varenicline seemed to be a likely c and i date for treating alcohol dependence . METHODS Alcohol dependent subjects ( n=40 ) were enrolled in a 13-week double-blind placebo controlled clinical trial . Subject visits were once per week . At each visit , subjects were tested for breath alcohol levels , provided self-report data on alcohol and nicotine use , and on mood and craving . In addition , subjects received once a week medical management ( MM ) . RESULTS There was no difference between varenicline and placebo treated groups on any of the drinking outcomes . Compared to placebo-treated subjects , varenicline treated subjects had decreased rates of alcohol craving and cigarette smoking , as well as greater mood improvements during the later part of the study ( weeks 6 - 13 ) . In addition , among subjects who were cigarette smokers , those treated with varenicline were significantly less likely to report heavy drinking during the trial . CONCLUSIONS Although varenicline was not significantly more effective than placebo at reducing drinking during the trial , its effects on alcohol craving and mood suggest that future investigation of the mechanism of action of varenicline , as well as additional clinical studies may be warranted . In particular , the findings regarding the influence of smoking status on heavy drinking among varenicline-treated subjects should be investigated in future studies", "OBJECTIVE In 2009 , the U.S. Food and Drug Administration issued a black box warning for varenicline regarding neuropsychiatric events . The authors used data from r and omized controlled trials and from a large Department of Defense ( DOD ) observational study to assess the efficacy and safety of varenicline . METHOD The authors reanalyzed data from the 17 placebo-controlled r and omized controlled trials ( N=8,027 ) of varenicline conducted by Pfizer , using complete intent-to-treat person-level longitudinal data to assess smoking abstinence and reports of suicidal thoughts and behavior , depression , aggression/agitation , and nausea and to compare effects in patients with ( N=1,004 ) and without ( N=7,023 ) psychiatric disorders . The authors also analyzed a large DOD data set to compare acute ( 30-day and 60-day ) rates of neuropsychiatric adverse events in patients receiving varenicline or nicotine replacement therapy ( N=35,800 ) and to assess reports of anxiety , mood , and psychotic symptoms and disorders , other mental disorders , and suicide attempt . RESULTS In the r and omized controlled trials , varenicline increased the risk of nausea ( odds ratio=3.69 , 95 % CI=3.03 - 4.48 ) but not rates of suicidal events , depression , or aggression/agitation . It significantly increased the abstinence rate , by 124 % compared with placebo and 22 % compared with bupropion . Having a current or past psychiatric illness increased the risk of neuropsychiatric events equally in treated and placebo patients . In the DOD study , after propensity score matching , the overall rate of neuropsychiatric disorders was significantly lower for varenicline than for nicotine replacement therapy ( 2.28 % compared with 3.16 % ) . CONCLUSIONS This analysis revealed no evidence that varenicline is associated with adverse neuropsychiatric events . The evidence supports the superior efficacy of varenicline relative to both placebo and bupropion , indicating considerable benefit without evidence of risk of serious neuropsychiatric adverse events , in individuals with and without a recent history of a psychiatric disorder", "BACKGROUND Prevalence rates of smoking are rising in developing countries . Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin . OBJECTIVE This study was conducted to evaluate the efficacy and tolerability of varenicline in population s of participants from Latin America , Africa , and the Middle East to investigate potential differences in the therapeutic response to varenicline . METHODS This multinational , r and omized , double-blind , placebo-controlled trial was conducted at 42 centers in 11 countries ( Latin America : Brazil , Colombia , Costa Rica , Mexico , and Venezuela ; Africa : Egypt and South Africa ; Middle East : Jordan , Lebanon , Saudi Arabia , and the United Arab Emirates ) . Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking ; smoked ≥10 cigarettes/d , with no cumulative period of abstinence > 3 months in the previous year ; and who had no serious or unstable disease within the previous 6 months . Subjects were r and omized in a 2:1 ratio to receive varenicline 1 mg or placebo , BID for 12 weeks , with a 12-week nontreatment follow-up . Brief smoking-cessation counseling was provided . The main outcome measures were carbon monoxide-confirmed continuous abstinence rate ( CAR ) at weeks 9 to 12 and weeks 9 to 24 . Adverse events ( AEs ) were recorded for tolerability assessment . RESULTS Overall , 588 subjects ( varenicline , 390 ; placebo , 198 ) were r and omized and treated . The mean ( SD ) ages of subjects in the varenicline and placebo groups were 43.1 ( 10.8 ) and 43.9 ( 10.8 ) years , respectively ; 57.7 % and 65.7 % were male ; and the mean ( SD ) weights were 75.0 ( 16.0 ) and 76.7 ( 16.3 ) kg ( range , 40.0 - 130.0 and 45.6 - 126.0 kg ) . CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo ( 53.59 % vs 18.69 % ; odds ratio [ OR ] = 5.76 ; 95 % CI , 3.74 - 8.88 ; P < 0.0001 ) , and this rate was maintained during weeks 9 to 24 ( 39.74 % vs 13.13 % ; OR = 4.78 ; 95 % CI , 2.97 - 7.68 ; P < 0.0001 ) . Nausea , headache , and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group . Serious AEs ( SAEs ) were reported in 2.8 % of varenicline recipients compared with 1.0 % in the placebo group , with 6 subjects reporting psychiatric SAEs compared with none in the placebo group . CONCLUSION Based on these data , varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America , Africa , and the Middle East . Clinical Trials.gov identifier : NCT00594204", "OBJECTIVE Effective smoking cessation treatments are needed for patients with schizophrenia , who , compared with the general population , have high rates of cigarette smoking and more difficulty quitting . We evaluated the safety and efficacy of varenicline for smoking cessation in out patients with stable schizophrenia or schizoaffective disorder . METHOD In this 12-week , r and omized , double-blind , multicenter trial ( May 8 , 2008 , to April 1 , 2010 ) , 127 smokers ( ≥ 15 cigarettes/d ) with DSM-IV-confirmed schizophrenia or schizoaffective disorder received varenicline or placebo ( 2:1 ratio ) . The primary outcome was safety and tolerability of varenicline assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks . Abstinence was defined as no smoking 7 days prior to weeks 12 and 24 , verified by carbon monoxide level . RESULTS Eighty-four participants received varenicline ; 43 , placebo . At 12 weeks ( end of treatment ) , 16/84 varenicline-treated patients ( 19.0 % ) met smoking cessation criteria versus 2/43 ( 4.7 % ) for placebo ( P = .046 ) . At 24 weeks , 10/84 ( 11.9 % ) varenicline-treated and 1/43 ( 2.3 % ) placebo-treated patients , respectively , met abstinence criteria ( P = .090 ) . Total adverse event rates were similar between groups , with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings . Rates of suicidal ideation adverse events were 6.0 % ( varenicline ) and 7.0 % ( placebo ) ( P = 1.0 ) . There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides . CONCLUSIONS Varenicline was well tolerated , with no evidence of exacerbation of symptoms , and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks . Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00644969", "CONTEXT The administration of nicotine transiently improves many neurobiological and cognitive functions in schizophrenia and schizoaffective disorder . It is not yet clear which nicotinic acetylcholine receptor ( nAChR ) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder . OBJECTIVE Because α4β2 is a key nAChR subtype for nicotinic actions , we investigated the effect of varenicline tartrate , a relatively specific α4β2 partial agonist and antagonist , on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans . DESIGN A double-blind , parallel , r and omized , placebo-controlled trial of patients with schizophrenia or schizoaffective disorder to examine the effects of varenicline on biomarkers at 2 weeks ( short-term treatment ) and 8 weeks ( long-term treatment ) , using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects . SETTING Outpatient clinics . PARTICIPANTS A total of 69 smoking and nonsmoking patients ; 64 patients completed week 2 , and 59 patients completed week 8 . Intervention Varenicline . MAIN OUTCOME MEASURES Prepulse inhibition , sensory gating , antisaccade , spatial working memory , eye tracking , processing speed , and sustained attention . RESULTS A moderate dose of varenicline ( 1 ) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment ( P = .006 ) , ( 2 ) reduced startle reactivity ( P = .02 ) regardless of baseline smoking status , and ( 3 ) improved executive function by reducing the antisaccadic error rate ( P = .03 ) regardless of smoking status . A moderate dose of varenicline had no significant effect on spatial working memory , predictive and maintenance pursuit measures , processing speed , or sustained attention by Conners ' Continuous Performance Test . Clinical ly , there was no evidence of exacerbation of psychiatric symptoms , psychosis , depression , or suicidality using a gradual titration ( 1-mg daily dose ) . CONCLUSIONS Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers . Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biological deficits", "CONTEXT The majority of cigarette smokers who achieve abstinence relapse within the first year and require many attempts before achieving permanent abstinence . Evidence to support pharmacological treatment for relapse prevention is insufficient . OBJECTIVE To determine whether smokers who quit after 12 weeks of treatment with varenicline , a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist , maintain greater continuous abstinence rates ( defined as not a single \" puff \" of a cigarette ) than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at multiple medical clinics in 7 countries with follow-up to 52 weeks after study baseline . Of 1927 cigarette smokers recruited between April 2003 and February 2004 and treated for 12 weeks with open-label varenicline titrated to 1 mg twice per day , 1236 ( 64.1 % ) did not smoke , use tobacco , or use nicotine replacement therapy during the last week of treatment and 62.8 % ( n = 1210 ) were r and omized to additional treatment or placebo . INTERVENTION Participants were r and omly assigned to receive either double-blind varenicline , 1 mg twice per day ( n = 603 ) , or placebo ( n = 607 ) for an additional 12 weeks . MAIN OUTCOME MEASURES Carbon monoxide-confirmed continued abstinence during weeks 13 to 24 and weeks 13 to 52 of the study . RESULTS The carbon monoxide-confirmed continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 ( 70.5 % vs 49.6 % ; odds ratio [ OR ] , 2.48 ; 95 % confidence interval [ CI ] , 1.95 - 3.16 ; P<.001 ) as well as for weeks 13 to 52 ( 43.6 % vs 36.9 % ; OR , 1.34 ; 95 % CI , 1.06 - 1.69 ; P = .02 ) . Adverse events reported in the open-label period were mostly mild ; no difference in adverse events between varenicline and placebo was observed during the double-blind period . CONCLUSIONS Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were r and omized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo . This advantage was maintained through the nontreatment follow-up to week 52 . Varenicline may be an efficacious , safe , and well-tolerated agent for maintaining abstinence from smoking . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00143286", "INTRODUCTION Long-term smokeless tobacco ( ST ) use is known to increase the risk for oropharyngeal cancer , heart attack , and stroke . Varenicline has recently been demonstrated to increase ST abstinence rates among Swedish snus users . We have conducted a pilot study to obtain preliminary evidence of efficacy of varenicline for the treatment of ST users in Midwestern United States . METHODS We conducted a r and omized , placebo-controlled Phase II clinical trial to evaluate the potential efficacy of 12 weeks of varenicline for the treatment of ST users with an a priori decision rule that a 1-tailed p < .20 for the comparison of the primary endpoint was evidence to conclude that future studies were warranted . Subjects were followed for 6 months after r and omization . RESULTS We r and omized 76 subjects ( 38 varenicline and 38 placebo ) . Subjects were similar at baseline with a mean age of 41 years , and all were male . The biochemically confirmed point prevalence tobacco abstinence rates at end of treatment were 55.3 % for varenicline and 42.1 % for placebo ( p = .126 ) and 47.4 % and 31.6 % ( p = .080 ) , respectively , at 6 months . Point prevalence ST abstinence rates at end of treatment for varenicline were 57.9 % and 42.1 % for placebo ( p = .084 ) and 57.9 % and 31.6 % ( p = .011 ) , respectively , at 6 months . Varenicline was associated with significantly less craving compared with placebo . Varenicline was well tolerated with nausea and sleep disturbance being the most common side effects . CONCLUSIONS Varenicline decreases craving and may be effective for increasing tobacco abstinence rates among ST users . Larger trials may be warranted to confirm these results", "The efficacy and safety of retreatment with varenicline in smokers attempting to quit were evaluated in this r and omized , double‐blind , placebo‐controlled , multicenter trial ( Australia , Belgium , Canada , the Czech Republic , France , Germany , the United Kingdom , and the United States ) . Participants were generally healthy adult smokers ( ≥10 cigarettes/day ) with ≥1 prior quit attempt ( ≥2 weeks ) using varenicline and no quit attempts in ≤3 months ; they were r and omly assigned ( 1:1 ) to 12 weeks ' varenicline ( n = 251 ) or placebo ( n = 247 ) treatment , with individual counseling , plus 40 weeks ' nontreatment follow‐up . The primary efficacy end point was the carbon monoxide – confirmed ( ≤10 ppm ) continuous abstinence rate for weeks 9–12 , which was 45.0 % ( varenicline ; n = 249 ) vs. 11.8 % ( placebo ; n = 245 ; odds ratio : 7.08 ; 95 % confidence interval : 4.34 , 11.55 ; P < 0.0001 ) . Common varenicline group adverse events were nausea , abnormal dreams , and headache , with no reported suicidal behavior . Varenicline is efficacious and well tolerated in smokers who have previously taken it . Abstinence rates are comparable with rates reported for varenicline‐naive smokers", "Varenicline is an effective and increasingly prescribed drug for smoking cessation , but has been associated with depressive symptoms and suicidal behavior . However , it remains unclear whether those changes in mood and behavior are directly related to varenicline use , or caused by smoking cessation itself or reflects depression and suicidality rates in smokers , independent of treatment . To investigate the influence of varenicline on mood and behavior independent of smoking and smoking cessation , we assessed the effects of varenicline on emotional processing ( a biomarker of depressogenic effects ) , emotion-potentiated startle reactivity , impulsivity ( linked with suicidal behavior ) , and cognitive performance in non-smoking subjects . We used a r and omized , double-blind design , in which we administered varenicline or placebo to healthy subjects over 7 days ( 0.5 mg/day first 3 days , then 1 mg/day ) . Cognitive and emotional processing was assessed by a battery of computerized tasks and recording of emotion-potentiated startle response . A total of 41 subjects were r and omized , with 38 subjects included in the analysis . The varenicline group did not differ from placebo in terms of negative biases in emotional processing or mood . However , compared with placebo , the varenicline group scored higher on working and declarative memory . In conclusion , short-term varenicline use did not influence negative biases in emotional processing or impulsivity in non-smoking subjects , thereby not supporting direct depressogenic or suicidal risk behavior-inducing effects . In contrast , varenicline may have cognitive-enhancing effects", "BACKGROUND With smoking rates far exceeding the general population , methadone-maintained ( MMT ) opiate-dependent smokers experience high rates of tobacco-related health consequences . Previous treatment studies have used nicotine replacement and produced low quit rates . METHODS We test , using a three-group r and omized design , the efficacy of varenicline versus placebo , in comparison with nicotine replacement therapy ( NRT ) that combines nicotine patch prescription plus ad libitum nicotine rescue , for smoking cessation . We recruited methadone-maintained smokers from nine treatment centers in southern New Engl and and provided six months of treatment , and a minimal behavioral intervention at baseline ( NCI 's 5A 's ) . Outcomes included carbon monoxide ( CO ) confirmed 7-day point smoking cessation prevalence at 6 months and self-reported change in mean cigarettes per day . RESULTS The 315 participants had a mean age of 40 , with 50 % male and 79 % non-Hispanic White , smoked an average of 19.6 ( ± 10.4 ) cigarettes/day , and had a mean daily methadone dose of 109 mg . Intent-to-treat analyses , with missing considered to be smoking , showed the rate of CO-confirmed 7-day abstinence at 6-months was 5.4 % overall , with varenicline 3.7 % compared to placebo 2.2 % , and NRT 8.3 % ( p>.05 ) . Adherence rates during the 7-days immediately prior to 6-month assessment were 34.2 % in varenicline , 34.4 % in placebo , and 48.8 % in NRT . Between baseline and 6-months there was an overall self-reported mean reduction of 8.3 cigarettes/day . CONCLUSION Varenicline did not increase quit rates over placebo . Smoking cessation rates in methadone-maintained smokers are low and novel treatment strategies are required", "Objective To compare the risk of suicide , self harm , and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy . Design Prospect i ve cohort study within the Clinical Practice Research Data link . Setting 349 general practice s in Engl and . Participants 119 546 men and women aged 18 years and over who used a smoking cessation product between 1 September 2006 and 31 October 2011 . There were 81 545 users of nicotine replacement products ( 68.2 % of all users of smoking cessation medicines ) , 6741 bupropion ( 5.6 % ) , and 31 260 varenicline ( 26.2 % ) users . Main outcome measures Outcomes were treated depression and fatal and non-fatal self harm within three months of the first smoking cessation prescription , determined from linkage with mortality data from the Office for National Statistics ( for suicide ) and Hospital Episode Statistics data ( for hospital admissions relating to non-fatal self harm ) . Hazard ratios or risk differences were estimated using Cox multivariable regression models , propensity score matching , and instrumental variable analysis using physicians ’ prescribing preferences as an instrument . Sensitivity analyses were performed for outcomes at six and nine months . Results We detected 92 cases of fatal and non-fatal self harm ( 326.5 events per 100 000 person years ) and 1094 primary care records of treated depression ( 6963.3 per 100 000 person years ) . Cox regression analyses showed no evidence that patients prescribed varenicline had higher risks of fatal or non-fatal self harm ( hazard ratio 0.88 , 95 % confidence interval 0.52 to 1.49 ) or treated depression ( 0.75 , 0.65 to 0.87 ) compared with those prescribed nicotine replacement therapy . There was no evidence that patients prescribed bupropion had a higher risk of fatal or non-fatal self harm ( 0.83 , 0.30 to 2.31 ) or of treated depression ( 0.63 , 0.46 to 0.87 ) compared with patients prescribed nicotine replacement therapy . Similar findings were obtained using propensity score methods and instrumental variable analyses . Conclusions There is no evidence of an increased risk of suicidal behaviour in patients prescribed varenicline or bupropion compared with those prescribed nicotine replacement therapy . These findings should be reassuring for users and prescribers of smoking cessation medicines", "OBJECTIVE We assessed the safety of long-term varenicline administration for smoking cessation . METHODS In this r and omized , double-blind , multicenter trial , eligible adult smokers ( 18 - 75 years ) who smoked an average of > or = 10 cigarettes/day were r and omized to either varenicline 1 mg twice daily ( BID ) or placebo for 52 weeks . Subjects made weekly clinic visits until week 8 , and then every 4 weeks until week 52 , with a follow-up visit at week 53 . The target quit date was the morning of the week 1 clinic visit . Brief counseling was provided at each visit , and vital signs , adverse events ( AEs ) , and smoking status were documented . Other laboratory measures were collected at specified visits . RESULTS A total of 251 subjects were r and omized to varenicline and 126 to placebo . Approximately half of the subjects in each arm completed the study ( 53.8 % varenicline ; 46.8 % placebo ) . Treatment-emergent AEs were observed in 96.4 % of varenicline- and 82.5 % of placebo-treated subjects during the study . Common varenicline-associated AEs were nausea ( 40.2 % ) , abnormal dreams ( 22.7 % ) , and insomnia ( 19.1 % ) . Most AEs were considered mild or moderate in intensity . AEs leading to discontinuation of varenicline treatment included nausea ( 7.6 % ) , insomnia ( 3.2 % ) , and abnormal dreams ( 2.4 % ) . A single varenicline-related serious AE , bilateral subcapsular cataracts , was observed . At week 52 , 7-day point prevalence abstinence rates were 36.7 % ( varenicline ) and 7.9 % ( placebo ) . CONCLUSIONS Varenicline 1 mg BID can be safely administered for up to 1 year . Varenicline was also a more effective smoking cessation aid than placebo throughout the study , supporting both its short- ( 12-week ) and long-term ( 52-week ) efficacy", "BACKGROUND AND OBJECTIVE Varenicline tartrate , a novel , selective , nicotinic acetylcholine receptor partial agonist , has been developed specifically as a smoking cessation drug . This study evaluated the efficacy of a st and ard regimen of varenicline compared with placebo for smoking cessation in 333 subjects in China , Singapore and Thail and . METHODS This 24-week , r and omized , double-blind , placebo-controlled trial of varenicline , 1 mg bd , consisted of a 12-week treatment period followed by a 12-week non-treatment follow-up period . The primary study end-point was the 4-week continuous abstinence rate defined as the proportion of subjects who reported total abstinence from smoking and other nicotine products from weeks 9 - 12 . A key secondary end-point was the continuous abstinence rate from weeks 9 - 24 , defined as the proportion of subjects who achieved the primary end-point as well as total abstinence from all tobacco products from weeks 13 - 24 . RESULTS Both end-points were achieved by a significantly higher proportion of subjects in the varenicline group than in the placebo group . The 4-week continuous abstinence end-point was achieved by 50.3 % and 31.6 % in the varenicline and placebo groups , respectively ( P = 0.0003 ) , while continuous abstinence from weeks 9 - 24 was achieved by 38.2 % and 25.0 % of subjects , respectively ( P = 0.0080 ) . The treatment effect was generalizable by treatment centre and country . Varenicline was safe and appeared to be well tolerated by most subjects . CONCLUSION Varenicline was significantly more efficacious for smoking cessation than placebo over a 12-week treatment period and a further 12-week non-treatment follow-up period in smokers from China , Singapore and Thail and . No significant side-effects were noted", "Objectives : To assess the efficacy and safety of varenicline ( Chantix ) for the treatment of alcohol dependence . Varenicline is a partial & agr;4&bgr;2 nicotinic acetylcholine agonist approved by the Food and Drug Administration for smoking cessation . It has reduced drinking in animal studies and in small studies of humans who were both heavy drinkers and smokers . This is the first multisite clinical trial of varenicline in a population of smokers and nonsmokers with alcohol dependence . Methods : Men and women ( n = 200 ) meeting the criteria for alcohol dependence were recruited across 5 clinical sites . Patients received double-blind varenicline or placebo and a computerized behavioral intervention . Varenicline was titrated during the first week to 2 mg/d , which was maintained during weeks 2 to 13 . Results : The varenicline group had significantly lower weekly percent heavy drinking days ( primary outcome ) ( adjusted mean difference = 10.4 ) , drinks per day , drinks per drinking day , and alcohol craving compared with the placebo group ( P < 0.05 ) . The average treatment effect on alcohol use was similar for smokers and nonsmokers . Varenicline was well-tolerated ; adverse events were expected and mild . Conclusions : Varenicline significantly reduced alcohol consumption and craving , making it a potentially viable option for the treatment of alcohol dependence", "In this double-blind , placebo-controlled trial , we compared varenicline ( 2 mg ) to placebo for treatment for cocaine and tobacco dependence in 31 methadone-maintained subjects . Subjects received weekly counseling during the 12-week study participation . Our results indicate that varenicline is safe to give to this subject population , as there were no adverse events related to medication during this study . Varenicline was no more effective than placebo for abstinence from cocaine . Treatment with varenicline was associated with a reduced number of cigarettes smoked per day , even though subjects received only a brief education for smoking cessation . The self-report reduction in smoking was corroborated by CO levels and the Fagerström Test of Nicotine Dependence . However , self-ratings of positive mood on the Positive Affect Negative Affect Schedule did significantly decrease in the varenicline group as compared to the placebo group , although this appears to be due to r and omization differences related to lifetime depression diagnosis . These preliminary findings may point to potential therapeutic value of varenicline for smoking cessation in cocaine users maintained on methadone", "BACKGROUND Varenicline , a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist , has been developed specifically for smoking cessation . In Japan , 39.3 % of men smoke and this is a major public health concern . OBJECTIVE The primary objective of this study was to evaluate the efficacy and dose-response relationship of varenicline in Japanese smokers . METHODS In this double-blind , placebo-controlled , r and omized , parallel-group study , subjects were r and omized to receive varenicline at 0.25 mg BID , 0.5 mg BID , 1 mg BID , or placebo for 12 weeks followed by a 40-week , nontreatment follow-up phase . The primary efficacy variable was the continuous abstinence rate ( CAR ) , defined as no reported smoking ( not even a puff ) or other nicotine use and confirmed by end-expiratory carbon monoxide level < or=10 ppm , during the last 4 weeks of treatment ( weeks 9 - 12 ) . Secondary end points included CARs for weeks 9 - 24 and 9 - 52 . Craving , withdrawal , and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale , the Brief Question naire on Smoking Urges , and the modified Cigarette Evaluation Question naire . The tolerability of varenicline was also evaluated . RESULTS Of 618 subjects who received treatment , 515 ( 83.3 % ) were classified as nicotine dependent ( scoring > or=5 on the Tobacco Dependence Screener ) , and constituted the primary analysis group . Of these , 385 ( 74.8 % ) subjects were male , and the mean age was within the range of 39.0 to 40.2 years . Across treatment groups , subjects cl aim ed to have smoked a mean of 23.1 to 24.9 cigarettes per day in the preceding 30 days , and the mean score on the Fagerström Test for Nicotine Dependence was within the range from 5.4 to 5.7 . The CAR for weeks 9 - 12 was significantly higher for all doses of varenicline compared with placebo ( 39.5 % [ 51/129 ] ) . The highest CAR of 65.4 % ( 85/130 ) was achieved with varenicline 1 mg BID ( odds ratio [ OR ] [ 95 % CI ] = 2.98 [ 1.78 - 4.99 ] ; P < 0.001 ) . The CAR for weeks 9 - 52 was significantly greater for varenicline 1 mg BID than placebo ( 34.6 % [ 45/130 ] vs 23.3 % [ 30/129 ] ; OR [ 95 % CI ] = 1.81 [ 1.04 - 3.17 ] ; P = 0.036 ) . The CARs for weeks 9 - 24 at 0.25 , 0.5 , and 1 mg BID were 33.6 % ( 43/128 ) , 35.2 % ( 45/128 ) , 37.7 % ( 49/130 ) , and for weeks 9 - 52 at 0.25 and 0.5 mg BID were 27.3 % ( 35/128 ) and 28.9 % ( 37/128 ) but failed to reach significance versus the placebo ( 29.5 % [ 38/129 ] for weeks 9 - 24 and 23.3 % [ 30/129 ] for weeks 9 - 52 ) . Treatment-emergent adverse events ( AEs ) were more prevalent among varenicline-treated subjects ( 79.1 % [ 121/153 ] at 0.25 mg BID , 80.6 % [ 125/155 ] at 0.5 mg BID , and 80.1 % [ 125/156 ] at 1 mg BID ) than placebo subjects ( 71.4 % [ 110/154 ] ) . The 3 most prevalent AEs at varenicline 1 mg BID were nasopharyngitis ( 35.9 % [ 56/156 ] ) , nausea ( 24.4 % [ 38/156 ] ) , and headache ( 10.3 % [ 16/156 ] ) , all of which were of mild or moderate intensity . Nausea was the only AE that appeared dose related ( 7.2 % [ 11/153 ] at 0.25 mg BID , 9.7 % [ 15/155 ] at 0.5 mg BID , and 24.4 % [ 38/156 ] at 1 mg BID ) versus placebo ( 7.8 % [ 12/154 ] ) . CONCLUSIONS Varenicline was associated with dose-dependent improvement in smoking abstinence rates during the last 4 weeks of treatment and in the longer term over 40 weeks of nontreatment follow-up . The dose associated with the highest efficacy was varenicline 1 mg BID", "OBJECTIVE To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation . RESEARCH DESIGN AND METHODS 320 healthy , motivated-to-quit smokers ( > or = 10 cigarettes/day ) aged 18 - 65 years , entered a multicenter , r and omized , double-blind , placebo-controlled study - conducted between December 26 , 2001 and June 24 , 2003 - with a 12-week treatment phase and 40-week , double-blind , non-treatment follow-up . Treatment consisted of varenicline or placebo in fixed doses ( Week 1 : titrated from 0.5 to 1.0 mg/day ) followed by a self-regulated flexible schedule ( Weeks 2 - 12 : 0.5 - 2.0 mg/day ) . MAIN OUTCOME MEASURES Primary outcomes included carbon monoxide-confirmed continuous abstinence rate ( CAR ) from smoking for Weeks 4 through 7 , 9 through 12 , and 9 through 52 . Secondary outcomes included CAR from Weeks 9 through 24 , 7-day point prevalence of abstinence , safety assessment s , and measures of craving , withdrawal , and smoking reward . RESULTS Superior CARs were observed in varenicline-treated ( n = 157 ) versus placebo participants ( n=155 ) for Weeks 4 through 7 ( 38.2 vs. 11.6 % ) , 9 through 12 ( 40.1 vs. 11.6 % ) , 9 through 24 ( 28.0 vs. 9.0 % ) , and 9 through 52 ( 22.3 vs. 7.7 % ) ( all p<0.001 ) . Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 ( 46.5 vs. 14.2 % ; p<0.001 ) , 24 ( 32.5 vs. 13.5 % ; p<0.001 ) , and 52 ( 28.0 vs. 13.5 % ; p=0.001 ) . Overall , medication compliance was high , although varenicline-treated , but not placebo , participants tended to taper down their dosage over time . Total treatment-emergent AEs were 77.1 % ( varenicline : 121/157 ) and 65.8 % ( placebo : 102/155 ) . Few AEs led to treatment discontinuation ( varenicline : 11/157 , 7.0 % and placebo : 7/155 , 4.5 % ) . Participants were primarily healthy Caucasians , so more research is necessary to determine how applicable these findings are to other population s. CONCLUSIONS A self-regulated , flexible dosing regimen of varenicline is well tolerated , with superior effectiveness versus placebo for smoking cessation", "OBJECTIVE The hospital can be an important opportunity for smoking cessation interventions . This is the first r and omized , double-blinded , placebo-controlled pilot trial utilizing varenicline and post-discharge , in-person behavioral treatment for hospitalized smokers . METHOD Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009 . The primary outcome was biochemically confirmed abstinence at 24 weeks following discharge . Secondary outcomes included withdrawal symptoms , motivation , utilization of treatment , and medical events . RESULTS Overall abstinence at 24 weeks was 27 % with no difference between varenicline and placebo treatment groups ( 23 % vs. 31 % ) . There were no significant differences in motivation to stop smoking or withdrawal symptoms . Over 40 % of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not ( 53.1 % vs. 8.5 % , p<0.01 ) . Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group ( 25 % vs. 5 % ; p<0.01 ) . Twenty-three subjects were re-hospitalized with no significant differences between treatment groups ( 13 varenicline vs. 10 placebo ) . CONCLUSION This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation , produced some hypothesis-generating findings , and suggested the potential benefit of face-to-face treatment following discharge", "BACKGROUND Smoking is the most important risk factor for COPD and accelerates its progression . Despite the health implication s , a large proportion of patients with COPD continue to smoke , so finding effective smoking cessation interventions for this population is paramount . To our knowledge , this is the first r and omized clinical trial to compare the efficacy and safety of varenicline tartrate vs placebo in smokers with mild to moderate COPD . METHODS In a 27-center , double-blind , multinational study , 504 patients with mild to moderate COPD ( postbronchodilator FEV1/FVC , < 70 % ; FEV1 percent predicted normal value , ≥50 % ) and without known psychiatric disturbances were r and omized to receive varenicline ( n=250 ) or placebo ( n=254 ) for 12 weeks , with a 40-week nontreatment follow-up . The primary end point was carbon monoxide-confirmed continuous abstinence rate ( CAR ) for weeks 9 to 12 . A secondary end point was CAR for weeks 9 to 52 . RESULTS CAR for weeks 9 to 12 was significantly higher for patients in the varenicline group ( 42.3 % ) than for those in the placebo group ( 8.8 % ) ( OR , 8.40 ; 95 % CI , 4.99 - 14.14 ; P<.0001 ) . CAR in the patients treated with varenicline remained significantly higher than in those treated with placebo through weeks 9 to 52 ( 18.6 % vs 5.6 % ) ( OR , 4.04 ; 95 % CI , 2.13 - 7.67 ; P<.0001 ) . Nausea , abnormal dreams , upper-respiratory tract infection , and insomnia were the most commonly reported adverse events ( AEs ) for patients in the varenicline group . Serious AEs were infrequent in both treatment groups . Two patients in the varenicline group and one patient in the placebo group died during the study . Reports of psychiatric AEs were similar for both treatment groups . CONCLUSIONS Varenicline was more efficacious than placebo for smoking cessation in patients with mild to moderate COPD and demonstrated a safety profile consistent with that observed in previous trials . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00285012 ; URL : www . clinical trials.gov", "BACKGROUND Rates of smoking in East Asian men range from > 35 % to > 60 % , and are increasing in women and the young . OBJECTIVE This study evaluated the efficacy and tolerability of 1 mg BID varenicline , a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist , for smoking cessation in smokers in Taiwan and Korea . METHODS A r and omized , double-blind , placebo-controlled , 12-week treatment , 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan . Eligible subjects , smoking > or=10 cigarettes/d , received brief smoking-cessation counseling and were r and omly assigned in a 1:1 ratio to varenicline 1 mg BID ( titrated during the first week ) or placebo . Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide < or=10 ppm . The primary end point was continuous abstinence rate ( CAR ) during the last 4 weeks of treatment . Secondary end points included CAR from weeks 9 to 24 and 7-day point prevalence ( PP ) of abstinence at weeks 12 and 24 . Craving , withdrawal , and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale , the Brief Question naire of Smoking Urges , and the modified Cigarette Evaluation Question naire . Observed or volunteered adverse-event data were recorded at clinic visits . RESULTS Overall , 126 subjects ( 84.9 % male ) received varenicline , and 124 ( 92.7 % male ) received placebo , Subjects were aged 21 to 73 years ( mean age , 39.7 and 40.9 years for varenicline and placebo groups , respectively ) , and the mean ( range ) body weights were 69.0 ( 44.8 - 110.0 ) kg and 71.4 ( 45.5 - 102.0 ) kg , respectively . Subjects had smoked for 3 to 52 years ( mean , 20.2 and 22.1 years in the varenicline and placebo groups , respectively ) . Subjects had smoked a mean of 23 cigarettes/d over the past month , with 51.6 % ( varenicline ) and 46.0 % ( placebo ) having made 1 or more prior serious quit attempts . Smoking-cessation rates at the end of treatment were 59.5 % with varenicline versus 32.3 % with placebo ( P < 0.001 ) . CARs through 12 weeks post-treatment ( weeks 9 - 24 ) were 46.8 % with varenicline and 21.8 % with placebo ( P < 0.001 ) . The 7-day PP was 67.5 % with varenicline versus 36.3 % with placebo at week 12 , and 57.1 % versus 29.0 % with placebo at week 24 ( both , P < 0.001 ) . Treatment-emergent , all-causality adverse events with an incidence > or= 5 % for varenicline were nausea ( 43.7 % for varenicline vs 11.3 % placebo ) , insomnia ( 15.1 % vs 13.7 % ) , increased appetite ( 7.9 % vs 6.5 % ) , constipation ( 7.1 % vs 2.4 % ) , anxiety ( 5.6 % vs 2.4 % ) , and abnormal dreams ( 5.6 % vs 0.8 % ) . Adverse events result ed in < 10 % treatment discontinuations overall . CONCLUSION Varenicline was an efficacious and well-tolerated pharmacotherapy for smoking cessation in this group of Asian smokers over a 12-week treatment period , and its effects persisted for a further 12-week follow-up period", "BACKGROUND Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation . There have been spontaneous postmarketing reports of neuropsychiatric adverse events ( NPAEs ) in smokers without a history of psychiatric illness quitting with varenicline . METHODS One hundred ten smokers without history of psychiatric illness ( screened by Structured Clinical Interview for DSM-IV ) were r and omized to 12 weeks of varenicline 1 mg twice daily ( n = 55 ) or placebo . Adverse events were solicited systematic ally . Depressive symptoms , anxiety , aggression , and irritability were measured at baseline and weekly using the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Scale ( HAM-A ) , and the Overt Aggression Scale-Modified ( OAS-M ) . The Profile of Mood States ( POMS ) was administered daily . Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods . RESULTS Participants ' mean baseline characteristics were 33 years of age , 22 cigarettes/day and Fagerström Test for Nicotine Dependence score > 7 . Reported NPAEs were similar between groups . No suicidal events were reported . There were no significant differences between groups for the MADRS ( treatment difference vs. placebo = .03 , 95 % confidence interval [ CI ] -.68-.73 ; NS ) , HAM-A ( treatment difference [ TD ] = .14 , 95 % CI -.62-.90 ; NS ) , OAS-M Aggression subscale ( TD = .5 , 95 % CI -1.18 - 2.18 ; NS ) , OAS-M Irritability subscale ( TD = .08 , 95 % CI -.17-.34 ; NS ) , and the POMS total scores ( TD = .5 , 95 % CI -.52 - 1.53 ; NS ) . CONCLUSIONS There were no significant differences between groups on measures of depressive symptoms , anxiety , or aggression/hostility . Systematic ally solicited NPAEs were similar between the varenicline and placebo groups", "OBJECTIVES This study examined the relation between smoking and suicide , controlling for various confounders . METHODS More than 50,000 predominantly White , middle-aged and elderly male health professionals were followed up prospect ively with biennial question naires from 1986 through 1994 . The primary end point was suicide . Characteristics controlled for included age , marital status , body mass index , physical activity , alcohol intake , coffee consumption , and history of cancer . RESULTS Eighty-two members of the cohort committed suicide during the 8-year follow-up period . In age-adjusted analyses with never smokers as the comparison group , the relative risk of suicide was 1.4 ( 95 % confidence interval [ CI ] = 0.8 , 2.3 ) among former smokers , 2.6 ( 95 % CI = 0.9 , 7.5 ) for light smokers ( < 15 cigarettes/day ) , and 4.5 ( 95 % CI = 2.3 , 8.8 ) among heavier smokers . After adjustment for potential confounders , the relative risks were 1.4 ( 95 % CI = 0.9 , 2.4 ) , 2.5 ( 95 % CI = 0.9 , 7.3 ) , and 4.3 ( 95 % CI = 2.2 , 8.5 ) , respectively . CONCLUSION We found a positive , dose-related association between smoking and suicide among White men . Although inference about causality is not justified , our findings indicate that the smoking-suicide connection is not entirely due to the greater tendency among smokers to be unmarried , to be sedentary , to drink heavily , or to develop cancers", "INTRODUCTION Varenicline ( Chantix ® ) is an efficacious first-line medication for smoking cessation . Studies suggest that one mechanism by which varenicline facilitates sustained smoking abstinence is by reducing the likelihood of relapse to smoking when a lapse , or slip , occurs during a quit attempt . The present study extends this line of research by conducting a prospect i ve laboratory study to examine the relapse prevention effects of varenicline following a programmed lapse . METHODS Daily smokers ( N = 47 ) completed a 5-week outpatient study in which they were r and omized to receive varenicline or placebo . The first week was a medication induction period that was immediately followed by a 4-week quit attempt . A programmed lapse ( 2 cigarettes smoked in the laboratory ) occurred on the second day of the quit attempt . RESULTS Participants receiving varenicline were slower to relapse and had greater total abstinence rates following lapse exposure . Participants in the varenicline group rated lapse cigarettes lower on measures of reward and intoxication and showed increased behavioral economic dem and elasticity for cigarettes ( reduced cigarette purchasing at higher prices ) compared with those receiving placebo . CONCLUSIONS These results demonstrate a relapse prevention effect of varenicline following smoking lapse exposure and suggest that an attenuation of reward from smoking and the blunting of subjective effects of smoking may underlie and /or contribute to this effect", "The authors examined the relation between cigarette smoking and suicide by conducting a cohort study of 300,000 male US Army personnel followed prospect ively from January 1987 through December 1996 for 961,657 person-years . They found that the risk of suicide increased significantly with the number of cigarettes smoked daily ( p for trend < 0.001 ) . In multivariable-adjusted analyses , smokers of more than 20 cigarettes a day , compared with never smokers , were more than twice as likely to commit suicide . For male active-duty army personnel , the dose-related association between smoking and suicide was not entirely explained by the greater tendency of smokers to be White , drink heavily , have less education , and exercise less often", "UNLABELLED Chinese translation BACKGROUND Depression is overrepresented in smokers . OBJECTIVE To evaluate smoking abstinence and changes in mood and anxiety levels in smokers with depression treated with varenicline versus placebo . DESIGN Phase 4 , multicenter , parallel , 1:1 allocation , double-blind , r and omization trial . R and omization , stratified by antidepressant use and depression score at baseline , was blocked in sizes of 4 . ( Clinical Trials.gov : NCT01078298 ) . SETTING 38 centers in 8 countries . PARTICIPANTS 525 adult smokers with stably treated current or past major depression and no recent cardiovascular events . INTERVENTION Varenicline , 1 mg twice daily , or placebo for 12 weeks , with 40-week nontreatment follow-up . MEASUREMENTS Primary outcome was carbon monoxide-confirmed continuous abstinence rate ( CAR ) for weeks 9 to 12 . Other outcomes included CARs assessed during nontreatment follow-up and ratings of mood , anxiety , and suicidal ideation or behavior . RESULTS 68.4 % versus 66.5 % of the varenicline and placebo groups , respectively , completed the study . Varenicline-treated participants had higher CARs versus placebo at weeks 9 to 12 ( 35.9 % vs. 15.6 % ; odds ratio [ OR ] , 3.35 [ 95 % CI , 2.16 to 5.21 ] ; P < 0.001 ) , 9 to 24 ( 25.0 % vs. 12.3 % ; OR , 2.53 [ CI , 1.56 to 4.10 ] ; P < 0.001 ) , and 9 to 52 ( 20.3 % vs. 10.4 % ; OR , 2.36 [ CI , 1.40 to 3.98 ] ; P = 0.001 ) . There were no clinical ly relevant differences between groups in suicidal ideation or behavior and no overall worsening of depression or anxiety in either group . The most frequent adverse event was nausea ( varenicline , 27.0 % ; placebo , 10.4 % ) . Two varenicline-group participants died during the nontreatment phase . LIMITATIONS Some data were missing , and power to detect differences between groups was low in rare events . Smokers with untreated depression , with co-occurring psychiatric conditions , or receiving mood stabilizers and antipsychotics were not included . CONCLUSION Varenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety . PRIMARY FUNDING SOURCE Pfizer", "IMPORTANCE It is estimated that more than half of those with serious mental illness smoke tobacco regularly . St and ard courses of pharmacotherapeutic cessation aids improve short-term abstinence , but most who attain abstinence relapse rapidly after discontinuation of pharmacotherapy . OBJECTIVE To determine whether smokers diagnosed with schizophrenia and bipolar disease have higher rates of prolonged tobacco abstinence with maintenance pharmacotherapy than with st and ard treatment . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled , parallel-group , relapse-prevention clinical trial conducted in 10 community mental-health centers . Of 247 smokers with schizophrenia or bipolar disease recruited from March 2008-April 2012 , 203 received 12-weeks ' open-label varenicline and cognitive behavioral therapy and 87 met abstinence criteria to enter the relapse prevention intervention . INTERVENTIONS Participants who had 2 weeks or more of continuous abstinence at week 12 of open treatment were r and omly assigned to receive cognitive behavioral therapy and double-blind varenicline ( 1 mg , 2 per day ) or placebo from weeks 12 to 52 . Participants then discontinued study treatment and were followed up to week 76 . MAIN OUTCOMES AND MEASURES Seven-day rate of continuous abstinence at study week 52 , the end of the relapse-prevention phase , confirmed by exhaled carbon monoxide . Secondary outcomes were continuous abstinence rates for weeks 12 through 64 based on biochemically verified abstinence and weeks 12 through 76 , based on self-reported smoking behavior . RESULTS Sixty-one participants completed the relapse-prevention phase ; 26 discontinued participation ( 7 varenicline , 19 placebo ) and were considered to have relapsed for the analyses ; 18 of these had relapsed prior to dropout . At week 52 , point-prevalence abstinence rates were 60 % in the varenicline group ( 24 of 40 ) vs 19 % ( 9 of 47 ) in the placebo group ( odds ratio [ OR ] , 6.2 ; 95 % CI , 2.2 - 19.2 ; P < .001 ) . From weeks 12 through 64 , 45 % ( 18 of 40 ) among those in the varenicline group vs 15 % ( 7 of 47 ) in the placebo group were continuously abstinent ( OR , 4.6 ; 95 % CI , 1.5 - 15.7 ; P = .004 ) , and from weeks 12 through 76 , 30 % ( 12 of 40 ) in the varenicline group vs 11 % ( 5 of 47 ) in the placebo group were continuously abstinent ( OR , 3.4 ; 95 % CI , 1.02 - 13.6 ; P = .03 ) . There were no significant treatment effects on psychiatric symptom ratings or psychiatric adverse events . CONCLUSIONS AND RELEVANCE Among smokers with serious mental illness who attained initial abstinence with st and ard treatment , maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates compared with cognitive behavioral therapy alone after 1 year of treatment and at 6 months after treatment discontinuation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00621777", "INTRODUCTION Nicotine replacement therapy to aid smoking reduction increases the probability of a future quit attempt among smokers not currently planning to quit smoking . We tested whether varenicline , a partial nicotine agonist , would also increase future quit attempts . METHODS This r and omized , placebo-controlled trial recruited 218 smokers who were interested in quitting but had no plans to quit in the next month . Participants used varenicline ( 2 mg/day ) or placebo for 2 - 8 weeks plus received brief counseling on methods to reduce cigarettes/day . The primary measure was the incidence of a quit attempt within 6 months of study entry . Secondary measures were point prevalence abstinence , motivation to stop smoking , and reduction in cigarettes/day . RESULTS Varenicline increased the incidence of a quit attempt more than placebo at the Nebraska site ( 73 % vs. 41 % ; p < .001 ) but not at the Vermont site ( 45 % vs. 51 % ; p = .45 ) . Varenicline increased most other measures of quit attempts , motivation and abstinence , independent of site . The beneficial effects of varenicline in quit attempts appeared to be mediated by greater reductions in cigarettes/day , dependence , craving , and cigarette satisfaction . Varenicline had a greater effect on quit attempts in less-dependent smokers , in minority smokers , and in those who had less prior cessation or reduction activity . Adverse events were minimal . CONCLUSIONS Varenicline increased quit attempts in smokers who are not currently trying to quit at one of the two study sites and improved most all secondary outcomes independent of site . This appeared to be due to decreasing cigarettes/day and level of dependence", "This study was design ed to investigate the multiple-dose pharmacokinetics , safety , and tolerability of the selective α4β2 nicotinic acetylcholine partial agonist , varenicline , in elderly ( 65 - 85 years old ) nonsmokers . Fifty male and female subjects with normal renal function for their age were r and omized to receive varenicline or placebo once or twice daily for 3 weeks in an investigator- and subject-blinded parallel-group design . Treatment regimens included weekly titration ( n = 14 ; days 1 - 7 , 0.5 mg once daily ; days 8 - 14 , 0.5 mg twice daily ; days 15 - 21 , 1 mg twice daily ) ; 2-week twice-daily titration ( n = 13 ; days 1 - 14 , 0.5 mg once daily ; days 15 - 21 , 0.5 mg twice daily ) ; 2-week once-daily titration ( n = 13 ; days 1 - 14 , 0.5 mg once daily ; days 15 - 21 , 1 mg once daily ) ; and placebo ( n = 10 ) . Approximate dose-proportional increases in systemic exposure of varenicline at steady state , based on maximum concentration and area under the plasma concentration-time curve over the 24-hour period at steady state , were observed across the dose range of 0.5 to 2 mg/d . Median time to maximum concentration was 3 hours . Mean elimination half-life was estimated to be approximately 24 to 32 hours and independent of dose . Varenicline was considered to be safe and well tolerated in this elderly nonsmoking population" ]
"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"
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[ "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." ]
[ "This study prospect ively evaluated the clinical performance of computer-assisted design and computer-assisted manufacturing (CAD/CAM)-generated In-Ceram Alumina core crowns in Japanese patients for up to 5 years . A total of 101 In-Ceram crowns with aluminium copings fabricated using the GN-I system were placed in Japanese patients . The crowns were evaluated using a California Dental Association ( CDA ) quality assessment system at baseline and at all follow-up examinations . Gingival condition was assessed using plaque and bleeding scores . The survival of anterior and posterior crowns was analysed according to the Kaplan-Meier method . The scores of gingival condition were compared between restored crowns and contralateral teeth using a t-test . During the observation period , six crowns were lost to follow-up . Five crowns were fractured from the copings and removed , and four crowns were removed for other reasons . Chipping within the porcelain was detected in three crowns , which were then polished . The cumulative survival rates after 60 months were 96·9 % for anterior crowns and 87·7 % for posterior ones , and there were no significant differences between anterior and posterior crowns . According to the CDA criteria , most of the crowns were rated as satisfactory during the observation period . There were significant differences in soft tissue conditions between In-Ceram crowns and control teeth at 2- and 5-year examinations . Despite the five fractures from copings , In-Ceram Alumina crowns with copings fabricated using the CAD/CAM ( GN-I system ) for replacing both anterior and posterior teeth showed predictable results during a 5-year observation period", "Objectives The purpose of this prospect i ve study was to evaluate the clinical outcome of anterior and posterior crowns made of a lithium-disilicate glass – ceramic framework material ( IPS e.max Press , Ivoclar Vivadent ) . Material s and methods A total of 104 single crowns were placed in 41 patients ( mean age , 34 ± 9.6 years ; 15 male , 26 female ) . Eighty-two anterior and 22 posterior crowns were inserted . All teeth received a 1-mm-wide chamfer or rounded shoulder preparation with an occlusal/incisal reduction of 1.5–2.0 mm . The minimum framework thickness was 0.8 mm . Frameworks were laminated by a prototype of a veneering material combined with an experimental glaze . Considering the individual abutment preconditions , the examined crowns were either adhesively luted ( 69.2 % ) or inserted with glass – ionomer cement ( 30.8 % ) . Follow-up appointments were performed 6 months after insertion , then annually . Replacement of a restoration was defined as failure . Results Four patients ( 10 crowns ) were defined as dropouts . For the remaining 94 crowns , the mean observation time was 79.5 months ( range , 34–109.7 months ) . The cumulative survival rate according to Kaplan – Meier was 97.4 % after 5 years and 94.8 % after 8 years . Applying log rank test , it was shown that the location of the crown did not significantly have an impact on the survival rate ( p = 0.74 ) and that the cementation mode did not significantly influence the occurrence of complications ( p = 0.17 ) . Conclusions The application of lithium-disilicate framework material for single crowns seems to be a reliable treatment option . Clinical relevance Crowns made of a lithium-disilicate framework material can be used clinical ly in the anterior and posterior region irrespective of an adhesive or conventional cementation when considering abutment preconditions", "PURPOSE This study aim ed to prospect ively analyze the outcomes of 304 feldspathic porcelain veneers prepared by the same operator , in 100 patients , that were in situ for up to 16 years . MATERIAL S AND METHODS A total of 304 porcelain veneers on incisors , canines , and premolars in 100 patients completed by one prosthodontist between 1988 and 2003 were sequentially included . Preparations were design ed with chamfer margins , incisal reduction , and palatal overlap . At least 80 % of each preparation was in enamel . Feldspathic porcelain veneers from refractory dies were etched ( hydrofluoric acid ) , silanated , and cemented ( Vision 2 , Mirage Dental Systems ) . Outcomes were expressed as percentages ( success , survival , unknown , dead , repair , failure ) . The results were statistically analyzed using the chi-square test and Kaplan-Meier survival estimation . Statistical significance was set at P < .05 . RESULTS The cumulative survival for veneers was 96 % + /- 1 % at 5 to 6 years , 93 % + /- 2 % at 10 to 11 years , 91 % + /- 3 % at 12 to 13 years , and 73 % + /- 16 % at 15 to 16 years . The marked drop in survival between 13 and 16 years was the result of the death of 1 patient and the low number of veneers in that period . The cumulative survival was greater when different statistical methods were employed . Sixteen veneers in 14 patients failed . Failed veneers were associated with esthetics ( 31 % ) , mechanical complications ( 31 % ) , periodontal support ( 12.5 % ) , loss of retention > 2 ( 12.5 % ) , caries ( 6 % ) , and tooth fracture ( 6 % ) . Statistically significantly fewer veneers survived as the time in situ increased . CONCLUSIONS Feldspathic porcelain veneers , when bonded to enamel substrate , offer a predictable long-term restoration with a low failure rate . The statistical methods used to calculate the cumulative survival can markedly affect the apparent outcome and thus should be clearly defined in outcome studies", "The aim of this prospect i ve clinical study was to investigate the long-term survival of Procera AllCeram all-ceramic crowns in the anterior and posterior regions . Between 1997 and 2005 , 155 Procera crowns with aluminum oxide cores were placed in 50 patients . Patients were recalled in 2005 for a clinical assessment . Thirty-nine patients with 135 crowns attended the recall examination . Of the 135 total crowns , 103 were located in the posterior region and 32 were located in the anterior region . The cumulative survival rate was 100 % in the anterior region and 98.8 % in the posterior region ( 1 crown fracture ) after 5 and 7 years . Clinical success was achieved irrespective of the tooth position , cement used ( resin composite or glass-ionomer cement ) , or the core design with reduced or conventional margins . Procera AllCeram seems to be a predictable technique for esthetic all-ceramic single crown restorations in the anterior and posterior regions", "OBJECTIVE Ceramic inlays and onlays are a tooth colored alternative to metallic restorations . Clinical long-term data are scarce though , especially about inlays and onlays having proximal margins in dentin . The present prospect i ve controlled clinical study evaluated the clinical performance of IPS Empress inlays and onlays with cuspal replacements and proximal margins below the cementoenamel junction over eight years . METHODS Ninety six ceramic restorations were placed in 34 patients by six dentists . The restorations were bonded with an enamel/dentin bonding system ( Syntac Classic ) and four different resin composite systems . The restorations were assessed after placement by two calibrated investigators using modified USPHS codes and criteria at the following time periods : baseline , 1,2,4,6 and 8 years . RESULTS Eight of the 96 restorations investigated had to be replaced ( failure rate 8 % ; Kaplan-Meier ) : Six inlays suffered cohesive bulk fractures , two teeth required endodontic treatment . After eight years of clinical service , significant deterioration ( Friedman 2-way ANOVA ; P < 0.05 ) was found for marginal adaptation of the remaining restorations . 98 % of the surviving restorations exhibited marginal deficiencies , independent of the luting composite . CONCLUSIONS IPS Empress inlays and onlays demonstrated to be successful even in large defects . Neither the absence of enamel margins , nor cuspal replacement significantly affected the quality of the restorations", "Procera AllCeram crowns were prospect ively evaluated clinical ly in both anterior and posterior regions in Japanese . One-hundred and one crowns were fabricated for 57 patients at the Tsurumi University Dental Hospital from August 2001 to October 2002 and evaluated according to the California Dental Association ( CDA ) quality evaluation system at baseline and annually at all follow-up examinations for 5 years . The plaque index ( PI ) and gingival index ( GI ) were recorded , and chipping and fracture were checked at the same time as well . A total of 75 Procera AllCeram crowns were evaluated , and the cumulative survival rate was 90.2 % over the 5-year clinical trial . Six crowns experienced fractures within the veneering porcelain and from aluminium oxide coping , all of which occurred on the premolar and molar regions , and they had to be removed . Small chipping was observed on three crowns . According to the CDA criteria , 98 % of Procera AllCeram crowns were rated as satisfactory , and PI and GI were comparable to those of control teeth during the observation period", "PURPOSE The aim of this prospect i ve study was to evaluate the clinical efficacy and long-term survival rate of three-unit fixed partial dentures ( FPDs ) made from lithium disilicate-based core ceramic . MATERIAL S AND METHODS Twenty-one three-unit FPDs were placed in 19 patients to replace single lost teeth in the esthetic area , following a study protocol that took clinical , esthetic , and radiologic aspects into consideration . Each case was review ed at 1 week following placement , at 6 months , and then annually for 10 years . Statistical analysis was performed using Kaplan-Meier survival analysis . RESULTS Out of the 19 patients , 14.3 % presented reversible postoperative sensitivity . Recession was observed in 24 % of dental posts , and 7.1 % presented marginal discoloration . Treatment did not increase either Bleeding or Plaque Index scores at prepared teeth ; secondary caries did not appear either . The restorations ' survival rate at the 10-year follow-up was 71.4 % ; six FPDs had fractured and one debonded . CONCLUSIONS Fracture failure rate was 28.6 % after 10 years ; a high percentage corresponded to connector fractures and occurred during the first 5 years . Lithium disilicate glass-ceramic FPDs present a higher risk of fracture than st and ard therapies ( metal-ceramic ) or other more recently developed ceramic material s. The prognosis for survival improves for Class I occlusion and nonparafunctional patients", "The purpose of this prospect i ve cohort study was to assess the performance of tooth-supported , long-span , zirconia fixed dental prostheses ( FDPs ) . Thirty FDPs with span lengths from 36 to 46 mm ( mean 40·33 mm ) , with 4 - 7 units and with connector dimensions ∼9 mm(2 ) were inserted ( 19 in the posterior region , 11 including anterior teeth ) using glass-ionomer cement . The performance of the FDPs was assessed ( aesthetic evaluation , failures , hypersensitivity/tooth vitality , secondary caries , pocket depth , decementation , and chipping ) at baseline and after 5 years . Cox regression analysis was performed to identify risk factors . There were 16 failures after 5 years . Framework fracture occurred for two FDPs , four FDPs had to be re-cemented , one abutment tooth had to be treated endodontically , one abutment tooth fractured and cohesive failure of the veneer occurred for eight . Four FDPs had to be replaced , so survival was 82 % . The aesthetics were rated as excellent by the patients at baseline and good at the 5-year recall . Cox regression analysis showed that both length [ P = 0·05 , exp(B ) = 1·22 ] and location [ P = 0·019 , exp(B ) = 4·09 ] of the FDP were risk factors for failure . Compared with the previously published 2-year results , the incidence of complications increased dramatically . Additionally , it was shown that long-span FDPs in the molar region are at greater risk of failure than FDPs in the anterior region", "PURPOSE The aim of the present study was to clinical ly evaluate the effect of two different adhesive/resin composite combinations for luting IPS Empress inlays with a special focus on luting gap wear and marginal adaptation . MATERIAL S AND METHODS In the course of a controlled prospect i ve clinical split-mouth study , 94 IPS Empress restorations were placed in 31 patients . The inlays were luted with EBS Multi + Compolute ( EC ; 3 M ESPE ) or with Syntac + Variolink II low ( SV ; Ivoclar Vivadent ) . At baseline and after 0.5 , 1 , 2 , 4 , and 8 years , the ceramic restorations were examined according to modified USPHS codes and criteria . Thirty-five selected sample s were investigated under an SEM regarding morphological changes ; marginal quality analysis was carried out using a stereo light microscope , and luting composite wear was scanned with a profilometer . RESULTS Eight patients ( including 25 restorations ) missed the recalls ; the recall rate at the last investigation was 72 % . After 96 months of clinical service , seven restorations in five patients ( six EC , one SV ) had to be replaced due to hypersensitivities ( n = 5 ) or inlay fractures ( n = 2 ) result ing in a survival rate of 90 % . Over the 8-year period , the restorations revealed no statistically significant differences in terms of surface roughness , color matching , proximal contact , sensitivity , or complaints ( p > 0.05 , Friedman test ) . Significant deteriorations were found for marginal integrity ( p < 0.05 ) . No significant differences were observed for the different luting systems ( p = 0.096 , Log rank test/ Mantel Cox ) . Marginal analysis revealed no statistical difference among the material s ( p > 0.05 ; Mann-Whitney U-test ) , however , the scans of the luting gap showed that Compolute was more prone to wear ( p < 0.05 ) . CONCLUSION For luting of ceramic inlays , no difference between the two luting systems was detectable . The overall failure rate after 8 years was 10 %", "OBJECTIVES The purpose of this study was to investigate the durability of extensive dentin-enamel-bonded posterior ceramic coverages in a 15 years follow-up . METHODS All extensive dentin-enamel-bonded posterior partial and complete all-ceramic coverages placed during the period November 1992-December 1998 were included . In 121 patients , 252 coverages ( IPS Empress ) were placed . The adhesive bonding to dentin and enamel was performed with three 3-step and one 2-step etch and rinse bonding . In 106 restorations the classic Syntac was used in combination with the dual-cured resin composite Variolink . The other restorations were luted with the chemically cured resin composite Bisfil 2B and bonded with 3-step etch and rinse systems , classic Gluma ( 37 ) , Allbond 2 ( 57 ) , Syntac ( 32 ) or the 2-step etch and rinse system , One step ( 20 ) . The ceramics were evaluated yearly by modified USPHS criteria during 15 years . RESULTS Postoperative sensitivity was registered in 4 patients during bite forces lasting for 2 - 4 weeks . Fifty-five of 228 coverages ( 24.1 % ) failed . The mean observation period of the acceptable coverages was 12.6 years ( range 11 - 15 years ) . The main reasons for failure were lost restorations ( 18 ) , ceramic fracture ( 16 ) , and secondary caries ( 11 ) . Significant differences in failure rate were observed between the dentin bonding agents but not between the two luting agents . Ceramic coverages placed on non-vital teeth failed in 39 % and on vital teeth in 20.9 % ( p=0.014 ) . Logistic regression indicated three significant predictors for failure of the coverages : gender and parafunctional habits of the patient and non-vitality of the tooth . SIGNIFICANCE The technique investigated showed advantages like less destruction of healthy tissue , and avoiding of endodontic treatment and /or deep cervical placement of restoration margins to obtain retention", "OBJECTIVES Midterm-evaluation of a prospect i ve 5-year clinical study on long-term performance and success rate of pressed-ceramic veneers with two extended preparation design s. METHODS Anterior teeth of 25 patients were restored with 66 extended veneers . Forty-two overlap veneers ( OV ) ( incisal-edge-reduction 0.5 - 1.5 mm , butt-joint ) and 24 full veneers ( FV ) were inserted . Both veneer design s were similar in buccal ( 0.5 mm ) and proximal ( 0.5 - 0.7 mm ) chamfer preparation , but differed in palatal extension . Ceramic veneers were fabricated with IPS Empress * and adhesively luted with dual-polymerizing composite Variolink II * ( * Ivoclar Vivadent ) . Clinical reevaluations were performed 6 , 12 , 25 , 39 , 45 , and 62 months after insertion of the veneers according to the modified USPHS- criteria . Absolute failures were recorded as survival-rate , relative failures demonstrated by Kaplan-Meier success-rate . RESULTS After an observation time up to 5 years , survival-rate of full veneers was 100 % , of overlap veneers 97.5 % due to one severe fracture . Kaplan-Meier- analysis of relative failures result ed in a success-rate of 85 % for FV and 72 % for OV . Reasons for relative failures were cracks , ceramic-cohesive-fractures , and loss-of-adhesion . No significant differences were found between the two veneer groups . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in enhanced marginal discoloration and decrease of marginal adaptation . SIGNIFICANCE Extended pressed-ceramic veneers ( both OV and FV ) proved to be reliable procedures to restore larger deficits in anterior teeth . Pronounced palatal extension of full veneers was not linked to a higher failure probability . Reliable adhesive bonding , as well as ceramic fatigue and fracture resistance are considered key factors for long-term success of extended-veneer restorations", "The aim of this r and omized controlled trial was to evaluate the clinical performance of lithium disilicate fixed partial dentures ( FPDs ) . Eighteen patients received lithium disilicate FPDs ( study group ) , and 19 patients received porcelain-fused-to-metal FPDs ( control ) . After 6 years , the survival probabilities were found to be 63 % in the study group and 95 % in the control group ( log-rank test , P = .028 ) . The data suggest that strict conditions should be considered before the use of lithium disilicate glass-ceramic for FPDs", "OBJECTIVES The purpose of this prospect i ve study was to evaluate the clinical outcome of crown-retained fixed dental prostheses ( FDPs ) made from a lithium-disilicate glass-ceramic ( IPS e.max Press , Ivoclar-Vivadent ) . METHODS Thirty-six three-unit FDPs were placed in 28 patients . The FDPs replaced teeth in the anterior ( 16 % ) and posterior ( 84 % ) regions . All teeth were prepared following a st and ardized protocol . The size of the proximal connector of the FDPs was 12 mm2 ( anterior ) or 16 mm2 ( posterior ) . FDPs were cemented either with glass-ionomer cement ( n=19 ) or composite resin ( n=17 ) . The following parameters were evaluated at baseline , 6 months after cementation and then annually ( at abutment and contralateral teeth ) : probing pocket depth , plaque index , bleeding on probing , and tooth vitality . RESULTS Three FDPs were defined as drop-out . The mean observation period of the remaining 33 FDPs was 86 months ( range : 67 - 98 months ) : two FDPs in two patients had to be replaced ( 6 % ) because of fractures . The 8-year survival rate according to Kaplan-Meier was 93 % . In addition , chipping of the veneering material was found in two FDPs ( 6 % ) . Two abutments ( 3 % ) of two restorations had to be treated endodontically ; and two FDPs ( 6 % ) lost retention and had to be recemented . These complications did not affect the function of the involved restorations clinical ly . There were no significant differences between the periodontal parameters of the test and control teeth . SIGNIFICANCE Short-span crown-retained three-unit FDPs made from lithium-disilicate glass-ceramic can be used clinical ly irrespective of an adhesive or conventional cementation", "PURPOSE The aim of this prospect i ve clinical cohort study was to determine the success rate of 3- to 5-unit zirconia frameworks for posterior fixed partial dentures ( FPDs ) after 5 years of clinical observation . MATERIAL S AND METHODS Forty-five patients who needed at least 1 FPD to replace 1 to 3 posterior teeth were included in the study . Fifty-seven 3- to 5-unit FPDs with zirconia frameworks were cemented with 1 of 2 resin cements ( Variolink or Panavia TC ) . The following parameters were evaluated at baseline , after 6 months , and 1 to 5 years after cementation at test ( abutments ) and control ( contralateral ) teeth : probing pocket depth , probing attachment level , Plaque Index , bleeding on probing , and tooth vitality . Intraoral radiographs of the FPDs were taken . Statistical analysis was performed using descriptive statistics , Kaplan-Meier survival analysis , and the McNemar test . RESULTS Twenty-seven patients with 33 zirconia FPDs were examined after a mean observation period of 53.4 + /- 13 months . Eleven patients with 17 FPDs were lost to follow-up . After the 3-year recall visit , 7 FPDs in 7 patients were replaced because they were not clinical ly acceptable due to biologic or technical complications . After 5 years of clinical observation , 12 FPDs in 12 patients had to be replaced . One 5-unit FPD fractured as a result of trauma after 38 months . The success rate of the zirconia frameworks was 97.8 % ; however , the survival rate was 73.9 % due to other complications . Secondary caries was found in 21.7 % of the FPDs , and chipping of the veneering ceramic in 15.2 % . There were no significant differences between the periodontal parameters of the test and control teeth . CONCLUSIONS Zirconia offers sufficient stability as a framework material for 3- and 4-unit posterior FPDs . The fit of the frameworks and veneering ceramics , however , should be improved", "OBJECTIVE The aim of this prospect i ve clinical study was to evaluate the survival rates of IPS Empress 2 ( Ivoclar Vivadent ) all-ceramic crowns and fixed partial dentures ( FPDs ) after an observation period of up to 5 years . METHOD AND MATERIAL S Forty-three patients ( 19 women and 24 men ) were included in this study . The patients were treated with a total of 58 adhesive bonded IPS Empress 2 restorations . A total of 27 single crowns were placed on molars and premolars , and 31 three-unit FPDs were placed in the anterior and premolar regions . Clinical follow-up examinations took place at 6 , 12 , 24 , 36 , 48 , and 60 months after insertion . Statistical analysis of the data was calculated using the Kaplan-Meier method . RESULTS Results of the 50-month analysis ( interquartile range , 33 to 61 months ) showed that the survival rate was 100 % for crowns and 70 % for FPDs . Six failures that occurred exclusively in the three-unit FPDs were observed . Framework fractures were recorded in three FPD units where the connector dimensions did not meet the manufacturer specifications . Only one FPD exhibited an irreparable partial veneer fracture , and 2 FPDs showed evidence of biologic failures . The accuracy of fit and esthetic parameters were clinical ly satisfactory for crowns and FPDs . CONCLUSION The results of this 5-year clinical evaluation suggest that IPS Empress 2 ceramic is an appropriate material for the fabrication of single crowns . Because of the reduced survival rates , strict conditions should be considered before the use of IPS Empress 2 material for the fabrication of three-unit FPDs", "Objectives This prospect i ve , r and omized clinical split-mouth study investigated the 5-year performance of InCeram Alumina posterior crowns cemented with three different luting cements . 4-META- and MDP-based cements were used for adhesive luting . Glass ionomer cement served as control . Material s and Methods Sixty patients were treated with 149 ( n = 62 Panavia F/MDP ; n = 59 SuperBond-C&B/4-META ; n = 28 Ketac Cem/glass ionomer ) InCeram Alumina crowns on vital molars and premolars in a comparable position . Follow-up examinations were performed annually up to 5 years after crown placement using the modified United States Public Health Service ( USPHS ) criteria . Kaplan – Meier survival analysis comprised secondary caries , clinical ly unacceptable fractures , root canal treatment and debonding . Kaplan – Meier success rate included restorations with minimal crevices , tolerable color deviations ( < 1 Vitashade ) , and clinical ly acceptable fractures . Logistic regression models with a r and om intercept were fitted . Results The 5-year Kaplan – Meier survival probabilities were : SuperBond-C&B 88.7 % , Panavia F 82.8 % , Ketac Cem 80.1 % with no significant difference ( p = .813 ) . Endodontical treatment was carried out on 7.4 % of all abutment teeth , and 5.4 % revealed secondary caries . Unacceptable ceramic fractures were observed in 7.4 % . Debonding was a rare complication ( 1.3 % ) . The 5 year Kaplan – Meier success rate was 91.6 % for SuperBond-C&B- , 87.4 % for Ketac Cem- and 86.3 % for Panavia F-bonded restorations with no significant difference ( p = .624 ) . All cement types showed significant marginal deterioration over time ( p < .0001 ) . Conclusions Posterior InCeram Alumina crowns showed acceptable long-term survival and success rates independent of luting agent used . Ceramic fractures , endodontical treatments and secondary caries were the most frequent failures . Clinical relevance Glass-infiltrated Alumina crowns in combination with adhesive as well as conventional cementation can be considered as a reliable treatment option in posterior teeth", "This prospect i ve study evaluated the clinical outcome of three-unit posterior fixed dental prostheses ( FDPs ) made of In-Ceram Zirconia . All 65 FDPs were inserted at the Department of Prosthodontics , School of Dentistry , Kiel , Germany , and cemented with glass-ionomer cement . Follow-ups were performed annually . During a mean observation time of 54.4 months , two FDPs failed ( one technical and one biologic failure ) . Two FDPs debonded and the veneering ceramic fractured in four cases . Three abutment teeth needed endodontic treatment and two additional abutment teeth exhibited secondary caries . Results suggest that posterior three-unit all-ceramic FDPs made from In-Ceram Zirconia may be a viable prosthetic treatment option with an outcome comparable to metal-ceramic FDPs", "BACKGROUND The authors conducted a prospect i ve study to evaluate the long-term outcome of crown-retained fixed dental prostheses ( FDPs ) made from monolithic lithium disilicate ceramic ( IPS e.max Press , Ivoclar Vivadent , Schaan , Liechtenstein ) . METHODS Faculty dentists at the Department of Prosthodontics , Propaedeutics and Dental Material s , School of Dentistry , Christian-Albrechts University at Kiel , Germany , placed 36 three-unit FDPs in 28 patients to replace six anterior and 30 posterior teeth . The proximal connector size ( height and width ) was 4 × 3 millimeters for anterior FDPs and 4 × 4 mm for posterior FDPs . FDPs were cemented either conventionally with glass ionomer cement ( n = 19 ) or adhesively with resin-based composite ( n = 17 ) . Patients made annual recall visits . RESULTS The mean ( st and ard deviation ) observation period was 121 ( 12.8 ) months . FDPs ' survival rate ( survival being defined as remaining in place either with or without complications ) was 100 percent after five years and 87.9 percent after 10 years , and their success rate ( success being defined as remaining unchanged and free of complications ) was 91.1 percent after five years and 69.8 percent after 10 years . The cementation method did not affect the outcome . CONCLUSION Three-unit FDPs made from monolithic lithium disilicate ceramic showed five- and 10-year survival and success rates that were similar to those of conventional metal-ceramic FDPs . CLINICAL IMPLICATION S If the manufacturer 's recommendations are followed , three-unit FDPs made from monolithic lithium disilicate ceramic may be a safe alternative to metal-ceramic FDPs regardless of the cementation method used", "This prospect i ve clinical trial aim ed at evaluating the clinical performance of three-unit posterior zirconia fixed dental prostheses ( FDPs ) after 5 years of clinical function . Thirty-seven patients received 48 three-unit zirconia-based FDPs . The restorations replaced either a premolar or a molar . Specific inclusion criteria were needed . Tooth preparation was st and ardized . Computer-aided design /computer-assisted manufacturing frameworks with a 9-mm2 cross section of the connector and a 0.6-mm minimum thickness of the retainer were made . The restorations were luted with resin cement . The patients were recalled after 1 , 6 , 12 , 24 , 36 , 48 , and 60 months . The survival and success of the ceramics and zirconia were evaluated . The technical and aesthetic outcomes were examined using the United States Public Health Service criteria . The biologic outcomes were analyzed at abutment and contralateral teeth . Descriptive statistics were performed . All FDPs completed the study , result ing in 100 % cumulative survival rate and 91.9 % and 95.4 % cumulative success rates for patients wearing one and two FDPs , respectively . No losses of retention were recorded . Forty-two restorations were rated alpha in all measured parameters . A minor chipping of the ceramics was detected in three restorations . No significant differences between the periodontal parameters of the test and control teeth were observed . Five-year clinical results proved that three-unit posterior zirconia-based FDPs were successful in the medium term for both function and aesthetic . Zirconia can be considered a promising substitute of metal frameworks for the fabrication of short-span posterior prostheses", "PURPOSE The aim of this prospect i ve study was to evaluate the clinical performance of fully sintered hot isostatic pressed yttria-partially-stabilized zirconia ( Denzir ) 3-unit fixed partial dentures ( FPDs ) . MATERIAL S AND METHODS Nineteen 3-unit FPDs were placed in 18 patients . Ten FPDs were placed in the maxilla and 9 in the m and ible . Two calibrated examiners evaluated the FPDs independently 1 week ( baseline ) , 1 year , 3 years , and 5 years after placement using the California Dental Association quality evaluation system . RESULTS All FPDs were intact at the 5-year examination . One FPD lost retention after 12 months but remained intact ; it was recemented and is still in function after 5 years . All FPDs were rated satisfactory over 5 years . No changes were seen in terms of color and anatomic form . The number of slightly rough or pitted occlusal surfaces increased approximately 30 % over 5 years . Visible evidence of ditching along the margin increased over time , but only for those FPDs luted with zinc phosphate cement . CONCLUSION The 5-year results indicate that yttria-partially-stabilized zirconia 3-unit FPDs with anatomically design ed frameworks are promising prosthetic alternatives , even in the premolar and molar regions . However , for all-ceramic FPDs with more units in function , further studies are necessary", "The aim of this prospect i ve clinical study was to investigate the long-term performance of all-ceramic veneers with overlap ( OV ) and full veneer ( FV ) preparation design s. Twenty-five patients were restored using 42 OV restorations ( incisal/palatal butt-joint margin ) and 24 FV restorations ( palatal rounded shoulder margin ) . All restorations were leucite-reinforced glass-ceramic anterior veneers . The 7-year Kaplan-Meier survival rate was 100 % for FV restorations and 97.6 % for OV restorations . The all-ceramic veneers revealed significant deterioration over time according to United States Public Health Service criteria , irrespective of the preparation design . Based on the 7-year results of this study , both preparation design s can be considered reliable treatment options for anterior teeth with extended deficits", "OBJECTIVES The aim of this prospect i ve clinical study was to assess the long-term clinical survival rate and the technical and biological complication rates of zirconia-based posterior FDPs . MATERIAL S AND METHODS Forty-five patients in need of one or more posterior FDPs received 57 three- to five-unit zirconia-based FDPs . The frameworks were fabricated by means of a prototype computer-aided manufacturing ( CAM ) system ( direct ceramic machining , DCM ) , first processing zirconia in the white stage . The frameworks were veneered with a prototype veneering ceramic . The FDPs were adhesively placed . At baseline , 6 months , and 1,2 , 3 , 5 , 8 and 10 years of function , the FDPs were examined for technical and /or biological complications . Furthermore , the periodontal health of the abutment teeth ( test ) and untreated control teeth was analyzed . Statistical analysis was performed applying descriptive statistics , Kaplan-Meier survival and multiple mixed effects regression tests . RESULTS Twenty-one patients with 26 FDPs were examined at a mean observation time of 10.7 + /- 1.3 years . A total of 16 FDPs were lost to follow-up . Fifteen FDPs had to be replaced due to technical/biological complications ; hence , the 10-year survival rate of the FDPs was 67 % . Three framework fractures occurred , result ing in a 10-year survival rate for the zirconia frameworks of 91.5 % . Chipping/fracture of the veneering ceramic was detected in 16 FDPs over 10 years ( complication rate 32 % ) . A significant correlation of the span of the FDPs and the incidence of chipping was observed : 4- and 5-unit FDPs had a 4.9 times higher probability for chipping than 3-unit FDPs . Marginal discrepancy/degradation was found in 90.7 % of the FDPs over 10 years . At 11 of the FDPs ( complication rate 27 % ) , secondary caries occurred . No difference of the periodontal health was found around test and control teeth . CONCLUSION The zirconia frameworks exhibited very good long-term stability . However , the zirconia-based FDPs frequently exhibited problems such as marginal deficiency or chipping of the veneering ceramic . Both problems may be associated with the prototype status of the system", "OBJECTIVE The purpose of this study was to evaluate the clinical performance of Procera AllCeram crowns placed over a 5-year period at three different private dental practice s. METHOD AND MATERIAL S Two hundred five Procera AllCeram crowns ( 50 anterior and 155 posterior ) were evaluated in a prospect i ve study from a minimum of 6 months to a maximum of 60 months , with a mean of 23.52 months . RESULTS A restoration was considered to be a failure when it impaired esthetic quality or function , thus necessitating remake of the crown . The survival rate was determined with the use of the Kaplan-Meier survival rate , which gave an overall survival rate of 96.7 % ( 100 % for the anterior crowns and 95.15 % for the posterior crowns ) . CONCLUSION The Procera AllCeram system seems to have a good prognosis for the posterior teeth and an excellent one for the anterior teeth", "The aim of this prospect i ve clinical split-mouth study was to investigate the longterm performance of pressed and computer-aided design /computer-assisted manufacture ( CAD/CAM ) all-ceramic partial-coverage restorations ( PCRs ) . Twentyfive patients were restored with 40 lithium disilicate pressed PCRs ( IPS e.max-Press , Ivoclar Vivadent ) and 40 leucite-reinforced glass-ceramic CAD/CAM PCRs ( ProCAD , Ivoclar Vivadent ) . All restorations were placed in vital first or second molars . The 7-year Kaplan-Meier survival rate was 100 % for pressed PCRs and 97 % for CAD/ CAM PCRs . Both systems showed significant deterioration over time in all modified United States Public Health Service criteria . Increased surface roughness and impaired color match were significantly more prevalent with pressed PCRs . Based on the 7-year data , both all-ceramic systems can be considered reliable treatment options for posterior PCRs", "PURPOSE This controlled clinical trial aim ed to evaluate IPS Empress inlays and onlays over 12 years . The null hypothesis was that different luting resins would have no influence on clinical outcome . MATERIAL S AND METHODS In the course of a prospect i ve clinical long-term trial , 96 ceramic inlays and onlays were placed in 34 patients using one adhesive ( Syntac ) and four different luting composites ( Tetric , Variolink Low , Variolink Ultra , Dual Cement ) . Recalls were carried out by two calibrated investigators using modified USPHS codes and criteria at baseline , 1 , 2 , 4 , 6 , 8 , and 12 years . RESULTS Fifteen of the 96 restorations had to be replaced ( failure rate 16 % ; Kaplan-Meier ) ; 12 of them suffered bulk fractures . After twelve years of clinical service , significantly more bulk fractures were found when light-curing composite was used for luting ( p < 0.05 ) . Fractures were noticed between 3 and 4 years of clinical service and later after 11 to 12 years ; aside from those times , no single fracture occurred . Secondary caries was not observed . CONCLUSION IPS Empress inlays and onlays exhibited satisfactory clinical outcomes over a 12-year clinical period . Restorations luted with dual-cured resin composites revealed significantly fewer bulk fractures", "OBJECTIVES Midterm-evaluation of a 5-year prospect i ve clinical splitmouth-investigation on survival rate and long-term behavior of all-ceramic partial coverage restorations ( PCRs ) on molars . Pressed ceramic and CAD/CAM fabricated PCRs were compared . METHODS 80 vital molars of 25 patients were restored with all-ceramic PCRs ( 40 IPS e.max Press*[IP ] and 40 ProCAD*[PC ] ) . IP-PCRs were heat pressed following the lost-wax method . PC-PCRs were fabricated with Cerec 3 * * and Cerec InLab * * CAD/CAM system ( * * Sirona Dental Systems , Bensheim , Germany ) . All PCRs were adhesively luted with a light-polymerizing composite ( Syntac*/Tetric * ) ( * Ivoclar Vivadent , Schaan , Liechtenstein ) . Clinical reevaluations were performed at baseline and 13 , 25 , and 36 months after insertion of the PCRs according to the modified United States Public Health Services ( USPHS ) criteria . Absolute failures were demonstrated by Kaplan-Meier survival rate . RESULTS After an observation time up to 3 years , survival rate of IP-PCRs was 100 % and 97 % for PC-PCRs due to one severe fracture . The PC-PCR had to be replaced after 9 months . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in significant decrease of marginal adaptation ( p=0.031 ) and enhanced marginal discoloration ( p<0.0001 ) . Both PCR ceramic material s demonstrated significant deteriorations in color match ( p<0.0001 ) and surface roughness ( p<0.0001 ) , IP-PCRs were significantly more affected ( p < or = 0.005 ) . Regarding anatomic form IP-PCRs performed significantly better ( p=0.0012 ) . CONCLUSION Pressed ceramic and CAD/CAM fabricated partial coverage restorations exhibited a reliable treatment option to restore larger defects in posterior teeth . Marginal degradation of the resin cement and deterioration of the all-ceramic material s during clinical function determine the clinical long-term performance of partial coverage restorations" ]
"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"
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[ "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." ]
[ "Background and Purpose — Several prognostic factors have been identified for outcome after stroke . However , there is a need for empirically derived models that can predict outcome and assist in medical management during rehabilitation . To be useful , these models should take into account early changes in recovery and individual patient characteristics . We present such a model and demonstrate its clinical utility . Methods — Data on functional recovery ( Barthel Index ) at 0 , 2 , 4 , 6 , and 12 months after stroke were collected prospect ively for 299 stroke patients at 2 London hospitals . Multilevel models were used to model recovery trajectories , allowing for day-to-day and between-patient variation . The predictive performance of the model was vali date d with an independent cohort of 710 stroke patients . Results — Urinary incontinence , sex , prestroke disability , and dysarthria affected the level of outcome after stroke ; age , dysphasia , and limb deficit also affected the rate of recovery . Applying this to the validation cohort , the average difference between predicted and observed Barthel Index was −0.4 , with 90 % limits of agreement from −7 to 6 . Predicted Barthel Index lay within 3 points of the observed Barthel Index on 49 % of occasions and improved to 69 % when patients ’ recovery histories were taken into account . Conclusions — The model predicts recovery at various stages of rehabilitation in ways that could improve clinical decision making . Predictions can be altered in light of observed recovery . This model is a potentially useful tool for comparing individual patients with average recovery trajectories . Patients at elevated risk could be identified and interventions initiated", "Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items", "Although visual neglect is a predictor of poor outcome after stroke , some patients regain independence , whilst others take up considerable rehabilitation re sources . Intensive treatment of visual neglect is available and a knowledge of the predictive features in the recovery of these patients would be helpful in the early selection of patients for treatment . A study was therefore carried out to determine the prognosis of patients presenting with visual neglect at two to three days after stroke . Linear logistic regression showed that the initial degree of paralysis ( measured by the Motricity Index ) , the severity of neglect ( measured by the Visual Neglect Recovery Index ) and the patient 's age were the significant predictors of independence ( Barthel score 20 ) , mild dependence ( Barthel 15 - 19 ) , and moderate/severe dependence ( Barthel 0 - 14 ) in surviving patients at three months and at six months . Regression equations correctly predicted 78 % of outcomes , and had a sensitivity and specificity for \" independence \" of 84 % and 90 % respectively , and a sensitivity and specificity for \" moderate/severe dependence \" of 89 % and 80 % . It is suggested that these equations may be useful in selecting comparable groups of patients for r and omised controlled trials of treatment of visual neglect", "A cohort study tracks two or more groups forward from exposure to outcome . This type of study can be done by going ahead in time from the present ( prospect i ve cohort study ) or , alternatively , by going back in time to comprise the cohorts and following them up to the present ( retrospective cohort study ) . A cohort study is the best way to identify incidence and natural history of a disease , and can be used to examine multiple outcomes after a single exposure . However , this type of study is less useful for examination of rare events or those that take a long time to develop . A cohort study should provide specific definitions of exposures and outcomes : determination of both should be as objective as possible . The control group ( unexposed ) should be similar in all important respects to the exposed , with the exception of not having the exposure . Observational studies , however , rarely achieve such a degree of similarity , so investigators need to measure and control for confounding factors . Reduction of loss to follow-up over time is a challenge , since differential losses to follow-up introduce bias . Variations on the cohort theme include the before-after study and nested case-control study ( within a cohort study ) . Strengths of a cohort study include the ability to calculate incidence rates , relative risks , and 95 % CIs . This format is the preferred way of presenting study results , rather that with p values", "Background and Purpose — Prediction models for ischemic stroke outcome have the potential to contribute prognostic information in the clinical and /or research setting . The importance of diffusion-weighted magnetic resonance imaging ( DWI ) in the prediction of clinical outcome , however , is unclear . The purpose of this study was to combine acute clinical data and DWI lesion volume for ischemic stroke patients to determine whether DWI improves the prediction of clinical outcome . Methods — Patients ( N=382 ) with baseline DWI data from the Glycine Antagonist In Neuroprotection and citicoline ( 010 and 018 ) trials were used to develop the prediction models by multivariable logistic regression . Data from prospect ively collected patients ( N=266 ) from the Acute Stroke Accurate Prediction Study were used to externally vali date the model equations . The models predicted either full recovery or nursing home – level disability/death , as defined by the National Institutes of Health Stroke Scale , Barthel Index , or modified Rankin Scale . Results — The full-recovery models with DWI lesion volume had areas under the receiver operating characteristic curves ( AUCs ) of 0.799 to 0.821 , and those without DWI lesion volume had AUCs of 0.758 to 0.798 . The nursing home – level disability/death models with DWI had AUCs of 0.832 to 0.882 , and those without DWI had AUCs of 0.827 to 0.867 . All models had mean absolute errors ≤0.4 for calibration . Conclusions — All 12 models had excellent discrimination and calibration , with 8 of 12 meeting prespecified performance criteria ( AUC ≥0.8 , mean absolute error ≤0.4 ) . Although DWI lesion volume significantly increased model explanatory power , the magnitude of increase was not large enough to be clinical ly important", "Background and Purpose — Longitudinal conducted studies show that neurologic and functional recovery show faster recovery in the first weeks poststroke . The aim of the present study was to study the effects of progress of time on observed improvements in motor strength , synergisms , and activities during the first 16 weeks poststroke . Methods — Based on data from a previous study , 101 patients with first-ever ischemic middle cerebral artery strokes were prospect ively investigated during the first 16 weeks after stroke . Progress of time was categorized into 8 biweekly time intervals and was used as the independent covariate in a first-order longitudinal regression model . The biweekly time change ( progress of time ) was related to improvement in upper and lower limb motor recovery assessed with Fugl-Meyer score and Motricity Index , reduction in visuospatial inattention based on the letter cancellation task , and improvement in walking ability , dexterity , and activities of daily living measured with the Functional Ambulation Categories , Action Research Arm test , and Barthel Index . Results — Time explained a significant change of 8.4 ( 42 % ) measurement units on the Barthel Index for the first 10 weeks poststroke , 1.1 ( 22 % ) measurement units on Functional Ambulation Categories , and 19 % on the Action Research Arm test for the first 6 and 8 weeks poststroke . Approximately 25 % ( for Fugl-Meyer – arm ) to 26 % ( for Motricity Index – arm ) of the significant change in measurements units was explained by time alone for the upper limb compared with 33 % for Fugl-Meyer – leg and 39 % for Motricity Index – leg of the lower limb . Time accounted for a reduction of 16 % in the letter cancellation task . Observed associations did not change after controlling for covariates such as age , gender , hemisphere of stroke , type of stroke , or intervention . Conclusion — Progress of time is an independent covariate that reflects spontaneous recovery of body functions and activities explaining ≈16 % to 42 % of the observed improvements in the first 6 to 10 weeks after stroke onset", "BACKGROUND AND PURPOSE Previous studies suggest that undernourished patients with acute stroke do badly . The data , however , are not robust . We aim ed to reliably assess the importance of baseline nutritional status as an independent predictor of long-term outcome after stroke in a large prospect i ve cohort enrolled in the Feed Or Ordinary Diet ( FOOD ) trial , a multicenter r and omized trial evaluating various feeding policies . METHODS Patients admitted to hospital with a recent stroke were enrolled in the FOOD trial . Data on nutritional status and other clinical predictors of outcome were collected at trial entry . At 6 months , the coordinating center collected data on survival and functional status ( modified Rankin Scale ) . Outcome assessment was done by research ers blinded to baseline assessment s and treatment allocation . RESULTS Between November 1996 and November 2001 , 3012 patients were enrolled , and 2955 ( 98 % ) were followed up . Of the 275 undernourished patients , 102 ( 37 % ) were dead by final follow-up compared with only 445 ( 20 % ) of 2194 patients of normal nutritional status ( odds ratio [ OR ] , 2.32 ; 95 % CI , 1.78 to 3.02 ) . After adjustment for age , prestroke functional state , and stroke severity , this relationship , although weakened , still held ( OR , 1.82 ; 95 % CI , 1.34 to 2.47 ) . Undernourished patients were more likely to develop pneumonia , other infections , and gastrointestinal bleeding during their hospital admission than other patients . CONCLUSIONS These data provide reliable evidence that nutritional status early after stroke is independently associated with long-term outcome . It supports the rationale for the FOOD trial , which continues to recruit and aims to estimate the effect of different feeding regimes on outcome after stroke and thus determine whether the association observed in this study is likely to be causal", "In a prospect i ve study , the prognostic value of clinical characteristics in 157 consecutive patients with spontaneous supratentorial intracerebral haemorrhage were examined by means of multivariate analysis . Two days after the event 37 ( 24 % ) patients had died . Factors independently contributing to the prediction of two day mortality were pineal gl and displacement on CT of 3 mm or more ( p less than 0.001 ) , blood glucose level on admission of 8.0 mmol/l or more ( p = 0.01 ) , eye and motor score on the Glasgow Coma Scale of eight out of 10 or less ( p = 0.022 ) and haematoma volume of 40 cm3 or more ( p = 0.037 ) . Between the third day and one year after the event another 46 of the 120 two day survivors had died ; the independent prognostic indicators for death during that period were : age 70 years or more ( p less than 0.001 ) and severe h and icap ( Rankin grade five ) on the third day ( p less than 0.001 ) . Functional independence ( Rankin grade two or less ) at one year was most common not only with the converse features of age less than 70 years ( p less than 0.01 ) and Rankin grade four or less on the third day ( p = 0.002 ) , but also with an eye and motor score on the Glasgow Coma Scale of nine or 10 on the third day ( p less than 0.001 ) . The 120 patients with intracerebral haemorrhage who were still alive two days after the event were matched with 120 patients with cerebral infa rct ion , according to age , level of consciousness on the third day after stroke ( Glasgow Coma Scale ) and h and icap ( Rankin grade ) . Survival and h and icap after one year did not differ between these two groups . The conclusion drawn is that it is not the cause ( intracerebral haemorrhage or cerebral infa rct ion ) but the extent of the brain lesion that determines the outcome in patients who survive the first two days", "BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome . The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone . The purpose of this study was to determine the multivariable relationship between infa rct volume , 6 clinical variables , and 3-month outcomes in ischemic stroke patients . METHODS Included in the study were 256 eligible patients from the R and omized Trial of Tirilazad Mesylate in Acute Stroke ( RANTTAS ) . Six clinical variables and 1-week infa rct volume were the prespecified predictor variables . The National Institutes of Health Stroke Scale , Barthel Index , and Glasgow Outcome Scale were the outcomes . Multivariable logistic regression techniques were used to develop the model equations , and bootstrap techniques were used for internal validation . Predictive performance of the models was assessed for discrimination with receiver operator characteristic ( ROC ) curves and for calibration with calibration curves . RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves . The areas under the ROC curves were statistically greater ( P<0.001 ) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability . CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients . Demonstration of this relationship with acute clinical variables and 1-week infa rct information supports future attempts to predict 3-month outcome with all acute variables", "Two hundred and six patients with acute stroke admitted consecutively to District General Hospitals , were studied for a period of six months . Significance tests conducted singly detected 21 factors present during the first 48 h of stroke , which were related to outcome six months later in terms of both mortality and functional recovery . Among these significant factors were various measures of perceptual dysfunction , including Albert 's Test . Multivariate statistical analysis which included discriminant analysis and linear logistic modelling , revealed six factors ( Albert 's Test Score , leg function , level of consciousness , arm power , weighted mental score and ECG changes ) which were significantly and independently related to outcome . A statistical model based on these factors predicted functional outcome with an overall accuracy of 67 per cent and mortality with an accuracy of 83 per cent . This model provides a useful basis for stratification in future r and omized controlled trial in stroke , and may have a role in the management of the individual stroke patient", "The prognosis of supratentorial haematomas is based on clinical signs and radiological features . The role of evoked potentials has not been evaluated systematic ally . In a prospect i ve study of supratentorial haemorrhage a number of clinical ( 17 ) , radiological ( 3 ) and evoked potential ( 2 ) parameters were evaluated employing univariate logistic regression analysis in 69 patients and multivariate logistic regression stepdown analysis in 51 patients . The outcome was grade d on the basis of the Barthel index ( BI ) score at 3 months as good ( BI ≥ 12 ) or poor ( death or BI < 12 ) recovery . Employing univariate analysis the significant prognostic variables were Glasgow Coma Scale , Canadian Neurological Scale , tendon reflex , associated medical complications , urinary incontinence , ventricular extension of the haematoma and motor evoked potentials . Using multivariate logistic regression analysis the best set of parameters in relation to outcome inlcuded Glasgow Coma Scale ( P < 0.05 ) , Canadian Neurological Scale ( P < 0.05 ) , tendon reflex ( P < 0.1 ) , ventricular extent ( P < 0.01 ) and motor evoked potentials ( P < 0.05 ) . From this study it is concluded that , in addition to clinical and radiological parameters , motor evoked potentials also have an important role in predicting outcome", "Background and Purpose — Increased circulating endothelial progenitor cells ( EPC ) have been associated with a low cardiovascular risk and may be involved in endothelial cell regeneration . The present study was design ed to evaluate the prognostic value of EPC in acute ischemic stroke . Methods — Forty-eight patients with a first-ever nonlacunar ischemic stroke were prospect ively included in the study within 12 hours of symptoms onset . Stroke severity was evaluated by the National Institutes of Health Stroke Scale , and functional outcome was assessed at 3 months by the modified Rankin Scale ( mRS ) . Infa rct volume growth between admission and days 4 to 7 was measured on multiparametric MRI . EPC colonies were defined as early outgrowth colony-forming unit-endothelial cell ( CFU-EC ) . The increment of CFU-EC was quantified during the first week and defined as the absolute difference between the number of CFU-EC at day 7 and admission . The influence of CFU-EC increase on good functional outcome ( mRS ≤2 ) and infa rct growth was analyzed by logistic regression and linear models . Results — Patients with good outcome ( n=25 ) showed a higher CFU-EC increment during the first week ( median [ quartiles ] , 23 [ 11 , 36 ] versus −3 [ −7 , 1 ] , P<0.0001 ) compared with patients with poor outcome . CFU-EC increment ≥4 during the first week was associated with good functional outcome at 3 months ( odds ratio , 30.7 ; 95 % CI , 2.4 to 375.7 ; P=0.004 ) after adjustment for baseline stroke severity , ischemic volume and thrombolytic treatment . For each unit increase in the CFU-EC the mean reduction in the growth of infa rct volume was 0.39 ( 0.03 to 0.76 ) mL ( P=0.033 ) . Conclusions — The increase of circulating EPC after acute ischemic stroke is associated with good functional outcome and reduced infa rct growth . These findings suggest that EPC might participate in neurorepair after ischemic stroke", "Objective : The NIH Stroke Scale ( NIHSS ) may not appropriately assess the spectrum of posterior circulation (PC)–related neurologic deficits . We determined the cutoff baseline NIHSS score that predicts independent daily life activity during the chronic stage in anterior circulation ( AC ) vs PC ischemic strokes . Methods : A total of 310 consecutive patients hospitalized within 3 days after the onset of an ischemic stroke were prospect ively enrolled in the study . Patients on thrombolytic therapy were excluded . In all patients , infa rcts and vascular lesions were identified primarily using magnetic resonance techniques . A favorable outcome was defined as a modified Rankin Scale score of ≤2 at 3 months poststroke . Results : In 101 patients with PC stroke , the total baseline NIHSS score was lower ( p < 0.001 ) , and the subscores of ataxia ( p < 0.001 ) and visual fields ( p = 0.043 ) were higher than in 209 patients with AC stroke . Multivariate-adjusted OR for the favorable outcome in patients with PC vs AC stroke was 2.339 ( 95 % CI 1.331–4.109 , p = 0.003 ) . A low baseline NIHSS score was independently predictive of a favorable outcome in both patients with PC ( OR 1.547 , 95 % CI 1.232–1.941 ) and AC ( 1.279 , 1.188–1.376 ) stroke . The optimal cutoff scores of the baseline NIHSS for the favorable outcome were ≤5 for patients with PC stroke ( sensitivity , 84 % ; specificity , 81 % ) and ≤8 for patients with AC stroke ( sensitivity , 80 % ; specificity , 82 % ) . Conclusions : The cutoff score of the baseline NIH Stroke Scale ( NIHSS ) for a favorable chronic outcome was relatively low in patients with PC stroke compared to patients with AC stroke . The NIHSS appears to have limitations with respect to its use when comparing the neurologic severity of PC and AC stroke", "Background and Purpose The purpose of this study was to analyze recovery of motor function in a cohort of patients presenting with an acute occlusion in the carotid distribution . Analysis of recovery patterns is important for estimating patient care needs , establishing therapeutic plans , and estimating sample sizes for clinical intervention trials . Methods We prospect ively measured the motor deficits of 104 stroke patients over a 6-month period to identify earliest measures that would predict subsequent motor recovery . Motor function was measured with the Fugl-Meyer Assessment . Fifty-four patients were r and omly assigned to a training set for model development ; 50 patients were assigned to a test set for model validation . In a second analysis , patients were stratified on basis of time and stroke severity . The sample size required to detect a 50 % improvement in residual motor function was calculated for each level of impairment and at three points in time . Results At baseline the initial Fugl-Meyer motor scores accounted for only half the variance in 6-month motor function ( r2=0.53 , p<0.001 ) . After 5 days , both the 5-day motor and sensory scores explained 74 % of the variance ( p<0.001 ) . After 30 days , the 30-day motor score explained 86 % of the variance ( p<0.001 ) . Application of these best models to the test set confirmed the results obtained with the training set . Sample -size calculations revealed that as severity and time since stroke increased , sample sizes required to detect a 50 % improvement in residual motor deficits decreased . Conclusions Most of the variability in motor recovery can be explained by 30 days after stroke . These findings have important implication s for clinical practice and research", "Background and Purpose — Intracerebral hemorrhage ( ICH ) is the most fatal and disabling stroke subtype . Widely used tools for prediction of mortality are fundamentally limited in that they do not account for effects of withdrawal of care and are not design ed to predict functional recovery . We developed an acute clinical score to predict likelihood of functional independence . Methods — We prospect ively characterized 629 consecutive patients with ICH at hospital presentation . Predictors of functional independence ( Glasgow Outcome Score ≥4 ) at 90 days were used to develop a logistic regression-based risk stratification scale in a r and om subset of two thirds and vali date d in the remaining one third of the cohort . Results — At 90 days , 162 ( 26 % ) patients achieved independence . Age , Glasgow Coma Scale , ICH location , volume ( all P<0.0001 ) , and pre-ICH cognitive impairment ( P=0.005 ) were independently associated with Glasgow Outcome Score ≥4 . The FUNC score was developed as a sum of individual points ( 0–11 ) based on strength of association with outcome . In both the development and validation cohorts , the proportion of patients who achieved Glasgow Outcome Score ≥4 increased steadily with FUNC score . No patient assigned a FUNC score ≤4 achieved functional independence , whereas > 80 % with a score of 11 did . The predictive accuracy of the FUNC score remained unchanged when restricted to ICH survivors only , consistent with absence of confounding by early withdrawal of care . Conclusions — FUNC score is a valid clinical assessment tool that identifies patients with ICH who will attain functional independence and thus , can provide guidance in clinical decision-making and patient selection for clinical trials", "Abstract . Objective : Disability and mortality represent the most relevant clinical outcome after acute ischemic stroke . However , vali date d and comprehensive prognostic models for recovery have not been developed . An accurate model including all previously suggested independent outcome predictors could improve the design and analysis of clinical trials . We therefore developed prognostic models for functional dependence and death after 100 days in a large cohort of stroke patients . Methods : From the German Stroke Data base , 1754 prospect ively collected records of patients with acute ischemic stroke were used for the development of prognostic models . Intubated patients and patients with low functional status before stroke were excluded . Functional independence was defined as a Barthel Index ≥95 after 100 days . Prognostic factors assessable within 72 hours after admission were identified by a systematic literature review . The final models of binary logistic regression analyses were internally vali date d and calibrated . Results : The result ing cross-vali date d and calibrated models correctly classified more than 80 % of the patients and yielded the following prognostic factors for functional independence : Age , right and left arm paresis at admission , NIH-Stroke Scale at admission , Rankin Scale 48–72 hours later , gender , prior stroke , diabetes , fever , lenticulostriate infa rct ion , neurological complications . The following variables were identified as prognostic factors for death : Age , NIH-Stroke Scale at admission , and fever . Conclusions : Our work gives an important insight into prognostic factors after acute ischemic stroke and presents predictive models with high prognostic accuracy . Together with a prospect i ve validation study , currently underway , we hence hope to improve the prediction of functional outcome after ischemic stroke", "Using death and functional status as end points , we prospect ively analyzed the outcome 6 months after spontaneous intracerebral hemorrhage in 166 patients admitted to an acute-care stroke unit on the first day of their stroke . Seventy-one patients ( 43 % ) died , 69 ( 42 % ) had a satisfactory outcome , and 26 ( 16 % ) had a poor functional outcome . Early ( 30-day ) survival was correlated with morphologic parameters on the initial computed tomogram ( hemorrhage size , midline shift , and intraventricular spread of the hemorrhage ) , while later ( 6-month ) survival was correlated with age . Using logistic regression , we found five independent predictors of satisfactory outcome at 6 months : age , hemorrhage size , intraventricular spread of the hemorrhage , limb paresis , and communication disorders . Of these , age was the most important predictor by far", "PURPOSE This study examined the relationship between depressive symptoms and time courses in achieving independence in basic activities of daily living ( BADL ) and instrumental activities of daily living ( IADL ) . METHODS At baseline , 1 , 3 , and 6 months after stroke , 459 stroke patients were prospect ively assessed . We used the Geriatric Depression Scale to determine depressive status . Outcomes were times to achieve independence in BADL ( Barthel > 95 ) and independ-ence in at least three IADL . We used the Kaplan-Meier method and time-dependent Cox proportional hazards regression to examine the relationship between depression and stroke recovery . RESULTS Depressed patients were 0.3 times less likely than nondepressed patients to achieve BADL of > 95 and 0.4 times less likely to be independent in three or more IADL . The cumulative percentages for the nondepressed patients to achieve a BADL of > 95 at 1 , 3 , and 6 months after stroke were 47 % , 63 % , and 72 % , and for the depressed patients , they were 19 % , 34 % , and 52 % , respectively . Similarly , the cumulative percentages for nondepressed patients to achieve complete independence in three or more IADL at 1 , 3 , and 6 months after stroke were 56 % , 72 % , and 85 % , and for the depressed patients , they were 32 % , 47 % , and 72 % , respectively . Depressed patients had poorer recovery patterns and took longer to achieve the outcomes . CONCLUSION Stroke patients with depressive symptoms progressed slower in achieving independence of BADL and IADL compared to patients without depressive symptoms", "OBJECTIVE To determine whether changes in nutritional status in the first week after acute ischemic stroke and undernutrition predicts poor clinical outcomes . DESIGN Prospect i ve observational study . SETTING Tertiary university hospital . PATIENTS We included 131 acute ischemic stroke patients who underwent nutritional assessment s within 24 hours and at 1 week after symptom onset . MAIN OUTCOME MEASURES Undernutrition was diagnosed when 1 or more of the following 5 parameters were present : ( 1 ) weight loss 10 % or more during the past 3 months or 6 % or more during the week after admission , ( 2 ) a weight index less than 80 % , ( 3 ) a serum albumin level less than 3.0 g/dL , ( 4 ) a transferrin level less than 150 mg/dL , or ( 5 ) a prealbumin level less than 10 mg/dL. We assessed poststroke complications and 3-month outcome using modified Rankin Scale responder analysis . RESULTS Of 131 patients included in this study , undernutrition was observed in 16 ( 12.2 % ) patients at admission and in 26 ( 19.8 % ) at 1 week . Multiple logistic regression analysis showed that baseline undernutrition independently predicted 1-week undernutrition ( odds ratio [ OR ] , 14.85 ; 95 % confidence interval [ CI ] , 3.52 - 62.76 ; P < .001 ) and poststroke complications ( OR , 6.72 ; 95 % CI , 1.09 - 41.56 ; P= .04 ) , and that 1-week undernutrition ( OR , 4.49 ; 95 % CI , 1.07 - 18.94 ; P= .04 ) and 1-week National Institutes of Health Stroke Scale score ( OR , 1.76 ; 95 % CI , 1.31 - 2.37 ; P < .001 ) independently predicted poor 3-month outcomes . CONCLUSIONS These findings suggest that acute ischemic stroke patients with baseline undernutrition are being undernourished during hospitalization . Strategic nutritional support , particularly in patients with baseline undernutrition , may improve clinical outcomes", "Objective : To compare the baseline National Institutes of Health Stroke Scale ( NIHSS ) score and the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) stroke subtype as predictors of outcomes at 7 days and 3 months after ischemic stroke . Methods : Using data collected from 1,281 patients enrolled in a clinical trial , subtype of stroke was categorized using the TOAST classification , and neurologic impairment at baseline was quantified using the NIHSS . Outcomes were assessed at 7 days and 3 months using the Barthel Index ( BI ) and the Glasgow Outcome Scale ( GOS ) . An outcome was rated as excellent if the GOS score was 1 and the BI was 19 or 20 ( scale of 0 to 20 ) . Analyses were adjusted for age , sex , race , and history of previous stroke . Results : The baseline NIHSS score strongly predicted outcome , with one additional point on the NIHSS decreasing the likelihood of excellent outcomes at 7 days by 24 % and at 3 months by 17 % . At 3 months , excellent outcomes were noted in 46 % of patients with NIHSS scores of 7 to 10 and in 23 % of patients with scores of 11 to 15 . After multivariate adjustment , lacunar stroke had an odds ratio of 3.1 ( 95 % CI , 1.5 to 6.4 ) for an excellent outcome at 3 months . Conclusions : The NIHSS score strongly predicts the likelihood of a patient ’s recovery after stroke . A score of ≥16 forecasts a high probability of death or severe disability whereas a score of ≤6 forecasts a good recovery . Only the TOAST subtype of lacunar stroke predicts outcomes independent of the NIHSS score", "Background and Purpose : Models are used to adjust for case mix and to stratify treatment allocation in clinical trials and can , if accurate enough , be used to aid decision-making in individual patients . We aim ed to vali date , in patients assessed within 6 hours of onset , a previously described six simple variable ( SSV ) model that was developed in stroke patients who were assessed sub-acutely . The explanatory variables in the model are age , living alone , independent pre-stroke , Glasgow Coma Scale verbal score , ability to lift arms and ability to walk . Methods : The six variables were collected at r and omisation in the Third International Stroke Trial ( IST3 ) trial of recombinant tissue plasminogen activator in ischaemic stroke . We assessed survival to 30 days and functional status at 6 months using the Oxford H and icap Scale . We constructed receiver operator characteristic ( ROC ) curves to establish the model ’s discriminatory performance and tested its calibration by charting predicted versus actual outcomes . Results : 537 patients ( mean age , 74 years ) were included , of whom 422 ( 79 % ) survived 30 days and 179 ( 33 % ) were alive and independent at 6 months . The SSV model had an area under the ROC curve of 0.73 for 30-day survival and 0.82 for independent survival at 6 months . Calibration was satisfactory . Conclusions : This study confirms the external validity of the SSV model in an ischaemic stroke population assessed within 6 hours of symptom onset . The SSV model comprising easily collected variables can therefore be used to stratify patients in hyper-acute stroke trials , but probably is not accurate enough for decision-making in individual patients", "Objectives : ( I ) To obtain biomechanical parameters and assessment scores applied at a very early stage after stroke that predict best the functional outcome after rehabilitation . ( II ) To evaluate the predictive value of changes ( i.e. increase or decrease ) of these parameters during the first week in relation to the predictive value of their absolute scores . Design : Prospect i ve outcome study . Subjects : Forty-one stroke patients , admitted to the stroke unit within 24 hours . Main outcome measures : Barthel Index , Rivermead Motor Assessment , Motor Club Assessment and Functional movement activities , NIH-Stroke scale ( NIH-SS ) , Grip strength . Results : Parameters assessed within the first hours after stroke correlated only weakly with the outcome . The best model predicting functional outcome and independence in activities of daily living of stroke patients after 6 months was that including NIH-SS , grip strength , age and previous stroke explaining 79 % of the variance . These parameters assessed on day 7 post-stroke are more predictive than the difference between stroke onset and day 7 post-stroke . Conclusion : Parameters for predicting outcome should not be assessed before day 7 post-stroke", "OBJECTIVE To develop a model for predicting outcome in the first few hours after the onset of an ischemic stroke on the basis of the clinical findings obtained during a rapid bedside examination . DESIGN Clinical records were retrieved from the data bank of a r and omized multicenter trial . The result ing case series was split into two subgroups that served as a \" training set \" and a \" test set . \" Logistic regression was applied to the training set to select the prognostic predictors among baseline clinical findings . The performances of the model based on independent prognostic predictors were then vali date d in the test set . SETTING Eleven primary care institutions ( either hospitals or university clinics ) participating in the Italian Acute Stroke Study on the efficacy of hemodilution and monosialoganglioside in acute ischemic stroke . PATIENTS Consecutive noncomatose patients ( N = 300 ) observed within the first 6 hours after the onset of a first supratentorial ischemic stroke . MAIN OUTCOME MEASURE Death or disablement 4 months after the index stroke . Disablement was defined as a score of 3 or higher on the Rankin Scale . RESULTS Age and CNS score defined six risk groups with a predicted 4-month poor outcome rate ranging from 10 % ( patients aged 70 years or younger and with an initial CNS score of 7 or higher ) to 89 % ( patients older than 70 years and with a CNS score of 4.5 or lower ) . When a risk of poor outcome of 60 % was taken as a cutoff , the accuracy of the prediction was 78 % + /- 6 % in the training set and 72 % + /- 9 % in the test set . CONCLUSION Long-term outcome can be predicted in the first few hours following an acute ischemic stroke by means of a simple model based on age and CNS score", "OBJECTIVE To determine whether physical function before stroke is an independent predictor of physical function and institutionalization 6 months after discharge from hospital in elderly stroke patients . DESIGN Population -based prospect i ve cohort design where incidence of stroke was monitored from 1982 through 1988 . Baseline demographic and health information including prestroke function was collected prospect ively . Eligible subjects who had a stroke were interviewed 6 months after discharge from hospital to assess outcomes . SETTING New Haven , Connecticut . PATIENTS Subjects were recruited from an initial sample of 2,812 older adults . Of 79 subjects who survived a first stroke at 6 months postdischarge , complete follow-up data were obtained on 63 subjects . MAIN OUTCOME MEASURE Physical function as measured by the Katz scale and institutionalization . RESULTS Fewer limitations in activities of daily living before stroke were associated with fewer limitation in physical function after stroke controlling for stroke severity and other relevant health and sociodemographic conditions ( p < .01 ) . Fewer limitations in gross mobility function before stroke were also independently associated with a lower risk of institutionalization ( p < .05 ) . CONCLUSION This study provides useful information in assessing the prognosis of elderly stroke patients upon admission to hospital . It also supports the concept of general frailty being a risk factor for poorer health and institutionalization overall in aged persons . Studies have shown that factors related to physical frailty , such as decline in muscle function , can be reversed . The effect of interventions aim ed at improving the physical function of the elderly on stroke incidence , stroke outcomes , and all-cause mortality , however , needs to be determined", "In a prospect i ve observational study , we assessed the relative value of conventional stroke risk factors and emerging markers in the prediction of functional outcome of patients surviving the acute phase of an ischemic non-embolic stroke . All available eligible patients consecutively admitted due to a first-ever acute ischemic non-embolic stroke during a 2-year period were evaluated . In a total of 105 patients ( 54 males , 51 diabetic ) a series of clinical , biochemical and imaging characteristics were recorded , including demographic data , blood pressure , serum glucose , insulin , lipids , inflammatory markers , intima-media thickness of the carotid arteries ( IMT ) , brain damage location and size of the infa rct volume . Barthel Activities of Daily Living Index ( BI ) scale was used to assess the severity of neurological deficit on admission and the functional outcome 6 months after discharge . Brain infa rct volume , stroke location in the anterior circulation , age , diabetes mellitus , IMT and plasma interleukin-1beta levels proved to be significant determinants of long-term functional outcome , assessed by BI disability score . ROC curve analyses indicated that the infa rct volume is superior to other predictors in the diagnosis of patients with unfavorable functional outcome ( BI<95 ) at 6 months post-discharge ( area under the curve , AUC=0.80 , 95 % confidence interval 0.64 - 0.95 ; p=0.003 ) . Significant differences in the mean infa rct volume were noted among age tertiles , with the diabetic patients in the 3rd tertile of age experiencing the worst outcome ( LSD test , p=0.019 ) . Taken together , the assessment of infa rct volume seems to have a significant predictive value regarding long-term functional outcome , especially in the elderly diabetic patients", "Abstract : Few well‐ design ed descriptive studies focus exclusively on patients after motor stroke . This study describes a cohort of participants after motor stroke and assesses the extent to which five key variables explain the variation in functional recovery 3 months after stroke . Prospect i ve data were collected ( N = 100 ) on age , lesion volume , motor strength , cognition , and poststroke function during the acute care hospital admission . Instruments included magnetic resonance imaging ( MRI ) to provide a measure of lesion volume , the Mini‐Mental State Examination ( MMSE ) and the Neurobehavioral Cognitive Status Examination ( NCSE ) to measure cognitive status , and the National Institutes of Health Stroke Scale ( NIHSS ) to measure motor strength . The Functional Independence Measure ( FIMTM ) was used to measure baseline function and functional recovery 3 months after stroke . Descriptive and hierarchical multiple regression analyses were used to describe the cohort and predict functional recovery . The means for key variables during acute care were 65 ( ±15 ) years of age , lesion volume 21.5 ( ±44.7 ) cm3 , NIHSS 6.34 ( ±3.55 ) , MMSE 24.38 ( ±4.82 ) , NCSE 64.33 ( ±13 ) , and FIMTM 94.05 ( ±19.31 ) . Age , cognitive status , and initial function accounted for 42 % of the variance in functional recovery 3 months after stroke . Results indicate that neuroscience nurses need to add cognition to their focus during the fast‐paced acute phase of care following motor stroke", "OBJECTIVE To compare the acute Allen 's Prognostic Score , Canadian Neurological Score , and subacute Barthel Index as predictors of outcome functional status and infa rct size at 3 months in patients with acute cortical infa rct ion . DESIGN A prospect i ve study of acute stroke predictors and outcome measurements in a cohort of sequential hospitalized patients . PATIENTS Fifty-one patients with acute cortical infa rct ion and without previous disability assessed 24 hours after onset with Allen 's Prognostic Score and the Canadian Neurological Score and at 7 days with the Barthel Index . MAIN OUTCOME MEASURES Mortality , Barthel Index , and volumetric measurement of infa rct size on computed tomography 3 months after stroke . RESULTS There were seven deaths . The outcome Barthel Index was measured in all 44 survivors , of whom 29 had computed tomography at the time outcome was determined . In a multivariate analysis , functional outcome was best predicted by Allen 's Prognostic Score , a score of less than -15 having a sensitivity of 82 % and specificity of 97 % in predicting a poor outcome ( Barthel Index , < or = 12 or death ) . Volumetric tissue loss was predicted only by Allen 's Prognostic Score ( r = .62 , P < .001 ) . CONCLUSIONS Allen 's Prognostic Score is a robust predictor of both functional outcome and tissue loss in acute cortical infa rct ion and has a potentially important role in the analysis of the results of acute stroke intervention trials", "Background : Common carotid artery intima – media thickness ( CCA-IMT ) is an independent and early marker of generalised atherosclerosis . Brain affected by atherosclerosis may be more vulnerable to an ischaemic insult . Objective : To investigate the association between CCA-IMT and functional outcome after an acute ischaemic stroke . Design : Prospect i ve cohort analysis . Methods : 284 consecutive patients ( mean ( SD ) age , 68.7 ( 12.7 ) years , 126 ( 44 % ) female ) with an acute ischaemic stroke had carotid ultrasonography , carried out by a single operator . Demographic data , vascular risk factors , initial stroke severity , and brain imaging findings were recorded . Outcome was assessed at seven days from stroke onset , at discharge from hospital , and at one year post-stroke . Results : CCA-IMT was not significantly associated with adverse short or long term functional outcome in univariate analysis , or after adjustment in a multivariate logistic regression analysis for demographic data , initial stroke severity , conventional vascular risk factors , and the characteristics of the ischaemic lesion . Age and initial stroke severity were the only independent predictors of outcome . Conclusions : CCA-IMT was not associated with adverse functional outcome after an ischaemic stroke . Adding CCA-IMT in a prediction model for stroke outcome would probably not improve the power of the model", "OBJECTIVE Establish the relation between age , gender , initial neurologic deficit , stroke location , prior stroke , hemisphere of stroke , and functional outcome in ischemic stroke . DESIGN Single group , multivariate , repeated measures design with 327 persons having ischemic stroke recruited from 20 participating centers . SETTING Twenty European stroke centers . PATIENTS Consecutive admissions of men and women between the ages of 40 and 85 yrs with a hemispheric stroke caused by middle cerebral artery ischemia and a Unified Neurological Stroke Scale score of 5 to 24 . INTERVENTIONS In patients enrolled in the trial received traditional rehabilitation therapies including physical therapy , occupational therapy , and speech therapy when appropriate . MAIN OUTCOME MEASURES Barthel Index computed at 7 to 10 days and 3 months poststroke . RESULTS Positive functional outcomes were significantly related to the absence of prior strokes , a younger age , a less severe initial neurologic deficit , stroke involving cortical structures , and dominant ( left hemisphere ) lesions . CONCLUSIONS Despite some inconsistencies in existing literature , st and ardized prospect i ve examination of outcome after stroke clearly demonstrated the effect of age , initial severity of stroke , and lesion location as predictors of functional outcome", "Objective : To externally vali date two prognostic models predicting functional outcome and survival 100 days after acute ischemic stroke . Methods : Using prospect ively collected data from 1,470 patients , the authors evaluated two previously developed models . Model I predicts incomplete functional recovery ( Barthel Index < 95 ) vs complete functional recovery with 11 variables , whereas model II predicts mortality vs survival with 3 variables . On admission to a participating hospital , patients were registered prospect ively and included according to defined criteria . Within 72 hours , predictive variables under investigation were assessed . Follow-up was performed 100 days after the event . Results : Model I correctly predicted 68.1 % of the patients who had incompletely recovered or had died and 85.7 % of the completely recovered patients , model II 46.9 % of the patients who had died and 95.9 % of the surviving patients . Both models performed better than the treating physicians ’ predictions made within 72 hours after admission . Conclusion : The result ing prognostic models are useful to correctly stratify treatment groups in clinical trials and to accurately predict the distribution of endpoint variables", "The aim of this study was to evaluate prospect ively early predictors for ambulation and motor outcome 6~months after stroke occurrence . Sixty-eight consecutive , first-ever , stroke survivors were prospect ively studied from the second week to the sixth month post stroke . Sex , age , stroke type , urinary incontinence , National Institutes of Health Stroke Scale ( NIHSS ) , and Trunk Control Test ( TCT ) scores were taken as independent variables . Gait ability and motor functional outcome at 6 months post-stroke were assessed . Age , sex , urinary incontinence , TCT and NIHSS were significantly related to final modified Rankin Scale ( mRS ) , motor portion of the Functional Independence Measure ( FIM ) and Berg Balance Scale ( BBS ) . Age and early TCT alone accounted for 61.1 % of the variance in the motor FIM rating ( at 6 months post-stroke ) . TCT < or= 50 on day 14 predicts non-independent walkers ( Functional Ambulation Categories ( FAC ) < 4 ) : sensitivity 83.3 % , specificity 85.7 % ) , OR : 30.0 , 95 % CI : 4.7 - 247.3 . In conclusion , early administered TCT predicts independent walking ability and motor functional outcome at six months post-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." ]
[ "Visceral leishmaniasis ( VL ) is a deadly vector-borne disease that causes an estimated 500 000 new cases a year . In India , Nepal and Bangladesh , VL is caused by Leishmania donovani , which is transmitted from man to man by the s and fly Phlebotomus argentipes . In 2005 , these three countries signed a memor and um of underst and ing to eliminate VL from the region . Integrated vector management is one of the pillars of this elimination strategy , alongside early case detection and treatment . We review ed the evidence of effectiveness of different vector control methods , to examine the potential role of insecticide treated bednets ( ITNs ) . Indoor residual spraying has shown poor impact for various reasons and resistance to DDT is emerging in Bihar . Environmental management performed poorly compared to insecticide based methods . ITNs could give individual protection but this still needs to be proven in r and omized trials . Given the constraints of indoor residual spraying , it is worthwhile to further explore the use of ITNs , in particular long lasting ITNs , as an additional tool in the VL elimination initiative", "INTRODUCTION American cutaneous leishmaniasis is endemic in Colombia , where approximately 6.000 new cases are reported every year . Current prevention and control measures are restricted to the diagnosis and treatment of cases . OBJECTIVE To evaluate the efficacy of a multifaceted intervention to prevent the transmission of Leishmania in the endemic focus of Tumaco , on the Pacific Coast of Colombia . MATERIAL S AND METHODS A group-r and omized trial was conducted . Twenty villages were matched according to prevalence of Leishmania infection , number of inhabitants and level of community participation , and then r and omly assigned to intervention or control . The intervention included deltamethrin-impregnated bednets , repellent ( 20 % diethyltoluamide and 0.5 % permethrin ) , modification of s and fly resting sites , and health education . Villages were under surveillance for one year and the use of the intervention measures monitored . The incidence of American cutaneous leishmaniasis and Leishmania infection in the two groups were compared , adherence to the intervention and adverse events were monitored , and the results were adjusted for village intraclass correlation . RESULTS Ten cases of American cutaneous leishmaniasis were confirmed in the intervention and 23 in the control group , OR = 0.42 , 95 % CI 0.14 - 1.26 . The intervention had a greater effect in children < 10 years old , in people living on the periphery of the village and in villages with a prevalence of infection in small children > 1 % . Adverse events associated with the use of the bednets and the repellent were reported in 2 % of the participants and were always mild . CONCLUSION Incident cases of American cutaneous leishmaniasis were reduced by 58 % in the intervention group . However , the small number of cases renders the effect estimate imprecise and precludes us to cl aim a protective effect for the intervention . Specific population s could be the targets of simpler and more cost-effective interventions in the future", "A large-scale intervention field trial of the effect of Olyset long-lasting insecticide-treated bednets on transmission of cutaneous leishmaniasis was carried out in 2 cities in the Islamic Republic of Iran from October 2003 to July 2005 . We enrolled 8620 individuals in 3000 households in 6 pairs of sectors in each city . Epidemiological and entomological surveys were carried out pre- and post-intervention . In both cities a statistically significant reduction was found in the incidence of new cases in intervention sectors who received bednets compared with control areas . Entomological surveys showed a reduction in numbers of female Phlebotomus sergenti captured indoors in intervention sectors", "Objective To test the effectiveness of large scale distribution of longlasting nets treated with insecticide in reducing the incidence of visceral leishmaniasis in India and Nepal . Design Paired cluster r and omised controlled trial design ed to detect a 50 % reduction in incidence of Leishmania donovani infection . Setting Villages in Muzaffarpur district in India and Saptari , Sunsari , and Morang districts in Nepal . Participants 13 intervention and 13 control clusters . 12 691 people were included in the analysis of the main outcome ( infection ) , and 19 810 were enrolled for the secondary ( disease ) end point . Intervention Longlasting insecticidal nets ( treated with deltamethrin ) were distributed in the intervention clusters in December 2006 . Main outcome measures Infection was determined by direct agglutination test at 12 and 24 months after the intervention in those who had negative results ( titre < 1:1600 ) at baseline . The effect estimate was computed as the geometric mean of the risk ratios for seroconversion for each cluster pair ( net/no net ) , with its 95 % confidence interval . Formal tests of effect of no intervention were obtained with a paired t test . Results There was no significant difference in the risk of seroconversion over 24 months in intervention ( 5.4 % ; 347/6372 ) compared with control ( 5.5 % ; 345/6319 people ) clusters ( risk ratio 0.90 , 95 % confidence interval 0.49 to 1.65 ) nor in the risk of clinical visceral leishmaniasis ( 0.99 , 0.46 to 1.40 ) . Adjustment for covariates did not alter these conclusions . Conclusions There is no evidence that large scale distribution of longlasting insecticidal nets provides additional protection against visceral leishmaniasis compared with existing control practice in the Indian subcontinent . The observed effect was small and not significant , though the confidence intervals did not exclude a 50 % change in either direction . Trial registration Clinical Trials NCT 2005 - 015374", "Abstract Objective : To measure the impact on transmission of leishmaniasis of curtains impregnated with insecticide . Design : Cluster r and omised controlled trial : household interview survey , observational study of people 's behaviour , entomological study with light trap captures of s and flies inside houses . Setting : 14 urban sectors in Trujillo , Venezuela . Participants : 2913 inhabitants of 569houses . Intervention : Sectors were paired according to their 12month cumulative incidence of cutaneous leishmaniasis , one sector in each pair was r and omly allocated to receive polyester curtains impregnated with lambdacyhalothrin ( intervention group ) while the other sector received curtains without insecticide or no curtains ( control groups ) . After 12 months a follow up household survey was conducted . Main outcome measures : Reduction in abundance of s and flies indoors and 12 month incidence of clinical cases of cutaneous leishmaniasis . Results : Transmission of cutaneous leishmaniasis occurred mainly in the domestic setting , with the incidence over 12 months of 4 % . The mean number of s and flies per trap per night was 16.After follow up the 12 month incidence of cutaneous leishmaniasis was 0 % in the intervention group and 8 % in the six pairs in the control group that received unimpregnated curtains ( mean difference 8 , 95 % confidence interval 4.22 to 11.78 ; P=0.001 ) . There were significantly fewer s and flies in the intervention group ( 2 v 15,mean difference 13 s and flies per trap ; 9 to 17 ; P<0.001 ) . Conclusion : Curtains impregnated with insecticide provide a high degree of protection against indoor transmission of cutaneous leishmaniasis", "Background Bangladesh , India and Nepal are working towards the elimination of visceral leishmaniasis ( VL ) by 2015 . In 2005 the World Health Organization/Training in Tropical Diseases launched an implementation research programme to support integrated vector management for the elimination of VL from Bangladesh , India and Nepal . The programme is conducted in different phases , from proof-of-concept to scaling up intervention . This study was design ed in order to evaluate the efficacy of the three different interventions for VL vector management : indoor residual spraying ( IRS ) ; long-lasting insecticide treated nets ( LLIN ) ; and environmental modification ( EVM ) through plastering of walls with lime or mud . Methods Using a cluster r and omized controlled trial we compared three vector control interventions with a control arm in 96 clusters ( hamlets or neighbourhoods ) in each of the 4 study sites : Bangladesh ( one ) , India ( one ) and Nepal ( two ) . In each site four villages with high reported VL incidences were included . In each village six clusters and in each cluster five households were r and omly selected for s and fly collection on two consecutive nights . Control and intervention clusters were matched with average pre-intervention vector densities . In each site six clusters were r and omly assigned to each of the following interventions : indoor residual spraying ( IRS ) ; long-lasting insecticide treated nets ( LLIN ) ; environmental management ( EVM ) or control . All the houses ( 50 - 100 ) in each intervention cluster underwent the intervention measures . A reduction of intra-domestic s and fly densities measured in the study households by overnight US Centres for Disease Prevention and Control light trap captures ( that is the number of s and flies per trap per night ) was the main outcome measure . Results IRS , and to a lesser extent EVM and LLINs , significantly reduced s and fly densities for at least 5 months in the study households irrespective of type of walls or whether or not people shared their house with cattle . IRS was effective in all sites but LLINs were only effective in Bangladesh and India . Mud plastering did not reduce s and fly density ( Bangladesh study ) ; lime plastering in India and one Nepali site , result ed in a significant reduction of s and fly density but not in the second Nepali site . ConclusionS and fly control can contribute to the regional VL elimination programme ; IRS should be strengthened in India and Nepal but in Bangladesh , where vector control has largely been ab and oned during the last decades , the insecticide treatment of existing bed nets ( coverage above 90 % in VL endemic districts ) could bring about an immediate reduction of vector population s ; operational research to inform policy makers about the efficacious options for VL vector control and programme performance should be strengthened in the three countries", "The efficacy of insecticide-treated window curtains ( ITCs ) for dengue vector control was evaluated in Thail and in a cluster-r and omized controlled trial . A total of 2,037 houses in 26 clusters was r and omized to receive the intervention or act as control ( no treatment ) . Entomological surveys measured Aedes infestations ( Breteau index , house index , container index , and pupae per person index ) and oviposition indices ( mean numbers of eggs laid in oviposition traps ) immediately before and after intervention , and at 3-month intervals over 12 months . There were no consistent statistically significant differences in entomological indices between intervention and control clusters , although oviposition indices were lower ( P < 0.01 ) in ITC clusters during the wet season . It is possible that the open housing structures in the study reduced the likelihood of mosquitoes making contact with ITCs . ITCs deployed in a region where this house design is common may be unsuitable for dengue vector control", "Abstract Objectives To measure the impact on the dengue vector population ( Aedes aegypti ) and disease transmission of window curtains and water container covers treated with insecticide . Design Cluster r and omised controlled trial based on entomological surveys and , for Trujillo only , serological survey . In addition , each site had a non-r and omised external control . Setting 18 urban sectors in Veracruz ( Mexico ) and 18 in Trujillo ( Venezuela ) . Participants 4743 inhabitants ( 1095 houses ) in Veracruz and 5306 inhabitants ( 1122 houses ) in Trujillo . Intervention Sectors were paired according to entomological indices , and one sector in each pair was r and omly allocated to receive treatment . In Veracruz , the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips ( an insect growth regulator ) . In Trujillo , the intervention comprised curtains treated with longlasting deltamethrin ( PermaNet ) plus water jar covers of the same material . Follow-up surveys were conducted at intervals , with the final survey after 12 months in Veracruz and nine months in Trujillo . Main outcome measures Reduction in entomological indices , specifically the Breteau and house indices . Results In both study sites , indices at the end of the trial were significantly lower than those at baseline , though with no significant differences between control and intervention arms . The mean Breteau index dropped from 60 % ( intervention clusters ) and 113 % ( control ) to 7 % ( intervention ) and 12 % ( control ) in Veracruz and from 38 % to 11 % ( intervention ) and from 34 % to 17 % ( control ) in Trujillo . The pupae per person and container indices showed similar patterns . In contrast , in nearby communities not in the trial the entomological indices followed the rainfall pattern . The intervention reduced mosquito population s in neighbouring control clusters ( spill-over effect ) ; and houses closer to treated houses were less likely to have infestations than those further away . This created a community effect whereby mosquito numbers were reduced throughout the study site . The observed effects were probably associated with the use of material s treated with insecticide at both sites because in Veracruz , people did not accept and use the pyriproxyfen chips . Conclusion Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission", "Background Visceral leishmaniasis ( VL ) control in the Indian subcontinent is currently based on case detection and treatment , and on vector control using indoor residual spraying ( IRS ) . The use of long-lasting insecticidal nets ( LN ) has been postulated as an alternative or complement to IRS . Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages . Methods A cluster-r and omized controlled trial with household P. argentipes density as outcome was design ed . Twelve clusters from an ongoing LN clinical trial — three intervention and three control clusters in both India and Nepal — were selected on the basis of accessibility and VL incidence . Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps ( LT ) and mouth aspiration methods . Ten cattle sheds per cluster were also monitored by aspiration . Findings A r and om effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9 % ( 95 % CI 1.80%–42.5 % ) as measured by means of LTs . Interpretation The ongoing clinical trial , design ed to measure the impact of LNs on VL incidence , will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs . The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program . Trial registration Clinical Trials.gov CT-2005 -", "ABSTRACT Screening homes is an effective way of reducing house entry by mosquitoes . Here , we assess how important blocking the eaves is for reducing house entry by anopheline and culicine mosquitoes for houses that have screened doors and no windows . Twelve houses , with two screened doors and no windows , in which a single adult male slept , were included in a simple crossover design . In the first period , six houses were r and omly selected and had the eaves blocked using a mixture of rubble and mortar ; the other six were left with open eaves . Mosquitoes were sample d using CDC light traps from each house twice a week for 4 wk . Mosquito control activities and the number and type of domestic animals within the compound was recorded on each sampling occasion . Before beginning the second sampling period , homes with blocked eaves had them opened , and those with open eaves had them closed . Mosquitoes were then sample d from each house for a further 4 wk . When houses had their eaves closed , a three-fold reduction in Anopheles gambiae s.l . Giles caught indoors was observed . However , there was no reduction in total culicine numbers observed . This study demonstrates that the eaves are the major route by which An . gambiae enters houses . By contrast , culicine mosquitoes enter largely through doors and windows . Sealing the eave gap is an important method for reducing malaria transmission in homes where doors and windows are screened", "OBJECTIVES Insecticide-treated bednets ( ITNs ) are effective in preventing nocturnally transmitted vector-borne diseases , but their effect on diurnally active dengue vectors has never been studied . We investigated the efficacy of ITNs in reducing Aedes aegypti population s and dengue transmission . METHODS A cluster-r and omized trial was carried out in Leogane , Haiti between July 2003 and July 2004 . The study area ( 1017 houses ) was divided into 18 sectors ( clusters ) : nine received ITNs ( Olyset(R ) long-lasting insecticidal bednets ) and nine were untreated controls . Entomological surveys [ measuring Breteau ( BI ) , house ( HI ) , container ( CI ) and pupae per person ( PPI ) indices and oviposition activity ] were undertaken at baseline and at 1 and 5 months post-intervention . All houses were georeferenced to enable spatial analysis . Control sectors received ITNs at 6 months , and a final entomological and attitudinal survey was undertaken at 12 months after baseline . Anti-dengue IgM seropositivity rates were measured at baseline and after 12 months . Efficacy of ITNs was assessed by WHO cone bioassays . RESULTS At 1-month post-intervention , entomological indices fell in all sectors , with HI and BI in the bednet sectors reduced by 6.7 ( 95 % CI -10.6 , -2.7 ; P < 0.01 ) and 8.4 ( 95 % CI -14.1 , -2.6 ; P < 0.01 ) respectively . Moreover at 1 month , ovitraps in control sectors were significantly more likely to be positive than in bednet sectors ( P < 0.01 ) . By 5 months , all indices remained low and HI , CI and BI were also significantly lower than that of baseline in the control arm . Curiously , at 5 months , HI , CI and BI were lower in the control arm than that in the bednet arm . A final survey , 12 months after the initial baseline study ( 5 months after bednets had been given to all households ) indicated that all indices were significantly lower than that at baseline ( P < 0.001 ) . Control houses located within 50 m of a bednet house had significantly lower CI ( Z = -2.67 , P = 0.008 ) and PPI ( Z = -2.19 , P = 0.028 ) at 1 month , an effect that extended to 100 m by 5 months ( Z = -2.03 , P = 0.042 and Z = -2.37 , P = 0.018 respectively ) , suggesting a spill-over effect of the bednets . An IgM serosurvey showed a 15.3 % decrease ( 95 % CI 5.0 - 25.5 % , P < 0.01 ) in the number of IgM-positive individuals from baseline to12 months later . CONCLUSIONS Insecticide-treated bednets had an immediate effect on dengue vector population s after their introduction , and over the next 5 - 12 months , the presence of ITNs may have continued to affect vector population s and dengue transmission", "Anthroponotic cutaneous leishmaniasis ( ACL ) is a significant public health problem in many towns and cities of south central Asia and the Middle East , result ing in disfigurement and disability which warrants preventive action . A r and omized controlled trial was conducted in 1997/98 amongst a non-immune study population of 3666 people in Kabul , Afghanistan , to compare the efficacy of insecticide-treated nets ( ITNs ) , insecticide-treated Islamic cloth wraps ( chaddars ) used to sleep in , and residual pyrethroid spraying of individual houses for the prevention of ACL . Dosages of insecticide were : ITNs with permethrin , 0.5 g/m2 ; chaddars with permethrin , 1 g/m2 ; rooms with lambdacyhalothrin , 30 mg/m2 . Cases of ACL were diagnosed on clinical criteria . At the end of the trial period ( 15 months ) the incidence of ACL amongst controls was 7.2 % , amongst ITN users 2.4 % ( OR 0.31 , 95 % CI 0.2 - 0.5 ) , amongst impregnated chaddar users 2.5 % ( OR 0.33 , 95 % CI 0.2 - 0.6 ) and amongst residents of sprayed houses 4.4 % ( OR 0.60 , 95 % CI 0.3 - 0.95 ) . ITNs and impregnated chaddars were equally effective , providing about 65 % protective efficacy , with approximately 40 % protective efficacy attributable to individual house spraying . No significant differences for age or sex were found between new cases in the intervention and control groups . No serious side-effects were reported and interventions were generally popular ; ITNs were the most popular , followed by residual spraying and then impregnated chaddars", "The prevalence of bedbugs ( Cimex hemipterus L. ) , chicken ticks ( Argas persicus Oken ) and headlice ( Pediculus capitis De Geer ) was surveyed in a rural area of The Gambia . At the beginning of the study 37.5 % of children 's beds were infested with bedbugs and 3.9 % with chicken ticks , whilst the prevalence rate of pediculosis in children under 10 years old was 28.8 % . Both bedbugs and headlice were clustered within compounds . Headlice prevalence increased with hair length and they were more common on girls than boys . Following this cross-sectional survey all bednets in the sixteen hamlets were either dipped in permethrin or a placebo . About 4 months later it was found that bedbugs and chicken ticks had disappeared from homes in which the bednets had been impregnated with permethrin . There was no reduction in hamlets with placebo-treated bednets . The rate of acquiring headlice between the two surveys was reduced by 91.1 % in children who slept under insecticide-treated bednets compared with children with placebo-treated bednets . There were also significantly fewer day-flying and crawling insects , except earwigs , in homes of children who slept under insecticide-treated bednets compared with those with placebo-treated nets . These additional benefits of permethrin-treated bednets should contribute to their widespread acceptance and utilization by the community for personal protection", "Prior to implementation of a r and omized controlled trial of insecticide (permethrin)-treated bed nets ( ITNs ) in western Kenya , ethnographic studies were conducted to underst and local perceptions of disease , sleeping patterns , and other factors that might affect use of ITNs . Educational activities took place prior to distribution , but immediately after distribution in Asembo only approximately half of the ITNs were in use . A qualitative study was then conducted to identify the community 's perceptions about ITNs and the ITN project . While participants ranked malaria as important and recognized that malaria prevention could be beneficial , they believed ITNs would be only partly effective due to the perception that malaria has multiple causes . Concerns expressed included fear of the insecticide , thought by some to be a toxic family planning aid , the taking of blood during clinical studies , and the mixing up of family ITNs during net re-treatment , which would violate cultural taboos . Attempts were made to allay fears by improved communication on these subjects and modification of the study design", "The effectiveness of bednets and curtains ( nylon mesh 64 per cm2 ) impregnated with deltamethrin at 26 mg a.i./m2 in reducing the biting nuisance caused by three phlebotomine s and fly species : Lutzomyia columbiana , Lu.lichyi and the predominant Lu.youngi ( Diptera : Psychodidae ) , was evaluated at La Guaira , a rural settlement in Valle de Cauca near Cali , Colombia . Pairs of volunteers collected s and flies under impregnated bednets , in rooms protected by impregnated curtains or in unprotected rooms in a r and omized matched design . Collection s were made in three houses per night on three consecutive nights , so that each house was sample d under each of the three treatments . This routine was repeated at 2-week intervals for 6 months . There was no significant difference between the overall numbers of s and flies collected in rooms with or without impregnated curtains . Only 0.14 s and flies/man-hour were caught on human bait under impregnated bednets , significantly fewer than the numbers collected on human bait outside the nets in the same room ( 1.91 ) or in unprotected rooms ( 3.29 ) . In a second set of experiments carried out in La Guaira and the neighbouring community of Jiguales , the effect of deltamethrin impregnation was evaluated by comparing numbers of s and flies collected on human bait under treated and untreated nets . Significantly fewer were collected under the impregnated nets ( 0.25 v. 0.69/man-hour ) . Wild-caught female Lu.youngi exposed to treated netting for 2 min in the laboratory all died with 24 h. The impact of deltamethrin-impregnated bednets was considered to be useful against Lu.youngi and other potential vectors of leishmaniasis in such communities" ]
"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"
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[ "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." ]
[ "Background A small , non-blinded , RCT ( r and omised controlled trial ) had reported that oral antibiotics reduced the incidence of mastitis in lactating women with Staphylococcus aureus ( S. aureus)- colonized cracked nipples . We aim ed to replicate the study with a more rigorous design and adequate sample size . Methods Our intention was to conduct a double-blind placebo-controlled trial to determine if an antibiotic ( flucloxacillin ) could prevent mastitis in lactating women with S. aureus-colonized cracked nipples . We planned to recruit two groups of 133 women with S. aureus-colonized cracked nipples . Results We spent over twelve months su bmi tting applications to five hospital ethics committees and seven funding bodies , before commencing the trial . Recruitment to the trial was very slow and only ten women were r and omized to the trial after twelve months , and therefore the trial was stopped early . Conclusions In retrospect we should have conducted a feasibility study , which would have revealed the low number of women in these Melbourne hospitals ( maternity wards and breastfeeding clinics ) with damaged nipples . The appropriate use of antibiotics for breastfeeding women with cracked nipples still needs to be tested", "Trial design A r and omised , parallel group , pragmatic trial . Setting A large UK maternity hospital . Participants Term infants < 2 weeks old with a mild or moderate degree of tongue-tie , and their mothers who were having difficulties breastfeeding . Objectives To determine if immediate frenotomy was better than st and ard breastfeeding support . Interventions Participants were r and omised to an early frenotomy intervention group or a ‘ st and ard care ’ comparison group . Outcomes Primary outcome was breastfeeding at 5 days , with secondary outcomes of breastfeeding self-efficacy and pain on feeding . Final assessment was at 8 weeks ; 20 also had qualitative interviews . Research ers assessing outcomes , but not participants , were blinded to group assignment . Results 107 infants were r and omised , 55 to the intervention group and 52 to the comparison group . Five-day outcome measures were available for 53 ( 96 % ) of the intervention group and 52 ( 100 % ) of the comparison group , and intention-to-treat analysis showed no difference in the primary outcome —Latch , Audible swallowing , nipple Type , Comfort , Hold score . Frenotomy did improve the tongue-tie and increased maternal breastfeeding self-efficacy . At 5 days , there was a 15.5 % increase in bottle feeding in the comparison group compared with a 7.5 % increase in the intervention group . After the 5-day clinic , 44 of the comparison group had requested a frenotomy ; by 8 weeks only 6 ( 12 % ) were breastfeeding without a frenotomy . At 8 weeks , there were no differences between groups in the breastfeeding measures or in the infant weight . No adverse events were observed . Conclusions Early frenotomy did not result in an objective improvement in breastfeeding but was associated with improved self-efficacy . The majority in the comparison arm opted for the intervention after 5 days", "BACKGROUND : Ankyloglossia has been associated with a variety of infant-feeding problems . Frenotomy commonly is performed for relief of ankyloglossia , but there has been a lack of convincing data to support this practice . OBJECTIVES : Our primary objective was to determine whether frenotomy for infants with ankyloglossia improved maternal nipple pain and ability to breastfeed . A secondary objective was to determine whether frenotomy improved the length of breastfeeding . METHODS : Over a 12-month period , neonates who had difficulty breastfeeding and significant ankyloglossia were enrolled in this r and omized , single-blinded , controlled trial and assigned to either a frenotomy ( 30 infants ) or a sham procedure ( 28 infants ) . Breastfeeding was assessed by a preintervention and postintervention nipple-pain scale and the Infant Breastfeeding Assessment Tool . The same tools were used at the 2-week follow-up and regularly scheduled follow-ups over a 1-year period . The infants in the sham group were given a frenotomy before or at the 2-week follow-up if it was desired . RESULTS : Both groups demonstrated statistically significantly decreased pain scores after the intervention . The frenotomy group improved significantly more than the sham group ( P < .001 ) . Breastfeeding scores significantly improved in the frenotomy group ( P = .029 ) without a significant change in the control group . All but 1 parent in the sham group elected to have the procedure performed when their infant reached 2 weeks of age , which prevented additional comparisons between the 2 groups . CONCLUSIONS : We demonstrated immediate improvement in nipple-pain and breastfeeding scores , despite a placebo effect on nipple pain . This should provide convincing evidence for those seeking a frenotomy for infants with signficant ankyloglossia", "BACKGROUND The negative outcomes associated with painful and damaged nipples have been widely documented in the breastfeeding literature . Numerous studies have been conducted evaluating topical preparations to treat nipple pain and damage with equivocal findings . No studies have evaluated the effectiveness of the increasingly popular all- purpose nipple ointment ( APNO ) . The purpose of this trial is to evaluate the effect of the APNO versus lanolin on nipple pain among breastfeeding women with damaged nipples . SUBJECTS AND METHODS A double-blind , r and omized controlled trial was conducted in a large single-site , tertiary-care hospital in Toronto , ON , Canada . Breastfeeding women ( n=151 ) identified as having damage to one or both nipples were r and omized to apply either APNO ( intervention group ) or lanolin ( control group ) to their nipples according to the trial protocol . The primary outcome was nipple pain at 1 week after r and omization measured using the Short Form McGill Pain Question naire . Additional outcomes at 1 week after r and omization and 12 weeks postpartum included nipple yeast symptoms and /or mastitis , rates of breastfeeding duration and exclusivity , and maternal satisfaction with infant feeding method and treatment ointment . RESULTS There were no significant group differences in mean pain scores at 1 week after r and omization . Women in the lanolin group reported significantly greater satisfaction with their infant feeding method and had nonsignificantly higher breastfeeding duration and exclusivity rates at 12 weeks postpartum . CONCLUSION Results suggest that APNO is not superior to lanolin in treating painful , damaged nipples", "Painful and /or damaged nipples associated with breastfeeding are common and represent a challenge for both the persons experiencing nipple pain and /or trauma and for those providing treatment . However , evidence -based data has been insufficient to demonstrably minimize these common reasons for failure to initiate or continue successful breastfeeding . The aim of this study was to evaluate the efficacy of specific- grade highly purified anhydrous ( HPA ) lanolin versus expressed breastmilk ( EBM ) for the treatment of painful and damaged nipples associated with breastfeeding in a prospect i ve controlled clinical trial evaluating 84 lactating mothers . Nipple trauma and healing rates were rated by the Nipple Trauma Score . Nipple pain intensity was assessed on a visual analog scale . Outcome parameters were in favor of the HPA lanolin group , reaching statistical significance for healing rates , nipple trauma and nipple pain . In our study , we found HPA lanolin more effective than EBM , inducing faster healing of nipple trauma ( absolute risk reduction of 0.43 ) and reducing nipple pain ( absolute risk reduction of 0.61 on day 3 ) . We concluded that HPA lanolin , combined with breastfeeding education , was more effective than EBM , combined with breastfeeding education , in reducing nipple pain and promoting healing of nipple trauma", "Pre- and perinatal variables commonly found to predict breast-feeding duration were examined to see whether they also predicted breast-feeding problems in the first week postpartum . One hundred and twenty-eight families who prenatally committed to breast-feeding for at least 6 weeks comprised the sample . The families were r and omly assigned to one of two groups : a group in which bottle feedings would be avoided in Weeks 2–6 postpartum and a group in which approximately one bottle per day would be given during the same period . Breastfeeding events most commonly experienced as problems in previous studies were also reported by mothers in this sample . Multiple regression analyses revealed that bottle use in the hospital , lower satisfaction with first breastfeeding , and group assignment were weakly predictive of the Breast-feeding Problem Score at 1 week , R2 = .154 , p = .0004 . The negative effect of hospital bottle use was greater for women in the bottle-restricted group than for women in the planned-bottle group", "The research undertaken in this study utilized a case-control group nested within a prospect i ve cohort which was followed for the first 3 months postpartum . Mothers with mastitis and their controls were requested to complete a self-report question naire design ed to investigate the association between the potential risk factors , identified from the literature , and lactation mastitis . Logistic regression analyses of the possible risk factors were performed separately for mothers who had not breastfed Obviously and those mothers who had breastfed at least one infant prior to this lactation/nalysis showed blocked duct(s ) and increased levels of stress were the significant pre icors for mastitis in mothers who had breastfed a previous infant and blocked duct(s ) , restriction from a tight bra , attachment difficulties , and nipple pain during a feed were the significant predictors for mastitis in first time breastfeeding mothers", "AIM This study investigated if a maternally reported , immediate improvement in breastfeeding following division of tongue-tie is due to a placebo effect . METHODS This r and omized controlled trial was conducted at Southampton General Hospital , Southampton , UK , in 2003 - 2004 . Sixty breastfed babies 5 - 115 days old ( mean , 32 days ; median , 23 days ) were r and omized to division ( Group A ) or non-division ( Group B ) . The mother and a trained observer were blinded and assessed breastfeeding before the intervention . Fifty-seven babies were analyzed because blinding failed in three of the babies in Group A. Following the intervention , the mother 's and observer 's views were noted , and then those infants allocated to non-division had their tongue-tie divided . RESULTS Seventy-eight percent ( 21 of 27 ) of mothers in Group A reported an immediate improvement in feeding following the intervention , compared with 47 % ( 14 of 30 ) in Group B ( two-tailed χ(2 ) p<0.02 ; 95 % confidence interval , 6 - 51 % ) . At 1-day follow-up , 90 % ( 54 of 60 ) reported improved feeding following division . At 3-month follow-up , 92 % ( 54 of 59 ) still reported improved feeding , with 51 % ( 30 of 59 ) continuing to breastfeed . CONCLUSIONS There is a real , immediate improvement in breastfeeding , detectable by the mother , which is sustained and does not appear to be due to a placebo effect", "BACKGROUND Sore nipples are common during lactation and remain the major reason for failing to establish successful breastfeeding . To formulate a peppermint gel and to evaluate its effect on the prevention of nipple crack associated with breast-feeding , a r and omized double-blinded clinical trial comparing the above formulation with modified lanolin and a neutral ointment was carried out . MATERIAL / METHODS Two hundred and sixteen primiparous participants were assigned r and omly to three groups . Each group applied only one of the above three preparations on both breasts for 14 days . Each group consisted of 72 primiparous mothers and was seen for a maximum of four follow-up visits within 14 days and a final visit at week 6 . The rate of nipple and areola crack and pain was evaluated . RESULTS The study groups were comparable in mean age and route of delivery . Nipple crack were less in mothers who received peppermint gel than in those who received lanolin ointment or placebo ( chi(2)=16.8 , df=6 , P=0.01 ) . Relative risk of nipple crack in the lanolin group ( RR : 2.41 , 95%CI : 1.20 - 3.01 ) was higher than in the peppermint group ( RR : 1.85 , 95%CI : 1.64 - 3.10 ) . CONCLUSIONS Prophylactic peppermint gel in breastfeeding lactating women is associated with fewer nipple cracks and is more effective than lanolin and placebo . It could be recommended for preventing of nipple crack along with teaching better breastfeeding technique at the initiation of breastfeeding", "PURPOSE Ankyloglossia ( \" tongue-tie \" ) occurs in nearly 5 % of neonates , but its clinical significance relating to breast-feeding difficulties is controversial . We tested the hypothesis that in infants with ankyloglossia referred because of breast-feeding difficulties , frenotomy alleviates the symptoms . METHODS Twenty-five mothers of healthy infants with ankyloglossia were recruited because of sore nipples . Infants were r and omized to either of 2 sequences : ( 1 ) frenotomy , breast-feeding , sham , breast-feeding ( n = 14 ) or ( 2 ) sham , breast-feeding , frenotomy , breast-feeding ( n = 11 ) . The mothers as well as all personnel taking care of the child after each sham or frenotomy procedure were masked as to the study sequence . In every sequence , and after each sham or frenotomy procedure , a st and ardized latch score and pain score were obtained from the mother . RESULTS There was a significant decrease in pain score after frenotomy than after sham ( P = .001 ) . There was also a nearly significant improvement in latch after the frenotomy in these mothers ( P = .06 ) . CONCLUSION Frenotomy appears to alleviate nipple pain immediately after frenotomy . We speculate that ankyloglossia plays a significant role in early breast-feeding difficulties , and that frenotomy is an effective therapy for these difficulties", "Background Nipple pain and damage in breastfeeding mothers are common causes of premature breastfeeding cessation . Peppermint water is popularly used for the prevention of nipple cracks in the North West of Iran . The aim of this study was to determine the effectiveness of peppermint water in the prevention of nipple cracks during breastfeeding in comparison with the application of expressed breast milk ( EBM ) . Methods One hundred and ninety-six primiparous breastfeeding women who gave birth between February and May 2005 in a teaching hospital in Tabriz , Iran , were r and omized to receive either peppermint water or EBM . Each woman was followed for up to three visits or telephone calls within 14 days and then by telephone call at week six postpartum . Results Women who were r and omized to receive peppermint water were less likely to experience nipple and areola cracks ( 9 % ) compared to women using EBM ( 27 % ; p < 0.01 ) . Women who used the peppermint water on a daily basis were less likely to have a cracked nipple than women who did not use peppermint water ( relative risk 3.6 , 95%CI : 2.9 , 4.3 ) . Nipple pain in the peppermint water group was lower than the expressed breast milk group ( OR 5.6 , 95 % CI : 2.2 , 14.6 ; p < 0.005 ) . Conclusion This study suggests that peppermint water is effective in the prevention of nipple pain and damage . Further studies are needed to assess the usefulness of peppermint water in conjunction with correct breastfeeding techniques . Trial registration number :", "BACKGROUND Sore nipples in breast-feeding mothers are a common cause of premature weaning , and are difficult to treat owing to recurrent trauma and exposure to the infant 's oral flora . OBJECTIVE To compare the safety and efficacy of a hydrogel moist wound dressing ( Elasto-gel , Southwest Technologies Inc , Baltimore , Md ) with the use of breast shells and lanolin cream in the treatment of maternal sore nipples associated with breast-feeding . DESIGN R and omized controlled trial comparing the above treatments for sore nipples . Patients were seen for a maximum of 3 follow-up visits within 10 days , or until the resolution of symptoms . SETTING The Maternal-Infant Lactation Center at the Mercy Hospital of Pittsburgh , Pittsburgh , Pa , a tertiary care teaching hospital in inner-city Pittsburgh . PATIENTS A referred sample of 42 breast-feeding women who presented to the Maternal-Infant Lactation Center for the treatment of sore nipples . All patients with breast infection or chronic unrelated pain conditions were excluded from the study . INTERVENTION After informed consent , patients were r and omized to receive either a hydrogel wound dressing or breast shells and lanolin . All patients underwent a history , physical examination of the infant and the mother 's breasts , assessment of breast-feeding technique , and breast-feeding instruction . MAIN OUTCOME MEASURES The degree of pain on self-report question naires and the change in scores for physical examination , breast-feeding technique , and pain behaviors during breast-feeding . RESULTS Although both treatments , in association with instruction in breast-feeding technique , were effective , greater improvement was seen in the group using breast shells and lanolin . This reached statistical significance for physician-rated healing ( P<.01 ) and self-reported pain ( P<.05 ) . There were significantly more infections in the dressing group ( P<.05 ) , which result ed in early discontinuation of the study . CONCLUSIONS Prevention of sore nipples by teaching proper technique on the initiation of breast-feeding should be instituted . For those cases in which sore nipples do develop , breast shells and lanolin in association with instruction in breast-feeding technique are more effective than moist wound dressings . Lanolin and shells should remain first-line therapy", "OBJECTIVE To determine the demographic , behavioral , and clinical factors associated with breastfeeding termination in the first 12 weeks postpartum . STUDY DESIGN This was a prospect i ve cohort study . POPULATION Breastfeeding women in Michigan and Nebraska were interviewed by telephone at 3 , 6 , 9 , and 12 weeks postpartum or until breastfeeding termination . OUTCOMES MEASURED We measured associations of demographic , clinical , and breastfeeding variables with weaning during the first 12 weeks postpartum . RESULTS A total of 946 women participated ; 75 % breastfed until 12 weeks . Women older than 30 years and women with at least a bachelor 's degree were more likely to continue breastfeeding in any given week . Mastitis , breast or nipple pain , bottle use , and milk expression in the first 3 weeks were all associated with termination . Beyond 3 weeks , women who expressed breast milk were 75 % less likely to discontinue breastfeeding than women who did not . Women who used a bottle for some feedings during weeks 4 to 12 were 98 % less likely to discontinue breastfeeding than women who did not use a bottle . \" Not enough milk \" was the most common reason given for termination in weeks 1 through 3 ( 37 % ) and weeks 4 through 6 ( 35 % ) ; \" return to work \" was the most common reason given in weeks 7 through 9 ( 53 % ) and weeks 10 through 12 ( 58 % ) . CONCLUSIONS Younger women and less educated women need additional support in their breastfeeding efforts . Counseling and assistance should be provided to women with pain and mastitis . Exclusive breastfeeding for the first 3 weeks should be recommended . After the first 3 weeks , bottles and manual expression are not associated with weaning and may improve the likelihood of continuing breastfeeding , at least until 12 weeks", "Sore , cracked nipples are commonly experienced by breastfeeding mothers . We have previously reported a strong correlation between sore , cracked nipples and S. aureus colonization . A prospect i ve , r and omized clinical trial was performed to compare four treatmnent regimes for S. aureus infected sore nipples . Eighty-four breastfeeding mothers were enrolled in the study . After 5 days to 7 days of treatment , only 8 % of mothers showed improvement in the \" optimal breastfeeding technique alone \" group , 16 % improved with topical mupiricin , 29 % improved with topical fusidic acid , yet 79 % improved with oral antibiotics ( p<.0001 ) . Optimal breastfeeding techniques and topical antibiotics ointment failed to heal most infected , sore , cracked nipples . Mastitis developed in 12 % to 35 % of mothers not treated with systemic antibiotics compared to 5 % of mothers treated with systemic antibiotics ( p<.005 ) . In conclusion , S. aureus infected sore , cracked nipples should be diagnosed as a potentially widespread impetigo vulgaris and treated aggressively with systemic antibiotics in order to improve healing and decrease the risk of developing mastitis due to an ascending lactiferous duct bacterial infection", "Health-promotion goals include increasing the duration of breastfeeding because of its irrefutable advantages to the mother and baby , society , and the environment . However , many mothers experience painful , sore nipples during breastfeeding and stop nursing before they intended ( Livingstone & Stringer , 1999 ) . The experimental trial described in this paper r and omized 94 breastfeeding women with sore nipples into three treatment groups . Midwives practicing in hospitals in Latvia assessed the participants ' breastfeeding practice s , then gave the mothers individualized education and corrective interventions using a guided documentation form , the Lactation Assessment Tool ( LATtrade mark ) . In addition , two groups were instructed to use commercial products on their breasts and nipples : breast shells and lanolin cream for one group , and glycerin gel therapy for the other . Nipple pain during breastfeeding was rated by the mothers on a 5-point verbal descriptor scale at each visit , and pain at the start of treatment was compared to pain at the last visit . Analysis of variance ( using Fisher 's Exact Test ) determined that no significant differences existed between the groups : F(2 , 86 ) = 1.34 , p > .05 . Almost all of the mothers experienced nipple healing , as assessed by the midwife . Mothers in the glycerin gel group were more satisfied with their treatment method , but this finding was not statistically significant . The results of this study indicate that effective care and perinatal education for nursing mothers with sore nipples should include assessment of breastfeeding positioning and latch-on , as well as education and corrective interventions using a guidance tool , whether or not commercial preparations are used", "BACKGROUND Nipple soreness is one reason why breastfeeding women wean their infants . This study examined the effectiveness of three topical agents -- USP-modified lanolin , warm water compresses , and expressed breast milk with air drying -- in alleviating nipple pain , and if early predictors of breastfeeding at six weeks could be determined . METHODS One hundred seventy-seven breastfeeding , primiparous women were r and omly assigned to one of four groups . All women received education about breastfeeding technique . Numeric rating scales were used to discriminate levels of pain intensity , pain affect , and strength of sucking on day 1 . Participants were interviewed by telephone on postpartum days 4 , 7 , and 14 , and during week 6 using the same scales . RESULTS No significant differences were found among groups for pain intensity , pain affect , or duration of breastfeeding . Results of a logistic regression indicated that older mothers and those who were exclusively breastfeeding ( no supplemental feeding ) were most likely to be breastfeeding six weeks postpartum . Raw scores supported the use of warm compresses . CONCLUSION Further investigation is required into ways of supporting young mothers and how caregivers provide support to breastfeeding mothers in the early weeks after childbirth", "OBJECTIVE To evaluate the use of hydrogel dressings for the prevention and treatment of nipple soreness in lactating women as compared with the common intervention of lanolin ointment . The hypothesis was as follows : Participants using hydrogel dressings as a preventive measure for nipple soreness will experience greater pain relief and a lower rate of nipple wounds as compared with the control group . The secondary hypothesis was that the reduction of nipple soreness in the treatment group would produce a longer duration of breastfeeding as compared with the control group . DESIGN A multicentered , prospect i ve , r and omized controlled clinical trial evaluating a sample of 106 lactating mothers . SETTING Study sites were the University of Alabama Medical Center at Birmingham ( an inner-city teaching hospital ) and Northeast Health System ( a community hospital in Beverly , Massachusetts ) . PARTICIPANTS Participants were older than age 18 , fluent in English , and had an operational telephone in the residence . Other inclusion criteria were singleton , vaginal deliveries ; no prior breastfeeding experience ; and written informed consent . INTERVENTIONS Participants were r and omized to either the lanolin ointment or the hydrogel dressings group and received instructions specific to their assignment . All participants received breastfeeding education provided by a board-certified lactation consultant . MAIN OUTCOME MEASURES During the initial 12 study days , participants identified pain intensity using a numeric pain intensity scale and verbal descriptor scale . Subjective data were collected via self-reported skin assessment s of the bilateral breasts , nipples , and areolae . Breastfeeding duration was established by a follow-up telephone call at 2 months . RESULTS The hydrogel dressings group had significantly greater reduction in pain score mean values at baseline , on study Day 10 , and on study Day 12 in comparison to the control group . Participants using the hydrogel dressings discontinued treatment sooner than participants in the lanolin ointment group . The lanolin ointment group had eight breast infections , whereas the hydrogel dressings group had none . CONCLUSION Hydrogel dressings are a safe , available treatment that provided more effective pain management for nipple soreness than the common intervention of lanolin ointment", "OBJECTIVE To evaluate effectiveness of water versus tea bag compresses in treatment of sore nipples during breastfeeding . DESIGN Prospect i ve , r and omized trial . SETTING Mother-infant care wards in a tertiary care teaching hospital . PARTICIPANTS Sixty-five primiparae with sore nipples who were breastfeeding after a vaginal delivery at 37 or more weeks gestation , who were 36 hours or less postpartum , and had combined mother-infant care . INTERVENTIONS Participants were assigned r and omly to one of six treatment groups with one of three regimens ( tea bag compress , water compress , or no compress ) r and omly assigned to right or left sides . Participants applied the treatments at least four times a day , from Days 1 to 5 postpartum . MAIN OUTCOME MEASURE Reduction of nipple pain . RESULTS Tea bag and water compresses were more effective than no treatment , with no statistically significant difference between the two types of compresses . CONCLUSION Warm water or tea bag compresses are an inexpensive , equally effective treatment for sore nipples during the early postpartum period", "The objective of this study was to prospect ively explore the influence ofwomen ’s experiences in preparing for and establishing breastfeeding on the duration of breastfeeding . A cohort of 490 women was surveyed at intervals during pregnancy and after giving birth . Data were collected on breastfeeding outcomes and experiences and analyzed using multiple logistic regression . After controlling for sociodemographic variables , women were less likely to be still fully breastfeeding at 6 to 10 weeks postpartum if they believed they needed more breastfeeding information prior to delivery or had experienced breastfeeding problems . Women were less likely to be fully breastfeeding at 4 months postpartum if they had experienced breastfeeding problems . This prospect i ve study demonstrated the influence ofwomen ’s preparedness for breastfeeding and their experiences in establishing breastfeeding on breastfeeding duration . Improvements in prenatal education about breastfeeding and management of breastfeeding problems are likely to increase breastfeeding duration", "This exploratory study compared the effect of two methods of breast feeding on breast engorgement , mastitis , infantile colic and duration of breast feeding . An opportunity sample of subjects was assigned either to the experimental group ( prolonged emptying of one breast at each feed ) ( n = 150 ) or to the control group ( both breasts equally drained at each feed ) in= 152 ) and both groups were followed prospect ively to 6 months after delivery . The experimental group had a lower incidence of breast engorgement in the first week ( 61.4 % versus 74.3 % ; p < 0.02 ) and colic over the first 6 months ( 12 % versus 23.4 % ; p < 0.02 ) . There was no significant difference between the two groups in the incidence of mastitis over 6 months and the length of breast feeding ( 16.510.3 weeks versus 17.510 weeks experimental versus control group ) . The majority of mothers in the experimental group ( 63 % ) felt it necessary to offer the second breast at the end of a feed to satisfy their infant 's hunger . The “ perceived insufficient milk supply syndrome ” was the main reason given for cessation of breast feeding in both groups . This study provides data to advise nursing mothers about these two methods of breast feeding . Breast engorgement , breast feeding methods , foremilk , hindmilk , infantile colic ,", "BACKGROUND Most mothers stop breast-feeding before the recommended 6 months post partum . A systematic review showed that breast-feeding support programs by health care professionals did not substantially improve breast-feeding outcomes beyond 2 months post partum . We conducted a r and omized controlled trial to evaluate the effect of peer ( mother-to-mother ) support on breast-feeding duration among first-time breast-feeding mothers . METHODS We recruited 256 breast-feeding mothers from 2 semi-urban community hospitals near Toronto and r and omly assigned them to a control group ( conventional care ) or a peer support group ( conventional care plus telephone-based support , initiated within 48 hours after hospital discharge , from a woman experienced with breast-feeding who attended a 2.5-hour orientation session ) . Follow-up of breast-feeding duration , maternal satisfaction with infant feeding method and perceptions of peer support received was conducted at 4 , 8 and 12 weeks post partum . RESULTS Significantly more mothers in the peer support group than in the control group continued to breast-feed at 3 months post partum ( 81.1 % v. 66.9 % , p = 0.01 ) and did so exclusively ( 56.8 % v. 40.3 % , p = 0.01 ) . Breast-feeding rates at 4 , 8 and 12 weeks post partum were 92.4 % , 84.8 % and 81.1 % respectively among the mothers in the peer support group , as compared with 83.9 % , 75.0 % and 66.9 % among those in the control group ( p < or = 0.05 for all time periods ) . The corresponding relative risks were 1.10 ( 95 % confidence interval [ CI ] 1.01 - 2.72 ) at 4 weeks , 1.13 ( 95 % CI 1.00 - 1.28 ) at 8 weeks and 1.21 ( 95 % CI 1.04 - 1.41 ) at 12 weeks post partum . In addition , when asked for an overall rating of their feeding experience , significantly fewer mothers in the peer support group than in the control group were dissatisfied ( 1.5 % v. 10.5 % ) ( p = 0.02 ) . Of the 130 mothers who evaluated the peer support intervention , 81.6 % were satisfied with their peer volunteer experience and 100 % felt that all new breast-feeding mothers should be offered this peer support intervention . INTERPRETATION The telephone-based peer support intervention was effective in maintaining breast-feeding to 3 months post partum and improving satisfaction with the infant feeding experience . The high satisfaction with and acceptance of the intervention indicates that breast-feeding peer support programs , in conjunction with professional health services , are effective", "OBJECTIVE To examine various comfort measures and evaluate their effects in alleviating nipple soreness . DESIGN Prospect ively r and omized , experimental study . SETTING Postpartum unit of a community teaching hospital . PATIENTS Seventy-three primiparous , postpartum , breastfeeding women . INTERVENTIONS Subjects were r and omly assigned to four groups , with all women receiving instruction about breastfeeding and using one of the following treatments : warm moist tea bag compress , warm water compress , expressed milk massaged into the nipple and areola and air dried , instruction only ( control group ) . The subjects completed a question naire each morning for 7 days regarding nipple soreness . MAIN OUTCOME MEASURE Effect of treatments on postpartum nipple pain . RESULTS Subjects in the warm water compress group demonstrated significantly less pain on Day 3 than did the tea or breast milk group . CONCLUSIONS Anticipatory guidance by obstetric nurses may assist breastfeeding women in treating their pain nonpharmacologically", "Sore and cracked nipples are common and may represent an obstacle to successful breastfeeding . In Italy , it is customary for health professionals to prescribe some type of ointment to prevent or treat sore and cracked nipples . The efficacy of these ointments is insufficiently documented . The incidence of sore and cracked nipples was compared between mothers given routine nipple care , including an ointment ( control group ) , and mothers instructed to avoid the use of nipple creams and other products ( intervention group ) . Breastfeeding duration was also compared between the two groups . Eligible mothers were r and omly assigned , after informed consent , to one of the two groups . No difference was found between the control ( n=96 ) and the intervention group ( n=123 ) in the incidence of sore and cracked nipples and in breastfeeding duration . However , several factors were associated with sore nipples and with breastfeeding duration . The use of a pacifier and of a feeding bottle in the hospital were both associated with sore nipples at discharge ( p=0.02 and p=0.03 , respectively ) . Full breastfeeding up to 4 months postpartum was significantly associated with the following early practice s : breastfeeding on dem and , rooming-in at least 20 hours/day , non-use of formula and pacifier , no test-weighing at each breastfeed . The incidence of sore and cracked nipples and the duration of breastfeeding were not influenced by the use of a nipple ointment . Other interventions , such as providing the mother with guidance and support on positioning and latching , and modifications of hospital practice s may be more effective in reducing nipple problems", "OBJECTIVE To compare the effect of rubbing breast milk versus lanolin in the treatment of symptoms of sore nipples . METHODS We carried out this r and omized clinical trial on 225 mothers with sore nipples in the Neonatal Intensive Care Unit of Imam Reza Hospital in Mashhad , Iran from April 2001 for 2 years . We r and omly divided the patients into 3 groups . The first group rubbed the hind milk on their nipples at the end of each breast-feeding session , and the second group used lanolin locally on the nipple 3 times a day , and cleaned the nipple with a wet cloth before infant feeding . The third group did not use anything ( control group ) . We corrected the breast-feeding technique of all mothers throughout the study . After the first visit , we reexamined the patient on the third , fifth , seventh and tenth days . We obtained information with interviewing and physical examination by using a question naire . We based the sore nipple improvement on absence of irritation according to mothers opinions . We analyzed the obtained information using the SPSS version 11.5 software , and the used tests were Chi-Square test , Mann-Whitney test , and Kruskal-Wallis test . RESULTS The first group ( breast milk users ) included 78 patients , the second group ( lanolin users ) included 74 patients , and the third group ( control group ) included 73 patients . The 3 groups were similar in gravidity , delivery method , pre-delivery breast feeding education , the beginning time of the first breast feeding , prior success breast feeding experiences , detergent agents usage for nipples , use of formula , and pacifier . Clinical manifestations , such as appearance time of symptoms , irritation and breast wound were not significantly different . The healing time was different in these 3 groups ( p=0.038 ) according to the mean ranking in the groups . The healing time in the lanolin group was longer than the breast milk group ( p=0.029 ) and the control group ( p=0.028 ) . No side effects were noted during the study . CONCLUSION This study suggests that , due to the better healing of the sore nipple with breast milk , its availability , without payment and side effect , breast milk is recommended for the treatment of sore nipples", "OBJECTIVE To determine whether , in infants with a tongue-tie and a feeding problem , the current medical treatment ( referral to a lactation consultant ) or immediate division works best and enables the infants to feed normally . METHODS Between March and July 2002 , all the babies in the district of Southampton with tongue-ties were followed in order to see if they had any feeding problems . If they developed problems , the mothers gave written consent and were enrolled in an ethics committee approved , r and omized , controlled trial , comparing 48 h of intensive lactation consultant support ( control ) with immediate division . RESULTS A total of 201 babies had tongue-tie , of whom 88 had breast-feeding or bottle-feeding problems . Thirty-one were not enrolled , so 57 were r and omized . Of the 29 controls , one improved ( 3 % ) and breast-fed for 8 months , but 28 did not . At 48 h , these 28 were offered division , which all accepted , and 27 improved ( 96 % ) and fed normally . Of the 28 babies who had immediate division , 27 improved and fed normally but one remained on a nipple shield ( P < 0.001 ) . Twenty-four mothers breast-fed for 4 months ( 24/40 , 60 % ) . Overall , division of the tongue-tie babies result ed in improved feeding in 54/57 ( 95 % ) babies . CONCLUSIONS This r and omized , controlled trial has clearly shown that tongue-ties can affect feeding and that division is safe , successful and improved feeding for mother and baby significantly better than the intensive skilled support of a lactation consultant", "OBJECTIVE To assess whether an antenatal teaching session on position and attachment of the baby on the breast had an effect on postnatal nipple pain , nipple trauma and breast feeding duration . The study was planned as a pilot study to allow an adequate sample size to be calculated for a larger study . DESIGN An observer blind experimental design was used . Women were r and omly assigned to either the experimental group teaching session or the control group . SETTING One public hospital in Western Australia . PARTICIPANTS 70 primiparae who intended to breast feed their baby were recruited from the antenatal clinic of the study hospital at 36 weeks ' gestation . INTERVENTION Antenatal group sessions on position and attachment of the baby on the breast were conducted by a lactation consultant . MEASUREMENTS AND FINDINGS During the first four postnatal days , position and attachment was measured by LATCH ( Latch on , Audible swallow , Type of nipple , Comfort and Help ) ( Jensen et al 1994 ) , nipple pain was measured by the Visual Analogue Scale ( VAS ) and nipple trauma was measured by the Nipple Trauma Index ( NTI ) . The analysis of variance ( ANOVA ) results indicated that the women in the experimental group were better able to attach the baby on the breast and had significantly less nipple pain and trauma than the control group . At six weeks postnatally , 31 of the 35 women in the experimental group were breast feeding compared to 10 of the 35 in the control group . CONCLUSIONS AND IMPLICATION S These initial findings suggest that midwives can make the best use of decreasing re sources by using practical ' h and s on ' antenatal group teaching as an effective strategy to increase breast feeding rates", "BACKGROUND Although lactation experts suggest that a correct positioning and attachment technique reduces breastfeeding problems and enhances long-term breastfeeding , evidence from r and omized trials is lacking . The objective of this study was to evaluate the effect of postpartum positioning and attachment education on breastfeeding outcomes in first-time mothers . METHOD A r and omized trial was performed in a public hospital in Adelaide , South Australia , where 160 first-time mothers were r and omly allocated to receive either structured one-to-one education ( experimental group ) or usual postpartum care ( control group ) within 24 hours of birth . The primary outcome was breastfeeding at 6 weeks and 3 and 6 months postpartum ; other outcomes were nipple pain and trauma in hospital and at 6 weeks and 3 and 6 months , and satisfaction with breastfeeding . RESULTS No significant differences occurred in breastfeeding rates between the groups at each endpoint , although a trend in the direction of lower rates was seen at each endpoint in the experimental group . This group reported less nipple pain on days 2 ( p = 0.004 ) and 3 ( p = 0.04 ) , but this was not sustained on follow-up . No differences were observed in nipple trauma in hospital or in self-reported nipple pain and /or trauma at the three endpoints . Experimental group women were less satisfied with breastfeeding at 3 and 6 months postpartum when using a one-item measure ; however , a multiple-item measure showed no significant differences at the three endpoints . CONCLUSIONS The intervention did not increase breastfeeding duration at any assessment time or demonstrate any differences between the groups on secondary outcomes . The trend toward lower breastfeeding rates in the experimental group suggests a need for a larger trial to evaluate whether or nor postpartum positioning and attachment education may negatively affect breastfeeding", "The purpose of the present prospect i ve study was to compare incision and drainage against needle aspiration for the treatment of breast abscesses in lactating women . During the 3-year study period , patients with breast abscesses were r and omized 1:1 to undergo either incision and drainage ( 23 patients ) or needle aspiration ( 22 patients ) . Ultrasound guidance was not used for any of these patients . Age , parity , localization of abscess , whether or not nipples were cracked , duration of symptoms and lactation , abscess diameter , pus culture results , breast infection history during any previous period of lactation , healing time , recurrence , cosmetic outcome in the case of incision and drainage , and volume of pus removed and number of aspirations needed in the case of aspiration were recorded . The treatment value of each of these techniques was investigated . Student 's t-test , Fisher 's exact test , a Chi-square test and the Mann-Whitney U-test were used for statistical analysis . In the incision and drainage group all patients were treated successfully , but 1 patient ( 4 % ) had a recurrence 2 months after complete healing and 16 patients ( 70 % ) in this group were not pleased with the cosmetic outcome . In the needle aspiration group , overall 3 patients were treated with a single aspiration and 10 patients ( 45 % ) with multiple aspirations , but 9 patients ( 41 % ) did not heal following needle aspiration and subsequently required incision and drainage in addition . No recurrences were observed in the needle aspiration group during the follow-up period . The risk factors for failure of needle aspiration for breast abscesses were abscesses larger than 5 cm in diameter , unusually large volume of aspirated pus , and delay in treatment . In conclusion , breast abscesses smaller than 5 cm in diameter on physical examination can be treated with repeated aspirations with good cosmetic results . Incision and drainage should be reserved for use in patients with larger 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." ]
[ "PURPOSE This r and omized , open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent st and ard-of-care ( SOC ) chemotherapy in patients with previously treated advanced triple-negative breast cancer ( TNBC ) . METHODS Patients with advanced TNBC , relapsed after anthracycline- and taxane-based chemotherapy , were r and omized to receive either sunitinib ( 37.5 mg/day ) or the investigator 's choice of SOC therapy . Progression-free survival was the primary endpoint . RESULTS Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy ( one-sided P = 0.888 ) . Median overall survival was not prolonged with sunitinib ( 9.4 months ) compared with SOC chemotherapy ( 10.5 months ; one-sided P = 0.839 ) . The objective response rate was 3 % with sunitinib and 7 % with SOC chemotherapy ( one-sided P = 0.962 ) . CONCLUSIONS Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC , for which identification of effective treatments and therapeutic targets remains an urgent need . TRIAL REGISTRATION NCT00246571", "BACKGROUND Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer . The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel , followed by doxorubicin plus cyclophosphamide , would increase the rates of pathological complete response in the breast in women with operable , human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response . METHODS We r and omly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel ( 100 mg per square meter of body-surface area on day 1 ) , docetaxel ( 75 mg per square meter on day 1 ) plus capecitabine ( 825 mg per square meter twice a day on days 1 to 14 ) , or docetaxel ( 75 mg per square meter on day 1 ) plus gemcitabine ( 1000 mg per square meter on days 1 and 8) for four cycles , with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles . Patients were also r and omly assigned to receive or not to receive bevacizumab ( 15 mg per kilogram of body weight ) for the first six cycles of chemotherapy . RESULTS The addition of capecitabine or gemcitabine to docetaxel therapy , as compared with docetaxel therapy alone , did not significantly increase the rate of pathological complete response ( 29.7 % and 31.8 % , respectively , vs. 32.7 % ; P=0.69 ) . Both capecitabine and gemcitabine were associated with increased toxic effects -- specifically , the h and -foot syndrome , mucositis , and neutropenia . The addition of bevacizumab significantly increased the rate of pathological complete response ( 28.2 % without bevacizumab vs. 34.5 % with bevacizumab , P=0.02 ) . The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups . The addition of bevacizumab increased the rates of hypertension , left ventricular systolic dysfunction , the h and -foot syndrome , and mucositis . CONCLUSIONS The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response , which was the primary end point of this study . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00408408 . )", "BACKGROUND The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting . Micrometastases are dependent on angiogenesis , suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting . We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer . METHODS For this open-label , r and omised phase 3 trial we recruited patients with central ly confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries . We r and omly allocated patients aged 18 years or older ( 1:1 with block r and omisation ; stratified by nodal status , chemotherapy [ with an anthracycline , taxane , or both ] , hormone receptor status [ negative vs low ] , and type of surgery ) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab ( equivalent of 5 mg/kg every week for 1 year ) . The primary endpoint was invasive disease-free survival ( IDFS ) . Efficacy analyses were based on the intention-to-treat population , safety analyses were done on all patients who received at least one dose of study drug , and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample . This trial is registered with Clinical Trials.gov , number NCT00528567 . FINDINGS Between Dec 3 , 2007 , and March 8 , 2010 , we r and omly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy . Most patients received anthracycline-containing therapy ; 1638 ( 63 % ) of the 2591 patients had node-negative disease . At the time of analysis of IDFS , median follow-up was 31·5 months ( IQR 25·6 - 36·8 ) in the chemotherapy-alone group and 32·0 months ( 27·5 - 36·9 ) in the bevacizumab group . At the time of the primary analysis , IDFS events had been reported in 205 patients ( 16 % ) in the chemotherapy-alone group and in 188 patients ( 14 % ) in the bevacizumab group ( hazard ratio [ HR ] in stratified log-rank analysis 0·87 , 95 % CI 0·72 - 1·07 ; p=0·18 ) . 3-year IDFS was 82·7 % ( 95 % CI 80·5 - 85·0 ) with chemotherapy alone and 83·7 % ( 81·4 - 86·0 ) with bevacizumab and chemotherapy . After 200 deaths , no difference in overall survival was noted between the groups ( HR 0·84 , 95 % CI 0·64 - 1·12 ; p=0·23 ) . Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab ( Cox interaction test p=0·029 ) . Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension ( 154 patients [ 12 % ] vs eight patients [ 1 % ] ) , severe cardiac events occurring at any point during the 18-month safety reporting period ( 19 [ 1 % ] vs two [ < 0·5 % ] ) , and treatment discontinuation ( bevacizumab , chemotherapy , or both ; 256 [ 20 % ] vs 30 [ 2 % ] ) ; we recorded no increase in fatal adverse events with bevacizumab ( four [ < 0·5 % ] vs three [ < 0·5 % ] ) . INTERPRETATION Bevacizumab can not be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer . Further follow-up is needed to assess the potential effect of bevacizumab on overall survival", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "INTRODUCTION A multicenter , open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival ( PFS ) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(- ) advanced breast cancer . PATIENTS AND METHODS Patients with HER2(- ) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were r and omized ( 1:1 ; planned enrollment 740 patients ) to receive intravenous ( I.V. ) paclitaxel 90 mg/m(2 ) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks . [ corrected ] RESULTS The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis . At data cutoff , 242 patients had been r and omized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel . Median PFS was shorter with sunitinib-paclitaxel ( 7.4 vs. 9.2 months ; hazard ratio [ HR ] 1.63 [ 95 % confidence interval ( CI ) , 1.18 - 2.25 ] ; 1-sided P = .999 ) . At a median follow-up of 8.1 months , with 79 % of sunitinib-paclitaxel and 87 % of bevacizumab-paclitaxel patients alive , overall survival analysis favored bevacizumab-paclitaxel ( HR 1.82 [ 95 % CI , 1.16 - 2.86 ] ; 1-sided P = .996 ) . The objective response rate was 32 % in both arms , but median duration of response was shorter with sunitinib-paclitaxel ( 6.3 vs. 14.8 months ) . Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel . This was primarily due to a high frequency of grade 3/4 , treatment-related neutropenia with sunitinib-paclitaxel ( 52 % ) precluding delivery of the prescribed doses of both drugs . CONCLUSION The sunitinib-paclitaxel regimen evaluated in this study was clinical ly inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer", "In February 2008 , the U.S. Food and Drug Administration ( FDA ) granted accelerated approval to bevacizumab ( Avastin ) in combination with paclitaxel as first-line treatment for HER-2 negative metastatic breast cancer . Approval was based on the results of E2100 , a cooperative-group r and omized trial that showed a 5.5-month increase in progression-free survival associated with the addition of bevacizumab to paclitaxel therapy.1,2 Confirmatory studies by Genentech , the manufacturer , however , showed that bevacizumab 's benefits for progression-free survival may be appreciably smaller than those shown in E2100 and have demonstrated convincingly that the addition of bevacizumab to the chemotherapy agents they have tested offers no . .", "PURPOSE The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival . To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer , AVAGAST included a prospect i ve , m and atory biomarker program . PATIENTS AND METHODS Patients with previously untreated , locally advanced or metastatic gastric cancer were r and omly assigned to bevacizumab ( n = 387 ) or placebo ( n = 387 ) in combination with chemotherapy . Blood and tumor tissue sample s were collected at baseline . Prespecified biomarkers included plasma vascular endothelial growth factor-A ( VEGF-A ) , protein expression of neuropilin-1 , and VEGF receptors-1 and -2 ( VEGFR-1 and VEGFR-2 ) . Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model . RESULTS Plasma was available from 712 patients ( 92 % ) , and tumor sample s were available from 727 patients ( 94 % ) . Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy . Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival ( hazard ratio [ HR ] , 0.72 ; 95 % CI , 0.57 to 0.93 ) versus patients with low VEGF-A levels ( HR , 1.01 ; 95 % CI , 0.77 to 1.31 ; interaction P = .07 ) . Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival ( HR , 0.75 ; 95 % CI , 0.59 to 0.97 ) versus patients with high neuropilin-1 expression ( HR , 1.07 ; 95 % CI , 0.81 to 1.40 ; interaction P = .06 ) . For both biomarkers , subgroup analyses demonstrated significance only in patients from non-Asian regions . CONCLUSION Plasma VEGF-A and tumor neuropilin-1 are strong biomarker c and i date s for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab", "BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor A , has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer . We evaluated the efficacy , measured according to the rate of pathological complete response ( absence of invasive and intraductal disease in the breast and the axillary lymph nodes ) , and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer . METHODS We r and omly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel , with or without concomitant bevacizumab . Patients with untreated HER2-negative breast cancer were eligible if they had large tumors , hormone-receptor-negative disease , or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy , and no increased cardiovascular or bleeding risk . RESULTS Overall , the rates of pathological complete response were 14.9 % with epirubicin and cyclophosphamide followed by docetaxel and 18.4 % with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab ( odds ratio with addition of bevacizumab , 1.29 ; 95 % confidence interval , 1.02 to 1.65 ; P=0.04 ) ; the corresponding rates of pathological complete response were 27.9 % and 39.3 % among 663 patients with triple-negative tumors ( P=0.003 ) and 7.8 % and 7.7 % among 1262 patients with hormone-receptor-positive tumors ( P=1.00 ) . Breast-conserving surgery was possible in 66.6 % of the patients in both groups . The addition of bevacizumab , as compared with neoadjuvant therapy alone , was associated with a higher incidence of grade 3 or 4 toxic effects ( febrile neutropenia , mucositis , the h and -foot syndrome , infection , and hypertension ) but with a similar incidence of surgical complications . CONCLUSIONS The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer . Efficacy was restricted primarily to patients with triple-negative tumors , in whom the pathological complete response is considered to be a reliable predictor of long-term outcome . ( Funded by Sanofi-Aventis and Roche , Germany ; Clinical Trials.gov number , NCT00567554 . )" ]
"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"
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[ "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]." ]
[ "We have investigated the role of aluminized metal foil ( space blanket , UN 320 ) , used pre-emptively , in post-anaesthetic shivering and patients ' subjective perception of cold after general anaesthesia of short duration . Sixty-eight ASA I and II patients undergoing orthopaedic and plastic surgery on the peripheries were allocated r and omly to two groups : those in group 1 were wrapped ( not less than 60 % of body surface area ) in the space blanket before induction of anaesthesia . In group 2 patients had st and ard surgical draping . In all subjects , anaesthesia was induced with fentanyl and propofol , and maintained with nitrous oxide and enflurane in oxygen , after a laryngeal mask airway was positioned . Patients were asked to grade their perception of cold on a visual analogue scale , before induction and on recovery . Skin ( dorsum of h and ) and core ( nasopharyngeal ) temperatures were recorded at 15-min intervals . Occurrence of shivering and cold scores were recorded by blinded observers . Groups were similar in age and gender ; duration of anaesthesia was also similar ( mean 41.6 ( SEM 4.8 ) vs 47.5 ( 3.3 ) min , respectively ) . The incidences of shivering were 15 % and 63 % in groups 1 and 2 , respectively ( P < 0.001 ) . Cold scores were 2.4 ( 0.4 ) and 5.7 ( 0.5 ) , respectively ( P < 0.001 ) . Skin temperatures increased with increasing duration of anaesthesia in both groups but were greater at 15 , 30 and 45 min in group 1 ( 33.38 ( 0.25 ) vs 31.56 ( 0.31 ) , 34.46 ( 0.25 ) vs 32.45 ( 0.31 ) and 35.22 ( 0.36 ) vs 33.13 ( 0.34 ) , respectively ; P < 0.001 each comparison ) . Core temperature increased slightly in group 1 and decreased in group 2 ( P = 0.11 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Background Keeping abdominal surgery patients warm is common and warming methods are needed in power outages during natural disasters . We aim ed to evaluate the efficacy of low-cost , low-power warming methods for maintaining normothermia in abdominal surgery patients . Methods Patients ( n = 160 ) scheduled for elective abdominal surgery were included in this prospect i ve clinical study . Five warming methods were applied : heated blood transfusion/fluid infusion vs. unheated ; wrapping patients vs. not wrapping ; applying moist dressings , heated or not ; surgical field rinse heated or not ; and applying heating blankets or not . Patients ’ nasopharyngeal and rectal temperatures were recorded to evaluate warming efficacy . Significant differences were found in mean temperatures of warmed patients compared to those not warmed . Results When we compared temperatures of abdominal surgery patient groups receiving three specific warming methods with temperatures of control groups not receiving these methods , significant differences were revealed in temperatures maintained during the surgeries between the warmed groups and controls . Discussion The value of maintaining normothermia in patients undergoing abdominal surgery under general anesthesia is accepted . Three effective economical and practically applicable warming methods are combined body wrapping and heating blanket ; combined body wrapping , heated moist dressings , and heating blanket ; combined body wrapping , heated moist dressings , and warmed surgical rinse fluid , with or without heating blanket . These methods are practically applicable when low-cost method is indeed needed", "BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P < 0.001 ) Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations", "Changes in mean body temperature and muscle protein metabolism were studied in elderly patients undergoing large bowel surgery . Two groups were studied : in one , efforts were made to maintain the patients normothermic during and after surgery by warming the fresh gases , the i.v . fluids , by placing warmed cotton padding around the exposed parts of the body and by covering the patients with a metallized plastic sheet in the recovery period . The other group received routine management . Otherwise the anaesthetic technique was comparable . The excretion of the amino acid 3-methylhistidine ( 3-MeH ) , an indicator of muscle protein breakdown , and urea nitrogen loss were measured in the urine collected the day before , and on the 2nd and 4th postoperative days . Prevention of heat loss during and after surgery caused a significant decrease in muscle protein degradation and nitrogen loss", "UNLABELLED Perioperative hypothermia poses a challenge because of its deleterious effects on patient recovery . The current practice of applying two cotton blankets on patients during surgery is thought to be less ideal than using reflective insulation or forced-air warming . We studied 300 patients who underwent unilateral total knee replacement and were r and omized equally to three groups : ( a ) the two-cotton-blanket group , ( b ) the one-reflective-blanket with one-cotton-blanket group , and ( c ) the forced-air-warming with one-cotton-blanket group . Tympanic temperature readings were taken before surgery in the induction room , on arrival at the recovery room , and at 10-min intervals until discharge from the recovery room . On arrival at the recovery room , the forced-air-warming group had significantly higher temperatures ( adjusted for sex , age , and patient 's induction room temperature ) of 0.577 degrees C + /- 0.079 degrees C ( 95 % confidence interval [ CI ] , 0.427 - 0.726 ; P < 0.001 ) and 0.510 degrees C + /- 0.08 degrees C ( 95 % CI , 0.349 - 0.672 ; P < 0.001 ) more than the reflective-blanket and two-cot-ton-blanket groups , respectively . The forced-air-warming group took a significantly ( P < 0.001 ) shorter time of 18.75 min ( 95 % CI , 13.88 - 23.62 ) to achieve a temperature of 36.5 degrees C in the recovery room as compared with 41.78 min ( 95 % CI , 36.86 - 46.58 ) and 36.43 min ( 95 % CI , 31.23 - 41.62 ) for the reflective-blanket and two-cotton-blanket groups , respectively . The reflective technology was less effective than using two cotton blankets , and the forced-air warming was most efficient in maintaining perioperative normothermia . IMPLICATION S Perioperative hypothermia has deleterious effects on patient recovery . We found in patients having knee surgery that reflective technology was less effective than using two cotton blankets , whereas active surface warming with the forced-air method was most effective in maintaining normothermia", "Mild intraoperative hypothermia is common . We therefore studied the effects of mild hypothermia on propofol pharmacokinetics , hepatic blood flow , and atracurium duration of action in healthy volunteers . Six young volunteers were studied on two r and omly assigned days , at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental , 3 mg/kg , and maintained with 70 % N2 O and 0.6 % isoflurane . Core hypothermia was induced by conductive and convective cooling . On the other study day , normothermia was maintained by a Bair Hugger Registered Trademark ( Augustine Medical , Inc. , Eden Prairie , MN ) forced-air warmer . Propofol , 1 mg/kg lean body mass ( LBM ) , then was given , followed by a 4-h infusion at 5 mg centered dot kg-1 centered dot h-1 . After 2 h , atracurium 0.5 mg/kg was administered as an intravenous bolus . Indocyanine green was administered for estimation of hepatic blood flow . Arterial blood was assayed for propofol and indocyanine green concentration . Pharmacokinetic analysis was performed using NONMEM . Results are reported as means + /- SEM . Propofol blood concentrations averaged approximate equals 28 % more at 34 degrees C than at 37 degrees C ( P < 0.05 ) . Hepatic blood flow decreased 23 % + /- 11 % in normothermic volunteers during the propofol infusion , and 33 % + /- 11 % in hypothermic volunteers ( P = not significant ) . A three-compartment mamillary model fitted the data best . Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit . The intercompartmental clearances were decreased in the presence of hypothermia . Core hypothermia prolonged the time to recovery of the first twitch in the train-of-four to 10 % of its control value ( T1 = 10 % ) after atracurium administration by approximate equals 60 % ( P < 0.05 ) , from 44 + /- 4 min to 68 + /- 7 min . In contrast , T1 = 25%-75 % remained unchanged . We conclude that 3 degrees C of core hypothermia increased propofol blood concentrations and prolonged atracurium duration of action . Hepatic blood flow was decreased during propofol administration , and this change was a significant predictor of propofol clearance , indicating that the effect of propofol on hepatic blood flow impairs the clearance of propofol itself . ( Anesth Analg 1995;80:1007 - 14", "Background and objective Unintentional hypothermia of a patient is a common adverse effect during surgical procedures . Many strategies can be used to reduce heat loss . The aim of this prospect i ve , r and omised , controlled study was to determine whether the use of the thermal suit ( T-Balance ) could prevent surgical patients from experiencing thermal loss better than conventional measures . Methods We examined a group of consecutive patients undergoing transurethral resection of the prostate under spinal anaesthesia . Forty patients were r and omised to receive the special textile clothing , thermal suit ( group 1 ) or the conventional clothing ( group 2 , control ) . Heated blankets and a forced-air warming device ( Bair-Hugger ) were used when any patient felt cold or body temperature decreased below 35 ° C . Body temperatures were measured via mouth using an infrared thermometer and recorded at given points ( T1–T10 ) during the procedure . Results The mean temperatures were higher ( about 0.5 ° C ) in group 1 than in group 2 at the entrance to the recovery room ( P = 0.03 ) . The mean maximal decrease in temperature was 0.56 ° C in group 1 and 1.31 ° C in group 2 ( P = 0.000 between groups ) . One patient in group 1 and seven patients in group 2 needed warming with a Bair-Hugger , and 15 out of 20 patients in group 2 needed extra blankets during surgery or recovery . Conclusion The use of the thermal suit is a good alternative to conventional measures of warming in reducing heat loss during surgical procedure under regional anaesthesia", "Hypothermia is one of the common complications in the perioperative period . Currently , normothermia is maintained with forced air warming ( FAW ) or passive heat retention methods . We compared the efficacy of the Mediwrap blanket with FAW in maintaining normothermia during intra-operative period in thoracic surgery in a prospect i ve r and omised controlled trial on 30 patients . Core temperature was measured at 30-min intervals in the perioperative period and the time taken to attain baseline in the postoperative periods in the two groups was compared . There was no difference in core temperatures between the groups during pre- and intra-operative period , with mean+/-S.D. final core temperatures of 36.2+/-0.6 degrees C with Mediwrap and 36+/-0.9 degrees C with the FAW blanket . However , the postoperative core temperatures were significantly higher in the Mediwrap group . The time required to reach baseline temperature was lower in the Mediwrap group with a mean+/-S.D. of 66+/-66 min as compared to 161+/-108 min in the FAW group . The Mediwrap blanket is as effective as the FAW blanket in maintaining core body temperature during thoracotomy when applied thirty minutes before the surgery", "OBJECTIVE Perioperative hypothermia might be detrimental to the patient undergoing off-pump coronary artery bypass surgery . We assessed the efficacy of the Allon thermoregulation system ( MTRE Advanced Technologies Ltd , Or-Akiva , Israel ) compared with that of routine thermal care in maintaining normothermia during and after off-pump coronary artery bypass surgery . METHODS Patients undergoing off-pump coronary artery bypass surgery were perioperatively and r and omly warmed with the 2 techniques ( n = 45 per group ) . Core temperature , hemodynamics , and troponin I , interleukin 6 , interleukin 8 , and interleukin 10 blood levels were assessed . RESULTS The mean temperature of the patients in the Allon thermoregulation system group ( AT group ) was significantly ( P < .005 ) higher than that of the patients receiving routine thermal care ( the RTC group ) ; less than 40 % of the latter reached 36 degrees C compared with 100 % of the former . The cardiac index was higher and the systemic vascular resistance was lower ( P < .05 ) by 16 % and 25 % , respectively , in the individuals in the AT group compared with in the individuals in the RTC group during the 4 postoperative hours . End-of-surgery interleukin 6 levels and 24-hour postoperative troponin I levels were significantly ( P < .01 ) lower in the patients in the AT group than in the RTC group . The RTC group 's troponin levels closely correlated with their interleukin 6 levels at the end of the operation ( R = 0.51 , P = .002 ) . CONCLUSIONS Unlike routine thermal care , the Allon thermoregulation system maintains core normothermia in more than 80 % of patients undergoing off-pump coronary artery bypass surgery . Normothermia is associated with better cardiac and vascular conditions , a lower cardiac injury rate , and a lower inflammatory response . The close correlation between the increased interleukin 6 and troponin I levels in the routine thermal care group indicates a potential deleterious effect of lowered temperature on the patient 's outcome", "We have studied the ability of reflective blankets to reduce net loss of body heat during regional anaesthesia for total hip arthroplasty . Thirty patients were allocated r and omly to either the study group ( insulated with reflective blankets ) or the control group ( no reflective blankets ) . Surgical and operation room draping , theatre temperature and i.v . fluid administration were st and ardized for all patients . Total body heat was deduced from core temperature ( aural canal ) and mean skin temperature ( four measuring sites ) . After 2 h of surgery , loss of body heat was reduced significantly in patients wrapped in reflective blankets ( 26 kJ ) compared with those in the control group ( 95 kJ )", "OBJECTIVES To evaluate the efficacy of two different nursing interventions regarding control of body heat loss , using blankets during the intraoperative period of elderly patients . METHODS This was an experimental , comparative , applied , longitudinal prospect i ve study with a quantitative approach . Eighty-one elderly patients undergoing elective surgery with a surgical time frame of at least one hour were selected by systematic probability sampling into two Experimental and one Control Group . Informed consent was obtained from participants . Data was collected by biophysiological measurement , using a tympanic thermometer . RESULTS After the homogeneity of variables - gender , surgical duration , age , BMR , anesthesia , room humidity and temperature , drugs and liquid infusion- had been demonstrated , the interventions were confronted . Incidence of hypothermia ( 59.3 % ) and body heat loss ( E1=-0.6 degrees C , E2=-0.6 degrees C and C=-0.7 degrees C ) were not significantly different between the groups ( p=0.85 and p=0.7 respectively ) . CONCLUSIONS Results show the need for associated extra body warming methods to maintain normothermia", "Purpose To determine the effect of covering the patient ’s head and face on the prevention of intraoperative hypothermia ( < 35.5 ° C ) . Methods This r and omized , prospect i ve trial included 44 adults undergoing elective abdominal surgery . After the induction of anesthesia with thiopental , in 44 patients their extremities and trunk were covered with towels and sheets . In addition , 22 patients ( covered group ) had their face and head fully covered . Anesthesia was maintained with N2O 50–66 % ( 2–3 L·min−1 ) and isoflurane ( < IMAC ) in oxygen combined with thoracic epidural anesthesia . Core temperature was measured at the tympanic membrane continuously and was recorded at 15 min intervals from the induction of anesthesia . Heat and moisture exchangers were used in their anesthetic circuit . Ambient temperature was maintained near 25 ° C . Results Neither group demonstrated intraoperative hypothermia . However , tympanic membrane temperature at 75 , 90 , 105 min in the covered group were higherthan those of control group ( 36.7 ± 0.4 ° C vs 36.5 ± 0.4 ° C , 36.8 ± 0.5 ° C vs 36.4 ± 0.5 ° C , 36.8 ± 0.5 ° C vs 36.4 ± 0.5 ° C , respectively , P < 0.05 ) . Conclusion Covering the patient ’s head and face maintains intraoperative core temperature . RésuméObjectifDéterminer si le fait de couvrir la tête et le visage des patients contribue à prévenir l’hypothermie peropératoire ( < 35,5 ° C).MéthodeLessai r and omisé et prospect if a porté sur 44 adultes subissant une intervention abdominale élective . Après l’induction de l’anesthésie avec du thiopental , on a couvert les extrémités et le tronc des 44 patients de serviettes et de draps . De plus , pour 22 d’entre eux ( le groupe couvert ) , on a aussi couvert complètement le visage et la tête . On a maintenu l’anesthésie avec du N2O 50–66 % ( 2 - 3 L·min−1 ) et de l’isoflurane ( < ICAM ) mêlé à de l’oxygène , combiné à une anesthésie péridurale thoracique . On a procédé à une mesure continue de la température central e , à la membrane tympanique , et on l’a notée aux 15 min depuis l’induction de l’anesthésie . Les échangeurs de chaleur et d’humidité ont été intégrés au circuit anesthésique . La température ambiante a été maintenue autour de 25 ° C.RésultatsAucun des patients n’a présenté d’hypothermie peropératoire . Cependant , la température prélevée à la membrane tympanique à 75 , 90 et 105 min dans le groupe couvert était plus élevée que dans le groupe témoin ( 36,7 ± 0,4 ° C vs 36,5 ± 0,4 ° C , 36,8 ± 0,5 ° C vs 36,4 ± 0,5 ° C , 36,8 ± 0,5 ° C vs 36,4 ± 0,5 ° C , respectivement , P < 0,05 ) . Conclusion Couvrir la tête et le visage maintient la température central e peropératoire", "Hypothermia is a common problem for surgical patients and can result in many complications . Because few studies compare methods of passive warming , we used an unblinded , prospect i ve , experimental , r and omized design to compare the effectiveness of two passive methods of normothermia management in the postanesthesia care unit ( PACU ) . We assigned a total of 578 adult ambulatory surgery patients to either a control group that was given two folded , warmed cotton blankets or a treatment group that was given a warmed , unfolded cotton sheet and cotton blanket . We recorded patients ' temperatures on their arrival in the PACU and at 30 minutes after arrival . The treatment group had temperatures that were significantly higher than those of the control group 30 minutes after arrival in the PACU , and the treatment group experienced a greater change in temperature from baseline measurements to those taken at 30 minutes . The treatment group also used fewer warmed blankets , result ing in cost savings for the PACU", "STUDY OBJECTIVE To compare the ability of forced-air warming and reflective insulation to maintain intraoperative normothermia . DESIGN Prospect i ve , r and omized clinical trial . SETTING Operating rooms of a general hospital . PATIENTS 20 ASA physical status I and II patients undergoing elective total hip arthroplasty . INTERVENTIONS Patients were r and omly assigned to be warmed intraoperatively using forced-air or reflective insulation . Inspired gases were conditioned using a heat- and -moisture exchanger in both groups , and infused intravenous fluids were warmed to 37 degrees C. MEASUREMENTS AND MAIN RESULTS Distal esophageal ( core ) temperatures decreased approximately 0.5 degrees C in both groups during the first 45 minutes of anesthesia . Subsequently , core temperatures increased slightly in the patients given forced-air warming . In contrast , core temperatures continued to decrease in patients covered with reflective insulation . After 135 minutes of anesthesia , core temperatures were 36.4 + /- 0.6 degrees C ( mean + /- SD ) in the forced-air group but only 35.4 + /- 0.6 degrees C in the insulated group ( p < 0.01 , unpaired t-test ) . These data indicate that forced-air warming is superior to reflective insulation . CONCLUSION Reflective insulation was unable to maintain intraoperative normothermia during total hip arthroplasty . Active warming , such as that provided by forced air , was required to prevent hypothermia", "We have measured aural canal ( core ) and skin temperatures , and body heat content in 45 patients undergoing elective hip arthroplasty . They received general anaesthesia which included thiopentone , vecuronium and enflurane and nitrous oxide in oxygen . Patients were allocated r and omly to three groups : group 1 , control ( n = 15 ) , received no intraoperative warming device ; group 2 had passive skin surface warming ( metallized plastic sheet , Thermolite ( n = 15 ) ; and group 3 had active skin surface warming ( forced heated air , Bair-Hugger ) ( n = 15 ) . Duration of surgery , fluid administration and the temperature and relative humidity of the operating theatre were similar for the three groups . Core temperature and mean body heat content decreased significantly during surgery in groups 1 and 2 ( aural canal temperature 1.5 and 1.0 degrees C , and mean body heat content 287 and 189 kJ , respectively ) , while in group 3 these variables remained near preoperative values ( P = 0.001 ) . Mean skin and h and temperatures decreased in the control group , increased in the active warming group and were unchanged in the passive warming group ( P < 0.005 ) , indicating that the forced heated air system was very efficient in providing thermal homeostasis during surgery , while the metallized plastic sheet was able to insulate the skin only from radiant and convective heat losses , without attenuating the reduction in core temperature", "BACKGROUND To compare passive thermal insulation by reflective blankets with forced-air active warming on the efficacy of normothermia maintenance and time for discharging from the recovery room after combined spinal/epidural anesthesia for total hip arthroplasty . METHODS DESIGN Prospect i ve , r and omized study . SETTING Inpatient anesthesia at three University Departments of orthopedic surgery . PATIENTS 50 ASA physical status I-III patients , who were scheduled for elective total hip arthroplasty . INTERVENTIONS Patients received combined spinal/epidural anesthesia ( CSE ) with intrathecal injection of 15 mg of 0.5 % hyperbaric bupivacaine . All procedures started 8 - 10 a.m. , and operating room temperature was maintained between 21 - 23 degrees C , with relative humidity ranging between 40 - 45 % . As warming therapy patients received either passive thermal insulation of the trunk , the two upper limbs and the unoperated lower limb with reflective blankets ( group passive , n = 25 ) , or forced-air active warming of the two upper limbs ( group active , n = 25 ) . Core temperature was measured before CSE placement ( baseline ) , and then every 30 min until recovery of normothermia . RESULTS Demographic data , duration of surgery , intraoperative blood losses , and crystalloid infusion were similar in the two groups . Arterial blood pressure decreased in both groups compared with baseline values , while no differences in heart rate were observed during the study . Core temperatures in passive group patients decreased more markedly than in actively warmed patients , with a 1 degree C difference between the two groups at the end of surgery ( p < 0.0005 ) . At recovery room entry seven patients in group active ( 24 % ) and 16 patients in group passive ( 64 % ) showed a core temperature < 36 degrees C ( p < 0.01 ) . Achievement of both discharging criteria and normothermia required 32 + /- 18 min in active group and 74 + /- 52 min in passive group ( p < 0.0005 ) . CONCLUSIONS Forced-air cutaneous warming allows the anesthesiologist to maintain normothermia during combined spinal/epidural anesthesia for total hip replacement even if the convective blanket is placed on a relatively small skin surface with reflex vasoconstriction . Maintaining core normothermia decreased the duration of postanesthesia recovery and may , therefore , reduce costs of care", "PURPOSE Adverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm ( AAA ) repairs to test the hypothesis that hypothermia ( temperature less than 34.5 degrees C ) is associated with increased morbidity and excess mortality rates . METHODS Two hundred sixty-two elective AAA repairs were retrospectively review ed for preoperative and intraoperative risk factors . Core temperature , age , Acute Physiology and Chronic Health Evaluation ( APACHE ) II and APACHE III scores ( raw and temperature-adjusted ) , fluid resuscitation , and perioperative organ dysfunction were recorded prospect ively . Outcome measures included lengths of stay in the intensive care unit and in the hospital , and hospital mortality rates . RESULTS Except for a higher risk of hypothermia in women ( p < 0.05 ) , by univariate analysis , preoperative risk factors were similar in patients in the hypothermic and normothermic groups . After operation , patients with hypothermia had significantly greater APACHE scores ( p < 0.0001 ) , and patients in the hypothermic nonsurvivor group took significantly longer to rewarm ( p < 0.05 ) , suggesting marked hypoperfusion . Patients with hypothermia had significantly greater fluid ( p < 0.05 ) , transfusion ( p < 0.01 ) , vasopressor ( p < 0.05 ) , and inotrope ( p < 0.05 ) requirements , result ing in significantly higher incidences of organ dysfunction ( 53.0 % vs 28.7 % , p < 0.01 ) and death ( 12.1 % vs 1.5 % , p < 0.01 ) and markedly prolonged lengths of stay in the unit ( 9.2 + /- 2.0 vs 5.3 + /- 0.6 , p < 0.05 ) and in the hospital ( 24.3 + /- 2.9 vs 15.0 + /- 0.08 , p < 0.01 ) . By multivariate analysis , female gender ( p = 0.004 ) was the only predictor of intraoperative hypothermia , whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure ( p < 0.05 ) . Organ failure ( p < 0.05 ) and acute myocardial infa rct ion ( p < 0.01 ) were independent predictors of death . CONCLUSIONS After AAA repair , patients with hypothermia have multiple physiologic derangements associated with adverse outcomes . Although multiple etiologic factors are interacting , body temperature is one variable that should be controlled during aortic surgery", "BACKGROUND Wound infection after clean surgery is an expensive and often underestimated cause of patient morbidity , and the benefits of using prophylactic antibiotics have not been proven . Warming patients during colorectal surgery has been shown to reduce infection rates . We aim ed to assess whether warming patients before short duration , clean surgery would have the same effect . METHODS 421 patients having clean ( breast , varicose vein , or hernia ) surgery were r and omly assigned to either a non-warmed ( st and ard ) group or one of two warmed groups ( local and systemic ) . We applied warming for at least 30 min before surgery . Patients were followed up and masked outcome assessment s made at 2 and 6 weeks . FINDINGS Analysis was done on an intention-to-treat basis . We identified 19 wound infections in 139 non-warmed patients ( 14 % ) but only 13 in 277 who received warming ( 5 % ; p=0.001 ) . Wound scores were also significantly lower ( p=0.007 ) in warmed patients . There was no significant difference in the development of haematomas or seromas after surgery but the non-warmed group were prescribed significantly more postoperative antibiotics ( p=0.002 ) . INTERPRETATION Warming patients before clean surgery seems to aid the prevention of postoperative wound infection . If applied according to the manufacturers guidelines these therapies have no known side-effects and might , with the support of further studies , provide an alternative to prophylactic antibiotics in this type of surgery", "Hypothermia is experienced by all patients undergoing major surgical procedures . Hypothermia can lead to postoperative complications affecting oxygenation with neurologic , immunologic , and metabolic consequences . Current methods of heat conservation used in the operating room include blanket warmers , fluid warmers , and anesthesia circuit warmers . These methods are often inadequate at maintaining a patient 's body temperature . The current study used a post-test-only control group design . Subjects in the treatment group had an insulated head cover applied within 1 minute of arrival in the operating room , while those in the control group did not . All subjects had routine heat conservation measures ( blanket warmers , fluid warmers , and anesthesia circuit humidifiers ) . Following induction of anesthesia , subjects ' temperatures were measured using an esophageal stethoscope with thermistor probe at 10 and 70 minutes . Results showed no significant differences between groups at either time point", "Twenty-six patients requiring orthopaedic surgery were anaesthetized and oesophageal and rectal temperature were monitored continuously . Twenty patients requiring a pneumatic tourniquet were allocated prospect ively to one of two groups : passive group ( Pg ) with reflective insulation on all available skin surface ( n = 10 ) and forced group ( Fg ) , with active warming by a forced air system ( n = 10 ) . Six patients without a tourniquet were used as a reference group ( Rg ) . The pneumatic tourniquet time was similar in the tourniquet groups . During tourniquet inflation , oesophageal temperature increased with time . The difference was significant compared with the reference group at approximately 20 min . At about 30 min , oesophageal temperature in group Fg was significantly higher than that in group Pg . After tourniquet deflation , temperature decreased transiently . Changes in rectal temperature were similar but delayed significantly . A mechanism to explain the increase in core temperature during pneumatic tourniquet use remains unclear . A redistribution mechanism by cooling of the blood in a cold and vasodilated limb could explain the decrease of temperature after tourniquet deflation", "STUDY OBJECTIVE to compare passive heat retention by low-flow anesthesia , alone and with additional thermal insulation by reflective blankets , with forced-air warming preventing intraoperative hypothermia during combined epidural-general anesthesia . DESIGN R and omized , controlled study . SETTING Inpatient anesthesia at a university department of orthopedic surgery . PATIENTS 30 ASA physical status I and II patients , who were scheduled for elective hip or knee arthroplasty and were free from systemic disease . INTERVENTIONS Patients received epidural block up to T10 by alkalinized lidocaine 2 % , and then were administered st and ard general anesthesia by means of low-flow rebreathing system ( fresh gas flow = 1 L/min ) . All procedures started between 8 and 10 AM , and operating room ( OR ) temperature was maintained between 21 degrees and 23 degrees C , with relative humidity ranging between 40 % and 45 % . For heat retention or warming therapy , patients received either low-flow anesthesia only ( control , n = 10 ) , low-flow anesthesia with additional reflective blankets ( blanket , n = 10 ) , or low-flow anesthesia with active forced-air warming ( forced-air , n = 10 ) . Tympanic temperature was measured at OR arrival ( baseline ) ; immediately following general anesthesia induction ; 30 , 60 , 90 , and 120 minutes from general anesthesia induction ; and at the end of surgery . MEASUREMENTS AND MAIN RESULTS Duration of anesthesia , invasiveness of surgery , and baseline core temperature were similar in the three groups . Core temperature decreased in all the three groups 30 minutes after general anesthesia induction compared with baseline ( p < 0.01 ) ; afterwards , it progressively decreased in the control and blankets groups ( p = 0.004 ) , with a reduction from baseline values measured at the end of surgery of 2.0 degrees C and 1.6 degrees C , respectively . In the forced-air group , after the initial significant decrease ( p = 0.01 vs. baseline ) , core temperature progressively increased to 35.8 + /- 0.6 degrees C , which was similar to preoperative values and significantly higher than either the control or blankets groups ( p = 0.004 ) . CONCLUSIONS During combined epidural-general anesthesia for elective hip and knee arthroplasty , passive heat retention by means of low-flow anesthesia alone and in combination with reflective blankets is ineffective in maintaining intraoperative normothermia and definitely inferior to active forced-air warning", "Hypothermia during prolonged surgery may be prevented by active and passive warming methods . We have compared r and omly two types of occlusive body wraps in groups of 20 patients . One wrap had additional reflective properties which , by reducing radiative in addition to convective and evaporative heat loss , was expected to improve heat conservation . Patients were studied during hepatopancreatobiliary surgery and both groups were similar in characteristics . Skin and core body temperatures increased and core temperature exceeded 37 degrees C in 40 % of patients in both groups . This continuous increase in temperature was unexpected and the observed heat gain may have been stimulated endogenously by the type of surgery rather than that supplied externally . Overall , mean hourly heat gain was similar in both groups : 71 ( SD 28 ) kJ h-1 in the reflective group and 67 ( 33 ) kJ h-1 in the other group", "BACKGROUND Most patients undergoing coronary artery bypass surgery demonstrate perioperative mild-to-moderate hypothermia ( < 36 degrees C ) . Patients undergoing off-pump coronary artery bypass ( OPCAB ) grafting may become even more severely hypothermic for want of cardiopulmonary bypass rewarming . One consequence is increased circulating catecholamine levels that induce an elevated systemic vascular resistance ( SVR ) , which causes a subsequent deterioration in cardiac output . MATERIAL S AND METHODS We assessed the ability of the Allon thermoregulatory ( AT ) system to maintain normothermia and its impact on hemodynamics and myocardial function in patients undergoing OPCAB surgery . In this study , the first 60 of 120 suitable patients were assigned to AT ( n = 40 ) or routine thermal care ( RTC ) ( n = 20 ) . Core body temperature , cardiac index ( CI ) , SVR , and cardiac-specific troponin I ( cTnI ) were analyzed perioperatively for patients in both groups . RESULTS Core body temperature was significantly higher in the AT group ( from 36.1 degrees C + /- 0.5 degrees C at induction of anesthesia to 37 degrees C + /- 0.5 degrees C during surgery ) than in the RTC group ( from 35.8 degrees C + /- 0.4 degrees C to 35.2 degrees C + /- 0.8 degrees C , respectively ; P < .01 ) . SVR was significantly lower , and CI was greater ( at comparable time points ) , whereas cTnI levels in the AT group were lower than in the RTC group from the end of surgery until 24 hours postoperatively ( 7.4 + /- 17.7 g/L versus 31.9 + /- 47.4 g/L ; P = .03 ) . These findings indicate the possibility for less ischemic damage sustained intraoperatively in the AT group . CONCLUSIONS Maintenance of perioperative normothermia ( 36.5 degrees C-37.5 degrees C ) during OPCAB procedures can be efficiently achieved with the Allon thermoregulation system . The system was found to be superior to other routinely used methods of temperature maintenance . Benefits may include lowering afterload ( as expressed by reduced SVR ) , an improved CI , and attenuation of myocardial injury ( as assessed by cTnI levels )", "Background : Intraoperative hypothermia initially results from internal redistribution of heat facilitated by anesthesia-induced vasodilatlon . Preinductlon skin-surface warming minimizes postinduction hypothermia in anesthetized volunteers . However , its efficacy might be reduced in surgical situations , because of multiple sources of heat loss . Methods : Intraoperative core and mean skin temperatures were measured during total hip arthroplasty in 16 patients , r and omly assigned to be covered preoperatlvely with a warming blanket for ≥90 min ( prewarmed group ) or not covered ( unwarmed group ) . Results : During the first hour of anesthesia , core temperature decreased more than twice as much in the unwarmed group ( −0.7 ± 0.1 ° C ; mean ± SE ) than in the prewarmed patients ( −0.3 ± 0.1 ° C ) . At the end of surgery , core temperature was 36.3 ± 0.1 ° C in the prewarmed group and 35.2 ± 0.2 ° C in the unwarmed group . During recovery , seven patients obviously shivered in the unwarmed group and none in the prewarmed group . Conclusions : Preanesthetic skin-surface warming reduces the initial postinductlon hypothermia in surgical patients , preventing intraoperative hypothermia and postoperative shivering even for procedures lasting 3 h or longer", "Background : Intraoperative hypothermia is common and persists for several hours after surgery . Hypothermia may prolong immediate recovery by augmenting anesthetic potency , delaying drug metabolism , producing hemodynamic instability , or depressing cognitive function . Accordingly , the authors tested the hypothesis that intraoperative hypothermia prolongs postoperative recovery . Methods : Patients undergoing elective major abdominal surgery ( n = 150 ) were anesthetized with isoflurane , nitrous oxide , and fentanyl . They were r and omly assigned to routine thermal management ( hypothermia ) or extra warming ( normothermia ) . Postoperative surgical pain was treated with patient‐controlled analgesia . Fitness for discharge from the post‐anesthesia care unit was evaluated at 20‐min intervals by investigators blinded to group assignment and postoperative core temperatures . Scoring was based on a modification of a previously published system that included activity , ventilation , consciousness , and hemodynamic responses . Patients were considered fit for discharge when they sustained a score of 80 % ( 13 points ) for at least two consecutive measurement periods . Results : Morphometric characteristics and anesthetic management were similar in each group . Final intraoperative core temperatures differed by [ nearly = ] 2 [ degree sign ] Celsius : 34.8 + /‐ 0.6 versus 36.7 + /‐ 0.6 [ degree sign ] Celsius ( mean + /‐ SD , P < 0.001 ) . Postoperative pain scores and postoperative use of patient‐controlled opioid were similar . Hypothermic patients required [ nearly = ] 40 min longer ( 94 + /‐ 65 vs. 53 + /‐ 36 min ) to reach fitness for discharge , even when return to normothermia was not a criterion ( P < 0.001 ) . Duration of recovery in the two groups differed by [ nearly = ] 90 min when a core temperature > 36 [ degree sign ] Celsius was also required ( P < 0.001 ) . Conclusion : Maintaining core normothermia decreases the duration of postanesthetic recovery and may , therefore , reduce costs of care", "BACKGROUND We evaluated the performance of a new temperature management system ( Allon Thermowrap , MTRE , Israel ) in maintaining normothermia during OPCAB ( Off-Pump Coronary Artery Bypass ) procedures and Zeus-robotic IMA ( internal mammary artery ) takedowns . MATERIAL / METHODS One hundred patients were prospect ively r and omized to either a conventional temperature management method ( thick blanket , warm intravenous fluids , operating room temperature 25 degrees C ) , or the new Allon Thermowrap system ( pads with temperature-controlled water circulation placed on the patient 's back , legs , and arms ) . The mean age , body surface area , total operating time , and OR air temperature were similar in both groups . RESULTS The Allon Thermowrap system maintained a higher bladder and nasopharyngeal temperature ( p<0.05 ) . The SVR decreased ( p<0.05 ) and the cardiac index increased ( p<0.05 ) in patients with a body temperature>35.80 degrees C. Without reaching a significant level , the postoperative blood loss was lower in the Allon Thermowrap group . CONCLUSIONS The Allon Thermowrap system significantly out-performed conventional techniques in achieving and maintaining normothermia during off-pump and robotic procedures", "Peroperative thermal losses were studied in 28 patients ( mean age 64 years ) operated for a total hip prosthesis under controlled hypotension . The patients were split into four groups according to the method of hypothermia prevention used : reflective blanket , heating humidifier of inhaled gases , combination of both techniques or no prevention at all . The thermal loss was quicker and more intense in the last group . The superiority of one prevention method over another could not be demonstrated , but the urgency of its implementation proved to be essential", "Assessment was made of whether a cold-room environment prior to surgical draping affected patient temperature or the incidence of shivering in the recovery room in patients undergoing major vascular surgery when warming blankets and warmed fluids were used to maintain intraoperative temperature . Forty-two patients scheduled to undergo major vascular surgery were r and omly assigned in equal numbers to a “ cold ” or “ warm ” room . Temperatures in the “ warm ” rooms were 22.2 C or above ( range 22.8–25.6 C ) until draping , and in “ cold ” rooms , 18.9 C or below ( range 13.9–17.8 C ) . Once surgical drapes were placed , the room temperature control was set at its minimum , 17 C. All intravenous fluids and blood were warmed to 37.5 C , and a heating blanket was maintained at 37.8 C before and during the operative procedure . Patient temperatures initially did not differ between groups . Despite significantly greater heat loss prior to draping in the cold-room group ( 0.63 ± 0.14 C ) than in the warm-room group ( 0.32 ± 0.10 C)(p < 0.01 ) , there were no differences in temperature in the recovery room , shivering , myocardial , renal , CNS , pulmonary , or graft morbidity in the two groups . In major intra-abdominal vascular operations the use of warming blankets and the practice of warming all fluids for infusion allow a comfortable room temperature without detriment to patient care", "BACKGROUND Perioperative hypothermia is a common complication of general anesthesia and occurs in up to 50 % of patients during ear , nose and throat ( ENT ) surgery . In this prospect i ve , r and omized controlled study the hypothesis that a new conductive warming blanket ( Barrier ® EasyWarm ® , Mölnlycke Health Care Erkrath , Germany ) is better in reducing the incidence of perioperative hypothermia in ENT surgery than insulation with a conventional hospital duvet alone was tested . MATERIAL S AND METHODS After approval of the local ethics committee and written informed consent 80 patients with a planned procedure time between 1 and 3 h were recruited . Anesthesia was induced and maintained using propofol , remifentanil and rocuronium and the core temperature was measured using an esophageal temperature probe . Patients in the study group were warmed at least 30 min prior to induction of anesthesia using the novel warming blanket ( Barrier ® EasyWarm ® ) and patients in the control group were insulated with a st and ard hospital duvet . Data were tested using Fisher 's exact test , Student 's t-test or the Mann-Whitney U-test as appropriate . Time-dependent changes in core temperature were evaluated using repeated measures analysis of variance ( ANOVA ) and post hoc Scheffé 's test . Results are expressed as mean ± SD or as median and interquartile range ( IQR ) as appropriate . A p < 0.05 was considered to be statistically significant . RESULTS The ANOVA did not identify a significantly higher core temperature in the study group at any time point . Furthermore , Fisher 's exact test showed no differences in the incidence of intraoperative ( 12 out of 29 versus 10 out of 32 patients , p = 0.44 ) or postoperative hypothermia ( 12 out of 29 versus 9 out of 32 patients , p = 0.30 ) between the groups . No adverse effects were observed . CONCLUSIONS In the studied patient group the new conductive warming blanket ( Barrier ® EasyWarm ® ) showed no superiority compared to conventional thermal insulation alone" ]
"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"
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[ "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." ]
[ "BACKGROUND Recent clinical and experimental data indicate that volatile anaesthetics may precondition myocardium against ischaemia and infa rct ion . The present clinical trial was design ed to verify the cardioprotective effects of desflurane in patients undergoing elective coronary artery bypass surgery . It was hypothesized that desflurane preconditioning would decrease postoperative release of troponin I and brain natriuretic peptide ( NT-proBNP ) . Besides , we have hypothesized that desflurane preconditioning would preserve the myocardium from the dysfunction following cardioplegic arrest . METHODS Twenty-eight patients were r and omly divided into two groups : Control group ( 14 patients ) and Desflurane group ( 14 patients ) . In Desflurane group ( DS ) patients , preconditioning was elicited after the onset of cardiopulmonary bypass via a 5-min exposure to desflurane ( 2.5 minimum alveolar concentration ) , followed by a 10-min washout before aortic cross-clamping and cardioplegic arrest . The control group ( C ) patients underwent an equivalent period ( 15 min ) of pre-arrest desflurane-free bypass . Haemodynamic measurements were obtained at six different times . The biochemistry markers of cellular damage and myocardial dysfunction ( troponin I , NT-proBNP ) were determined . Left ventricular ( LV ) function was assessed using tissue Doppler imaging ( TDI ) of mitral annulus . Two-factor repeated- measures analysis of variance was used to evaluate differences over time between groups for all parameters determined in plasma sample s and for all TDI-derived variables . RESULTS After surgery , both the troponin I values ( 2.04+/-1.09 ng/ml vs 1.44+/-0.77 ng/ml , p<0.01 after 24h and 1.62+/-0.96 ng/ml vs 1.00+/-0.24 ng/ml , p<0.01 after 72 h respectively ) and those of the NT-proBNP ( 2187+/-282.9 ng/l vs 885.4+/-117.35 ng/l , p<0.01 after 24h and 3097.9+/-226.2 vs 1393.6+/-312.07 ng/l , p<0.01 after 72 h respectively ) were less in the desflurane-treated patients . The values of TDI of mitral annulus were constantly better in desflurane-treated patients . CONCLUSIONS We can conclude that the use of desflurane in these patients provides a pharmacological preconditioning so as to reduce myocardial necrosis and improve the cardiac performance in the postoperative period", "Background The present study investigated the effects of propofol , desflurane , and sevoflurane on recovery of myocardial function in high-risk coronary surgery patients . High-risk patients were defined as those older than 70 yr with three-vessel disease and an ejection fraction less than 50 % with impaired length-dependent regulation of myocardial function . Methods Coronary surgery patients ( n = 45 ) were r and omly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with desflurane or sevoflurane . Cardiac function was assessed perioperatively and during 24 h postoperatively using a Swan-Ganz catheter . Perioperatively , a high-fidelity pressure catheter was positioned in the left and right atrium and ventricle . Response to increased cardiac load , obtained by leg elevation , was assessed before and after cardiopulmonary bypass ( CPB ) . Effects on contraction were evaluated by analysis of changes in dP/dtmax . Effects on relaxation were assessed by analysis of the load-dependence of myocardial relaxation . Postoperative levels of cardiac troponin I were followed for 36 h. Results After CPB , cardiac index and dP/dtmax were significantly lower in patients under propofol anesthesia . Post-CPB , leg elevation result ed in a significantly greater decrease in dP/dtmax in the propofol group , whereas the responses in the desflurane and sevoflurane groups were comparable with the responses before CPB . After CPB , load dependence of left ventricular pressure drop was significantly higher in the propofol group than in the desflurane and sevoflurane group . Troponin I levels were significantly higher in the propofol group . Conclusions Sevoflurane and desflurane but not propofol preserved left ventricular function after CPB in high-risk coronary surgery patients with less evidence of myocardial damage postoperatively", "Background : Two preconditioning stimuli should induce a more consistent overall cell protection . We hypothesized that remote ischemic preconditioning ( RIPC , second preconditioning stimulus ) applied during isoflurane inhalation ( first preconditioning stimulus ) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting . Methods : In this placebo-controlled r and omized controlled study , patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping . Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance . The primary outcome was high-sensitivity cardiac troponin T release . Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide , high-sensitivity C-reactive protein , S100 protein , and short- and long-term clinical outcomes . Gene expression profiles were obtained from atrial tissue using microarrays . Results : RIPC ( n = 27 ) did not reduce high-sensitivity cardiac troponin T release when compared with placebo ( n = 28 ) . Likewise , N-terminal pro-brain natriuretic peptide , a marker of myocardial dysfunction ; high-sensitivity C-reactive protein , a marker of perioperative inflammatory response ; and S100 , a marker of cerebral injury , were not different between the groups . The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infa rct ions was higher in the RIPC group than the placebo group ( 14/27 vs. 6/28 , P = 0.036 ) . However , there was no difference in the 6-month cardiovascular outcome . N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism ( P = 0.001 ) and DNA-damage signaling ( P < 0.001 ) , but not with RIPC-induced changes in gene expression . Conclusions : RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting", "OBJECTIVE The purpose of this study was to evaluate the effects of volatile anesthesia versus total intravenous anesthesia on cardiac troponin release in off-pump coronary artery bypass grafting ( OPCAB ) . DESIGN The authors performed a multicenter r and omized controlled study to compare cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for cardiac surgery on the beating heart , which is an excellent model of human myocardial ischemia . SETTING Three university hospitals . PARTICIPANTS The authors r and omly assigned 57 patients to desflurane ( volatile anesthetic ) and 55 patients to propofol ( intravenous anesthetic ) in addition to an opiate-based anesthesia for OPCAB . INTERVENTIONS The 2 groups of patients received either desflurane ( volatile anesthetic ) or propofol in addition to an opiate-based anesthesia for OPCAB . Peak postoperative troponin I release was measured as a marker of myocardial necrosis . Prolonged hospitalization was considered as a secondary outcome . MEASUREMENTS AND MAIN RESULTS Patient mean age was 69 years , and 82 % were men . There was a significant ( p < 0.001 ) reduction in postoperative median ( 25th-75th percentiles ) peak of troponin I in patients receiving volatile anesthetics , 1.2 ( 0.9 - 1.9 ) ng/dL , compared with patients receiving total intravenous anesthesia , 2.7 ( 2.1 - 4.0 ) ng/dL. This myocardial protection result ed in a reduced ( p = 0.04 ) number ( percentage ) of patients requiring postoperative inotropes , 20 ( 35 % ) versus 31 ( 56 % ) , and a reduced number ( percentage ) of patients su bmi tted to prolonged hospitalization ( > or = 7 days ) , 7 ( 12 % ) versus 20 ( 36 % ) in the 2 groups ( p = 0.005 ) . One patient receiving total intravenous anesthesia died within 30 days of surgery . CONCLUSIONS Myocardial damage measured by cardiac troponin release could be reduced by volatile anesthetics during OPCAB . Because patients underwent cardiac surgery on the beating heart , these results could have implication s for cardiac patients undergoing noncardiac surgery", "Background The value of postoperative cardiac troponin I ( cTnI ) has been shown to indicate a higher risk of in-hospital death after cardiac surgery . The authors therefore assessed the long-term prognostic value of cTnI in patients undergoing elective coronary artery bypass grafting . Methods Consecutive patients ( n = 202 ) were included and divided into two groups according to the postoperative value of cTnI ( < or ≥ 13 ng/ml ) . In-hospital mortality and nonfatal cardiac events ( delayed extubation > 24 h ; postoperative requirement of inotropic agent ; ventricular and supraventricular arrhythmia ; postoperative myocardial infa rct ion ) were recorded . Survivors were then followed up over a 2-yr period . Data are median and odds ratio ( 95 % confidence interval ) . Results Of all patients , 174 ( 86 % ) had a low cTnI ( 4.1 ng/ml ; range , 1.1–12.6 ) and 28 ( 14 % ) had a high cTnI ( 23.8 ng/ml ; range , 13.4–174.6 ) . In-hospital mortality was not significantly different ( 4 vs. 2 % ) , whereas long-term mortality ( 18 vs. 3 % , P = 0.006 ) and mortality from cardiac cause ( 18 vs. 1 % , P < 0.001 ) was greater in patients with a high cTnI. A high cTnI was a significant factor predicting death ( odds ratio , 7.3 [ 2.0–27.1 ] ) or death from cardiac causes ( odds ratio , 37.4 [ 4.2–334.4 ] ) . Nonfatal cardiac events were also more frequent in the hospital ( 64 vs. 41 % , P = 0.02 ) and within the 2-yr follow-up period ( 39%vs . 16 % , P = 0.03 ) in patients with high cTnI. Conclusion A high postoperative peak of cTnI is associated with increased risk of death , death from cardiac causes , and nonfatal cardiac events within 2 yr after coronary artery bypass grafting", "BACKGROUND Activation of the kinase cascade ( protein kinase C ( PKC ) , tyrosine kinase ( TK ) , and mitogen-activated protein kinase ( MAPK ) is a key feature of the transduction pathway , elicited by preconditioning signals and mediating their cardioprotective effects . We assessed whether such an activation occurred during cardiac operations and could thus represent a target for cardioprotective strategies . METHODS A total of 20 patients undergoing coronary artery bypass grafting surgery were studied . During the first 10 minutes of cardiopulmonary bypass ( CPB ) , 10 were treated with sevoflurane ( 2.5 minimum alveolar concentration ) , an inhalational anesthetic that mimics preconditioning through a similar activation of the kinase cascade . Ten case-matched patients undergoing 10 minutes of sevoflurane-free CPB served as controls . Right atrial biopsies were taken before and 10 minutes after CPB and were then processed for the measurement of PKC , TK , and p38 MAPK activities by enzyme assay techniques . Troponin I was also monitored over the first 2 postoperative days . RESULTS Compared with pre-CPB values , PKC and p38 MAPK activities ( in nanomoles per milligram of protein per minute and arbitrary units , respectively ) increased significantly and to the same extent in both groups : PKC , from 20.7+/-0.7 to 29.9+/-3.9 in controls ( p = 0.037 ) and from 18.4+/-1.1 to 23.9+/-1.8 in sevoflurane ( p = 0.016 ) ; p38 MAPK , from 88.6+/-8.5 to 312.9+/-66.2 in controls ( p = 0.005 ) and from 114.6+/-14.7 to 213.4+/-51.8 in sevoflurane ( p = 0.045 ) . Conversely , sevoflurane triggered a significant increase in TK activity ( from 68.5+/-1.4 to 83.7+/-2.9 picomoles per milligram of protein per minute p = 0.0015 ) which did not occur in controls ( from 67.5+/-1.9 to 76.8+/-4.2 picomoles per milligram of protein per minute , p = 0.09 ) . Likewise , the peak postoperative value of troponin I was not different between controls and sevoflurane-treated patients ( 3.4+/-0.6 vs 2.4+/-0.4 , p = 0.21 ) . CONCLUSIONS Cardiopulmonary bypass triggers an activation of the kinase cascade that is mechanistically linked to opening of potassium channels . The direct opening of these channels by the anesthetic sevoflurane does not increase kinase activation further , nor does it improve markers of cell necrosis , thus suggesting that pharmacologically targeting potassium channels may overlap the preconditioning-like effects of CPB alone", "Background : Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion . In clinical studies , the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period . The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration . Methods : Elective coronary surgery patients were r and omly assigned to four different anesthetic protocol s ( n = 50 each ) . In a first group , patients received a propofol based intravenous regimen ( propofol group ) . In a second group , propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass ( SEVO pre group ) . In a third group , propofol was replaced by sevoflurane after completion of the coronary anastomoses ( SEVO post group ) . In a fourth group , propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation ( SEVO all group ) . Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively . Results : Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group . Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group . In the SEVO pre and SEVO post groups , stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group . Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group . Conclusion : In patients undergoing coronary artery surgery with cardiopulmonary bypass , the cardioprotective effects of sevoflurane were clinical ly most apparent when it was administered throughout the operation", "Background Sevoflurane has been shown to protect against myocardial ischemia and reperfusion injury in animals . The present study investigated whether these effects were clinical ly relevant and would protect left ventricular ( LV ) function during coronary surgery . Methods Twenty coronary surgery patients were r and omly assigned to receive either target-controlled infusion of propofol or inhalational anesthesia with sevoflurane . Except for this , anesthetic and surgical management was the same in all patients . A high-fidelity pressure catheter was positioned in the left ventricle and the left atrium . LV response to increased cardiac load , obtained by leg elevation , was assessed before and after cardiopulmonary bypass ( CPB ) . Effects on contraction were evaluated by analysis of changes in dP/dtmax . Effects on relaxation were assessed by analysis of the load dependence of myocardial relaxation ( R = slope of the relation between time constant & tgr ; of isovolumic relaxation and end-systolic pressure ) . Postoperative concentrations of cardiac troponin I were followed during 36 h. Results Before CPB , leg elevation slightly increased dP/dtmax in the sevoflurane group ( 5 ± 3 % ) , whereas it remained unchanged in the propofol group ( 1 ± 6 % ) . After CPB , leg elevation result ed in a decrease in dP/dtmax in the propofol group ( −5 ± 4 % ) , whereas the response in the sevoflurane group was comparable to the response before CPB ( 5 ± 4 % ) . Load dependence of LV pressure fall ( R ) was similar in both groups before CPB . After CPB , R was increased in the propofol group but not in the sevoflurane group . Troponin I concentrations were significantly lower in the sevoflurane than in the propofol group . Conclusions Sevoflurane preserved LV function after CPB with less evidence of myocardial damage in the first 36 h postoperatively . These data suggest a cardioprotective effect of sevoflurane during coronary artery surgery", "Background and objectives : To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass , we performed a multicentre r and omized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans . Methods : We r and omly assigned 75 patients to propofol ( intravenous anaesthetic ) and 75 patients to desflurane ( volatile anaesthetic ) in addition to an opiate‐based anaesthesia for coronary artery bypass grafting . Peak postoperative troponin I release was measured as a marker of myocardial necrosis . Results : There was a significant ( P < 0.001 ) difference in the postoperative median ( 25th‐75th percentiles ) peak of troponin I in patients receiving propofol 5,5 ( 2,3‐9,5 ) ng dL−1 when compared to patients receiving desflurane 2,5 ( 1,1‐5,3 ) ng dL−1 . The median ( interquartile ) troponin I area under the curve analysis confirmed the results : 68 ( 30.5‐104.8 ) vs. 36.3 ( 17.9‐86.6 ) h ng dL−1 ( P = 0.002 ) . Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support ( 24/75 , 32.0 % vs. 31/75 , 41.3 % , P = 0.04 ) , and tends toward a reduction in number of Q‐wave myocardial infa rct ion , time on mechanical ventilation , intensive care unit and overall hospital stay . Conclusions : Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery", "OBJECTIVE To evaluate changes in cardiac troponin-I levels after major vascular surgery and their association with early and late postoperative cardiac complications . DESIGN Prospect i ve , observational investigation . SETTING University teaching hospital . PATIENTS 75 consecutive patients undergoing major vascular surgery . INTERVENTIONS All patients received a st and ard sevoflurane-fentanyl anesthesia during the procedure . Blood levels of creatine kinase with MB subtype and cardiac troponin-I were assessed before surgery and then everyday for the first 3 days after surgery . At the same time , 12-lead electrocardiography was also performed , and occurrence of any cardiac adverse event was recorded . Patients were then followed up for 1 month after surgery . MEASUREMENT AND MAIN RESULTS Troponin-I levels increased in 25 patients ( 33 % ) during the first 3 days after surgery ; 9 of these patients ( 12 % ) had myocardial infa rct ion . At univariate analysis , uncontrolled hypertension was the only risk factor for perioperative infa rct ion ( odds ratio , 16 ; ( 95 % confidence interval , 3 - 74 ) ; however , multivariate logistic regression analysis failed to show statistically significant associations . Increases in troponin-I had a 100 % sensitivity and 75 % specificity in detecting myocardial ischemia with a 36 % positive and 100 % negative predictive values . Severe cardiac complication 1 month after surgery was reported in 5 patients ( 6.6 % ) . The increase of cardiac troponin-I levels during the first 3 postoperative days was associated with an increased frequency of major cardiac complication at 1-month follow-up ( P = 0.003 ) , with a 100 % sensitivity , 71 % specificity , and 100 % negative predictive value . CONCLUSIONS Myocardial infa rct ion after major noncardiac vascular surgery occurs in up to 12 % of cases . Perioperative monitoring of troponin-I plasma levels may help to identify patients at increased risk for cardiac morbidity not only early after surgery but also during the first postoperative month", "Objective —To investigate whether administration of isoflurane prior to cardiopulmonary bypass ( CPB ) could partly account for the observed protection of the myocardial function and to decrease myocardial injury in patients undergoing coronary artery bypass grafting ( CABG ) . Methods —Thirty‐four patients with stable angina who were scheduled for isolated elective CABG operations were r and omized into the control group or isoflurane ( ISO ) group . In the ISO group , isoflurane was inhaled for 5 min followed by another 5‐min washout period before commencing CPB . The control group did not receive isoflurane . Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively . Results —There were no adverse effects related to isoflurane . Cardiac index ( CI ) increased postoperatively as compared with the baseline . In the ISO group , there was a tendency for a greater increase of CI than that in the control group ( p = 0.054 , ANOVA for repeated measurements ) . At 1 h after CPB , the change of CI was much higher in the ISO group than that in the controls ( p = 0.001 ) . Both the creatine kinase cardiac isoenzyme ( CK‐MB ) and troponin I ( TnI ) reached peak value at 6 h after CPB . Isoflurane patients released slightly less CK‐MB than the controls postoperatively , but the difference was not significant ( p = 0.16 , ANOVA for repeated measurements ) . The release of TnI was similar in both groups ( p = 0.65 , ANOVA for repeated measurements ) . Conclusions —Administration of isoflurane prior to commencing CPB may bring an improvement in early hemodynamic performance after CABG operations", "BACKGROUND In experimental and clinical studies , volatile anaesthesia has proven to possess cardioprotective properties . However , no r and omized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available . We therefore compared isoflurane-sufentanil vs propofol-sufentanil anaesthesia in patients undergoing coronary artery bypass grafting . METHODS One hundred patients were r and omly assigned to receive isoflurane-sufentanil ( I ) ( n = 51 ) or propofol-sufentanil ( P ) ( n = 49 ) anaesthesia , aim ed at the same hypnotic depth . Postoperative concentrations of cardiac troponin I ( cTnI ) were followed for 72 h. Secondary outcome variables were length of stay ( LOS ) in the intensive care unit ( ICU ) and in hospital , and 30 day and 1 yr mortality and morbidity , defined as acute myocardial infa rct ion , arrhythmias , and cardiac dysfunction . Groups were compared by an on-treatment analysis , using linear mixed models for repeated measures . RESULTS Eighty-four patients completed the protocol ( I : 41 vs P : 43 ) . Postoperative cTnI concentrations increased to a maximum of I : 2.72 ng ml(-1 ) ( 1.78 - 5.85 ) and P : 2.64 ng ml(-1 ) ( 1.67 - 4.83 ) , but did not differ between groups ( P=0.11 ) . LOS in the ICU and in hospital was similar [ ICU I : 18 ( 17.0 - 21.5 ) vs P : 19 ( 17.0 - 22.0 ) h ; hospital I : 9 ( 6.5 - 8.0 ) vs P : 8 ( 6.0 - 9.0 ) days ] . Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups . One year after surgery , two patients had died of non-cardiac causes . No between-group differences in cardiac morbidity were found . CONCLUSIONS In this study , the use of isoflurane-sufentanil in comparison with propofol-sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels", "Background and objectives Peroperative myocardial infa rct ion ( MI ) is the most common cause of morbidity and mortality . What is the role of general anesthesia in this process ? Is general anesthesia a risk for myocardial infa rct ion ? The present study was design ed to determine whether the measurement of serum levels of cardiac troponin I ( cTnI ) , a highly sensitive and specific marker for cardiac injury , would help establish the diagnosis of myocardial infa rct ion in two different types of anesthesia . Method Elective abdominal hysterectomy was planned with the permission of the ethic committee in 40 patients who were 20–45 years range , in ASA-I group , and have a Goldman Cardiac Risk Index-0 . The patients were divided into two groups . Isoflurane + N2O was administrated to first group , and Propofol + Fentanyl to second group . cTnI levels were determined before anesthesia , after induction before surgery and 9 hours after the second period respectively . Results There was no significant difference between the groups by the means of demographic properties , hemodynamic parameters and cTnI levels , and the cTnI levels were determined under the basal levels in all sample s. Conclusion General anesthesia is not a risk for myocardial infa rct ion to state eliminating risk factors and protection hemodynamia cardiac", "OBJECTIVES To analyze the hemodynamic effects and myocardial injury using troponin-T and creatine phosphokinase ( CPK-MB ) with isoflurane and compare it with a control group in patients undergoing off-pump coronary artery bypass ( OPCAB ) surgery . DESIGN This prospect i ve , r and omized study was performed in patients scheduled for elective OPCAB surgery during February 2007 to February 2009 . SETTING Tertiary care , university teaching hospital . PARTICIPANTS Forty-five patients undergoing elective OPCAB surgery . INTERVENTIONS Patients were r and omly allotted to receive either isoflurane ( inspired concentration between 1.0 % and 2.5 % ) or propofol ( 1.5 to 3.5 mg/kg/h ) during OPCAB surgery . The concentration of these agents was titrated such that the BIS value was maintained between 50 and 60 . MEASUREMENTS AND MAIN RESULTS The hemodynamic data were measured and recorded after induction of anesthesia ( baseline ) , during the distal anastomosis of each coronary artery , and 5 and 30 minutes after giving protamine . In addition , blood sample s for troponin-T and CPK-MB were obtained after induction ( baseline ) , after 6 hours and 24 hours postoperatively . The cardiac index was significantly higher in the isoflurane group at all stages , except during distal anastomosis of the diagonal branch of the left anterior descending artery ( p < 0.05 ) . There was a significant increase in troponin-T levels at 6 and 24 hours after surgery in the propofol group ( from 0.037 ± 0.013 ng/mL to 0.098 ± 0.045 ng/mL and 0.081 ± 0.025 ng/mL , respectively , p < 0.05 ) . Significant increases in the troponin-T levels were observed at 6 hours ( from 0.033 ± 0.011 ng/mL to 0.052 ± 0.025 ng/mL , ( p < 0.05 ) in the isoflurane group , and the levels in the propofol group were significantly higher than the isoflurane group at 6 and 24 hours after surgery ( p < 0.05 ) . The CPK-MB levels increased in both groups , but were not statistically different . CONCLUSIONS Isoflurane provides protection against myocardial damage in a clinical ly used dosage as documented by lower levels of troponin-T in patients undergoing OPCAB surgery", "BACKGROUND This study was undertaken to compare the in vivo effects of isoflurane , sevoflurane , and propofol anesthesia on ischemia- and reperfusion-mediated free-radical injury and oxidative stress during coronary artery bypass graft surgery . We also compared the effects of these anesthetic agents on levels of end products of lipid peroxidation and nitric oxide ( NO ) in human right atrial tissue and blood . METHODS Sixty patients scheduled to undergo elective coronary surgery with cardiopulmonary bypass ( CPB ) were enrolled . Patients were r and omly allocated to receive 1 of 3 different anesthetic protocol s : propofol ( group A ) , isoflurane ( group B ) , or sevoflurane ( group C ) . We recorded global hemodynamic data ( mean arterial pressure , mean pulmonary artery pressure , central venous pressure , pulmonary capillary wedge pressure , cardiac output , cardiac index , and systemic vascular resistance index ) just before the start of surgery , before the start of CPB , 15 minutes after the end of CPB , at the end of the operation , 6 hours after installation in the intensive care unit , and 12 and 24 hours later . Sample s of the right atrial appendage were harvested before and after exposure of the heart to blood cardioplegia and short-term reperfusion under conditions of CPB . Biochemical and oxidative stress parameters were analyzed in both blood and tissue . RESULTS Hemodynamic parameters were kept stable throughout in all groups . Troponin I increased transiently with all used anesthetic regimens , but this increase was significantly lower in groups B and C. After clamp removal , lipid peroxidation in patients who received propofol ( group A ) was less than in patients who received isoflurane ( group B ) or sevoflurane ( group C ) ( P= .001 , P= .005 , respectively ) . Although the 3 groups showed no statistically significant differences in tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase , propofol significantly lowered NO production in atrial tissue after clamp removal and induced less NO production than sevoflurane ( P < .05 ) . CONCLUSION Inhalation anesthetics such as isoflurane and sevoflurane preserved cardiac function in coronary surgery patients after CPB with less evidence for myocardial damage than propofol . Furthermore , propofol induced lower blood levels of lipid peroxidation than isoflurane and sevoflurane . Propofol also increased glutathione peroxidase activity but induced less NO production compared to sevoflurane . These findings also support the cardioprotective properties that are demonstrated by hemodynamic parameters", "A r and omised study of 414 patients undergoing coronary artery surgery with cardiopulmonary bypass was conducted to compare the effects of a volatile anaesthetic regimen with either deesflurane or sevoflurane , and a total intravenous anaesthesia ( TIVA ) regimen on postoperative troponin T release . The primary outcome variable was postoperative troponin T release , secondary outcome variables were hospital length of stay and 1‐year mortality . Maximal postoperative troponin T values did not differ between groups ( TIVA : 0.30 [ 0.00–4.79 ] ng.ml−1 ( median [ range ] ) , sevoflurane : 0.33 [ 0.02–3.68 ] ng.ml−1 , and desflurane : 0.39 [ 0.08–3.74 ] ng.ml−1 ) . The independent predictors of hospital length of stay were the EuroSCORE ( p < 0.001 ) , female gender ( p = 0.042 ) and the group assignment ( p < 0.001 ) . The one‐year mortality was 12.3 % in the TIVA group , 3.3 % in the sevoflurane group , and 6.7 % in the desflurane group . The EuroSCORE ( p = 0.003 ) was the only significant independent predictor of 1‐year mortality", "Volatile anesthetics exert cardioprotective properties in experimental and clinical studies . We design ed this study to investigate the effects of sevoflurane on left ventricular ( LV ) performance during minimally invasive direct coronary artery bypass grafting ( MIDCAB ) without cardiopulmonary bypass . Fifty-two patients scheduled for MIDCAB surgery were r and omly assigned to a propofol or a sevoflurane group . Apart from the anesthetics used , there was no difference in surgical and anesthetic management . After determination of cardiac troponin T , creatine kinase , and creatine kinase MB , electrocardiographic ( ECG ) data and echocardiography variables ( myocardial performance index and early to atrial filling velocity ratio ) the left anterior descending coronary artery ( LAD ) was clamped until anastomosis with the left internal mammary artery was completed . During LAD occlusion and during reperfusion , echocardiography measurements were repeated . Blood sample s were obtained repeatedly for up to 72 h. After LAD occlusion , myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 ± 0.12 and 1.29 ± 0.35 to 0.49 ± 0.10 and 1.13 ± 0.22 , respectively , whereas there was no change in the sevoflurane group . In the propofol group myocardial performance index remained increased ( 0.47 ± 0.11 ) compared with baseline during reperfusion . There were no significant differences in ECG and laboratory values between groups . In conclusion , during a brief period of ischemia in patients undergoing MIDCAB surgery , sevoflurane preserved myocardial function better than propofol", "Background Cardiac surgery is associated with some degree of myocardial injury . Preconditioning first described in 1986 was pharmacologic and non- pharmacologic . Among the long list of anesthetic drugs , isoflurane as an inhaling agent along with midazolam and propofol as injectable substances have been documented to confer some preconditioning effects on myocardium . Objectives In this study cardiac Troponin T ( cTnT ) , as a reliable marker , was used for evaluating myocardial injury . Methods This prospect i ve double blind study was comprised of 60 patients scheduled for CABG and were r and omly assigned into three groups who received infusion of propofol or midazolam or isoflorane . Surgical procedures and anesthetics were similar for 3 groups . cTnT measured preoperatively and at 12 , 24 and 36hr after arrival in ICU . Results There were no statistically significant differences in mean cTnT levels between three groups in the preoperative period and 12 - 24 hours after arrival in ICU . However , mean cTnT in 3 groups at 36 hours after arrival in ICU were different ( P < 0.013 ) and cTnT level was significantly higher in midazolam group ( P<0.001 ) and lowest in isoflurane group ( P=0.002 ) . Conclusion There were significant differences on cTnT levels between anesthetic groups of isofluran , midazolam and propofol at 36 hr after surgery . Preconditioning effect of isoflurane was higher than the other two groups", "BACKGROUND Several studies have highlighted that volatile anaesthetics improve myocardial protection in cardiopulmonary bypass coronary surgery . However , the haemodynamic effect of desflurane in off-pump coronary surgery has not been clarified yet . Our study hypothesis was that desflurane-fentanyl anaesthesia could decrease myocardial injury markers and improve haemodynamics compared to propofol-fentanyl in patients undergoing off-pump coronary surgery . METHODS DESIGN Prospect i ve , r and omised open-lable study . Sixty elective patients with left ventricular ejection fraction above 30 % received either desflurane ( group D , n = 32 ) or propofol ( group P , n = 28 ) , in addition to fentanyl and vecuronium bromide anaesthesia for off-pump coronary surgery . Assessment of haemodynamic function included thermodilution continuous cardiac output and right ventricular end diastolic volume . RESULTS No significant differences in cardiac output , stroke volume and mean arterial pressure were noted between groups . The only observed difference in haemodynamic profile was that group D demonstrated improved stability , expressed as left ventricular stroke work index ( LVSWI ) . Decrease in LVSWI after performing distal anastomoses was smaller in D compared to P ( median value : -14.3 and -19.8 [ g m m⁻² beat⁻¹ ] ) , respectively ( P = 0.029 ) . Oxygen uptake index ( VO₂I ) and oxygen extraction ratio ( OER ) after skin incision were lower in D , while blood lactate concentration was slightly higher after surgery in D compared to P. The groups did not differ with respect to CK-MB and troponin I concentration . CONCLUSIONS This study demonstrated no difference between desflurane and propofol anaesthesia for off-pump coronary surgery in major haemodynamic parameters , as well as in myocardial injury markers and the long-term outcome . However , the study indicated that desflurane might accelerate recovery of myocardial contractility , as assessed by LVSWI . Lower oxygen uptake and elevated lactate under desflurane anaesthesia indicated a discrete shift towards anaerobic metabolism . CLINICAL TRIAL REGISTRATION INFORMATION NCT00528515 ( http://www . clinical trials.gov/ ct2/show/NCT00528515?term = NCT00528515&rank = 1 )", "Background The relationship between cardiac enzyme ( CE ) release following coronary artery bypass surgery ( CABG ) and medium term outcome is unclear . We sought to determine the relationship between post-operative CE release and one-year survival following isolated CABG . Methods Over three years 3,024 consecutive patients underwent isolated CABG . Patient characteristics were prospect ively recorded in a cardiac surgical data base . CE release , taken as the highest single measurement recorded in the first 24 hours post-op , was abstract ed from an electronic archive . All cause mortality was taken from a national registry of deaths . Results Data were complete for 2,860 ( 94.6 % ) patients . CK-MB isoenzyme ( reference range 5–24 U/l ) was recorded in 2,568 ( 89.8 % ) , total CK in 292 (10.2%).CE release three or more times the upper limit of the reference range ( ULR ) were recorded in 498 ( 17.4 % ) patients , 163 ( 5.7 % ) patients had CE more than six times ULR . There were 122 deaths ( 4.3 % ) . Cox proportional hazards analysis showed that CE release 3–6 times ULR ( adjusted HR 2.1 [ 95 % CI : 1.6 to 2.6 ] , p = 0.002 ) and CE release six or more times the ULR ( adjusted HR 5.0 [ 95 % CI : 4.5 to 5.4 ] , p < 0.001 ) were independently associated with increased one-year mortality . Conclusion Cardiac enzyme release following CABG is associated with increased one-year all-cause mortality . The definition of peri-operative myocardial infa rct ion following CABG should include elevation of CK-MB three or more times the upper limit of normal", "Background Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia . It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide , a biochemical marker for myocardial dysfunction . In addition , several variables associated with the protective effects of preconditioning were evaluated . Methods Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were r and omly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo ( oxygen – air mixture only ) or sevoflurane 4 vol% ( 2 minimum alveolar concentration ) . No other volatile anesthetics were administered at any time during the study . Treatment was strictly blinded to anesthesiologists , perfusionists , and surgeons . Biochemical markers of myocardial dysfunction and injury ( brain natriuretic peptide , creatine kinase – MB activity , and cardiac troponin T ) , and renal dysfunction ( cystatin C ) were determined . Results of Holter electrocardiography were recorded perioperatively . Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial sample s. Results Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide , a sensitive biochemical marker of myocardial contractile dysfunction . Pronounced protein kinase C & dgr ; and & egr ; translocation was observed in sevoflurane-preconditioned myocardium . In addition , postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients . No differences between groups were found for perioperative ST-segment changes , arrhythmias , or creatine kinase – MB and cardiac troponin T release . Conclusions Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest . This study demonstrated for the first time translocation of protein kinase C isoforms & dgr ; and & egr ; in human myocardium in response to sevoflurane", "AIM The cardioprotective effects afforded by volatile anesthetics , i.e. isoflurane , during heart surgery may be due to preconditioning of the myocardium through the activation of KATP channels . The aims of this study were to establish whether glibenclamide prevents the isoflurane-induced cardioprotection in diabetic patients undergoing coronary surgery ( CABG ) and whether this cardioprotective effect can be restored by preoperative shift from glibenclamide to insulin therapy . METHODS We enrolled 60 patients undergoing CABG . Twenty consecutive non-diabetic patients were r and omized to receive conventional anesthesia ( CA ) or conventional anesthesia plus isoflurane ( ISO ) ( added to the inspired oxygen before starting cardiopulmonary bypass ) ; 40 consecutive diabetic patients in chronic treatment with oral glibenclamide were r and omized to conventional anesthesia ( G-CA ) , conventional anesthesia plus isoflurane ( G-ISO ) , conventional anesthesia after shifting to insulin ( I-CA ) or conventional anesthesia plus isoflurane after shifting to insulin ( I-ISO ) . Serum levels of cardiac troponin I ( CTnI ) and CK-MB , as markers of ischemic injury , were obtained 1 , 24 , 48 and 96 hours , postoperatively . RESULTS Postoperative peak levels of CTnI and CK-MB were lower in ISO than in CA ( 0.5+/-0.3 vs 2.8+/-2.2 ng/ml , p<0.05 and 61+/-27 vs 79+/-28 U/L , p<0.05 , respectively ) , as well as in I-CA and I-ISO than G-CA and G-ISO groups ( 0.5+/-0.7 and 0.7+/-0.9 vs 3.5+/-3 and 2.7+/-2.5 ng/ml , p<0.05 ; 47+/-7 and 41+/-5 vs 85+/-28 and 50+/-23 U/L , p<0.05 , respectively ) . No significant differences were detected in postoperative hemodynamic variables or in-hospital outcome . CONCLUSION This prospect i ve r and omized study shows a cardioprotective effect of preoperative administration of isoflurane during CABG . Such an effect is prevented by glibenclamide , but can be restored in diabetic patients by preoperative shift from glibenclamide to insulin", "We investigated if increasing propofol 's dosage to augment its antioxidant capacity during cardiopulmonary bypass ( CPB ) could confer cardiac protection . Fifty-four coronary artery bypass graft surgery patients were r and omly assigned to small-dose propofol ( Group P ; n = 18 ) , large-dose propofol ( Group HiP ; n = 18 ) , or isoflurane Group ( Group I ; n = 18 ) . After the induction , anesthesia was maintained with an inspired concentration of isoflurane 1%–3.5 % ( Group I ) or a continuous infusion of propofol 60 & mgr;g · kg−1 · min−1 ( Group P ) throughout the surgery . In Group HiP , this dose of propofol was increased to 120 & mgr;g · kg−1 · min−1 for 10 min before the onset of CPB until 15 min after aortic unclamping and then decreased to 60 & mgr;g · kg−1 · min−1 until the end of surgery . The duration of aortic cross-clamping was 83 ± 24 , 88 ± 22 , and 81 ± 20 min in Group P , Group HiP , and Group I , respectively ( P > 0.1 ) . Plasma malondialdehyde , a marker of oxidative stress , was significantly lower at 8 h after CPB , and Troponin I was lower at 24 h after CPB in Group HiP compared with Group P and Group I ( P < 0.05 ) . There was a significant reduction in inotropic requirements for separation from CPB in Group HiP compared with Group I. Postoperative systemic vascular resistance was significantly reduced in Group HiP as compared with Group I. Mean cardiac index was significantly higher at 24 h after CPB in Group HiP compared with Group P and Group I ( P < 0.05 ) ( Group I , 2.2 ± 0.1 ; Group P , 2.3 ± 0.2 ; and Group HiP , 2.8 ± 0.3 L · min−1 · m−2 , respectively ) . The duration of intensive care unit stay was significantly shorter in Group Hi-P compared with Group I. We conclude that administration of a large dose of propofol during CPB attenuates postoperative myocardial cellular damage as compared with isoflurane or small-dose propofol anesthesia", "The aim of the study was to evaluate the effects of sevoflurane and propofol on the activity of mitochondrial function related to ischemia-reperfusion injury , myocardial damage biomarkers release and clinical parameters in the postoperative period . Seventy-two patients scheduled for elective coronary artery bypass graft surgery with cardiopulmonary bypass were r and omized into two groups : 36 patients received sevoflurane during anesthesia ( Group S ) and 36 patients received propofol ( Group P ) . To investigate the functional activity of mitochondria , we used skinned fibers prepared from biopsies of right atrial tissue before cardioplegia and after the aorta cross-clamp removal ( within 10 - 15 minutes after reperfusion ) . Patients ’ clinical data ( length of stay in ICU , hemodynamic parameters , duration of mechanical ventilation ( MV ) and the amount of lactate and troponin I in the blood serum ) were evaluated postoperatively . The results showed that , before cardioplegia and after reperfusion , there was no significant difference in the mitochondrial routine and State 3 respiration rates between the groups . The effect of cytochrome c was higher in Group P. Troponin I concentration at the 12th hour after the surgery was 2.2 ± 0.8 ng/mL in Group S and 3.5 ± 1.1 ng/mL in Group P ( p<0.001 ) . There were no significant differences in the duration of mechanical ventilation , hemodynamic parameters and length of stay in the ICU between the groups . We conclude that sevoflurane slightly protects the mitochondrial outer membrane from ischemia-reperfusion injury and the loss of cytochrome c , yet has the similar effect on clinical parameters in the postoperative period when compared to propofol", "Myocardial ischemic damage is reduced by volatile anaesthetics in patients undergoing low‐risk coronary artery bypass graft surgery ; few and discordant results exist in other setting s. We therefore performed a r and omised controlled trial ( sevoflurane vs. propofol ) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery", "OBJECTIVE To investigate the effect of long-term sevoflurane anesthesia on markers of myocardial damage or toxicity . METHODS Forty adult patients scheduled for upper abdominal surgery with general anesthesia for 4 hours or more were r and omly divided into Group S and PR ( n=20 each ) . After anesthesia induction , patients of Group S were maintained with only sevoflurane , and patients of Group PR with target-controlled infusion of propofol 2 - 4 microg/ml and remifentanil 4 - 8 ng/ml . Anesthesia was titrated to control blood pressure and heart rate change at less than 20 percent of baseline values . Blood sample s were draw at pre-induction , 4 h and 24 h post-induction respectively . Serum level of cardiac troponin I , creatine kinase MB and myoglobin were analyzed . RESULTS There were no significant changes of troponin I , creatine kinase MB and myoglobin in Group S between pre-induction and 4 h or 24 h post-induction ( P > 0.05 ) . And there was also no significant differences as compared with Group PR ( P > 0.05 ) . CONCLUSION At the concentration range of 1.6%-3 % , long-term sevoflurane anesthesia does not cause detectable changes of markers of myocardial damage or toxicity", "BACKGROUND Experimental evidence suggests that the inhalational anesthetic sevoflurane has a cardioprotective effect . Our objective was to determine if sedation with sevoflurane will reduce infa rct size in patients with acute myocardial infa rct ion ( MI ) who are treated with primary percutaneous coronary intervention ( PCI ) . METHODS We r and omized 50 patients presenting with a first acute ST-elevation MI treated by primary PCI within 6 hours from symptom onset to sedation with sevoflurane inhalation or st and ard sedation ( control ) . Coronary flow at the end of PCI was assessed by corrected Thrombolysis In Myocardial Infa rct ion frame count . Myocardial reperfusion was assessed by ST-segment resolution 60 minutes post-PCI . Infa rct size was assessed by release of creatinine kinase ( CK ) and troponin T. RESULTS There was no difference in the primary end point : troponin T or CK release adjusted to the area at risk , between groups . However , among patients with anterior MI , there was a trend toward lower CK ( P = .05 ) and nonsignificant decrease in troponin ( P = .11 ) levels in the sevoflurane group . Corrected Thrombolysis In Myocardial Infa rct ion frame count was 12.3 ± 1.5 in the sevoflurane group and 15.6 ± 9.1 in the control group ( P = .16 ) . There was more ST resolution in patients treated by sevoflurane 80.7 % ± 25.8 % versus 56.6 % ± 35.7 % ( P = .01 ) . Sevoflurane had no significant adverse effect during administration . CONCLUSIONS Sevoflurane administration during primary PCI did not reduce infa rct size . There was a trend toward a reduction in infa rct size among patients with anterior MI . Sevoflurane administration was associated with improvement in ST-segment resolution", "Background Sevoflurane , like other halogenated anesthetics , has been shown to have a protective effect on the myocardium at risk after an ischemic injury . The current study tested the hypothesis that such beneficial effects , so far mainly seen in the laboratory , are reproducible in humans . Methods After institutional review board approval , 20 patients scheduled to undergo elective off-pump coronary artery bypass surgery were r and omized to receive general anesthesia with either sevoflurane or propofol . Except for this , anesthetic and surgical management was the same in both groups . For assessing myocardial injury , troponin I and myocardial fraction of creatine kinase were determined during the first 24 postoperative hours . Systemic hemodynamic variables were measured before , during , and after completion of coronary artery bypass . Results Troponin I concentrations increased significantly more in propofol-anesthetized patients than in patients anesthetized with sevoflurane . Conclusion Patients receiving sevoflurane for off-pump coronary artery surgery had less myocardial injury during the first 24 postoperative hours than patients receiving propofol . The results further support cardioprotective effects of sevoflurane", "Either isoflurane preconditioning or high-dose propofol treatment has been shown to attenuate myocardial IRI ( ischaemia/reperfusion injury ) in patients undergoing CABG ( coronary artery bypass graft ) surgery . It is unknown whether isoflurane and propofol may synergistically attenuate myocardial injury in patients . The present study investigated the efficacy of IsoPC ( isoflurane preconditioning ) , propofol treatment ( postconditioning ) and their synergy in attenuating postischaemic myocardial injury in patients undergoing CABG surgery using CPB ( cardiopulmonary bypass ) . Patients ( n = 120 ) selected for CABG surgery were r and omly assigned to one of four groups ( n = 30 each ) . After induction , anaesthesia was maintained either with fentanyl and midazolam ( control ; group C ) ; with propofol at 100 μg x kg(-1 ) of body weight x min(-1 ) before and during CPB followed by propofol at 60 μg x kg(-1 ) of body weight x min(-1 ) for 15 min after aortic declamping ( group P ) ; with isoflurane 1 - 1.5 % end tidal throughout the surgery ( group I ) or with isoflurane 1 - 1.5 % end tidal before CPB and switching to propofol at 100 μg x kg(-1 ) of body weight x min(-1 ) during CPB followed by propofol at 60 μg x kg(-1 ) of body weight x min(-1 ) for 15 min after aortic declamping ( group IP , i.e. IsoPC plus propofol postconditioning ) . A joint isoflurane and propofol anaesthesia regimen synergistically reduced plasma levels of cTnI ( cardiac troponin I ) and CK-MB ( creatine kinase MB ) and f-FABP ( heart-type fatty acid-binding protein ) ( all P < 0.05 compared with control , group P or group I ) and facilitated postoperative myocardial functional recovery . During reperfusion , myocardial tissue eNOS ( endothelial NO synthase ) protein expression in group IP was significantly higher , whereas nitrotyrosine protein expression was lower than those in the control group . In conclusion , a joint isoflurane preconditioning and propofol anaesthesia regimen synergistically attenuated myocardial reperfusion injury in patients", "OBJECTIVE To investigate the value of cardiac troponin I ( cTnI ) levels in assessing myocardial protection by remifentanil precondition against myocardial injury induced by off-pump coronary artery bypass ( OPCAB ) . METHODS Twenty-four patients undergoing OPCAB were r and omized into control and remifentanil preconditioning group ( n=12 ) . All the patients received pretreatment with oral diazepam ( 10 mg ) , intramuscular morphine ( 10 mg ) and hyosine ( 0.3 mg ) . General anesthesia was induced with midazolam ( 0.08 mg/kg ) , etomi date ( 0.1 - 0.3 mg/kg ) , fentanyl ( 5 - 10 microg/kg ) , and rocuronium ( 1 mg/kg ) , and maintained with isoflurane inhalation and propofol infusion . Intermittent fentanyl and pipecuronium were given intravenously . In remifentanil preconditioning group , remifentanil ( 5 microg/kg in 50 ml normal saline ) was infused in 10 min after anesthesia induction , and only NS was administered in the control group . Blood sample s were obtained before and at 0 , 2 , 6 , 24 , and 48 h after the operation to determine serum cTnI levels . RESULTS In both of the two groups , the cTnI levels increased significantly at the postoperative time points ( 0 , 2 , 6 , 24 , and 48 h ) as compared with those before the operation ( P<0.05 ) . The cTnI levels of remifentanil preconditioning group were markedly decreased after the operation in comparison with those of the control group ( P<0.05 ) . CONCLUSION Remifentanil preconditioning decreases the cTnI levels and reduces myocardial injury induced by OPCAB", "Context Volatile anaesthetics may have direct cardioprotective properties due to effects similar to ischaemic preconditioning and postconditioning . Clinical results in cardiac surgery patients are controversial and may be related to the timing of administration of anaesthetics intraoperatively . Objective We hypothesised that the cardioprotective effect of sevoflurane in coronary bypass graft surgical patients would be greater if administration during anaesthesia continued in the ICU for at least 4 h postoperatively until weaning from mechanical ventilation . Design Double-blind , double-dummy , prospect i ve , r and omised and controlled clinical trial . Setting In a single centre between June 2006 and June 2007 . Patients Seventy-five adult patients were assigned r and omly to receive anaesthesia and postoperative sedation either with propofol ( control , n = 37 ) or sevoflurane ( n = 36 ) . Interventions Myocardial biomarkers were measured before surgery , at the time of admission to the intensive care unit and at 6 , 24 , 48 and 72 h. The need for inotropic support , and lengths of stay in the intensive care unit and hospital were also recorded . Main outcome measures Elevation of myocardial biomarkers was the primary endpoint . The secondary endpoints were haemodynamic events and lengths of stay in the intensive care unit and hospital . Results Necrosis biomarkers increased significantly in the postoperative period in both groups with no significant differences at any time . Inotropic support was needed in 72.7 and 54.3 % of patients in the propofol and sevoflurane groups , respectively ( P = 0.086 ) . There were no significant differences in haemodynamic variables , incidence of arrhythmias , myocardial ischaemia or and lengths of stay in the ICU and hospital between the two groups . Conclusion In patients undergoing coronary bypass graft surgery , continuous administration of sevoflurane as a sedative in the ICU for at least 4 h postoperatively did not yield significant improvements in the extent and time course of myocardial damage biomarkers compared to propofol", "OBJECTIVE Myocardial ischemic damage is reduced by volatile anesthetics in patients undergoing coronary artery bypass graft surgery , but it is unknown whether this benefit exists in patients undergoing valvular surgery with ischemia-reperfusion injury related to cardioplegic arrest and cardiopulmonary bypass . This study compared cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for mitral valve surgery . DESIGN R and omized controlled study . SETTING University hospital . PARTICIPANTS One hundred twenty patients undergoing mitral valve surgery . INTERVENTIONS Fifty-nine patients received the volatile anesthetic desflurane for 30 minutes before cardiopulmonary bypass , whereas 61 patients received a total intravenous anesthetic with propofol . All patients had an opioid-based anesthetic for the mitral valve surgery . MEASUREMENTS AND MAIN RESULTS Peak postoperative troponin I release was measured as a marker of myocardial necrosis after mitral valve surgery . Patient mean age was 60 years , and 54 % were men . There was no significant ( p = 0.7 ) reduction in median ( 25th-75th percentiles ) postoperative peak troponin , 11.0 ( 7.5 - 17.4 ) ng/dL in the desflurane group versus 11.5 ( 6.9 - 18.0 ) ng/dL in the propofol group . A subgroup of patients with concomitant coronary artery disease had the expected reduction ( p = 0.02 ) of peak troponin I in those receiving desflurane , 14.0 ( 9.7 - 17.3 ) ng/dL , when compared with patients receiving total intravenous anesthesia , 31.6 ( 15.7 - 52.0 ) ng/dL. CONCLUSIONS Myocardial damage measured by cardiac troponin release was not reduced by volatile anesthetics in patients undergoing mitral valve surgery , whereas it was reduced in patients with concomitant coronary artery disease", "OBJECTIVE The aim of this prospect i ve r and omized study was to compare the myocardial protective effects of sevoflurane and isoflurane during coronary bypass surgery . METHODS After induction of general anesthesia with etomi date 0.3 mg/kg , a bolus dose of pancuronium 0.1 mg/kg and remifentanil 1 mcg/kg was administered . For the maintenance of anesthesia , patients received either sevoflurane ( n=20 ) at 2 - 4 % or isoflurane ( n=20 ) at 1 - 2 % . Arterial blood sample s were obtained as follows : before induction of anesthesia , after aortic unclamping , at postoperative period . Troponin-T , creatine kinase ( CK ) , and creatine kinase-MB ( CKMB ) values were measured in all obtained sample s. Statistical analysis was performed using two-way ANOVA analysis and Mann-Whitney test . RESULTS Heart rate was significantly higher in the sevoflurane group during the aortic side-clamp period , at the 10th minute and 20th minute after cardiopulmonary bypass ( CPB ) ending . The CK-MB values at 24th postoperative hour in the sevoflurane group were found to be significantly lower from the isoflurane group . The troponin-T values following the removal of the cross-clamp ( 1.015 ( 0.935 - 1.850 ) ng/ml vs 1.469 ( 1.290 - 1.645 ) ng/ml , p<0.001 ) and those at the 24th postoperative hour ( 5.345±0.654 ng/ml vs 8.715±1.020 ng/ml , p<0.001 ) were significantly lower in the sevoflurane group when compared to those in the isoflurane group . CONCLUSION Sevoflurane provides a better myocardial protection than isoflurane , as may be inferred by the lower levels of the myocardial injury markers troponin-T and CK-MB observed with sevoflurane", "Ischaemic damage to the myocardium inevitably occurs during coronary artery surgery . However , the extent of the damage may be influenced by the anaesthetic technique used . The most sensitive and reliable marker of myocardial damage is currently thought to be troponin T. We conducted a prospect i ve , r and omised , single‐blind pilot study to determine the baseline values of troponin T release after off‐pump coronary artery bypass surgery in 30 patients r and omly allocated to receive either propofol , isoflurane or isoflurane and high thoracic epidural analgesia . All other treatment was st and ardised . Patients undergoing emergency surgery and those with unstable angina were excluded . Blood sample s were taken at 0 , 3 , 6 , 12 , 24 and 48 h after surgery for troponin T analysis . Mean troponin T levels at 24 h were not significantly different between the groups ( p = 0.41 ) . These data allows appropriate power calculations for further , large‐scale studies to determine the anaesthetic technique that provides optimal myocardial protection", "This r and omised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane ( S group ) versus propofol ( P group ) , during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery , on myocardial injury . Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50 . In both groups , a targeted concentration of remifentanil 20 ng.ml-1 was maintained during anaesthesia . The concentrations of creatine kinase MB and troponin I were measured before the start of surgery , on admission to the intensive care unit , and at 12 and 24 hours after intensive care unit admission . The postoperative values of creatine kinase MB ( S group : 15.08±18.97 , 20.78±20.92 , 12.76±12.82 vs 2.09±1.54 ng.ml-1 ; P group : 10.99±13.15 , 27.16±56.55 , 11.88±18.80 vs 1.84±1.67 ng.ml-1 ) and troponin I ( S group : 3.56±5.19 , 5.66±7.89 , 3.35±4.55 vs 0.52±1.90 ng.ml-1 ; P group : 2.42±3.33 , 4.11±6.01 , 3.04±5.31 vs 0.43±1.28 ng.ml-1 ) were significantly higher than preoperative values in both groups but there were no significant differences between the two groups . There were no significant differences in time to extubation ( S group , 476±284 minutes ; P group , 450±268 minutes ) and intensive care unit length of stay ( S group , 2775±1449 minutes ; P group , 2797±1534 minutes ) between the two groups . In conclusion , sevoflurane and propofol at equipotent doses guided by bispectral index with remifentanil 20 ng.ml-1 had similar creatine kinase MB and troponin I values", "UNLABELLED The aim of the study is to investigate cardioprotective properties of sevoflurne during coronary bypass surgery with extracorporeal circulation . METHODS 60 patients with coronary heart disease ( left ventricular ejection fraction 61,3 + 1,0 % ) underwent surgery with extracorporeal circulation . Inhalation anesthesia with Sevoflurane and TIVA were performed . Hemodynamic , troponin level , KFK , protein of heart shock in plasma ( PHS 70 ) and PHS in myocard were monitored . RESULTS patients who were administrated with Sevoflurane had lower level of troponin than patients of second group . In postperfusion period the amount of PHS 70 in myocard increased in 1.6 times than in preperfusion period in comparison to TIVA method this figure did not change . There was negative correlation in level of PHS 70 in plasma and troponin in first day after the operation ( r = -0,61 p < 0,05 ) and second day ( r = - 0,76 , p < 0,05 ) . In conclusion Sevoflurane had affected hemodynamic less than TIVA . Increased level of PHS has cardioprotective effects", "Perioperative myocardial ischemia contributes to postoperative morbidity and mortality . Remote intermittent ischemia ( RI ) has been shown to benefit patients undergoing coronary artery bypass graft ( CABG ) surgery by decreasing postoperative cardiac troponin levels . In addition , there is evidence that volatile anesthetics may provide myocardial protection . In this prospect i ve r and omized controlled trial we tested the hypothesis that RI is cardioprotective under a strict anesthetic regime with volatile anesthesia until cardiopulmonary bypass ( CPB ) . We also assessed whether RI modulates postoperative cytokine and growth factor concentrations . Fifty-four patients referred for elective CABG surgery without concomitant valve or aortic surgery were r and omized to three 5-min cycles of left upper limb ischemia by cuff inflation ( RI ) or placebo without cuff inflation ( Plac ) . All patients received the volatile anesthetic isoflurane ( 1.15–1.5 vol% ) before CPB and the intravenous anesthetic propofol ( 3–4 mg/kg/h ) thereafter until the end of surgery . Cardiac arrest during CPB was induced by intermittent cross-clamp fibrillation , or by blood cardioplegia . We excluded patients older than 85 years , with unstable angina , significant renal disease , and those taking sulfonylureas . Troponin I ( cTnI ) was measured preoperatively and after 6 , 12 , 24 and 48 h. In addition , brain natriuretic peptide ( BNP ) , creatine kinase ( CKMB ) and a panel of cytokines and growth factors were analyzed perioperatively . Although cTnI , BNP and CKMB all increased post-CABG , there were no significant differences between RI and Plac groups ; area under the curve for cTnI 189.4 ( 183.6 ) ng/mL/48 h and 183.0 ( 155.2 ) ng/mL/48 h mean ( SD ) , p = 0.90 , respectively , despite a tendency to a shorter ( p < 0.07 ) cross-clamp time in the treatment group . Similarly , there were no differences between groups in the central venous concentrations of numerous cytokines and growth factors . In patients undergoing CABG surgery RI does not provide myocardial protection under a strict anesthetic regime with volatile anesthesia until CPB , and RI was not associated with changes in cytokines", "OBJECTIVE Anesthetic preconditioning may contribute to the cardioprotective effects of sevoflurane in patients having coronary artery bypass surgery . We investigated whether 2 different sevoflurane administration protocol s can induce preconditioning in patients having coronary artery bypass . METHODS Thirty patients were r and omly allocated to 1 of 3 groups . All patients received a total intravenous anesthesia with sufentanil ( 0.3 microg(-1 ) x kg x h(-1 ) ) and propofol as target controlled infusion ( 2.5 microg/mL ) . The control group had no further intervention ; 10 minutes prior to establishing the extracorporeal circulation , patients of the sevoflurane-I group received 1 minimum alveolar concentration of sevoflurane for 5 minutes . Patients of the sevoflurane-II group received ( 2 times ) 5 minutes of sevoflurane , interspersed by 5-minute washout 10 minutes prior to extracorporeal circulation . Troponin I was measured as marker of cardiac cellular damage . RESULTS Peak levels of troponin I release were observed at 4 hours after cardiopulmonary bypass and were not affected by 1 cycle of sevoflurane administration ( controls : 14 + /- 3 ng/mL vs sevoflurane-I group , 14 + /- 3 ng/mL ) . Two periods of sevoflurane preconditioning significantly reduced cellular damage compared with controls ( peak troponin I level sevoflurane-II group , 7 + /- 2 ng/mL ) . CONCLUSION These data show that sevoflurane-induced preconditioning is reproducible in patients having coronary artery bypass but depends on the preconditioning protocol used", "OBJECTIVE To examine the role of sevoflurane in myocardial protection in patients undergoing coronary artery bypass graft ( CABG ) surgery . DESIGN Prospect i ve , r and omized , controlled , double-blinded study . SETTING Veterans Administration Medical Center ( VAMC ) , Buffalo , New York . SUBJECTS Twenty-one patients undergoing CABG were included in the study . Eleven patients were r and omized to receive sevoflurane , and 10 patients served as controls . INTERVENTION Total intravenous anesthesia was provided for both study and control groups by infusion of propofol , fentanyl , and midazolam . Sevoflurane 2 % was added to the cardioplegia solution in the experimental group . MEASUREMENTS AND MAIN RESULTS Neutrophil beta-integrins ( CD11b/CD18 ) , tumor necrosis factor alpha ( TNF-alpha ) , and interleukin (IL)-6 were measured as indicators of the inflammatory response to myocardial ischemia-reperfusion injury . Blood sample s were obtained from the aorta and coronary sinus before ( T1 ) and immediately after cardiopulmonary bypass ( CPB ) ( T2 ) and , in addition , from a peripheral artery 6 hours ( T3 ) after CPB . Myocardial function was determined in all patients at each time point . Left ventricular stroke work index ( LVSWI ) was calculated as an estimation of left ventricular function . Left ventricular regional wall motion abnormality ( RWMA ) was assessed by transesophageal echocardiography at T1 and T2 time points . TNF-alpha was detectable only in the control group in arterial sample s at T3 . IL-6 levels ( pg/mL ) were found to be lower in the sevoflurane group compared with controls at T2 arterial circulation ( 38.2 + /- 21.1 v 60.6 + /- 19.1 , p < 0.05 ) as well as in the coronary circulation ( 38.4 + /- 19.9 v 118.2 + /- 23.5 , p < 0.01 ) at T2 . CD11b/CD18 increased 79 % after CPB in the control group while only increasing 36 % in the sevoflurane group ( p < 0.05 ) . The post-CPB LVSWI was back to its baseline values in the sevoflurane group , whereas it was still significantly depressed in the control group . Eight of 10 patients in the control group showed a transient new-onset RWMA in either the septal or anteroseptal regions . Only 2 of 11 patients in the sevoflurane group showed transient RWMA of the LV . CONCLUSIONS Sevoflurane decreases the inflammatory response after CPB , as measured by the release of IL-6 , CD11b/CD18 , and TNF-alpha . Myocardial function after CPB , as assessed by RWMA and LVSWI , was also improved with sevoflurane . The role of sevoflurane in myocardial protection and the inflammatory response to myocardial reperfusion should be considered", "PURPOSE The benefits of intraoperative administration of halogenated agents in patients undergoing cardiac surgery have been shown by numerous studies . The mechanisms of preconditioning and postconditioning appear to be the cause of these benefits . The possibility of maintaining the early postoperative sedation with halogenated agents , after its intraoperative administration , can increase their benefits . PATIENTS AND METHODS This is a prospect i ve trial with 60 patients undergoing coronary artery bypass graft surgery divided into 3 groups according to the administration of hypnotic drugs in the intraoperative and postoperative periods ( sevoflurane , sevoflurane : SS , sevoflurane-propofol : SP , propofol-propofol : PP ) . For the first 48 hours , hemodynamic parameters , the need for inotropic drugs , N-terminal pro-brain natriuretic peptide , and troponin I plasmatic concentrations were obtained . RESULTS There were significant differences between group SS and the other 2 groups in the levels of N-terminal pro-brain natriuretic peptide ( SS [ 501±280 pg/mL ] compared with SP [ 1270±498 pg/mL ] and PP [ 1775±527 pg/mL ] [ P<.05 ] ) and troponin I ( SS [ 0.5±0.4 ng/mL ] compared with SP [ 1.61±1.30 ng/mL ] and PP [ 2.27±1.5 ng/mL ] [ P<.05 ] ) and a lower number of inotropic drugs . CONCLUSION Sevoflurane administration in patients undergoing off-pump coronary artery bypass graft , in the operating room and the intensive care unit , decreases myocardial injury markers compared with patients who only received sevoflurane in the intraoperative period , but both were a better option to decrease levels of myocardial markers when compared with the propofol group", "OBJECTIVE Cardioprotective properties have been shown with halogenated volatile agents . It was hypothesized that low-dose isoflurane administered before aortic cross-clamping may reduce the amount of dobutamine required to improve impaired postoperative cardiac function after various types of cardiac surgery . DESIGN A prospect i ve , r and omized trial . SETTING An anesthesia and intensive care unit , university hospital . PARTICIPANTS Two hundred eighty cardiac surgery patients . INTERVENTIONS All patients allocated to either isoflurane treatment ( T ) or no treatment ( control group [ C ] ) received total intravenous anesthesia . In the treatment group , isoflurane was administered at a 0.5 minimum alveolar concentration ( MAC ) from tracheal intubation to initiation of cardiopulmonary bypass ( CPB ) . During weaning from CPB , dobutamine was introduced by using a hemodynamically driven decision tree . MEASUREMENTS AND MAIN RESULTS The number of patients receiving dobutamine was comparable ( 66 v 78 , p = 0.07 , in T and C groups , respectively ) . The total amount of postoperative dobutamine indexed to patient weight , considered as the primary endpoint , was reduced in the isoflurane-treated group ( 4.2 + /- 8 v 7.2 + /- 15 , p < 0.02 , in T and C , respectively ) . Isoflurane was identified as an independent variable significantly ( odds ratio [ confidence interval ] ) influencing the total amount of postoperative dobutamine ( 0.53 [ 0.31 - 0.92 ] , p < 0.02 ) . Postoperative troponin I release at 20 hours was not affected by isoflurane treatment . CONCLUSIONS This study revealed that exposure to 0.5 MAC isoflurane before CPB reduced the total amount of dobutamine required to normalize postoperative cardiac dysfunction in various types of cardiac surgical patients", "OBJECTIVE To determine whether sevoflurane , because of its lower blood/gas partition coefficient , compared with isoflurane as the primary anesthetic agent , allows earlier tracheal extubation and assessment of cognitive function after off-pump coronary artery bypass ( OPCAB ) surgery . DESIGN Prospect ively , patients were r and omly assigned to receive sevoflurane or isoflurane as their primary anesthetic . Intraoperative opioids were limited to 5 microg/kg of fentanyl . SETTING Two university hospitals with active cardiac surgery programs . PARTICIPANTS One hundred one OPCAB surgery patients who met inclusion ary and exclusionary criteria participated with institutional review board approval . INTERVENTIONS Mini-Mental Status Examination , Memory Recall Test , and Observer Assessment of Anxiety and Sedation scales were administered preoperatively , postextubation , at 90 minutes , and between 12 to 24 hours . Pain scores were obtained every 15 minutes after extubation for 90 minutes . MEASUREMENTS AND MAIN RESULTS Sevoflurane patients were extubated earlier than isoflurane patients ( Sevo , 176 + /- 217 minutes and Iso , 257 + /- 279 min , p = 0.02 ) . Although both agents produced similar postanesthetic cognitive profiles , cognitive testing occurred approximately 90 minutes earlier in the sevoflurane group . Verbal rating scale for pain scores > 5 were more frequent for sevoflurane than isoflurane patients ( p = 0.03 ) . CONCLUSIONS Both sevoflurane and isoflurane may be safely used as maintenance agents in OPCAB . Sevoflurane has the advantage of allowing earlier extubation and evaluation of cognitive and neurologic function after OPCAB", "Background : Volatile anesthetics protect the myocardium during coronary surgery . This study hypothesized that the use of a volatile agent in the anesthetic regimen would be associated with a shorter intensive care unit ( ICU ) and hospital length of stay ( LOS ) , compared with a total intravenous anesthetic regimen . Methods : Elective coronary surgery patients were r and omly assigned to receive propofol ( n = 80 ) , midazolam ( n = 80 ) , sevoflurane ( n = 80 ) , or desflurane ( n = 80 ) as part of a remifentanil-based anesthetic regimen . Multiple logistic regression analysis was used to identify the independent variables associated with a prolonged ICU LOS . Results : Patient characteristics were similar in all groups . ICU and hospital LOS were lower in the sevoflurane and desflurane groups ( P < 0.01 ) . The number of patients who needed a prolonged ICU stay ( > 48 h ) was also significantly lower ( propofol : n = 31 ; midazolam : n = 34 ; sevoflurane : n = 10 ; desflurane : n = 15 ; P < 0.01 ) . Occurrence of atrial fibrillation , a postoperative troponin I concentration greater than 4 ng/ml , and the need for prolonged inotropic support ( > 12 h ) were identified as the significant risk factors for prolonged ICU LOS . Postoperative troponin I concentrations and need for prolonged inotropic support were lower in the sevoflurane and desflurane group ( P < 0.01 ) . Postoperative cardiac function was also better preserved with the volatile anesthetics . The incidence of other postoperative complications was similar in all groups . Conclusions : The use of sevoflurane and desflurane result ed in a shorter ICU and hospital LOS . This seemed to be related to a better preservation of early postoperative myocardial function", "Objectives . To compare the cardioprotective effects of anesthetic preconditioning by isoflurane with ischemic preconditioning . Methods . A total of 45 patients scheduled for elective coronary artery bypass graft ( CABG ) surgery were r and omized to preconditioning either by 3 episodes of 1-minute aortic cross-clamping followed by 4 minutes of reperfusion after each episode , a 10-minute exposure to isoflurane 2.5 % followed by 5 minutes of washout , or no preconditioning technique ( control group ) . Hemodynamic data , cardiac troponin I ( cTnI ) , creatine kinase isoenzyme MB ( CK-MB ) release , need for inotropic support , hospital stay , and adverse cardiac events were measured and recorded . Results . Preconditioned patients showed marked improvement in hemodynamic data , less need for inotropic support , and less postoperative increase in the serum levels of CK-MB and cTnI. No significant difference in hospital stay was found . Also , 4 patients in the control group had adverse cardiac events versus 1 patient in the isoflurane and ischemic groups in 1 year of follow-up . Conclusions . Based on this very small sample size , these data support a cardioprotective effect of isoflurane and ischemic preconditioning during CABG surgery", "Abstract Objective . We investigated the myocardial protective effect of sevoflurane in patients receiving off-pump coronary artery bypass grafting ( OPCABG ) and the role of brain natriuretic peptide ( BNP ) . Design . Forty-eight patients receiving elective OPCABG were r and omly assigned to a control group , and to 0.75 MAC , 1.0 MAC and 1.5 MAC sevoflurane groups . Blood sample s were collected and levels of BNP and cardiac troponin I ( cTnI ) were measured before anesthesia , and immediately , 24 , 48 and 72 h after surgery . Results . Dopamine was necessary to maintain blood pressure in the sevoflurane groups , but not in the control group ( p < 0.002 ) . 1.0 MAC sevoflurane significantly decreased post-surgical cTnI levels ( p < 0.001 ) . 0.75 MAC had no significant effect , and increasing sevoflurane concentrations to 1.5 MAC caused no further decrease in cTnI concentrations . There was no significant difference in BNP level among the groups ( p = 0.227 ) or between any two groups , although values of BNP showed a significant correlation with cTnI values in control subjects immediately after ( r = 0.847 ) and 24 h after ( r = 0.661 ) surgery . Conclusions . Our results demonstrated that 1.0 MAC and 1.5 MAC sevoflurane can exert a significant myocardial protective effect . BNP can not be used to predict the myocardial protective effect of sevoflurane in OPCABG", "AIMS AND OBJECTIVES The objective of the study was to evaluate the myocardial protective effect of volatile agents-sevoflurane and desflurane versus total intravenous anesthesia ( TIVA ) with propofol in offpump coronary artery bypass surgery ( OPCAB ) by measuring cardiac troponin-T ( cTnT ) as a marker of myocardial cell death . MATERIAL S AND METHODS The study was conducted on 139 patients scheduled to undergo elective OPCAB surgery . The patients were r and omly allocated to receive anesthesia with sevoflurane , desflurane or TIVA with propofol . The cTnT levels were measured preoperatively , at arrival in postoperative intensive care unit , at 8 , 24 , 48 and 96 hours thereafter . RESULTS The changes in cTnT levels at all time intervals were comparable in the three groups . CONCLUSION The study did not reveal any difference in myocardial protection after OPCAB with either sevoflurane or desflurane or TIVA using propofol as assessed by measuring serial cTnT values", "Background and objectives : Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practice d routinely . Experimentally , isoflurane , a commonly used volatile anaesthetic agent , provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning . The aim of our study was to investigate whether pre‐ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery . Methods : Forty patients scheduled for elective coronary artery bypass graft operations were prospect ively r and omized into the control or isoflurane groups . In the isoflurane group , isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5‐min washout period before aortic cross‐clamping . The control group received a time‐matched period of isoflurane‐free cardiopulmonary bypass . The conduction of anaesthesia and surgery were st and ardized in all patients . Haemodynamic data , troponin I release and inotropic support were measured and recorded perioperatively . Results : There were no adverse effects related to isoflurane administration . In the isoflurane group , the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre‐bypass value ( P < 0.05 ) , whereas no difference was found in the control group . At 15 min after cardiopulmonary bypass and 6 h after surgery , the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group ( P < 0.05 ) . There was a consistently lower release of troponin I in the isoflurane group compared to the control group . Compared to the controls , the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery ( P = 0.042 ) . Conclusions : The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinical ly feasible and providing optimal cardiac protection", "OBJECTIVE Volatile anesthetics reduce the risk of myocardial infa rct ion and mortality in coronary artery surgery . Recently , the American College of Cardiology/American Heart Association Guidelines suggested the use of volatile anesthetic agents for the maintenance of general anesthesia during noncardiac surgery in patients at risk for perioperative myocardial ischemia , but no r and omized experience to document the cardioprotective effects of these agents exists in this setting . Therefore , the authors performed a prospect i ve , r and omized , controlled trial to compare the effects of sevoflurane versus total intravenous anesthesia , in terms of postoperative cardiac troponin I release in patients undergoing noncardiac surgery . DESIGN A r and omized , controlled trial . SETTING A teaching hospital . PARTICIPANTS Eighty-eight consecutive patients undergoing noncardiac surgery . INTERVENTIONS Patients were allocated r and omly to receive either volatile anesthetic ( 44 patients ) as the main anesthetic agent or total intravenous anesthesia ( TIVA ) ( 44 patients ) . MEASUREMENTS Postoperative cardiac troponin I release was measured as a marker of myocardial necrosis . Patients with detectable postoperative troponin I in the sevoflurane group ( 12/44 , 27.3 % ) were similar to those in the propofol group ( 9/44 , 20.5 % ; p = 0.6 ) . There was no significant reduction of postoperative median peak cTnI release ( 0.16 ± 0.71 ng/mL in the sevoflurane group compared with the TIVA group , 0.03 ± 0.08 ng/mL ; p = 0.4 ) . Three patients died at the 1-year follow-up for noncardiac causes ( 2 in the TIVA group ) . CONCLUSIONS In the authors ' experience , patients undergoing noncardiac surgery did not benefit from anesthesia based on halogenated anesthetics . Further studies are necessary to evaluate the cardioprotective effects of volatile agents in noncardiac surgery", "A RECURRING decision that has to be made in planning a controlled clinical trial of a new treatment is the size of the patient sample necessary . In this decision , a major determinant is ethical , fo ...", "Volatile anaesthetics have been shown to exert cardioprotective properties in experimental and clinical studies . However , the mode of administration may influence these cardioprotective effects . The present study was design ed to compare the effect of interrupted administration of sevoflurane before cardiopulmonary bypass with continuous sevoflurane administration and with propofol‐only anaesthesia , on cardioprotection as assessed by left ventricular performance and myocardial cell damage during coronary artery bypass grafting . Forty‐two patients scheduled for coronary bypass surgery were r and omly assigned to one of three groups : propofol‐only ( P ; n = 14 ) , continuous ( SevoC ; n = 14 ) and interrupted sevoflurane administration ( SevoI ; n = 14 ) . Myocardial cell damage as assessed by Troponin T ( cTNT ) and creatine kinase MB ( CK‐MB ) were chosen as the primary endpoints and echocardiographic myocardial performance index ( MPI ) measurements were also performed . Up to 48 h postoperatively , in group SevoI , postoperative cTNT values ( mean ( SD ) 0.13 ( 0.04 ) ng.ml−1 ) were significantly ( p < 0.05 ) lower than both the P ( 0.26 ( 0.31 ) ng.ml−1 ) and SevoC ( 0.25 ( 0.17 ) ng.ml−1 ) groups . CK‐MB levels were also significantly ( p < 0.05 ) lower in the SevoI group at 24 h after surgery and MPI significantly improved compared with both the P and SevoC groups . There was , however , no difference with respect to cytokine release and length of stay in either the intensive care unit or in the hospital . We conclude that prior interrupted sevoflurane administration confers some cardioprotection as compared with continuous sevoflurane administration or propofol‐based anaesthesia", "The purpose of the investigation was to study whether isoflurane and sevoflurane might be used for pharmacological myocardial preconditioning ( PMP ) in patients with coronary heart disease during myocardial revascularization on the working ( Part I ) and arrested ( Part II ) heart and to develop a possible procedure for PMP . Part I deals with the study of the effect of PMP with halogen-containing anesthetics during myocardial revascularization on the working heart . The study included 66 patients who were divided into 4 groups ; 1 ) sevoflurane feeding was started just after anesthesia induction and it lasted until some coronary arteries were ligated ; 2 ) sevoflurane was fed for 15 min ; 3 ) isoflurane was used ; 4 ) controls . The markers of myocardial lesion ( troponin T , I ) were measured and the incidence of perioperative myocardial ischemia and needs for inotropic support were also analyzed . Part II was dedicated to the study of the effect of PMP during myocardial revascularization under extracorporeal circulation ( EC ) . The study covered 65 patients who were divided into 4 groups ; 1 ) sevoflurane was administered throughout the anesthesia until the aorta was ligated ; 2 ) it was used for 15 min before aortic ligation ; 3 ) sevoflurane was employed only to induce anesthesia ; 4 ) controls . The variables similar to those in Part I of the investigation were chosen to assess the results of this study . The use of sevoflurane and isoflurane reduces a risk for myocardial ischemic lesion during myocardial revascularization both under EC and on the working heart . Short-term ( 15-min ) use of an agent before myocardial ischemia suffices for PMP to develop its effect . The effect of PMP has its duration that is 76 min , as shown by our findings", "BACKGROUND Experimental studies indicate that isoflurane , a commonly used volatile anesthetic , mimics the cardioprotective effects of ischemic preconditioning , probably through ATP-sensitive K+ ( KATP ) channel activation . The aim of this study was to evaluate the impact of isoflurane during coronary bypass surgery ( CABG ) on troponin I release . MATERIAL AND METHODS Forty consecutive patients with chronic stable angina and multivessel disease undergoing isolated CABG were r and omized to a control ( 16 men and 4 women , aged 51 to 73 years , mean 62 ) or isoflurane ( 15 men and 5 women , aged 51 to 77 years , mean 65 ) group before aortic cross-clamping and cardioplegia . Serum levels of troponin I and creatine kinase (CK)-MB , as markers of ischemic injury , were obtained at 24 hours after CABG . Regional wall motion score and left ventricular ejection fraction ( LVEF ) at transthoracic echocardiography were assessed 5 days postoperatively . Comparisons between groups were performed in the entire population and , subsequently , in those patients with preoperative LVEF < 50 % . RESULTS There were no significant differences between isoflurane-treated patients and controls in cross-clamp time ( 49 + /- 14 vs 51 + /- 13 min , p = ns ) , peak values of troponin I ( 0.9 + /- 0.7 vs 1.4 + /- 1.3 ng/ml , p = ns ) and CK-MB ( 62 + /- 27 vs 64 + /- 27 U/l , p = ns ) , or postoperative echocardiographic score ( 26 + /- 7 vs 22 + /- 5 , p = ns ) and LVEF ( 53 + /- 10 vs 55 + /- 7 % , p = ns ) . When the comparisons were restricted to those patients with preoperative LVEF < 50 % , at 24 hours the isoflurane-treated patients exhibited a smaller release of troponin I and of CK-MB than controls ( 1.1 + /- 0.7 vs 2.3 + /- 1.3 ng/ml , p = 0.03 , and 39 + /- 10 vs 57 + /- 22 U/l , p = 0.04 , respectively ) . CONCLUSIONS Isoflurane reduces myocardial injury in patients with impaired left ventricular function undergoing CABG ; thus , it can be safely used as an additional cardioprotective tool during routine CABG in high-risk patients with poor left ventricular function", "In several recent clinical trials on cardiac surgery patients , remote ischaemic preconditioning ( RIPC ) showed a powerful myocardial protective effect . However , the effect of RIPC has not been studied in patients undergoing off-pump coronary artery bypass graft surgery . We evaluated whether RIPC could induce myocardial protection in off-pump coronary artery bypass graft surgery patients . Patients undergoing elective off-pump coronary artery bypass graft surgery were r and omly allocated to the RIPC ( n=65 ) or control group ( n=65 ) . After induction of anaesthesia , RIPC was induced by four cycles of five-minute ischaemia and reperfusion on the upper limb using a pneumatic cuff . Anaesthesia was maintained with sevoflurane , remifentanil and vecuronium . Myocardial injury was assessed by troponin I before surgery and 1 , 6 , 12 , 24 , 48 and 72 hours after surgery . There were no statistical differences in troponin I levels between RIPC and control groups ( P=0.172 ) . Although RIPC reduced the total amount of troponin I ( area under the curve of troponin increase ) by 26 % , it did not reach statistical significance ( RIPC group 53.2∓72.9 hours.ng/ml vs control group 67.4∓97.7 hours.ng/ml , P=0.281 ) . In this study , RIPC by upper limb ischaemia reduced the postoperative myocardial enzyme elevation in offpump coronary artery bypass graft surgery patients , but this did not reach statistical significance . Further study with a larger number of patients may be needed to fully evaluate the clinical effect of RIPC in off-pump coronary artery bypass graft surgery patients", "OBJECTIVE The effects of sevoflurane on proinflammatory cytokines related to ischemic-reperfusion injury are not clear . The hypothesis was tested that sevoflurane decreases myocardial ischemic-reperfusion injury by suppressing proinflammatory cytokines . DESIGN Prospect i ve , r and omized study . SETTING A medical university heart center . PARTICIPANTS Twenty-three patients undergoing coronary artery bypass surgery allocated r and omly into 2 groups . INTERVENTIONS Anesthesia for 23 patients undergoing coronary artery bypass surgery was maintained using either fentanyl ( 30 microg/kg ) with propofol ( 2 - 8 mg/kg/h ) in the control group ( n = 10 ) or fentanyl ( 30 microg/kg ) with 0.5 % to 1.0 % sevoflurane in the sevoflurane group ( n = 13 ) . MEASUREMENTS AND MAIN RESULTS Interleukin (IL)-6 , IL-8 , IL-10 , and IL-1 receptor antagonist ( IL-1ra ) were measured by enzyme-linked immunosorbent assay . Troponin-T and creatine kinase-MB isoenzyme ( CK-MB ) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry , respectively . Serum IL-6 and IL-8 concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta ( p < 0.001 ) . The increases were greater in the control group than in the sevoflurane group ( p < 0.05 ) . Serum IL-10 and IL-1ra concentrations in both groups increased significantly over baseline from 60 minutes after declamping the aorta ( p < 0.001 ) . There were no differences between the two groups . Serum troponin-T and CK-MB concentrations increased significantly in both groups from 60 minutes after declamping the aorta ( p < 0.001 ) ; the increases were greater in the control group ( p < 0.05 ) . CONCLUSION Sevoflurane suppressed the production of IL-6 and IL-8 , but not IL-10 and IL-1ra . Changes in the balance between pro- and anti-inflammatory cytokines may be one of the most important mechanisms of myocardial protection caused by sevoflurane", "BACKGROUND Whether remote ischaemic preconditioning , an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia , is beneficial for patients undergoing coronary artery bypass graft surgery is unknown . We did a single-blinded r and omised controlled study to establish whether remote ischaemic preconditioning reduces myocardial injury in these patients . METHODS 57 adult patients undergoing elective coronary artery bypass graft surgery were r and omly assigned to either a remote ischaemic preconditioning group ( n=27 ) or to a control group ( n=30 ) after induction of anaesthesia . Remote ischaemic preconditioning consisted of three 5-min cycles of right upper limb ischaemia , induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg , with an intervening 5 min of reperfusion during which the cuff was deflated . Serum troponin-T concentration was measured before surgery and at 6 , 12 , 24 , 48 , and 72 h after surgery . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00397163 . FINDINGS Remote ischaemic preconditioning significantly reduced overall serum troponin-T release at 6 , 12 , 24 , and 48 h after surgery . The total area under the curve was reduced by 43 % , from 36.12 microg/L ( SD 26.08 ) in the control group to 20.58 microg/L ( 9.58 ) in the remote ischaemic preconditioning group ( mean difference 15.55 [ SD 5.32 ] ; 95 % CI 4.88 - 26.21 ; p=0.005 ) . INTERPRETATION We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary centre could benefit from remote ischaemic preconditioning , using transient upper limb ischaemia", "BACKGROUND Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infa rct size . The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass ( CPB ) has a cardioprotective effect in patients undergoing coronary surgery . METHODS Seventy-two patients were r and omized in two centres . The intervention group ( S ) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB , the control group did not . The primary outcome was the postoperative troponin Ic peak . A biopsy of the atrium was taken during canulation for enzyme dosages . Results are expressed as mean ( SD ) . RESULTS Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups : peak of troponin Ic was 4.4 ( 5.6 ) in S group vs 5.2 ( 6.6 ) ng ml(-1 ) in control group ( ns ) . Intratissular ecto-5'-nucleotidase activity was 7.1 ( 4.3 ) vs 8.5 ( 11.9 ) , protein kinase C activity was 27.1 ( 15.7 ) vs 29.2 ( 28.7 ) , tyrosine kinase activity was 101 ( 54.1 ) vs 98.5 ( 63.3 ) , and P38 MAPKinase activity was 131.1 ( 76.1 ) vs 127.1 ( 86.8 ) nmol mg protein(-1 ) min(-1 ) in S group and control group , respectively ( ns ) . However there were fewer patients with low postoperative cardiac index in S group ( 11 % in S vs 35 % in control group , P < 0.05 ) when considering the per protocol population . In S group , 25 % of patients required an inotropic support during the postoperative period , vs 36 % of patients in control group ( ns ) . CONCLUSIONS This study did not show a significant preconditioning signal after 15 min of sevoflurane administration . The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels", "Background / Aims : Study eluci date s and compares the mitochondrial bioenergetic-related molecular basis of sevoflurane and propofol cardioprotection during aortic valve replacement surgery due to aortic valve stenosis . Methods : Twenty-two patients were prospect ively r and omized in two groups regarding the anesthetic regime : sevoflurane and propofol . Hemodynamic parameters , biomarkers of cardiac injury and brain natriuretic peptide ( BNP ) were measured preoperatively and postoperatively . In tissue sample s , taken from the interventricular septum , key mitochondrial molecules were determined by Western blot , real time PCR , as well as confocal microscopy and immunohisto- and immunocyto-chemical analysis . Results : The protein levels of cytochrome c oxidase and ATP synthase were higher in sevoflurane than in propofol group . Nevertheless , cytochrome c protein content was higher in propofol than sevoflurane receiving patients . Propofol group also showed higher protein level of connexin 43 ( Cx43 ) than sevoflurane group . Besides , immunogold analysis showed its mitochondrial localization . The mRNA level of mtDNA and uncoupling protein ( UCP2 ) were higher in propofol than sevoflurane patients , as well . On the other h and , there were no significant differences between groups in hemodynamic assessment , intensive care unit length of stay , troponin I and BNP level . Conclusions : Our data indicate that sevoflurane and propofol lead to cardiac protection via different mitochondrially related molecular mechanisms . It appears that sevoflurane acts regulating cytochrome c oxidase and ATP synthase , while the effects of propofol occur through regulation of cytochrome c , Cx43 , mtDNA transcription and UCP2", "Background and objectives : Volatile anaesthetics have gained more popularity recently due to the potential for cardiac protection . Ultra‐fast‐track anaesthesia implies the immediate extubation after cardiac surgery . The purpose of this prospect i ve r and omized double‐blind controlled study is to compare the cardioprotective effects of sevoflurane and isoflurane in off‐pump cardiac bypass surgery . Methods : Forty patients undergoing elective off‐pump cardiac bypass surgery with high thoracic epidural analgesia and immediate extubation at the end of surgery were r and omized into two groups . During surgery , anaesthesia was provided with either 1 minimum alvelolar anaesthetic concentration of sevoflurane or 1 minimum alvelolar anaesthetic concentration of isoflurane . Troponin‐T , creatine kinase‐MB , left ventricular wall motion anomalies , time to extubation , respiratory functions and haemodynamic parameters were compared between the two groups by analysis of variance . Results : All patients were successfully extubated in the operating theatre with minimal postoperative pain . Serial creatine kinase‐MB and troponin‐T concentrations were not significantly different between the two volatile agents . Haemodynamic stability throughout surgery and contractility was not different between groups . However , extubation time was significantly shorter with sevoflurane ( 10 ± 5 min ) compared to isoflurane ( 18 ± 4 min ) . Conclusion : This study indicates that during off‐pump cardiac bypass surgery , sevoflurane and isoflurane provide the same ischaemic cardioprotective effects . There is no difference for heart contractility and haemodynamic values during and after off‐pump cardiac bypass surgery between the two agents . Sevoflurane allows a more rapid recovery from anaesthesia , but this does not translate into better pulmonary function or haemodynamics . Both agents are similar in ultra‐fast‐track off‐pump cardiac bypass surgery", "In coronary surgery patients the use of a volatile anesthetic regimen with sevoflurane was associated with a better recovery of myocardial function and less postoperative release of troponin I. In the present study we investigated whether these cardioprotective properties were also apparent in the cardiac surgical setting of aortic valve replacement ( AVR ) surgery for the correction of aortic stenosis . Thirty AVR surgery patients were r and omly assigned to receive either target-controlled infusion of propofol or inhaled anesthesia with sevoflurane . Cardiac function was assessed perioperatively using a pulmonary artery catheter . Perioperatively , a high-fidelity pressure catheter was positioned in the left ventricle . Postoperative concentrations of cardiac troponin I were followed for 48 h. After cardiopulmonary bypass ( CPB ) , stroke volume and dP/dtmax were significantly higher in the patients with sevoflurane . Post-CPB , the effects of an increase in cardiac load on dP/dtmax were similar to pre-CPB in the sevoflurane group ( 1.0 % ± 5.4 % post-CPB versus 1.3 % ± 8.6 % pre-CPB ) but more depressed in the propofol group ( −8.2 % ± 4.4 % post-CPB versus 0.1 % ± 4.9 % pre-CPB ) . The rate of relaxation was significantly slower post-CPB in the propofol group . Postoperative levels of troponin I were significantly lower in the sevoflurane group . Our data indicate that the use of a volatile anesthetic regimen in AVR surgery was associated with better preservation of myocardial function and a reduced postoperative release of troponin", "OBJECTIVE Myocardial ischemic damage is reduced by volatile anesthetics in patients undergoing coronary artery bypass graft surgery . The authors tested the hypothesis that low-dose sevoflurane could decrease perioperative myocardial damage , as measured by cTnI release , when compared with placebo , in patients undergoing interventional cardiology procedures . DESIGN A single-blind , r and omized controlled trial . SETTING A university hospital . PARTICIPANTS Thirty patients undergoing stenting procedures ( May 2005 ) were included in the present study . INTERVENTIONS The authors r and omly assigned 16 patients to breathe sevoflurane ( expired end-tidal concentration 1 % ) and 14 patients to breathe a placebo oxygen/air mix before stenting procedures . MEASUREMENTS AND MAIN RESULTS Postprocedural cardiac troponin I release was measured as a marker of myocardial necrosis . Sixteen patients had detectable cardiac troponin I levels after stenting procedures , with no difference between groups : 10 in the sevoflurane group ( 16 patients ) versus 6 in the placebo group ( 14 patients ) ( p = 0.3 ) . No difference in the amount of postprocedural median ( interquartile range ) cardiac troponin I release was noted between the sevoflurane group , 0.15 ( 0 - 4.73 ) ng/mL , and the placebo group , 0.14 ( 0 - 0.87 ) ng/mL ( p = 0.4 ) . CONCLUSIONS Myocardial damage measured by cardiac troponin release was not reduced by the volatile anesthetic sevoflurane during interventional cardiology procedures in this study" ]
"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"
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[ "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" ]
[ "BACKGROUND Prophylaxis for venous thromboembolism is routinely performed for all patients undergoing bariatric surgery . However , there is disagreement regarding the optimal dosing and duration of anticoagulant therapy . Furthermore , there is little data regarding the incidence of asymptomatic deep venous thrombosis ( DVT ) in this population . Our objective was to conduct a pilot r and omized double blind study to evaluate the pharmacodynamic parameters of 2 different anticoagulation medications ( enoxaparin and fondaparinux ) administered to patients undergoing bariatric surgery . METHODS From July 2010 to August 2013 , 198 consecutive bariatric surgery patients from an academic institution were r and omized in a double blinded manner to receive either 40 mg enoxaparin twice daily or 5 mg fondaparinux sodium once daily . Antifactor Xa activity was measured on all patients in both study arms , 3 hours after the first dose ( on the day of the operation ) , immediately before the second dose ( postoperative day one ) , and 3 hours after the second dose . At the routine 2 week postoperative visit , patients underwent magnetic resonance venography ( MRV ) to detect DVT . The primary outcome was attainment of therapeutic antifactor Xa levels . The secondary outcome was DVT , as detected by MRV . Safety outcomes were perioperative bleeding , perioperative complications , and death . RESULTS Of 198 patients r and omized , 177 underwent MRV and 137 had interpretable antifactor Xa levels . Nearly half of the patients ( 47.4 % ) did not attain target prophylactic antifactor Xa levels . Adequate antifactor Xa levels were more common with fondaparinux ( 74.2 % ) than with enoxaparin ( 32.4 % ) . Antifactor Xa levels were also associated with preoperative D-dimer level . 4 of the 175 patients who underwent MRV developed DVT , 2 in each arm of the study . No major adverse events occurred in either arm . CONCLUSION Fondaparinux was much more likely to produce target prophylactic antifactor Xa levels than enoxaparin . Both regimens appear to be equally effective at reducing the risk of DVT . Further prospect i ve studies are needed to determine the optimal DVT prophylaxis regimen in the bariatric surgical population", "Background The incidence of venous thromboembolism ( VTE ) after bariatric surgery is uncertain . Methods Using the re sources of the Rochester Epidemiology Project and the Mayo Bariatric Surgery Registry , we identified all residents of Olmsted County , Minnesota , with incident VTE after undergoing bariatric surgery from 1987 through 2005 . Using the date s of bariatric surgery and VTE events , we determined the cumulative incidence of VTE after bariatric surgery by using the Kaplan – Meier estimator . Cox proportional hazards modeling was used to assess patient age , sex , weight , and body mass index as potential predictors of VTE after bariatric surgery . Results We identified 396 residents who underwent 402 bariatric operations . The most common operation was an open Roux-en-Y gastric bypass ( n = 228 ) . Eight patients had VTE that developed within 6 months ( 7 within 1 month ) after surgery ; five events occurred after hospital discharge but within 1 month after bariatric surgery . The cumulative incidence of VTE at 7 , 30 , 90 , and 180 days was 0.3 , 1.9 , 2.1 , and 2.1 % , respectively ( 180-day 95 % confidence interval ( CI ) , 0.7–3.6 % ) . Patient age was a predictor of postoperative VTE ( hazard ratio , 1.89 per 10-year increase in age ; 95 % CI , 1.01–3.55 ; P = 0.05 ) . Conclusions In our population -based study , bariatric surgery had a high risk of VTE , especially for older patients . Because most VTE events occurred after hospital discharge , a r and omized controlled trial of extended outpatient thromboprophylaxis is warranted in patients undergoing open Roux-en-Y gastric bypass for medically complicated obesity", "Background Obese patients have a higher risk of venous thromboembolism when immobilized due to surgery . The objective of this study was to assess anti-factor Xa activity in adolescent bariatric surgical patients receiving prophylactic enoxaparin . Methods Four morbidly obese adolescents undergoing laparoscopic sleeve gastrectomy were enrolled . Enoxaparin was administered ( 40 mg subcutaneous ( SC ) if BMI ≤50 kg/m2 or 60 mg SC if BMI > 50 kg/m2 ) for prevention of venous thromboembolism every 12 h starting after induction of anesthesia until discharge . Plasma anti-factor Xa activity was assessed over 12 h after the first dose and used as a surrogate marker for enoxaparin levels . Non-compartmental analysis of anti-factor Xa activity levels was performed and compared with previously published studies . Results Patients recruited were 16 to 18 years of age with a mean BMI of 52.6 ± 5.8 kg/m2 ( > 99th BMI percentile ) . Peak anti-factor Xa activity ranged from 0.20 to 0.23 IU/mL in our study population , compared to 0.38 to 0.53 IU/mL in the cited lean comparator groups . Conclusions Our current dosing practice of 40 mg SC for individuals with a BMI ≤50 kg/m2 and 60 mg for individuals with a BMI ≥50 kg/m2 result ed in anti-factor Xa activity that was sufficient for adequate thromboprophylaxis in adolescent bariatric surgical patients . Our data also demonstrates lower drug exposures in the obese when compared to lean patients . Therefore , r and omized controlled efficacy and safety studies are urgently needed to guide the use of low-molecular-weight heparins in the pediatric and adolescent obese population", "BACKGROUND Venous thromboembolism ( VTE ) after laparoscopic bariatric surgery is a significant cause of morbidity and mortality . The objective of the present study was to study the incidence of symptomatic VTE in extended thromboprophylaxis regimens using dalteparin at an independent hospital in Engl and , United Kingdom . METHODS A prospect i ve data base of all patients undergoing bariatric surgery was retrospectively analyzed . All patients underwent VTE prophylaxis regimen using perioperative and extended postoperative low-molecular-weight heparin ( dalteparin 2500 IU preoperatively , followed by 5000 IU daily postoperatively ) . The treatment period was 1 week for laparoscopic gastric b and ing or 3 weeks for all other procedures . Inferior vena cava filters were used in selected patients with thrombophilia , a history of pulmonary embolism , or > 1 episode of deep vein thrombosis . The endpoint was the incidence of symptomatic VTE . RESULTS A total of 735 patients underwent laparoscopic bariatric surgery , all of whom received dalteparin . The postoperative VTE incidence was 0 % . The 30-day and 90-day all-cause mortality rate was 0 % . A total of 3 adverse bleeding events occurred . CONCLUSION An extended VTE prophylaxis regimen using low-molecular-weight heparin is simple and effective and was associated with a low incidence of bleeding complications", "BACKGROUND The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain , because clinical practice is different between countries and r and omized trials are lacking . OBJECTIVES The primary objective of this r and omized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles ( MPs ) . SETTING University hospital . METHODS A total of 164 patients scheduled for gastric bypass were allocated to 3 groups ( A , B , and C ) of enoxaparin treatment ( 4000 , 6000 , or 2 × 4000 IU , respectively ) . Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2 . Doppler screening of the lower limbs was performed at D1 , D9 , and D30 . Bleeding ( BE ) and thrombotic events ( TE ) were recorded during the first postoperative month . Total MPs were measured at D0 , D9 , and D30 . MPs of leucocyte , platelet , and granulocyte origin were assessed in one third of the patients from each group . The 3 groups were compared by ANOVA . RESULTS A total of 135 patients were analyzed . The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8 % , 56.4 % , and 27.3 % of the patients reached the target in groups A , B , and C , respectively ( P<.001 ) . No TE was detected . BE occurred in 1 , 2 , and 6 patients in groups A , B , and C , respectively ) . Total MPs remained unchanged over time . While no significant variation was observed in the other groups , platelet GP1 b(+)-MPs increased ( P = .01 ) at D9 in group C , suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 ( P = .04 ) . CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution . CONCLUSIONS This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk , with the most likely efficient reduction of procoagulant MPs . ( Surg Obes Relat Dis 2015;0:000 - 000 . ) © 2015 American Society for Metabolic and Bariatric Surgery . All rights reserved", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Objective : To compare two enoxaparin dosing strategies at achieving prophylactic anti-Xa levels in women with a body mass index ( BMI ) ⩾35 ( kg m−2 ) postcesarean delivery . Study Design : Women with BMI ⩾35 were r and omized to receive prophylactic enoxaparin at a fixed dose of 40 mg daily or weight-based dosing of 0.5 mg kg−1 twice daily . The primary outcome was the proportion of subjects with peak anti-Xa levels in the prophylactic range of 0.2 to 0.6 IU ml−1 . Result : From August 2013 through February 2014 , 84 demographically similar women completed the protocol . In the weight-based group , 88 % ( 37/42 ) of the women reached prophylactic anti-Xa levels versus 14 % ( 6/42 ) in the fixed dose group ( odds ratio 44.4 , 95 % confidence interval 12.44 , 158.48 , P<0.001 ) . No anti-Xa level exceeded 0.48 IU ml−1 . There were no venous thromboembolic or bleeding events requiring reoperation or transfusion in either group . Conclusion : Compared with fixed dosing daily , weight-based dosing twice daily more effectively achieved prophylactic anti-Xa levels without reaching the therapeutic range", "Background The optimal dose of low molecular weight heparin ( LMWH ) to prevent venous thromboembolism ( VTE ) after bariatric surgery remains controversial . The aim of this multicentre , open-label , pilot study was to evaluate the efficacy and safety of two different doses of the LMWH parnaparin administered to patients undergoing bariatric surgery . Methods Patients were r and omised to receive 4,250 IU/day ( group A ) or 6,400 IU/day ( group B ) of parnaparin s.c . for 7–11 days . Bilateral colour Doppler ultrasound of the lower limb was performed before surgery and at the end of the treatment period . The primary efficacy outcome was a composite of asymptomatic and symptomatic deep vein thrombosis , symptomatic pulmonary embolism and death from any cause during treatment . The primary safety endpoint was major and clinical ly relevant non-major bleeding . Results A total of 258 patients underwent r and omization ; 8 subjects were excluded following the safety analysis . One hundred thirty-one patients [ 106 females ; mean age , 40.3 years ( st and ard deviation ( SD ) ±9.6 ) ; mean body mass index ( BMI ) , 44.6 kg/m2 ( SD ±5.4 ) ] were assigned to group A and 119 patients [ 93 females ; mean age , 41.5 years ( SD ±9.9 ) ; mean BMI , 44.2 kg/m2 ( SD ±5.4 ) ] were assigned to group B. The rate of the primary efficacy outcome was 1.5 % ( two cases ; 95 % confidence interval ( CI ) , 0.2–6.0 % ) in group A as compared with 0.8 % ( one case ; 95 % CI , 0.4–5.3 % ) in group B ( p = ns ) . The composite incidence of major bleeding and clinical ly relevant non-major bleeding was 6.1 % ( eight cases ; 95 % CI , 2.9–12.1 % ) in group A and 5.0 % ( six cases ; 95 % CI , 2.1–11.1 % ) in group B ( p = ns ) . Conclusions A parnaparin dose of 4,250 IU/day seems suitable for VTE prevention in patients undergoing bariatric surgery", "OBJECTIVE : To compare the adequacy of venous thromboembolism prophylaxis based on anti-Xa concentrations between weight-based enoxaparin dosing and body mass index ( BMI ) –stratified dosing in morbidly obese women after cesarean delivery . METHODS : A prospect i ve sequential cohort study of women with BMI s of 40 or greater who underwent cesarean delivery was conducted . Participants received either weight-based or BMI -stratified enoxaparin dosing to prevent venous thromboembolism formation . The weight-based regimen was 0.5 mg/kg of enoxaparin every 12 hours . In the BMI -stratified regimen , women with BMI s of 40–59.9 received 40 mg enoxaparin every 12 hours and women with BMI s of 60 or greater received 60 mg every 12 hours . The primary outcome was an anti-Xa concentration in the adequate thromboprophylaxis range ( 0.2–0.6 international units/mL ) . Secondary outcomes included enoxaparin dosage , timing of dosing and anti-Xa concentration , estimated surgical blood loss , postoperative changes in hemoglobin and platelets , wound hematoma , and adverse reactions to enoxaparin . Univariate analysis was used to compare dosing regimens . RESULTS : Forty-two morbidly obese women received weight-based enoxaparin , and 43 received BMI -stratified dosing . Anti-Xa concentrations were significantly higher in the weight-based group compared with the BMI -stratified group ( 0.29±0.08 international units/mL compared with 0.17±0.07 international units/mL , P<.001 ) . Thirty-six participants ( 86 % ) on weight-based dosing had anti-Xa concentrations within the prophylactic range compared with 11 ( 26 % ) on BMI -stratified dosing ( P<.001 ) . No participant had an anti-Xa concentration of 0.6 international units/mL or greater , the therapeutic threshold for venous thromboembolism prophylaxis . CONCLUSION : In morbidly obese women after cesarean delivery , weight-based dosing of enoxaparin for venous thromboembolism prophylaxis is significantly more effective than BMI -stratified dosing in achieving adequate anti-Xa concentrations . LEVEL OF EVIDENCE :", "BACKGROUND We report our experience dosing and monitoring enoxaparin with anti-factor Xa activity ( anti-FXaA ) levels for venous thromboembolism prophylaxis in trauma patients ( TP ) . MATERIAL S AND METHODS TP receiving st and ard , non-weight-based dosed enoxaparin administered every 12 h for venous thromboembolism prophylaxis with peak anti-FXaA levels measured were prospect ively monitored and evaluated and those whose first anti-FXaA levels ≥ or < 0.2 IU/mL were compared . Anti-FXaA levels and enoxaparin dose ( mg/kg actual body weight ) were evaluated for correlation . RESULTS Of the fifty-one TP included , initial anti-FXaA levels were < 0.2 IU/mL in 37 ( 72.5 % ) whose dose was lower than those within target range ( 0.38 [ 0.32 - 0.42 ] mg/kg versus 0.45 [ 0.39 - 0.48 ] mg/kg , P = 0.003 ) . Thirty-seven TP achieved anti-FXaA level ≥0.2 IU/mL ( 23 requiring dose increases ) at a dose of 0.49 [ 0.44 - 0.54 ] mg/kg . Correlation between dose and anti-FXaA levels for the initial 51 anti-FXaA levels ( r = 0.360 , P = 0.009 ) and for all 103 anti-XaA levels ( r = 0.556 , P < 0.001 ) was noted . CONCLUSIONS Non-weight-based enoxaparin dosing did not achieve target anti-FXaA levels in most TP . Higher anti-FXaA levels correlated with larger weight-based enoxaparin doses . Weight-based enoxaparin dosing ( i.e. , 0.5 mg/kg subcutaneously every 12 h ) would better achieve target anti-FXaA levels", "BACKGROUND Morbidly obese patients undergoing gastric bypass surgery are at risk for postoperative venous thromboembolism . Evidence -based recommendations regarding the dosing and duration of thromboprophylaxis are lacking for morbidly obese surgical patients . The aims of this study were to evaluate the safety and efficacy of an extended duration , body mass index ( BMI ) -stratified enoxaparin thromboprophylaxis regimen in patients undergoing Roux-en-Y gastric bypass and to determine the result ant antifactor Xa ( AFXa ) activity in morbidly obese surgical patients . METHODS In this prospect i ve open trial , 223 patients ( 75 % female , mean BMI 50.4 kg/m2 ) undergoing Roux-en-Y gastric bypass were assigned to receive enoxaparin 40 mg ( BMI < or=50 kg/m2 ) , n = 124 ) or 60 mg ( BMI > 50 kg/m2 ) , n = 99 ) every 12 hours during hospitalization and once daily for 10 days after discharge . The AFXa levels were monitored serially , and dose adjustments were made for results outside the target prophylactic range ( .2-.4 IU/mL + /- 10 % ) after the third dose . The safety and efficacy outcomes were major bleeding and venous thromboembolism . RESULTS Roux-en-Y gastric bypass was performed laparoscopically in 208 subjects ( 93 % ) . The duration of surgery averaged 99.5 + /- 31 minutes , and the median length of hospitalization was 3 days . Target prophylactic AFXa concentration was achieved by 74 % of patients after the third enoxaparin dose ; none reached the full anticoagulation concentration . One patient developed nonfatal venous thromboembolism ( .45 % ) . Four patients required transfusion ( 1.79 % ) . Bleeding was not associated with a high AFXa concentration . CONCLUSION This BMI -stratified , extended enoxaparin dosing regimen provided well-tolerated , effective prophylaxis against venous thromboembolism in patients undergoing gastric bypass surgery", "BACKGROUND The optimal amount of thromboembolic prophylaxis to use in bariatric surgery is still unresolved . OBJECTIVE The aim of this study was to determine the optimal pharmacologic prophylaxis with minimal bleeding complications for bariatric patients . SETTING A nonr and omized clinical study of 400 consecutive bariatric patients surgically treated between 2008 and 2013 at Peijas Hospital . METHODS The patients , who either underwent mainly a sleeve gastrectomy or a Roux-en-Y gastric bypass , were divided consecutively into 3 subgroups with different approaches to pharmacologic enoxaparin prophylaxis . For the first 100 operated patients ( high-dose group ) , enoxaparin was given at a dose of 40 mg twice daily , starting 1 day before the operation . The next 100 patients ( intermediate-dose group ) received 40 mg of enoxaparin twice daily , without the dose on the morning of the operation . The last 200 patients ( low-dose group ) received enoxaparin 40 mg once daily , starting 1 day before the operation and without the dose on the morning of the operation . The primary endpoints in this study were a major bleeding complication and a venous thromboembolism . RESULTS There were no thromboembolic complications in this study . The difference in bleeding complications between the high-dose group and low-dose group was -10.5 % ( 95 % CI from -18.1 % to -3.0 % ) , and the difference between high-dose group and intermediate-dose group was -9 % ( 95 % CI from -17.4 % to -.6 % ) . Age and preoperative weight had no effect on bleeding complications , but hypertension significantly increased the amount of bleeding complications ( P = .01 , 95 % CI from 1.55 % to 29.7 % ) . CONCLUSION Thromboembolic complications are avoidable . Enoxaparin ( 40 mg ) given once daily was the safest with regard to bleeding complications . High blood pressure elevates the risk for bleeding", "Background There are limited data on appropriate dosing of low-molecular-weight heparins ( LMWHs ) for venous thromboembolism ( VTE ) prophylaxis in bariatric surgery . The primary objective of this preliminary study was to evaluate the preoperative effects of increasing doses of the LMWH parnaparin on coagulation in severely obese patients undergoing bariatric surgery . Methods Severely obese patients ( BMI > 50 kg/m2 ) were administered three increasing single doses of parnaparin ( 3200 , 4250 , and 6400 IU ) on the three consecutive days leading up to biliointestinal bypass surgery . Activated partial thromboplastin time ( APTT ) , anti-factor IIa and anti-factor Xa levels were measured 1 h before and 4 h after dosing . The highest dose ( 6400 IU/day ) was continued from the day of surgery until day 30 ( recovery period ) . Intermittent pneumatic compression and stockings were applied during surgery and the recovery period , respectively . Lower limb echoDoppler and phleboscintigraphy , and pulmonary scintigraphy were used for VTE detection . Results Ten patients ( mean BMI 52.4 kg/m2 ) were recruited into this study . During the preoperative dosing phase , parnaparin dose-dependently prolonged APTT , with the 6400 IU dose significantly prolonging APTT versus the lower doses . Meanwhile , anti-factor Xa and anti-factor IIa activity was increased by the 4250 and 6400 IU doses . After surgery , one patient with heparin resistance experienced pulmonary embolization . No bleeding complications were observed . Conclusion The dose – response data reported in this preliminary study suggest that parnaparin doses of 4250 and 6400 IU may provide effective prophylaxis for VTE in patients undergoing bariatric surgery . However , given the small number of patients , larger , well-controlled trials are required to confirm these findings", "Background : Obese patients undergoing bariatric surgery are at a high risk of developing fatal pulmonary embolism or post-thrombotic syndrome . The prophylactic use of low molecular weight heparins ( LMWHs ) is correlated with a significant reduction in post-operative venous thrombosis in patients undergoing orthopedic or general surgery . In morbidity obese patients , the limited number of comparative trials are too sparse to allow a consensus on the effective dose and dosing schedule . Methods : In a prospect i ve study to evaluate the effect of two doses of nadroparin as prophylaxis for venous thromboembolism following bariatric surgery , 60 consecutive patients undergoing Rouxen-Y gastric bypass were r and omized to receive either 0.6 ml ( 5700 IU ) or 1.0 ml ( 9500 IU ) of nadroparin started pre-operatively and then given once daily post-operatively until discharge . Results : No statistically significant differences between the two groups were detected in any of the measured coagulation parameters either preoperatively or at days 1 , 3 and 5 postoperatively . No thrombotic events were observed pre- or post- operatively , and no patient developed meta-thrombotic syndrome at the 3 and 6 months follow-up . No bleeding events occurred in the patients given the lower dose compared with two major hemorrhages in those given the higher dose . Conclusion : Our results indicate that 0.6 ml ( 5700 IU ) of nadroparin once daily is safe and well-tolerated , and it is as effective in prophylaxis of venous thromboembolism as the higher dose of 1 ml ( 9500 IU ) , in such high risk patients", "BACKGROUND St and ard venous thromboembolism ( VTE ) prophylaxis with enoxaparin results in inadequate protection in certain patients , with subtherapeutic plasma anti-Xa levels associated with elevated VTE rates . We hypothesized that many trauma patients would be subtherapeutic on the st and ard prophylactic dose of enoxaparin . Our goal was to adjust the enoxaparin dose to achieve target anti-Xa levels to take advantage of the drug based on its pharmacologic properties . METHODS Patients admitted to the trauma service were included if they received at least three doses of prophylactic enoxaparin and underwent at least two screening venous duplex . Peak plasma anti-Xa levels of 0.2 IU/mL or less were considered low , and the dose was increased by 10 mg twice daily until adequate anti-Xa levels were obtained . A strict screening venous duplex protocol was followed . Patients were excluded if they were diagnosed with a deep venous thrombosis before beginning enoxaparin or did not have correctly timed anti-Xa levels . RESULTS Sixty-one trauma patients met inclusion criteria . There were three patients diagnosed with VTE ( 4.9 % ) . Patients had a mean age of 45.9 years and were predominantly male ( 70.5 % ) . Of the 61 patients , 18 ( 29.5 % ) had therapeutic anti-Xa levels on st and ard enoxaparin 30 mg twice daily . Compared with patients who had therapeutic anti-Xa levels on enoxaparin 30 mg twice daily , the 43 patients ( 70.5 % ) who were subtherapeutic were more likely to be male , have greater body weight , and larger body surface area . There were no significant bleeding events in the group that received an enoxaparin dose adjustment . CONCLUSION Most patients had subtherapeutic anti-Xa levels while on enoxaparin 30 mg twice daily , suggesting inadequate VTE prophylaxis . The need for routine use of a higher dose of prophylactic enoxaparin in trauma patients and the effects of routinely dose adjusting enoxaparin on VTE rates should be the study of future prospect i ve , r and omized trials . LEVEL OF EVIDENCE Therapeutic study , level IV", "BACKGROUND Morbidly obese patients undergoing bariatric surgery are at risk for developing venous thromboembolic events . Data regarding the appropriate dosing strategy in this special population is limited . OBJECTIVE To evaluate 2 different dosing regimens of enoxaparin in a prospect i ve cohort of patients undergoing laparoscopic sleeve gastrectomy . SETTING University hospital , Israel METHODS : The study cohort consisted of 54 patients divided into 2 groups . Group I received 40 mg enoxaparin every 24 hours , and group II received 60 mg enoxaparin every 24 hours . Anti-factor Xa ( FXa ) levels from each patient were obtained 3 to 4 hours after administration of the third dose of enoxaparin . Levels between .2 and 0.5 U/mL were considered appropriate . Five additional patients were selected as controls . RESULTS There were 31 patients in group I and 23 patients in group II . There was a statistically significant difference between anti-FXa levels achieved in each group : .247 U/mL in group I ( range , .15-.39 ) versus .346 U/mL ( range , .24-.8 ) in group II . Both groups achieved mean anti-FXa levels in the range design ated appropriate with a high proportion of patients achieving appropriate levels ( group I : 80.6 % ; group II : 91.3 % ) . Univariate analyses found that total weight and sex were significantly correlated with anti-FXa levels . However , a multivariate analysis including enoxaparin dose found that only enoxaparin dose remained significantly correlated with anti-FXa levels . CONCLUSION In the absence of sufficient data regarding clinical efficacy and safety of different dosing regimens both dosing regimens studied are reasonable choices for venous thromboembolic events prophylaxis after bariatric surgery", "INTRODUCTION We prospect ively evaluated 30-day thromboembolic and bleeding events in 2 groups of laparoscopic gastric bypass patients receiving different anticoagulation regimens . METHODS The first cohort of patients received enoxaparin 40 mg subcutaneously preoperatively , 40 mg subcutaneously on postoperative day 0 , and twice daily until discharge . The second cohort of patients received unfractionated heparin 5,000 units subcutaneously preoperatively , nothing on postoperative day 0 , and 5,000 units 3 times per day until discharge . RESULTS The incidence of deep venous thrombosis in both cohorts was 0 . There was 1 pulmonary embolism in the heparin cohort ( P = .999 ) . Fourteen patients ( 5.9 % ) in the enoxaparin cohort required postoperative transfusions compared with 3 patients ( 1.3 % ) in the heparin cohort ( P = .011 ) . Four patients ( 1.7 % ) in the enoxaparin cohort required re-exploration for bleeding . CONCLUSION Both enoxaparin and heparin are effective at preventing thromboembolic events following laparoscopic gastric bypass . Heparin is the preferred agent due to the excessive bleeding complications encountered with enoxaparin", "Recent reports confirm that the st and ard dose of enoxaparin in obese patients is often subtherapeutic , leading to a higher incidence of venous thromboembolism . All patients receiving subcutaneous enoxaparin 30 mg twice a day ( b.i.d . ) for venous thromboembolism prophylaxis were prospect ively enrolled in this study . Trough antiXa levels were obtained and any level less than 0.1 IU/mL was considered subtherapeutic and the final dosage requirement was recorded . Body mass index ( BMI ) , abdominal wall thickness , and fluid balance were collected . Thirty-four patients were prospect ively enrolled in the study , 14 ( 50 % ) of which had a BMI > 30 . Sixty-five per cent of obese patients were initially nontherapeutic , compared with 53 per cent of the nonobese ( P = 0.73 ) . However , elevated BMI ( P < 0.05 ) and abdominal wall thickness ( P < 0.05 ) correlated to an increased final dose required to attain an anti Xa ≥0.1 when not initially therapeutic , whereas fluid balance demonstrated no correlation ( P = 0.232 ) . Subcutaneous enoxaparin dosing of 30 mg b.i.d . is not sufficient for the majority adult trauma patients in the intensive care unit , regardless of BMI . When enoxaparin 30 mg b.i.d . is initially subtherapeutic , obese patients may require a larger dose necessary to achieve necessary anticoagulation", "BACKGROUND Women undergoing caesarean section are at higher risk for thromboembolic complications following delivery than other parturients . The aim of this study was to determine whether higher doses of enoxaparin based on body weight are safe and more likely to achieve plasma anti-Xa levels within the accepted thromboprophylactic range . METHODS We undertook a prospect i ve cohort study of 80 women undergoing caesarean section in a tertiary obstetric hospital with > 6000 deliveries per year . Enoxaparin was administered after caesarean section using the Royal College of Obstetricians and Gynaecologists weight-adjusted dosing guidelines . Plasma anti-Xa levels were measured at baseline and 3 - 4 h after enoxaparin administration on days one and three postoperatively . The main outcomes of interest were plasma anti-Xa levels and the proportion of patients with plasma anti-Xa levels in the range of 0.2 - 0.4 IU/mL. RESULTS The proportion of women with anti-Xa levels between 0.2 and 0.4 IU/mL was 72 % ( 95 % CI 60 - 81 % ) . Unadjusted mean anti-Xa levels were 0.26 ± 0.09 IU/mL and 0.28 ± 0.08 IU/mL on day one and day three respectively . No woman had levels > 0.48 IU/mL. CONCLUSION The majority of women receiving weight-based enoxaparin thromboprophylaxis following caesarean section achieved plasma anti-Xa levels within the putative thromboprophylactic range . No woman achieved levels associated with an increased risk of bleeding ( > 0.8 IU/mL ) . These findings provide a safety basis for a large prospect i ve study using this regimen", "Background Morbidly obese patients are at increased risk to develop venous thromboembolism ( VTE ) , especially after bariatric surgery . Adequate postoperative thrombosis prophylaxis is of utmost importance . It is assumed that morbidly obese patients need higher doses of low molecular weight heparin ( LMWH ) compared to normal-weight patients ; however , current guidelines based on relative efficacy in obese population s are lacking . Objectives First , we will evaluate the relationship between body weight descriptors and anti-Xa activity prospect ively . Second , we will determine the dose-linearity of LMWH in morbidly obese patients . Setting This study was performed in a general hospital specialized in bariatric surgery . Methods Patients were scheduled for a Roux-en-Y gastric bypass with a total bodyweight ( TBW ) of ≥ 140 kg . Patients ( n = 50 , 64 % female ) received a daily postoperative dose of 5700 IU of nadroparin for 4 weeks . Anti-Xa activity was determined 4 h after the last nadroparin administration . To determine the dose linearity , anti-Xa was determined following a preoperative dose of 2850 IU nadroparin in another 50 patients ( 52 % ) . Results TBW of the complete group was 148.5 ± 12.6 kg . Mean anti-Xa activity following 5700 IU nadroparin was 0.19 ± 0.07 IU/mL. Of all patients , 32 % had anti-Xa levels below the prophylactic range . Anti-Xa activity inversely correlated with TBW ( correlation coefficient − 0.410 ) and lean body weight ( LBW ; correlation coefficient − 0.447 ) ; 67 % of patients with a LBW ≥ 80 kg had insufficient anti-Xa activity concentrations . No VTE events occurred . Conclusions In morbidly obese patients , a postoperative dose of 5700 IU of nadroparin result ed in subprophylactic exposure in a significant proportion of patients . Especially in patients with LBW ≥ 80 kg , a higher dose may potentially be required to reach adequate prophylactic anti-Xa levels", "BACKGROUND One risk of bariatric surgery is venous thromboembolism and the optimal strategy to reduce risk requires further clarification . OBJECTIVES The objectives of this study were to identify antiXa goal attainment with the institutional st and ard chemoprophylaxis , analyze discordance between antiXa and thrombin generation assay ( TGA ) in terms of adequacy of anticoagulation , and to identify correlations between patient characteristics or covariates and markers of coagulation status . SETTING Large academic medical center in Northeastern United States . METHODS A total of 60 sleeve gastrectomy patients were enrolled in this institutional review board-approved , prospect i ve cohort study . Patients received the institutional st and ard prophylactic therapy ( subcutaneous enoxaparin 40 mg twice daily or unfractionated heparin [ UFH ] ) . The UFH dose was weight based , 5000 units ( < 120 kg ) or 7500 units ( ≥120 kg ) every 8 hours . Various measures of coagulation status were measured at or near steady state . RESULTS Patients receiving enoxaparin achieved goal antiXa more frequently compared with the UFH group , and statistical significance was demonstrated ( 93.8 % versus 4.5 % , respectively ; P < .0001 ) . Target endogenous thrombin potential reduction from baseline was more frequently obtained in the enoxaparin group versus UFH ( 50 % versus 27.7 % , respectively ; P = .12 ) . AntiXa was below the limit of detection for the majority of UFH patients ; while TGA suggested patients did experience anticoagulation at some level of effectiveness . Endogenous thrombin potential change in the enoxaparin group was correlated to several measures of body composition . CONCLUSIONS Patients receiving enoxaparin achieved goal antiXa more often versus UFH . There was discordance between antiXa and TGA-based assessment of coagulation status . TGA may provide a more robust assessment of the adequacy of chemoprophylaxis", "Introduction There is lack of data on the pharmacodynamics of low-molecular-weight heparins in obese patients . Background The aims of this study are to investigate the correlation between anti-factor Xa ( anti-Xa ) levels and body weight with fixed-dose enoxaparin after bariatric surgery and to investigate the percentage of patients that reach the desired prophylactic range for anti-Xa levels . Methods Blood for anti-Xa peak levels measurement was drawn 3–5 h after administration of enoxaparin at the planned visit 8–16 days after surgery . Patients were included in three categories : < 110 kg ( group 1 ) , 110–150 kg ( group 2 ) , and > 150 kg ( group 3 ) . Results Fifty-one patients were included ( 43.9 ± 9.9 years , 75 % women ) . Mean anti-Xa level was 0.37 ± 0.14 IU/ml . This level was the highest in group 1 ( 0.47 ± 0.13 IU/ml ) and lowest in group 3 ( 0.23 ± 0.07 ) . No subprophylactic ( < 0.2 IU/ml ) anti-Xa levels were detected in group 1 , whereas this was observed in 38 % in patients in group 3 . Supraprophylactic levels ( > 0.5 IU/ml ) were most often present in group 1 ( 36 % ) . With multivariable regression analysis , body weight ( β −0.720 ( 95 % confidence interval −.717 ; −.993 ) , p < 0.001 ) was an independent predictor of anti-Xa levels , whereas lean body was not independently associated . This was confirmed in a non-linear mixed effects analysis of the data . Conclusions Patients with excessive body weight may not be adequately treated with fixed-dose enoxaparin thromboprophylaxis while patients with lower body weight may have an increased bleeding risk . Body weight is a better predictor of anti-Xa levels compared to lean body weight" ]
"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"
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[ "[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"
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[ "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"
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[ "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"
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[ "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 AUS$614 per patient ( AUS$ = 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" ]