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Clinical NLP Lab 22

MS20

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 int Output:

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 .

MS21

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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

MS22

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 atorv Output:

This present meta- analysis suggests that statin pretreatment might be effective in improving myocardial perfusion in STEMI patients

MS23

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

In conclusion , there is a lack of evidence of effectiveness for most waterpipe interventions .

MS24

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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 .

MS25

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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 .

MS26

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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 .

MS27

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 dos Output:

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 .

MS28

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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

MS29

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

Because of insufficient method ological quality of most prognostic studies , the predictive value of many clinical determinants for outcome of ADL remains unclear .

MS210

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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

MS211

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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 .

MS212

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 recept Output:

VEGF-A level is a reasonable c and i date biomarker for bevacizumab in the treatment of breast cancer .

MS213

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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

MS214

***TASK*** the task is to summarize an input biomedical literature in six sentences ***INPUT*** the input is a biomedical literature ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 Output:

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