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30760312	[ "22776744", "23912836", "22922316", "12821234", "20175775", "23996433", "25271670", "3493740", "20585012", "29167228", "25529339", "16793845", "16697324", "16053970", "6274653", "7126994", "22723290" ]	[ "Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension", "Double-blind, placebo-controlled clinical trial with a rho-kinase inhibitor in pulmonary arterial hypertension.", "Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism.", "Beraprost therapy for pulmonary arterial hypertension.", "Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies", "Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension", "Adipose-derived stem cells attenuate pulmonary arterial hypertension and ameliorate pulmonary arterial remodeling in monocrotaline-induced pulmonary hypertensive rats", "Effect of bone marrow mesenchymal stem cells on experimental pulmonary arterial hypertension", "Predicting Survival in Pulmonary Arterial Hypertension: Insights From the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL)", "Contribution of Impaired Parasympathetic Activity to Right Ventricular Dysfunction and Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension", "Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.", "Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions", "Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan.", "Ambrisentan therapy for pulmonary arterial hypertension.", "Clinical efficacy of low dose recombinant tissue-type plasminogen activator for the treatment of acute intermediate-risk pulmonary embolism", "Efficacy and Safety of Low Dose Recombinant Tissue-Type Plasminogen Activator for the Treatment of Acute Pulmonary Thromboembolism", "The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension." ]	[ "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", "BACKGROUND We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension ( PAH ) in animal models . In the present study , we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 ( fasudil hydrochloride ) , a specific Rho-kinase inhibitor ( AT-877ER ) on PAH . METHODS AND RESULTS 23 PAH patients were treated with either placebo ( 10/2 females/males , 51 ± 16 years , idiopathic PAH ( IPAH ) in 6 , PAH associated with connective tissue disease ( CTD-PAH ) in 3 , PAH with congenital heart disease ( CHD-PAH ) in 2 , and portal PAH in 1 ) or AT-877ER ( 6/5 females/males , 47 ± 14 years , IPAH in 2 , CTD-PAH in 5 , and CHD-PAH in 4 ) ; 3 patients were excluded . We performed a 6-min walk test and right heart catheterization in the remaining 20 patients , before and 3 months after the treatment ( placebo n=11 , AT-877ER n=9 ) . Although there were no significant differences between the 2 groups for the 6-min walk distance , pulmonary hemodynamics tended to be improved in the AT-877ER group , especially the prevalence of improved cardiac index from baseline , which was significantly higher in the AT-877ER than in the placebo group . In the AT-877ER group , serum levels of hydroxyfasudil , an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure . CONCLUSIONS Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH", "UNLABELLED Pulmonary arterial hypertension ( PAH ) is characterized by functional and structural changes in the pulmonary vasculature , and despite the drug treatment that made significant progress , the prognosis of patients with advanced PH remains extremely poor . In the present study , we investigated the early effect of bone marrow mesenchymal stem cells ( BMSCs ) on experimental high blood flow-induced PAH model rats and discussed the mechanism . BMSCs were isolated , cultured from bone marrow of Sprague-Dawley ( SD ) rat . The animal model of PAH was created by surgical methods to produce a left-to-right shunt . Following the successful establishment of the PAH model , rats were r and omly assigned to three groups ( n=20 in each group ) : sham group ( control ) , PAH group , and BMSC group ( received a sublingual vein injection of 1 - 5 × 10(6 ) BMSCs ) . Two weeks after the administration , BMSCs significantly reduced the vascular remodeling , improved the hemodynamic data , and deceased the right ventricle weight ratio to left ventricular plus septal weight ( RV/LV+S ) ( P<0.05 ) . Real-time reverse transcription-polymerase chain reaction ( RT-PCR ) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1β ( IL-1β ) , IL-6 , and tumor necrosis factor-α ( TNF-α ) were reduced ( P<0.05 ) ; the expression of matrix metallo proteinase-9 ( MMP-9 ) was lower ( P<0.05 ) ; vascular endothelial growth factor ( VEGF ) was higher in BMSC group than those in PAH group ( P<0.05 ) . CONCLUSION Sublingual vein injection of BMSCs for 2 weeks , significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH ; decreased pulmonary vascular remodeling and inflammation ; and enhanced angiogenesis", "OBJECTIVES The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind , r and omized , placebo-controlled trial in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death . Despite the risks from its delivery system , continuous intravenous epoprostenol remains the most efficacious treatment currently available . METHODS A total of 116 patients with World Health Organization ( WHO ) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled . Patients were r and omized to receive the maximal tolerated dose of beraprost sodium ( median dose 120 microg four times a day ) or placebo for 12 months . The primary end point was disease progression ; i.e. , death , transplantation , epoprostenol rescue , or > 25 % decrease in peak oxygen consumption ( VO(2 ) ) . Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2 ) , Borg dyspnea score , hemodynamics , symptoms of PAH , and quality of life . RESULTS Patients treated with beraprost exhibited less evidence of disease progression at six months ( p = 0.002 ) , but this effect was not evident at either shorter or longer follow-up intervals . Similarly , beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m ( p = 0.010 and 0.016 , respectively ) compared with placebo , but not at either 9 or 12 months . Drug-related adverse events were common and were related to the disease and /or expected prostacyclin adverse events . CONCLUSIONS These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time", "Doppler‐defined pulmonary hypertension ( PH ) in sickle cell disease ( SCD ) is associated with 40 % mortality at 40 months . To assess the effect of bosentan in SCD‐PH , two r and omized , double‐blind , placebo‐controlled , 16‐week studies were initiated . Safety concerns are particularly relevant in SCD due to comorbid conditions . ASSET‐1 and ‐2 enrolled patients with pulmonary arterial hypertension ( PAH ) and pulmonary venous hypertension ( PH ) , respectively . Haemodynamics and 6‐min walk distance ( 6MWD ) were obtained at baseline and week 16 . The studies were terminated due to slow site initiation and patient enrolment ( n = 26 ) . Bosentan appeared to be well tolerated . Although sample sizes were limited , in ASSET‐1 at baseline , 6MWD correlated with cardiac output ( CO ; P = 0·006 ) with non‐significant inverse correlations between 6MWD and pulmonary vascular resistance ( PVR ; P = 0·07 ) and between 6MWD and right atrial pressure ( P = 0·08 ) . In ASSET‐2 at baseline , there was a non‐significant correlation between 6MWD and CO ( P = 0·06 ) . Due to limited sample sizes , efficacy endpoints were not analysed . However , in both studies , non‐significant increases in CO were observed with bosentan compared to placebo . Similarly , non‐significant decreases in PVR were observed with bosentan . Limited data in SCD‐PH suggest that a low 6MWD predicts a low CO . St and ard‐dose bosentan appears to be well tolerated . Further investigation is warranted . Clinical trials.gov registration numbers NCT00310830 , NCT00313196 , NCT00360087", "Our previous studies have shown that bone marrow mesenchymal stem cells ( BMSCs ) can inhibit the progression of pulmonary artery hypertension ( PAH ) in the monocrotaline ( MCT ) model in the short term . The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation . PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study . Postoperatively , the animals were r and omly divided into three groups ( n = 10 in each group ) : control , PAH group , and BMSCs implantation group . Six months after injection , immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced ( P < 0.05 ) ; the area of collagen fibers in lung tissue was lower ( P < 0.05 ) , and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased ( P < 0.05 ) . Immunofluorescence showed that the cells have the ability to differentiate between von Willebr and factor and vascular endothelial growth factor . Six months after intravenous injection , BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation", "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", "Background — Factors that determine survival in pulmonary arterial hypertension ( PAH ) drive clinical management . A quantitative survival prediction tool has not been established for research or clinical use . Methods and Results — Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management ( REVEAL ) were analyzed to assess predictors of 1-year survival . We identified independent prognosticators of survival and derived a multivariable , weighted risk formula for clinical use . One-year survival from the date of enrollment was 91.0 % ( 95 % confidence interval [ CI ] , 89.9 to 92.1 ) . In a multivariable analysis with Cox proportional hazards , variables independently associated with increased mortality included pulmonary vascular resistance > 32 Wood units ( hazard ratio [ HR ] , 4.1 ; 95 % CI , 2.0 to 8.3 ) , PAH associated with portal hypertension ( HR , 3.6 ; 95 % CI , 2.4 to 5.4 ) , modified New York Heart Association/World Health Organization functional class IV ( HR , 3.1 ; 95 % CI , 2.2 to 4.4 ) , men > 60 years of age ( HR , 2.2 ; 95 % CI , 1.6 to 3.0 ) , and family history of PAH ( HR , 2.2 ; 95 % CI , 1.2 to 4.0 ) . Renal insufficiency , PAH associated with connective tissue disease , functional class III , mean right atrial pressure , resting systolic blood pressure and heart rate , 6-minute walk distance , brain natriuretic peptide , percent predicted carbon monoxide diffusing capacity , and pericardial effusion on echocardiogram all predicted mortality . Based on these multivariable analyses , a prognostic equation was derived and vali date d by bootstrapping technique . Conclusions — We identified key predictors of survival based on the patient 's most recent evaluation and formulated a contemporary prognostic equation . Use of this tool may allow the individualization and optimization of therapeutic strategies . Serial follow-up and re assessment are warranted . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00370214", "Background : The beneficial effects of parasympathetic stimulation have been reported in left heart failure , but whether it would be beneficial for pulmonary arterial hypertension ( PAH ) remains to be explored . Here , we investigated the relationship between parasympathetic activity and right ventricular ( RV ) function in patients with PAH , and the potential therapeutic effects of pyridostigmine ( PYR ) , an oral drug stimulating the parasympathetic activity through acetylcholinesterase inhibition , in experimental pulmonary hypertension ( PH ) . Methods : Heart rate recovery after a maximal cardiopulmonary exercise test was used as a surrogate for parasympathetic activity . RV ejection fraction was assessed in 112 patients with PAH . Expression of nicotinic ( & agr;-7 nicotinic acetylcholine receptor ) and muscarinic ( muscarinic acetylcholine type 2 receptor ) receptors , and acetylcholinesterase activity were evaluated in RV ( n=11 ) and lungs ( n=7 ) from patients with PAH undergoing heart/lung transplantation and compared with tissue obtained from controls . In addition , we investigated the effects of PYR ( 40 mg/kg per day ) in experimental PH . PH was induced in male rats by SU5416 ( 25 mg/kg subcutaneously ) injection followed by 4 weeks of hypoxia . In a subgroup , sympathetic/parasympathetic modulation was assessed by power spectral analysis . At week 6 , PH status was confirmed by echocardiography , and rats were r and omly assigned to vehicle or treatment ( both n=12 ) . At the end of the study , echocardiography was repeated , with additional RV pressure-volume measurements , along with lung , RV histological , and protein analyses . Results : Patients with PAH with lower RV ejection fraction ( < 41 % ) had a significantly reduced heart rate recovery in comparison with patients with higher RV ejection fraction . In PAH RV sample s , & agr;-7 nicotinic acetylcholine receptor was increased and acetylcholinesterase activity was reduced versus controls . No difference in muscarinic acetylcholine type 2 receptor expression was observed . Chronic PYR treatment in PH rats normalized the cardiovascular autonomic function , demonstrated by an increase in parasympathetic activity and baroreflex sensitivity . PYR improved survival , increased RV contractility , and reduced RV stiffness , RV hypertrophy , RV fibrosis , RV inflammation , and RV & agr;-7 nicotinic acetylcholine receptor and muscarinic acetylcholine type 2 receptor expression , as well . Furthermore , PYR reduced pulmonary vascular resistance , RV afterload , and pulmonary vascular remodeling , which was associated with reduced local and systemic inflammation . Conclusions : RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH , with an inadequate adaptive response of the cholinergic system in the RV . Enhancing parasympathetic activity by PYR improved survival , RV function , and pulmonary vascular remodeling in experimental PH", "BACKGROUND No effective pharmacotherapy for acute respiratory distress syndrome ( ARDS ) exists , and mortality remains high . Pre clinical studies support the efficacy of mesenchymal stem ( stromal ) cells ( MSCs ) in the treatment of lung injury . We aim ed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS . METHODS The STem cells for ARDS Treatment ( START ) trial was a multicentre , open-label , dose-escalation , phase 1 clinical trial . Patients were enrolled in the intensive care units at University of California , San Francisco , CA , USA , Stanford University , Stanford , CA , USA , and Massachusetts General Hospital , Boston , MA , USA , between July 8 , 2013 , and Jan 13 , 2014 . Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube , a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure ( PEEP ) , and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph . The first three patients were treated with low dose MSCs ( 1 million cells/kg predicted bodyweight [ PBW ] ) , the next three patients received intermediate dose MSCs ( 5 million cells/kg PBW ) , and the final three patients received high dose MSCs ( 10 million cells/kg PBW ) . Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events . The trial is registered with Clinical Trials.gov , number NCT01775774 . FINDINGS No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients . Serious adverse events were subsequently noted in three patients during the weeks after the infusion : one patient died on study day 9 , one patient died on study day 31 , and one patient was discovered to have multiple embolic infa rcts of the spleen , kidneys , and brain that were age-indeterminate , but thought to have occurred before the MSC infusion based on MRI results . None of these severe adverse events were thought to be MSC-related . INTERPRETATION A single intravenous infusion of allogeneic , bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS . Based on this phase 1 experience , we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory , systemic , and biological endpoints . FUNDING The National Heart , Lung , and Blood Institute", "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", "OBJECTIVES We sought to determine the optimal dose of the selective endothelin A ( ET(A ) ) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension ( PAH ) ; for observation only , an open-label ( OL ) bosentan arm was included . BACKGROUND Endothelin is a mediator of PAH . In a preliminary PAH study , the selective ET(A ) receptor antagonist sitaxsentan improved six-min walk ( 6MW ) distance , World Health Organization ( WHO ) functional class ( FC ) , and hemodynamics . METHODS In this double-blind , placebo-controlled 18-week study , 247 PAH patients ( idiopathic , or associated with connective tissue disease or congenital heart disease ) were r and omized ; 245 patients were treated : placebo ( n = 62 ) , sitaxsentan 50 mg ( n = 62 ) or 100 mg ( n = 61 ) , or OL ( 6MW tests , Borg dyspnea scores , and WHO FC assessment s third-party blind ) bosentan ( n = 60 ) . The primary end point was change in 6MW distance from baseline to week 18 . Secondary end points included change in WHO FC , time to clinical worsening , and change in Borg dyspnea score . RESULTS At week 18 , patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group ( 31.4 m , p = 0.03 ) , and an improved WHO FC ( p = 0.04 ) . The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m ( p = 0.07 ) and for OL bosentan , 29.5 m ( p = 0.05 ) . The incidence of elevated hepatic transaminases ( > 3x the upper limit of normal ) was 6 % for placebo , 5 % for sitaxsentan 50 mg , 3 % for sitaxsentan 100 mg , and 11 % for bosentan . CONCLUSIONS Treatment with the selective ET(A ) receptor antagonist sitaxsentan , orally once daily at a dose of 100 mg , improves exercise capacity and WHO FC in PAH patients , with a low incidence of hepatic toxicity", "OBJECTIVES The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan , an oral endothelin type A receptor-selective antagonist , in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options . Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH . METHODS In this double-blind , dose-ranging study , 64 patients with idiopathic PAH or PAH associated with collagen vascular disease , anorexigen use , or human immunodeficiency virus infection were r and omized to receive 1 , 2.5 , 5 , or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan . The primary end point was an improvement from baseline in 6-min walk distance ( 6MWD ) ; secondary end points included Borg dyspnea index , World Health Organization ( WHO ) functional class , a subject global assessment , and cardiopulmonary hemodynamics . RESULTS At 12 weeks , ambrisentan increased 6MWD ( + 36.1 m , p < 0.0001 ) with similar and statistically significant increases for each dose group ( range , + 33.9 to + 38.1 m ) . Improvements were also observed in Borg dyspnea index , WHO functional class , subject global assessment , mean pulmonary arterial pressure ( -5.2 mm Hg , p < 0.0001 ) , and cardiac index ( + 0.33 l/min/m2 , p < 0.0008 ) . Adverse events were mild and unrelated to dose , including the incidence of elevated serum aminotransferase concentrations > 3 times the upper limit of normal ( 3.1 % ) . CONCLUSIONS Ambrisentan appears to improve exercise capacity , symptoms , and hemodynamics in patients with PAH . The incidence and severity of liver enzyme abnormalities appear to be low", "Objectives : To investigate the efficacy and safety of initial thrombolysis by recombinant tissue-type plasminogen activator ( rt-PA ) in compared with anticoagulant therapy in patients with acute intermediate-risk pulmonary embolism ( PE ) . Methods : Sixty-six patients with acute intermediate-risk PE were r and omly assigned to receive rt-PA or LMWH between June 2014 and June 2017 in our department . We obtained information regarding the difference in the right ventricle/left ventricle ( RV/LV ) ratio , pulmonary artery systolic pressure ( PASP ) , clinical symptoms improvement , PE-related mortality , hemodynamic decompensation , recurrent PE , and major and minor bleeding . Results : In the rt-PA group , the mean PASP was reduced from 52.0±12.2 at baseline to 34.8±9.4 ( p<0.001 ) and the mean RV/LV ratio was reduced from 1.26±0.22 at baseline to 0.96±0.18 ( p<0.001 ) at 24 hours . In the LMWH group , the mean PASP was 53.4±12.8 at baseline and 48.5±11.9 at 24 hours ( p=0.11 ) , and the mean RV/LV ratio was 1.22±0.19 at baseline and 1.17±0.21 at 24 hours ( p=0.31 ) . In comparison with the LMWH group , there was a significant reduction in PASP and an improvement in the symptom severity in the rt-PA group . At 90 days , there was no difference in mortality , recurrent venous thromboembolism and major bleeding as a safety outcome , but increased minor bleeding and decreased hemodynamic decompensation occurred in the rt-PA group . Conclusions : In patients with acute intermediate-risk PE , low dose thrombolytic therapy is considered safe and effective , it can be recommended as an alternative option in clinical treatment", "Background Optimal dosing of the recombinant tissue-type plasminogen activator ( rt-PA ) is important in treating pulmonary thromboembolism ( PTE ) . The aim of this study was to compare the efficacy and safety of a 50 mg/2 h rt-PA regimen with a 100 mg/2 h rt-PA regimen in patients with acute PTE . Methods A prospect i ve , r and omized , multicenter trial was conducted in which 118 patients with acute PTE and either hemodynamic instability or massive pulmonary artery obstruction were r and omly assigned to receive a treatment regiment of either rt-PA at 50 mg/2 h ( n = 65 ) or 100 mg/2 h ( n = 53 ) . The efficacy was determined by observing the improvements of right ventricular dysfunctions ( RVDs ) on echocardiograms , lung perfusion defects on ventilation perfusion lung scans , and pulmonary artery obstructions on CT angiograms . The adverse events , including death , bleeding , and PTE recurrence , were also evaluated . Results Progressive improvements in RVDs , lung perfusion defects , and pulmonary artery obstructions were found to be similarly significant in both treatment groups . This is true for patients with either hemodynamic instability or massive pulmonary artery obstruction . Three ( 6 % ) patients in the rt-PA 100 mg/2 h group and one ( 2 % ) in the rt-PA 50 mg/2 h group died as the result of either PTE or bleeding . Importantly , the 50 mg/2 h rt-PA regimen result ed in less bleeding tendency than the 100 mg/2 h regimen ( 3 % vs 10 % ) , especially in patients with a body weight < 65 kg ( 14.8 % vs 41.2 % , P = .049 ) . No fatal recurrent PTE was found in either group . Conclusions Compared with the 100 mg/2 h regimen , the 50 mg/2 h rt-PA regimen exhibits similar efficacy and perhaps better safety in patients with acute PTE . These findings support the notion that optimizing rt-PA dosing is worthwhile when treating patients with PTE . Trial registration clinical trials.gov ; Identifier :", "RATIONALE Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension ( PAH ) , the minimal important difference ( MID ) of the 6-minute walk test ( 6MWT ) has not been well defined for this population of patients . OBJECTIVES To estimate the MID in the 6MWT in patients with PAH . METHODS Study subjects from the clinical trial of tadalafil in PAH , a 16-week , parallel-group , r and omized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist , were eligible . 6MWT was performed using a st and ardized protocol . Distributional and anchor-based methods were used to estimate the MID ; the latter method used the Physical Component Summary Score ( PCS ) of the Medical Outcomes Study 36-item short form ( SF-36 ) . MEASUREMENTS AND MAIN RESULTS Four hundred five subjects were analyzed . Domains of the SF-36 were weakly to modestly associated with 6MWT . Change in the PCS of the SF-36 was most strongly associated with change in 6MWT ( r = 0.40 , P < 0.001 ) and thus was selected as the anchor for subsequent anchor-based analyses . Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m , whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS Using both distributional and anchor-based methods , the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implication s for ( 1 ) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy , and ( 2 ) sample size calculations for future study design" ]	Conclusions SC therapy is effective for PAH in pre clinical studies . These results may help to st and ardise pre clinical animal studies and provide a theoretical basis for clinical trial design in the future .	Background Despite significant progress in drug treatment , the prognosis of patients with advanced pulmonary arterial hypertension ( PAH ) remains extremely poor . Many pre clinical studies have reported the efficacy of stem cell ( SC ) therapy for PAH ; however , this approach remains controversial . The aim of this systematic review and meta- analysis is to assess the potential efficacy of SC therapy for PAH .
19588356	[ "10869264", "18448495", "23984728", "11907289", "15358690", "16697324", "10783653", "7658874", "23846611", "10430735", "26699168", "24937643", "10733441", "16801459", "16793845", "16053970", "15684287" ]	[ "Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure.", "A randomised, controlled trial of bosentan in severe COPD", "Macitentan and morbidity and mortality in pulmonary arterial hypertension.", "Bosentan therapy for pulmonary arterial hypertension.", "Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2", "Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan.", "[Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to pulmonary fibrosis].", "Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure", "Balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension", "Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis.", "Selexipag for the Treatment of Pulmonary Arterial Hypertension.", "Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia.", "Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease", "Bosentan Therapy in Patients With Eisenmenger Syndrome: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study", "Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions", "Ambrisentan therapy for pulmonary arterial hypertension.", "Survival with first-line bosentan in patients with primary pulmonary hypertension" ]	[ "BACKGROUND Elevated plasma endothelin-1 ( ET-1 ) levels in patients with chronic heart failure correlate with pulmonary artery pressures and pulmonary vascular resistance . ET(A ) receptors on vascular smooth muscle cells mediate pulmonary vascular contraction and hypertrophy . We determined the acute hemodynamic effects of sitaxsentan , a selective ET(A ) receptor antagonist , in patients with chronic stable heart failure receiving conventional therapy . METHODS AND RESULTS This multicenter , double-blind , placebo-controlled trial enrolled 48 patients with chronic New York Heart Association functional class III or IV heart failure ( mean left ventricular ejection fraction 21+/-1 % ) treated with ACE inhibitors and diuretics . Patients with a baseline pulmonary capillary wedge pressure > /=15 mm Hg and a cardiac index < /=2.5 L. min(-1 ) . m(-2 ) were r and omized to 1 of 3 doses ( 1.5 , 3.0 , or 6.0 mg/kg ) of sitaxsentan or placebo as an intravenous infusion over 15 minutes . Hemodynamic responses were assessed by catheterization of the right side of the heart for 6 hours . Sitaxsentan decreased pulmonary artery systolic pressure , pulmonary vascular resistance , mean pulmonary artery pressure , and right atrial pressure ( P</=0.001 , 0.003 , 0.017 , and 0.031 , respectively ) but had no effect on heart rate , mean arterial pressure , pulmonary capillary wedge pressure , cardiac index , or systemic vascular resistance . Plasma ET-1 levels were elevated at baseline and decreased with sitaxsentan . CONCLUSIONS In patients with moderate to severe heart failure receiving conventional therapy , acute ET(A ) receptor blockade caused selective pulmonary vasodilation associated with a reduction in plasma ET-1 . Sitaxsentan may be of value in the treatment of patients with pulmonary hypertension secondary to chronic heart failure", "Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease ( COPD ) . It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise , thus increasing exercise tolerance in patients with severe COPD . In the present double-blind , placebo-controlled study , 30 patients with severe or very severe COPD were r and omly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks . The primary end-point was change in the 6-min walking distance . Secondary end-points included changes in health-related quality of life , lung function , cardiac haemodynamics , maximal oxygen uptake and pulmonary perfusion patterns . Compared with placebo , patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance ( mean±sd 331±123 versus 329±94 m ) . There was no change in lung function , pulmonary arterial pressure , maximal oxygen uptake or regional pulmonary perfusion pattern . In contrast , arterial oxygen pressure dropped , the alveolar – arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan . The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest", "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 . )", "BACKGROUND Endothelin-1 is a potent vasoconstrictor and smooth-muscle mitogen . In a preliminary study , the orally administered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension . The present trial investigated the effect of bosentan on exercise capacity in a larger number of patients and compared two doses . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 213 patients with pulmonary arterial hypertension ( primary or associated with connective-tissue disease ) to receive placebo or to receive 62.5 mg of bosentan twice daily for 4 weeks followed by either of two doses of bosentan ( 125 or 250 mg twice daily ) for a minimum of 12 weeks . The primary end point was the degree of change in exercise capacity . Secondary end points included the change in the Borg dyspnea index , the change in the World Health Organization ( WHO ) functional class , and the time to clinical worsening . RESULTS At week 16 , patients treated with bosentan had an improved six-minute walking distance ; the mean difference between the placebo group and the combined bosentan groups was 44 m ( 95 percent confidence interval , 21 to 67 ; P<0.001 ) . Bosentan also improved the Borg dyspnea index and WHO functional class and increased the time to clinical worsening . CONCLUSIONS The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily . Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension", "The efficacy and safety of combining bosentan , an orally active dual endothelin receptor antagonist and epoprostenol , a continuously infused prostagl and in , in the treatment of pulmonary arterial hypertension ( PAH ) was investigated . In this double-blind , placebo-controlled prospect i ve study , 33 patients with PAH started epoprostenol treatment ( 2 ng·kg−1min−1 starting dose , up to 14±2 ng·kg−1min−1 at week 16 ) and were r and omised for 16 weeks in a 2:1 ratio to bosentan ( 62.5 mg b.i.d for 4 weeks then 125 mg b.i.d ) or placebo . Haemodynamics , exercise capacity and functional class improved in both groups at week 16 . In the combination treatment group , there was a trend for a greater ( although nonsignificant ) improvement in all measured haemodynamic parameters . There were four withdrawals in the bosentan/epoprostenol group ( two deaths due to cardiopulmonary failure , one clinical worsening , and one adverse event ) and one withdrawal in the placebo/epoprostenol group ( adverse event ) . This study showed a trend but no statistical significance towards haemodynamics or clinical improvement due to the combination of bosentan and epoprostenol therapy in patients with pulmonary arterial hypertension . Several cases of early and late major complications were reported . Additional information is needed to evaluate the risk/benefit ratio of combined bosentan-epoprostenol therapy in pulmonary arterial hypertension", "OBJECTIVES We sought to determine the optimal dose of the selective endothelin A ( ET(A ) ) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension ( PAH ) ; for observation only , an open-label ( OL ) bosentan arm was included . BACKGROUND Endothelin is a mediator of PAH . In a preliminary PAH study , the selective ET(A ) receptor antagonist sitaxsentan improved six-min walk ( 6MW ) distance , World Health Organization ( WHO ) functional class ( FC ) , and hemodynamics . METHODS In this double-blind , placebo-controlled 18-week study , 247 PAH patients ( idiopathic , or associated with connective tissue disease or congenital heart disease ) were r and omized ; 245 patients were treated : placebo ( n = 62 ) , sitaxsentan 50 mg ( n = 62 ) or 100 mg ( n = 61 ) , or OL ( 6MW tests , Borg dyspnea scores , and WHO FC assessment s third-party blind ) bosentan ( n = 60 ) . The primary end point was change in 6MW distance from baseline to week 18 . Secondary end points included change in WHO FC , time to clinical worsening , and change in Borg dyspnea score . RESULTS At week 18 , patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group ( 31.4 m , p = 0.03 ) , and an improved WHO FC ( p = 0.04 ) . The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m ( p = 0.07 ) and for OL bosentan , 29.5 m ( p = 0.05 ) . The incidence of elevated hepatic transaminases ( > 3x the upper limit of normal ) was 6 % for placebo , 5 % for sitaxsentan 50 mg , 3 % for sitaxsentan 100 mg , and 11 % for bosentan . CONCLUSIONS Treatment with the selective ET(A ) receptor antagonist sitaxsentan , orally once daily at a dose of 100 mg , improves exercise capacity and WHO FC in PAH patients , with a low incidence of hepatic toxicity", "Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension . Aerosolized prostagl and in (PG)I2 caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mmHg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn.s.cm-5 ( p < 0.005 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left-shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn.s.cm-5 . In contrast , both intravenous PGI2 and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition PGI2 infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI2 analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI2 or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis", "Heart failure is commonly associated with high plasma concentrations of endothelin-1 , a powerful vasoconstrictor produced by endothelium . The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist , bosentan . 24 patients with chronic heart failure received r and omly and double blind two intravenous infusions of either placebo or bosentan ( 100 mg followed after 60 min by 200 mg ) . Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period . Baseline endothelin-1 and big-endothelin-1 concentrations , which were above the normal range in all patients , correlated directly with the extent of pulmonary hypertension , with left and right heart filling pressures , and with pulmonary vascular resistance and inversely with cardiac index . Compared with placebo , bosentan reduced mean arterial pressure by 7.7 % ( 95 % CI 7.1 - 9.7 ) , pulmonary artery pressure by 13.7 % ( 10.5 - 16.9 ) , right atrial pressure by 18.2 % ( 12.0 - 24.4 ) , and pulmonary artery wedged pressure by 8.6 % ( 5.3 - 12.0 ) ; it increased cardiac index by 13.6 % ( 9.1 - 18.2 ) , decreased systemic vascular resistance by 16.5 % ( 13.2 - 19.8 ) , and decreased pulmonary vascular resistance by 33.2 % ( 22.4 - 44.0 ) . Heart rate did not change . Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged . These findings indicate that , in patients with chronic heart failure who have high circulatory endothelin-1 concentrations , this peptide contributes to maintenance of vascular tone . The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients", "Objective To examine the effect of balloon pulmonary angioplasty ( BPA ) on chronic thromboembolic pulmonary hypertension ( CTEPH ) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy . Design Observational cohort study . Setting Referred patients with inoperable or persistent CTEPH . Patients Twenty consecutive CTEPH patients ( 10 females ) , aged 60±10 years . Interventions BPA . Main outcome measures Right heart catheterisation , functional capacity ( cardiopulmonary exercise testing ( CPET ) and NYHA class ) and blood sample d biomarkers N-terminal pro-brain natriuretic peptide ( NT-proBNP ) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA . Results Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries . Two deaths occurred following the first BPA , with an overall 10 % periprocedural death rate . Reperfusion oedema complicated seven procedures . Comparisons before and after BPA showed significant haemodynamic improvements , including decreased mean pulmonary artery pressure ( mPAP ) ( 45±11 mm Hg vs 33±10 mm Hg ; p<0.001 ) and increased cardiac output ( 4.9±1.6 L/min vs 5.4±1.9 L/min ; p=0.011 ) . Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class ( 3.0±0.5 vs 2.0±0.5 ; p<0.001 ) and CPET ( 13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min ; p<0.001 ) . Seventeen patients ( 85 % ) were alive after 51±30 months of follow-up . Conclusions BPA may offer an alternative form of treatment in selected CTEPH patients . While prognostic markers such as haemodynamics , functional capacity and biomarkers improve , significant periprocedural complications must be recognised . R and omised trials are warranted", "Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension . Aerosolized prostagl and in (PG)I(2 ) caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mm Hg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn . s. cm(-)(5 ) ( p < 0.05 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn . s. cm(-)(5 ) . In contrast , both intravenous PGI(2 ) and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition , PGI(2 ) infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI(2 ) analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI(2 ) or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis", "BACKGROUND In a phase 2 trial , selexipag , an oral selective IP prostacyclin-receptor agonist , was shown to be beneficial in the treatment of pulmonary arterial hypertension . METHODS In this event-driven , phase 3 , r and omized , double-blind , placebo-controlled trial , we r and omly assigned 1156 patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses ( maximum dose , 1600 μg twice daily ) . Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist , a phosphodiesterase type 5 inhibitor , or both . The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period ( defined for each patient as 7 days after the date of the last intake of selexipag or placebo ) . RESULTS A primary end-point event occurred in 397 patients --41.6 % of those in the placebo group and 27.0 % of those in the selexipag group ( hazard ratio in the selexipag group as compared with the placebo group , 0.60 ; 99 % confidence interval , 0.46 to 0.78 ; P<0.001 ) . Disease progression and hospitalization accounted for 81.9 % of the events . The effect of selexipag with respect to the primary end point was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving treatment at baseline ( including those who were receiving a combination of two therapies ) . By the end of the study , 105 patients in the placebo group and 100 patients in the selexipag group had died from any cause . Overall , 7.1 % of patients in the placebo group and 14.3 % of patients in the selexipag group discontinued their assigned regimen prematurely because of adverse events . The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin , including headache , diarrhea , nausea , and jaw pain . CONCLUSIONS Among patients with pulmonary arterial hypertension , the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo . There was no significant difference in mortality between the two study groups . ( Funded by Actelion Pharmaceuticals ; GRIPHON Clinical Trials.gov number , NCT01106014 . )", "RATIONALE Pulmonary hypertension ( PH ) associated with fibrotic idiopathic interstitial pneumonia ( IIP ; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia ) confers important additional morbidity and mortality . OBJECTIVES To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group . METHODS In a r and omized , double-blind , placebo-controlled study , 60 patients with fibrotic IIP and right heart catheter confirmed PH were r and omized 2:1 to bosentan ( n = 40 ) or placebo ( n = 20 ) . The primary study endpoint was a fall from baseline pulmonary vascular resistance index ( PVRi ) of 20 % or more over 16 weeks . MEASUREMENTS AND MAIN RESULTS Sixty patients ( 42 men ; mean age , 66.6 ± 9.2 yr ) , with a mean pulmonary artery pressure of 36.0 ( ± 8.9 ) mm Hg , PVRi 13.0 ( ± 6.7 ) Wood Units/m(2 ) and reduced cardiac index of 2.21 ( ± 0.5 ) L/min/m(2 ) were recruited to the study . Accounting for deaths and withdrawals , paired right heart catheter data were available for analysis in 39 patients ( bosentan = 25 , placebo = 14 ) . No difference in the primary outcome was detected , with seven ( 28.0 % ) patients receiving bosentan , and four ( 28.6 % ) receiving placebo achieving a reduction in PVRi of greater than or equal to 20 % ( P = 0.97 ) at 16 weeks . There was no change in functional capacity or symptoms between the two groups at 16 weeks , nor any difference in rates of serious adverse events or deaths ( three deaths in each group ) . CONCLUSIONS This study shows no difference in invasive pulmonary hemodynamics , functional capacity , or symptoms between the bosentan and placebo groups over 16 weeks . Our data do not support the use of the dual endothelin-1 receptor antagonist , bosentan , in patients with PH and fibrotic IIP . Clinical trial registered with www . clinical trials.gov ( NCT 00637065 )", "Pulmonary hypertension is characterized by progressive elevation of pulmonary artery pressure and vascular resistance , often leading to right ventricular failure and death ( 1 - 3 ) . Continuous intravenous infusion of epoprostenol improves prognosis and symptoms in patients with primary ( idiopathic ) pulmonary hypertension ( 4 - 8 ) . R and omized , controlled clinical trials of epoprostenol for secondary pulmonary hypertension have not been conducted . Pulmonary hypertension frequently complicates the scleroderma spectrum of disease , which includes diffuse scleroderma , limited scleroderma ( the CREST syndrome [ calcinosis cutis , the Raynaud phenomenon , esophageal dysfunction , sclerodactyly , and telangectasia ] ) , and the overlap syndrome . These multisystem diseases are characterized by connective tissue and vascular abnormalities ; vascular lesions are prominent in all affected tissues ( 9 ) . Pulmonary hypertension occurs in up to 33 % of patients with diffuse scleroderma and 10 % to 50 % of those with the CREST syndrome ( 10 , 11 ) , in which it is one of the leading causes of death ( 12 , 13 ) . Pulmonary hypertension in the scleroderma spectrum of disease may be associated with interstitial pulmonary fibrosis or may consist of a direct involvement of small and medium-sized pulmonary arteries and arterioles with smooth-muscle hyperplasia , medial hypertrophy , and intimal proliferation ( 10 , 13 , 14 ) . Principal involvement of the pulmonary vasculature is more common in the CREST syndrome , whereas patients with pulmonary hypertension and diffuse scleroderma more often have interstitial lung disease ( 13 ) . No therapies have been proven effective for pulmonary hypertension secondary to the scleroderma spectrum of disease . Small numbers of patients have responded to captopril ( 15 ) , nifedipine ( 16 - 20 ) , and prazosin . In a short-term study of intravenous epoprostenol in seven patients with scleroderma ( two with diffuse scleroderma and five with limited scleroderma ) , six had a decrease in mean pulmonary artery pressure and pulmonary vascular resistance ( 21 ) . In a small study of pulmonary hypertension secondary to connective tissue disease , long-term infusion therapy with a prostacyclin analogue , iloprost , result ed in improvement in New York Heart Association ( NYHA ) functional class and quality of life but a variable hemodynamic response ( 22 ) . Results from a single-center , uncontrolled study suggest that long-term , continuously infused epoprostenol therapy can produce hemodynamic and symptomatic responses in patients with connective tissue disease who have severe pulmonary hypertension that is refractory to conventional medical therapy ( 23 ) . The rationale for using continuous epoprostenol infusion to treat pulmonary hypertension secondary to the scleroderma spectrum of disease was based on the efficacy of this therapy for primary pulmonary hypertension ( 4 - 8 ) and recognition that scleroderma is a disease characterized by vasospasm and structural changes in the walls of blood vessels . Prostacyclin is a naturally occurring substance produced by vascular endothelium that has vasodilating , antiplatelet aggregation , and cytoprotective effects ( 24 - 33 ) . Endogenous production of prostacyclin is decreased in an animal model of neonatal pulmonary hypertension ( 34 ) and in adult humans with pulmonary hypertension ( 35 ) . Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in patients with primary pulmonary hypertension ( 36 ) . Endothelial dysfunction also plays an important role in the vascular manifestations of the scleroderma spectrum of disease ( 37 , 38 ) , including the Raynaud phenomenon and digital ischemia , which cause considerable morbidity . Calcium-channel blockers ( 39 - 45 ) , enalapril ( 46 ) , and intermittent intravenous infusions of prostacyclin ( 47 - 49 ) and iloprost ( 50 - 54 ) improve the Raynaud phenomenon in some patients . Mixed results have been obtained with oral prostacyclin analogues ( 55 , 56 ) , and a recent multicenter trial of oral iloprost showed no benefit ( 57 ) . The effect of long-term , continuously infused epoprostenol on the severity of the Raynaud phenomenon and on digital ulcer counts has not been previously evaluated . Our 12-week multicenter , open-label , r and omized study was design ed to determine whether the beneficial effect of epoprostenol seen in patients with primary pulmonary hypertension could be extended to patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . Our objective was to evaluate the effects of continuous infusion of epoprostenol on exercise capacity in patients with pulmonary hypertension secondary to the scleroderma spectrum of disease . A secondary objective was assessment of the effects of long-term continuous epoprostenol infusion on cardiopulmonary hemodynamics , Borg Dyspnea Score , Dyspnea-Fatigue Rating , NYHA functional class , survival , and safety . Vasospastic manifestations , such as the Raynaud phenomenon and digital ulcerations , were also followed . Methods Patient Selection Eligible patients had pulmonary hypertension secondary to the scleroderma spectrum of disease in accordance with the inclusion and exclusion criteria summarized in Table 1 . For the purpose s of this study , the scleroderma spectrum of disease was defined as systemic sclerosis with diffuse or limited scleroderma ( 58 ) ; systemic sclerosis that overlapped with another connective tissue disease ; or the presence of definite features of systemic sclerosis , including the Raynaud phenomenon and positive test result for antinuclear antibody , plus positive test results for anticentromere antibody , anti-Scl 70 antibody , or nailfold capillary abnormalities . Systemic sclerosis with limited cutaneous involvement ( the CREST syndrome ) was defined as the presence of any three of the following conditions : subcutaneous calcinosis , the Raynaud phenomenon , esophageal dysfunction ( defined clinical ly ) , sclerodactyly , or telangectasia . Patients with interstitial lung disease of a more than mild degree were not included in the study because such patients were thought to be less likely to show benefit . Table 1 . Key Inclusion and Exclusion Criteria On the basis of a previous 12-week study of the effects of epoprostenol infusion in patients with severe primary pulmonary hypertension ( 6 ) and using the 6-minute walk test as the primary outcome measure , we calculated that 50 patients per treatment group would provide 80 % power to detect a difference of 50 meters in the average change from baseline , at an level of 0.05 ( two-tailed t-test ) . R and omization and Treatment The protocol was approved by the institutional review boards of the 17 participating centers . After giving informed consent , 111 eligible patients were r and omly assigned ( 1:1 ) to receive continuous epoprostenol infusion ( Flolan , Glaxo Wellcome , Inc. , Research Triangle Park , North Carolina ) plus conventional therapy or to receive conventional therapy alone . Investigators contacted a central r and omization center to obtain treatment assignment , which was based on a stratified r and omized block design . Assignments were stratified on the basis of vasodilator use at baseline ( yes or no ) and exercise capacity at baseline ( 50 to<200 m or 200 m ) and were r and omized within blocks . Fifty-six patients were assigned to receive epoprostenol plus conventional therapy , and 55 patients were assigned to receive conventional therapy alone . Investigators were not blinded to treatment group assignment ; however , independent blinded observers assessed the primary efficacy measure , exercise capacity . Patients taking calcium-channel blockers at study entry continued to take them during the study period . Adjustments in concomitant medications were allowed during the study on the basis of clinical judgment . Patients in both groups were to receive oral anticoagulants during the study ; 94 of the 111 enrolled patients took warfarin . Venous access for epoprostenol infusion ( in the epoprostenol group only ) was obtained by insertion of a permanent indwelling central venous catheter . Epoprostenol was infused continuously by a portable infusion pump ( CADD-1 Model 5100 HF , SIMS Deltec , St. Paul , Minnesota ) . Patients were instructed in sterile technique , catheter care , and drug preparation and administration . Epoprostenol therapy was initiated at a low dose ( usually 2 ng/kg of body weight per minute ) . During the 12-week study , doses were adjusted on the basis of signs or symptoms consistent with persistent pulmonary hypertension in the absence of intolerable adverse effects ( Figure 1 ) . Figure 1 . Epoprostenol dosing . Outcome Measures The primary measure of efficacy was exercise capacity , as defined by the distance a patient could walk in 6 minutes . Trained observers at each site who were not otherwise involved in patient care administered the 6-minute walk test . All patients wore an ambulatory infusion pump and a hospital gown over their clothes to mask the presence or absence of a long-term indwelling catheter , thereby blinding testers to the patients ' treatment groups . Each patient performed one practice walk test . A st and ardized , unencouraged 6-minute walk test was performed as described elsewhere ( 59 ) at baseline and at 1 , 6 , and 12 weeks . The 6-minute walk test has been shown to provide meaningful outcome data in assessing potential therapy for patients with pulmonary hypertension ( 6 ) . Secondary measures of efficacy were cardiopulmonary hemodynamics measured by performing right-heart catheterization using st and ard techniques at baseline and week 12 ; the Borg Dyspnea Score ( 60 ) , obtained immediately after completion of the 6-minute walk test at baseline and 1 , 6 , and 12 weeks ( 6 , 59 ) ; the Dyspnea-Fatigue Rating , obtained before the 6-minute walk test at baseline and weeks 1 , 6 , and 12 ( 61 ) ; NYHA functional class ( 62 ) , measured at baseline and weeks 1 , 6 , and 12 ; digital ulcer counts , done at baseline and weeks 6 and 12 ; and the severity of the Raynaud phenomenon ,", "Background — Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with consequent intracardiac right-to-left shunt and hypoxemia in patients with preexisting congenital heart disease . Because Eisenmenger syndrome is associated with increased endothelin expression , patients may benefit from endothelin receptor antagonism . Theoretically , interventions that have some effect on the systemic vascular bed could worsen the shunt and increase hypoxemia . Methods and Results — The Bosentan R and omized Trial of Endothelin Antagonist Therapy-5 ( BREATHE-5 ) was a 16-week , multicenter , r and omized , double-blind , placebo-controlled study evaluating the effect of bosentan , a dual endothelin receptor antagonist , on systemic pulse oximetry ( primary safety end point ) and pulmonary vascular resistance ( primary efficacy end point ) in patients with World Health Organization functional class III Eisenmenger syndrome . Hemodynamics were assessed by right- and left-heart catheterization . Secondary end points included exercise capacity assessed by 6-minute walk distance , additional hemodynamic parameters , functional capacity , and safety . Fifty-four patients were r and omized 2:1 to bosentan ( n=37 ) or placebo ( n=17 ) for 16 weeks . The placebo-corrected effect on systemic pulse oximetry was 1.0 % ( 95 % confidence interval , −0.7 to 2.8 ) , demonstrating that bosentan did not worsen oxygen saturation . Compared with placebo , bosentan reduced pulmonary vascular resistance index ( −472.0 dyne · s · cm−5 ; P=0.0383 ) . The mean pulmonary arterial pressure decreased ( −5.5 mm Hg ; P=0.0363 ) , and the exercise capacity increased ( 53.1 m ; P=0.0079 ) . Four patients discontinued as a result of adverse events , 2 ( 5 % ) in the bosentan group and 2 ( 12 % ) in the placebo group . Conclusions — In this first placebo-controlled trial in patients with Eisenmenger syndrome , bosentan was well tolerated and improved exercise capacity and hemodynamics without compromising peripheral oxygen saturation", "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", "OBJECTIVES The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan , an oral endothelin type A receptor-selective antagonist , in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Pulmonary arterial hypertension is a life-threatening and progressive disease with limited treatment options . Endothelin is a vasoconstrictor and smooth muscle cell mitogen that plays a critical role in the pathogenesis and progression of PAH . METHODS In this double-blind , dose-ranging study , 64 patients with idiopathic PAH or PAH associated with collagen vascular disease , anorexigen use , or human immunodeficiency virus infection were r and omized to receive 1 , 2.5 , 5 , or 10 mg of ambrisentan once daily for 12 weeks followed by 12 weeks of open-label ambrisentan . The primary end point was an improvement from baseline in 6-min walk distance ( 6MWD ) ; secondary end points included Borg dyspnea index , World Health Organization ( WHO ) functional class , a subject global assessment , and cardiopulmonary hemodynamics . RESULTS At 12 weeks , ambrisentan increased 6MWD ( + 36.1 m , p < 0.0001 ) with similar and statistically significant increases for each dose group ( range , + 33.9 to + 38.1 m ) . Improvements were also observed in Borg dyspnea index , WHO functional class , subject global assessment , mean pulmonary arterial pressure ( -5.2 mm Hg , p < 0.0001 ) , and cardiac index ( + 0.33 l/min/m2 , p < 0.0008 ) . Adverse events were mild and unrelated to dose , including the incidence of elevated serum aminotransferase concentrations > 3 times the upper limit of normal ( 3.1 % ) . CONCLUSIONS Ambrisentan appears to improve exercise capacity , symptoms , and hemodynamics in patients with PAH . The incidence and severity of liver enzyme abnormalities appear to be low", "Primary pulmonary hypertension ( PPH ) is a progressive disease with high mortality . Administration of i.v . epoprostenol has demonstrated improved exercise tolerance , haemodynamics , and survival . The orally active , dual endothelin receptor antagonist bosentan improves exercise endurance , haemodynamics , and functional class over the short term . To determine the effect of first-line bosentan therapy on survival , this study followed 169 patients with PPH treated with bosentan in two placebo-controlled trials and their extensions . Data on survival and alternative treatments were collected from September 1999 ( start of the first placebo-controlled study ) to December 31 , 2002 . Observed survival up to 36 months was reported as Kaplan-Meier estimates and compared with predicted survival as determined for each patient by the National Institutes of Health Registry formula . Kaplan-Meier survival estimates were 96 % at 12 months and 89 % at 24 months . In contrast , predicted survival was 69 % and 57 % , respectively . In addition , at the end of 12 and 24 months , 85 % and 70 % of patients , respectively , remained alive and on bosentan monotherapy . Factors that predicted a worse outcome included World Health Organization Functional Class IV and 6-min walk distance below the median ( 358 m ) at baseline . First-line bosentan therapy was found to improve survival in patients with advanced primary pulmonary hypertension" ]	There was a trend for endothelin receptor antagonists to reduce mortality ( OR 0.48 ; 95 % CI 0.21 to 1.09 ) , and limited data suggest that endothelin receptor antagonists improve Borg dyspnoea score and cardiopulmonary haemodynamics in symptomatic patients . Hepatic toxicity was not common , and endothelin receptor antagonists were well tolerated in this population . Endothelin receptor antagonists can increase exercise capacity , improve WHO/NYHA functional class , prevent WHO/NYHA functional class deterioration , reduce dyspnoea and improve cardiopulmonary haemodynamic variables in patients with pulmonary arterial hypertension with WHO/NYHA functional class II and III . However , there was only a trend towards endothelin receptor antagonists reducing mortality in patients with pulmonary arterial hypertension . Efficacy data are strongest in those with idiopathic pulmonary hypertension	BACKGROUND Pulmonary arterial hypertension is a devastating disease , which leads to right heart failure and premature death . Recent evidence suggests that endothelin receptor antagonists may be promising drugs in the treatment of pulmonary arterial hypertension . OBJECTIVES To evaluate the efficacy of endothelin receptor antagonists in pulmonary arterial hypertension .
23893797	[ "22494866", "28100342", "17307412", "22122887", "16084157", "5954842", "21880651", "22319064", "20118154", "3305080", "20298994", "21521833", "18546233", "15945105", "24106745", "16996831", "26385956" ]	[ "Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial.", "[The effect on myocardial perfusion and clinical outcome of intracoronary nicorandil injection prior to percutaneous coronary intervention in ST-segment elevation myocardial infarction].", "Early abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: a randomized study.", "Intracoronary Compared to Intravenous Abciximab in Patients with ST Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention Reduces Mortality, Target Vessel Revascularization and Reinfarction after 1 Year", "Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction (ADVANCE MI) trial.", "Intracoronary Nicorandil and the Prevention of the No-Reflow Phenomenon During Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction", "Routine use of the transradial approach in primary percutaneous coronary intervention: procedural aspects and outcomes in 2209 patients treated in a single high-volume centre", "Prehospital Abciximab in ST-Segment Elevation Myocardial Infarction: Results of the Randomized, Double-Blind MISTRAL Study", "Cardioprotective Effects of Ischemic Postconditioning in Patients Treated With Primary Percutaneous Coronary Intervention, Evaluated by Magnetic Resonance", "Impact of chronic statin-pretreatment on myocardial damage as assessed by Cardiac Magnetic Resonance findings in patients with acute ST-elevation myocardial infarction", "Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial.", "One-Year Clinical Outcome of Interventionalist- Versus Patient-Transfer Strategies for Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction: Results From the REVERSE-STEMI Study", "Concordant improvements in coronary flow reserve and ST‐segment resolution during percutaneous coronary intervention for acute myocardial infarction: A benefit of postconditioning", "Brief repetitive balloon occlusions enhance reperfusion during percutaneous coronary intervention for acute myocardial infarction: A pilot study", "No cardioprotective benefit of ischemic postconditioning in patients with ST-segment elevation myocardial infarction.", "Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial.", "Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial." ]	[ "BACKGROUND Postconditioning ( PC ) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention ( PPCI ) , nevertheless clinical experience is limited . We aim ed to explore the cardioprotective effect of PC using cardiac magnetic resonance ( CMR ) in ST-elevation myocardial infa rct ion ( STEMI ) patients treated by PPCI . METHODS A total of 78 patients with first STEMI ( aged 59±12 years ) referred for PPCI , were stratified for STEMI location and r and omly assigned to conventional PPCI or PPCI with PC . All patients , with occluded infa rct related artery and no collateral circulation , received abciximab intravenously before PPCI . After reperfusion by effective direct stenting , control subjects underwent no further intervention , while in treated patients PC was performed within 1 min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon . Primary end-point was infa rct size ( IS ) reduction , expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10 days after index PPCI . RESULTS All baseline characteristics but diabetes ( p=0.06 ) were balanced between groups . Postconditioning patients trended toward a larger IS compared to those treated by st and ard PPCI ( 20±12 % vs 14±10 % , p=0.054 ) . After exclusion of diabetics , PC group still showed a trend to larger IS ( p=0.116 ) . Major adverse events seem to be more frequent in PC group irrespective to diabetic status ( p=0.053 and p=0.080 , respectively ) . CONCLUSIONS This prospect i ve , r and omized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab . ( Clinical Trial Registration -unique identifier : NCT01004289 )", "Objective : To investigate the effect of intracoronary administration of nicor and il prior to primary percutaneous coronary intervention ( PPCI ) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . Methods : A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospect i ve controlled r and omized trial . Patients were assigned into three groups with r and om number table : the nicor and il group ( patients received intracoronary administration of 6 mg nicor and il after guide wire or balloon successfully crossed the target lesion , n=53 ) , the nitroglycerin group ( patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion , n=52 ) and the control group ( patients received routine treatment , n=53 ) . The primary outcomes were myocardial perfusion , including the levels of corrected TIMI frame count ( cTFC ) , and the incidence of no reflow or slow flow after PPCI . The secondary outcomes included the incidence of major adverse cardiovascular events ( MACE ) during hospitalization ( all-cause death , reperfusion arrhythmia within 2 hours after PPCI , angina within 24 hours after PPCI , new heart failure or worsening cardiac function , and repeat revascularization ) and within 3 months of follow-up ( all-cause death , nonfatal myocardial infa rct ion , repeat revascularization , post-infa rct ion angina , and re-hospitalization for congestive heart failure ) . Results : The age of enrolled patients was ( 62.9±11.3 ) years old , and 130 cases ( 82.3 % ) of them were male . The median time of symptom-onset to balloon was 4.50 ( 3.20 , 6.43 ) hours . There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames , (24.74±8.66)frames , and (27.06±10.40)frames ) , incidence of no reflow or slow flow after PPCI(5.7%(3/53 ) , 13.5%(7/52 ) , and 22.6%(12/53 ) ) , ST-segment resolution at 2 hours after procedure(90.6%(48/53 ) , 84.6%(44/52 ) , and 74.5%(38/53 ) ) , and reperfusion arrhythmia at 2 hours after procedure(15.1%(8/53 ) , 36.6%(19/52 ) , and 34.0%(18/53 ) ) among the 3 groups(P<0.01 or 0.05 ) . In the multivariate logistic regression models , intracoronary administration of nicor and il could lower the cTFC level ( OR=0.17 , 95%CI 0.10 - 0.41 , P=0.001 ) , acted as a protecting factor on lowering the incidence of no reflow or slow flow ( OR=0.13 , 95%CI 0.02 - 0.96 , P=0.045 ) and reperfusion arrhythmia ( OR=0.26 , 95%CI 0.09 - 0.74 , P=0.012 ) , as well as facilitating the ST-segment resolution at 2 hours after procedure ( OR=4.62 , 95%CI 1.14 - 18.82 , P=0.033 ) . However , observed parameters were similar between intracoronary administration of nitroglycerin group compared with control group ( all P>0.05 ) . MACE within 3 months of follow-up were similar among the 3 groups(all P>0.05 ) . Conclusion : Intracoronary administration of nicor and il prior to balloon dilation can significantly improve the myocardial perfusion and reduce the occurrence of reperfusion arrhythmia during PPCI for STEMI , but does not affect the short-term prognosis in STEMI patients", "BACKGROUND Early abciximab administration before primary percutaneous coronary intervention ( PPCI ) for ST-segment elevation myocardial infa rct ion ( STEMI ) is recommended in practice guidelines . However , the evidence supporting abciximab use before and during transfer for PPCI is limited . We investigated the effect of early abciximab administration on early reperfusion , ST-segment resolution , enzymatic infa rct size , and left ventricular function in patients with first anterior wall STEMI . METHODS A total of 59 nonshock patients with STEMI admitted < 12 hours to remote hospitals with anticipated delay to PPCI of < 90 minutes were r and omly assigned to 2 study groups : 27 patients received abciximab before transfer to catheterization laboratory ( Early group ) , and 32 patients received abciximab immediately before PPCI ( Late group ) . RESULTS Angiography revealed more frequent infa rct -related artery patency in the Early group than in the Late group ( TIMI 2 + 3 : 48 % vs 20 % , P = .04 ) . Better ST-segment resolution of > 50 % 60 minutes after PPCI was found in Early group than in the Late group ( 84 % vs 56.7 % , P = .04 ) . The area under the curve for creatine kinase-MB indicated a significantly greater extent of myocardial injury in the Late group versus the Early group ( 8324 + /- 4185 vs 5938 + /- 3949 U/L . h , P = .04 ) . There was a significant difference in the 30-day left ventricular end-systolic volume index ( P = .02 ) and end-diastolic volume index ( P = .05 ) in the echocardiography favoring the Early group . CONCLUSIONS Early abciximab administration before transfer for PPCI in patients with first anterior wall STEMI results in more frequent infa rct -related artery patency before PPCI , better myocardial tissue perfusion after PPCI , with lower enzymatic infa rct size and lower degree of left ventricular remodeling during 30-day follow-up", "Objectives : Administration of the glycoprotein IIb/IIIa inhibitor abciximab to patients with ST segment elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( pPCI ) improves outcome . Data have suggested that an intracoronary ( IC ) bolus might be superior to the st and ard intravenous ( IV ) administration . We have previously reported reduced short-term mortality and need for target vessel revascularization ( TVR ) with the IC route . We now present long-term data from our r and omized trial on IC versus IV abciximab in pPCI-treated STEMI patients . Methods : A total of 355 pPCI-treated STEMI patients were r and omized to either IC or IV bolus abciximab followed by a 12-hour IV infusion . Patients were followed for 1 year to observe mortality , TVR or myocardial infa rct ion ( MI ) and the combination of these . Results : The two treatment arms ( IV , n = 170 ; IC , n = 185 ) were similar with regard to baseline characteristics . Mortality was reduced from 10 % in the IV group to 2.7 % in the IC group ( p = 0.004 ) . TVR and MI were also reduced with IC administration ( TVR : 14.1 vs. 7.6 % , p = 0.04 ; MI : 11.8 vs. 5.4 % , p = 0.03 ) . Consequently , patients in the IC treatment arm had a relative risk reduction of 55 % for the combined endpoint after 1 year ( p = 0.002 ) compared to the IV treatment arm . Conclusions : In pPCI-treated STEMI patients treated with abciximab , IC bolus administration result ed in a significant reduction in mortality , TVR and MI compared to IV bolus administration", "BACKGROUND Facilitated percutaneous coronary intervention (PCI)--simultaneous administration of glycoprotein IIb/IIIa inhibitors and reduced-dose fibrinolytics before primary PCI for ST-segment elevation myocardial infa rct ion (STEMI)--may be a promising reperfusion strategy . METHODS The ADVANCE MI trial was intended to evaluate facilitated PCI in 5640 STEMI patients but was prematurely terminated as a result of slow recruitment over 12 months at 30 centers in the United States . Patients with STEMI with planned primary PCI were r and omly assigned to receive eptifibatide + 50 % of st and ard-dose tenecteplase ( which equated to 0.25 mg/kg intravenous bolus ) or eptifibatide + placebo before PCI and r and omized in a 2 x 2 factorial design to unfractionated heparin or enoxaparin . RESULTS A total of 148 patients were r and omized ( 74 patients in each treatment arm ) and formed the \" as-r and omized \" intention-to-treat population . However , only 69 patients actually received eptifibatide + tenecteplase , and 77 actually received eptifibatide + placebo ( 2 patients did not receive eptifibatide and 4 patients r and omized to tenecteplase did not receive this therapy)--these 146 patients formed the \" as-treated \" population . Among both population s , epicardial infa rct artery patency and myocardial tissue perfusion on pre-PCI angiography were improved in the tenecteplase group , but ST-segment resolution at 60 minutes was similar . The frequency of the primary end point of death or new/worsening severe heart failure at 30 days was higher among patients treated with eptifibatide + tenecteplase in the \" as-treated \" ( 10 % vs 3 % , P = .09 ) and the \" as-r and omized \" ( 11 % vs 1 % , P = .02 ) population s. Bleeding complications were 2-fold higher with eptifibatide + tenecteplase . Analysis of the results by treatment with unfractionated heparin versus enoxaparin demonstrated similar findings . CONCLUSIONS Although definitive conclusions can not be made as a result of the small sample size and premature study termination , facilitated PCI with eptifibatide + reduced-dose tenecteplase was associated with improved angiographic flow patterns , increases in adverse clinical outcomes , and higher bleeding rates compared with eptifibatide + placebo administered before primary PCI for STEMI", "Background This study aim ed to investigate intracoronary nicor and il treatment on the no-reflow phenomenon ( NRP ) during primary percutaneous coronary intervention ( PCI ) in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) and to compare nicor and il with sodium nitroprusside . Material / Methods Patients with sustained acute STEMI who underwent primary PCI ( N=120 ) were r and omly assigned to three groups : the nicor and il-treated group ( N=40 ) had 2 mg of nicor and il injected into the coronary artery at 2 mm beyond the occlusion with balloon pre-dilation ; the sodium nitroprusside-treated group ( N=40 ) underwent the same procedure , but with 200 μg of sodium nitroprusside ; the control group ( N=40 ) received PCI and balloon pre-dilation only . Coronary angiography , incidence of NRP , hypotensive episodes , ST-segment resolution ( STR ) rate , levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , creatine kinase-MB ( CK-MB ) , cardiac troponin I ( cTnI ) , wall motion score index ( WMSI ) , and left ventricular ejection fraction ( LVEF ) were measured before and after primary PCI . Major adverse cardiovascular events ( MACEs ) post-PCI and at three-month follow-up were recorded . Results Patients in the sodium nitroprusside and nicor and il groups had significantly improved thrombolysis in myocardial infa rct ion ( TIMI ) scores , TIMI myocardial perfusion grade ( TMPG ) , and ST-segment elevation resolution ( STR ) ( P<0.05 ) , and a significantly lower incidence of NRP ( P=0.013 ) . The incidence of intraoperative hypotension in the sodium nitroprusside group was significantly greater than the nicor and il and control groups ( P=0.035 ) . Conclusions Patients with sustained acute STEMI undergoing primary PCI , treated with intracoronary nicor and il had a reduced incidence of the NRP , improved myocardial perfusion and cardiac function", "Objective To examine the feasibility of a routine transradial approach ( TRA ) in primary percutaneous coronary intervention ( PPCI ) for acute ST-segment elevation myocardial infa rct ion ( STEMI ) . Design A single-centre observational study with prospect i ve data collection . Setting A high-volume interventional centre in Amsterdam , The Netherl and s. Patients Procedural data were analysed for 2209 consecutive patients presenting with STEMI without cardiogenic shock , between January 2001 and December 2008 . Interventions PPCI routinely performed by the TRA . Main Outcome Measures The primary outcomes of interest were the need for crossover to another vascular access site , the achievement of procedural success and their trends over time . Secondary outcome measures were trends in total procedural duration , fluoroscopy times and use of equipment . Results In a total of 2209 procedures the radial artery was the primary access site , comprising 96.1 % of all procedures performed during the study period . In 84 cases ( 3.8 % ) access site crossover was needed . Crossover rates decreased from 5.9 % in 2001–2 to 1.5 % in 2007–8 ( p=0.001 ) . The procedural success rate was 94.1 % , which remained stable over the years . Despite an increased complexity of PPCI ( more non-left anterior descending infa rct -related arteries , thrombus aspiration and multivessel PPCI ) , total procedural duration decreased from 38 min ( IQR 28–50 ) in 2001–2 to 24 min ( 18–33 ) in 2007–8 , p<0.001 for trend . Conclusions Systematic use of the TRA in PPCI yields low access site crossover , high procedural success rates and excellent procedural performances . It can therefore represent the primary access site in the vast majority of STEMI patients", "Background — The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue . We sought to investigate whether in-ambulance initiation of abciximab in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) improves ST-segment elevation resolution ( STR ) after primary percutaneous coronary intervention ( PCI ) . Methods and Results — MISTRAL ( Myocardial Infa rct ion with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace ) is a prospect i ve , r and omized , double-blind study . Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance ( ambulance group , n=127 ) or in the catheterization laboratory ( hospital group , n=129 ) . The primary end point was complete ( > 70 % ) STR after PCI . Complete STR was not significantly different between the 2 groups ( before PCI , 21.6 % versus 15.5 % , P=0.28 ; after PCI , 70.3 % versus 65.8 % , P=0.49 ) . Thrombolysis In Myocardial Infa rct ion ( TIMI ) 2 to 3 flow rates before PCI tended to be higher in the ambulance group ( 46.8 % versus 35 % , P=0.08 ) but not after PCI ( 70.3 % versus 65.8 % , P=0.49 ) . Slow flow tended to be lower ( 5.6 % versus 13.4 % , P=0.07 ) , and distal embolization occurred significantly less often in the ambulance group ( 8.1 % versus 21.1 % , P=0.008 ) . One- and 6-month major adverse cardiac event rates were low and similar in both groups . Conclusions — Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI . However , it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure . Larger studies are needed to confirm these results . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00638638", "Background —Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention ( PPCI ) in patients with ST-segment – elevation myocardial infa rct ion . However , because clinical experience is limited , we examined the cardioprotective effects of postconditioning , using cardiac MRI in patients treated with PPCI . Methods and Results —One hundred eighteen patients with ST-segment – elevation myocardial infa rct ion referred for PPCI were r and omly assigned to have either conventional PPCI or PPCI with postconditioning . Postconditioning was performed immediately after obtained reperfusion with 4 balloon occlusions , each lasting 30 seconds , followed by 30 seconds of reperfusion . The primary end point was myocardial salvage after 3 months as judged by delayed enhancement cardiac MRI . We found a 19 % relative reduction of infa rct size in the postconditioning group ( 51±16 % of total area at risk versus 63±17 % , P<0.01 ) , corresponding to a 31 % increase in salvage ratio . The number of patients developing heart failure was significantly fewer in the postconditioning group ( 27 % versus 46 % , P=0.048 ) . No significant evidence of interaction between the impact of postconditioning and the location of the culprit lesion or size of the myocardium at risk was detected ( P=0.21 and P=0.71 ) . Conclusions —Mechanical postconditioning reduces infa rct size in patients with ST-segment – elevation myocardial infa rct ion treated with PPCI . The impact of mechanical postconditioning seems to be independent of the size of myocardium at risk . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique Identifier : NCT00507156", "Background Recent data have demonstrated a lower mortality in acute ST-elevation myocardial infa rct ion ( STEMI ) patients with previous treatment with statins , especially in patients with high risk profiles . Moreover , a significant reduction in enzymatic infa rct size in non-STEMI patients could be observed . However , systematic data of the impact of chronic statin pre-treatment on myocardial damage and reperfusion injury assessed with the gold st and ard cardiac magnetic resonance imaging ( CMR ) are lacking . The aim of our prospect i ve study was therefore to assess the effects of a chronic statin pre-treatment on myocardial damage as assessed by CMR in patients with acute reperfused STEMI .", "OBJECTIVES This study sought to determine the efficacy of high-dose atorvastatin in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing primary percutaneous coronary intervention ( PCI ) . BACKGROUND Previous r and omized trials have demonstrated that statin pre-treatment reduced major adverse cardiac events ( MACEs ) in patients with stable angina pectoris and acute coronary syndrome . However , no r and omized studies have been carried out with STEMI patients in a primary PCI setting . METHODS A total 171 patients with STEMI were r and omized to 80-mg atorvastatin ( n = 86 ) or 10-mg atorvastatin ( n = 85 ) arms for pre-treatment before PCI . All patients were prescribed clopidogrel ( 600 mg ) before PCI . After PCI , both groups were treated with atorvastatin ( 10 mg ) . The primary end point was 30-day incidence of MACE including death , nonfatal MI , and target vessel revascularization . Secondary end points included corrected thrombolysis in myocardial infa rct ion frame count , myocardial blush grade , and ST-segment resolution at 90 min after PCI . RESULTS MACE occurred in 5 ( 5.8 % ) and 9 ( 10.6 % ) patients in the 80-mg and 10-mg atorvastatin pre-treatment arms , respectively ( p = 0.26 ) . Corrected thrombolysis in myocardial infa rct ion frame count was lower in the 80-mg atorvastatin arm ( 26.9 + /- 12.3 vs. 34.1 + /- 19.0 , p = 0.01 ) . Myocardial blush grade and ST-segment resolution were also higher in the 80-mg atorvastatin arm ( 2.2 + /- 0.8 vs. 1.9 + /- 0.8 , p = 0.02 and 61.8 + /- 26.2 vs. 50.6 + /- 25.8 % , p = 0.01 ) . CONCLUSIONS High-dose atorvastatin pre-treatment before PCI did not show a significant reduction of MACEs compared with low-dose atorvastatin but did show improved immediate coronary flow after primary PCI . High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion . ( Efficacy of High-Dose AtorvaSTATIN Loading Before Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infa rct ion [ STATIN STEMI ] ; NCT00808717 )", "Background — Traditional reperfusion options for patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) presenting to non- primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI . A third option , involving interventionalist transfer , was examined in the REVERSE-STEMI study . Methods and Results — A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were r and omized to receive PPCI with either an interventionalist- ( n=165 ) or a patient-transfer ( n=169 ) strategy . The primary end point of door-to-balloon ( D2B ) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events ( MACE ) at 1-year clinical follow-up were compared between the 2 groups . Compared with the patient-transfer strategy , the interventionalist-transfer strategy result ed in a significantly shortened D2B time ( median , 92 minutes versus 141 minutes ; P<0.0001 ) , with more patients having first balloon angioplasty within 90 minutes ( 21.2 % versus 7.7 % , P<0.001 ) . This treatment strategy also was associated with higher left ventricular ejection fraction ( 0.60±0.07 versus 0.57±0.09 , P<0.001 ) and improved 1-year MACE-free survival ( 84.8 % versus 74.6 % , P=0.019 ) . Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE ( hazard ratio , 0.63 ; 95 % CI , 0.45 to 0.88 ; P=0.003 ) . Conclusions — The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital , particularly in a congested cosmopolitan region where patient transfers could be prolonged . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00713557", "Objective : To assess the effect of ischemic postconditioning on indices of coronary microvascular function during percutaneous coronary intervention ( PCI ) for acute ST segment elevation myocardial infa rct ion ( STEMI ) . Background : Myocardial tissue level perfusion remains suboptimal in many patients with STEMI despite restoration of ante grade flow in the epicardial coronary artery . Methods : Twenty‐four patients with an evolving anterior STEMI were r and omized to undergo a previously‐vali date d ischemic postconditioning protocol or usual care during PCI . The extent of resolution of ST segment elevation along with Doppler‐tip catheter velocimetry was used as indices of myocardial reperfusion and microvascular function , respectively . Results : Postconditioned patients exhibited a greater , and therefore more rapid , extent of ST segment resolution ( postconditioning , 70 % ± 15 % ; control , 48 % ± 16 % ; P = 0.0002 ) by the end of the procedure . Postconditioned patients also exhibited a greater hyperemic coronary vasodilator response at the completion of the procedure ( coronary flow velocity reserve , CFVR : postconditioning , 2.2 ± 0.1 ; control , 1.5 ± 0.1 ; P < 0.0001 ) . The end‐procedure CFVR was directly related to the extent of the ST segment resolution ( r = 0.85 ) but inversely related to the absolute magnitude of ST segment elevation at end procedure ( r = −0.76 ) . Peak serum creatine kinase was significantly lower in postconditioned patients ( postconditioning , 1,524 ± 435 IU/l ; control , 1,862 ± 561 IU/l ; P = 0.03 ) . Conclusions : Ischemic postconditioning , as described , can be expeditiously performed during PCI for STEMI . Concordant changes in coronary flow reserve and ST segment resolution , measures of microcirculatory function , and myocardial perfusion , were greater in postconditioned patients . © 2008 Wiley‐Liss ,", "The objective of this study was to determine whether acutely ischemic myocardium may be conditioned during percutaneous coronary intervention for acute myocardial infa rct ion . Ischemic preconditioning is a powerful cardioprotective mechanism that limits infa rct size in animal investigations and ischemic sequelae during percutaneous coronary intervention in man . However , the conditioning stimulus in all these studies has been applied prior to the defining episode of ischemia . Seventeen patients undergoing percutaneous coronary intervention for acute myocardial infa rct ion were r and omly assigned to a st and ard ischemic preconditioning protocol ( n = 10 ) or a usual‐care control group ( n = 7 ) . ST segment shift response and Doppler‐derived distal coronary velocity data were compared . Despite similar degrees of baseline ST segment elevation , the magnitude of final ST segment elevation in the conditioning group was less than that in controls at the protocol conclusion ( conditioning , 1.60 ± 0.8 mV ; control , 4.0 ± 0.5 mV ; P < 0.001 ) . The rate of ST segment resolution was greater in the conditioning group ( conditioning , 0.28 ± 0.1 mV/min ; control , 0.12 ± 0.1 mV/min ; P = 0.02 ) . Distal coronary velocimetry indicated significant improvement in coronary flow velocity reserve in the conditioning group at the protocol conclusion ( conditioning , 1.8 ± 0.2 ; control , 1.4 ± 0.1 ; P < 0.008 ) . Brief periods of occlusion and reperfusion during percutaneous intervention for acute myocardial infa rct ion mitigate the extent of ischemic injury and improve distal myocardial perfusion . Such ischemic conditioning represents a potentially useful adjunct to strategies for enhancing reperfusion during acute myocardial infa rct ion . © 2005 Wiley‐Liss ,", "BACKGROUND Postconditioning is a potential cardioprotective strategy that has demonstrated conflicting and variable reductions in infa rct size in human trials . OBJECTIVES To determine whether postconditioning could increase the extent of myocardial salvage in patients with acute ST-segment elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention ( PPCI ) . METHODS One hundred two patients ( aged 57 ± 11 years ; 88 % male ) were r and omly assigned to a postconditioning or st and ard protocol . Cardiovascular magnetic resonance imaging was performed 3 days after PPCI to measure the volumetric extent of myocardial necrosis and the area at risk . RESULTS With similar time-to-reperfusion ( 170 ± 84 minutes in the postconditioning group vs. 150 ± 70 minutes in the st and ard group , P = 0.22 ) , the myocardial salvage index was not significantly different between the postconditioned group and the control group , averaging 42 ± 22 % vs. 33 ± 21 % , respectively ( P = 0.08 ) . Furthermore , postconditioning was not associated with a smaller infa rct size compared to controls ( 13 ± 7 g/m(2 ) vs. 15 ± 8 g/m(2 ) , respectively , P = 0.18 ) . CONCLUSIONS Postconditioning does not significantly increase myocardial salvage or reduce infa rct size in patients with STEMI undergoing PPCI . However , the possibility of a more modest impact of postconditioning can not be excluded with our sample size", "BACKGROUND Early restoration of epicardial flow before primary percutaneous coronary intervention ( PCI ) for ST-segment elevation myocardial infa rct ion ( STEMI ) has been associated with improved clinical outcomes . METHODS We hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor eptifibatide in the emergency department ( ED ) would yield superior epicardial flow and myocardial perfusion before primary PCI compared with initiating eptifibatide after diagnostic angiography in the cardiac catheterization laboratory ( CCL ) . Three hundred forty-three patients with STEMI were r and omized to either early ED eptifibatide ( n = 180 ) or CCL eptifibatide ( n = 163 ) . RESULTS The primary end point ( pre-PCI corrected TIMI frame count ) was significantly lower ( faster flow ) with early eptifibatide ( 77.5 + /- 32.2 vs 84.3 + /- 30.7 , P = .049 ) . The incidence of normal pre-PCI TIMI myocardial perfusion was increased among patients treated in the ED versus CCL ( 24 % vs 14 % , P = .026 ) . There was no excess of TIMI major or minor bleeding among patients treated in the ED versus CCL ( 6.9 % [ 12/174 ] vs 7.8 % [ 11/142 ] , P = NS ) . CONCLUSION A strategy of early initiation of eptifibatide in the ED before primary PCI for STEMI yields superior pre-PCI TIMI frame counts , reflecting epicardial flow , and superior TIMI myocardial perfusion compared with a strategy of initiating eptifibatide in the CCL without an increase in bleeding risk", "AIMS Remote ischaemic conditioning ( RIC ) and postconditioning ( PostC ) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in experimental and clinical ST-elevation myocardial infa rct ion ( STEMI ) trials . However , their combined effects have not been studied in detail . The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control . METHODS AND RESULTS This prospect i ve , controlled , single-centre study r and omized 696 STEMI patients to one of the following three groups : ( i ) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention ( PCI ) ; ( ii ) PostC in addition to PCI ; and ( iii ) conventional PCI ( control ) . The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance ( CMR ) imaging within 3 days after infa rct ion . Secondary endpoints included infa rct size and microvascular obstruction ( MVO ) assessed by CMR . The combined clinical endpoint consisted of death , reinfa rct ion , and new congestive heart failure within 6 months . The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group ( 49 [ interquartile range 30 - 72 ] vs. 40 [ interquartile range 16 - 68 ] , P = 0.02 ) . Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI ( P = 0.39 ) . The secondary endpoints , including infa rct size and MVO , showed no significant differences between groups . Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups ( P = 0.44 ) . CONCLUSION Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC. CLINICAL TRIALSGOV NCT02158468" ]	This present meta- analysis suggests that statin pretreatment might be effective in improving myocardial perfusion in STEMI patients	BACKGROUND To achieve sufficient myocardial perfusion in ST-segment elevation myocardial infa rct ion ( STEMI ) patients receiving primary percutaneous coronary intervention ( PPCI ) , many adjunctive therapies have been proposed . Previous trials have reported variances in myocardial perfusion improvement for statin pretreatment , which made it inconvincible to confirm the beneficial effects of statins . Therefore , we performed a systematic review and meta- analysis to determine whether statin pretreatment was effective in improving myocardial perfusion . HYPOTHESIS Statin pretreatment could improve myocardial perfusion in STEMI patients undergoing PPCI .
27167891	[ "18719977", "18236304", "25957438", "23674839", "15804687", "21218733", "18713509", "22140149", "21575309", "18713508", "24629480", "20418383", "15359920", "22092459", "3655638", "9224127", "15173269" ]	[ "Prevalence of and Associations with Waterpipe Tobacco Smoking among U.S. University Students", "Waterpipe tobacco smoking: knowledge, attitudes, beliefs, and behavior in two U.S. samples.", "Waterpipe Tobacco Smoking Prevalence and Correlates in 25 Eastern Mediterranean and Eastern European Countries: Cross-Sectional Analysis of the Global Youth Tobacco Survey.", "Beliefs and perceptions toward quitting waterpipe smoking among cafe waterpipe tobacco smokers in Bahrain.", "Are waterpipe users interested in quitting?", "Waterpipe smoking in Kuwait.", "Cigarettes and waterpipe smoking among medical students in Syria: a cross-sectional study.", "Patterns of water-pipe and cigarette smoking initiation in schoolchildren: Irbid longitudinal smoking study.", "Waterpipe tobacco use among Iranian university students: correlates and perceived reasons for use.", "Knowledge, attitudes and practice of university students regarding waterpipe smoking in Pakistan.", "Behavioral cessation treatment of waterpipe smoking: The first pilot randomized controlled trial.", "Water pipe tobacco smoking among university students in Jordan.", "Water-pipe smoking effects on pulmonary permeability using technetium-99m DTPA inhalation scintigraphy", "Intention to smoke tobacco using a waterpipe among students in a southeastern U.S. College.", "Mortality in relation to cigarette and pipe smoking: 16 years' observation of 25,000 Swedish men.", "Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases", "Association between exclusive pipe smoking and mortality from cancer and other diseases." ]	[ "Background Although waterpipe tobacco smoking seems to be increasing on U.S. university campuses , these data have come from convenience sample s. Purpose We aim ed to determine the prevalence of and associations with waterpipe tobacco smoking among a r and om sample of students . Methods We surveyed a r and om sample of graduate and undergraduate students at a large , urban university . We used multivariate modeling to determine independent associations between belief-related predictors and waterpipe tobacco smoking . Results Of the 647 respondents , waterpipe smoking was reported in 40.5 % , over the past year in 30.6 % , and over the past 30 days in 9.5 % . Over half of the sample ( 52.1 % ) perceived that tobacco smoking from a waterpipe was less addictive than cigarette smoking . In fully adjusted multivariate models , 1-year waterpipe smoking was associated with low perceived harm ( OR = 2.54 , 95 % CI = 1.68 , 3.83 ) , low perceived addictiveness ( OR = 4.64 , 95 % CI = 3.03 , 7.10 ) , perception of high social acceptability ( OR = 20.00 , 95 % CI = 6.03 , 66.30 ) , and high perception of popularity ( OR = 4.72 , 95 % CI = 2.85 , 7.82 ) . Conclusions In this sample , lifetime waterpipe use was as common as lifetime cigarette use . Perception of harm , perception of addictiveness , social acceptability , and popularity were all strongly related to waterpipe smoking", "Despite evidence of increasing waterpipe tobacco smoking prevalence among U.S. young adults , little is known about the knowledge , attitudes , beliefs , and smoking patterns of waterpipe users in this population . To address this lack of knowledge , two convenience sample s of U.S. waterpipe users were surveyed -- one from a Richmond , Virginia , waterpipe café ( n=101 ) , the other from an Internet forum called HookahForum.com ( n=100 ) . Sixty percent reported first-time waterpipe use at or before age 18 . Daily waterpipe use was reported by 19 % , weekly use by 41 % , and monthly use by 29 % . Waterpipe use was more common during the weekend ( 75 % ) than during weekdays ( 43 % ) . Forty-four percent reported spending > or=60 min smoking tobacco during a waterpipe session . The majority of waterpipe users owned a waterpipe ( 57 % ) and purchased it on the Internet ( 71 % ) . Many waterpipe users smoked the sweetened and flavored tobacco ( i.e. , maassel ) , and fruit flavors were the most popular ( 54 % ) . Past month use of cigarettes , tobacco products other than cigarettes or waterpipe , and alcohol was 54 % , 33 % , and 80 % respectively , and 36 % reported past-month marijuana use . Most waterpipe users were confident about their ability to quit ( 96 % ) , but only a minority ( 32 % ) intended to quit . Most waterpipe users believed waterpipe tobacco smoking was less harmful and addictive than cigarettes . These results are from small convenience sample s ; more detailed study of a larger group of r and omly sample d U.S. waterpipe tobacco smokers will be valuable in underst and ing this behavior and developing effective strategies to prevent it", "INTRODUCTION Waterpipe tobacco smoking is highly prevalent among young people in some setting s. There is an absence of nationally representative prevalence studies of waterpipe tobacco use and dual use with other tobacco products in young people . METHODS We conducted a secondary analysis of the Global Youth Tobacco Survey , a nationally representative cross-sectional study of students aged 13 - 15 years . Of 180 participating countries , 25 included optional waterpipe tobacco smoking questions : 15 Eastern Mediterranean and 10 Eastern European countries . We calculated the prevalence of current ( past 30-day ) waterpipe tobacco use , including dual waterpipe and other tobacco use , and used logistic regression models to identify sociodemographic correlates of waterpipe tobacco smoking . Individual country results were combined in a r and om effects meta- analysis . RESULTS Waterpipe tobacco smoking prevalence was highest in Lebanon ( 36.9 % ) , the West Bank ( 32.7 % ) and parts of Eastern Europe ( Latvia 22.7 % , the Czech Republic 22.1 % , Estonia 21.9 % ) . These countries also recorded greater than 10 % prevalence of dual waterpipe and cigarette use . In a meta- analysis , higher odds of waterpipe tobacco smoking were found among males ( Adjusted odds ratio [ AOR ] = 1.37 , 95 % confidence interval [ CI ] = 1.18 % to 1.59 % ) , cigarette users ( AOR = 6.95 , 95 % CI = 5.74 % to 8.42 % ) , those whose parents ( AOR = 1.54 , 95 % CI = 1.31 % to 1.82 % ) or peers smoked ( AOR = 3.53 , 95 % CI = 2.97 % to 4.20 % ) and those whose parents had higher educational attainment ( Father , AOR = 1.47 , 95 % CI = 1.14 % to 1.89 % ; Mother , AOR = 1.62 , 95 % CI = 1.07 % to 2.46 % ) . We report on regional- and country income-level differences . CONCLUSIONS Waterpipe tobacco smoking , including dual waterpipe and cigarette use , is alarmingly high in several Eastern Mediterranean and Eastern European countries . Ongoing waterpipe tobacco smoking surveillance is warranted", "INTRODUCTION There is a rising prevalence of waterpipe smoking worldwide , but still a paucity of information on perceptions toward quitting waterpipe use . We set out to establish the beliefs and perceptions of café waterpipe smokers toward quitting waterpipe smoking in the Kingdom of Bahrain . METHODS A cross-sectional study . A r and om sample of 20 of 91 cafés serving waterpipe tobacco in Bahrain was taken . A question naire was administered in each café to 20 participants aged 18 and above . RESULTS Three hundred eighty participants completed question naires from waterpipe smokers . Eighty-four percent of participants were Bahraini and 71 % had a university degree . Mean age was 28.9 years . Average age of waterpipe smoking initiation was 20.3 years . The majority of waterpipe users chose flavored tobacco . Sixty-one percent smoked waterpipe tobacco daily with a mean smoking time of 2.6hr/day . Seventy-two percent considered waterpipe tobacco as harmful as or more harmful than cigarettes , but 67 % considered cigarettes as more addictive . Eighty-two percent stated that they could quit waterpipe at any time , but only 40 % were interested in quitting . Interest in quitting smoking was related to 4 variables : a physician mentioning the need to quit smoking , being non-Bahraini , having a family with a hostile attitude toward waterpipe smoking , and not considering oneself \" hooked \" on waterpipe tobacco . CONCLUSIONS Waterpipe smokers in Bahrain cafés are frequent and high users . Health professionals must consider waterpipe smoking in all consultations and health promotion messages . A partnership between health professionals and disapproving members of families may be an effective strategy in encouraging waterpipe smokers to quit", "Waterpipe smoking has increased dramatically worldwide in recent years , with an estimated 100 million daily users . Research on this traditional Middle Eastern tobacco use method is in its infancy , and little is known about users ' cessation-related attitudes and experiences . A r and om sample of 268 narghile ( waterpipe ) smokers ( 40 % female ; mean age = 30 years ; range = 18 - 68 ) was obtained from cafes and restaurants in Aleppo , Syria . The majority of users ( 86.5 % ) believed they could quit using waterpipes at any time , but that belief was inversely related to perceived dependence , with only 48.7 % of those who thought they were \" very hooked \" believing they could quit . Interest in quitting was expressed by 28.4 % of subjects , with the majority ( 89.2 % ) reporting health concerns as a primary reason , and 59.2 % having made an unsuccessful quit attempt in the past year . In a logistic regression model , independent predictors of interest in quitting included being married , having smoked for fewer years , not increasing the frequency of smoking over time , and having family members who do not smoke a waterpipe and disapprove of its use . Results indicate that a sizable percentage of waterpipe users express interest in quitting and have tried unsuccessfully in the past to quit . Waterpipe use needs to be considered in developing effective tobacco use cessation programs in the Middle East", "A nonr and om sampIe of 2972 Kuwaitis answered a question naire about smoking behaviour and beliefs . More than one-third ( 35 % ) were nonsmokers , 45 % smoked only the waterpipe , 12 % only cigarettes and 8 % both waterpipe and cigarettes . Compared with cigarette smokers , waterpipe smokers were more likely to be female and to be unskilled manual workers than professionals or students . Waterpipe smokers started the habit at an older age on average than cigarette smokers . Most waterpipe smokers smoked only 1 bowl per day , and smoked mostly at coffee houses . Factor analysis of beliefs about waterpipe smoking result ed in 4 groups of beliefs which explained 50 % of the variance . The results are discussed in terms of public health policy and possible risk reduction strategies", "OBJECTIVES To investigate tobacco use , beliefs and attitudes among medical students in Syria . METHODS A cross-sectional study of a r and om sample of 570 medical students ( first and fifth year ) registered at the Damascus University Faculty of Medicine in 2006 - 2007 . We used a self-administered question naire for demo-graphic information , smoking behaviour ( cigarette , waterpipe ) , family and peer smoking , attitudes and beliefs about smoking and future role in advising patients to quit smoking . RESULTS The overall prevalence of tobacco use was 10.9 % for cigarettes ( 15.8 % men , 3.3 % women ) , 23.5 % for waterpipe ( 30.3 % men , 13.4 % women ) and 7.3 % for both ( 10.1 % men , 3.1 % women ) . Both smoking methods were more popular among the fifth year students ( 15.4 % and 27 % ) compared to their younger counterparts ( 6.6 % and 19.7 % ) . Regular smoking patterns predominated for cigarettes ( 62 % ) , while occasional use patterns predominated for waterpipes ( 83 % ) . More than two thirds of students ( 69 % ) thought they might not address or would have difficulty addressing smoking in their future patients . CONCLUSION The level of tobacco use among Syrian medical students is alarming and highlights the rapidly changing patterns of waterpipe use , especially among female students . Medical schools should work harder to tackle this phenomenon and address it more efficiently in their curricula", "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", "SETTING Waterpipe smoking is becoming a global health crisis among youth . OBJECTIVE To identify the prevalence of waterpipe use among Iranian university students and to explore perceived reasons for use . METHODS A r and om sample of 1024 university students at two major universities in South Iran was enrolled in the study . A three-part question naire ( baseline data , tobacco smoking status and perceived reasons for waterpipe use ) was used . Students filled out the self-administered question naire in their classrooms . RESULTS The prevalence of waterpipe smoking in the respondents ' lifetime and in the last 30 days was 42.5 % and 18.7 % , respectively . The mean age at initiation of waterpipe smoking was 16.3 ± 3.2 years . Ever smoking was positively associated with age and male sex , whereas no association was found regarding marital status . The highest odds of lifetime waterpipe smoking were observed in students with close friends who smoked the waterpipe ( 5.94 , 95%CI 4.26 - 8.30 ) . The most important perceived reason for waterpipe smoking as stated by students was enjoyment ( 55.8 % ) . CONCLUSION Given the alarming prevalence of waterpipe smoking , preventive measures should be adopted among university students taking into account the influence of peers , siblings and parents in the lessening social tolerance of waterpipe smoking", "OBJECTIVES To study the awareness , perceptions and practice of university students in Karachi , Pakistan , with regard to shisha ( waterpipe ) smoking . DESIGN Cross-sectional survey conducted among students at four different universities of Karachi , selected through r and om cluster sampling . RESULTS A total of 450 participants , 59.6 % males ( n=268 ) and 40.4 % females ( n=182 ) , were included in the study . About half of the participants reported having ever smoked shisha ( n=241 , 53.6 % ) . On examining factors associated with starting shisha smoking , curiosity was found to be the most common reason ( n=148 , 61.4 % ) , followed by pleasure-seeking ( n=113 , 46.9 % ) , peer pressure ( n=55 , 22.8 % ) , boredom ( n=43 , 17.8 % ) and stress ( n=26 , 10.8 % ) . Of 241 participants who had ever smoked waterpipes , the majority ( n=149 , 61.8 % ) were current smokers . A vast majority of participants ( n=269 , 60 % ) considered waterpipe smoking to be less unhealthy than cigarette smoking . Boredom in youth , use of waterpipe in leisure activities and peer pressure were identified as the most common reasons for the escalating popularity of waterpipe smoking in Pakistan . CONCLUSIONS Waterpipe smoking is very popular among Pakistani university students , and knowledge among university students about the dangers of waterpipe smoking is alarmingly low", "BACKGROUND Waterpipe use has increased dramatically in the Middle East and other parts of the world . Many users exhibit signs of dependence , including withdrawal and difficulty quitting , but there is no evidence base to guide cessation efforts . METHODS We developed a behavioral cessation program for willing-to-quit waterpipe users , and evaluated its feasibility and efficacy in a pilot , two arm , parallel group , r and omized , open label trial in Aleppo , Syria . Fifty adults who smoked waterpipe ≥3 times per week in the last year , did not smoke cigarettes , and were interested in quitting were r and omized to receive either brief ( 1 in-person session and 3 phone calls ) or intensive ( 3 in-person sessions and 5 phone calls ) behavioral cessation treatment delivered by a trained physician in a clinical setting . The primary efficacy end point of the developed interventions was prolonged abstinence at three months post-quit day , assessed by self-report and exhaled carbon monoxide levels of < 10 ppm . Secondary end points were 7 day point-prevalent abstinence and adherence to treatment . RESULTS Thirty percent of participants were fully adherent to treatment , which did not vary by treatment group . The proportions of participants in the brief and intensive interventions with prolonged abstinence at the 3-month assessment were 30.4 % and 44.4 % , respectively . Previous success in quitting ( OR=3.57 ; 95 % CI=1.03 - 12.43 ) predicted cessation . Higher baseline readiness to quit , more confidence in quitting , and being unemployed predicted a better adherence to treatment ( all p-values < 0.05 ) . CONCLUSIONS Brief behavioral cessation treatment for waterpipe users appears to be feasible and effective", "INTRODUCTION Although water pipe tobacco smoking is common in Lebanon and Syria , prevalence in neighboring Jordan is uncertain . The purpose s of this study were ( a ) to assess the prevalence of water pipe tobacco smoking among university students in Jordan and ( b ) to determine associations between sociodemographic variables and water pipe tobacco smoking in this population . METHODS A trained interviewer administered a question naire among r and omly selected students at four prominent universities in Jordan . The question naire assessed sociodemographic data , personal history of water pipe tobacco use , and attitudes regarding water pipe tobacco smoking . We used logistic regression to determine independent associations between sociodemographic and attitudinal factors and each of two dependent variables : ever use of water pipe and use at least monthly . RESULTS Of the 548 participants , 51.8 % were male and mean age was 21.7 years . More than half ( 61.1 % ) had ever smoked tobacco from a water pipe , and use at least monthly was reported by 42.7 % . Multivariable analyses controlling for all relevant factors demonstrated significant associations between ever use and only two sociodemographic factors : ( a ) gender ( for women compared with men , odds ratio [ OR ] = 0.11 , 95 % CI = 0.07 - 0.17 ) and ( b ) income ( for those earning 500 - 999 Jordanian dinar ( JD ) monthly vs. < 250 JD monthly , OR = 2.37 , 95 % CI = 1.31 - 4.31 ) . There were also significant associations between perception of harm and addictiveness and each outcome . DISCUSSION Water pipe tobacco smoking is highly prevalent in Jordan . Although use is associated with male gender and upper middle income levels , use is widespread across other sociodemographic variables . Continued surveillance and educational interventions emphasizing the harm and addictiveness of water pipe tobacco smoking may be valuable in Jordan", "Objective Although extensive work has been done on cigarette smoking and its effects on pulmonary function , there are limited number of studies on water-pipe smoking . The effects of water-pipe smoking on health are not widely investigated . The aim of this study was to determine the effects of water-pipe smoking on pulmonary permeability . Methods Technetium-99 m DTPA inhalation scintigraphy was performed on 14 water-pipe smoker volunteers ( all men , mean age 53.7 ± 9.8 ) and 11 passive smoker volunteers ( 1 woman , 10 men , mean age 43.8 ± 12 ) . Clearance half-time ( T 1/2 ) was calculated by placing a monoexponential fit on the time activity curves . Penetration index ( PI ) of the radioaerosol was also calculated . Results PI was 0.58 ±0.14 and 0.50 ± 0.12 for water-pipe smokers ( WPS ) and passive smokers ( PS ) respectively . T1/2 of peripheral lung was 57.3 ± 12.7 and 64.6 ± 13.2 min , central airways was 55.8 ± 23.5 and 80.1 ± 35.2 min for WPS and PS , respectively ( p ≤ 0.05 ) . FEV1/FVC% was 82.1 ± 8.5 ( % ) and 87.7 ± 6.5 ( % ) for WPS and PS , respectively ( 0.025 < p ≤ 0.05 ) . Conclusions We suggest that water-pipe smoking effects pulmonary epithelial permeability more than passive smoking . Increased central mucociliary clearance in water-pipe smoking may be due to preserved humidity of the airway tracts", "OBJECTIVE Guided by the Theory of Reasoned Action , this study examined the association of behavioral beliefs , attitudes , normative beliefs , and subjective norms with waterpipe tobacco smoking intention in college students . DESIGN AND SAMPLE A cross-sectional design was used . A Web-based survey was sent to a r and om sample of 1,000 undergraduate students from a public institution in the southeast to recruit participants . MEASURES The Theory of Reasoned Action Waterpipe Question naire , a modified version of the Fishbein-Ajzen-Hanson Question naire , was used to capture modal constructs of the Theory of Reasoned Action related to waterpipe use . Cronbach 's α coefficients for the scales of the Theory of Reasoned Action Waterpipe Question naire ranged from .76 to .95 . RESULTS Of the sample ( n=223 ) , 13.5 % currently smoked a waterpipe and 61 % had ever done so . Using multiple regression , attitudes , behavioral beliefs , and subjective norms were associated with intention to smoke a waterpipe in the next 3 months and collectively explained 35 % of the variance in intention . The full model , which included all the constructs of the Theory of Reasoned Action , demographic variables , and tobacco use variables , explained 83 % of the variance in intention to smoke a waterpipe in the next 3 months . CONCLUSIONS This study provides valuable information that may be used to target students at risk for waterpipe smoking and serves as a starting point in developing theoretically driven interventions to prevent waterpipe smoking", "In a r and om sample of 25,129 Swedish men who responded to a question naire on smoking habits in 1963 the cause specific mortality was followed through 1979 . In the cohort , 32 % smoked cigarettes , 27 % a pipe , and 5 % cigars . There were clear covariations ( p less than 0.001 ) between the amount of tobacco smoked and the risk of death due to cancer of the oral cavity and larynx , oesophagus , liver , pancreas , lung , and bladder as well as due to bronchitis and emphysema , ischaemic heart disease , aortic aneurysm , and peptic ulcer . Pipe smokers showed similar risk levels to cigarette smokers . There was a close to linear increase in lung cancer risk in relation to the amount of tobacco smoked for cigarette , pipe , and cigar smokers , respectively . An increasing risk of ischaemic heart disease with amount smoked was seen among both cigarette and pipe smokers . A similar fraction of inhalers in Swedish cigarette and pipe smokers may explain the similarity in risks", "Abstract Objective : To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three smoking related diseases – lung cancer , ischaemic heart disease , and chronic obstructive lung disease . Design : A prospect i ve study of 21 520 men aged 35 - 64 years when recruited in 1975 - 82 with detailed history of smoking and measurement of carboxyhaemoglobin . Main outcome measures : Notification of deaths ( to 1993 ) classified by cause . Results : Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers ( 8.1 g/day v 20 g/day ) , but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes ( 8.1 g ) and had higher carboxyhaemoglobin saturations ( 1.2 % v 1.0 % , P<0.001 ) , indicating that they inhaled tobacco smoke to a greater extent . They had a 51 % higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes ( relative risk 1.51 ; 95 % confidence interval 0.96 to 2.38 ) , a 68 % higher risk than lifelong non-smokers ( 1.68 ; 1.16 to 2.45 ) , a 57 % higher risk than former cigarette smokers who gave up smoking over 20 years before entry ( 1.57 ; 1.04 to 2.38 ) , and a 46 % lower risk than continuing cigarette smokers ( 0.54 ; 0.38 to 0.77 ) . Conclusion : Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes . Much of the effect is due to the reduction in the quantity of tobacco smoked , and some is due to inhaling less . Men who switch do not , however , achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes . All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers . Key messages The health risks from smoking pipes or cigars are less than those from smoking cigarettes , but there is little direct evidence on these risks in cigarette smokers who switch to pipes or cigars This prospect i ve study shows that smokers who switch from cigarettes to pipes or cigars halve their combined risk of dying of lung cancer , ischaemic heart disease , or chronic obstructive lung disease compared with continuing smokers , but their risk was still about 50 % higher than that of lifelong non-smokers Some of this reduction in risk was due to reduced inhaling , but most of it was due to a reduction in the amount of tobacco smoked The best option is either not to smoke or to give up altogether ; failing that , switching to pipes or cigars is better than continuing to smoke", "BACKGROUND Although many studies have examined the adverse health effects of pipe smoking combined with other forms of tobacco use , few have included large numbers of exclusive pipe smokers . The prevalence of pipe smoking has declined since the 1960s , yet usage is still common regionally , especially among older population s. METHODS Using Cox proportional hazards models , we examined the association between pipe smoking and mortality from tobacco-related cancers and other diseases in a cohort of U.S. men enrolled in the Cancer Prevention Study II , an American Cancer Society prospect i ve study . The cohort of 138 307 men included those who reported , in their 1982 enrollment question naire , exclusive current or former use of pipes ( n = 15,263 men ) or never use of any tobacco product ( n = 123,044 men ) . Analyses were based on 23 589 men who died during 18 years of follow-up . RESULTS Current pipe smoking , compared with never use of tobacco , was associated with an increased risk of death from cancers of the lung ( relative risk [ RR ] = 5.00 , 95 % confidence interval [ CI ] = 4.16 to 6.01 ) , oropharynx ( RR = 3.90 , 95 % CI = 2.15 to 7.08 ) , esophagus ( RR = 2.44 , 95 % CI = 1.51 to 3.95 ) , colorectum ( RR = 1.41 , 95 % CI = 1.15 to 1.73 ) , pancreas ( RR = 1.61 , 95 % CI = 1.24 to 2.09 ) , and larynx ( RR = 13.1 , 95 % CI = 5.2 to 33.1 ) , and from coronary heart disease ( RR = 1.30 , 95 % CI = 1.18 to 1.43 ) , cerebrovascular disease ( RR = 1.27 , 95 % CI = 1.09 to 1.48 ) , and chronic obstructive pulmonary disease ( RR = 2.98 , 95 % CI = 2.17 to 4.11 ) . These risks were generally smaller than those associated with cigarette smoking and similar to or larger than those associated with cigar smoking . Relative risks of lung cancer showed statistically significant increases with number of pipes smoked per day , years of smoking , and depth of inhalation and decreases with years since quitting . CONCLUSION Results from this large prospect i ve study suggest that pipe smoking confers a risk of tobacco-associated disease similar to cigar smoking" ]	In conclusion , there is a lack of evidence of effectiveness for most waterpipe interventions .	Waterpipe tobacco smoking is growing in popularity despite adverse health effects among users . We systematic ally review ed the literature , search ing MEDLINE , EMBASE and Web of Science , for interventions targeting prevention and cessation of waterpipe tobacco smoking .
28753768	[ "22706696", "5425353", "19819762", "4570513", "26814279", "21269397", "15860388", "20300220", "3845056", "24262772", "27481311", "22321388", "27561310", "23347100", "25893421", "14961048", "19620493" ]	[ "How do doctors refer to patient-reported outcome measures (PROMS) in oncology consultations?", "Sexual Therapy for Women with Multiple Sclerosis and Its Impact on Quality of Life", "Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion.", "Patient-Reported Outcomes Measurement Information System (PROMIS) instruments among individuals with symptomatic knee osteoarthritis: a cross-sectional study of floor/ceiling effects and construct validity", "Performance of a Patient Reported Outcomes Measurement Information System (PROMIS) Short Form in Older Adults with Chronic Musculoskeletal Pain.", "Impact of sacral neuromodulation on female sexual function and his correlation with clinical outcome and quality of life indexes: a monocentric experience.", "Effects of short-term moderate exercise training on sexual function in male patients with chronic stable heart failure.", "Sexual impairment and its effects on quality of life in patients with rectal cancer.", "The CopenHeartSF trial—comprehensive sexual rehabilitation programme for male patients with implantable cardioverter defibrillator or ischaemic heart disease and impaired sexual function: protocol of a randomised clinical trial", "Method of administration of PROMIS scales did not significantly impact score level, reliability, or validity.", "Impact of National Institutes of Health Gastrointestinal PROMIS Measures in Clinical Practice: Results of a Multicenter Controlled Trial", "Effects of vaginal prolapse surgery on sexuality in women and men; results from a RCT on repair with and without mesh.", "Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia", "Prospective, multidimensional evaluation of sexual disorders in men after laser photovaporization of the prostate.", "Development and Validation of a Single-Item Screener for Self-Reporting Sexual Problems in U.S. Adults", "Quality of life, mood, and sexual function: a path analytic model of treatment effects in men with erectile dysfunction and depressive symptoms", "Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function." ]	[ "Purpose We conducted a secondary qualitative analysis of consultations between oncologists and their patients to explore how patient-reported outcome measures ( PROMs ) data were referred to in the process of ( 1 ) eliciting and exploring patients ’ concerns ; ( 2 ) making decisions about supportive treatment and ( 3 ) making decisions about chemotherapy and other systemic treatments . Methods We purposively sample d audio recordings of 18 consultations from the intervention arm and 4 from the attention control arm of a previous UK r and omised controlled trial of the feedback of PROMs data to doctors ( Velikova et al. in J Clin Oncol 22(4):714–724 [ 1 ] ) . We used a combination of content and conversation analysis to examine how opportunities for discussion of health-related quality of life issues are opened up or closed down within the consultation and explore why this may or may not lead to changes in patient management . Findings Explicit reference to the PROMs data provided an opportunity for the patient to clarify and further elaborate on the side effects of chemotherapy . High scores on the PROMs data were not explored further if the patient indicated they were not a problem or were not related to the cancer or chemotherapy . Symptomatic treatment was more often offered for problems like nausea , constipation , pain and depression but much less so for fatigue . Doctors discussed fatigue by providing a cause for the fatigue ( e.g. the chemotherapy ) , presenting this as ‘ something to be expected ’ , minimising its impact or moving on to another topic . Chemotherapy regimens were not changed on the basis of the PROMs data alone , but PROMs data were sometimes used to legitimise changes . Conclusions Explicit mention of PROMs data in the consultation may strengthen opportunities for patients to elaborate on their problems , but doctors may not always know how to do this . Our findings have informed the development of a training package to enable doctors to optimise their use of PROMs data within the consultation", "Objective : Multiple Sclerosis ( MS ) is a disease with a detrimental effect on functional status . The present study investigated the effect of a sexual therapy program on the quality of life ( QOL ) of women with multiple sclerosis . Method : Women with multiple sclerosis and sexual dysfunction ( n = 30 ) were selected , and were r and omly assigned into the treatment ( n = 15 ) , or the control groups ( n = 15 ) . Participants of the treatment group ( n = 15 ) received 12 weekly sessions of sexual therapy . Participants in both groups completed the Female Sexual Function Inventory ( FSFI ) and the MS Quality of Life- 54 ( MSQOL-54 ) in the onset of the program and at the end of the program . Results : ANCOVA(s ) using pre-test scores as covariate(s ) revealed that in comparison to the control condition , MS patients within the treatment group showed a significant improvement in their sexual desire ( 0.0001 ) , arousal ( 0.022 ) , lubrication ( 0.001 ) , orgasm ( 0.001 ) , satisfaction ( 0.0001 ) , overall quality of life ( 0.001 ) , energy ( 0.023 ) , cognitive function ( 0.005 ) , and social function ( 0.001 ) at the end of the program . In addition , they were less limited in their roles due to the emotional and health problems . Conclusion : The present study revealed that addressing sexual dysfunction in MS patients could improve their quality of life . In the future , this research can extend its results , and apply the same method to men with MS to find whether sexual therapy enhances their quality of life", "BACKGROUND CONTEXT Sex life and sexual function may be affected by low back pain ( LBP ) . Sexual dysfunction after anterior lumbar fusion is reported in both men and women , but focus is mainly on impaired male biological function ( retro grade ejaculation ) as this may cause infertility . This has led to concern as to whether anterior surgery should be employed in men , at least in younger age groups . PURPOSE To investigate how chronic low back pain ( CLBP ) of assumed discogenic origin affects sex life and sexual function in patients considered for surgical treatment , whether this is affected by surgical treatment ( total disc replacement [ TDR ] or posterolateral fusion [PLF]/posterior lumbar interbody fusion [ PLIF ] ) , and if so , are there differences between the surgical procedures undertaken . STUDY DESIGN A r and omized controlled trial comparing TDR and instrumented lumbar spine fusion , performed either as a PLF or PLIF . PATIENT SAMPLE One hundred fifty-two patients were included in this r and omized controlled trial to compare the effect on CLBP of either TDR via an anterior retroperitoneal approach or instrumented posterior lumbar fusion , PLF or PLIF . OUTCOME MEASURES Global assessment of back pain , back pain ( visual analog scale [ VAS ] 0 - 100 ) , function ( Oswestry Disability Index [ ODI ] 0 - 100 ) , quality of life ( EQ5D [ EuroQol ] 0 - 1 ) , and answers on specific sexual function . METHODS Outcome was assessed using data from the Swedish Spine Register ( SweSpine ) . In ODI , one question , ODI 8 , reflects the impact of back pain on sex life . This question was analyzed separately . Patients also answered a gender-specific question naire preoperatively and at the 2-year follow-up to determine any sexual dysfunction regarding erection , orgasm , and ejaculation . Follow-up was at 1 and 2 years . RESULTS Before surgery , 34 % reported that their sex life caused some extra LBP , and an additional 30 % that their sex life was severely restricted by LBP . After surgery , sex life improved in both groups , with a strong correlation to a reduction of LBP . The gender-specific question naire used to measure sexual function after 2 years revealed no negative effect of TDR or Fusion in men regarding erection or retro grade ejaculation . However , 26 % of all men in the Fusion group , compared with 3 % in the TDR group , reported postoperative deterioration in the ability to achieve orgasm , despite a reduction of LBP . CONCLUSIONS Impairment of sex life appears to be related to CLBP . An improvement in sex life after TDR or lumbar fusion was positively correlated to a reduction in LBP . Total disc replacement in this study , performed through an anterior retroperitoneal approach , was not associated with greater sexual dysfunction compared with instrumented lumbar fusion performed either as a PLF or as a PLIF . Sexual function , expressed as orgasm , deteriorated in men in the Fusion group postoperatively , in spite of this group reporting less LBP after 2 years", "Background The psychometric properties of Patient Reported Outcomes Measurement Information System ( PROMIS ) instruments have been explored in a number of general and clinical sample s. No study , however , has evaluated the psychometric function of these measures in individuals with symptomatic knee osteoarthritis ( KOA ) . The aim of this project was to evaluate the construct ( structural ) validity and floor/ceiling effects of four PROMIS measures in this population . Methods We conducted a secondary analysis of baseline data from a r and omized trial comparing Tai Chi and physical therapy . Participants completed four PROMIS static short-form instruments ( i.e. , Anxiety , Depression , Physical Function , and Pain Interference ) as well as six well-vali date d ( legacy ) measures that assess pain , function , and psychological health . We calculated descriptive statistics and percentages of participants scoring the minimum ( floor ) and maximum ( ceiling ) possible scores for PROMIS and legacy measures . We also estimated the association between PROMIS scores and scores on legacy measures using Spearman ’s rank correlations coefficients . Results Data from 204 participants were analyzed . Mean age of the sample was 60 years ; 70 % were female . The PROMIS Anxiety and Depression had floor effects with 17 and 24 % of participants scoring the minimum , respectively . PROMIS Anxiety and Depression scores had strongest associations with general mental health , including stress ( Perceived Stress Scale , r ≥ 0.65 ) and depression ( Beck Depression Index-II , r = 0.70 ) . PROMIS Pain Interference scores correlated most strongly with measures of whole body pain ( Short-Form 36 Bodily Pain , r = −0.73 ) and physical health ( Short-Form 36 Physical-Component Summary , r = −0.73 ) ; their correlations were lower with other legacy measures , including with the WOMAC knee-specific pain ( r = 0.47 ) . PROMIS Physical Function scores had stronger associations with scores on the Short-Form 36 Physical Function ( r = 0.79 ) than with scores on other legacy measures . Conclusion The four PROMIS static-short forms performed well among individuals with symptomatic knee osteoarthritis as evidence d in correlations with legacy measures . PROMIS Anxiety and Depression target general mental health ( e.g. , stress , depression ) , and PROMIS Pain Interference and Physical Function static-short forms target whole-body outcomes among participants with symptomatic knee osteoarthritis . Floor effects in the PROMIS Anxiety and Depression scores should be considered if needing to distinguish among patients with very low levels of these outcomes .Trial registration Clinical trials.gov NCT01258985 . Registered 10 December", "OBJECTIVE To assess reliability , validity , and responsiveness of a 29-item short-form version of the Patient Reported Outcomes Measurement Information System ( PROMIS ) and a novel “ impact score ” calculated from those measures . DESIGN Prospect i ve cohort study . SETTING Rural primary care practice s. SUBJECTS Adults aged ≥ 55 years with chronic musculoskeletal pain , not currently receiving prescription opioids . METHODS Subjects completed the PROMIS short form at baseline and after 3 months . Patient subsets were compared to assess reliability and responsiveness . Construct validity was tested by comparing baseline scores among patients who were or were not applying for Worker 's Compensation ; those with higher or lower catastrophizing scores ; and those with or without recent falls . Responsiveness was assessed with mean score changes , effect sizes , and st and ardized response means . RESULTS Internal consistency was good to excellent , with Cronbach 's alpha between 0.81 and 0.95 for all scales . Among patients who rated their pain as stable , test-retest scores at 3 months were around 0.70 for most scales . PROMIS scores were worse among patients seeking or receiving worker 's compensation , those with high catastrophizing scores , and those with recent falls . Among patients rating pain as “ much less ” at 3 months , absolute effect sizes for the various scales ranged from 0.24 ( Depression ) to 1.93 ( Pain Intensity ) . CONCLUSIONS Results indicate that the PROMIS short 29-item form may be useful for the study of patients with chronic musculoskeletal pain . Our findings also support use of the novel “ impact score ” recommended by the National Institutes of Health ( NIH ) Task Force on Research St and ards for Chronic Low Back Pain", "INTRODUCTION Lower urinary tract symptoms ( LUTS ) have a profound impact on physical , social , and sexual well-being . Sacral neuromodulation ( SNM ) may have a positive effect on sexuality , though few studies have so far evaluated its impact on female sexual function . AIM To prospect ively assess changes in sexual function , clinical outcome and quality of life after SNM in female patients with overactive bladder ( OAB ) and their possible correlation with improvement in urinary symptoms and quality of life indexes . MAIN OUTCOME MEASURES Correlations between differences in Female Sexual Function Index ( FSFI ) scores and in clinical outcome and correlations between differences in FSFI , SF36 , and IQoL scores were evaluated by Spearman 's coefficient . Comparison between preoperative , midterm follow-up ( MFU ) , and last follow-up ( FFU ) visits were performed by generalized linear model ( GLM ) for repeated measurements . METHODS Between May 2003 and December 2008 , 30 consecutive female patients ( median age 53 years , range 35 - 79 ) with OAB underwent the two-stage procedure of SNM . Only 16 ( 53 % ) patients were considered eligible ; these completed a bladder diary , the FSFI , the Status of Health question naire ( SF36 ) and the Incontinence Quality of Life Index ( IQoL ) before implantation and on follow-up examinations . RESULTS The results were analyzed before implantation , on MFU ( median MFU 22.5 months ) and on FFU ( median FFU period 36.3 months ) . Regarding sexuality , the mean improvement in the total FSFI score was 27.9 % on MFU and 29.3 % on FFU . Only four patients ( 25 % ) showed a > 50 % improvement in global FSFI score on MFU , and 3 ( 25 % ) on FFU . A significant correlation was found between clinical improvement and improvement in sexual function . No significant correlation was found between differences in FSFI and quality of life indexes ( IQoL and SF36 ) . CONCLUSION Our results demonstrate that improvement in the quality of sexual function in female patients with OAB correlates with improvement in urinary symptoms", "BACKGROUND Patients with chronic heart failure ( CHF ) have sexual dysfunction that impairs quality of life . Recent trials have demonstrated that exercise training ( ET ) improves quality of life ( QOL ) of CHF patients , but it is not established whether this benefit may be associated with an improvement in sexual dysfunction . OBJECTIVE To determine whether ET can improve sexual dysfunction in patients with CHF . METHODS We prospect ively studied 59 male patients ( 57+/-9 years ) with stable CHF in sinus rhythm and without prostatic disease . Patients were r and omized into two groups . A group ( T , n = 30 ) underwent supervised cycle ergometer ET at 60 % of peak VO2 , three times a week , 60 min each session , for 8 weeks . A group ( NT , n = 29 ) was not exercised . Medications were not changed during the study . On study entry and at 8 weeks all patients underwent a symptom-limited cardiopulmonary exercise testing , brachial artery endothelium-dependent ( ED ) and endothelium-independent ( EI ) vasomotor responses , QOL and sexual activity profile assessment ( SAP ) by question naire . RESULTS At 8 weeks , no changes were observed in control patients . In trained patients , however , peak VO2 improved by 18 % ( P < 0.005 ) and was correlated with QOL ( r = 0.80 ; P < 0.001 ) . Flow-mediated dilation improved in trained patients ( from 2.29+/-1.13 % to 5.04+/-1.7 % , P = 0.0001 ) , while EI dilation ( after 0.3 mg sublingual NTG ) did not . In group T , all three domains ( i.e. Domain 1=relationship with the partner ; Domain 2 = quality of penile erection ; Domain 3 = personal wellness ) were significantly improved from baseline ( total score patients : from 3.49+/-3.4 to 6.17+/-3.2 , P < 0.001 ; partners : from 2.47+/-2.7 to 4.87+/-2.5 , P < 0.001 ) . Pre-post training change in SAP total score was correlated with changes in coronary risk profile ( r = -0.49 ; P = 0.01 ) , peak VO2 ( r = 0.67 ; P < 0.001 ) and QOL ( r = 0.73 ; P = 0.01 ) . Multivariate analysis selected the improvement in ED-vasomotor response as the strongest independent predictor of SAP improvement ( r = 0.63 , P < 0.001 ) . CONCLUSIONS In stable CHF , cycle ergometer ET significantly improves brachial artery endothelial dysfunction , suggesting a systemic effect of leg exercise . This benefit was correlated with improvements in sexual activity", "BACKGROUND The effects of rectal surgery on patients ' postoperative quality of life ( QOL ) and sexual function has been little studied to date . The present study aims to address this issue . METHODS 519 patients who had undergone surgery for rectal cancer from January 1997 to January 2003 were included in the study . The EORTC-QLQ-C-30 question naire and an additional , tumor-specific module were administered prospect ively multiple times over a 2-year period : before surgery , on discharge from the hospital , and at 3 , 6 , 12 , and 24 months after surgery . Comparisons were made between men and women , different age groups , and different surgical procedures : abdominoperineal resection ( APR ) versus anterior resection ( AR ) . RESULTS There were significant differences between men and women on scales of function and symptoms . Women had worse scores for physical function and overall quality of life and higher values for fatigue . Sexual life was impaired in both men and women , but the impairment was significantly more severe in men , and men felt more distressed by it than women did . Physical function and overall quality of life were better in patients aged 69 and younger , while patients aged 70 and older suffered from fatigue . Younger patients had a more severe impairment of sexuality , which , over the time period of the study , led to severe emotional symptoms . Sexuality was more severely impaired in patients who had undergone APR than in those who had undergone AR . CONCLUSION These findings show that the quality of life is changed by surgery for rectal cancer and is influenced by the patient 's sex and age , as well as by the particular surgical approach used", "Introduction Sexuality is an important part of people ’s physical and mental health . Patients with heart disease often suffer from sexual dysfunction . Sexual dysfunction has a negative impact on quality of life and well-being in persons with heart disease , and sexual dysfunction is associated with anxiety and depression . Treatment and care possibilities seem to be lacking . Studies indicate that non-pharmacological interventions such as exercise training and psychoeducation possess the potential of reducing sexual dysfunction in patients with heart disease . The CopenHeartSF trial will investigate the effect of a comprehensive sexual rehabilitation programme versus usual care . Methods and analysis CopenHeartSF is an investigator-initiated r and omised clinical superiority trial with blinded outcome assessment , with 1:1 central r and omisation to sexual rehabilitation plus usual care versus usual care alone . Based on sample size calculations , 154 male patients with impaired sexual function due to implantable cardioverter defibrillator or ischaemic heart disease will be included from two university hospitals in Denmark . All patients receive usual care and patients allocated to the experimental intervention group follow a 12-week sexual rehabilitation programme consisting of an individualised exercise programme and psychoeducative consultation with a specially trained nurse . The primary outcome is sexual function measured by the International Index of Erectile Function . The secondary outcome measure is psychosocial adjustment to illness by the Psychosocial Adjustment to Illness Scale , sexual domain . A number of explorative analyses will also be conducted . Ethics and dissemination CopenHeartSF is approved by the regional ethics committee ( no H-4 - 2012 - 168 ) and the Danish Data Protection Agency ( no 2007 - 58 - 0015 ) and is performed in accordance with good clinical practice and the Declaration of Helsinki in its latest form . Registration Clinical trials.gov identifier : NCT01796353", "OBJECTIVES To test the impact of the method of administration ( MOA ) on score level , reliability , and validity of scales developed in the Patient Reported Outcomes Measurement Information System ( PROMIS ) . STUDY DESIGN AND SETTING Two nonoverlapping parallel forms each containing eight items from each of three PROMIS item banks ( Physical Function , Fatigue , and Depression ) were completed by 923 adults with chronic obstructive pulmonary disease , depression , or rheumatoid arthritis . In a r and omized crossover design , subjects answered one form by interactive voice response ( IVR ) technology , paper question naire ( PQ ) , personal digital assistant ( PDA ) , or personal computer ( PC ) and a second form by PC , in the same administration . Method equivalence was evaluated through analyses of difference scores , intraclass correlations ( ICCs ) , and convergent/discriminant validity . RESULTS In difference score analyses , no significant mode differences were found and all confidence intervals were within the prespecified minimal important difference of 0.2 st and ard deviation . Parallel-forms reliabilities were very high ( ICC = 0.85 - 0.93 ) . Only one across-mode ICC was significantly lower than the same-mode ICC . Tests of validity showed no differential effect by MOA . Participants preferred screen interface over PQ and IVR . CONCLUSION We found no statistically or clinical ly significant differences in score levels or psychometric properties of IVR , PQ , or PDA administration compared with PC", "OBJECTIVES : The National Institutes of Health ( NIH ) created the Patient Reported Outcomes Measurement Information System ( PROMIS ) to allow efficient , online measurement of patient-reported outcomes ( PROs ) , but it remains untested whether PROMIS improves outcomes . Here , we aim ed to compare the impact of gastrointestinal ( GI ) PROMIS measures vs. usual care on patient outcomes . METHODS : We performed a pragmatic clinical trial with an off-on study design alternating weekly between intervention ( GI PROMIS ) and control arms at one Veterans Affairs and three university-affiliated specialty clinics . Adults with GI symptoms were eligible . Intervention patients completed GI PROMIS symptom question naires on an e-portal 1 week before their visit ; PROs were available for review by patients and their providers before and during the clinic visit . Usual care patients were managed according to customary practice s. Our primary outcome was patient satisfaction as determined by the Consumer Assessment of Healthcare Providers and Systems question naire . Secondary outcomes included provider interpersonal skills ( Doctors ’ Interpersonal Skills Question naire ( DISQ ) ) and shared decision-making ( 9-item Shared Decision Making Question naire ( SDM-Q-9 ) ) . RESULTS : There were 217 and 154 patients in the GI PROMIS and control arms , respectively . Patient satisfaction was similar between groups ( P>0.05 ) . Intervention patients had similar assessment s of their providers ’ interpersonal skills ( DISQ 89.4±11.7 vs. 89.8±16.0 , P=0.79 ) and shared decision-making ( SDM-Q-9 79.3±12.4 vs. 79.0±22.0 , P=0.85 ) vs. controls . CONCLUSIONS : This is the first controlled trial examining the impact of NIH PROMIS in clinical practice . One-time use of GI PROMIS did not improve patient satisfaction or assessment of provider interpersonal skills and shared decision-making . Future studies examining how to optimize PROs in clinical practice are encouraged before widespread adoption", "INTRODUCTION In pelvic organ prolapse ( POP ) repair , the use of synthetic mesh is not only increasing but also a subject of discussion . The focus shifts from anatomical toward functional outcome , with sexual function being an important parameter . One of the concerns with mesh usage in POP surgery is the possible negative effect on sexual function . AIM To compare and assess sexual function in women and men after primary cystocele repair with or without trocar-guided transobturator mesh . METHODS One hundred twenty-five women with a symptomatic cystocele stage ≥ II were included in this multicenter r and omized controlled trial and assessed at baseline and 6-month follow-up . MAIN OUTCOME MEASURES Female sexual function was measured by the Female Sexual Function Index ( FSFI ) and male sexual function by the Male Sexual Health Question naire . A subgroup analysis of women with a participating partner was performed . RESULTS In the mesh group , 54/59 women vs. 53/62 in the anterior colporrhaphy group participated . In men , 29 vs. 30 participated . After surgery , FSFI scores were comparable for both treatment groups . However , within group analysis showed significant improvement on the domains pain ( effect size = 0.5 ) , lubrication ( effect size = 0.4 ) , and overall satisfaction ( effect size = 0.5 ) in the colporrhaphy group . This improvement was not observed in the mesh group . A subgroup of women with a participating partner reported significantly higher baseline domain scores as compared with other women and did not report a significant improvement of sexual functioning irrespective of treatment allocation . Worsening of baseline sexual function was reported by 43 % of women in the mesh group compared with 18 % in anterior colporrhaphy group ( P = 0.05 ) . Male sexual functioning did not change in either group . CONCLUSIONS Women after an anterior colporrhaphy report a significant and clinical ly relevant improvement of their sexual functioning , whereas women after a mesh procedure did not", "Objective The Patient-Reported Outcomes Measurement Information System ( PROMIS ) was developed to st and ardize measurement of clinical ly relevant patient-reported outcomes . This study evaluated the reliability and construct validity of select PROMIS static short-form ( SF ) instruments in women with fibromyalgia . Design Analysis of baseline data from the Fibromyalgia Activity Study with TENS ( FAST ) , a r and omized controlled trial of the efficacy of transcutaneous electrical nerve stimulation . Setting Dual site , university-based outpatient clinics . Subjects Women aged 20 to 67 years diagnosed with fibromyalgia . Methods Participants completed the Revised Fibromyalgia Impact Question naire ( FIQR ) and 10 PROMIS static SF instruments . Internal consistency was calculated using Cronbach alpha . Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis . Results PROMIS static SF instruments had fair to high internal consistency ( Cronbach α = 0.58 to 0.94 , P < 0.05 ) . PROMIS ' physical function ' domain score was highly correlated with FIQR ' function ' score ( r = -0.73 ) . The PROMIS ' total ' score was highly correlated with the FIQR total score ( r = -0.72 ) . Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for ' physical function , ' r = -0.63 for ' global , ' and r = -0.57 for ' symptom ' domain . PROMIS ' physical function , ' ' global , ' and ' symptom ' scores explained 58 % of the FIQR total score variance . Conclusions Select PROMIS static SF instruments demonstrate convergent validity with the FIQR , a legacy measure of fibromyalgia disease severity . These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia", "INTRODUCTION A few studies have investigated the impact of photovaporization of the prostate ( PVP ) on sexual function and were mainly focused on erectile function . AIMS To comprehensively evaluate the impact of PVP on sexual function . METHODS A prospect i ve evaluation involved sexually active patients needing surgical relief of bladder outlet obstruction due to benign prostatic enlargement in a single center between August 2007 and November 2011 . All patients underwent PVP using the GreenLight HPS ™ 120W system ( AmericanMedicalSystems , Minnetonka , MN , USA ) . MAIN OUTCOME MEASURES Patients were evaluated preoperatively and postoperatively by International Prostate Symptom Score ( I-PSS ) , I-PSS question 8 , uroflowmetry parameters ( maximum urinary flow rate [ Qmax ] and postvoid residual [ PVR ] volume ) , Danish Prostate Symptom Score Sexual items ( DAN-PSSsex ) , and overall sexual satisfaction using a seven- grade Likert scale . Operative parameters and postoperative complications were also assessed . Preoperative and postoperative values were compared using the Pearson chi-square test and the Wilcoxon paired test . A multivariable model was used to investigate the determinants of variation of global sexual satisfaction . RESULTS One hundred and two consecutive patients with 12-month follow-up data were included in the analysis . Urinary parameters ( I-PSS , Qmax , and PVR ) were significantly improved compared with preoperative values . Compared with baseline , postoperative erection symptom score was not significantly different , whereas ejaculation symptom score was significantly worse . Global DAN-PSSsex score was unchanged , but DAN-PSSsex symptom score was worse ( P = 0.04 ) and DAN-PSSsex bother score was significantly improved ( P < 0.0001 ) . Global sexual satisfaction was significantly improved compared with baseline ( P = 0.02 ) and was significantly associated with I-PSS but not with erection and ejaculation score in a multivariable model . CONCLUSION Ejaculation is the main sexual function impacted by PVP . Despite this , sexual satisfaction and bother due to sexual symptoms were significantly improved , probably due to the positive impact of urinary symptom relief", "Background Brief self- assessment of sexual problems in a clinical context has the potential to improve care for patients through the ability to track trends in sexual problems over time and facilitate patient – provider communication about this important topic . However , instruments design ed for research are typically too long to be practical in clinical practice . Objective To develop and vali date a single-item self-report clinical screener that would capture common sexual problems and concerns for men and women . Design We created three c and i date screener items , refined them through cognitive interviews , and administered them to a large sample . We compared the prevalence of responses to each item and explored the discrepancies between items . We evaluated the construct validity of the items by comparing them to scores on the Patient-Reported Outcomes Measurement Information System ® Sexual Function and Satisfaction ( PROMIS ® SexFS ) measure . Participants Local patients participated in two rounds of cognitive interviews ( n = 7 and n = 11 ) . A probability-based r and om sample of U.S. adults comprised the item-testing sample ( n = 3517).Main Measures The items were as follows : 1 ) a yes/no item on any sexual problems or concerns ( “ general screener ” ) , 2 ) a yes/no item on problems experienced for 3 months or more during the past 12 months , with a list of examples ( “ long list screener ” ) , and 3 ) an item identical to the long list screener except that examples appeared individually as response options and respondents could check all that applied ( “ checklist screener”).Key Results All of the screeners tested showed evidence for basic validity and had minimal missing data . Percentages of women and men endorsing the screeners were 10 % and 15 % ( general ) ; 20 % and 17 % ( long list ) ; and 38 % and 30 % ( checklist ) , respectively . Participants who endorsed the screeners had lower function compared to those who did not endorse them . Conclusions We recommend the checklist screener for its specificity and ability to identify specific problems associated with decreased sexual function", "Erectile dysfunction ( ED ) is commonly associated with depressed mood and diminished quality of life ( QoL ) , but few studies have investigated the causal associations involved . Therefore , we evaluated the correlation between several measures of mood , QoL , and sexual function in a retrospective analysis of a sample of depressed men ( n=152 ) , with ED enrolled in a clinical trial of sildenafil citrate ( VIAGRA ® ) . Strong correlations were observed at baseline among measures of erectile function ( EF ) , mood , and overall QoL. Significant treatment effects were observed on all three domains , with significant interactions between changes in mood and QoL. Based on multiple regression and path analysis , a model was developed in which EF changes were associated with improved mood and quality of sexual life , which result ed in improved partner satisfaction , family life , and overall life satisfaction . These data suggest that QoL changes associated with ED therapy may be mediated by changes in sexual function , mood , and family relationships", "PURPOSE Although it is the most powerful predictor of early prostate cancer treatment-related complications and quality -of-life ( QOL ) outcomes , most studies do not stratify results by baseline function . Further , reporting functional outcomes as averaged numerical results may obscure informatively disparate courses . Using levels of treatment-related dysfunction , we address these problems and present the final QOL outcomes of our prospect i ve cohort study of patients with early prostate cancer . METHODS We created categories for sexual , bowel , and urinary function , measured using numerical scores of the vali date d Prostate Cancer Symptom Indices and stratified into \" normal , \" \" intermediate \" and \" poor \" levels of function by incorporating patient-reported symptom and distress information . We present QOL outcomes for 409 patients 36 months after radical prostatectomy , external-beam radiation therapy , and brachytherapy . RESULTS Different levels of baseline sexual , bowel , and urinary function produced distinctive treatment-related changes from baseline to 36 months . In general , the average scale increases in dysfunction were greatest among patients with normal baseline function , although patients with normal and intermediate baseline function had similar increases in sexual dysfunction . For patients whose baseline urinary obstruction/irritation was poor , both average scale scores and most patients ' level of function improved after treatment , particularly after surgery . CONCLUSION The use of functional levels to stratify treatment-related outcomes by pretreatment functional status and to display the proportions of patients with improved , stable , or worsened function after treatment provides information that more specifically conveys the expected impact of treatment to patients choosing among localized prostate cancer treatments" ]	Several PROMs have been identified to evaluate sexual function in neurologic patients . Strong evidence was found only for the Multiple Sclerosis Intimacy and Sexuality Question naire-15 and Multiple Sclerosis Intimacy and Sexuality Question naire-19 for patients with MS , although evidence was lacking for certain measurement properties as well .	CONTEXT Impaired sexual function has a significant effect on quality of life . Various patient-reported outcome measures ( PROMs ) are available to evaluate sexual function . The quality of the PROMs to be used for neurologic patients remains unknown . OBJECTIVE To systematic ally review which vali date d PROMs are available to evaluate sexual function in neurologic patients and to critically assess the quality of the validation studies and measurement properties for each identified PROM .
24417824	["28059013","10205319","12631049","8526579","19142085","24634929","3127999","24068549","22683955","1(...TRUNCATED)	["A Carbohydrate-Rich Beverage Prior to Surgery Prevents Surgery-Induced Immunodepression: A Randomi(...TRUNCATED)	["BACKGROUND Fasting before surgery is still common care in a lot of western hospitals . Overnight f(...TRUNCATED)	"Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient c(...TRUNCATED)	"INTRODUCTION Surgical stress in the presence of fasting worsens the catabolic state , causes insuli(...TRUNCATED)
28416626	["11692018","25082804","23920426","4501739","19066101","26660118","16018519","25156220","15569871","(...TRUNCATED)	["Management and Prognostic Features of Intracerebral Hemorrhage During Anticoagulant Therapy: A Swe(...TRUNCATED)	["Background and Purpose — Patients treated with oral anticoagulants ( ACs ) have an increased ri(...TRUNCATED)	"Conclusions — In observational studies , reinstitution of anticoagulation after ICH was associate(...TRUNCATED)	"Background and Purpose — The safety and efficacy of restarting anticoagulation therapy after intr(...TRUNCATED)
25767129	["24030388","22048460","27116918","21830838","21295286","23536105","22697191","22888309","21810630",(...TRUNCATED)	["Varenicline, smoking cessation, and neuropsychiatric adverse events.","Adjunctive Varenicline Trea(...TRUNCATED)	["OBJECTIVE In 2009 , the U.S. Food and Drug Administration issued a black box warning for varenicli(...TRUNCATED)	"This meta- analysis found no evidence of an increased risk of suicide or attempted suicide , suicid(...TRUNCATED)	"OBJECTIVE To determine the risk of neuropsychiatric adverse events associated with use of varenicli(...TRUNCATED)
26949760	["15202752","26086947","11951800","15732546","25010879","20608298","19544814","26428908","8803392","(...TRUNCATED)	["Clinical performance of large, all-ceramic CAD/CAM-generated restorations after three years: a pil(...TRUNCATED)	["BACKGROUND Adhesively luted all-ceramic restorations preserve and stabilize weakened tooth structu(...TRUNCATED)	"Overall , the 5-year complication rates were low .\nThe most frequent complications were secondary (...TRUNCATED)	"OBJECTIVE The purpose of this systematic review was to compare the survival and complication rates (...TRUNCATED)
21474812	["12411652","26121986","15618441","17060137","4673522","24153026","9684063","12735531","15753416","1(...TRUNCATED)	["Trunk Control as an Early Predictor of Comprehensive Activities of Daily Living Function in Stroke(...TRUNCATED)	["Background and Purpose — Prediction of activities of daily living ( ADL ) functions at an early (...TRUNCATED)	"Because of insufficient method ological quality of most prognostic studies , the predictive value o(...TRUNCATED)	"BACKGROUND AND PURPOSE Knowledge about robust and unbiased factors that predict outcome of activiti(...TRUNCATED)

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This is a copy of the MS^2 dataset, except the input source documents of its train, validation and test splits have been replaced by a dense retriever. The retrieval pipeline used:

query: The background field of each example
corpus: The union of all documents in the train, validation and test splits. A document is the concatenation of the title and abstract.
retriever: facebook/contriever-msmarco via PyTerrier with default settings
top-k strategy: "max", i.e. the number of documents retrieved, k, is set as the maximum number of documents seen across examples in this dataset, in this case k==17

Retrieval results on the train set:

Recall@100	Rprec	Precision@k	Recall@k
0.4764	0.2395	0.2271	0.2418

Retrieval results on the validation set:

Recall@100	Rprec	Precision@k	Recall@k
0.4364	0.2125	0.2131	0.2074

Retrieval results on the test set:

Recall@100	Rprec	Precision@k	Recall@k
0.4481	0.2224	0.2254	0.2100

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