***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Few epidemiological studies have investigated the relative importance of major coronary risk factors in the two sexes within the same study population . In particular , it is not clear whether smoking carries a similar risk of coronary heart disease in men and women . METHODS AND RESULTS The associations between smoking , serum lipids , blood pressure , and myocardial infa rct ion were examined in a population -based prospect i ve study of 11,843 men and women aged 35 to 52 years at entry . During 12 years , 495 cases of first myocardial infa rct ion among men and 103 cases among women were identified .  Myocardial infa rct ion incidence was 4.6 times higher among men . The incidence was increased sixfold in women and threefold in men who smoked at least 20 cigarettes per day compared with never-smokers , and the rate in female heavy smokers exceeded that of never-smoking men . Multivariate analysis identified current smoking as a stronger risk factor in women ( relative risk , 3.3 ; 95 % confidence interval [ CI ] , 2.1 to 5.1 ) than in men ( relative risk , 1.9 ; 95 % CI , 1.6 to 2.3 ) . Among those under 45 years old at entry , the smoking-related sex difference was more pronounced ( in women : relative risk , 7.1 ; 95 % CI , 2.6 to 19.1 ) ( in men : relative risk , 2.3 ; 95 % CI , 1.6 to 3.2 ) . Serum total cholesterol , HDL cholesterol , and systolic blood pressure were also highly significant predictors in both sexes . CONCLUSIONS Smoking was a stronger risk factor for myocardial infa rct ion in middle-aged women than in men . Relative risks associated with serum lipids and blood pressure were similar despite large sex differences in myocardial infa rct ion incidence rates BACKGROUND Up to three quarters of patients with gastroesophageal reflux disease ( GERD ) have symptoms , such as heartburn , but no macroscopic evidence of erosive esophagitis , making symptomatic GERD a common clinical problem in the primary care setting . OBJECTIVE To compare the efficacy and safety of omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; and placebo in the treatment of symptomatic GERD without erosive esophagitis . METHODS Patients with a history of heartburn ( > or = 12 months ) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week , r and omized , double-blind , placebo-controlled trial . The absence of erosive esophagitis was established through endoscopy . Eligible patients were r and omized to 1 of 3 treatment groups : omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; or placebo . Patients were assessed at weeks 2 and 4 . The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data : daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment . The efficacy of omeprazole for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea was also assessed . RESULTS Of 359 r and omized patients , 355 were included in the statistical analysis ( intention-to-treat population ) . Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group ( 62 % , day 7 ; 74 % , day 27 ) than in the 10-mg omeprazole group ( 41 % , day 7 ; 49 % , day 27 ) or the placebo group ( 14 % , day 7 ; 23 % ; day 27 ) . Complete resolution of heartburn every day during the last treatment week was significantly ( P < or = .002 ) higher in the 20-mg omeprazole group ( 48 % ) than in the 10-mg omeprazole ( 27 % ) or placebo ( 5 % ) group . Omeprazole was significantly ( P < or = .003 ) more effective than placebo for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea . CONCLUSIONS Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief . Omeprazole , 20 mg once daily , was superior to omeprazole , 10 mg once daily , and to placebo in providing early and sustained resolution of heartburn , as well as treatment of other troublesome GERD symptoms Peptic ulcer bleeding is a serious medical problem with significant morbidity and mortality . Endoscopic therapy significantly reduces further bleeding , surgery and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients . The efficacy of large-dose proton pump inhibitor ( PPI ) therapy in reducing re-bleeding after endoscopic therapy has been supported by evidence derived from r and omized controlled trials . It may be premature to recommend small-dose intravenous injection PPI after endoscopic hemostasis in patients with bleeding ulcers . An up date d systematic review shows that PPI therapy before endoscopy significantly reduces the proportion with major stigmata and requirement for endoscopic therapy at index endoscopy . Some studies show that there is no significant difference between oral and intravenous PPIs in raising intragastric pH. However , clinical data is lacking in patients with peptic ulcer bleeding to date Background Dexlansoprazole MR , a modified‐release formulation of dexlansoprazole , an enantiomer of lansoprazole , effectively heals erosive oesophagitis Abstract In this study , we aim ed to determine the association between  gastroesophageal reflux disease ( GERD )  and subsequent coronary heart disease ( CHD ) development , if any , and to evaluate whether longer use of proton pump inhibitors ( PPIs ) increases the risk of CHD .  Patients diagnosed with GERD between 2000 and 2011 were identified as the study cohort ( n = 12,960 ) . Patients without GERD were r and omly selected from the general population , frequency-matched with the study group according to age , sex , and index year , and evaluated as the comparison cohort ( n = 51,840 ) . Both cohorts were followed up until the end of 2011 to determine the incidence of CHD . The risk of CHD was evaluated in both groups by using Cox proportional hazards regression models . The GERD patients had a greater probability of CHD than the cohort without GERD did ( log-rank test , P < 0.001 and 11.8 vs 6.5 per 1000 person-years ) . The GERD cohort had a higher risk of CHD than the comparison cohort did after adjustment for age , sex , hypertension , diabetes , hyperlipidemia , alcohol-related illness , stroke , chronic obstructive pulmonary disease , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis ( adjusted hazard ratio [ aHR ] : 1.49 , 95 % confidence interval [ CI ] : 1.34–1.66 ) . The risk of CHD was greater for the patients treated with PPIs for more than 1 year ( aHR = 1.67 , 95 % CI = 1.34–2.08 ) than for those treated with PPIs for < 1 year ( aHR = 1.56 , 95 % CI = 1.39–1.74).Our population -based cohort study results indicate that GERD was associated with an increased risk of developing CHD , and that PPI use for more than 1 year might increase the risk of CHD Background — The clinical significance of the interaction between clopidogrel and proton pump inhibitors ( PPIs ) remains unclear . Methods and Results — We examined the relationship between PPI use and 1-year cardiovascular events ( cardiovascular death , myocardial infa rct ion , or stroke ) in patients with acute coronary syndrome r and omized to clopidogrel or ticagrelor in a prespecified , nonr and omized subgroup analysis of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial . The primary end point rates were higher for individuals on a PPI ( n=6539 ) compared with those not on a PPI ( n=12 060 ) at r and omization in both the clopidogrel ( 13.0 % versus 10.9 % ; adjusted hazard ratio [ HR ] , 1.20 ; 95 % confidence interval [ CI ] , 1.04–1.38 ) and ticagrelor ( 11.0 % versus 9.2 % ; HR , 1.24 ; 95 % CI , 1.07–1.45 ) groups . Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI ( PPI versus non-PPI gastrointestinal treatment : clopidogrel , HR , 0.98 ; 95 % CI , 0.79–1.23 ; ticagrelor , HR , 0.89 ; 95 % CI , 0.73–1.10 ) . In contrast , patients on no gastric therapy had a significantly lower primary end point rate ( PPI versus no gastrointestinal treatment : clopidogrel , HR , 1.29 ; 95 % CI , 1.12–1.49 ; ticagrelor , HR , 1.30 ; 95 % CI , 1.14–1.49 ) . Conclusions — The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel .  However , a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment . Therefore , in the PLATO trial , the association between PPI use and adverse events may be due to confounding , with PPI use more of a marker for , than a cause of , higher rates of cardiovascular events . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00391872 BACKGROUND Gastrointestinal complications are an important problem of antithrombotic therapy . Proton-pump inhibitors ( PPIs ) are believed to decrease the risk of such complications , though no r and omized trial has proved this in patients receiving dual antiplatelet therapy . Recently , concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel . METHODS We r and omly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo , in addition to aspirin . The primary gastrointestinal end point was a composite of overt or occult bleeding , symptomatic gastroduodenal ulcers or erosions , obstruction , or perforation . The primary cardiovascular end point was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , revascularization , or stroke . The trial was terminated prematurely when the sponsor lost financing . RESULTS We planned to enroll about 5000 patients ; a total of 3873 were r and omly assigned and 3761 were included in analyses . In all , 51 patients had a gastrointestinal event ; the event rate was 1.1 % with omeprazole and 2.9 % with placebo at 180 days ( hazard ratio with omeprazole , 0.34 , 95 % confidence interval [ CI ] , 0.18 to 0.63 ; P<0.001 ) . The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo ( hazard ratio , 0.13 ; 95 % CI , 0.03 to 0.56 ; P = 0.001 ) . A total of 109 patients had a cardiovascular event , with event rates of 4.9 % with omeprazole and 5.7 % with placebo ( hazard ratio with omeprazole , 0.99 ; 95 % CI , 0.68 to 1.44 ; P = 0.96 ) ; high-risk subgroups did not show significant heterogeneity . The two groups did not differ significantly in the rate of serious adverse events , though the risk of diarrhea was increased with omeprazole . CONCLUSIONS Among patients receiving aspirin and clopidogrel , prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding . There was no apparent cardiovascular interaction between clopidogrel and omeprazole , but our results do not rule out a clinical ly meaningful difference in cardiovascular events due to use of a PPI . ( Funded by Cogentus Pharmaceuticals ; Clinical Trials.gov number , NCT00557921 . ) Objective Gastroesophageal reflux disease ( GERD ) is a common disease which can cause troublesome symptoms and affect quality of life . In addition to esophageal complications , GERD may also be a risk factor for extra-esophageal complications . Both GERD and coronary artery disease ( CAD ) can cause chest pain and frequently co-exist . However , the association between GERD and acute myocardial infa rct ion ( AMI ) remain unclear 
    Output:
    
There is no clear evidence of an association between PPI monotherapy and increased cardiovascular risk