***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: Approximately 14 million patients in the United States regularly take nonsteroidal anti-inflammatory drugs(NSAIDs ) for various types of arthritis [ 1 ] for relief of pain , stiffness , and other symptoms . However , these benefits are obtained at a price . Use of NSAIDs is associated with various gastrointestinal side effects . Minor side effects such as nausea , dyspepsia , anorexia , abdominal pain , flatulence , and diarrhea may affect 10 % to 60 % of patients [ 2 ] . Symptomatic ulcers and potentially life-threatening ulcer complications such as upper gastrointestinal bleeding , perforation , and gastric outlet obstruction are reported in 2 % to 4 % of patients who take NSAIDs for a year [ 3 ] . The chance of hospitalization or death from a gastrointestinal adverse event is 1.3 % to 1.6 % per year in patients with rheumatoid arthritis [ 4 ] . These infrequent but potentially serious gastrointestinal side effects of NSAIDs have become a major health care problem because of the many patients at risk [ 5 ] . General physicians and rheumatologists caring for patients with symptoms of chronic arthritis may be reluctant to ab and on using NSAIDs , which help most of these patients , in order to protect the few who may develop serious complications from use of these drugs . On the other h and , gastroenterologists see fewer patients for arthritis but many with serious gastrointestinal complications . Life-threatening events such as perforation or serious hemorrhage from NSAID-induced ulcers , which often develop with little or no warning [ 6 ] , are a real problem because of the many patients at risk . Various agents have been used in attempts to reduce the incidence of NSAID-induced gastrointestinal lesions . In one endoscopic study , cimetidine at a dose of 300 mg four times a day showed no benefit in healing NSAID-related lesions compared with placebo , and 400 mg at bedtime provided no benefit in preventing these lesions compared with placebo [ 7 ] . Antacids ( magnesium-aluminum hydroxide , 10 to 20 mL as needed to a dose as high as 60 mL daily ) and sucralfate have recently been reported to reduce dyspeptic symptoms in arthritic patients receiving NSAIDs in whom gastropathic lesions ( but not ulcers ) were shown endoscopically [ 8 , 9 ] . The surface-active antiulcer drug sucralfate was ineffective in preventing ulcers in persons receiving NSAIDs [ 10 , 11 ] , and the histamine-2-receptor antagonist ranitidine did not prevent gastric ulcers but did reduce the frequency of duodenal ulcers [ 12 , 13 ] . Results of preliminary studies indicate that the effects of omeprazole parallel those of ranitidine [ 14 ] . A recent study [ 15 ] in achlorhydric patients showed that NSAID-induced ulcers develop in the absence of gastric acid . In contrast , several clinical trials have shown that the incidence of endoscopically visible erosions and ulcers associated with NSAID use can be reduced by cotherapy with the synthetic prostagl and in misoprostol [ 16 - 19 ] . However , it was not proved that preventing endoscopic lesions would prevent clinical ly serious complications of NSAID-induced gastrointestinal ulcers [ 20 ] . Our objective was to determine whether concurrent therapy with misoprostol reduces the incidence of serious upper gastrointestinal complications in older patients with chronic rheumatoid arthritis who are taking NSAIDs .  Because most patients taking NSAIDs do not routinely have endoscopy , we investigated the incidence of these complications during clinical care as actually practice d. A second goal was to better define which patients were at increased risk for development of serious NSAID-induced upper gastrointestinal complications . Methods Patients Ambulatory patients at least 52 years of age who had chronic rheumatoid arthritis , defined by American College of Rheumatology criteria [ 21 ] , and who were expected to be taking 1 of 10 specified NSAIDs at predefined minimum doses for 6 months were sought from practice s of family medicine , internal medicine , or rheumatology . Of these practice s , 661 in the United States and 3 in Canada enrolled at least one patient between July 1991 and August 1993 . For all patients , a medical history was elicited , a physical examination was done , and a modified Health Assessment Question naire that included eight items on activities of daily living was administered [ 22 ] . Patients were excluded if they had had active peptic ulcer disease within 30 days of study enrollment ; were taking or expected to need antiulcer medication ( histamine-2 blockers , sucralfate , omeprazole ) or any experimental medication during the study ; had the Zollinger-Ellison syndrome , pyloric or duodenal obstruction , previous gastric resection or vagotomy , gastroesophageal reflux disease , varices , or cirrhosis ; had a history of inflammatory bowel disease , upper gastrointestinal tract malignancies , hepatitis , alcoholism , or bleeding diathesis ; were estimated to have a life expectancy of less than 8 months or had do-not-resuscitate status ; were women of child-bearing potential ; or could not tolerate misoprostol or any prostagl and in . The following were the minimum NSAID doses ( mg/d ) allowed : aspirin , 2000 ; diclofenac , 100 ; flurbiprofen , 200 ; ibuprofen , 1200 ; indomethacin , 75 ; ketoprofen , 150 ; naproxen , 750 ; piroxicam , 20 ; sulindac , 200 ; or tolmetin , 1200 . Patients were allowed to receive more than one NSAID . Intervention Eligible patients were r and omly assigned to receive either misoprostol or placebo in the form of 200- micrograms tablets from coded bottles supplied by the manufacturer . Patients were r and omly assigned in blocks of four , so that in each block , half the patients would receive misoprostol and half would receive placebo . Because blocks were assigned to investigators , patients were r and omly assigned within the individual centers . Investigators were not informed about the r and omization procedure but were told only that the study was r and omized and double-blind . Patients were instructed to begin taking half a tablet with meals and at bedtime each day for 10 days and then , if the drug was tolerated , to increase the dose to a whole tablet four times a day for the rest of the study . If the drug was not tolerated , the patients were instructed to reduce the dose back to half a tablet four times a day . Patients could continue therapy with arthritis disease-modifying agents ( such as gold or corticosteroids ) and were allowed to take antacids that did not contain magnesium . Patients purchased their own arthritis medications or antacids and reported their consumption when seen monthly for examination and counts of study medication tablets . Physicians were instructed to watch closely for clinical signs of gastrointestinal bleeding or other possible gastrointestinal complications , to inquire about symptoms , and to investigate suspicious episodes by appropriate clinical procedures . Outcome Measures All suspicious events , regardless of presumed cause , were to be reported , along with all available patient data , to the study medical officer ( HWD ) and then to an external review committee . This committee consisted of a gastroenterologist ( FS ) , a rheumatologist ( Kenneth Br and t , MD , Indiana University ) , and an epidemiologist ( Marie Griffin , MD , MPH , V and erbilt University ) . The committee determined , without unblinding the r and omization code , whether the patient had upper gastrointestinal bleeding ; other ulcer complications ; or a problem such as hemorrhoids , diverticulitis , colon polyps , or cancer . It developed definitions of what were considered to be complications related to NSAID use and categories of such complications . The committee reached consensus and assigned such events to one of the following categories of definite upper gastrointestinal complications : 1 . perforated ulcer , proved at surgery ; 2 . gastric outlet obstruction caused by proven ulceration and stricture , proved by endoscopy ; 3 . hematemesis , with endoscopically proven gastric or duodenal ulceration or erosion ; 4 . active or recent visualized bleeding from endoscopically proven ulceration or erosion ; 5 . melena , with endoscopically proven ulceration or erosion ; 6 . heme-positive stool , with endoscopically proven ulceration or erosion , plus either a ) a decrease in hematocrit of at least 0.05 or b ) orthostatic change in the pulse rate ( from sitting to st and ing ) of at least 20 beats per minute or decrease in  systolic blood pressure of at least 20 mm Hg and a decrease in diastolic blood pressure of 10 mm Hg ; 7 . hematemesis  , without endoscopically proven ulceration or erosion  ; and 8 . melena , with heme-positive stool and without endoscopically proven ulceration or erosion . The committee also defined categories of events not involving clinical ly significant bleeding : 9 . report of melena with no other data ; 10 . heme-positive stools , with endoscopically proven ulceration or erosion and without active bleeding ; and 11 . report of melena and heme-negative stools when the stools were tested . Sample Size Calculation and Statistical Methods The placebo group was expected to have an incidence of serious NSAID-induced upper gastrointestinal complications of about 2 % per year or about 1 % during the 6-month study period . We estimated that the misoprostol group might have 40 % to 50 % fewer complications and that 60 % to 70 % of patients would complete the study . Given an less than 0.05 and power greater than 0.80 , we planned in the protocol to assess the number of such complications observed , without unblinding the study , after 7500 patients had been followed . We did this to confirm the incidence assumptions and adjust the study size if necessary . We used the Fisher exact test to compare occurrence of events in the treatment groups . To identify risk factors , we evaluated the relation between the occurrence of serious upper gastrointestinal complications and patient characteristics using logistic regression . Supplementary time-to-event analyses were done using the log-rank test and Kaplan-Meier curves . The study was supported by a grant from G.D. Searle & Co. Data Abstract Objective : To assess whether the way in which the results of a r and omised controlled trial and a systematic review are presented influences health policy decisions . Design : A postal question naire to all members of a health authority within one regional health authority . Setting : Anglia and Oxford regional health authorities . Subjects : 182 executive and non-executive members of 13 health authorities , family health services authorities , or health commissions . Main outcome measures : The average score from all  health authority members in terms of their willingness to fund a mammography programme or cardiac rehabilitation programme  according to four different ways of presenting the same results of research evidence —namely , as a relative risk reduction , absolute risk reduction , proportion of event free patients , or as the number of patients needed to be treated to prevent an adverse event . Results : The willingness to fund either programme was significantly influenced by the way in which data were presented . Results of both programmes when expressed as relative risk reductions produced significantly higher scores when compared with other methods ( P<0.05 ) . The difference was more extreme for mammography , for which the outcome condition is rarer . Conclusions : The method of reporting trial results has a considerable influence on the health policy decisions made by health authority members The results of a r and omized clinical trial can be reported using relative and /or absolute estimators of treatment effect . These various measures convey different information , and the choice can influence the physician 's appreciation of the size of treatment effect and , subsequently , treatment decisions . We compare the estimators with respect to the clinical ly relevant information conveyed to physicians , and identify which clinical questions can and can not be answered directly by each . We also identify opportunities for misinterpretation when one estimator is substituted for another , or when an estimator is mislabeled . Clinical ly important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement , relative risk reduction , and risk difference and its reciprocal , number needed to treat . This is true of estimates of treatment effect derived from a single trial and also from meta- analysis of a group of trials . Because the control group 's risk affects the numerical value of the odds ratio , the odds ratio can not substitute for the risk ratio in conveying clinical ly important information to physicians . This is especially important when large treatment effects are shown in trials carried out in population s at high baseline risk 17,187 patients entering 417 hospitals up to 24 h ( median 5 h ) after the onset of suspected acute myocardial infa rct ion were r and omized , with placebo control , between i ) a 1 h intravenous infusion of 1.5 million units of streptokinase ; ii ) 1 month of 160 mg/day enteric-coated aspirin ; iii ) both active treatments ; or iv ) neither . Streptokinase alone and aspirin alone each produced a highly significant reduction in 5 week vascular mortality : 791/8592 ( 9.2 % ) vascular deaths among patients allocated streptokinase infusion versus 1029/8595 ( 12.0 % ) among those allocated placebo infusion ( odds reduction : 25 % + /- 4 ; 2p less than 0.00001 ) ; 804/8587 ( 9.4 % ) 
    Output:
    
As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer .
They use explicit methods and quality st and ards to reduce bias .
They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies .
Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately .
Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale .
In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful .
As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target .