***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: AIMS To investigate the incidence , risk factors and natural history of gallstone disease , a r and om sample of females belonging to a rural population was enrolled in a ten-year longitudinal study . METHODS The study has been performed in a small town on the hills south of Rome . In 1985 , a r and om sample of 426 females , aged 20 - 69 years , was screened by real-time ultrasonography for gallstones and previous cholecystectomy .  Screening methods included anthropometry , collection of a blood sample and a question naire on the occurrence of abdominal symptoms . During 1995 , all these subjects were invited for a 10-year follow-up examination . RESULTS The overall 10-year incidence of gallstone disease was 6.3 % ( 5.5 % of new gallstones and 0.8 % of cholecystectomies ) . Only 23.1 % of the women with gallstones were aware of their condition . More than three quarters ( 76.9 % ) had not suffered biliary pain . Univariate and multivariate analyses demonstrated a positive independent association of new gallstone disease with body mass index and parity . Out of the initially asymptomatic gallstone women , 15.4 % experienced at least one episode of biliary pain , 23.1 % were su bmi tted to elective cholecystectomy and 61.5 % remained asymptomatic . CONCLUSIONS The study demonstrates a high incidence of gallstone disease in women belonging to a rural free-living population in Italy and suggests body mass index and parity as possible true risk factors . Moreover , it confirms that a remarkable proportion of asymptomatic patients become symptomatic and eventually undergo cholecystectomy BACKGROUND Rofecoxib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain , with similar analgesic efficacy to ibuprofen and naproxen sodium . Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide ; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis . OBJECTIVE The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg , and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate to severe pain after the surgical extraction of > or = 2 third molars were r and omized to receive a single dose of rofecoxib 50 mg , 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg given every 8 hours ) , or placebo . Patients rated pain intensity , pain relief , and global assessment s at prespecified times throughout the 24-hour period after initial dosing . Overall analgesic efficacy was determined by total pain relief over 8 hours ( TOPAR8 ) and 24 hours ( TOPAR24 ) and patient global assessment s at 8 and 24 hours . Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief . Peak analgesic effect was the maximum pain relief attained during the first 8 hours . The duration of analgesic effect was determined by median time to rescue analgesia use . RESULTS A total of 305 patients were r and omized to treatment : 121 received rofecoxib , 121 received diclofenac sodium , and 63 received placebo . The baseline demographics were similar among the groups . Overall , 61.3 % experienced moderate pain and 38.7 % experienced severe pain ; 53.1 % were female ; and the mean age was 23.4 years . The overall analgesic efficacy , as assessed by TOPAR8 , of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg ( 20.5 vs 8.2 ) and placebo ( 20.5 vs 5.9 ) . Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo . TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 64.1 vs 25.1 ) and placebo ( 64.1 vs 19.2 ) . At 24 hours , the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo . The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo ( median times : 31 minutes , > 4 hours , and > 4 hours , respectively ) . The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium ( 3.2 vs 1.5 ) and placebo ( 3.2 vs 1.1 ) . The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium ( median times : > 24 hours vs 1 hour and 37 minutes ) and placebo ( > 24 hours vs 1 hour and 37 minutes ) . Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy ( total pain relief and patient global assessment ) , but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain , osteoarthritis , and rheumatoid arthritis and did not differ significantly from placebo . Overall , both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated , although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group . CONCLUSIONS A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours , more rapid onset of analgesia , greater maximum analgesic effect , and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery . Compared with 3 doses of enteric-coated diclofenac sodium 50 mg ( 50 mg every 8 hours ) , a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Sixty patients were treated in the emergency ward for biliary colic . Cholelithiasis was proven by ultrasonography . Twenty patients ( group I ) were treated by placebo . Twenty patients ( group II ) were treated by papaverine , and 20 patients were treated by diclofenac sodium ( Voltaren ) ( group III ) . Twenty more patients ( group IV ) with low back pain ( LBP ) were treated with diclofenac sodium ( Voltaren ) as a control to assess the analgesic effect of Voltaren . Two interesting observations were made : Voltaren was proven more efficient for pain relief ( P<0.002 ) , and none of the patients treated with Voltaren were in need of hospitalization and immediate surgery . In comparison , nine patients of the other two groups progressed to acute cholecystitis and needed surgical intervention . The possible anticolic and anti-biliary inflammation properties and the indications for use of Voltaren are discussed In this double blind , prospect i ve study , the relative efficacy of Diclofenac + Pitofenone + Fenpiverinium ( Manyana ) and Analgin + Pitofenone + Fenpiverinium ( Baralgan ) in 200 patients of biliary , ureteric and intestinal colic was evaluated . Patients were given these coded drugs thrice daily for five days starting from day 0 to day 5 . The results of the present clinical evaluation demonstrated that Manyana appeared to be superior to Baralgan in biliary and ureteric colic while it was therapeutically equivalent to Baralgan in reducing the pain intensity in intestinal colic . Both the medications were tolerated well and there were no side-effects reported OBJECTIVES Patients presenting to the emergency department ( ED ) with suspected biliary colic often require intravenous ( IV ) analgesia . The choice of IV analgesia typically includes opioids and ketorolac . Although ultrasound ( US ) is the initial diagnostic study in these patients , nondiagnostic scans and a high clinical suspicion may require the patient to undergo hepatobiliary scintigraphy ( HIDA ) . Opioids such as morphine interfere with the HIDA scan and thus may limit its value as an analgesic in the ED for these patients . Analgesics that do not interfere with HIDA scanning include ketorolac and butorphanol , an opioid agonist-antagonist . This study evaluates the efficacy of IV ketorolac compared to butorphanol for the treatment of biliary colic pain in the ED . METHODS Between June 2005 and February 2007 , a convenience sample of patients presenting to the ED with abdominal pain suspected to be biliary colic were r and omized to receive either 30 mg of IV ketorolac or 1 mg of IV butorphanol .  Pain level was assessed using a 1 to 10 " faces " visual analog pain scale initially , as well as 15 and 30 minutes after medication infusion . Side effect profiles and the need for rescue analgesia were also assessed . Patients and clinicians were blinded to the study drug given . RESULTS Forty-six patients were enrolled in the study . Both groups had similar demographics and baseline pain scores . The mean ( + /-st and ard deviation [ SD ] ) pain score in the butorphanol group decreased from 7.1 ( + /-1.7 ) to 2.1 ( + /-2.2 ) after 30 minutes . The mean ( + /-SD ) pain score in the ketorolac group decreased from 7.4 ( + /-2.0 ) to 3.1 ( + /-3.3 ) after 30 minutes . Both groups had similar needs for rescue analgesia . Side effects included dizziness and sedation with  butorphanol and nausea with ketorolac . CONCLUSIONS Although limited by small sample size and convenience sample , this study demonstrates that both ketorolac and butorphanol provide pain relief in biliary colic . Both agents should be considered reasonable options in the ED treatment of biliary colic , especially in patients that may undergo HIDA Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input 
    Output:
    
The generalisability of the review is low as most of the RCTs included neither elderly people nor participants with comorbidities , who are more prone to complications as compared to others with biliary colic .
The beneficial effect of NSAIDs compared with placebo on pain relief was confirmed when we applied Trial Sequential Analysis .The quality of evidence according to GRADE criteria was moderate for the comparison of NSAIDs versus placebo regarding the outcome lack of pain relief and low or very low for the other outcomes and comparisons .