***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: OBJECTIVE To estimate the relative risk for peptic ulcer disease that is associated with the use of oral corticosteroids . DESIGN A nested case-control study . SETTING Tennessee Medicaid program . PARTICIPANTS The case patients ( n = 1415 ) were hospitalized between 1984 and 1986 for gastric or duodenal ulcer or for upper gastrointestinal hemorrhage of unknown cause . The controls ( n = 7063 ) were r and omly selected from Medicaid enrollees not meeting the study criteria for inclusion as case patients . MEASUREMENTS AND MAIN RESULTS The estimated relative risk for the development of peptic ulcer disease among current users of oral corticosteroids was 2.0 ( 95 % CI , 1.3 to 3.0 ) . However , the risk was increased only in those who concurrently received nonsteroidal anti-inflammatory drugs ( NSAIDs ) ; these persons had an estimated relative risk associated with current corticosteroid use of 4.4 ( CI , 2.0 to 9.7 ) . In contrast , the estimated relative risk for those corticosteroid users not receiving NSAIDs was 1.1 ( CI , 0.5 to 2.1 ) . Persons concurrently receiving corticosteroids and NSAIDs had a risk for peptic ulcer disease that was 15 times greater than that of nonusers of either drug . CONCLUSION Discrepant findings among earlier studies regarding steroids and the risk for peptic ulcer disease could in part be due to differences in the use of NSAIDs among study participants . The high risk for peptic ulcer disease associated with combined use of NSAIDs and corticosteroids indicates the need to prescribe this drug combination cautiously OBJECTIVE To estimate the costs of glucocorticoid associated adverse events  ( GAEs ) in patients with rheumatoid arthritis ( RA ) . METHODS We conducted a literature review of studies reporting GAEs in RA patients , and developed a Markov model with the following GAEs : fractures ( vertebral , hip , pelvic ) , hypertension , diabetes , gastrointestinal complications , pneumonia , urinary tract infection , cataract and , in an extended model , myocardial infa rct ion ( MI ) and stroke . Two-year total costs were calculated using direct medical costs ( 2001 US dollars [ USD ] ) and by running 10,000 Monte Carlo simulations with probability values r and omly selected from the GAE literature . RESULTS On average ,  glucocorticoid users spent USD 445 more than non-users , or USD 0.46 for each dollar spent on purchasing the drug . When adding MI and stroke , users spent on average USD 430 more than non-users , or USD 0.44 for each dollar spent on purchasing the drug ; this incremental cost ranged from USD 193 to USD 682 if MI and stroke were excluded , respectively . In 70 % of the simulations there were more deaths among users than among non-users , in both the model with and without MI and stroke . CONCLUSIONS Although results varied depending on attributed GAEs , in general glucocorticoid users spent more than non-users on GAE treatment , and had higher mortality . Patients , providers and policy makers should consider these potential costs of GAEs when making treatment decisions OBJECTIVE To determine the influence of low-dose prednisolone on atherosclerosis , endothelial function , and risk factors for atherosclerosis in patients with early rheumatoid arthritis ( RA ) . METHODS At start of the first disease modifying antirheumatic drug , 67 patients with early , active RA were r and omized to either 7.5 mg prednisolone daily ( n = 34 ) or no prednisolone ( n = 33 ) . In the prednisolone group , 21 were treated for 2 years and 13 continuously . After a mean of 5 years intima-media thickness ( IMT ) and calculated intima-media area ( cIMa ) of the carotid arteries were determined by B-mode ultrasound .  Endothelial function was determined by flow-mediated dilatation ( FMD ) of the brachial artery . RESULTS IMT [ median ( interquartile range ) 0.675 mm ( 0.58 - 0.82 ) vs 0.673 mm ( 0.0.62 - 0.80 ) ] , cIMa [ 13.7 mm2 ( 11.45 - 20.37 ) vs 14.1 mm2 ( 12.34 - 17.38 ) ] , prevalence of atherosclerotic plaques ( 82.3 % vs 81.9 % ) , and endothelial function [ FMD% ( mean + /- SD ) 3.88 % + /- 2.8 vs 3.74 % + /- 2.9 ] did not differ between patients treated with and those not treated with prednisolone . There were no differences in lumen diameter of carotid arteries , or levels of lipoproteins , glucose , and blood pressure . Patients treated for at least 4 years ( and currently treated ) with prednisolone had a trend to higher systolic blood pressure ( 157 + /- 29 mm Hg ) compared with untreated patients ( 141 + /- 28 mm Hg ; p = 0.06 ) and had higher cholesterol levels ( 5.6 mmol/L + /- 1.39 vs 4.9 + /- 28 ; p = 0.03 ) . In the whole cohort , age and HDL were independently associated with IMT ; age , HDL , and blood pressure with cIMa ; and age and serum creatinine with presence of atherosclerotic plaques . CONCLUSION Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA . However , total cholesterol was higher in patients treated with prednisolone BACKGROUND The adverse effects of oral corticosteroids are widely recognised but there are few quantitative data on which to base advice to patients . In a two part cross sectional study we compared adverse effects in patients with lung disease taking oral corticosteroids and control subjects and related the adverse effects to corticosteroid dose in the patient group . METHODS Data on oral corticosteroid use , lifestyle , fractures , and other possible adverse effects were collected by question naire and compared between a community based cohort of patients taking continuous or frequent intermittent oral corticosteroids for asthma , chronic obstructive pulmonary disease , or alveolitis and age and sex matched control subjects . Dose related effects were explored in the corticosteroid group using cumulative dose quartiles and multiple logistic regression . RESULTS A total of 367 patients ( ⩾50 years , 48 % female ) and 734 control subjects completed the question naire . The cumulative incidence of fractures since the time of diagnosis was 23 % for patients taking oral corticosteroids and 15 % in the control group ( odds ratio ( OR ) 1.8 ; 95 % confidence interval ( CI ) 1.3 to 2.6 ) . Patients were more likely to have had a fracture of the vertebrae ( OR 10 ; 95 % CI 2.9 to 34 ) , hip ( OR 6 ; 95 % CI 1.2 to 30 ) , and ribs or sternum ( OR 3.2 , 95 % CI 1.6 to 6.6 ) than control subjects . They also reported a significant increase in cataracts , use of antacids , muscle weakness , back pain , bruising , oral c and idiasis , and having fewer teeth . The effects of oral corticosteroids were dose related : the odds ratio for patients in the highest compared with the lowest cumulative dose quartile ( median prednisolone dose 61 g versus 5 g ) ranged from 2 for all fractures to 9 for vertebral fractures and bruising . CONCLUSIONS By quantifying the morbidity associated with the use of oral corticosteroids , this study should help to rationalise their long term use We reexamined the association between corticosteroid therapy and subsequent  peptic ulceration or gastrointestinal hemorrhage  by pooling data from 71 controlled clinical trials in which patients were r and omized to systemic corticosteroids ( or ACTH )  or to  nonsteroid therapy . Of 3064 steroid-treated patients evaluated for peptic ulcer , 55 ( 1.8 per cent ) had ulcers , as compared with 23 of 2897 controls ( 0.8 per cent ) ( relative risk , 2.3 ; 95 per cent confidence interval , 1.4 to 3.7 ) . Of 3135 steroid-treated patients evaluated for gastrointestinal hemorrhage , 78 ( 2.5 per cent ) had bleeding , as compared with 48 of 2976 controls ( 1.6 per cent ) ( relative risk , 1.5 ; 95 per cent confidence interval , 1.1 to 2.2 ) . The incidence of ulcers varied directly with the dosage of steroids . When separate analyses were performed for studies that were double-blind , used only oral steroids , used only parenteral steroids , or excluded patients with a history of ulcer , the trend remained consistent but did not always reach statistical significance . This study strongly suggests that corticosteroids do increase the risk of peptic ulcers and gastrointestinal hemorrhage The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials . The overall rate of infectious complications was 12.7 % in the 2,111 patients r and omly allocated to systemic corticosteroids  and 8.0 % in the 2,087 controls  ( relative risk [ RR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.3 - 1.9 ; P less than .001 ) . The risk of infection was particularly high in patients with neurologic diseases ( RR , 2.8 ; 95 % CI , 1.9 - 4.3 ; P less than .001 ) and less pronounced in patients with intestinal ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = .02 ) , hepatic ( RR , 1.4 ; 95 % CI , 0.9 - 2.3 ; P = .25 ) , and renal ( RR greater than 1 ; P = .03 ) diseases . The rate was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg of prednisone . With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo , a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice We conducted a case – control study on  fracture risk  associated with the use of orally administered prednisolone/prednisone , budesonide , methylprednisolone , and hydrocortisone to assess if the various preparations were associated with different fracture patterns . Cases were all subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . Adjustments were made for concurrent diseases , use of other drugs , and a number of other factors . Oral prednisolone/prednisone was associated with a dose-dependent increase in fracture risk starting from a dose of around 6.7 mg/day . Oral budesonide was not associated with an increase in overall fracture risk , but the doses in general were low ( <3 mg/day ) . Oral hydrocortisone was not associated with overall risk of fractures . Oral methylprednisolone was only used intermittently and was not associated with an increase in overall fracture risk at the low doses used . After termination of oral prednisolone/prednisone , it took more than 1 year for fracture risk to return to the levels of the background population . Oral prednisolone is associated with a dose-dependent increase in overall fracture risk .  Budesonide at low doses did not seem to be associated with fracture risk .  Hydrocortisone was not associated with an increase in the risk of fractures . It may take a year from last use of prednisolone/prednisone before fracture risk returns to that of the general population OBJECTIVE To identify factors that contribute to a decreased Z score of volumetric spine bone mineral density ( ZvSBMD ) and the development of vertebral fractures ( VF ) in children receiving chronic systemic corticosteroid therapy ( SCT ) ; to describe their outcome after 2 years , and to define predictive threshold values for ZvSBMD for VF . METHODS Fifty-five children on SCT for > or= 6 months were prospect ively followed for 2 years . In children with a ZvSBMD > -1.5 , we prescribed preventive measures for osteoporosis and densitometry annually . In children with ZvSBMD < or= -1.5 , we prescribed spine x-rays and those with VF received alendronate . The association between clinical and biochemical variables and the presence of VF or ZvSBMD were analyzed by logistic regression or multiple regression analysis . The threshold value of ZvSBMD for predicting VF was determined by ROC curve and the probability of having a VF was modeled by multiple logistic regressions . RESULTS Children who do not develop osteoporosis at first evaluation tend to maintain normal ZvSBMD after two 
    Output:
    
Dose-response relationships were documented for fractures , acute myocardial infa rct ion , hypertension , and peptic ulcer .
The costs of managing AEs that may occur with corticosteroids can be substantial .
Based on the findings from this review , systemic corticosteroids are a common cause of AEs that may be costly to payers