***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 determine whether patients with rheumatoid arthritis ( RA ) are at increased risk of hospitalized infection and whether the risk varies by RA treatment . METHODS A retrospective cohort study was conducted using data from a medical and pharmacy cl aims managed-care data base from 1999 to 2006 . A total of 24,530 patients were included in the RA cohort ; a r and om sample of non-RA patients served as a comparison cohort ( n = 500,000 ) .  Rates of hospitalized infection were compared between the cohorts . A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk . RESULTS A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection . The rate of first hospitalized infection was higher in the RA cohort [ adjusted hazard ratio = 2.03 ; 95 % confidence interval ( CI ) 1.93 - 2.13 ] . In the case-control analysis , the current use of biological disease modifying antirheumatic drugs ( DMARD ) was associated with slightly increased risk of hospitalized infection [ rate ratio ( RR ) = 1.21 ; 95 % CI 1.02 - 1.43 ] . Methotrexate and hydroxychloroquine were associated with decreased risk .  Oral corticosteroid use increased risk ( RR = 1.92 ; 95 % CI 1.67 - 2.21 ) , and there was a dose-related effect [ < or = 5 mg/day : RR = 1.32 ( 95 % CI 1.06 - 1.63 ) , 6 - 10 mg/day : RR = 1.94 ( 95 % CI 1.53 - 2.46 ) , > 10 mg/day : RR = 2.98 ( 95 % CI 2.41 - 3.69 ) ] . CONCLUSION These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA . Oral corticosteroid use was associated with a dose-related increase . Biological DMARD use was associated with slightly elevated risk ; however , this may reflect confounding and channeling bias OBJECTIVES To compare budesonide , a locally acting glucocorticoid with minimal systemic exposure , with conventional glucocorticoid treatment and placebo in rheumatoid arthritis . METHODS A double blind , r and omised , controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis , comparing budesonide 3 mg daily , budesonide 9 mg daily , prednisolone 7.5 mg daily , and placebo . Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment . RESULTS There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo ( 28 % for tender and 34 % for swollen joint counts , p<0.05 ) . Prednisolone 7.5 mg gave similar results , while budesonide 3 mg was less effective . ACR20 response criteria were met by 25 % of patients on placebo , 22 % on budesonide 3 mg , 42 % on budesonide 9 mg , and 56 % on prednisolone 7.5 mg . A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks . There was no evidence that budesonide provided a different pattern of symptom control from prednisolone , or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment . Adverse effects attributable to glucocorticoids were equally common in all groups . CONCLUSIONS The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment , are maintained for three months , and are not associated with any rebound in symptoms after stopping treatment Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits . Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology . However , because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval , it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure . To investigate this issue , we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically ( 5.3 ± 1.0 years , mean ± SE ) with low to moderate doses of prednisone ( 7.5 ± 0.8 mg , mean ± SE ) or without glucocorticoids .  In both groups , delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind , placebo-controlled crossover design . Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se , acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall . Thus , these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result , at least in part , from acute and reversible glucocorticoid effects on memory retrieval OBJECTIVE To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis ( RA ) . METHODS At the start of their initial treatment with a disease-modifying antirheumatic drug ( DMARD ) , patients with early ( duration < or = 1 year ) active RA were r and omly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years . Radiographs of the h and s and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde . Remission was defined as a Disease Activity Score in 28 joints of < 2.6 . Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years . RESULTS Of the 250 patients included , 242 completed the study and 225 had radiographs available both at baseline and at 2 years . At 2 years , the median and interquartile range ( IQR ) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group ( 1.8 [ IQR 0.5 - 6.0 ] versus 3.5 [ IQR 0.5 - 10 ] ; P = 0.019 ) . In the prednisolone group , there were fewer newly eroded joints per patient after 2 years ( median 0.5 [ IQR 0 - 2 ] versus 1.25 [ IQR 0 - 3.25 ] ; P = 0.007 ) . In the prednisolone group , 25.9 % of patients had radiographic progression beyond the smallest detectable difference compared with 39.3 % of patients in the no-prednisolone group ( P = 0.033 ) . At 2 years , 55.5 % of patients in the prednisolone group had achieved disease remission , compared with 32.8 % of patients in the no-prednisolone group ( P = 0.0005 ) . There were few adverse events that led to withdrawal . Bone loss during the 2-year study was similar in the 2 treatment groups . CONCLUSION Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA , provided a high remission rate , and was well tolerated . Therefore , the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA Objective This 9-month open-label extension of the Circadian Administration of Prednisone in Rheumatoid Arthritis Study ( CAPRA 1 ) investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release ( MR ) prednisone for up to 12 months . Methods Of 288 patients with rheumatoid arthritis originally r and omised to MR or immediate-release ( IR ) prednisone , 249 continued with prednisone chronotherapy ( 2–10 mg/day ) in the 9-month open-label extension . Duration of morning stiffness of the joints ( MS ) , disease activity scores ( DAS28 ) , American College of Rheumatology ( ACR20 ) responses and plasma levels of interleukin 6 ( IL-6 ) were assessed . Safety was analysed from adverse event reports and laboratory investigations . Results During the 3-month double-blind phase , patients in the MR group achieved a reduction in MS of 33.1 % while no change was observed in the IR group . After 6 months of treatment , MS was reduced in the IR/MR group by 54 % and in the MR/MR group by 56 % . MS reduction after 12 months was 45 % ( IR/MR group ) and 55 % ( MR/MR group ) . Plasma levels of IL-6 declined on MR treatment . DAS28 was reduced from 5.8 to 4.8 ( MR/MR group ) and 4.9 ( IR/MR group ) , respectively . 37 % of the 219 patients who completed the 12-month study achieved improvement according to the ACR20 criteria . Adverse events did not differ from the known profile of low-dose prednisone . Conclusions Prednisone chronotherapy with the MR tablet was safe and well tolerated and provided a sustained improvement which result ed in a better benefit to risk ratio of low-dose glucocorticoid treatment for at least 12 months BACKGROUND Treatment strategies for tight control of early rheumatoid arthritis ( RA ) are highly effective but can be improved . OBJECTIVE To investigate whether adding prednisone , 10 mg/d , at the start of a methotrexate (MTX)-based treatment strategy for tight control in early RA increases its effectiveness . DESIGN A 2-year , prospect i ve , r and omized , placebo-controlled , double-blind , multicenter trial ( CAMERA-II [ Computer Assisted Management in Early Rheumatoid Arthritis trial-II ] ) . ( International St and ard R and omised Controlled Trial Number : IS RCT N 70365169 ) SETTING 7 hospitals in the Netherl and s. PATIENTS 236 patients with early RA ( duration < 1 year ) . INTERVENTION Patients were r and omly assigned to an MTX-based , tight control strategy starting with either MTX and prednisone or MTX and placebo . Methotrexate treatment was tailored to the individual patient at monthly visits on the basis of predefined response criteria aim ing for remission . MEASUREMENTS The primary outcome was radiographic erosive joint damage after 2 years . Secondary outcomes included response criteria , remission , and the need to add cyclosporine or a biologic agent to the treatment . RESULTS Erosive joint damage after 2 years was limited and less in the group receiving MTX and prednisone ( n = 117 ) than in the group receiving MTX and placebo ( n = 119 ) . The MTX and prednisone strategy was also more effective in reducing disease activity and physical disability , achieving sustained remission , and avoiding the addition of cyclosporine or biologic treatment . Adverse events were similar in both groups , but some occurred less in the MTX and prednisone group . LIMITATION A tight control strategy for RA implies monthly visits to an outpatient clinic , which is not always feasible . CONCLUSION Inclusion of low-dose prednisone in an MTX-based treatment strategy for tight control in early RA improves patient outcomes . PRIMARY FUNDING SOURCE Catharijne Foundation OBJECTIVE To determine whether the incidence of herpes zoster is elevated in patients with rheumatoid arthritis ( RA ) and whether herpes zoster is associated with use of disease-modifying antirheumatic drugs ( DMARDs ) in patients with RA . METHODS Two retrospective cohort studies were conducted using data from a US integrated managed care data base ( PharMetrics cl aims data base ) from 1998 - 2002 and the UK General Practice Research Data base ( GPRD ) between 1990 - 2001 . Rates of herpes zoster among patients with RA and r and omly sample d non-RA patients were compared . A nested case-control analysis was performed within each RA cohort to examine the effect of current treatment on herpes zoster risk . RESULTS A total of 122,272 patients with RA from the PharMetrics data base and 38,621 from the GPRD were included . The adjusted hazard ratios of herpes zoster for patients with RA compared with non-RA patients were 1.91 ( 95 % confidence interval [ 95 % CI ] 1.80 - 2.03 ) in the PharMetrics data base and 1.65 ( 95 % CI 1.57 - 1.75 ) in the GPRD . In the PharMetrics data base , current use of biologic DMARDs alone was associated with herpes zoster ( odds ratio [ OR ] 1.54 , 95 % CI 1.04 - 2.29 ) , as was 
    Output:
    
FINDINGS We identified 1030 papers and selected for analysis 26 observational studies and six systematic review s. The major side effects of GCs in RA are bone loss , risk of cardiovascular events and risk of infections as evidence d by large observational studies and not necessarily RCTs .
Others associations were reported with herpes zoster , tuberculosis , hyperglycemia , cutaneous abnormalities , gastrointestinal perforation , respiratory infection and self-reported health problems such as cushingoid phenotype , ecchymosis , parchment-like skin , epistaxis , weight gain and sleep disturbance .
Other potential adverse effects of GCs were studied but no association was found .
These included psychological disorders , dermatophytosis , brain diseases , interstitial lung disease , memory deficit , metabolic syndrome , lymphoma , non-Hodgkin 's lymphoma , renal function and cerebrovascular accidents .
Recent observational data and systematic review s suggest that GCs can lead to relatively alarming and burdensome side effects in RA .
This is particularly true for patients who have longer term and higher dose therapies .