Primary studies included in this broad synthesis

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Estudio primario

No clasificado

Glucocorticoid therapy and risk of bladder cancer.

Revista British journal of cancer
Año 2009
Enlaces Pubmed DOI PubMed Central

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BACKGROUND: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. METHODS: In a population-based case-control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. RESULTS: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24-2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17-3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26-4.36). CONCLUSION: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.

Estudio primario

No clasificado

Glucocorticoid use and risk of atrial fibrillation or flutter: a population-based, case-control study.

Revista Archives of internal medicine
Año 2009
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BACKGROUND: Glucocorticoid use is associated with increased risk of myocardial infarction, stroke, and heart failure, but data are limited on the risk of atrial fibrillation or flutter. We examined whether glucocorticoid use is associated with the risk of atrial fibrillation or flutter. METHODS: For this population-based, case-control study, we identified all patients with a first hospital diagnosis of atrial fibrillation or flutter from January 1, 1999, through December 31, 2005, in Northern Denmark (population, 1.7 million). For each case we selected 10 population controls matched by age and sex. We obtained data on glucocorticoid prescriptions within 60 days (current users) or longer before the index date (former users), comorbidity, and medications from medical databases. We used conditional logistic regression to compute odds ratios (ORs), controlling for potential confounders. RESULTS: Among 20,221 patients with atrial fibrillation or flutter, 1288 (6.4%) were current glucocorticoid users and 2375 (11.7%) were former users. Among 202,130 population controls, 5245 (2.6%) were current glucocorticoid users and 19 940 (9.9%) were former users. Current glucocorticoid use was associated with an increased risk of atrial fibrillation or flutter compared with never use (adjusted OR, 1.92; 95% confidence interval [CI], 1.79-2.06). Among new glucocorticoid users, the adjusted OR was 3.62 (95% CI, 3.11-4.22) and among long-term users it was 1.66 (95% CI, 1.53-1.80). The increased risk remained robust in patients with and without pulmonary and cardiovascular diseases. Former glucocorticoid use was not associated with increased risk (adjusted OR, 1.00; 95% CI, 0.96-1.06). CONCLUSION: Current glucocorticoid use was associated with an almost 2-fold increased risk of atrial fibrillation or flutter.

Estudio primario

No clasificado

Dose-related patterns of glucocorticoid-induced side effects.

Revista Annals of the rheumatic diseases
Año 2009
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OBJECTIVE: To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. METHODS: Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. RESULTS: The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). CONCLUSION: The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.

Estudio primario

No clasificado

Use of oral glucocorticoids and risk of skin cancer and non-Hodgkin's lymphoma: a population-based case-control study.

Revista British journal of cancer
Año 2009
Enlaces Pubmed DOI PubMed Central

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In North Jutland County, Denmark, we investigated whether use of oral glucocorticoids was associated with an increased risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), and non-Hodgkin's lymphoma (NHL). From the Danish Cancer Registry we identified 5422 BCC, 935 SCC, 983 MM, and 481 NHL cases during 1989-2003. Using risk-set sampling we selected four age- and gender-matched population controls for each case from the Civil Registration System. Prescriptions for oral glucocorticoids before diagnosis were obtained from the Prescription Database of North Jutland County on the basis of National Health Service data. We used conditional logistic regression to estimate incidence rate ratios (IRRs), adjusting for chronic medical diseases (information about these were obtained from the National Patient Registry) and use of other immunosuppressants. We found slightly elevated risk estimates for BCC (IRR, 1.15 (95% CI: 1.07-1.25)), SCC (IRR, 1.14 (95% CI: 0.94-1.39)), MM (IRR, 1.15 (95% CI: 0.94-1.41), and NHL (IRR, 1.11 (95% CI: 0.85-1.46)) among users of oral glucocorticoids. Our study supports an overall association between glucocorticoid use and risk of BCC that cannot be explained by the presence of chronic diseases or concomitant use of other immunosuppressants.

Estudio primario

No clasificado

Lesión de la mucosa gástrica en pacientes con lupus eritematoso sistémico que reciben tratamiento con metilprednisolona pulso.

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Revista British journal of clinical pharmacology
Año 2009
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OBJETIVOS: Si los glucocorticoides inducen lesión de la mucosa gástrica sigue siendo incierto. Hemos investigado si mismas altas dosis de esteroides causaron lesiones de la mucosa gástrica en el lupus eritematoso sistémico (LES) y se evalúan los posibles factores de riesgo de lesión de la mucosa. MÉTODOS: En este estudio prospectivo vinculado, 67 pacientes con LES que habían recibido tratamiento con metilprednisolona pulso se inscribieron. Cada paciente fue sometido a examen endoscópico y tejidos y muestras de sangre antes y después de la terapia con esteroides pulso. Lesión de la mucosa se diagnostica si la escala de lesiones de seguimiento fue superior a la escala inicial. Parámetros examinados incluyen la infección por Helicobacter pylori, la ciclooxigenasa (COX) -1 y COX-2, y antiinflamatorio no esteroideo actual (AINE), incluyendo el uso de la aspirina. RESULTADOS: Once (16,4%) de los 67 casos que presentaron lesiones de la mucosa gástrica después de la terapia del pulso tuvieron tasas significativamente más altas de la historia de úlcera péptica, uso de AINEs / aspirina, menor tromboxano B gástrica (2) y la prostaglandina E (2) niveles en comparación con los casos sin lesión de la mucosa gástrica (P <0,05). La infección por H. pylori no fue un factor de riesgo de lesión de la mucosa gástrica. El análisis de regresión logística multivariante mostró que el uso de AINEs / aspirina fue el único factor de riesgo de lesión de la mucosa gástrica en estos pacientes (OR 26,99, IC del 95% 4,91, 148,57, P <0,0001). Tratamiento con esteroides pulso sola no induce lesiones de la mucosa gástrica en cincuenta pacientes con LES sin tomar NSAID / aspirina. CONCLUSIONES: El uso de AINEs / aspirina, pero no la infección por H. pylori, aumenta la lesión de la mucosa gástrica en pacientes con LES que recibieron tratamiento con metilprednisolona pulso. Esteroides en dosis muy alta de novo no parecen inducir lesión de la mucosa gástrica en estos pacientes. A inscribirse estudio de casos y controles más grandes se necesita una población heterogénea de aclarar el papel de los glucocorticoides en la lesión de la mucosa gástrica.

Estudio primario

No clasificado

Corticosteroids increase risk for acute myocardial infarction in rheumatoid arthritis. The effects of careful modeling of cumulative exposure.

Revista Poster presented at: American College of Rheumatology 2009 Annual Meeting;
Año 2009

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Estudio primario

No clasificado

Notable difference between the development of vertebral fracture and osteonecrosis of the femoral head in patients treated with high-dose glucocorticoids for systemic rheumatic diseases.

Revista Internal medicine (Tokyo, Japan)
Año 2009
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OBJECTIVE: Vertebral fracture (VF) and osteonecrosis of the femoral head (OFH) are serious concerns in patients with rheumatic diseases treated with high-dose glucocorticoids (GCs). We comparatively examined the risk factors of VF and OFH in patients who had recently received high-dose GC therapy. PATIENTS AND METHODS: Patients with rheumatic diseases receiving GCs (> or =0.5 mg/kg/day for prednisolone equivalent) within the past 2 months were enrolled in this study, and treated with 200 mg/day of etidronate cyclically. The bone mineral density (BMD) of the lumbar spine (L2-4) was examined by QDR2000. OFH was evaluated by magnetic resonance imaging (MRI). [ClinicalTrials.gov identifier: NCT00679978]. RESULTS: Forty-four patients completed the 2-year study including annual X-rays and the BMD analysis. MRI evaluation at entry and 2 years was performed in 41 patients. The BMD values with anteroposterior (AP) and lateral views decreased by 6.4% and 9.7%, respectively, in the first year, but were stable in the second year. Eleven patients developed VF and 9 patients developed OFH. The risk factors for VF included previous VF and a low BMD value (T score<-1.5) of AP view at baseline with an odds ratio (OR) of 14.9 (95%CI 2.9-76.4), while the risk factor for OFH was a recent maximum GC dosage (>1.2 mg/kg/day versus< or =; OR=7.7, 95%CI 1.3-45.5) and a decrease in BMD value of lateral view (>15% versus< or =; OR=6.7, 95% CI 1.2-36.1) in the first year. CONCLUSION: The development of VF relies on the predisposing factors, while that of OFH depends on the response to high-dose GC therapy.

Estudio primario

No clasificado

Incidence of symptomatic vertebral fracture with high-dose glucocorticoid treatment in the Chiba-Shimoshizu Rheumatic Cohort between 1986 and 2006.

Revista Endocrine journal
Año 2009
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We investigated the incidence of symptomatic vertebral fracture in patients who required long-term high-dose glucocorticoid (GC) treatment. The patients with collagen vascular diseases (aged 18 years or older) were registered to Chiba-Shimoshizu Rheumatic Cohort from 1986 to 2006. The study included the patients who were newly treated with the initial dose more than 20 mg prednisolone equivalent per day at least for more than 6 months. Among 700 patients (female/ male: 539/161, mean age: 46.7 years, mean initial GC dose: 39.9 mg/day), 167 patients (23.8%) had at least one symptomatic vertebral fracture. Age and daily GC dose were significantly higher in the symptomatic fracture group than the no symptomatic fracture group. Cox regression model demonstrated that the relative risk for symptomatic vertebral fracture is independently higher in female patients, and in patients with initial higher age, and in those patients with initial higher GC dose and GC dose-increase, but lower with cumulative higher GC dose. High-dose GC treatment causes significantly high prevalence of symptomatic vertebral fracture in patients with collagen vascular disease. Age, female, higher initial GC dose and GC dose-increase are the risk factors for the symptomatic vertebral fracture in those patients.

Estudio primario

No clasificado

Dexamethasone and the risk for adrenal suppression in multiple myeloma.

Revista Leukemia
Año 2009
Enlaces Pubmed DOI PubMed Central www.scopus.com

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Estudio primario

No clasificado

Postmenopausal Canarian women receiving oral glucocorticoids have an increased prevalence of vertebral fractures and low values of bone mineral density measured by quantitative computer tomography and dual X-ray absorptiometry, without significant changes in parathyroid hormone.

Revista European journal of internal medicine
Año 2008
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BACKGROUND: Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Moreover, in this setting, the importance of secondary hyperparathyroidism is still controversial. DESIGN, PATIENTS AND METHODS: Cross-sectional observational study performed on 1177 consecutive Canary postmenopausal women who attended our Bone Metabolic Unit. The Patient Group was composed of 88 postmenopausal women who were taking oral corticosteroids in dose higher than 7.5 mg/day of prednisone or equivalent for more than 6 months (OG group). The Control Group included 838 postmenopausal women who did not take steroids. A complete validated questionnaire for osteoporosis risk assessment and a complete physical examination were performed. A lateral X-ray of the spine was performed on every woman. Bone mineral density (BMD) was measured at the lumbar spine (LS) by dual X-ray Absorptiometry (DXA) and QCT and at the femoral neck by DXA. Fasting serum and 24 hour urine was collected and biochemical markers of bone remodelling were studied. RESULTS: Both groups were comparable in general characteristics and calcium intake. The OG group showed lower values of BMD estimated both by DXA and QCT (p<0.05). LS BMD was closely correlated by using both methods (r=0.636, p<0.001). The OG group showed lower values of osteocalcin (p=0.023) and TRAP (p=0.026) without significant differences in PTH. Patients in OG group had a higher prevalence of vertebral fractures than controls (13.3% vs 8.6%; crude values: p=0.049, OR: 1.63 (0.99-2.67); age adjusted: p=0.003, OR 2.29 (1.33-9.93)). CONCLUSIONS: In postmenopausal Canarian women, chronic glucocorticoid therapy is associated with low bone mineral density, measured either by DXA or QCT, with evidence of low turnover and high prevalence of fractures without significant changes in PTH. DXA and QCT provide similar information in the assessment of this high risk population.