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Concept: Corticosteroid

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Objective To determine the frequency of prescriptions for short term use of oral corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures) associated with their use.Design Retrospective cohort study and self controlled case series.Setting Nationwide dataset of private insurance claims.Participants Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014.Main outcome measures Rates of short term use of oral corticosteroids defined as less than 30 days duration. Incidence rates of adverse events in corticosteroid users and non-users. Incidence rate ratios for adverse events within 30 day and 31-90 day risk periods after drug initiation.Results Of 1 548 945 adults, 327 452 (21.1%) received at least one outpatient prescription for short term use of oral corticosteroids over the three year period. Use was more frequent among older patients, women, and white adults, with significant regional variation (all P<0.001). The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Prescriptions were provided by a diverse range of specialties. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P<0.001).Conclusion One in five American adults in a commercially insured plan were given prescriptions for short term use of oral corticosteroids during a three year period, with an associated increased risk of adverse events.

Concepts: Time, Epidemiology, Clinical trial, Asthma, Corticosteroid, Respiratory system, Upper respiratory tract, Upper respiratory tract infection

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Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.

Concepts: Human Genome Project, Rheumatology, Ulcerative colitis, Corticosteroid, Systemic lupus erythematosus, Lupus erythematosus, Autoimmune diseases, Proteinuria

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Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

Concepts: Nephrology, Corticosteroid, Systemic lupus erythematosus, Glomerulonephritis, Immunosuppressive drug, Lupus nephritis, Cyclophosphamide, Mycophenolic acid

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Background Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children. Methods We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis. Results Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01). Conclusions In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

Concepts: Asthma, Hospital, Risk, Corticosteroid, Glucocorticoid, Long acting beta-adrenoceptor agonist, Fluticasone, Fluticasone/salmeterol

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At times, the Food and Drug Administration (FDA) must grapple with safety concerns related to off-label uses of FDA-approved medications. Over the past several years, we have sought to understand the risk of serious neurologic events that occur after the epidural injection of glucocorticoids (corticosteroids) - a procedure that is commonly performed in the United States in an effort to manage radicular neck and back pain. The FDA has not approved any injectable glucocorticoid product for epidural administration, so any such use is considered off-label - part of the practice of medicine and not regulated by the FDA. In 2009, . . .

Concepts: Pharmacology, Medicine, United States, Corticosteroid, Glucocorticoid, Pharmaceutical drug, Food and Drug Administration, Injection

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Therapy for idiopathic sudden sensorineural hearing loss is still controversial. Although there are no evidenced-based studies, therapy with systemic steroids is widely accepted as the gold standard. Intratympanic administration of steroids appears to be an alternative or additional method of management without the disadvantage of systemic side effects and, therefore, makes therapy accessible for patients with contraindication for systemic steroids.

Concepts: Medical terms, Corticosteroid, Cytochrome P450, Cochlear implant, Steroid, Ear, Tinnitus, Legal terms

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The characteristic lesion of alopecia areata is a smooth bald patch on the scalp. When there is no bald surface it is called alopecia areata incognita. To date, all cases of alopecia areata reported as so-called ‘incognito’ have shown a diffuse involvement of the scalp as in acute telogen effluvium. Recently, we have observed two patients who showed localised hair thinning of the scalp without bald spots. Histopathologically, the lesions were typical of alopecia areata with peribulbar lymphocytic infiltrates. The response to corticosteroid treatment and its clinical course were also compatible with alopecia areata.

Concepts: Anatomical pathology, Corticosteroid, Ablative brain surgery, Lesion, Baldness, Alopecia areata, Conditions of the skin appendages, Telogen effluvium

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To evaluate the efficacy and tolerability of budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline in adults with persistent asthma not adequately controlled with inhaled corticosteroid (ICS) therapy alone.

Concepts: Asthma, Corticosteroid, Glucocorticoid, Prednisolone, Prednisone

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OBJECTIVES:To evaluate the outcomes of corticosteroid-treated microscopic colitis (MC) in a population-based cohort, and to compare these outcomes in patients treated with prednisone or budesonide.METHODS:A historical cohort study of Olmsted County, Minnesota residents diagnosed with collagenous or lymphocytic colitis (LC) between 1986 and 2010 was performed using the Rochester Epidemiology Project.RESULTS:Of 315 patients with MC, 80 (25.4%) were treated with corticosteroids. The median age at colitis diagnosis was 66.5 years (range: 16-95) and 78.7% were female. Forty patients (50%) had LC and 40 (50%) had collagenous colitis. Prednisone was used in 17 patients (21.2%) and budesonide in 63 (78.8%); 56 (75.6%) had complete response and 15 (20.3%) had partial response. Patients treated with budesonide had a higher rate of complete response than those treated with prednisone (82.5 vs. 52.9%; odds ratio, 4.18; 95% CI, 1.3-13.5). Six patients were lost to follow-up. The remaining 74 had a median follow-up of 4 years (range 0.2-14). Fifty patients out of the 71 who responded (70.4%) had a recurrence after corticosteroid discontinuation. Patients treated with budesonide were less likely to recur than those treated with prednisone (hazard ratio, 0.38; 95% CI, 0.18-0.85; P=0.02). After 397 person years of follow-up in the 73 patients with long-term data, 47 (64.4%) required maintenance with corticosteroids.CONCLUSION:Patients with MC often respond to corticosteroid therapy, but with a high relapse rate. Budesonide had a higher response rate and a lower risk of recurrence than prednisone.Am J Gastroenterol advance online publication, 8 January 2013; doi:10.1038/ajg.2012.416.

Concepts: Epidemiology, Asthma, Relative risk, Gastroenterology, Corticosteroid, Collagenous colitis