ArticleLiterature Review

Corticosteroid-Induced Adverse Events in Adults

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Abstract

Corticosteroids represent the most important and frequently used class of anti-inflammatory drugs and are the reference therapy for numerous neoplastic, immunological and allergic diseases. However, their substantial efficacy is often counter-balanced by multiple adverse events. These corticosteroid-induced adverse events represent a broad clinical and biological spectrum from mild irritability to severe and life-threatening adrenal insufficiency or cardiovascular events. The purpose of this article is to provide an overview of the available data regarding the frequency, screening and prevention of the adverse events observed in adults during systemic corticosteroid therapy (topically administered corticosteroids are outside the remit of this review). These include clinical (i.e. adipose tissue redistribution, hypertension, cardiovascular risk, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency, infections, mood disorders, ophthalmological disorders, skin disorders, menstrual disorders, aseptic necrosis, pancreatitis) and biological (i.e. electrolytes homeostasis, diabetogenesis, dyslipidaemia) events. Lastly, data about the prescription of corticosteroids during pregnancy are provided. This review underscores the absence of data on many of these adverse events (e.g. lipodystrophy, dyslipidaemia). Our intent is to present to practitioners data that can be used in a practical way to both screen and prevent most of the adverse events observed during systemic corticosteroid therapy.

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... Outside the field of leprosy, the adverse events of corticosteroids have been well documented for the treatment of diverse pathologies. 8 In a multi-centre randomised, double blind clinical trial the effectiveness of a longer, 32 weeks course of prednisolone was compared with the commonly accepted treatment regimens of 20 weeks in improving and restoring clinically established recent sensory and/or motor loss (from now on called the clinical trial). 9 In a parallel randomised, double-blind and placebo-controlled trial, prednisolone was given for 20 weeks to patients who had only subclinical nerve impairment, as assessed by nerve conduction studies (NCS) and/or Warmth Detection Thresholds (WDT) 1 (from now on called the subclinical trial). ...
... One possible reason for losing patients to follow-up is side effects of the treatment, and therefore potentially the number of SAE could have been higher than reported. 8,19 Obvious differences are seen in the incidence of minor adverse events between the project sites and one could also wonder whether these could be attributed to ethnic differences and/ or differences in alertness in noticing and recording of (minor) adverse events. 20 It should be born in mind that the studies took place in six projects in four countries with structurally differing leprosy programs. ...
... Outside leprosy, adverse events due to corticosteroids have been extensively reviewed by Fardet for many other clinical conditions. 8,18 Because of its completeness and clinical grouping, the classification of adverse events as developed by Fardet seems most suitable to follow in future leprosy clinical projects using steroids or other immune-suppressive drugs. 8,24 Though it is important to have a protocol, or guideline document, for the treatment of nerve function impairment, ideally treatment for reaction/NFI should be patient centred. ...
... In the 1950s, the use of cortisone in schizophrenia patients was reported in several small studies without randomization or placebo-control (Clark and Eik-Nes, 1956;Polatin et al., 1955). So far, no placebo-controlled trials were performed studying the effects of corticosteroids have not been studied in patients with schizophrenia, possibly due to the risk for developing neuropsychiatric side-effects (Fardet et al., 2012(Fardet et al., , 2007. ...
... Only patients with an optimal, stable dose (for at least three weeks) of antipsychotic medication were included and treating physicians were urged to keep the antipsychotic treatment as stable as possible during the sixweek treatment period. Study medication was initiated with 40 mg/day, as this low to moderate dose is associated with few neuro-psychiatric side effects (Fardet et al., 2012(Fardet et al., , 2007, and was tapered off gradually to zero in six weeks. ACE Pharmaceuticals (The Netherlands) manufactured the placebo and composed the study medication kits, which consisted of six study medication boxes. ...
... As prednisolone might induce neuro-psychiatric side-effects in a dosedependent fashion (Fardet et al., 2012(Fardet et al., , 2007, extra procedures were implemented to ensure patient safety. At each visit, potential adverse events (AEs) and concomitant medication were monitored by the study physician. ...
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Objective Immune dysregulation may be involved in the pathophysiology of schizophrenia. Given the need for new treatment options in schizophrenia, anti-inflammatory medication could be a potential treatment in this illness. Methods In this double-blind, placebo-controlled clinical trial, patients with schizophrenia, schizoaffective disorder or psychosis NOS were randomized 1:1 to either prednisolone or placebo, in addition to their regular antipsychotic medication. Patients diagnosed with schizophrenia for less than 7 years and on antipsychotics, were treated with prednisolone or placebo, tapered-off within six weeks in the following schedule: 40 mg/day for 3 days and 30 mg/day for 4 days, followed by a decrease of 5 mg/day per week during the remaining 5 weeks. Change in symptom severity relative to baseline was compared between treatment arms, as measured through the Positive and Negative Syndrome Scale total score. Results In total, 68 patients signed informed consent and were screened on eligibility criteria, of whom 42 patients were randomized to either prednisolone or placebo, with 39 patients completing the treatment and tapering phase. Due to recruitment difficulties, the study was terminated prematurely. Symptom severity decreased significantly in both the prednisone and placebo treatment arm (p < 0.001). The degree of improvement was not significantly different between treatment arms (p = 0.96). No serious adverse events occurred during the treatment phase. Discussion There is no indication that prednisolone has a beneficial effect on symptom severity, as adjunctive treatment in patients with schizophrenia, as compared to placebo. Conclusion Adjunctive treatment with prednisolone did not improve symptom severity compared to placebo in patients with schizophrenia.
... Oral steroid use increases the risk of sepsis (RR = 5. [124,125]. In addition, all but occasional use of steroids is associated with exacerbations of pre-existing mental illness, mood disorders, steroid dementia, and akathisia [126]. The use of high doses of steroids for 1 or more months can lead to the development of acute psychosis and affective disorders [126]. ...
... In addition, all but occasional use of steroids is associated with exacerbations of pre-existing mental illness, mood disorders, steroid dementia, and akathisia [126]. The use of high doses of steroids for 1 or more months can lead to the development of acute psychosis and affective disorders [126]. One of the most severe complications is osteonecrosis, which occurs in 5-25% of patients receiving high doses of steroids for several months [127,128]. ...
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Since the beginning of the COVID-19 pandemic, clinical, radiological, and histopathological studies have provided evidence that organizing pneumonia is a possible consequence of the SARS-CoV2 infection. This post-COVID-19 organizing pneumonia (PCOP) causes persisting dyspnea, impaired pulmonary function, and produces radiological abnormalities for at least 5 weeks after onset of symptoms. While most patients with PCOP recover within a year after acute COVID-19, 5–25% of cases need specialized treatment. However, despite substantial resources allocated worldwide to finding a solution to this problem, there are no approved treatments for PCOP. Oral corticosteroids produce a therapeutic response in a majority of such PCOP patients, but their application is limited by the anticipated high-relapse frequency and the risk of severe adverse effects. Herein, we conduct a systematic comparison of the epidemiology, pathogenesis, and clinical presentation of the organizing pneumonias caused by COVID-19 as well as other viral infections. We also use the clinical efficacy of corticosteroids in other postinfection OPs (PIOPs) to predict the therapeutic response in the treatment of PCOP. Finally, we discuss the potential application of a candidate anti-inflammatory and antifibrotic therapy for the treatment of PCOP based on the analysis of the latest clinical trials data.
... 3 In the USA, nearly 1.2% of the adult population receive long-term oral corticosteroids. 4 Glucocorticoids are important in the treatment of many inflammatory, allergic, immunological and malignant disorders; the toxicity of glucocorticoids is one of the commonest causes of iatrogenic illness associated with chronic inflammatory disease, which requires strict monitoring of patients. After several weeks of treatment, 60-80% of patients report an adverse effect of treatment. ...
... After several weeks of treatment, 60-80% of patients report an adverse effect of treatment. 4 In developed countries, bone-related adverse effects are the most reported, mainly osteoporosis, 5 whereas in Africa metabolic effects are the most reported. 6,7 Long-term oral corticosteroids have an important role in dermatological care in Madagascar. ...
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Background: Long-term oral corticosteroids have an important role in dermatological care in Madagascar. However, significant adverse effects have been associated with continuous exposure to oral corticosteroids. Objective: We aim to assess the adverse effects of long-term corticosteroid therapy in patients seen in the Department of Dermatology at the University Hospital Joseph Raseta Befelatanana Antananarivo (UH/JRB), Madagascar, and to identify the risk factors associated with these adverse effects. Methods: A cross-sectional study was conducted during 4 months to assess the adverse effects of long-term corticosteroid therapy in patients seen in the Department of Dermatology. Patients treated with oral corticosteroids for more than 3 months were included in our study. Results: The prevalence of long-term use of oral corticosteroids in the Department of Dermatology of UH/JRB was 34.28%. A total of 51 patients were included and adverse effects occurred in 64.70% of this population. Repetitive infections and cutaneous adverse reactions were the most frequent adverse effects, in 23.52% and 11.76% of cases, respectively. There were no correlations between age, gender, type of disease treated, the molecule used or daily dose and the risk of adverse effects. Patients who received a corticosteroid dose of more than 40 mg daily (longer than 3 months) or a high cumulative dose of corticosteroids had a high risk of adverse effects. Conclusion: Repetitive infections and cutaneous adverse reactions are the most frequent adverse effects of long-term oral corticosteroid use. Prescribing the lowest effective dose may reduce the risk of these adverse effects. Furthermore, prevention of the adverse effects of corticosteroids through diet, calcium and vitamin D supplementation is strongly recommended during long-term oral corticosteroid therapy.
... 1,2 It has been well recognized for more than a half century that long-term use of oral corticosteroids is associated with subsequent adverse events, including Cushingoid features, gastrointestinal (GI) bleeding, infections, glaucoma, hyperglycemia, cardiovascular diseases, and osteoporosis. [3][4][5][6][7][8] Clinicians therefore caution against long-term use of oral corticosteroids unless the potential benefits outweigh the potential risks. ...
... Previous studies [3][4][5][6][7][8] have reported the adverse effects of long-term corticosteroid use on the GI, immune, and ophthalmologic systems; however, to our knowledge, it remains unknown whether corticosteroid bursts are associated with adverse effects on these systems, especially in children. Thus, we chose 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) as the outcomes of interest in this study. ...
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Importance The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children. Objective To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children. Design, Setting, and Participants This cohort study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020. Exposure Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days). Main Outcomes and Measures Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts. Results Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma. Conclusions and Relevance This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.
... Corticosteroids (CS) are commonly utilized across many clinical specialties in medicine despite having well-known complications including avascular necrosis (AVN), osteoporosis, upper gastrointestinal (GI) bleeding, myocardial infarction, reactivation tuberculosis, cataracts, diabetes, and psychosis. 1 In the era of SARS-Cov-2 (COVID- 19), highdose dexamethasone therapy has shown to significantly reduce 28-day mortality for select COVID-19 patients. [2][3][4] Consequently, a literature review on the complications of steroid therapy is timely. ...
Article
Relevance to Patient Care and Clinical Practice: Corticosteroids are among the most prescribed medications, particularly during the COVID-19 era. The literature has clearly highlighted the dangers of prolonged, high-dose corticosteroid use, which is important for clinicians to consider before treating patients in their clinical practices. Objective: The objective of this article is to review the literature on complications of corticosteroid use, review corticosteroid pharmacokinetics, and provide an updated reference on risks associated with corticosteroid therapy, especially at higher doses. Data Sources: A conventional literature search of PubMed was conducted without restrictions on publication date. Search terms included “corticosteroids,” “avascular necrosis,” “gastrointestinal bleeding,” and “complications.” Study Selection and Data Extraction: Pertinent systematic review/meta-analyses and randomized controlled trials were reviewed for study inclusion. Data Synthesis: Corticosteroids were associated with complications including avascular necrosis, gastrointestinal bleeding, myocardial infarction, heart failure, cerebrovascular events, diabetes mellitus, psychiatric syndromes, ophthalmic complications, tuberculosis reactivation, and bacterial sepsis. Increased daily and cumulative doses were associated with increased excess risk of complications. Cumulative doses greater than 430 mg prednisone equivalent were shown to increase the excess risk of avascular necrosis, with progressively higher rates with higher doses. Risk of gastrointestinal bleeding was significantly increased with corticosteroid usage in the in-patient but not out-patient setting. Conclusion: Since corticosteroids have been associated with the aforementioned severe complications and frequent medicolegal malpractice claims, counseling and informed consent should be performed when prescribing moderate-high dosages of corticosteroids. Further research is needed to characterize the long-term effects of corticosteroid usage in COVID-19 patients.
... Glucocorticoids (GCs) are commonly used worldwide for the treatment of various diseases (1,2). GC treatment is associated with several adverse effects such as osteoporosis, hypertension, insulin resistance, infections, mood disturbances, cataract formation, and increased risk of cardiovascular disease (3)(4)(5)(6)(7)(8). ...
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Objective The aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. Methods This was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. Results Cases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). Conclusion Oral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.
... Dexamethasone, a corticosteroid, was used as anti-inflammatory drugs to treat COVID-19. However, it produced the side effects of hyperglycemia and hyperlipemia, and even caused diabetes in serious cases (Fardet et al., 2007). After 12 days of dexamethasone injection, comparing with that in the normal rats, the blood glucose level in the dexamethasone-injected rats was significantly increased by 43.2% (Fig. 1b), demonstrating that dexamethasone injection successfully induced glucose metabolism disorder in rats. ...
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Halocynthia roretzi has been cultured and utilized as a nutritious seafood in Southeastern Asia for many years because of its abundance active molecules. Here, we reported that feeding of H. roretzi tissues resulted in improving oral glucose tolerance in rats. To screen the active components, we identified 950 chemical compounds from H. roretzi metabolome. Furthermore, 11 molecules with the activity of regulating blood glucose and lipids were selected based on structural identity. Among them, two natural products, hesperetin and astaxanthin were selected for further quantitative detection. The results showed that concentrations of hesperetin and astaxanthin in the tissues of H. roretzi were calculated to be 13.7 ± 9.5 and 167.9 ± 48.4 µg/100 g, respectively. The high content of astaxanthin in H. roretzi indicates its potential roles and functions in anti-diabetes activity. Taken together, our results showed that H. roretzi could be used as a functional food supplement for regulating lipid/glucose metabolism.
... [25][26][27] Thus to prevent it, any preexisting comorbid conditions that can increase the risk of adverse effects should be treated before administration begins, and the screening program should be conducted periodically. 28,29 Differences in therapeutic effectiveness and adverse effects between 12 weeks and >12 weeks corticosteroid use ...
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Objectives Main therapy for leprosy reactions is 12 weeks corticosteroids according to World Health Organization recommendations, but recovery cannot be achieved and recurrence occurs. Long duration of administration was thought to provide better clinical improvement. Evidence of the efficacy of corticosteroids in leprosy reactions is still lacking, and optimal dose and duration of therapy vary, while the need for long-term high-dose corticosteroids makes it difficult to avoid adverse effects. Methods This is a retrospective cohort study analyzing the difference between therapeutic effectiveness and adverse effects of 12 weeks and >12 weeks corticosteroids, involving all new leprosy patients without age restriction, at Cipto Mangunkusumo Hospital and Cakung Community Health Center in Indonesia during 1 January 2015–31 December 2017. Secondary data were collected from medical records, and observations carried out until December 2018. Therapeutic effectiveness was assessed from clinical improvement to corticosteroids discontinuation, without 3 months recurrence after first cycle was completed. Adverse effects were assessed by all corticosteroids-related side effects. Results Of 195 patients, 57 (29.2%) used 12 weeks corticosteroids, and 138 (70.8%) for >12 weeks. Effectiveness occurred in 38 (66.7%) of 12 weeks group and 106 (76.8%) of >12 weeks group (relative risk = 0.604, 95% confidence interval = 0.307–1.189, p = 0.143). Of 145 patients, adverse effects occurred in 12 (31.6%) of 12 weeks group and 70 (65.4%) of >12 weeks group (relative risk = 0.244, 95% confidence interval = 0.111–0.538, p < 0.001). Of 171 adverse effects, 37.4% were mild such as dyspepsia, skin disorders, and lipodystrophy, while 62.6% were severe in the form of neuropsychiatric disorders, eye disorders, cardiovascular disease, gastrointestinal bleeding, metabolic-hormonal abnormalities, and reactivation of infections. Conclusion There is no effectiveness difference in the form of clinical improvement without 3 months recurrence, between 12 weeks and >12 weeks corticosteroid, while longer administration causes 4 times more events.
... Moreover, we could not demonstrate any association between dexamethasone and CAPA because we used dexamethasone in most HD patients with COVID-19. However, dexamethasone may remain harmful in HD patients because it is a long-acting glucocorticoid that leads to infection, gastrointestinal bleeding, hyperglycemia and venous thromboembolism [22]. In the present study, gastrointestinal bleeding was observed in two patients and one of the two patients died due to gastrointestinal bleeding. ...
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Background Coronavirus Disease 2019-associated pulmonary aspergillosis (CAPA) is a fatal complication in the general population. However, there are few reports on CAPA in patients undergoing hemodialysis (HD). Methods This retrospective observational cohort study was conducted at a single center between December 2020 and June 2021. We enrolled 21 HD patients with Coronavirus Disease 2019 (COVID-19) undergoing treatment and divided them into two groups: CAPA and non-CAPA (COVID-19 with and without pulmonary aspergillosis); we evaluated their characteristics, clinical outcomes, and comorbidities. Results The log-rank test revealed that the 90-day survival rate after the initiation of treatment for COVID-19 was significantly lower in the CAPA (n = 6) than in the non-CAPA group (n = 15) (P = 0.0002), and the 90-day mortality rates were 66.6% and 0% in the CAPA and non-CAPA groups, respectively. In the CAPA group, four patients died due to respiratory failure (on days 6 and 20), gastrointestinal bleeding (day 8), and sepsis (day 33); the RT-PCR for SARS-CoV-2 remained positive when they died. The remaining two patients survived, and the negative conversion of RT-PCR for SARS-CoV-2 was confirmed on days 10 and 15. The negative conversion of serum (1, 3)-β-D-glucan (BDG) was confirmed on day 15 in one patient; the BDG remained positive on day 64 in the other. Conclusions CAPA is a fatal complication in HD patients and the general population. Therefore, clinicians should consider the possibility of testing for CAPA in patients undergoing hemodialysis. Mycological workups may be helpful for the early detection of CAPA.
... Our data on structural and functional changes in the parenchyma of the testes and their bloodstream are fully consistent with modern ideas about the nature of hormonal effects on the genital area and may be a consequence of the side effects of prednisolone, which are embedded in Cushing's syndrome, diabetes and metabolic syndrome [5,6,7]. These include a significant increase in animal body weight as a result of increased appetite and the development of alimentary obesity, as well as an increase in the weight and volume of the testes with increased functional activity on the background of full blood vessels due to dilation of their lumen. ...
Article
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Objective: The aim: To investigate the nature of morphofunctional changes in the parenchyma and bloodstream of the testes of white rats with prolonged administration of high doses of prednisolone. Patients and methods: Material and methods: The experiments were performed on rats fed daily for 1, 3, 7, 14 and 28 days. prednisolone was administered intramuscularly at a rate of 0.4 mg / kg. Massometric, organometric, histological and morphometric studies were performed. Results: Results: Administration of high doses of prednisolone resulted in a significant increase in body weight and testicular weight and volume. As the drug was administered, spermatogenesis was activated. The number of immature forms of germ cells increased significantly. At the same time, the specific number of mature forms of sperm decreased. This led to a significant increase in the diameter of the convoluted tubules, the thickness of the spermatogenic epithelium, as well as the index of spermatogenesis. The increase in indicators was especially intense until the 7th day of observation, after which its rate decreased, although the dynamics remained unchanged. The thickness of the protein shell tended to decrease. The detected changes occurred against the background of dilation and plethora of arteries, especially up to 7-14 days of the experiment, after which their intensity decreased slightly. This was accompanied by a simultaneous reversible narrowing of the lumen of small arteries and arterioles. Conclusion: Conclusion: Thus, long-term administration of high doses of prednisolone promotes the activation of spermatogenesis with an increase in immature forms of germ cells and a simultaneous decrease in the proportion of mature sperm. Increased vascular blood supply, especially in the early period. In the long run, the capacity of small arteries and arterioles is reduced, as well as the degree of activation of spermatogenesis.
... Glucocorticoids are drugs that have immunosuppressive and anti-inflammatory effects in appropriate therapeutic doses, although there are many side effects encountered during glucocorticoid use (6). While osteoporosis is a recognized and common side effect affecting bone metabolism, avascular necrosis is a less frequent side effect (7,8). ...
... Risk attributes covered the frequency of adverse events, severity of adverse events, adverse event type, and steroid dosing. Higher steroid doses are associated with worse and more prolonged adverse events [59][60][61][62] and were therefore deemed to be a risk concept for the purposes of this categorisation. Although just under half of studies included a treatment risk attribute, the number of treatment risk attributes assessed relative to the number of symptom or treatment benefit attributes is small. ...
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Background Regulators have called for greater emphasis on the role of the patient voice to inform medical product development and decision making, and expert guidelines and reports for asthma and chronic obstructive pulmonary disease (COPD) both explicitly recommend the consideration of patient preferences in the management of these diseases. Discrete choice experiments (DCEs) are commonly used to quantify stakeholders’ treatment preferences and estimate the trade-offs they are willing to make between outcomes such as treatment benefits and risks.Objective The aim of this systematic literature review is to provide an up-to-date and critical review of DCEs published in asthma and COPD; specifically, we aim to evaluate the subject of preference studies conducted in asthma and COPD, what attributes have been included, stakeholders’ preferences, and the consistency in reporting of instrument development, testing and reporting of results.MethodsA systematic review of published DCEs on asthma and COPD treatments was conducted using Embase, Medline and the Cochrane Database of Systematic Reviews. Studies were included if they included a DCE conducted in a relevant population (e.g. patients with asthma or COPD or their caregivers, asthma or COPD-treating clinicians, or the general population), and reported quantitative outcomes on participants’ preferences. Study characteristics were summarised descriptively, and descriptive analyses of attribute categories, consistency in reporting on key criteria, and stakeholder preferences were undertaken.ResultsA total of 33 eligible studies were identified, including 28 unique DCEs. The majority (n = 20; 71%) of studies were conducted in a patient sample. Studies focused on inhaler treatments, and included attributes in five key categories: symptoms and treatment benefits (n = 23; 82%), treatment convenience (n = 19; 68%), treatment cost (n = 17; 61%), treatment risks (n = 13; 46%), and other (n = 10; 36%). Symptoms and treatment benefits were the attributes most frequently ranked as important to patients (n = 26, 72%), followed by treatment risks (n = 7, 39%). Several studies (n = 9, 32%) did not qualitatively pre-test their DCE, and a majority did not report the uncertainty in estimated outcomes (n = 18; 64%).ConclusionsDCEs in asthma and COPD have focused on treatment benefits and convenience, with less evidence generated on participants’ risk tolerance. Quality criteria and reporting standards are needed to promote study quality and ensure consistency in reporting between studies.
... Avascular Necrosis (AVN) of the femoral head is a known complication of long-term steroid therapy in the treatment of ITP. Perioperative care and anesthetic management pose great risks and challenges while managing a patient with ITP (Table 1) [2]. After taking written informed consent, we hereby present a successfully managed case of chronic ITP diagnosed with bilateral AVN femoral head. ...
Article
The treatment of Idiopathic thrombocytopenic purpura (ITP) includes long-term steroid therapy. Avascular Necrosis of the femoral head, Diabetes Mellitus, and various secondary infections are the complications of such long-term steroid medications. We after taking informed consent are presenting a successfully managed case of 52 years old patient with chronic ITP, diagnosed with bilateral AVN femoral head and posted for unilateral core decompression and fibular graft surgery. Atraumatic airway management, adequate platelet transfusion and meticulous hemodynamic and coagulation profile monitoring are some of the major peri-operative concerns in a patient of ITP. A meticulous knowledge of various anesthetic considerations can help in improving the prognosis of a patient of ITP posted for surgery.
... There are several limitations to the current treatment paradigm for ICI-associated enterocolitis. First, although corticosteroids are effective at inducing clinical response and remission, prolonged high-dose exposure is associated with corticosteroid-related AEs, including an increased risk of infections [65]. These issues are especially relevant in the heavily comorbid patient population with malignancies. ...
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Background Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment.AimsWe aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis.MethodsMEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case–control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence.ResultsA total of 160 studies (n = 1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies.Conclusions Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies.
... Symptomatic corticosteroid-induced adrenal insufficiency has become a very rare event due to improved knowledge of the risk of post-corticosteroid-induced adrenal insufficiency and suitable prevention measures [4]. All patients undergoing corticosteroid therapy undergo adrenal insufficiency risk [5]. ceptor, and angiotensin-converting enzyme. ...
... Current extracts of E. Purpurea are made of its roots, leaves, flowers, and the seeds of different subtypes of the Echinacea family, such as E. purpurea, E. pallidaand, and E. angustifolia in the United States [7]. E. Purpurea preparations are used as anti-inflammatory agents and as therapies for upper respiratory tract and urinary tract infections [8][9][10]. E. Purpurea preparations are also used to prevent respiratory tract infections in children [11]. ...
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Background: The use of herbal products is increased among people wordwide. Regarding lacking evidence on the use of herbal medication in children, this study was aimed to determine the effects of Echinacea Purpurea extract on anxiety-like behavior in neonatal rats. Materials and Methods: Forty male Wister strain pups in four groups received i.p injections of E. Purpurea extract (40, 80, and 250 mg/kg) or saline on 5th to 9th postnatal days. All pups were examined for anxiety test on the 22nd postnatal day in the elevated plus-maze test. During the test, parameters include percentage of open arm time (%OAT), percentage of open arm entry (%OAE), head dipping, rearing and locomotor activity have been measured. Results: In the present study, administration of 40, 80 and 250mg/kg doses of the E. Purpurea extract revealed a significant decrease in the %OAT compared to saline group (P<0.01). The E. Purpurea extract decreased head dipping parameters (P<0.01) and increased rearing parameters (P<0.01). E. Purpurea did not significantly change the locomotor activity.Conclusions: The results of present study showed that postnatal administration of E. Purpurea extract increases anxiety in neonatal rats comparing to control group. [GMJ.2017;6(1):52-60]
... High-dose administration of glucocorticoids for extended periods of time (>60 d) can be associated with serious side effects such as increased blood glucose and osteoporosis. [28][29][30] A recent study showed that short-term treatment with dex (1 mg$kg -1 $d -1 ) for 7 d significantly decreased inflammatory response and improved skeletal muscle contractile function in a mouse hindlimb tourniquet-induced IR model. 31 Using a validated mouse model of skin frostbite injury, 10 the current study investigated the effects of dex on frostbite-induced skin injuries and whether inflammation-related leukocyte infiltration and proinflammatory cytokines are involved in frostbite injury. ...
Article
Introduction: Frostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model. Methods: Treatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg·kg-1·d-1) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylin-eosin staining, and Masson's trichrome staining; density of inflammatory cytokines IL-1β and TNFα using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance. Results: After frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature. Conclusions: In this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.
... In severe asthma, patients can be dependent on oral CS agents with symptoms worsening upon withdrawal [12,24]. Due to well-known and serious systemic side effects [25], however, long term use of oral CS is not advised and guidelines now recommend prioritizing anti-Th2 therapies for asthma control [12,24]. Oral CS is recommended for acute conditions, such as exacerbations of asthma, and has been shown to signi cantly reduce the risk of hospitalization and relapse following discharge [26]. ...
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Background: Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action. Results: Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex. Conclusions: Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.
... Our primary objective was to determine the rate of CIMC. A sample size calculation was performed based on an anticipated 40% rate of CS-induced mood change in IBD patients, based on previously published studies primarily focused on other immunological conditions (13,28,29) using a 95% confidence interval with precision of 0.15 and an anticipated drop out rate of 20%. The original target sample size was 50. ...
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Background Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients’ quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population. Methods In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity. Results Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change. Conclusions Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.
... In severe asthma, patients can be dependent on oral CS agents with symptoms worsening upon withdrawal [12,24]. Due to well-known and serious systemic side effects [25], however, long term use of oral CS is not advised and guidelines now recommend prioritizing anti-Th2 therapies for asthma control [12,24]. Oral CS is recommended for acute conditions, such as exacerbations of asthma, and has been shown to significantly reduce the risk of hospitalization and relapse following discharge [26]. ...
Article
Full-text available
Background Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action. Results Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~ 10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex. Conclusions Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.
... These events are dose dependent, as shown in a meta-analysis in which all corticosteroid-induced adverse events reported in all available studies have been described; hazard ratios for all neuropsychiatric side effects, except panic disorder, did not exceed 1.3 for dosages up to 40mg prednisolone (34). As prednisolone carries the risk for neuropsychiatric side-effects, extra safety rules are necessary when testing its efficacy as augmentation therapy for schizophrenia in the current study (35). ...
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Background: The symptom severity of a substantial group of schizophrenia patients (30-40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients.. Corticosteroids are effective in various chronic inflammatory and auto-immune disorders. From the group of glucocorticosteroids, prednisolone has minor mineral-corticosteroid potencies, can adequately pass the blood-brain barrier (BBB) and its side-effects and safety profile are well known. Therefore, a study into treatment with prednisolone can provide as a proof of concept for immune modulation as a treatment for schizophrenia. Method: In total 90 subjects, aged 18-70 years, diagnosed with schizophrenia, schizoaffective or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) 295.*) or psychosis NOS (not otherwise specified) (298.9) will be included. The time interval between the onset of psychosis and study entry should not exceed seven years. Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks. Study medication will be initiated at 40 mg for three days, after which it will be tapered down within 6 weeks after initiation, following current treatment guidelines. Primary outcome is change in symptom severity, expressed as change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of treatment. Cognitive functioning (measured through the Brief Assessment of Cognition in Schizophrenia; BACS) and change in Global Assessment Functioning (GAF) will be assessed, in addition to various immunological biomarkers. Secondary outcomes are a 4- and 6-month follow-up assessment of PANSS, BACS, GAF scores and immunological biomarkers. Additionally, a subgroup of patients can participate in the magnetic resonance imaging (MRI) part of the study where MR spectroscopy, structural, functional and diffusion MRI will be conducted. Discussion: It is expected that prednisolone addition to current antipsychotic medication use will reduce symptom severity and will improve cognition when compared to placebo. Trial registration: ClinicalTrails.gov NCT02949232 registered at 31 October 2016, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02949232?term=corticosteroid&cond=schizophrenia&rank=3 ; EudraCT-number 2014-000520-14 and 2017-000163-32.
Article
Purpose: To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU). Methods: A systematic review and meta-analysis of observational studies was performed. Pooled results are presented as mean difference or standardized mean difference (std diff) and 95% confidence intervals (CI). Visual acuity (VA), intraocular inflammation grade, central macular thickness, corticosteroid (CS) sparing effect and adverse events were evaluated. Results: Ten studies were included finally for quantitative and qualitative synthesis. ADA therapy resulted in 0.124 (95%CI: 0.084, 0.165) logMAR improvement in VA. In addition, ADA therapy resulted in decreased grade of intraocular inflammation [std diff, -1.187 (95%CI: -1.508, -0.866)] and macular thickness [std diff, -0.564 (95%CI: -0.843, -0.286)] and caused a decrease in CS dosage [std diff, -1.809 (95%CI: -2.420, -1.198)]. The pooled rate of overall adverse events for ADA in 301 patients was 8.5% (95%CI: 0.039, 0.177). Conclusion: ADA is an efficient therapy that improves VA and controls intraocular inflammation, macular edema and retinal vasculitis. As the disease exposure time increased, improvement in VA was less. The safety and CS-sparing effect of ADA were demonstrated with few adverse effects. The results provided evidence that ADA can be used safely and efficiently as the first-line drug in patients with BU.
Article
Background Data on health care consumption and costs of asthma in the French population are scarce. Objectives The study objective was to describe the burden of asthma according to GINA treatment steps in the CONSTANCES cohort. Methods Data from 162,725 participants included between 2012-2019 were extracted. Participants were considered as current asthmatics if asthma was reported at inclusion and asthma symptoms and/or treatments were reported in 2019. Participants were classified in three categories according to GINA treatment steps. The results were compared to non-asthmatic participants matched with a propensity score calculated on age, sex, region of residence, precariousness score and year of inclusion. Results Among 162,725 participants aged 18–69 years, 6783 asthmatics (1566 not treated for asthma, 2444 + 251 GINA steps 1 + 2, 1054 + 1315 GINA steps 3 + 4, and 153 GINA step 5) were matched with 6783 controls. Average annual ambulatory cost and average annual hospitalization cost were respectively €1925 and €719 for asthmatics versus €1376 and €511 for participants without asthma (p < 0,0001). Cardiovascular risk factors, co-morbidities, visits and hospitalizations were higher for asthma participants as compared to controls and increased with GINA steps, as well as inpatient and outpatient costs. However, for cardiovascular risk factors and co-morbidities, differences were non-significant in multivariate analyses. Pharmacy costs were ten times higher for GINA step 5 participants than for GINA steps 1–2 participants: €3187 versus €393 (p < 0,0001). Conclusion mean cost of asthma was estimated at €757 per patient/year and increased with GINA treatment step.
Article
Systemic lupus erythematosus (SLE) is an auto-immune disease of a relapsing-remitting nature that can cause multiorgan damage depending on several factors, mainly the disease activity. Young age women are the most likely to be affected by the disease and the female-to-male prevalence ratio is approximately 1:10. As the number of SLE patients has been increasing in the last few decades, the annual number of deaths due to the disease and its complications has increased as well, and one of the most important systems to which high mortality is attributed is the cardiovascular system, leading to premature atherosclerosis and other events such as endocarditis and valve disease. In addition to the classical cardiovascular risk factors, studies have found a positive correlation between SLE and other cardio-harmful diseases such as metabolic syndrome and dyslipidemia. Moreover, some of the medications used in the treatment of SLE place a heavy burden on the heart. The article reviews the shared pathophysiology of SLE and cardiovascular disease along with the most common SLE- associated cardiac risks, events, and management.
Article
Background Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma (SA). Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO), and nuclear/extra-nuclear antigens (ANAs) have been reported. Objective To describe the prevalence and clinical characteristics of asthmatics with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity. Methods We analysed anti-EPX, anti-MARCO, and ANAs in 218 sputum samples collected prospectively from 148 asthmatics, and evaluated their association with lung function parameters, blood/airway inflammation, severity indices, and exacerbations. Additionally, 107 of these patients consented to fill out an autoimmune checklist to determine personal/family history of systemic autoimmune disease and symptoms. Results Out of the 148 patients, 59 (40%) were anti-EPX IgG positive, 53 (36%) were anti-MARCO IgG positive, and 65 (50%) had ≥2 nuclear/extra-nuclear autoreactivities. A composite airway autoreactivity score (CAAS) demonstrated that 82 patients (55%) had ≥2 airway autoreactivities (considered as CAAS ⁺ ). Increased airway eosinophil degranulation (OR:15·1; CI:1·1–199·4), blood leukocytes (OR:3·5; CI:1·3–10·1), reduced blood lymphocytes (OR:0·19; CI:0·04–0·84) predicted CAAS ⁺ . A third of CAAS ⁺ patients reported an exacerbation, associated with increased anti-EPX and/or anti-MARCO IgG (p<0·05). While no association was found between family history or personal diagnosis of autoimmune disease, 30% of CAAS ⁺ asthmatics reported Sicca symptoms (p=0·02). Current anti-inflammatory (inhaled/oral corticosteroids and/or adjunct anti-IL-5 biologics) treatment does not attenuate airway autoantibodies, irrespective of eosinophil suppression. Conclusion We report 55% of moderate-to-severe asthmatics to have airway autoreactivity that persists despite anti-inflammatory treatment, and is associated with exacerbations.
Article
Objectives: There is a paucity of literature about the methylprednisolone induced liver injury in multiple sclerosis (MS) patients. In this study, we intended to investigate the incidence, severity, and risk factors for liver injury in MS patients treated with pulsed methylprednisolone therapy. Methods: This is a prospective observational study on MS patients treated with methylprednisolone pulses. All MS subjects with relapses who were referred to Sina Hospital between May 2020 to May 2021 were included in the study. They were evaluated for the demographic, clinical characteristics, and liver function tests. Liver injury was diagnosed if there was an elevation of serum aminotransferase levels above the upper normal limit (45 IU/L). Results: A total of 314 individuals participated in the study. The prevalence of liver injury after treatment with pulsed methylprednisolone therapy was 2.86%. None of the cases with liver injury were severe. Univariate regression analysis demonstrated that the patients with liver injury had a significantly higher frequency of hyperlipidemia (p: 0.002), alcohol abuse (p: 0.021), and non-alcoholic fatty liver disease (NAFLD) (p: 0.005) compared to those without liver injury. Multivariate regression analysis showed that hyperlipidemia (p: 0.04, odds ratio (OR): 6.31), and history of alcohol abuse (p: 0.007, OR: 36.71) were significantly associated with liver injury. Conclusions: Our study highlights the importance of a close follow-up of the liver function tests in MS patients following pulsed methylprednisolone therapy, particularly in patients with NAFLD, hyperlipidemia, and history of alcohol-abusing.
Article
Résumé Des médicaments appartenant à différentes classes thérapeutiques, pour certains largement prescrits et parfois sur une période prolongée, peuvent interagir avec le métabolisme des micronutriments. Ces interactions peuvent altérer l’absorption intestinale en augmentant le pH gastrique, en complexant les sels biliaires ou en modifiant la flore intestinale. Des médicaments peuvent agir sur les étapes du métabolisme d’un micronutriment, réduire son activité par diminution de la synthèse de sa forme active ou par compétition, par augmentation de son catabolisme ou de son élimination. Connaître les conséquences des traitements médicamenteux sur le métabolisme des micronutriments permet d’être vigilant sur l’apparition d’éventuelles carences, de les contrôler biologiquement et d’adapter les apports en vitamines, minéraux et/ou oligo-éléments de façon ciblée et individuelle.
Article
Objectives: To explore the effect of glucocorticoid therapy on the growth and development of children with bronchiolitis. Methods: A total of 143 children with bronchiolitis who were treated with glucocorticoids from February 2017 to March 2018 were enrolled. The medical data were retrospectively collected, including height, weight, course of the disease, and diagnosis and treatment plan at initial admission. After three years of treatment, physical development indices were measured, growth and development were evaluated by Z-score, and related hematological parameters were measured, including osteocalcin, serum phosphorus, and insulin-like growth factor-1. Results: As for the children with bronchiolitis, the incidence rates of growth retardation and obesity increased significantly after three years of glucocorticoid therapy (P<0.05). The children treated with glucocorticoids for ≥29 days showed a significantly higher incidence rate of obesity than those treated with glucocorticoids for <29 days (P<0.05), while nebulized glucocorticoid treatment had no effect on the growth and development (P>0.05). Compared with the children with growth retardation, the children with normal development had significantly higher levels of serum phosphorus and insulin-like growth factor-1 (P<0.05). Conclusions: Glucocorticoid therapy can adversely affect long-term growth and development in children with bronchiolitis.
Article
Objective: Xiaoyao san (XYS) is a classic traditional Chinese medicinal formula. It has been clinically administered to regulate liver function. However, its mechanisms in glucocorticoid-induced hepatic steatosis are unknown. This study aimed to investigate whether XYS protects against corticosterone (CORT)-induced hepatic steatosis, and to explore its mechanism. Methods: High-fat diet mice induced with hepatic steatosis by 2 mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks. The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids (triglyceride, total cholesterol, and free fatty acids). The mechanism of XYS against hepatic steatosis was investigated by network pharmacology, immunohistochemistry , western blotting, and gain-of-function/loss-of-function experiments. Results: XYS alleviated CORT-induced steatosis, decreased plasma lipids, and inhibited glucocorticoid receptor (GR) activation in the liver. Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein (ADFP). Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression. Conclusions: XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism. Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis, and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.
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Prior to 2005, our existing knowledge of inflammatory patterns in CRS came nearly exclusively from studies with Western patients, and those studies indicated that nasal polyps were “eosinophilic” and characterized by the expression of interleukin (IL)-5 and other type 2 cytokines, whereas CRSsNP resembled a type 1 disease with expression of IFN-gamma [1, 2]. However, less eosinophilic and more neutrophilic inflammation was found in patients with CRSwNP in Asia, when compared with Europe and North America [3]. Chinese patients with CRSwNP demonstrated neutrophil-biased inflammation as compared to their Caucasian counterparts [4]. Approximately 80% of CRSwNP patients in the Western world display a type 2 signature [5, 6], whereas between 20% and 60% display that signature in China, Korea, and Thailand, respectively [3]. By measuring the value of ECP/MPO, Wang et al. [7] found that cases of CRSwNP in regions of Europe, Japan, and Australia showed an eosinophilic dominance (eosinophilic > 50%) rather than a non-eosinophilic dominance (eosinophilic < 50%) such as cases found in Beijing and Chengdu in China. Another study found that <50% of CRSwNP cases in Beijing showed eosinophilic inflammation [8]. The results from different geographic regions indicated that the immunological patterns of CRS were not the same in all ethnic populations [9].
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The inconsistent findings from early studies in twins suggest that both genetic and environmental factors contribute to the pathogenesis of CRS. The genetic architecture of CRS is complex, and the heritability for CRS has been shown to range from 13% to 53% [1–3]; the highest heritability shown in the triad of aspirin intolerance, nasal polyposis, and asthma [2]. The mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene [4] and in dynein axonemal heavy chain 5 (DNAH5) gene [5], which have been identified for cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), respectively, exhibit similar features with CRS, and thus provide further evidence for the role of a genetic component in the aetiology of CRS.
Chapter
Oral corticosteroids (OCS) are a mainstay of treatment in the management of chronic rhinosinusitis (CRS) and are considered by many doctors to constitute a key component of “maximal” medical therapy [1]. Corticosteroids are used in CRS for their anti-inflammatory effects, which are complex but vitally involve in the regulation of prostaglandin secretion [2]. Their anti-fibroblast effects are commonly utilized to reduce postoperative scar formation [1]. Mechanistically, corticosteroids bind to the glucocorticoid receptor and lead to gene transcriptional changes, which result in several effects, including changes in carbohydrate and fat metabolism, reduced protein synthesis, increased fat redistribution and protein breakdown [2]. Calcium absorption is reduced and excretion might increase the risk of osteoporosis. Moreover, corticosteroids can have a negative feedback effect on the anterior pituitary gland and hypothalamus, thereby resulting in depressed secretion of adrenocorticotropic hormone and corticotropin-releasing hormone, which can take several weeks to start once the corticosteroids are stopped [3].
Article
Resumen La artritis psoriásica (AP) es una artritis inflamatoria crónica que pertenece a la familia de las espondiloartritis. Se estima que su prevalencia es del orden del 0,01-0,2% en la población general y podría llegar al 40% en los pacientes con psoriasis cutánea. Se trata de una enfermedad heterogénea y compleja, cuyas manifestaciones clínicas articulares y extraarticulares pueden ser extremadamente variables, lo que a menudo provoca un retraso diagnóstico y terapéutico. La afectación del aparato locomotor asocia en grados diversos manifestaciones axiales con raquialgias inflamatorias, que predominan a nivel cervicodorsal, y sacroilitis, a veces asintomática, una afectación entesítica que puede ser diseminada así como una afectación articular periférica que ataca prioritariamente a manos y pies. Además de la afectación cutánea de la psoriasis, esta artritis puede acompañarse de uveítis o también de una enfermedad inflamatoria intestinal. Reconocida actualmente como una entidad propia, la AP se ha confundido durante mucho tiempo con otras artritis, en particular con la artritis reumatoide. Su evolución puede ser grave, causando impotencia funcional y un deterioro importante de la calidad de vida; requiere un seguimiento clínico, biológico y radiológico apropiado. La reciente mejora de los conocimientos fisiopatológicos ha permitido el rápido desarrollo de biofármacos y terapias dirigidas (antifactor de necrosis tumoral alfa, antiinterleucina 12/23, antiinterleucina 17, apremilast, anticinasa Janus), eficaces contra la mayor parte de los diferentes síntomas, complementando así el arsenal terapéutico anteriormente existente (antiinflamatorios no esteroideos, inyección local de corticoides, metotrexato, leflunomida, sulfasalazina).
Article
India is passing through a significant impact of Wuhan origin coronavirus disease 2019 (COVID-19) pandemic in the second wave. Mucormycosis is emerging as a larger problem for our patients as compared to the first wave. Several plausible explanations have been put forth –but none has been proven as yet. We herein report eight cases of COVID-19-associated rhino-orbital mucormycosis diagnosed and managed at our center. We observed a higher risk among middle-aged men, with known or covert diabetes who received high-dose steroids and/or prolonged oxygen for COVID-19 management.
Article
Introduction: Acute liver injury and progression to acute liver failure can be life-threatening conditions that require prompt careful clinical assessment and therapeutic management. Areas covered: The aim of this article is to review the safety and side effect profile of pharmacological therapies used in the treatment of acute liver injury with specific focus on hepatic toxicity. We performed an extensive literature search with the terms “acute liver injury”, “acute liver failure”, “therapy”, “safety”, “adverse reactions” and “drug induced liver injury”. A thorough discussion of the main drugs and devices used in patients with acute liver injury and acute liver failure, its safety profile and the management of complications associated to therapy of these conditions is presented. Expert opinion: Several pharmacological approaches are used in acute liver injury and acute liver failure in an empirical basis. Whilst steroids are frequently tried in serious drug-induced liver injury there is concern on a potential harmful effect of these agents because of the higher mortality in patients receiving the drug, hence statistical approaches such as propensity score matching might help resolve this clinical dilemma. Likewise, properly designed clinical trials using old and new drugs for subjects with serious drug-induced liver injury are clearly needed.
Article
Objective To review the literature on corticosteroid use and provide recommendations on patient counseling and/or consent to promote judicious prescribing and reduce the incidence of corticosteroid-related lawsuits. Method A conventional literature search of PubMed on corticosteroid-related medicolegal cases was undertaken. Search terms included “medicolegal,” “otolaryngology,” and “adrenocorticosteroids.” A medical subjects headings search with the keywords “adrenal cortex hormones” and “jurisprudence” was also performed. Results Corticosteroids have been reported as the third most frequent medication involved in malpractice claims, oftentimes leading to disproportionately costly payments. The most common specialties found to be involved in corticosteroid related medicolegal cases included dermatology (12%), primary care (10%), and neurologists or neurosurgeons (6%). The most common complications encountered were avascular necrosis (39%), changes in mood (16%), infection (14%), and vision changes (14%). Only a few cases corticosteroid-related litigation regarding otolaryngologists were identified. More frequent causes for otolaryngology claims were intraoperative complications, deficits in diagnoses, and failures or delays in treatment. Three medicolegal pitfalls regarding corticosteroid use were identified from this review included: (1) insufficient advising, (2) lack of or incomplete informed consent, and (3) the significance of the patient-physician relationship. Conclusion Despite the scarcity of corticosteroid-related medicolegal literature pertaining to otolaryngologists, corticosteroids are one of the most widely prescribed medications in the field of otolaryngology and have been shown to have a high rate of medical malpractice claims in medicine. Counseling and consenting the patient, as well as developing a strong physician-patient relationship, are integral processes in addressing any adverse effects occurring during therapy, and may also help to decrease the incidence and success of litigation against otolaryngologists.
Article
Background The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1–6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. Aim The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. Methods A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 h post infusion and late reactions for more than 24 h. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). Results Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2–66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. Conclusions In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.
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Introduction: Nonspecific inflammatory bowel diseases include Crohn’s disease (CD) and ulcerative colitis (CU – colitis ulcerosa), which are chronic diseases characterized by periods of exacerbation and remission. Extraintestinal complications caused by the disease and the applied treatment, mainly steroid therapy, constitute a predisposition to infections and mental disorders such as depressive disorders with apathy, slowness of movement or agitation, and even manic syndromes. Aim and method: The aim of this study was to review the literature on the occurrence of primary and secondary mental disorders in the course of inflammatory bowel diseases. The literature in the Google Scholar database was reviewed using the following keywords: colitis ulcerosa, Crohn disease, depression, mental disorders, inflammatory bowel disease. The time descriptors 2011-2021 were also used. Conclusions: The review of epidemiological studies shows that the most common mental disorders in nonspecific inflammatory bowel diseases are anxiety and depression disorders. The effect of steroid therapy on the development of mental disorders is equally significant. Most of the available empirical data relating to corticosteroids confirm the correlation between the drugs and depressive symptoms, and other psychiatric effects, including mania and psychosis. Summary: As with most chronic diseases, the prevalence of anxiety and depression disorders is higher in nonspecific inflammatory bowel diseases than in the general population.
Article
Background There are limited studies on healthcare resource use (HCRU) among adult asthma patients in Japan using real-world evidence, and analysis on acute treatment and associated costs stratified by disease severity is further limited. This study aimed to characterize the disease burden of severe asthma patients in Japan in terms of HCRU and comorbid medical conditions, with particular interest in oral corticosteroid (OCS) dependency. Methods This retrospective cohort study of asthma patients used data from a claims database of diagnosis procedure combination hospitals in Japan. The severe asthma cohort included patients treated with OCS for more than 180 days in one year before the index date, with at least one asthma diagnosis claim. Comorbidity and drug use in the look-back period, HCRU, assumed OCS-related adverse events, and asthma exacerbations in the follow-up period were analyzed. Results Costs associated with the treatment of severe asthma were approximately twice that of mild/moderate asthma, and the annual median cost of patients hospitalized due to asthma reached ¥448,000 (USD $4073). Annual asthma exacerbation rate was higher in the severe asthma cohort than in the mild/moderate cohort. Patients with longer OCS use in the previous year had higher risks of secondary adrenal insufficiency, osteoporosis, and pneumonia in the following year. Conclusions OCS use among asthma patients in Japan incurred greater medical and economic burden. Better understanding of the disease characteristics including the severity of asthma and appropriate management of disease burden will lead to more optimal use of healthcare resources in Japan.
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Objectives This study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review of electronic medical records in a single-centred hospital. Design All patients admitted to the outpatient department of Jinshan Hospital, Fudan University, Shanghai, between 1 January 2018 and 31 December 2018 were evaluated. Individuals aged 18 years or above and with at least one dispensing for PPIs were identified as PPI users. New PPI users were defined as a subject who did not receive any dispensing for PPIs in the year prior to the index date. Baseline characteristics of PPI users and their therapies were described by treatment indication, economic indicators and co-prescription, overall and separately. Setting The prescription database was retrieved from the hospital information system of Jinshan Hospital, Fudan University. Results Among 18 435 identified PPI users in 2018, 14 219 patients (aged 18 years or above) who had at least one dispensing PPIs were new users (77%), and among them, men accounted for 47%. The mean treatment duration was 23 days. Omeprazole was the most commonly prescribed drug. PPIs are inappropriately prescribed in 50% (13 589/25 850) of prescriptions. Prescription appropriateness analysis indicated that the unapproved indications for PPI new users accounted for 47%; among them, the proportion of gastritis diagnosis was 34%. The proportion of PPI new users with co-prescription of glucocorticosteroids (GCs) who have risk factors accounted for 24% and lower than other co-prescription. A majority of PPI users (73%) reported high-dose PPI prescription. The defined daily dose of oral pantoprazole was the highest, and injectable omeprazole had the highest defined daily cost. In contrast, only the drug utilisation index value of oral esomeprazole was less than 1.0. Conclusion The results indicate the challenge of PPI use was accompanied by unapproved indications, frequent inappropriate co-prescription with GCs and excessive dosages. Efforts should be paid to promote rational use and ensure the choice of suitable PPI therapy in the future.
Article
Resumen Introducción El uso de infliximab (IFX) en enfermedad inflamatoria intestinal (EII) se ha asociado con un riesgo de 1-6% de reacciones a la infusión. La utilidad de premedicación con corticoides, paracetamol y/o antihistamínicos es controvertido. Objetivo Evaluar si en pacientes con EII que utilizan IFX hay diferencias en las reacciones secundarias a infusión entre aquellos que utilizan o no premedicación. Métodos Estudio descriptivo, observacional, retrospectivo en pacientes con EII, que han utilizado IFX entre enero 2009 y julio 2019. Se definieron como reacciones agudas aquellas ocurridas en las primeras 24 hrs.postinfusión y tardías después de ese período, clasificándose en leves, moderadas y severas. Se usó estadística descriptiva y de asociación (χ²; p < 0,05). Resultados Se incluyeron 1.263 infusiones en un total de 64 pacientes, 52% hombres. Mediana de infusiones por paciente 22 (2-66). El 100% de las infusiones en inducción fueron con premedicación y en mantenimiento el 57%. La premedicación fue realizada con hidrocortisona, clorfenamina y paracetamol. La mayoría de las reacciones fueron agudas, de gravedad leve a moderada y ningún paciente necesitó descontinuar IFX. En mantenimiento hubo 9/718 (1,2%) reacciones a la infusión con premedicación y 4/358 (1,1%) sin ésta, sin diferencias significativas (p = 0,606). En inducción hubo 8/187 (4,3%) reacciones a la infusión, significativamente mayor al compararlas con ambos grupos de mantenimiento. Conclusión En esta cohorte de pacientes, el no usar premedicación en fase de mantenimiento de IFX no aumentó el número de eventos adversos a este fármaco. Estos resultados sugieren que su indicación no sería necesaria.
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Self-medication is a wide spread behavior, particularly among elderly patients. Self-medication involves not only the consumption of over-the-counter products but also the re-use of formerly prescribed drugs without medical supervision. This practice may lead to severe adverse health events. Here we report a case of old female, presented with cushingoid face and hyperglycemia due to self-medication of high dose Prednisolone for longer duration. Symptomatic treatment was given to stabilize the patient. Patient was warned regarding the adverse effects of drugs and strictly advised to use medication only under medical supervision.
Article
Objective Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. Methods We used the claims sampling data during January 2015 from the national database made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age‐ and sex‐matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi‐squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch’s t‐test. Results Synthetic glucocorticoids were prescribed to 3.1% (n=18,122) of 581,990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non‐recipients: antipsychotics, 1.8% (n=321) vs. 1.1% (n=201) (p=1.4×10‐7); antidepressants, 4.0% (n=724) vs. 2.0% (n=359) (p=8.7×10‐30); anxiolytics/hypnotics, 16.7% (n=3,029) vs. 10.2% (n=1,841) (p=2.7×10‐75); and mood stabilizers, 1.3% (n=238) vs. 0.7% (n=120) (p=3.6×10‐10), respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. Conclusion Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross‐sectional nature of this study.
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Background Systemic corticosteroids (SCS) may cause complications for patients with asthma. Objective We sought to better understand the burden of SCS use in persistent asthma, including health care costs. Methods Adult patients with persistent asthma were identified in the IBM MarketScan databases from 1/2003 to 7/2016. The index date was set as the first SCS prescription for SCS users or algorithm-matched for non-SCS users. Patients were required to have ≥1 year of data before and after the index date. Based on the number of SCS claims in the first year after index, patients were categorized into 3 SCS groups: 0 SCS claims, 1‒3 claims, and 4+ claims. Inverse probability of treatment weights was applied to adjust for differences between SCS and non-SCS users. Analyses included weighted and multivariate modeling to assess SCS-related complications and costs during a 3-year follow-up. Results 86,786 SCS users (1‒3 claims: 76,690; 4+ claims: 10,096) and 91,409 non-SCS users were included; 45% remained 3 years post-index. In multivariate analysis, the 3-year risk of developing any chronic complication was 6% greater for those with 1–3 claims and 26% greater for those with 4+ claims compared with non-SCS users (p<0.001). Multivariate-adjusted health care costs over 3 years were significantly greater as 4+ users incurred $22,311 greater total costs, $4,627 greater asthma-related costs, and $2,647 greater chronic complication related costs than non-SCS users (p<0.001). Conclusions In this study, adults with persistent asthma receiving SCS treatment had greater odds of complications and greater associated costs over 3 years than matched non-SCS asthma patients.
Article
Background: Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown. Objective: To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure. Design: Self-controlled case series. Setting: Entire National Health Insurance Research Database of medical claims records in Taiwan. Participants: Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015. Measurements: Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy. Results: Of 15 859 129 adult participants, 2 623 327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days. Limitation: Persons younger than 20 years or older than 64 years were not included. Conclusion: Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy. Primary funding source: National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
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Among 718 consecutively monitored hospitalized medical patients who received prednisone, adverse reactions were recorded in 121 (16.9 per cent). Of these, 82 experienced acute reactions (11.4 per cent of the total series), and 39 (5.4 per cent) had a more gradual onset of the reactions. The daily dose of prednisone was analyzed in 594 patients in whom adverse reactions were not recorded and in the 82 patients with acute reactions. While there was a striking dose-response relationship for acute psychiatric reactions, there was no correlation between dose and gastrointestinal side effects, diabetes, superinfections, and leukocytosis.
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Popularization of the dexamethasone suppression test has focused attention on the relation between cortisol metabolism and mood and behavior. This article considers the biochemistry, physiology, and pharmacology of cortisol and cortisol-like substances. In addition, the effects of external stresses on cortisol metabolism and circadian rhythmicity of secretory patterns are reviewed. Finally, managing exogenous cortisol excess in a clinical setting is discussed.
Article
Objective. Non-steroidal anti-inflammatory drugs (NSAIDs) are used in nearly every patient with rheumatoid arthritis (RA) as part of a comprehensive management programme, but their use can be associated with side-effects. Low dose corticosteroid (<10 mguday prednisone) in the treatment of RA is controversial. Although it is effective and possibly disease modifying, concerns exist about potential adverse events. We assessed costs and health effects of corticosteroids compared with NSAIDs and cyclo-oxgenase-2 (COX-2) inhibitors. Methods. Markov (state transition) models were used to simulate a cohort of RA patients taking disease-modifying antirheumatic drugs and either corticosteroids or NSAIDs. The regimens were assumed to be equally effective for the control of RA. Data on incidence, costs and consequences of adverse events from corticosteroids and from NSAIDs were taken from the literature. Costs were measured in 1999 US dollars; health effects expressed as quality-adjusted life years (QALYs). Sensitivity analyses were performed including best-case scenarios (0.5 3 adverse event rate) and worst-case scenarios (1.5 3 adverse event rate). Results. In the base-case analysis corticosteroids were superior to NSAIDs. The sensitivity analyses of adverse event rate, using best-case and worst-case scenarios, and age showed that the results were sensitive to each combination of adverse event rate and age. In contrast, the sensitivity analyses of costs and utilities were robust. Using misoprostol or omeprazole prophylaxis with NSAIDs would make corticosteroids cost-effective. Compared with NSAIDs with COX-2 specific inhibition, corticosteroids were still cost-effective. Conclusion. Corticosteroids are more cost-effective than NSAIDs and COX-2 inhibitors in the long-term treatment of RA.
Article
Bacteremia occurred in thirty-seven of 140 patients with renal homotransplants seen over a five and a half year period; it was fatal in thirteen. Ten patients had multiple bacteremic episodes. Hospital-associated bacteria such as Staphylococcus, Serratia and Pseudomonas were the predominant organisms. Of the fifty patients who were examined at autopsy during the period of study, twenty died of bacterial infections and twelve of nonbacterial “opportunistic” infections.
Article
Budesonide (Entocort® EC Capsules) is an oral corticosteroid with a high degree of topical activity and low systemic bioavailability (≈11%). This action is achieved by a high affinity for the glucocorticoid receptor and an extensive first-pass hepatic metabolism. The budesonide capsule has been formulated to dissolve in a pH dependent manner, delivering most of the drug to the ileum and ascending colon, areas of the intestine most commonly affected by Crohn’s disease. In large (n ≥ 176), well designed clinical trials of 10 to 12 weeks’ duration in patients with active, mild to moderate Crohn’s disease, budesonide (9 mg/day) was significantly more effective in inducing remission than placebo or mesalazine (mesalamine) slow release, and demonstrated similar efficacy to recommended dosages of prednisolone. Results of health-related quality-of-life assessments support clinical data, showing a significantly greater improvement among patients treated with budesonide than with placebo or mesalazine slow release. Oral budesonide was well tolerated in clinical trials of up to 16 weeks’ duration. In these studies, the incidence of adverse events associated with budesonide (9 mg/day) was similar to that seen with placebo and mesalazine slow release. The rate of glucocorticoid-related adverse effects observed with budesonide was significantly less than that reported with prednisolone. Conclusion: Oral budesonide 9 mg/day offers efficacy that is superior to mesalazine slow release and placebo, and similar to prednisolone in the treatment of patients with active mild to moderate Crohn’s disease involving the ileum and/or ascending colon. Budesonide is generally well tolerated and the incidence of adverse events is similar to that seen with placebo or mesalazine slow release. Glucocorticoid-related adverse effects are significantly less frequent during short-term therapy with budesonide than with prednisolone. Thus, for the medical management of patients with active mild to moderate Crohn’s disease, oral budesonide has superior efficacy to mesalazine slow release and a more favourable tolerability profile than prednisolone. Pharmacodynamic Properties Budesonide is a nonhalogenated corticosteroid with a high affinity for the glucocorticoid receptor (15-fold greater than prednisolone). The drug undergoes extensive first-pass hepatic metabolism (about 90%) to form compounds with negligible corticosteroid activity; the resultant systemic bioavailability is, therefore, low. Budesonide (administered as a solution) was about twice as active as beclomethasone dipropionate and more than 1000 times more active than prednisolone and hydrocortisone in inducing cutaneous vasoconstriction after topical application. In general, the effect on erythrocyte sedimentation rate (ESR), C-reactive protein and serum orosomucoid concentrations was not significantly different after treatment with budesonide (Entocort® EC Capsules) 9 mg/day or prednisolone 40 mg/day. After 12 weeks of treatment, the mean leucocyte count increased significantly in patients receiving prednisolone 40 mg/day, but decreased slightly with budesonide 9 mg/day. In short-term studies (up to 12 weeks) in patients with mild to moderate, active Crohn’s disease, tapered dosages of prednisolone caused a significantly greater decrease in morning cortisol concentrations and response to corticotropin stimulation than budesonide at dosages of up to 15 mg/day. Compared with mesalazine (mesalamine) slow release 2g twice daily, budesonide 9mg once daily decreased plasma cortisol concentrations to a greater degree, but the difference was not statistically significant. A dose-dependent suppression of morning plasma cortisol concentrations and response to corticotropin stimulation was demonstrated with budesonide, and dosages of 9 and 15mg decreased plasma cortisol concentrations significantly more than placebo. Compared with prednisolone, budesonide caused a significantly lower increase in mean fasting blood glucose concentrations and mean serum creatinine concentrations after 4 and 8 weeks of treatment. Budesonide did not impair osteoblast activity in patients with active Crohn’s disease, whereas methylprednisolone did. Pharmacokinetic Properties Budesonide capsules contain granules that are coated to prevent dissolution in gastric pH. At a pH >5.5, budesonide is slowly released from a matrix of ethylcellulose during its passage through the small intestine. Plasma concentrations of budesonide increased linearly in response to doses of 3 to 15 mg/day. After a single oral dose of budesonide 9mg, the maximum plasma concentration (Cmax) is approximately 4 nmol/L and is attained at about 3 hours. The mean systemic bioavailability following oral administration of budesonide is approximately 11%, indicating an extensive first-pass metabolism. Food did not significantly affect the systemic availability and Cmax of orally administered budesonide, however, absorption was delayed, probably due to delayed gastric emptying. Excretion is mainly via the kidneys, but patients with renal impairment are not expected to be at an increased risk of adverse effects. The systemic availability of oral budesonide in patients with liver cirrhosis is increased by approximately 2.5-fold compared with that in healthy volunteers. Clinical Efficacy Oral budesonide induced remission in patients with active mild to moderate Crohn’s disease significantly more than placebo or mesalazine slow release, and at a rate similar to that of prednisolone, in controlled clinical trials. Clinical remission was achieved by approximately 50 to 60% of patients after 8 to 10 weeks of treatment with budesonide 9 mg/day. In two placebo-controlled trials, patients receiving budesonide 9 mg/day showed a higher rate of remission than those receiving placebo after 8 weeks of treatment; however, the difference was only significant in one study (51 vs 20%, p < 0.001). In the other study, remission rates were 48, 53 and 33% in patients receiving budesonide 9mg once daily, 4.5mg twice daily or placebo, respectively. In a randomised, controlled trial comparing mesalazine slow release 2g twice daily with budesonide 9mg once daily, remission rates in patients treated with budesonide were significantly higher at 8, 12 and 16 weeks. In studies comparing budesonide with prednisolone 40mg daily (tapered after 2 weeks), prednisolone induced remission in 60 and 65% of patients after 8 weeks of treatment; these response rates were not significantly different to those seen with budesonide 9mg once daily (52 and 60%). Results from a recent meta-analysis support the results of clinical trials by indicating that oral budesonide is significantly more effective than placebo, and in one study, more effective than mesalazine slow release, in inducing remission of mild to moderate Crohn’s disease. Meta-analysis results also indicate that budesonide induced remission at a similar rate to prednisolone in patients with a Crohn’s Disease Activity Index (CDAI) score ≤300, but appeared less likely to induce remission than conventional steroids in patients with a CDAI score >300. Budesonide once daily improved health-related quality of life significantly more than placebo and mesalazine slow release in patients with active mild to moderate Crohn’s disease. Tolerability Oral budesonide is well tolerated and a similar proportion of patients receiving budesonide 9 mg/day or placebo experienced adverse effects or withdrew from placebo-controlled trials because of adverse effects. The most common adverse events reported in clinical trials were headache (21%), respiratory infection (11%), nausea (11%) and symptoms of hypercorticism. The incidence of adverse events was similar in patients receiving budesonide 9mg once daily or mesalazine slow release 2g twice daily. However, patients randomised to budesonide had fewer severe adverse events than those in the mesalazine group. Compared with prednisolone in controlled, short-term clinical trials, budesonide 9mg once daily caused significantly fewer glucocorticoid-related adverse effects. Haematological and biochemical variables did not differ significantly between treatment groups receiving budesonide 3, 9 or 15 mg/day or placebo. Dosage and Administration Oral budesonide is indicated for the treatment of adults with mild to moderate, active Crohn’s disease of the ileum and/or ascending colon. The recommended dosage is 9mg once daily, taken in the morning, for a period of up to 8 weeks. The capsule should be swallowed whole, not chewed or broken. Tapering of dosage, to 6 mg/day for 2 weeks, can be implemented before complete cessation of the drug. A repeat 8-week course can be given for recurring episodes of active Crohn’s disease. A reduction in the dose of budesonide should be considered in patients with moderate to severe liver disease and if concomitant therapy with cytochrome P450 3A4 inhibitors is indicated. Grapefruit juice should be avoided during therapy. Although budesonide has a lower systemic effect than conventional steroids and causes less suppression of adrenal function, general warnings concerning corticosteroids should be followed.
Article
Purpose: To quantify risk for the occurrence of hyperglycemia requiring initiation of hypoglycemic therapy in patients treated with oral glucocorticoids. Patients and Methods: A case-control study of enrollees in the New Jersey Medicaid program 35 years of age or older. The 11 855 case patients had newly initiated treatment with a hypoglycemic agent (oral or insulin) between 1981 and 1990. The 11 855 controls represented a random sample of other Medicaid enrollees. Results: In patients using oral glucocorticoids, the estimated relative risk for development of hyperglycemia requiring treatment was 2.23 (95% confidence interval, 1.92 to 2.59) as compared with nonusers. Risk increased with increasing average daily steroid dose, in hydrocortisone-equivalent milligrams; the odds ratio was 1.77 for 1 to 39 mg/d, 3.02 for 40 to 79 mg/d, 5.82 for 80 to 119 mg/d, and 10.34 for 120 mg/d or more. The estimated effects persisted after adjustment for a variety of potentially confounding demographic, health service utilization, and medication use variables. Conclusion: The findings of this population-based study quantify the risk of developing hyperglycemia requiring hypoglycemic therapy after oral glucocorticoid use. The magnitude of risk increases substantially with increasing glucocorticoid dose. These findings demonstrate the utility of large-scale health claims databases in defining the risk of important adverse drug effects.(Arch Intern Med. 1994;154:97-101)
Article
Corticosteroids were used during seventy pregnancies in 55 asthmatic patients. In this series there was one spontaneous abortion and 71 live births (including two sets of twins). There were no maternal, fetal, or neonatal deaths. On the basis of recorded gestation, slightly more premature births were noted in this series than would be expected in the general population. However, there was no increased incidence of toxemia, uterine hemorrhage, or congenital malformations when compared to the general population, Corticosteroids, when indicated for the treatment of severe asthma, do not appear to noticeably increase the risk of maternal or fetal complications, and thus should not be contraindicated in pregnancy. (JAMA 233:804-807, 1975)
Article
• During a ten-year period, aseptic necrosis of the femoral head developed in six patients with pulmonary disease treated with corticosteroids. Five of the six patients had severe bronchial asthma. The sixth patient had desquamative interstitial pneumonia. The literature provides some insight into the possible pathogenesis of corticosteroid-related aseptic necrosis of the femoral head and factors that may prevent this complication. (Arch Intern Med 140:1473-1475, 1980)
Article
Among the complications of anti-inflammatory steroid therapy is aseptic necrosis of the femoral and humeral heads, an effect not predicted from animal experiments. The pathogenesis of this steroid-related degenerative process is obscure. The first case report of aseptic necrosis of bone occurring in association with the administration of cortisone was published in 1957.1 However, a more recent report has included an instance of this phenomenon which was observed in 1952.2We have recently observed seven such cases in the 750-bed VA Hospital, Pittsburgh, and one instance in another hospital of the University of Pittsburgh Medical Center. Our cases closely resemble others which have been reported. Because of the increasing frequency with which degeneration of the femoral and humeral heads occurring in association with corticosteroid therapy is being observed, and since much of the pertinent literature is not in English-language journals, our experience is being reported together with a
Article
• A 14-valent pneumococcal vaccine was administered to 39 recipients of allogeneic bone marrow transplants, and their type-specific antibody responses were compared with normal control subjects. Preimmunization antibody levels in patients were twofold to 12-fold lower than those levels in control subjects for all serotypes. Mean postimmunization antibody levels for each serotype were also considerably lower in patients (range, 56 to 859 ng of antibody nitrogen per milliliter) than in control subjects (range, 727 to 5,626 ng/mL). Poor antibody responses were primarily associated with early vaccination after transplantation, corticosteroid therapy for graft-v-host disease and other illnesses, and the male sex. Antibody responses of patients not given corticosteroids and vaccinated more than seven months after transplantation improved with time after transplantation. Postvaccination infection occurred in five patients who were vaccinated early after transplantation. Pneumococcal vaccination has limited potential for providing protection in marrow transplant recipients except in the cases of those patients who are not receiving corticosteroids and are vaccinated more than seven months after transplantation. (Arch Intern Med 1983;143:1735-1737)
Article
A patient with acute lymphocytic leukemia developed acute pancreatitis during induction therapy with corticosteroids and asparaginase. Postmortem examination showed changes consistent with hemorrhagic pancreatitis and fat necrosis over the pancreas and omentum. Corticosteroids were thought to be responsible for pancreatitis in this patient since "hemorrhagic pancreatitis" has not been previously described with asparaginase. We recommend careful follow-up of serum and urinary amylase values in patients receiving induction therapy with these agents. (Arch Intern Med 138:1726, 1978)
Article
Aim: To study the immediate tolerance of high-dose intravenous pulse steroids. PATIENTS ET METHOD: Prospective study over a six months period in 146 consecutive patients treated by three pulses of 250, 500 or 1000 mg/d methylprednisolone for various eye diseases. Daily monitoring including: standardized questionnaire, electrocardiogram, automated blood pressure measurements, fasting blood glucose and kaliemia. Results: One hundred and twenty-nine patients (88,4%) had one ore more side effect(s), mainly transient and of mild intensity, the first one being neuropsychological disturbances (insomnia in half the patients). Myocardial ischemia was observed in three patients (2,1%) with known coronary insufficiency or high cardiovascular risk, blood pressure levels of at least 180/110 mmHg were recorded in five hypertensive patients (3,4%), bradycardia occurred in 14 patients (9,7%), symptomatic in one. After the first pulse, we observed a mean 54+/-30% increase of fasting glucose (P <0,001), followed during the next pulses by a spontaneous slow return toward baseline values in non diabetic patients, contrasting with additional hyperglycemic effects in diabetics, and a mean 5,4+/-10,3% increase of kaliemia (P <0,001) staying unchanged during the next pulses, and suggesting a rapid potassium efflux from the cell as a direct effect of methylprednisolone. Conclusion: Severe complications of pulse methylprednisolone, mainly cardiovascular, are strongly related to underlying comorbidities. Glucose monitoring is necessary only in diabetic patients. Potassium movements suggest a risk of hypokalicystia, of potential danger in patients with cardiac disease. A close clinical, blood pressure and electrocardiographic monitoring is needed during the whole treatment.
Article
Objectives. – To analyse steroid psychiatric related complications in aged (> 65 years old) with temporal arteritis (TA).Methods. – Retrospective cohort studyPatients. – In a cohort of 126 elderly patients with a diagnosis of TA and followed with a mean period of 64 months, clinical and biological presentations, outcome and corticoid adverse effects were recorded throughout the follow-up period.Results. – Twenty patients (16%), (mean age: 73 ± 7,9 years, male n = 6) exhibited corticosteroid related psychiatric complications. Symptoms appear to be dose dependent and generally begin during the first month of treatment. Psychiatric disorders were as follow: mood disturbances (n = 8), depression (n = 6), mania (n = 3), anxiety neurosis (n = 2) and dementia (n = 1). Three patients were hospitalized in psychiatric units and 2 in nursing home. Psychiatric adverse affects appears to be more frequent with prednisone than prednisolone (P
Article
Steroid myopathy is one of the various side effects of prolonged treatments, particularly with the 9α fluorinated steroids. The receptor protein probably plays a major role with a decrease in protein synthesis. There is no mean to detect this myopathy before clinical signs appear. Neither muscular testing nor enzymes nor electromyography give arguments and muscular biopsy is aggressive. Low density scanner and MNR could help diagnosis. Frequency of disease is not known. A total cumulative maintenance steroid dosage of 400 mg can be sufficient. Proximal muscles are usually involved, quadriceps and other pelvic girdle muscles being more severely affected. Fast twitch glycolytic type IIB fibers are particularly susceptible. Physical exercise is effective in preventing myopathy. Nevertheless, no special rehabilitation program has been tested for the moment in human beings.
Article
Background & Aims: Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon. Methods: Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded. Results: One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of
Article
OBJECTIVE We have shown previously that in contrast to the standard high-dose 250-μg ACTH test, a low-dose 1-μg ACTH stimulation test correctly identified all patients with pituitary disease who had impaired hypothalamo–pituitary–adrenal (HPA) function. In this study we further compared the performances of these two tests as screening procedures for possible HPA impairment.DESIGNA comparison of the 1-μg and the 250-μg ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test.SUBJECTSA total of 89 subjects were investigated: 27 healthy normal controls, 43 patients with pituitary disease and normal HPA function, and 19 patients with various pituitary diseases and impaired HPA function.MEASURESAll 89 subjects underwent stimulation with 1 μg ACTH; 80 also underwent the high-dose 250-μg ACTH test. A receiver operating characteristic analysis (ROC) was performed to compare the tests.RESULTSUsing a stimulated cortisol > 500 nmol/l as the criterion for a normal response, the 1-μg ACTH stimulation identified 18 of the 19 subjects with impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6.2% sensitivity with a likelihood ratio of 0.875 for a negative test). All normal controls, and 36/43 patients with preserved HPA function, passed the 1-μg ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered.CONCLUSIONS More sensitive and accurate, the low-dose 1-μg ACTH test is as simple and safe as the standard 250-μg test. We suggest it should replace it in screening for adrenal insufficiency.
Article
The objective of this paper is to study the possible additive effect of corticosteroids to the known effect of indomethacin on potency of the human ductus arteriosus. Systolic and diastolic blood flow of the fetal ductus arteriosus was measured by echo Doppler at 26-32 weeks of gestation. Four groups of patients were studied according to the treatment they have received: group A (exposure to indomethacin and betamethasone); group B (indomethacin alone); group C (betamethasone); and group D (controls). Children in whom ductal constriction was noted in utero were followed by repeat cardiac echo Doppler examinations at the age of 1 to 2 years. In group A (indomethacin and betamethasone) fetal ductal constriction was significantly higher (p = 0.02) and occurred in 1 1 out of 15 fetuses (73.3%), compared with 5 out of 14 (37.2%) of the fetuses in group B (indomethacin alone). In group C (betamethasone) and D fetuses (no treatment), no significant ductal constriction was observed. Pathological tricuspid regurgitation and right ventricular dilation were found more frequently in fetuses from group A. No long-term sequella was noted in the infants in whom ductal constriction had been noted in utero. Corticosteroids and indomethacin have a synergistic effect on the frequency and severity of fetal ductus arteriosus constriction. In short-term treatment this effect is transient, and has no deleterious effects bn fetal and neonatal cardiac function.
Article
Metacortandralone and metacortandracin, two new synthetic steroids, were subjected to clinical trial by the National Institute of Arthritis and Metabolic Diseases. The biological experiments in animals conducted by the investigators who prepared these steroids indicated that the compounds possess three to four times the activity of cortisone or hydrocortisone. The chemical, toxicologic, and biological studies performed prior to our studies in man will be reported by them elsewhere. The antirheumatic, anti-inflammatory, metabolic, and endocrinologic effects of metacortandralone were studied in seven patients with rheumatoid arthritis. The patients were selected by the following criteria: (1) arthritis of more than two years' duration, (2) unequivocal activity of the disease process, ( 3 ) joint changes that were partially or completely reversible, and (4) therapy previously administered that was of conventional type and produced unsatisfactory results.COMPOSITION OF SERIES Three patients had taken adequate doses of salicylates but had not received steroid therapy before admission
Article
Although therapeutic experience with cortisone has been accumulated rapidly during the past four years, the limits of therapeutic usefulness and the hazards of this and similar compounds still await precise definition. There is considerable evidence to support the view that the administration of adrenal cortical hormones may suppress adrenal function and induce adrenal atrophy. The extent, duration, and potential seriousness of this hazard in medical and surgical practice are, however, only now becoming apparent. A year ago, Fraser and co-workers1 reported a postoperative death that was regarded as the result of acute postoperative adrenal cortical insufficiency associated with atrophy and functional suppression of the adrenal cortex induced by previous treatment with cortisone. We wish to describe two additional examples of the same surgical complication, with further observations on the occurrence in man of adrenal atrophy induced by cortisone.REPORT OF CASES Case 1. *—A woman, 54 years of age,
Article
The complications of long-term corticosteroid therapy were reviewed in 100 elderly patients who were treated for chronic obstructive airways disease (n = 76), rheumatoid arthritis (n = 19) and ulcerative colitis (n = 5). The incidence of side effects was high (40%) and appeared to be dose-related. Osteoporosis (16%) and hypertension (12%) were the most common. Hypokalaemia occurred infrequently despite the fact that 69 patients were also prescribed diuretics. A further group of 36 patients receiving corticosteroids for polymyalgia rheumatica and giant cell arteritis also seemed to demonstrate a dose-related effect on the incidence of complications although this could not be confirmed statistically.
Article
National steroid cards were designed to inform patients treated with corticosteroids of the dose and potential hazards of treatment. Recent reports of severe chickenpox associated with steroid treatment1 2 have highlighted a potential need to amend the current steroid card. In May 1994 the Chief Medical Officer wrote to all doctors in the United Kingdom regarding the hazards of exposure to chickenpox.3 With this background, we asked patients taking oral steroid treatment about the information they had received from their doctors. Patients, methods, and results Between September and November 1994 all patients who presented to the outpatient pharmacy of Chelsea and Westminster Hospital with a prescription for oral prednisolone were interviewed. Patients completed a standardised questionnaire asking their age, whether they carried a steroid card, if they had had chickenpox, and their doctors' instructions on stopping steroids and side effects. Patients were also asked about the condition for which they considered the prednisolone had been prescribed, together with the dose and duration of treatment. A total of 105 consecutive patients presented with a prescription for steroids during the three month study. Of these, 102 (46 male and 56 female) patients (or accompanying immediate family with a child patient) fully completed the questionnaire; the median age of patients was 50 years (range 1 to 92). About one in seven patients were unable to give details of the condition for which they had been prescribed steroids. Over a third of the patients had received their first course of oral steroids during the survey period. Of the 66 patients who had been treated previously with steroids, 45 (67%) carried a steroid card; this included 14 patients who had been treated for less than one month, 20 for one to six months, and 32 for more than six months. Previous chickenpox was acknowledged in 75 and denied in 21; six of the 102 patients surveyed were uncertain. Doctors' instructions on not stopping treatment suddenly was recalled by 60 patients, and 63 acknowledged being given advice on potential side effects of steroids. Only 24 confirmed that the doctor had specifically asked about chickenpox and only 15 had been advised about chickenpox in association with their treatment. All 27 patients who recalled no previous chickenpox (or were uncertain of it) had received no specific information from their doctor at the time of the steroid prescription about the potential hazards of chickenpox. Comment This survey highlights a need to update steroid cards for the benefit of both patients and prescribing doctors. Steroid cards were designed in 1961 by the Department of Health and to our knowledge have not been modified since their introduction. Distribution is through the Royal Pharmaceutical Society of Great Britain. The cards do not give specific warnings about the hazards of chickenpox with steroid treatment. Although most of the survey patients who had previously been treated with steroids carried a steroid card, only half could recall of their doctor's advice on side effects. Even though the true prevalence of immunity to varicella in patients who are uncertain of previous chickenpox infection may be high,2 there is a clear risk for those who do not have antibodies to varicella.1 2 The universal omission of advice regarding exposure to chickenpox in those patients within the present survey who had no recall of having had chickenpox reinforces the need for written instructions regarding potential severe adverse reactions with steroids.3 4 Patient information leaflets detailing drug precautions have been included by the manufacturers in only a limited number of steroid preparations but are due to be included with all steroid preparations as part of the Medicines Control Agency's patient pack initiative. As with other drug safety warnings, dated amendments should be made regularly if the steroid card is to have clinical relevance, particularly as it is reproduced in each edition of the British National Formulary. Our hospital now issues a separate written warning regarding chickenpox with all prescriptions for corticosteroids. Footnotes Funding None. Conflict of interest None.References1.↵Dowell SF, Bresee JS.Severe varicella associated with steroid use.Paediatrics1993; 92:223–8.OpenUrlFREE Full Text2.↵Rice RB, Simmons K, Carr R, Banatvala J.Near fatal chickenpox during prednisolone treatment.BMJ1994; 309:1069–70.OpenUrlFREE Full Text3.↵Department of Health.Corticosteroids and varicella-zoster virus. CMO's update 2.London:DoH,1994.4.↵Severe chickenpox associated with systemic corticosteroids.Current problems in Pharmacovigilence, Vol 20.London:Committee on Safety of Medicines,1994.
Article
Intravenous hydrocortisone in high doses is often prescribed when immunosuppression is required urgently, such as in the treatment of acute asthma. It is also sometimes used when patients are unable to take oral prednisolone. This practice is potentially dangerous, however, as high dose hydrocortisone may precipitate clinically significant hypokalaemia in susceptible patients. The importance of this effect is emphasised by the following report. Case report A 63 year old man with a history of alcohol abuse presented with a two day history of haematemesis, melaena, and blackouts. He admitted drinking 3.4 litres of beer a day but denied drinking in the week before admission because of indigestion. On examination he was pale with a generalised purpuric rash. The liver was enlarged to 5 cm below the costal margin, and he had a small retinal haemorrhage. A full blood count showed a haemoglobin concentration of 51 g/l, a white cell count of 8.8x109/l, and a platelet count of 4x109/l. Electrolyte analysis showed the following plasma concentrations: sodium 131 mmol/l (normal 133-144 mmol/l), potassium 3.7 mmol/l (normal 3.4-5.2 mmol/l), total calcium 1.92 mmol/l (normal 2.26-2.60 mmol/l), urea 9 mmol/l (normal 2.5-7.5 mmol/l), and creatinine 91 μmol/l (normal 50-100 μmol/l). A coagulation screen gave a thrombin time of 12.5 s (control 13.0 s), a prothrombin time of 14.2 s (control 13.7 s), a kaolin cephalin clotting time of 39.3 s (control 40.8 s), and a reduced thrombotest result of 60%. (The thrombotest is a combined assay of the activities of factors II, VII, IX, and X.) Liver function tests showed the following serum bilirubin concentrations: 11 μmol/l (normal 1-17 μmol/l), albumin 24g/l (normal 35-50 g/l), and (gamma)-glutamyltrans-ferase 60 IU/l (normal <45 IU/l). An electrocardiogram showed a short PR interval of 0.08 s (figure 1). Heart size appeared normal on chest radiography, but there …
Article
Readers will learn the importance of psychiatric symptomatology with corticosteroid drug therapy, especially when combined with other medications. A brief history of corticosteroid use over the last five decades was complied utilizing MEDLINE and PSYCHOINFO as sources of information which include peer-reviewed research articles, case studies, and relevant reviews in English. Corticosteroids are routinely prescribed for a variety of allergic and immunologic illnesses. Psychiatric side effects from corticosteroids include mania, depression and mood disturbances. Psychiatric symptoms usually occur within the first two weeks of corticosteroid therapy and seem to be dose related. Treatment with lithium or antipsychotics may be helpful. Physicians should carefully monitor patients for psychiatric and cognitive side effects of corticosteroid use.
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Objectives: To assess the effects of bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. Search strategy: We searched the Cochrane Musculoskeletal Group trials register, Medline up to 1997 and Embase1988-1997), and selected hand searching of reference lists was conducted. Hand searching of scientific abstracts from relevant meetings for the last five years was also done. An electronic search in Current Contents was done for the last six months. The Cochrane Controlled Trials Register (CCTR) will be searched for future updates. All languages were included in the search. For practical reasons only those in English were included, but all languages will be retrieved and translated for future updates. Selection criteria: All controlled clinical trials (CCTs) dealing with prevention or treatment of corticosteroid-induced osteoporosis with bisphosphonates of any type and reporting the outcomes of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. Data collection and analysis: All data extraction was performed by two independent reviewers. Outcomes of interest included change in bone mineral density (BMD) at the lumbar spine and femoral neck at six and 12 months. If present, data on number of new fractures and withdrawals due to adverse effects were also extracted. All data extraction was performed by two independent reviewers. Both continuous and dichotomous data were analyzed using fixed effects models. When significant heterogeneity was present, a random effects model was used. Main results: A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0. 01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant. Reviewer's conclusions: Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.
Article
A patient with a potassium wasting nephropathy secondary to chemotherapy simulating Bartter's syndrome is described. A 64-year-old woman with diffuse histiocytic lymphoma developed persistent hypokalemia following a course of Cytopan (cyclophosphamide), Adriamycin (doxorubicin), vincristine, and prednisone (CHOP)—Bleo. The diagnosis of a functional Bartter's syndrome was concluded following evaluation of serial plasma renins, aldosterone levels, and urinary electrolytes. Evidence is suggestive that a subpopulation of patients receiving chemotherapy may develop a functional Bartter's syndrome, and it is important to consider this diagnosis in patients who develop hypokalemia subsequent to chemotherapy introduction.
Article
Evidence for the teratogenicity of corticosteroids in humans is limited and has resulted in inconsistent recommendations regarding their use during early pregnancy. We examined the association between women's corticosteroid use during the periconceptional period (1 month before to 3 months after conception) and delivering infants with selected congenital anomalies. Data were derived from a population-based case-control study that included cases of orafacial clefts (n = 662), conotruncal heart defects (n = 207), neural tube defects (n = 265), and limb reduction defects (n = 165). Information on medication use was collected via maternal telephone interviews. Corticosteroid use was associated with an increased risk for isolated cleft lip with or without cleft palate (odds ratio 4.3, 95% confidence interval 1.1–17.2) and isolated cleft palate (odds ratio 5.3, 95% confidence interval 1.1–26.5). Increased risks were not observed for the other anomaly groups studied. These data in conjunction with other epidemiologic data suggest a possible causal association between cleft lip and palate and corticosteroid use. Am. J. Med. Genet. 86:242–244, 1999. © 1999 Wiley-Liss, Inc.
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We determined the comparative efficacy of vitamin D, calcitonin, fluoride, and bisphosphonates for the management of corticosteroid-induced osteoporosis using meta-regression models. A systematic search for trials was conducted using MEDLINE, bibliographic references, abstracts from national meetings, and contact with pharmaceutical companies and content experts. We included all randomized controlled trials, lasting at least 6 months, of adult patients on oral corticosteroids that evaluated treatment comparisons between vitamin D, calcitonin, bisphosphonates, or fluoride either with no therapy/calcium or with each other and that reported extractable results. The outcome measure of interest was change in lumbar spine bone mineral density (BMD). We identified 45 eligible trials, which provided 49 eligible treatment comparisons (some trials had three arms or more). Our results indicated that bisphosphonates were the most effective class (effect size 1.03; 95% CI: 0.85, 1.17); results were similar even when newer generations of nitrogen-containing bisphosphonates were excluded from analysis. We found the efficacy of bisphosphonates was enhanced further when used in combination with vitamin D (effect size, 1.31; 95% CI: 1.07, 1.50). Vitamin D and calcitonin were more effective than no therapy/calcium (effect size, 0.46; 95% CI: 0.27, 0.62; and effect size, 0.51; 95% CI: 0.33, 0.67, respectively) and were of similar efficacy, but both were significantly less effective than bisphosphonates. Fluoride appeared effective, but there were too few studies (n = 5) to draw robust conclusions regarding its efficacy compared with the other three therapies. In summary, bisphosphonates are the most effective of evaluated agents for managing corticosteroid-induced osteoporosis. The efficacy of bisphosphonates is enhanced further with concomitant use of vitamin D.
Article
Bei allen Patienten nach Herztransplantation, die mit einer dreifachen immunsuppressiven Therapie unter Einschlu von Glucocorticoiden behandelt werden, mu nach einer Therapiedauer von ber einem Jahr mit der Suppression der Hypothalamus-HVL-NNR-Achse gerechnet werden. Daraus ergeben sich Konsequenzen fr die berwachung in Situationen whrend und nach erhhtem Steroidbedarf sowie bei der Beendigung der Steroidtherapie.In 20 patients we studied the function of the corticotropic pituitary and adrenal gland 13 to 45 month (m=27.1) after heart transplantation (HTx). For prophylactic immunosuppression all patients were treated with tripple drug therapy, including Cyclosporine A, Azathioprin and Prednisolone. After performing the CRH-test we could demonstrate, that in all patients, treated with Prednisolone (0.09–0.15 mg/kg/day) for more than 1 year, adrenal insufficiency was evident. Patients must be controlled carefully, if therapy with steroids is stopped thereafter, not only because of increased risk of rejection but also because metabolic disturbance caused by adrenal insufficiency may occur. In case of elevated demand of steroids (i.e. infections or surgery), adequate substitution with glucocorticosteroids is needed.
Article
Background: Ocular hypertension and open-angle glaucoma are well-known side-effects of treatment with topical ophthalmic glucocorticoids. There is uncertainty about the risk of these disorders with oral glucocorticoid therapy. Methods: Data from the Quebec universal health insurance programme for the elderly were used to identify 9793 patients with a new diagnosis of ocular hypertension or open-angle glaucoma, or on newly prescribed treatment for these disorders (cases). 38,325 controls were randomly selected from ophthalmology patients seen in the same month and year as the case (index date). Current use of oral glucocorticoids was defined as that within 14 days of the index date. All glucocorticoid doses were converted to the equivalent amount of hydrocortisone. The case-control analysis was done by conditional logistic regression and adjusted for age, sex, systemic hypertension, diabetes mellitus, ophthalmic glucocorticoids, glucocorticoid injections, and variables related to general health. Findings: The mean ages of cases and controls were similar (74.9 [SD 6.3] vs 74.7 [6.4]). The adjusted odds ratio of ocular hypertension or open-angle glaucoma for current users of oral glucocorticoids compared with non-users was 1.41 (95% CI 1.22-1.63). There was a dose-related increase in the adjusted odds ratios for current users: 1.26 (1.01-1.56) for less than 40 mg per day of hydrocortisone, 1.37 (1.06-1.76) for patients on 40-79 mg per day, and 1.88 (1.40-2.53) for patients on 80 mg or more per day. The odds ratios also increased with the duration of treatment over the first 11 months of exposure. Interpretation: The use of oral glucocorticoids increases the risk of ocular hypertension or open-angle glaucoma in elderly patients. In patients in this age-group who need long-term treatment with high doses of oral glucocorticoids, monitoring of intraocular pressure may be justified.
Article
Hyperlipidemia is a common feature after organ transplantation. Most studies have evaluated the lipid profile in recipients of a particular graft, usually renal. In the present work, we studied the lipid profiles of 30 long-term stable liver transplant patients (LTP) and compared their pattern with 40 long-term stable renal transplant patients (RTP) matched for gender, age, and time from transplantation. There were no significant differences between both groups in body mass index, serum glucose, serum creatinine, or urinary protein excretion. In contrast, RTP had higher pre-transplant total cholesterol and triglycerides, received higher doses of steroids (both average and cumulative) and had higher cycosplorine blood levels. After a mean time of 60 months after transplantation, RTP exhibited higher levels of total serum cholesterol (226 +/- 26 vs. 180 +/- 39 mg/dl; p = 0.000 002) and low-density lipoprotein (LDL) cholesterol (152 +/- 22 vs. 112 +/- 37 mg/dl; p = 0.00001). In contrast, there were no differences between RTP and LTP in high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, or lipoprotein (a) [Lp(a)]. By univariate analysis in the whole group, renal graft, prednisone daily dose, cyclosporine blood levels, pre-transplant cholesterol, and triglycerides were associated with increased post-transplant cholesterol levels. By multivariate analysis, prednisone daily dose was the only independent variable predicting increased post-transplant serum cholesterol levels. The present data show that hypercholesterolemia is more frequent among RTP than among LTP. In addition, our data suggest that corticosteroid therapy, rather than the transplanted organ, may be the major contributor to this difference.
Article
Osteoporosis is a major complication of long-term corticosteroid administration, but the magnitude of the effect in patients with chronic obstructive pulmonary disease (COPD) is not well defined. In a cross-sectional study, we evaluated the association between steroid use and vertebral fractures in 312 men, 50 yr of age or older, with COPD. Subjects were evaluated according to their corticosteroid use: Never Steroid Users (NSU) (n = 117), Inhaled Steroid Users (ISU) (n = 70), and Systemic Steroid Users (SSU) (n = 125). The prevalence of one or more vertebral fractures was 48.7% in the NSU group, 57.1% in the ISU group, and 63.3% in the SSU group. Compared with NSU, SSU were two times as likely to have one or more vertebral fractures: age-adjusted odds ratio (OR) = 1.80; 95% CI, 1.08 to 3.07. This relationship was primarily due to a strong association between continuous systemic steroid use and vertebral fractures: age-adjusted OR = 2.36; 95% CI, 1.26 to 4.38. In addition, fractures in SSU were more likely to be multiple and more severe. A weaker relationship existed between inhaled steroid use and vertebral fractures: age-adjusted OR = 1.35; 95% CI, 0.77 to 2.56 compared with NSU. These data indicate that vertebral fractures are common in older men with COPD; the likelihood of these fractures is greatest in those men using continuous systemic steroids.