Systemic glucocorticoid use in Denmark: a population-based prevalence study

OBJECTIVES: Glucocorticoid (GC) use is widespread and associated with many adverse effects. Thus, it is important to ascertain GC utilisation patterns. In this study, we examined the annual prevalence of prescription users and amount of use of systemic GCs. DESIGN: Population-wide prevalence study. SETTING: The primary healthcare and hospital sectors in Denmark from 1999 to 2015. RESULTS: Approximately 3% of the Danish population redeemed at least one prescription for a systemic GC annually between 1999 and 2015, with annual prevalence remaining constant over the period. However, after adjusting for age and sex, we observed a decrease in annual prevalence from 1999 to 2015, with a prevalence ratio of 0.92 (95% CI 0.91 to 0.92). Annual prevalence was highest among the elderly (7.0%–8.2% among persons 65–79 years of age and 8.4%–10% among persons 80+ years of age). Prednisolone was the most frequently redeemed systemic GC, with annual prevalence increasing from 1.4% to 2.1% during the 1999–2015 period. The amount of systemic GCs provided to the hospital sector increased from 2.3 defined daily doses (DDD)/1000 inhabitants/day in 1999 to 3.5 DDD/1000 inhabitants/day in 2015, while the amount provided to the primary healthcare sector remained constant in the range of 10–11 DDD/1000 inhabitants/day. CONCLUSION: We found a high prevalence of systemic GC use of 3% with a remarkably high prevalence in elderly of up to 10%, wherefore continued awareness of its effects is mandated

Fifteen-year nationwide trends in systemic glucocorticoid drug use in Denmark

Abstract Objective Glucocorticoid treatment of inflammatory disorders is associated with significant adverse effects related to glucocorticoid excess as well as adrenal insufficiency. This necessitates awareness of its use. We therefore investigated trends in systemic glucocorticoid use as well as morbidity and comedications among users. Design Cross-sectional drug utilisation study. Methods We conducted a population-based study of 926,314 users of systemic glucocorticoids (oral and injectable formulations) from 1999 to 2014 using Danish nationwide registries. We computed annual prevalence and incidence of systemic glucocorticoid use and prevalence of comedications and morbidity. Further, we assessed the annual amount of disease-modifying drug use. Results Of the 926,314 users of systemic glucocorticoids, 54% were female and median age at first-time use was 55 years. The annual prevalence was ≈ 3%, while the incidence was ≈ 1.4/100 person years (p-y). Both figures remained constant from 1999 to 2014. In the elderly, the annual prevalence was 6.7–7.7% (60–79 years of age) and 9.7–11% (≥80 years of age). Incidence increased among persons aged ≥80 years from 3.0/100 p-y in 1999 to 3.6/100 p-y in 2014. Concomitantly, the annual amount of for example methotrexate, azathioprine and tumour necrosis factor (TNF)-alpha agents increased and new biological agents emerged. The most frequent comedications were antibiotics (49%), cardiovascular drugs (38%) and NSAIDs (37%). Conclusions Our findings confirm a widespread use of systemic glucocorticoids, especially in the elderly, which prevails despite increased use of disease-modifying drugs. The continuously prevalent use of glucocorticoid use constitutes a challenge for the endocrine community

Prevalence of lifestyle characteristics in glucocorticoid users and non-users: a Danish population-based cross-sectional study

OBJECTIVES Lifestyle may affect observed associations between glucocorticoid use and adverse events. This study aimed to investigate whether lifestyle differ according to use of systemic glucocorticoids. DESIGN Population-based cross-sectional study. SETTING The Central Denmark Region. PARTICIPANTS 30 245 adults (≥25 years of age) who participated in a questionnaire-based public health survey in 2010. OUTCOME MEASURES Systemic glucocorticoid use was categorised as never use, current use (prescription redemption ≤90 days before completing the questionnaire), recent use (prescription redemption 91–365 days before completing the questionnaire), former use (prescription redemption >365 days before completing the questionnaire) and according to cumulative dose expressed in prednisolone equivalents (<100, 100–499, 500–999, 1000–1999, 2000–4999, ≥5000 mg). We computed the prevalence of lifestyle factors (body mass index, smoking, alcohol intake, physical activity and dietary habits) according to glucocorticoid use. We then estimated age-adjusted prevalence ratios (aPRs) and 95% CIs, comparing the categories of glucocorticoid users versus never users. All analyses were stratified by sex. RESULTS Of the 30 245 participants (53% women, median age 53 years), 563 (1.9%) were current users, 885 (2.9%) were recent users, 3054 (10%) were former users and 25 743 (85%) were never users. Ever users of glucocorticoids had a slightly higher prevalence of obesity than never users (18% vs 14%, aPR=1.4, 95% CI 1.2 to 1.5 in women and 17% vs 15%, aPR=1.2, 95% CI 1.1 to 1.4 in men). In women, ever users of glucocorticoids had a slightly lower prevalence of high-risk alcohol consumption compared with never users (17% vs 20%, aPR=0.8, 95% CI 0.7 to 1.0). Smoking, diet and physical activity did not differ substantially according to use of glucocorticoids. CONCLUSION Our study provides a framework for quantifying potential uncontrolled confounding by lifestyle factors in studies of systemic glucocorticoids

Clinical indicators of adrenal insufficiency following discontinuation of oral glucocorticoid therapy: A Danish population-based self-controlled case series analysis

BACKGROUND: Biochemical adrenal insufficiency induced by glucocorticoid treatment is prevalent, but data on the clinical implications are sparse. We investigated clinical consequences of glucocorticoid-induced adrenal insufficiency after oral glucocorticoid cessation. METHODS: We conducted a Danish population-based self-controlled case series utilizing medical registries. In this design each individual serves as their own control allowing event rates to be compared as a function of time and treatment. Clinical indicators of adrenal insufficiency were defined as diagnoses of gastrointestinal symptoms, hypotension, cardiovascular collapse, syncope, hyponatremia, and hypoglycaemia. We included 286,680 persons who discontinued long-term (≥ 3 months) oral glucocorticoid treatment. We defined five risk periods and a reference period (before treatment): period 0 (on treatment), withdrawal period (1 month before and after cessation), followed by three consecutive 2 month-risk periods after withdrawal (periods 2–4). RESULTS: Median age at cessation was 69 years and 57% were female. Median treatment duration was 297 days and median cumulative dose was 3000 mg prednisolone equivalents. The incidence rates of hypotension, gastrointestinal symptoms, hypoglycemia and hyponatremia were increased in the withdrawal period compared to before treatment started (reference period). Incidence rate ratios comparing the withdrawal period with the reference period were 2.5 [95% confidence interval (CI): 1.4–4.3] for hypotension, 1.7 (95% CI: 1.6–1.9) for gastrointestinal symptoms, 2.2 (95% CI: 0.7–7.3) for hypoglycemia, and 1.5 (95% CI: 1.1–2.0) for hyponatremia. During 7 months of follow up, the rates of hypotension and gastrointestinal symptoms remained elevated compared to the reference period. Risk factors included use of antibiotics, increasing average daily dose of glucocorticoids, cumulative dose, and age. CONCLUSION: Oral glucocorticoid withdrawal was associated with adverse outcomes attributable to adrenal insufficiency. Our study underscores the need for future research to establish evidence-based clinical guidance on management of patients who discontinue oral glucocorticoids

Glucocorticoid-induced adrenal insufficiency: replace while we wait for evidence?

Glucocorticoids are, besides non-steroidal anti-inflammatory drugs, the most widely used anti-inflammatory medications. Prevalence studies indicate substantial use of both systemic and locally acting agents. A recognised adverse effect of glucocorticoid treatment is adrenal insufficiency, which is highly prevalent based on biochemical testing, but its clinical implications are poorly understood. Current evidence, including randomised trials and observational studies, indicates substantial variation among patients in both risk and course of glucocorticoidinduced adrenal insufficiency, but both are currently unpredictable. Oral and intra-articular formulations, as well as long-term and high-dose treatments, carry the highest risk of glucocorticoid-induced adrenal insufficiency defined by biochemical tests. However, no route of administration, treatment duration, or dose can be considered without risk. More research is needed to estimate the risk and temporal pattern of glucocorticoid-induced adrenal insufficiency, to investigate its clinical implications, and to identify predictors of risk and prognosis. Randomized trials are required to evaluate whether hydrocortisone replacement therapy mitigates risk and symptoms of glucocorticoid-induced adrenal insufficiency in patients discontinuing glucocorticoid treatment. This review aims to provide an overview of the available evidence, pointing to knowledge gaps and unmet needs.Diabetes mellitus: pathophysiological changes and therap

Attendance in a national screening program for diabetic retinopathy:a population-based study of 205,970 patients

AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments

Reading, Trauma and Literary Caregiving 1914-1918: Helen Mary Gaskell and the War Library

This article is about the relationship between reading, trauma and responsive literary caregiving in Britain during the First World War. Its analysis of two little-known documents describing the history of the War Library, begun by Helen Mary Gaskell in 1914, exposes a gap in the scholarship of war-time reading; generates a new narrative of "how," "when," and "why" books went to war; and foregrounds gender in its analysis of the historiography. The Library of Congress's T. W. Koch discovered Gaskell's ground-breaking work in 1917 and reported its successes to the American Library Association. The British Times also covered Gaskell's library, yet researchers working on reading during the war have routinely neglected her distinct model and method, skewing the research base on war-time reading and its association with trauma and caregiving. In the article's second half, a literary case study of a popular war novel demonstrates the extent of the "bitter cry for books." The success of Gaskell's intervention is examined alongside H. G. Wells's representation of textual healing. Reading is shown to offer sick, traumatized and recovering combatants emotional and psychological caregiving in ways that she could not always have predicted and that are not visible in the literary/historical record