Observational UK cohort study to describe intermittent oral corticosteroid prescribing patterns and their association with adverse outcomes in asthma.

INTRODUCTION: Oral corticosteroids (OCS) for asthma are associated with increased risks of developing adverse outcomes (adverse outcomes); no previous study has focused exclusively on intermittent OCS use. METHODS: This historical (2008-2019) UK cohort study using primary care medical records from two anonymised, real-life databases (OPCRD and CPRD) included patients aged≥4 years with asthma receiving only intermittent OCS. Patients were indexed on their first recorded intermittent OCS prescription for asthma and categorised by OCS prescribing patterns: one-off (single), less frequent (≥90 day gap) and frequent (<90 day gap). Non-OCS patients matched 1:1 on gender, age and index date served as controls. The association of OCS prescribing patterns with OCS-related AO risk was studied, stratified by age, Global Initiative for Asthma (GINA) 2020 treatment step, and pre index inhaled corticosteroid (ICS) and short-acting ß2-agonist (SABA) prescriptions using a multivariable Cox-proportional hazard model. FINDINGS: Of 476 167 eligible patients, 41.7%, 26.8% and 31.6% had one-off, less frequent and frequent intermittent OCS prescribing patterns, respectively. Risk of any AO increased with increasingly frequent patterns of intermittent OCS versus non-OCS (HR; 95% CI: one-off 1.19 (1.18 to 1.20), less frequent 1.35 (1.34 to 1.36), frequent 1.42 (1.42 to 1.43)), and was consistent across age, GINA treatment step and ICS and SABA subgroups. The highest risks of individual OCS-related adverse outcomes with increasingly frequent OCS were for pneumonia and sleep apnoea. CONCLUSION: A considerable proportion of patients with asthma receiving intermittent OCS experienced a frequent prescribing pattern. Increasingly frequent OCS prescribing patterns were associated with higher risk of OCS-related adverse outcomes. Mitigation strategies are needed to minimise intermittent OCS prescription in primary care.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

A retrospective analysis of myocardial preservation techniques during coronary artery bypass graft surgery: are we protecting the heart?

BACKGROUND: Retrograde perfusion into coronary sinus during coronary artery bypass graft (CABG) surgery reduces the need for cardioplegic interruptions and ensures the distribution of cardioplegia to stenosed vessel territories, therefore enhancing the delivery of cardioplegia to the subendocardium. Peri-operative myocardial injury (PMI), as measured by the rise of serum level of cardiac biomarkers, has been associated with short and long-term clinical outcomes. We conducted a retrospective analysis to investigate whether the combination of antegrade and retrograde techniques of cardioplegia delivery is associated with a reduced PMI than that observed with the traditional methods of myocardial preservation. METHODS: Fifty-four consecutive patients underwent CABG surgery using either antegrade cold blood cardioplegia (group 1, n = 28) or cross-clamp fibrillation (group 2, n = 16) or antegrade retrograde warm blood cardioplegia (group 3, n = 10). The study primary end-point was PMI, evaluated with total area under the curve (AUC) of high-sensitivity Troponin-T (hsTnT), measured pre-operatively and at 6, 12, 24, 48 and 72 hours post-surgery. Secondary endpoints were acute kidney injury (AKI) and inotrope scores, length of intensive care unit (ICU) and hospital stay, new onset atrial fibrillation (AF) and clinical outcomes at 6 weeks (death, non-fatal myocardial infarction, coronary artery revascularization, stroke). RESULTS: There was evidence that mean total AUC of hsTnT was different among the three groups (P = 0.050). In particular mean total AUC of hsTnT was significantly lower in group 3 compared to both group 1 (-16.55; 95% CI: -30.08, -3.01; P = 0.018) with slightly weaker evidence of a lower mean hsTnT in group 3 when compared to group 2 (-15.13; 95% CI -29.87, -0.39; P = 0.044). There was no evidence of a difference when comparing group 2 to group 1 (-1.42,; 95% CI: -12.95, 10.12, P = 0.806). CONCLUSIONS: Our retrospective analysis suggests that, compared to traditional methods of myocardial preservation, antegrade retrograde cardioplegia may reduce PMI in patients undergoing first time CABG surgery.