COMPARATIVE RISK OF INFECTION FOR FIRST-LINE CSDMARD THERAPY IN RHEUMATOID ARTHRITIS: A MULTINATIONAL COHORT ANALYSIS OF REAL WORLD DATA

Background/Aims Infections on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) are an important concern for rheumatoid arthritis (RA) patients, especially during the COVID-19 pandemic. However comparative safety data between csDMARDs have been conflicting and limited in power. The objective was to assess the comparative safety of serious, opportunistic and all infections (including nonserious) of first-line csDMARDs in RA through a large multinational observational study. Methods We evaluated first-line new users of methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SZ) and leflunomide (LEF) monotherapy. Data was obtained from four US databases (IQVIA US Ambulatory EMR (AMBER), Optum® De-identified Clinformatics® Datamart (Optum), IBM MarketScan® Medicare Supplemental Database (MDCR), and IBM MarketScan Commercial Database (CCAE)), one from Germany (IQVIA Disease Analyser Germany EMR (Germany)), and another from the UK (IQVIA UK The Health Improvement Network). Patients included were ≥18 years with a RA diagnosis between 2005-2019, without prior inflammatory arthritis, cancer or infection (in the preceding 30 days). Serious infections were defined as those requiring hospitalisation or resulting in death within 30 days;opportunistic infections were defined as per published EULAR consensus. Patients were followed from 1-day following treatment initiation to the earliest of treatment discontinuation, switching, or addon plus 14 days, or loss to follow-up. Cox proportional-hazards models for MTX against each csDMARD with large-scale propensity score stratification were performed. A large set of negative control outcomes were used to calibrate hazard ratios (cHR) to account for potential residual confounding. Estimates were pooled where homogeneity across sources was adequate (I2<0.4). Results A total of 247,511 patients were included (MTX: 141,647;HCQ: 73,286, SSZ: 16,521, LEF: 16,057), with pooled incidence rates of serious, opportunistic and all infections across sources for MTX users of 33.7, 20.1 and 311.8 per 1,000 pyrs, respectively. With MTX as the referent, for all infections, the pooled cHR (with 95% Confidence Intervals) for SSZ was 0.73 (0.62, 0.86);HCQ, 0.96 (0.89, 1.04);and LEF, 0.74 (0.50, 1.08). The serious infection pooled cHR for SSZ was 0.75 (0.58, 0.97) and for LEF, 0.93 (0.61, 1.40). For opportunistic infections, pooled cHR for HCQ was 1.04 (0.92, 1.19). Conclusion SSZ, LEF and less consistently HCQ had a lower risk of all (including non-serious) infections, compared to MTX. SSZ and LEF were associated with a 25% reduction in the expected risk of all infections. SSZ was associated with a 25% lower risk of serious infections relative to MTX. In the first large scale observational network study assessing comparative risk of infection with csDMARDs there were differences between drugs in risk for all infections, with potential implications for clinical care.

Incidence of cardiac complications during index hospitalisation with covid-19 in Australia: Aus-covid study

Introduction: Cardiac complications of COVID-19 include acute cardiac injury, myopericarditis, cardiomyopathy and arrhythmias. This study aimed to describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. Methods: AUS-COVID is a multicentre observational cohort study across 21 Australian hospitals including all index hospitalisations with laboratory-proven COVID-19 in patients aged 18 years or older. All consecutive patients entered in the AUS-COVID Registry by 28 January 2021 were included in the present study. Results: Six hundred and forty-four hospitalised patients (62.5 ± 20.1 years old, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (0.5%) patients developed high grade atrioventricular (AV) block. Two (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. Conclusions: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

Association of hypertension with mortality in patients hospitalised with covid-19

Introduction: To assess whether hypertension is an independent risk factor for mortality amongst patients hospitalised with COVID-19 and to evaluate the impact of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on mortality in patients with a background of hypertension. Methods: This observational cohort study included all consecutive index hospitalisations with laboratory proven COVID-19 aged 18 years or older across 21 Australian hospitals entered in the AUS-COVID Registry by 22nd January 2021. Patients were excluded if their past medical or medication history was not available or if they were transferred to another hospital in which case mortality outcomes were not available. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs.Results: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (aOR 1.09, 95% CI 1.07-1.12, p<.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13-6.53, p=.026), chronic kidney disease (aOR 2.33, 95% CI 1.02-5.32, p=.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06-4.85, p=.035) (Figure 1). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48-1.77, p=.81). Amongst patients with hypertension, ACE inhibitors (aOR 1.37, 95% CI 0.61-3.08, p=.61) and ARBs (aOR 0.64, 95% CI 0.27-1.49, p=.30) did not affect mortality. Conclusions: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

Jumping into the virtual environment implications and possibilities for arts education

To start off this special issue on COVID-19 and K-12 arts education, this article places the impact of COVID-19 on public education into context, and drills down to how the pandemic affected the delivery of arts education. The article begins with an overview of the inequities revealed in our public education system by COVID-19. While many of these have been revealed and studied before, the pandemic brought them to the routine attention of the public in a way that earlier advocacy and research efforts have not. The article then addresses how these inequities have influenced the availability and quality of arts education offered during the pandemic, showcasing the continued “second class” status of arts education in public education planning and delivery. Finally, the article ends with some positive outcomes one year into the pandemic for arts education, suggesting possibilities for the future post pandemic, as well as implications and potential warning signs for the next 24 months to come. © 2021 Taylor & Francis Group, LLC.

Mental health needs during COVID-19: Responses in pediatric health care

Until recently, children have not been central in news of the COVID-19 pandemic;however, the pandemic has certainly impacted them. Recent studies suggest that both parental and children’s mental health has worsened since the onset of the pandemic. These changes are most pronounced in families facing more hardship, and children already at high risk for mental health concerns are even more vulnerable as a result of the pandemic. Children’s hospitals have responded in varied ways to these concerns, providing telehealth mental health visits, offering webinars on perti-nent topics, and adding supportive content on their web-sites. This article features specific programs of Children’s Mercy with hospitals in both Kansas City, MO, and Overland Park, KS, as well as several other institutions, and outlines resources for nurses to share with families. © 2020, Anthony J. Jannetti Inc.. All rights reserved.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Longitudinal analysis of biochemical and haematological features of cancer patients with COVID-19

Background: Cancer patients (pts) are at increased risk of severe COVID-19 infection and death. Older pts, men and those with haematological malignancies and receiving anti-tumour therapy within 14 days appear to be at highest risk for poor outcomes. In general populations, severe COVID-19 infection has been associated with neutrophilia, raised lactate dehydrogenase (LDH) and C-reactive protein (CRP). Cancer and its treatment affect many haematological and biochemical parameters. We examined whether COVID-19 infection affected these compared to pts’ baseline parameters by longitudinal tracking. We also investigated whether changes were associated with poor outcome. Methods: Consecutive pts with solid or haematological malignancies presenting with index symptoms and testing positive for SARS-CoV-2 at a tertiary oncology centre were identified following institutional board approval. Clinical and laboratory data were extracted from the pt record. Paired T-tests were used for longitudinal sampling and ANOVA/Chi squared for outcomes. Results: 52 pts tested positive (27 male, 25 female;median age 63). 80.5% had solid cancers, and 19.5% haematological. 31/52 pts were lymphopenic prior to infection. Comparing mean pre-infection counts (6 months-14 days=PRE) with mean counts from the 5 days following positive test (DURING) lymphocyte counts significantly decreased during infection (p<0.0001). Platelets were significantly reduced DURING vs. PRE COVID-19 (p=0.0028). 17/52 pts developed transient (median 2 days) neutropenia (<2x109/L) DURING infection (6 pts <1x109/L, 2 pts <0.5x109/L), 8/17 attributed to cancer/cancer therapy, the rest had no underlying cause. 8/17 pts received growth factor support. Reduced lymphocytes/neutrophils/platelets at diagnosis were not associated with oxygen requirement (O2) or death. Different CRP trajectories were observed when comparing pts grouped by discharge/ O2/death. Higher CRP and LDH at diagnosis were associated with admission (p=0.02 CRP/0.2 LDH), O2 (p=0.0002 CRP/p<0.01 LDH) and death (p=0.069 CRP/p=0.04 LDH). Updated analysis will be presented. Conclusions: Infection with SARS-CoV-2 commonly affects haematological parameters in cancer pts. High CRP and LDH are associated with poor outcomes. Legal entity responsible for the study: The Christie NHS Foundation Trust. Funding: Has not received any funding. Disclosure: R. Lee: Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb;Speaker Bureau/Expert testimony: Astra Zeneca. A. Armstrong: Shareholder/Stockholder/Stock options, Husband has shares: Astra Zeneca. T. Cooksley: Speaker Bureau/Expert testimony: Bristol Myers Squibb. All other authors have declared no conflicts of interest.