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Oral corticosteroid (OCS) use in severe asthma remains all too common despite advances in asthma treatment. Use of OCS is associated with significant toxicity that can have a lasting adverse impact on a patient's overall health. Monoclonal antibodies have been developed that reduce both the rate of occurrence of OCS-treated exacerbations and the OCS requirements in patients with oral corticosteroid-dependent asthma. This article describes strategies to prevent and best manage endocrine complications associated with OCS use and provides guidance on OCS dose management after the introduction of steroid-sparing therapies. (1) We identify OCS-dependent patients and assess for comorbidities including bone health, glycemic control, and adrenal function; (2) we begin attempts at OCS dose optimization before or soon after introducing a steroid-sparing biologic therapy; (3) we taper OCS, using explicit criteria for asthma control; (4) we assess hypothalamic-pituitary-adrenal axis integrity once a physiologic dose of OCS is achieved to guide further the rate of OCS taper; and (5) we manage corticosteroid-related comorbidities as detailed in this article.

Patients surviving an ICU admission for deliberate self-harm are at high risk of recurrent self-harm or suicide after discharge. It is unknown whether mental health follow-up after discharge (with either a family physician or psychiatrist) reduces this risk.What is the association between mental health follow-up after discharge and recurrent self-harm among patients admitted to the ICU for intentional self-harm?Population-based cohort study of consecutive adults (≥ 18 years of age) from Ontario, Canada, who were admitted to ICU because of intentional self-harm between 2009 and 2017. We categorized patients according to follow-up, with early follow-up indicating 1 to 21 days after discharge, late follow-up indicating 22 to 60 days after discharge, and no follow-up indicating within 60 days of discharge. We conducted analyses using a cause-specific extended Cox regression model to account for varying time for mental health follow-up relative to the outcomes of interest. The primary outcome was recurrent ICU admission for self-harm within 1 year of discharge.We included 9,569 consecutive adults admitted to the ICU for deliberate self-harm. Compared with receiving no mental health follow-up, both early follow-up (hazard ratio [HR], 1.37; 95% CI, 1.07-1.75) and late follow-up (HR, 1.69; 95% CI, 1.22-2.35) were associated with increased risk in recurrent ICU admission for self-harm. As compared with no follow-up, early follow-up (HR, 1.10; 95% CI, 0.70-1.73]) was not associated with death resulting from suicide, but late follow-up (HR, 1.54; 95% CI, 1.37-1.83) was associated with an increase in death resulting from suicide.Among adults admitted to the ICU for deliberate self-harm, mental health follow-up after discharge was not associated with reduced risk of recurrent ICU admission for self-harm or death resulting from suicide, and patients seeking outpatient follow-up may be those at highest risk of these outcomes. Future research should focus on additional and novel methods of risk mitigation in this vulnerable population.

Azithromycin has immunomodulatory actions, and its beneficial effects have been demonstrated in asthmatic adults. Data on children are limited.Does the addition of oral azithromycin to standard therapy in children with poorly controlled asthma improve asthma control compared with standard treatment alone?This open-label randomized controlled trial included children (5-15 years of age) with poorly controlled asthma defined by Asthma Control Test (ACT) and Childhood Asthma Control Test (CACT) score of ≤ 19. They were randomized to receive azithromycin (10 mg/kg) three times weekly for 3 months along with standard treatment or standard treatment alone. The primary outcome was the ACT and CACT scores at 3 months. Secondary outcomes were asthma control according to Global Initiative for Asthma (GINA) guidelines, the number of exacerbations, change in spirometry parameters, change in fractional exhaled nitric oxide (Feno) level, positive throat swab results, and side effects.The trial included 120 children (89 boys; 60 in each group). The mean ± SD age was 9.9 ± 3 years. The baseline parameters were similar between the groups. Mean ± SD ACT and CACT scores (available for 115 children) at 3 months of intervention were 21.71 ± 2.17 vs 18.33 ± 2.19 (P .001) in the azithromycin and control groups, respectively. The numbers of children with well-controlled asthma according to GINA guidelines were 41 of 56 vs 10 of 56 in the azithromycin and control groups, respectively (P .001). The median number of exacerbations requiring emergency visit and steroid use were fewer in the azithromycin group: 0 (interquartile range [IQR], 3) vs 1 [IQR, 6]; P .001). No difference was found in Feno level, spirometry parameters, positive throat swab results, and adverse effects between the groups.The use of azithromycin in children with poorly controlled asthma resulted in improved asthma control and reduced exacerbations.Clinical Trials Registry - India; No.: CTRI/2019/06/019727; URL: www.ctri.nic.in.

Air pollution poses a great environmental risk to health. Outdoor fine particulate matter (particulate matter with an aerodynamic diameter 103 million disability-adjusted life years lost according to the Global Burden of Disease Report. The World Health Organization attributes 3.8 million additional deaths to indoor air pollution. Air pollution can harm acutely, usually manifested by respiratory or cardiac symptoms, as well as chronically, potentially affecting every organ in the body. It can cause, complicate, or exacerbate many adverse health conditions. Tissue damage may result directly from pollutant toxicity because fine and ultrafine particles can gain access to organs, or indirectly through systemic inflammatory processes. Susceptibility is partly under genetic and epigenetic regulation. Although air pollution affects people of all regions, ages, and social groups, it is likely to cause greater illness in those with heavy exposure and greater susceptibility. Persons are more vulnerable to air pollution if they have other illnesses or less social support. Harmful effects occur on a continuum of dosage and even at levels below air quality standards previously considered to be safe.

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Various case reports have associated transient sinus bradycardia with Remdesivir (RDV) therapy for SARS-CoV2 infection. Pallotto et al., Gubitosa et al., and Touafchia et al. all reported the association of Remdesivir with increased risk of bradycardia in small samples of patients treated with RDV for COVID-19. To our knowledge, no large studies looked at this side effect of RDV therapy. We aimed to analyze the association between sinus bradycardia and Remdesivir therapy for COVID-19. METHODS: A retrospective case-control analysis was done for 1535 patients with SARS-CoV2 infection who were admitted to four teaching hospitals in an urban area in 2020. The mean age was 66 years (SD of 16.7, range 18-99), with 774 males (50.4%). Patients were divided into cases (treated with RDV) and controls (not treated with RDV). Multivariate logistic regression methods were used to analyze the associations between independent variables and outcomes. Pulse rate variables were recorded as pulse rate at day-0, day-3, day-7, and incidence of bradycardia on three consecutive days during admission. Other variables recorded were age, gender, comorbidities, prior history of cardiac disease/arrhythmias, concomitant medications (including AV nodal blockers, dexamethasone, Albuterol, and Lasix), and ICU admission. Survival analysis was run for 7-day and 30-day mortality, as well as survival to hospital discharge. RESULTS: 1415 patients were included in the final analysis, after the exclusion of 120 patients with previous heart blocks. 600 patients (39.1%) were in the Remdesivir group, and 935 patients (60.9%) were in the control group. Between both groups, a total of 454 patients (29.6%) had transient bradycardia on three consecutive days during hospitalization. A multivariate regression analysis was done after adjusting for all confounding variables (age, gender, history of cardiac diseases, AV-nodal blocking drugs, dexamethasone, furosemide, and albuterol therapy). It was seen that there was no statistically significant association between RDV therapy and persistent transient bradycardia (transient bradycardic events on three consecutive days) (Odds Ratio 0.823, 95% confidence interval (CI) 0.594-1.134, p=0.236). There was no statistically significant association of RDV therapy with patients having any bradycardia event during hospitalization in a sub-analysis (Odds Ratio 0.888, 95% confidence interval (CI) 0.665-1.184, p=0.419). Also, RDV failed to show any statistically significant mortality benefit (OR 1.1, CI 0.75-1.62, p=0.6). CONCLUSIONS: Our findings indicate that although transient sinus bradycardia in patients with COVID-19, can be triggered by severe hypoxia, inflammatory damage to AV-nodal cells, or exaggerated response to medications, there was no statistically significant association of RDV therapy with the risk of developing bradycardia. RDV therapy should not be withheld in patients at risk of developing bradycardia. CLINICAL IMPLICATIONS: Remdesivir therapy did not increase the risk of developing bradycardia in our patient population. RDV therapy should not be withheld in patients at risk of developing bradycardia. Larger RCTs are needed to validate these findings. DISCLOSURES: No relevant relationships by Rahul Bollam, source=Web Response No relevant relationships by Bhagat Kondaveeti, source=Web Response No relevant relationships by Florencio Mamauag, source=Web Response No relevant relationships by Kainat Saleem, source=Web Response No relevant relationships by Manasi Sejpal, source=Web Response No relevant relationships by Megha Sood, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response No relevant relationships by Rosalie Traficante, source=Web Response No relevant relationships by Syed Arsalan Zaidi, source=Web Response