Impact of COVID-19 measures on exacerbation rates and healthcare visits in US asthma patients.

Objective: To compare exacerbation rates and healthcare resource utilization (HCRU) in real-world patients in the United States who had moderate-to-severe asthma on medium- or high-dose inhaled corticosteroid/long-acting ß2-agonist therapy at different stages before and after the pandemic. Methods: This noninterventional, retrospective study described demographics, exacerbations, HCRU, and medication use in patients from a US-wide healthcare claims database in 4 consecutive years anchored around March 15, 2020 (start date of the first emergency health measures against coronavirus disease 2019 [COVID-19], or the first lockdown, in the United States, termed "restriction onset" hereafter). Four cohorts of patients potentially eligible for moderate-to-severe asthma clinical trials at the beginning (index) of each of four 1-year periods (March 15, 2018, 2019, 2020, 2021, respectively) were built. Exacerbations, healthcare visits, and asthma medication use were counted in the 1-year period after the index for each cohort. Results: The prevalence of patients with one or more exacerbation per year decreased by 10.00% in the first year after the restriction onset compared with the year before and attenuated over time to 6.37% in the second year. The proportion of inpatient, emergency department, and physician's office visits remained stable over the time periods evaluated for all patients and those patients who experienced one or more exacerbations. Asthma treatment of patients who experienced one or more exacerbations also remained stable over the 4 years. Conclusion: The effect of COVID-19 public health measures on asthma exacerbation rates might have affected clinical trials being run during this period and should be considered in their analysis. Asthma clinical trials run under pandemic hygiene restrictions should consider lower exacerbation frequency in their study design, while treatment and healthcare visits seem unchanged.

Zinc Supplementation Induced Transcriptional Changes in Primary Human Retinal Pigment Epithelium: A Single-Cell RNA Sequencing Study to Understand Age-Related Macular Degeneration.

Zinc supplementation has been shown to be beneficial to slow the progression of age-related macular degeneration (AMD). However, the molecular mechanism underpinning this benefit is not well understood. This study used single-cell RNA sequencing to identify transcriptomic changes induced by zinc supplementation. Human primary retinal pigment epithelial (RPE) cells could mature for up to 19 weeks. After 1 or 18 weeks in culture, we supplemented the culture medium with 125 µM added zinc for one week. RPE cells developed high transepithelial electrical resistance, extensive, but variable pigmentation, and deposited sub-RPE material similar to the hallmark lesions of AMD. Unsupervised cluster analysis of the combined transcriptome of the cells isolated after 2, 9, and 19 weeks in culture showed considerable heterogeneity. Clustering based on 234 pre-selected RPE-specific genes divided the cells into two distinct clusters, we defined as more and less differentiated cells. The proportion of more differentiated cells increased with time in culture, but appreciable numbers of cells remained less differentiated even at 19 weeks. Pseudotemporal ordering identified 537 genes that could be implicated in the dynamics of RPE cell differentiation (FDR < 0.05). Zinc treatment resulted in the differential expression of 281 of these genes (FDR < 0.05). These genes were associated with several biological pathways with modulation of ID1/ID3 transcriptional regulation. Overall, zinc had a multitude of effects on the RPE transcriptome, including several genes involved in pigmentation, complement regulation, mineralization, and cholesterol metabolism processes associated with AMD.

Exercise and Acceptance and Commitment Therapy for Chronic Pain: A Case Series with One-Year Follow-Up.

INTRODUCTION: There is growing evidence to support Acceptance and Commitment Therapy (ACT) in the management of chronic pain. However, there is a need for further research evaluating ACT combined with physical exercise, and few studies have assessed the long-term impact of this type of intervention. This case series reports on the acceptability and impact of an ACT-based multidisciplinary pain management programme on a range of health outcomes in both the short and long-term. METHODS: Seventy-three participants completed an 8-week group-based, pain management programme. The programme combined weekly sessions of ACT with education and exercise classes. Self-report outcome measures were completed at baseline, post-intervention and at one-year follow-up. The measures assessed pain intensity and interference, psychological distress, self-efficacy, pain acceptance, values-based action, pain catastrophizing, fear avoidance and healthcare utilization. Pedometers were worn to objectively measure physical activity. Data were analyzed using linear mixed modelling. Ethical approval for this study was granted by the Mater Misericordiae University Hospital (MMUH) Institutional Review Board (Reference 1/378/1541). RESULTS: Eighty-six percent of respondents reported being satisfied with the intervention. Improvements were observed in most of the self-report outcomes post-intervention and many changes were maintained at one-year. There was also a significant increase in average daily step-count. CONCLUSION: A pain management programme combining ACT with exercise appears to be an acceptable treatment option for people with chronic pain. While improvements were observed in both the short and long-term, further fully powered RCTs with long-term follow-up are required to test the effectiveness of this type of intervention.