Diagnosis and Treatment of Pneumonia in Urgent Care Clinics: Opportunities for Improving Care.

Background: Community-acquired pneumonia is a well-studied condition; yet, in the urgent care setting, patient characteristics and adherence to guideline-recommended care are poorly described. Within Intermountain Health, a nonprofit integrated US health care system based in Utah, more patients present to urgent care clinics (UCCs) than emergency departments (EDs) for pneumonia care. Methods: We performed a retrospective cohort study 1 January 2019 through 31 December 2020 in 28 UCCs within Utah. We extracted electronic health record data for patients aged ≥12 years with ICD-10 pneumonia diagnoses entered by the bedside clinician, excluding patients with preceding pneumonia within 30 days or missing vital signs. We compared UCC patients with radiographic pneumonia (n = 4689), without radiographic pneumonia (n = 1053), without chest imaging (n = 1472), and matched controls with acute cough/bronchitis (n = 15 972). Additional outcomes were 30-day mortality and the proportion of patients with ED visits or hospital admission within 7 days after the index encounter. Results: UCC patients diagnosed with pneumonia and possible/likely radiographic pneumonia by radiologist report had a mean age of 40 years and 52% were female. Almost all patients with pneumonia (93%) were treated with antibiotics, including those without radiographic confirmation. Hospital admissions and ED visits within 7 days were more common in patients with radiographic pneumonia vs patients with "unlikely" radiographs (6% vs 2% and 10% vs 6%, respectively). Observed 30-day all-cause mortality was low (0.26%). Patients diagnosed without chest imaging presented similarly to matched patients with cough/acute bronchitis. Most patients admitted to the hospital the same day after the UCC visit (84%) had an interim ED encounter. Pneumonia severity scores (pneumonia severity index, electronic CURB-65, and shock index) overestimated patient need for hospitalization. Conclusions: Most UCC patients with pneumonia were successfully treated as outpatients. Opportunities to improve care include clinical decision support for diagnosing pneumonia with radiographic confirmation and development of pneumonia severity scores tailored to the UCC.

Prospectively Assessed Long-Term Outcomes of Patients with E-Cigarette- or Vaping-associated Lung Injury.

Rationale: E-cigarette- or vaping-associated lung injury (EVALI) was first identified in 2019. The long-term respiratory, cognitive, mood disorder, and vaping behavior outcomes of patients with EVALI remain unknown. Objectives: To determine the long-term respiratory, cognitive, mood disorder, and vaping behavior outcomes of patients with EVALI. Methods: We prospectively enrolled patients with EVALI from two health systems. We assessed outcomes at 1 year after onset of EVALI using validated instruments measuring cognitive function, depression, anxiety, post-traumatic stress, respiratory disability, coronavirus disease (COVID-19) infection, pulmonary function, and vaping behaviors. We used multivariable regression to identify risk factors of post-EVALI vaping behaviors and to identify whether admission to the intensive care unit (ICU) was associated with cognitive, respiratory, or mood symptoms. Results: Seventy-three patients completed 12-month follow-up. Most patients were male (66.7%), young (mean age, 31 ± 11 yr), and White (85%) and did not need admission to the ICU (59%). At 12 months, 39% (25 of 64) had cognitive impairment, whereas 48% (30 of 62) reported respiratory limitations. Mood disorders were common, with 59% (38 of 64) reporting anxiety and/or depression and 62% (39 of 63) having post-traumatic stress. Four (6.4%) of 64 reported a history of COVID-19 infection. Despite the history of EVALI, many people continued to vape. Only 38% (24 of 64) reported quitting all vaping and smoking behaviors. Younger age was associated with reduced vaping behavior after EVALI (odds ratio, 0.93; P = 0.02). ICU admission was not associated with cognitive impairment, dyspnea, or mood symptoms. Conclusions: Patients with EVALI, despite their youth, commonly have significant long-term respiratory disability; cognitive impairment; symptoms of depression, anxiety, post-traumatic stress; and persistent vaping.

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium.

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151-171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389-407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227-3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE-Bruch's membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE-BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD.