@article {1451, title = {Biomarker Detection and Validation for Corneal Involvement in Patients With Acute Infectious Conjunctivitis.}, journal = {JAMA Ophthalmol}, year = {2024}, month = {2024 Aug 15}, abstract = {

IMPORTANCE: Infectious conjunctivitis can lead to corneal involvement and result in ocular morbidity. The identification of biomarkers associated with corneal involvement has the potential to improve patient care.

OBJECTIVE: To identify biomarkers in patients with acute infectious conjunctivitis.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study took place from December 2016 to March 2024. Analyses were performed in 3 phases. First, logistic regression and machine learning algorithms were used to predict the probability of demonstrating corneal involvement in patients with presumed infectious conjunctivitis. Second, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to confirm the most important biomarker gene identified by the algorithm. Third, the biomarker gene was validated in prospectively collected conjunctival samples of adult patients from 3 outpatient centers in Thailand and 1 in India. Patients with signs and symptoms of infectious conjunctivitis and onset within less than 14 days were eligible. Exclusion criteria were the inability to consent, presumed toxicity, or allergic conjunctivitis.

EXPOSURES: Acute infectious conjunctivitis.

MAIN OUTCOMES AND MEASURES: The identification and validation of ocular surface gene expression associated with corneal findings on slitlamp examination.

RESULTS: Thirteen genes exhibited a 1.5-log2 fold change in expression in patients with corneal involvement compared to patients without corneal involvement. Using the 13 genes to train and cross validate, logistic regression produced the highest mean area under the receiver operating characteristic curve (AUROC; 0.85; 95\% CI, 0.84-0.86) for corneal involvement. The removal of apolipoprotein E (APOE) from the gene ensemble led to a decline in predictive performance of the logistic regression classifier (from mean AUROC 0.85 [95\% CI, 0.84-0.86] to 0.74 [95\% CI, 0.73-0.75]; adjusted P = .001 [Tukey test]). Orthogonal testing of APOE expression level with RT-qPCR showed that APOE expression was higher in patients with corneal involvement compared to patients without (median [IQR], 0.23 [0.04-0.47] vs 0.04 [0.02-0.06]; P = .004 [Mann-Whitney U test]). Using a Youden index of 0.23 Δ threshold cycle, APOE had a sensitivity of 56\% (95\% CI, 33-77) and a specificity of 88\% (95\% CI, 79-93) in 106 samples with conjunctivitis at Aravind, India (P < .001 [Fisher exact test]). When applied to a different patient population in Thailand, the same criteria could discriminate between disease states (58 samples; sensitivity, 47\%; 95\% CI, 30-64 and specificity, 93\%; 95\% CI, 77-99; P = .001 [Fisher exact test]).

CONCLUSIONS AND RELEVANCE: The results from this study suggest that the host conjunctival immune response can be meaningfully interrogated to identify biomarkers for ocular surface diseases.

}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2024.2891}, author = {Seitzman, Gerami D and Prajna, Lalitha and Prajna, N Venkatesh and Sansanayudh, Wiwan and Satitpitakul, Vannarut and Laovirojjanakul, Wipada and Chen, Cindi and Zhong, Lina and Ouimette, Kevin and Redd, Travis and Deiner, Michael C and Porco, Travis C and McLeod, Stephen D and Lietman, Thomas M and Hinterwirth, Armin and Doan, Thuy} } @article {851, title = {Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial.}, journal = {JAMA}, year = {2021}, month = {2021 Jul 16}, abstract = {

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2.

Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14.

Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization.

Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92).

Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21.

Results: Among 263 participants who were randomized (median age, 43 years; 174 [66\%] women; 57\% non-Hispanic White and 29\% Latinx/Hispanic), 76\% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50\%; placebo: 50\%; prevalence difference, 0\%; 95\% CI, -14\% to 15\%; P \> .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4\%; 95\% CI, -1\% to 9\%; P = .16).

Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection.

Trial Registration: ClinicalTrials.gov Identifier: NCT04332107.

}, issn = {1538-3598}, doi = {10.1001/jama.2021.11517}, author = {Oldenburg, Catherine E and Pinsky, Benjamin A and Brogdon, Jessica and Chen, Cindi and Ruder, Kevin and Zhong, Lina and Nyatigo, Fanice and Cook, Catherine A and Hinterwirth, Armin and Lebas, Elodie and Redd, Travis and Porco, Travis C and Lietman, Thomas M and Arnold, Benjamin F and Doan, Thuy} }