Derivation and external validation of a prediction model for pneumococcal urinary antigen test positivity in patients with community-acquired pneumonia.

Objective: Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity. Methods: Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity. Results: Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27-11.46), severe CAP on admission (OR 1.76, 95% CI 1.56-1.98), substance abuse (OR 1.57, 95% CI 1.27-1.93), smoking (OR 1.23, 95% CI 1.09-1.39), and hyponatremia (OR 1.35, 95% CI 1.17-1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52-0.82), congestive heart failure (OR 0.72, 95% CI 0.63-0.83), obesity (OR 0.71, 95% CI 0.60-0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45-0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests. Conclusion: Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship.

Protection Conferred by Delta and BA.1/BA.2 Infection Against BA.4/BA.5 Infection and Hospitalization: A Retrospective Cohort Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. METHODS: This retrospective cohort study included individuals tested for coronavirus disease 2019 by polymerase chain reaction during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection to the hospitalization rate for initially positive patients divided by the ratio for initially negative patients, stratified by age and adjusted for age, sex, comorbid conditions, and vaccination using logistic regression. RESULTS: A total of 20 987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (adjusted PF, 11.9% [95% confidence interval, .8%-21.8%]); P = .04) and minimal protection against hospitalization (10.7% [4.9%-21.7%]; P = .003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95% confidence interval, 36.2%-54.1%; P < .001) protection against BA.4/BA.5 reinfection and 18.8% (10.3%-28.3%; (P < .001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. CONCLUSIONS: Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization and none against infection.

Protection Against the Omicron Variant Offered by Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study.

BACKGROUND: Previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant. METHODS: This retrospective cohort study included 635 341 patients tested for SARS-CoV-2 via polymerase chain reaction from 9 March 2020 to 1 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021-1 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization. RESULTS: Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0-22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4-74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1-36.7), whereas full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8-63.1). CONCLUSIONS: Previous infection offered less protection against Omicron than was observed in past waves. Immunity against future waves will likely depend on the degree of similarity between variants.

Urinary Antigen Testing for Respiratory Infections: Current Perspectives on Utility and Limitations.

Pneumonia is a leading cause of hospitalization and death due to infection worldwide. Streptococcus pneumoniae and Legionella pneumophila remain among the most commonly identified bacterial pathogens. Unfortunately, more than half of all pneumonia cases today lack an etiologic diagnosis due to limitations in traditional microbiological methods like blood and sputum cultures, which are affected by poor sample collection, prior antibiotic administration, and delayed processing. Urinary antigen tests (UATs) for S. pneumoniae and L. pneumophila have emerged as powerful tools for improving the diagnosis of bacterial respiratory infections, enabling physicians to administer early directed therapy and improve antimicrobial stewardship. UATs are simple, rapid, and non-invasive diagnostic tests with high specificity (>90%) and moderate sensitivity (<80%). The potential impact of urinary antigen testing is especially significant for respiratory infections caused by Legionella. While all recommended community-acquired pneumonia (CAP) therapies are adequate for treating pneumococcal pneumonia, only certain antibiotics are effective against Legionella. Delayed therapy for Legionella is associated with worse clinical outcomes, which underscores the importance of rapid diagnostic methods like UATs. Despite their potential impact, current American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines argue against the routine use of urinary antigen testing for S. pneumoniae and L. pneumophila, except in patients with severe CAP and those with epidemiological risk factors for Legionella. Further research is necessary to evaluate the impact of early targeted treatment due to positive UAT results, as well as optimal strategies for UAT utilization. The purpose of this review is to summarize the UATs available for bacterial respiratory infections, describe current guidelines on their usage, and assess their impact on clinical outcomes and targeted therapy.

Duration of Severe Acute Respiratory Syndrome Coronavirus 2 Natural Immunity and Protection Against the Delta Variant: A Retrospective Cohort Study.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be highly protective against reinfection and symptomatic disease. However, effectiveness against the Delta variant and duration of natural immunity remain unknown. METHODS: This retrospective cohort study included 325 157 patients tested for SARS-CoV-2 via polymerase chain reaction (PCR) from 9 March 2020 to 31 December 2020 (Delta variant analysis) and 152 656 patients tested from 9 March 2020 to 30 August 2020 (long-term effectiveness analysis) with subsequent testing through 9 September 2021. The primary outcome was reinfection, defined as a positive PCR test >90 days after the initial positive test. RESULTS: Among 325 157 patients tested before 31 December 2020, 50 327 (15.5%) tested positive. After 1 July 2021 (Delta dominant period), 40 (0.08%) initially positive and 1494 (0.5%) initially negative patients tested positive. Protection of prior infection against reinfection with Delta was 85.4% (95% confidence interval [CI], 80.0-89.3). For the long-term effectiveness analysis, among 152 656 patients tested before 30 August 2020, 11 186 (7.3%) tested positive. After at least 90 days, 81 (0.7%) initially positive and 7167 (5.1%) initially negative patients tested positive. Overall protection of previous infection was 85.7% (95% CI, 82.2-88.5) and lasted up to 13 months. Patients aged >65 years had slightly lower protection. CONCLUSIONS: SARS-CoV-2 infection is highly protective against reinfection with Delta. Immunity from prior infection lasts at least 13 months. Countries facing vaccine shortages should consider delaying vaccinations for previously infected patients to increase access.

Derivation and Validation of a Risk Factor Model to Identify Medical Inpatients at Risk for Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis is recommended for hospitalized medical patients at high risk for VTE. Multiple risk assessment models exist, but few have been compared in large datasets. METHODS: We constructed a derivation cohort using 6 years of data from 12 hospitals to identify risk factors associated with developing VTE within 14 days of admission. VTE was identified using a complex algorithm combining administrative codes and clinical data. We developed a multivariable prediction model and applied it to three validation cohorts: a temporal cohort, including two additional years, a cross-validation, in which we refit the model excluding one hospital each time, applying the refitted model to the holdout hospital, and an external cohort. Performance was evaluated using the C-statistic. RESULTS: The derivation cohort included 155,026 patients with a 14-day VTE rate of 0.68%. The final multivariable model contained 13 patient risk factors. The model had an optimism corrected C-statistic of 0.79 and good calibration. The temporal validation cohort included 53,210 patients, with a VTE rate of 0.64%; the external cohort had 23,413 patients and a rate of 0.49%. Based on the C-statistic, the Cleveland Clinic Model (CCM) outperformed both the Padua (0.76 vs. 0.72, p = 0.002) and IMPROVE (0.68, p < 0.001) models in the temporal cohort. C-statistics for the CCM at individual hospitals ranged from 0.68 to 0.78. In the external cohort, the CCM C-statistic was similar to Padua (0.70 vs. 0.66, p = 0.17) and outperformed IMPROVE (0.59, p < 0.001). CONCLUSION: A new VTE risk assessment model outperformed recommended models.

The diversity of lobula plate tangential cells (LPTCs) in the Drosophila motion vision system.

To navigate through the environment, animals rely on visual feedback to control their movements relative to their surroundings. In dipteran flies, visual feedback is provided by the wide-field motion-sensitive neurons in the visual system called lobula plate tangential cells (LPTCs). Understanding the role of LPTCs in fly behaviors can address many fundamental questions on how sensory circuits guide behaviors. The blowfly was estimated to have ~ 60 LPTCs, but only a few have been identified in Drosophila. We conducted a Gal4 driver screen and identified five LPTC subtypes in Drosophila, based on their morphological characteristics: LPTCs have large arborizations in the lobula plate and project to the central brain. We compared their morphologies to the blowfly LPTCs and named them after the most similar blowfly cells: CH, H1, H2, FD1 and FD3, and V1. We further characterized their pre- and post-synaptic organizations, as well as their neurotransmitter profiles. These anatomical features largely agree with the anatomy and function of their likely blowfly counterparts. Nevertheless, several anatomical details indicate the Drosophila LPTCs may have more complex functions. Our characterization of these five LPTCs in Drosophila will facilitate further functional studies to understand their roles in the visual circuits that instruct fly behaviors.