Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Clinically significant mutations in HIV-infected patients with lung adenocarcinoma.

BACKGROUND: Lung cancer is a major cause of death in HIV-infected (HIV+) persons. In this study, we compared the prevalence of tumour EGFR and KRAS mutations in a cohort of lung adenocarcinoma patients by HIV status. METHODS: We collected data from 55 HIV+ patients with lung adenocarcinoma matched to 136 uninfected comparators. We compared the prevalence of EGFR and KRAS mutations by HIV status. We then compared survival by HIV status and by cancer mutation status among HIV+ subjects. RESULTS: Presence of KRAS and EGFR genetic alterations did not vary by HIV status (all P>0.1). There was no difference in overall survival by HIV status or by mutation status among HIV+ subjects. CONCLUSIONS: We found no major differences in the prevalence of EGFR or KRAS lung adenocarcinoma mutations by HIV status, suggesting that mutational testing should be conducted similarly regardless of the HIV status.

Separating the rash from the chaff: novel clinical decision support deployed during the mpox outbreak.

A clinical decision support system, EvalMpox, was developed to apply person under investigation (PUI) criteria for patients presenting with rash and to recommend testing for PUIs. Of 668 patients evaluated, an EvalMpox recommendation for testing had a positive predictive value of 35% and a negative predictive value of 99% for a positive mpox test.

Development and implementation of a clinical decision support system tool for the evaluation of suspected monkeypox infection.

Monkeypox virus was historically rare outside of West and Central Africa until the current 2022 global outbreak, which has required clinicians to be alert to identify individuals with possible monkeypox, institute isolation, and take appropriate next steps in evaluation and management. Clinical decision support systems (CDSS), which have been shown to improve adherence to clinical guidelines, can support frontline clinicians in applying the most current evaluation and management guidance in the setting of an emerging infectious disease outbreak when those guidelines are evolving over time. Here, we describe the rapid development and implementation of a CDSS tool embedded in the electronic health record to guide frontline clinicians in the diagnostic evaluation of monkeypox infection and triage patients with potential monkeypox infection to individualized infectious disease physician review. We also present data on the initial performance of this tool in a large integrated healthcare system.

Decreased Overall Survival in HIV-associated Non-small-cell Lung Cancer.

INTRODUCTION: This study aimed to compare demographics, disease characteristics, and outcomes of patients with HIV-infection with non-small-cell lung cancer (NSCLC) with the general NSCLC population. PATIENTS AND METHODS: A retrospective cohort study was used to compare the HIV-infected and -uninfected groups. Medical records of all patients who were HIV-positive diagnosed with NSCLC between 2000 and 2016 at Yale New Haven Hospital (New Haven, CT) were reviewed and compared with the general Yale NSCLC population regarding demographics, NSCLC characteristics, treatment, and survival. Log-rank tests and Kaplan-Meier curves were used to analyze survival differences. Unadjusted and adjusted Cox proportional hazard models were used to assess predictors of survival. RESULTS: Thirty-five patients with HIV-NSCLC and 5187 general patients with NSCLC were identified. The median age at cancer diagnosis was 54 years (interquartile range [IQR], 49-59 years) for patients with HIV-NSCLC versus 68 years (IQR, 61-76 years) for patients with NSCLC (P < .001). Both groups had high rates of tobacco use. At the time of NSCLC diagnosis, 80% of patients with HIV-NSCLC were on antiretroviral therapy, 60% had an HIV-1 RNA < 400 copies/mL, and their median CD4 was 407 cells/µL (IQR, 218-592 cells/µL). Histology, cancer stage, and first-line cancer treatment regimens were not significantly different between groups. The overall median survival was 12.4 months (95% confidence interval [CI], 7.2-20.4 months) for patients with HIV-NSCLC versus 22.8 months (95% CI, 21.2-24.1 months) for general patients with NSCLC. Patients with HIV-NSCLC had decreased survival at 2 years (P = .028) and 3 years (P = .014) compared with general patients with NSCLC. HIV status was an independent risk factor for poorer outcomes when controlling for other factors (hazard ratio, 1.8; 95% CI, 1.24-2.62). CONCLUSION: Despite similar histology, stage, and treatment between groups, patients with HIV had worse outcomes for NSCLC.

Genomic Drivers of Multidrug-Resistant Shigella Affecting Vulnerable Patient Populations in the United States and Abroad.

Multidrug-resistant (MDR) Shigella infections have been identified globally among men who have sex with men (MSM). The highly drug-resistant phenotype often confounds initial antimicrobial therapy, placing patients at risk for adverse outcomes, the development of more drug-resistant strains, and additional treatment failures. New macrolide-resistant Shigella strains complicate treatment further as azithromycin is a next-in-line antibiotic for MDR strains, and an antibiotic-strain combination confounded by gaps in validated clinical breakpoints for clinical laboratories to interpret macrolide resistance in Shigella We present the first high-resolution genomic analyses of 2,097 U.S. Shigella isolates, including those from MDR outbreaks. A sentinel shigellosis case in an MSM patient revealed a strain carrying 12 plasmids, of which two carried known resistance genes, the pKSR100-related plasmid pMHMC-004 and spA-related plasmid pMHMC-012. Genomic-epidemiologic analyses of isolates revealed high carriage rates of pMHMC-004 predominantly in U.S. isolates from men and not in other demographic groups. Isolates genetically related to the sentinel case further harbored elevated numbers of unique replicons, showing the receptivity of this Shigella lineage to plasmid acquisition. Findings from integrated genomic-epidemiologic analyses were leveraged to direct targeted clinical actions to improve rapid diagnosis and patient care and for public health efforts to further reduce spread.IMPORTANCE Multidrug-resistant Shigella isolates with resistance to macrolides are an emerging public health threat. We define a plasmid/pathogen complex behind infections seen in the United States and globally in vulnerable patient populations and identify multiple outbreaks in the United States and evidence of intercontinental transmission. Using new tools and sequence information, we experimentally identify the drivers of antibiotic resistance that complicate patient treatment to facilitate improvements to clinical microbiologic testing for their detection. We illustrate the use of these methods to support multiagency efforts to combat multidrug-resistant Shigella using publicly available tools, existing genomic data, and resources in clinical microbiology and public health laboratories to inform credible actions to reduce spread.

Preventing Infectious Complications of Immunomodulation in COVID-19 in Foreign-Born Patients.

Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.

Superficial Cutaneous Zygomycosis Presenting as Resistant Intertrigo: A Case Report.

Zygomycosis is an angioinvasive fungal infection with a high mortality rate. Cutaneous zygomycosis is the second most common form of the disease, typically characterized by necrotic eschars in an immunocompromised host. We report an unusual case of superficial intertrigo resistant to conventional therapies caused by Mucor circinelloides in a patient with HIV and diabetes.