Increased mortality in hospital- compared to community-onset carbapenem-resistant enterobacterales infections.

BACKGROUND: The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI). METHODS: Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI. RESULTS: Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P < 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P < 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%-64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P < 0.001]. CONCLUSION: We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality.

Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales.

BACKGROUND: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

Opportunities for Integration in the Dual Medicare-Medicaid Population: North Carolina Landscape Analysis.

Background: NC Medicaid is amid a transformation to value-based care models. The transformation requires the consideration of models that may best serve the 1 in 5 NC Medicaid beneficiaries who are dually enrolled in Medicare. The lack of integration of Medicare and Medicaid administration, financing, and care may contribute to suboptimal health outcomes and care experiences. Integrating Medicare and Medicaid to improve care for dually enrolled individuals requires knowledge of the demographic, eligibility, and enrollment trends, as well as the medical needs of these individuals throughout North Carolina. Methods: We performed a cross-sectional analysis of 2019 NC Medicaid administrative enrollment data and 2015-2020 Medicare and Medicaid public use files. Results: Nearly half of North Carolina's full-benefit dual-eligible (FBDE) population was eligible for Medicare due to disability. About one-third of the FBDE population lost full Medicaid benefits at some point during 2019; of these, 65% were under age 65. Most FBDE beneficiaries were enrolled in Medicaid fee-for-service, with 3.5% enrolled in Community Alternatives Program (CAP) waivers, 2% in Medicaid waivers for beneficiaries with behavioral health or intellectual and developmental disabilities (BH/IDD) or traumatic brain injury (TBI), and 1% in the Program of All-Inclusive Care for the Elderly (PACE). Enrollment in Medicare Duals Special Needs Plans (D-SNPs) increased from 7.3% of the FBDE population in 2015 to 32.5% in 2021. Limitations: This descriptive, cross-sectional evaluation of North Carolina duals may not be generalizable to other time periods and contexts. Conclusion: Medicare-Medicaid integration presents an opportunity to improve the value of care for dual-eligible beneficiaries and aligns with the goals of NC Medicaid transformation. Integration strategies that leverage the current infrastructure may minimize disruption of services for beneficiaries and mitigate the impacts of unstable enrollment, particularly among working-age adults and disabled beneficiaries. The diversity within the dual-eligible populations requires a strategy designed to improve health equity across race, disability, eligibility, geography, and health care needs.

International Epidemiology of Carbapenemase-Producing Escherichia coli.

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-ß-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.

Linking Medicare-Medicaid Claims for Patient-Centered Outcomes Research Among Dual-Eligible Beneficiaries.

BACKGROUND: Evaluation of Medicare-Medicaid integration models' effects on patient-centered outcomes and costs requires multiple data sources and validated processes for linkage and reconciliation. OBJECTIVE: To describe the opportunities and limitations of linking state-specific Medicaid and Centers for Medicare & Medicaid Services administrative claims data to measure patient-centered outcomes for North Carolina dual-eligible beneficiaries. RESEARCH DESIGN: We developed systematic processes to (1) validate the beneficiary ID linkage using sex and date of birth in a beneficiary ID crosswalk, (2) verify dates of dual enrollment, and (3) reconcile Medicare-Medicaid claims data to support the development and use of patient-centered outcomes in linked data. PARTICIPANTS: North Carolina Medicaid beneficiaries with full Medicaid benefits and concurrent Medicare enrollment (FBDE) between 2014 and 2017. MEASURES: We identified need-based subgroups based on service use and eligibility program requirements. We calculated utilization and costs for Medicaid and Medicare, matched Medicaid claims to Medicare service categories where possible, and reported outcomes by the payer. Some services were covered only by Medicaid or Medicare, including Medicaid-only covered home and community-based services (HCBS). RESULTS: Of 498,030 potential dual enrollees, we verified the linkage and FBDE eligibility of 425,664 (85.5%) beneficiaries, including 281,174 adults enrolled in Medicaid and Medicare fee-for-service. The most common need-based subgroups were intensive behavioral health service users (26.2%) and HCBS users (10.8%) for adults under age 65, and HCBS users (20.6%) and nursing home residents (12.4%) for adults age 65 and over. Medicaid funded 42% and 49% of spending for adults under 65 and adults 65 and older, respectively. Adults under 65 had greater behavioral health service utilization but less skilled nursing facility, HCBS, and home health utilization compared with adults 65 and older. CONCLUSIONS: Linkage of Medicare-Medicaid data improves understanding of patient-centered outcomes among FBDE by combining Medicare-funded acute and ambulatory services with Medicaid-funded HCBS. Using linked Medicare-Medicaid data illustrates the diverse patient experience within FBDE beneficiaries, which is key to informing patient-centered outcomes, developing and evaluating integrated Medicare and Medicaid programs, and promoting health equity.

Evaluating Telehealth Uptake Among North Carolina Medicaid Beneficiaries With Musculoskeletal Conditions: Insights From the COVID-19 Pandemic.

BACKGROUND: The shift from in-person to virtual visits, known as telehealth (TH), during the COVID-19 pandemic was a significant change for North Carolina (NC) Medicaid beneficiaries seeking treatment for musculoskeletal (MSK) conditions, as remote care for these conditions was previously unavailable. We used this policy change to investigate factors associated with TH uptake and whether TH availability mitigated disparities in access to care or affected emergency department (ED) visits among these beneficiaries. RESEARCH DESIGN: Using 2019-2021 NC Medicaid claims, we identified beneficiaries receiving treatment for MSK conditions before COVID-19 (March 2019-February 2020) and analyzed uptake of newly available TH during COVID-19 (April 2020-March 2021). We used descriptive analysis and Poisson generalized estimating equations to quantify TH uptake, factors associated with TH uptake, and the association with ED visits during COVID-19. RESULTS: Black and Hispanic beneficiaries were less likely to use TH compared with White and non-Hispanic counterparts (10%, P <0.001 and 20%, P =0.03, respectively). Adults eligible for Tailored Plans, specialized NC Medicaid plans for those with significant behavioral health needs or intellectual/developmental disabilities, were less likely to use TH [adjusted risk ratio (ARR):0.83, 95% CI (0.78, 0.87)]; youth eligible for Tailored Plans were more likely to use TH [ARR:1.28, 95% CI (1.16, 1.42)]. Lower county-level internet access was associated with lower TH use [ARR: 0.85, 95% CI (0.82, 0.99)]. No statistical difference in ED utilization was observed between TH users and non-users. CONCLUSIONS: TH has the potential to deliver convenient care to beneficiaries with MSK conditions who can access it. Further research and policy changes should explore and address underlying factors driving disparities and improve equitable access to care for this population.

Virological and care outcomes of community ART distribution: Experience with the PODI+ model in Kinshasa, Democratic Republic of the Congo.

INTRODUCTION: Differentiated service delivery models for HIV treatment can minimize unnecessary burdens on health systems and promote efficient delivery of antiretroviral therapy (ART). Under the PODI+ (poste de distribution communautaire) model, ART multi-month dispensation (MMD) was provided by lay workers (peers) in communities. We compared outcomes among clinically stable adults living with HIV receiving MMD via PODI+ or health facility (HF). METHODS: Clients receiving MMD at nine HFs and two PODI+ sites in Kinshasa were followed prospectively for one year (2018-2020). Medication possession ratio (MPR) was measured as proportion of total days with medication during the study through record abstraction at 3-month intervals. Viral load was assessed at enrollment and 12 months. We compared MPR and viral load suppression by arm and examined associations and potential confounders using unadjusted and adjusted odds ratios (AOR). Likert-style client satisfaction was collected during 12-month interviews and described by arm. RESULTS: Odds of maintaining viral load suppression at 12 months for PODI+ participants were two times that for HF participants. In adjusted models, PODI+ participants had 1.89 times the odds of being suppressed at 12 months compared to HF participants (95% CI: 1.10, 3.27). No significant differences in MPR were found between groups (OR: 0.86, 0.38-1.99). Older participants had significantly higher odds of MPR (AOR: 1.02, 95% CI: 1.01, 1.03) and viral suppression (AOR: 1.03, 95% CI: 1.00, 1.07). Satisfaction with services was ≥87% overall, but PODI+ participants rated time spent at site, provider attributes and other care aspects more favorably. CONCLUSIONS: Participants receiving MMD via peer-run community distribution points had similar MPR, but better virological outcomes and greater satisfaction with care than clinically similar participants receiving MMD through facilities. PODI+ could be a useful model for expansion to serve larger clinic populations from overburdened health facilities, particularly as policy shifts towards more inclusive MMD eligibility requirements.

Telehealth Utilization Among Adult Medicaid Beneficiaries in North Carolina with Behavioral Health Conditions During the COVID-19 Pandemic.

OBJECTIVE: We examined factors associated with telehealth utilization during COVID-19 among adult Medicaid beneficiaries with behavioral health conditions. DATA SOURCES AND STUDY SETTING: NC Medicaid 2019-2021 beneficiary and claims data. STUDY DESIGN: This retrospective cohort study examined and compared behavioral health service use pre-COVID-19 (03/01/2019 to 02/28/2020) and during COVID-19 (04/01/2020 to 03/31/2021). Telehealth users included those with at least one behavioral health visit via telehealth during COVID-19. Descriptive statistics were calculated for overall sample and by telehealth status. Multilevel modified Poisson generalized estimating equation examined associations between telehealth use and patient- and area-level characteristics. DATA COLLECTION/EXTRACTION METHODS: We identified individuals ages ≥ 21-64, diagnosed with a behavioral health condition, and had at least one behavioral-health specific visit before COVID-19. PRINCIPAL FINDINGS: Almost two-thirds of the cohort received behavioral health services during COVID-19, with half of these beneficiaries using telehealth. Non-telehealth users had steeper declines in service use from pre- to during COVID-19 compared to telehealth users. Beneficiaries identifying as Black, multiracial or other were significantly less likely to use telehealth (ARR = 0.86; 95% CI: (0.83, 0.89)); (ARR = 0.92; 95% CI: (0.87, 0.96)) compared to White beneficiaries. Those eligible for Medicaid through the blind/disabled programs and who qualified for a state-specific specialized behavioral health plan were more likely to use telehealth (17% and 20%, respectively). CONCLUSIONS: During the pandemic, telehealth facilitated continuity of care for beneficiaries with behavioral health conditions. Future research should aim to investigate how to reduce the digital divide and ensure equitable access to telehealth.

Health Care Use and Spending Among Need-Based Subgroups of Medicare Beneficiaries With Full Medicaid Benefits.

Importance: Beneficiaries dual eligible for Medicare and Medicaid account for a disproportionate share of expenditures due to their complex care needs. Lack of coordination between payment programs creates misaligned incentives, resulting in higher costs, fragmented care, and poor health outcomes. Objective: To inform the design of integrated programs by describing the health care use and spending for need-based subgroups in North Carolina's full benefit, dual-eligible population. Design, Setting, and Participants: This cross-sectional study using Medicare and North Carolina Medicaid 100% claims data (2014-2017) linked at the individual level included Medicare beneficiaries with full North Carolina Medicaid benefits. Data were analyzed between 2021 and 2022. Exposure: Need-based subgroups: community well, home- and community-based services (HCBS) users, nursing home (NH) residents, and intensive behavioral health (BH) users. Measures: Medicare and Medicaid utilization and spending per person-year (PPY). Results: The cohort (n = 333 240) comprised subgroups of community well (64.1%, n = 213 667), HCBS users (15.0%, n = 50 095), BH users (15.2%, n = 50 509), and NH residents (7.5%, n = 24 927). Overall, 61.1% reported female sex. The most common racial identities included Asian (1.8%), Black (36.1%), and White (58.7%). Combined spending for Medicare and Medicaid was $26 874 PPY, and the funding of care was split evenly between Medicare and Medicaid. Among need-based subgroups, combined spending was lowest among community well at $19 734 PPY with the lowest portion (38.5%) of spending contributed by Medicaid ($7605). Among NH residents, overall spending ($68 359) was highest, and the highest portion of spending contributed by Medicaid (70.1%). Key components of spending among HCBS users' combined total of $40 069 PPY were clinician services on carrier claims ($14 523) and outpatient facility services ($9012). Conclusions and relevance: Federal and state policy makers and administrators are developing strategies to integrate Medicare- and Medicaid-funded health care services to provide better care to the people enrolled in both programs. Substantial use of both Medicare- and Medicaid-funded services was found across all need-based subgroups, and the services contributing a high proportion of the total spending differed across subgroups. The diversity of health care use suggests a tailored approach to integration strategies with comprehensive set benefits that comprises Medicare and Medicaid services, including long-term services and supports, BH, palliative care, and social services.

Metabolite, protein, and tissue dysfunction associated with COVID-19 disease severity.

Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19.

The fushi tarazu zebra element is not required for Drosophila viability or fertility.

Expression of genes in precisely controlled spatiotemporal patterns is essential for embryonic development. Much of our understanding of mechanisms regulating gene expression comes from the study of cis-regulatory elements (CREs) that direct expression of reporter genes in transgenic organisms. This reporter-transgene approach identifies genomic regions sufficient to drive expression but fails to provide information about quantitative and qualitative contributions to endogenous expression, although such conclusions are often inferred. Here we evaluated the endogenous function of a classic Drosophila CRE, the fushi tarazu (ftz) zebra element. ftz is a pair-rule segmentation gene expressed in seven stripes during embryogenesis, necessary for formation of alternate body segments. Reporter transgenes identified the promoter-proximal zebra element as a major driver of the seven ftz stripes. We generated a precise genomic deletion of the zebra element (ftzΔZ) to assess its role in the context of native chromatin and neighboring CREs, expecting large decreases in ftz seven-stripe expression. However, significant reduction in expression was found for only one stripe, ftz stripe 4, expressed at ∼25% of wild type levels in ftzΔZ homozygotes. Defects in corresponding regions of ftzΔZ mutants suggest this level of expression borders the threshold required to promote morphological segmentation. Further, we established true-breeding lines of homozygous ftzΔZ flies, demonstrating that the body segments missing in the mutants are not required for viability or fertility. These results highlight the different types of conclusions drawn from different experimental designs and emphasize the importance of examining transcriptional regulatory mechanisms in the context of the native genomic environment.