Nasopharyngeal angiotensin converting enzyme 2 (ACE2) expression as a risk-factor for SARS-CoV-2 transmission in concurrent hospital associated outbreaks.

BACKGROUND: Widespread human-to-human transmission of the severe acute respiratory syndrome coronavirus two (SARS-CoV-2) stems from a strong affinity for the cellular receptor angiotensin converting enzyme two (ACE2). We investigate the relationship between a patient's nasopharyngeal ACE2 transcription and secondary transmission within a series of concurrent hospital associated SARS-CoV-2 outbreaks in British Columbia, Canada. METHODS: Epidemiological case data from the outbreak investigations was merged with public health laboratory records and viral lineage calls, from whole genome sequencing, to reconstruct the concurrent outbreaks using infection tracing transmission network analysis. ACE2 transcription and RNA viral load were measured by quantitative real-time polymerase chain reaction. The transmission network was resolved to calculate the number of potential secondary cases. Bivariate and multivariable analyses using Poisson and Negative Binomial regression models was performed to estimate the association between ACE2 transcription the number of SARS-CoV-2 secondary cases. RESULTS: The infection tracing transmission network provided n = 76 potential transmission events across n = 103 cases. Bivariate comparisons found that on average ACE2 transcription did not differ between patients and healthcare workers (P = 0.86). High ACE2 transcription was observed in 98.6% of transmission events, either the primary or secondary case had above average ACE2. Multivariable analysis found that the association between ACE2 transcription (log2 fold-change) and the number of secondary transmission events differs between patients and healthcare workers. In health care workers Negative Binomial regression estimated that a one-unit change in ACE2 transcription decreases the number of secondary cases (ß = -0.132 (95%CI: -0.255 to -0.0181) adjusting for RNA viral load. Conversely, in patients a one-unit change in ACE2 transcription increases the number of secondary cases (ß = 0.187 (95% CI: 0.0101 to 0.370) adjusting for RNA viral load. Sensitivity analysis found no significant relationship between ACE2 and secondary transmission in health care workers and confirmed the positive association among patients. CONCLUSION: Our study suggests that ACE2 transcription has a positive association with SARS-CoV-2 secondary transmission in admitted inpatients, but not health care workers in concurrent hospital associated outbreaks, and it should be further investigated as a risk-factor for viral transmission.

Demographic and Clinical Correlates of the Cost of Potentially Preventable Hospital Encounters in a Community Health Center Cohort.

This study sought to describe the cost of hospital care for ambulatory care-sensitive conditions (ACSCs) and to identify independent predictors of high-cost hospital encounters related to an ACSC among an urban community health center cohort. The authors conducted a retrospective cohort study of individuals engaged in care in a large, multisite community health center in New Haven, Connecticut, with any Medicaid claims between June 1, 2018 and March 31, 2020. Prevention Quality Indicators of the Agency for Healthcare Research and Quality were used to identify ACSCs. The primary outcome was a high-cost episode of care for an ACSC (in the top quartile within a 7-day period). Multivariable logistic regression was used to identify independent predictors of high-cost episodes by ACSCs among sociodemographic and clinical variables as covariates. Among 8019 included individuals, a total of 751 episodes of hospital care involving ACSCs were identified. The median episode cost was $793, with the highest median cost of care related to heart failure ($4992), followed by diabetes ($1162), and chronic obstructive pulmonary disease ($1141). In adjusted analyses, male gender (P < 0.01), increasing age (P = 0.02), and ACSC type (P < 0.01) were associated with higher costs of care; race/ethnicity was not. Community health centers in urban settings seeking to reduce the cost of care of potentially preventable hospitalizations may target disease-/condition-specific groups, particularly individuals of increasing age with congestive heart failure and diabetes mellitus. These findings may inform return-on-investment calculations for care coordination and other enabling services programming.

Laboratory Exposures from an Unsuspected Case of Human Infection with Brucella canis.

We report a case of human infection with a Brucella canis isolate in an adult in Canada who was receiving a biologic immunomodulating medication. We detail subsequent investigations, which showed that 17 clinical microbiology staff had high-risk exposures to the isolate, 1 of whom had a positive result for B. canis.

Analysis of Care Coordination Needs for Families of Children with Special Health Care Needs.

OBJECTIVES: To identify the diverse services required by families of children with special health care needs (CSHCN) and identify the specific care coordination (CC) efforts associated with the most common types of observed diagnoses. Requested services were categorized into specific sectors, and CC efforts were quantified by observed diagnoses and defined sectors. METHODS: CC service data were extracted and analyzed from patient encounters over 4 years (2009-2013) in a department database. This included descriptive information about referrals and linkages to medical, dental, and behavioral health providers and to state, private, and community agencies. Diagnostic classifications and CC sectors were defined to enable categorization. RESULTS: A total of 2682 CSHCN records were reviewed. The majority (59%) required services/resources in 1 to 2 sectors, 24% required services/resources in 3 to 5 sectors, and 17% required services/resources in 6 or more sectors. Including informational service, the most frequently required sectors across the study population were education, financial, medical/dental, social connections, and advocacy. Children diagnosed with autism spectrum disorder had the highest needs across all sectors. CONCLUSION: Most CSHCN and their families use a substantial amount of CC time and effort to secure services from diverse sectors. High-quality and efficient CC requires an understanding of the specific needs of these CSHCN and their families and how to link them to a diverse array of services and resources.

Current Pediatric Emergency Department Innovative Programs to Improve the Care of Psychiatric Patients.

Emergency departments (EDs) across North America have become a safety net for patients seeking mental health (MH) services. The prevalence of families seeking treatment of children in MH crisis has become a national emergency. To address MH access and improve quality and efficient management of children with MH conditions, the authors describe ED projects targeting this vulnerable population. Five North American health care systems volunteered to feature projects that seek to reduce ED visits and/or improve the care of MH patients: Allina Health, Nationwide Children's Hospital, Children's Hospital of Eastern Ontario, Connecticut Children's Medical Center, and Rhode Island Hospital.

Phase I/II trial of 5-fluorouracil and a noncytotoxic dose level of suramin in patients with metastatic renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is recognized as a neoplasm resistant to chemotherapy. In vitro experiments demonstrated that suramin, at noncytotoxic doses, enhanced the activity of chemotherapy including 5-fluorouracil (5-FU) in xenograft models. PATIENTS AND METHODS: A phase I/II trial of noncytotoxic suramin in combination with weekly 5-FU in patients with metastatic RCC was conducted. The treatment consisted of intravenous (i.v.) suramin followed by a 500 mg/m2 i.v. bolus of 5-FU given 4.5 hours after starting suramin. In the phase I portion, a cohort of 6 patients received a suramin dose calculated to achieve a plasma level of 10-50 micromol/L. Therapy was administered once weekly for 6 doses, followed by 2 weeks off. This was followed by a phase II portion in which the primary goal was to determine the objective response rate. RESULTS: Twenty-three patients were enrolled in the study: 6 in the phase I portion and 17 in phase II. Seventy-eight percent of patients were men, the mean age was 58.8 years, 96% had previous nephrectomy, and 70% had received previous systemic therapy. Histologic subtype was clear cell in 91%. Dose-limiting toxicity was observed in 1 of 6 patients (grade 3 hypersensitivity related to suramin infusion). The suramin dosing nomogram used in phase I and II portions of the trial yielded the desired plasma level of 10-50 micromol/L from 4.5 hours to 48 hours after infusion in 94 of 115 treatments. No objective responses were noted, and the median time to treatment failure was 2.5 months. The major toxicities (all grades) were fatigue (83%), nausea/vomiting (78%), diarrhea (61%), and chills (61%). CONCLUSION: Suramin levels expected to reverse fibroblast growth factor-induced resistance can be achieved with the dosing regimen used in this study. The toxicity observed with suramin and 5-FU was acceptable. The combination does not have clinical activity in patients with metastatic RCC.