Increased Vaccine Uptake Among Eligible Patients at a Veterans Affairs Hospital Through an Inpatient COVID-19 Vaccination Program, Atlanta, Georgia, 2021.

OBJECTIVE: Inpatient vaccination is an opportunity to increase vaccine uptake among patients at high risk for severe COVID-19 illness. We designed and implemented a hospital-based COVID-19 vaccination program with the aim of increasing documentation of vaccine eligibility and COVID-19 vaccination to eligible inpatients before discharge. METHODS: We integrated a templated note into the electronic medical records and trained health care personnel to screen inpatients and document COVID-19 vaccine eligibility at the Atlanta Veterans Affairs Medical Center. Vaccination staff deployed to inpatient wards administered the vaccine to eligible and consenting patients at the bedside. We calculated the number of inpatients whose vaccine eligibility was assessed and documented during a 4-week period after health care personnel were trained. We used the Wald χ2 test to compare the proportion of eligible patients who were vaccinated before discharge 4 weeks before (March 29-April 23, 2021) and 4 weeks after (May 3-28, 2021) the training period. RESULTS: During the 4 weeks before the training period, COVID-19 vaccine eligibility was not routinely assessed and documented. Of 793 inpatients discharged during the 4 weeks after the training period, 470 (59%) had COVID-19 vaccine eligibility documented. Of 86 patients who were eligible for vaccination, 61 (71%) received COVID-19 vaccination before discharge. COVID-19 vaccination rates during hospitalization increased significantly from 16 of 769 inpatients (2%) during the 4 weeks before training to 61 of 793 inpatients (8%) during the 4 weeks after training (P < .001). CONCLUSION: An inpatient vaccination program that integrated COVID-19 vaccination into discharge planning increased vaccine screening and uptake. Future studies are needed to identify barriers to vaccination and strategies to increase vaccine uptake among those who are hesitant.

Evaluation of a Virtual Training to Enhance Public Health Capacity for COVID-19 Infection Prevention and Control in Nursing Homes.

CONTEXT: Between April 2020 and May 2021, the Centers for Disease Control and Prevention (CDC) awarded more than $40 billion to health departments nationwide for COVID-19 prevention and response activities. One of the identified priorities for this investment was improving infection prevention and control (IPC) in nursing homes. PROGRAM: CDC developed a virtual course to train new and less experienced public health staff in core healthcare IPC principles and in the application of CDC COVID-19 healthcare IPC guidance for nursing homes. IMPLEMENTATION: From October 2020 to August 2021, the CDC led training sessions for 12 cohorts of public health staff using pretraining reading materials, case-based scenarios, didactic presentations, peer-learning opportunities, and subject matter expert-led discussions. Multiple electronic assessments were distributed to learners over time to measure changes in self-reported knowledge and confidence and to collect feedback on the course. Participating public health programs were also assessed to measure overall course impact. EVALUATION: Among 182 enrolled learners, 94% completed the training. Most learners were infection preventionists (42%) or epidemiologists (38%), had less than 1 year of experience in their health department role (75%), and had less than 1 year of subject matter experience (54%). After training, learners reported increased knowledge and confidence in applying the CDC COVID-19 healthcare IPC guidance for nursing homes (≥81%) with the greatest increase in performing COVID-19 IPC consultations and assessments (87%). The majority of participating programs agreed that the course provided an overall benefit (88%) and reduced training burden (72%). DISCUSSION: The CDC's virtual course was effective in increasing public health capacity for COVID-19 healthcare IPC in nursing homes and provides a possible model to increase IPC capacity for other infectious diseases and other healthcare settings. Future virtual healthcare IPC courses could be enhanced by tailoring materials to health department needs, reinforcing training through applied learning experiences, and supporting mechanisms to retain trained staff.

Molecular surveillance for large outbreaks of tuberculosis in the United States, 2014-2018.

OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity.

Investigation of Bacterial Infections Among Patients Treated With Umbilical Cord Blood-Derived Products Marketed as Stem Cell Therapies.

Importance: The number of clinics marketing stem cell products for joint diseases, chronic pain, and most recently, COVID-19, has increased despite warnings from the US Food and Drug Administration that stem cell products for these and other indications have not been proven safe or effective. Objective: To examine bacterial infections in 20 patients who received umbilical cord blood-derived products marketed as stem cell treatment. Design, Setting, and Participants: This case series is a national public health investigation including case-finding, medical record review and abstraction, and laboratory investigation, including sterility testing of products and whole-genome sequencing of patient and product isolates. Participants included patients who developed bacterial infections following administration of umbilical cord blood-derived products marketed as stem cell treatment during August 2017 to September 2018. Data analysis was performed from March 2019 to September 2021. Exposures: Umbilical cord blood-derived products marketed as stem cell treatment. Main Outcomes and Measures: Data were collected on patient infections and exposures. The Centers for Disease Control and Prevention performed sterility testing on undistributed and distributed vials of product marketed as stem cell treatment and performed whole-genome sequencing to compare patient and product bacterial isolates. Results: Culture-confirmed bacterial infections were identified in 20 patients (median [range] age, 63 [2-89] years; 13 male patients [65%]) from 8 US states who sought stem cell treatment for conditions including pain, osteoarthritis, rheumatoid arthritis, and injury; all but 1 required hospitalization. The most frequently isolated bacteria from patients with infections were common enteric species, including Escherichia coli (14 patients) and Enterobacter cloacae (7 patients). Of unopened, undistributed products sampled for testing, 65% (22 of 34 vials) were contaminated with at least 1 of 16 bacterial species, mostly enteric. A patient isolate from Arizona matched isolates obtained from products administered to patients in Florida, and patient isolates from Texas matched undistributed product sent from the company in California. Conclusions and Relevance: Unapproved stem cell products can expose patients to serious risks without proven benefit. Sequencing results suggest a common source of extensive contamination, likely occurring during the processing of cord blood into product. Patients and health care practitioners who are considering the use of unapproved products marketed as stem cell treatment should be aware of their unproven benefits and potential risks, including serious infections.

Tuberculosis Genotype Clusters and Transmission in the U.S., 2009-2018.

INTRODUCTION: In the U.S., universal genotyping of culture-confirmed tuberculosis cases facilitates cluster detection. Early recognition of the small clusters more likely to become outbreaks can help prioritize public health resources for immediate interventions. METHODS: This study used national surveillance data reported during 2009-2018 to describe incident clusters (≥3 tuberculosis cases with matching genotypes not previously reported in the same county); data were analyzed during 2020. Cox proportional hazards regression models were used to examine the patient characteristics associated with clusters doubling in size to ≥6 cases. RESULTS: During 2009-2018, a total of 1,516 incident clusters (comprising 6,577 cases) occurred in 47 U.S. states; 231 clusters had ≥6 cases. Clusters of ≥6 cases disproportionately included patients who used substances, who had recently experienced homelessness, who were incarcerated, who were U.S. born, or who self-identified as being of American Indian or Alaska Native race or of Black race. A median of 54 months elapsed between the first and the third cases in clusters that remained at 3-5 cases compared with a median of 9.5 months in clusters that grew to ≥6 cases. The longer time between the first and third cases and the presence of ≥1 patient aged ≥65 years among the first 3 cases predicted a lower hazard for accumulating ≥6 cases. CONCLUSIONS: Clusters accumulating ≥3 cases within a year should be prioritized for intervention. Effective response strategies should include plans for targeted outreach to U.S.-born individuals, incarcerated people, those experiencing homelessness, people using substances, and individuals self-identifying as being of American Indian or Alaska Native race or of Black race.

MYCN-Amplified Neuroblastoma Is Addicted to Iron and Vulnerable to Inhibition of the System Xc-/Glutathione Axis.

MYCN is amplified in 20% to 25% of neuroblastoma, and MYCN-amplified neuroblastoma contributes to a large percent of pediatric cancer-related deaths. Therapy improvements for this subtype of cancer are a high priority. Here we uncover a MYCN-dependent therapeutic vulnerability in neuroblastoma. Namely, amplified MYCN rewires the cell through expression of key receptors, ultimately enhancing iron influx through increased expression of the iron import transferrin receptor 1. Accumulating iron causes reactive oxygen species (ROS) production, and MYCN-amplified neuroblastomas show enhanced reliance on the system Xc- cystine/glutamate antiporter for ROS detoxification through increased transcription of this receptor. This dependence creates a marked vulnerability to targeting the system Xc-/glutathione (GSH) pathway with ferroptosis inducers. This reliance can be exploited through therapy with FDA-approved rheumatoid arthritis drugs sulfasalazine (SAS) and auranofin: in MYCN-amplified, patient-derived xenograft models, both therapies blocked growth and induced ferroptosis. SAS and auranofin activity was largely mitigated by the ferroptosis inhibitor ferrostatin-1, antioxidants like N-acetyl-L-cysteine, or by the iron scavenger deferoxamine (DFO). DFO reduced auranofin-induced ROS, further linking increased iron capture in MYCN-amplified neuroblastoma to a therapeutic vulnerability to ROS-inducing drugs. These data uncover an oncogene vulnerability to ferroptosis caused by increased iron accumulation and subsequent reliance on the system Xc-/GSH pathway. SIGNIFICANCE: This study shows how MYCN increases intracellular iron levels and subsequent GSH pathway activity and demonstrates the antitumor activity of FDA-approved SAS and auranofin in patient-derived xenograft models of MYCN-amplified neuroblastoma.

Analysis of Severe Adverse Events Reported Among Patients Receiving Isoniazid-Rifapentine Treatment for Latent Mycobacterium tuberculosis Infection-United States, 2012-2016.

We analyzed data from 2012 to 2016 for patients who were hospitalized or who died after ≥1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension, and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment.