Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE).

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.

Cost-Effectiveness of the Use of Autologous Cell Harvesting Device Compared to Standard of Care for Treatment of Severe Burns in the United States.

INTRODUCTION: When introducing a new intervention into burn care, it is important to consider both clinical and economic impacts, as the financial burden of burns in the USA is significant. This study utilizes a health economic modeling approach to estimate cost-effectiveness and burn center budget-impact for the use of the RECELL® Autologous Cell Harvesting Device to prepare autologous skin cell suspension (ASCS) compared to standard of care (SOC) split-thickness skin graft (STSG) for the treatment of severe burn injuries requiring surgical intervention for definitive closure. METHODS: A hospital-perspective model using sequential decision trees depicts the acute burn care pathway (wound assessment, debridement/excision, temporary coverage, definitive closure) and predicts the relative differences between use of ASCS compared to SOC. Clinical inputs and ASCS impact on length of stay (LOS) were derived from clinical trials and real-world use data, American Burn Association National Burn Repository database analyses, and burn surgeon interviews. Hospital resource use and unit costs were derived from three US burn centers. A budget impact calculation leverages Monte Carlo simulation to estimate the overall impact to a burn center. RESULTS: ASCS treatment is cost-saving or cost-neutral (< 2% difference) and results in lower LOS compared to SOC across expected patient profiles and scenarios. In aggregate, ASCS treatment saves a burn center 14-17.3% annually. Results are sensitive to, but remain robust across, changing assumptions for relative impact of ASCS use on LOS, procedure time, and number of procedures. CONCLUSIONS: Use of ASCS compared to SOC reduces hospital costs and LOS of severe burns in the USA. FUNDING: AVITA Medical.

Economic Spillovers From Public Investments in Medical Countermeasures: A Case Study of a Burn Debridement Product.

OBJECTIVE: The US federal government invests in the development of medical countermeasures for addressing adverse health effects to the civilian population from chemical, biological, and radiological or nuclear threats. We model the potential economic spillover effects in day-to-day burn care for a federal investment in a burn debridement product for responding to an improvised nuclear device. METHODS: We identify and assess 4 primary components for projecting the potential economic spillover benefits of a burn debridement product: (1) market size, (2) clinical effectiveness and cost-effectiveness, (3) product cost, and (4) market adoption rates. Primary data sources were the American Burn Association's 2015 National Burn Repository Annual Report of Data and published clinical studies used to gain European approval for the burn debridement product. RESULTS: The study results showed that if approved for use in the United States, the burn debridement product has potential economic spillover benefits exceeding the federal government's initial investment of $24 million a few years after introduction into the burn care market. CONCLUSIONS: Economic spillover analyses can help to inform the prioritizing of scarce resources for research and development of medical countermeasures by the federal government. Future federal medical countermeasure research and development investments could incorporate economic spillover analysis to assess investment options. (Disaster Med Public Health Preparedness. 2017;11:711-719).

A Conceptual Framework for Allocation of Federally Stockpiled Ventilators During Large-Scale Public Health Emergencies.

Some types of public health emergencies could result in large numbers of patients with respiratory failure who need mechanical ventilation. Federal public health planning has included needs assessment and stockpiling of ventilators. However, additional federal guidance is needed to assist states in further allocating federally supplied ventilators to individual hospitals to ensure that ventilators are shipped to facilities where they can best be used during an emergency. A major consideration in planning is a hospital's ability to absorb additional ventilators, based on available space and staff expertise. A simple pro rata plan that does not take these factors into account might result in suboptimal use or unused scarce resources. This article proposes a conceptual framework that identifies the steps in planning and an important gap in federal guidance regarding the distribution of stockpiled mechanical ventilators during an emergency.

Assessing the Capacity of the US Health Care System to Use Additional Mechanical Ventilators During a Large-Scale Public Health Emergency.

OBJECTIVE: A large-scale public health emergency, such as a severe influenza pandemic, can generate large numbers of critically ill patients in a short time. We modeled the number of mechanical ventilators that could be used in addition to the number of hospital-based ventilators currently in use. METHODS: We identified key components of the health care system needed to deliver ventilation therapy, quantified the maximum number of additional ventilators that each key component could support at various capacity levels (ie, conventional, contingency, and crisis), and determined the constraining key component at each capacity level. RESULTS: Our study results showed that US hospitals could absorb between 26,200 and 56,300 additional ventilators at the peak of a national influenza pandemic outbreak with robust pre-pandemic planning. CONCLUSIONS: The current US health care system may have limited capacity to use additional mechanical ventilators during a large-scale public health emergency. Emergency planners need to understand their health care systems' capability to absorb additional resources and expand care. This methodology could be adapted by emergency planners to determine stockpiling goals for critical resources or to identify alternatives to manage overwhelming critical care need.

Estimates of the demand for mechanical ventilation in the United States during an influenza pandemic.

An outbreak in China in April 2013 of human illnesses due to avian influenza A(H7N9) virus provided reason for US public health officials to revisit existing national pandemic response plans. We built a spreadsheet model to examine the potential demand for invasive mechanical ventilation (excluding "rescue therapy" ventilation). We considered scenarios of either 20% or 30% gross influenza clinical attack rate (CAR), with a "low severity" scenario with case fatality rates (CFR) of 0.05%-0.1%, or a "high severity" scenario (CFR: 0.25%-0.5%). We used rates-of-influenza-related illness to calculate the numbers of potential clinical cases, hospitalizations, admissions to intensive care units, and need for mechanical ventilation. We assumed 10 days ventilator use per ventilated patient, 13% of total ventilator demand will occur at peak, and a 33.7% weighted average mortality risk while on a ventilator. At peak, for a 20% CAR, low severity scenario, an additional 7000 to 11,000 ventilators will be needed, averting a pandemic total of 35,000 to 55,000 deaths. A 30% CAR, high severity scenario, will need approximately 35,000 to 60,500 additional ventilators, averting a pandemic total 178,000 to 308,000 deaths. Estimates of deaths averted may not be realized because successful ventilation also depends on sufficient numbers of suitably trained staff, needed supplies (eg, drugs, reliable oxygen sources, suction apparatus, circuits, and monitoring equipment) and timely ability to match access to ventilators with critically ill cases. There is a clear challenge to plan and prepare to meet demands for mechanical ventilators for a future severe pandemic.

User-managed inventory: an approach to forward-deployment of urgently needed medical countermeasures for mass-casualty and terrorism incidents.

The user-managed inventory (UMI) is an emerging idea for enhancing the current distribution and maintenance system for emergency medical countermeasures (MCMs). It increases current capabilities for the dispensing and distribution of MCMs and enhances local/regional preparedness and resilience. In the UMI, critical MCMs, especially those in routine medical use ("dual utility") and those that must be administered soon after an incident before outside supplies can arrive, are stored at multiple medical facilities (including medical supply or distribution networks) across the United States. The medical facilities store a sufficient cache to meet part of the surge needs but not so much that the resources expire before they would be used in the normal course of business. In an emergency, these extra supplies can be used locally to treat casualties, including evacuees from incidents in other localities. This system, which is at the interface of local/regional and federal response, provides response capacity before the arrival of supplies from the Strategic National Stockpile (SNS) and thus enhances the local/regional medical responders' ability to provide life-saving MCMs that otherwise would be delayed. The UMI can be more cost-effective than stockpiling by avoiding costs due to drug expiration, disposal of expired stockpiled supplies, and repurchase for replacement.

Medical planning and response for a nuclear detonation: a practical guide.

This article summarizes major points from a newly released guide published online by the Office of the Assistant Secretary for Preparedness and Response (ASPR). The article reviews basic principles about radiation and its measurement, short-term and long-term effects of radiation, and medical countermeasures as well as essential information about how to prepare for and respond to a nuclear detonation. A link is provided to the manual itself, which in turn is heavily referenced for readers who wish to have more detail.

Clinical utility of gene-expression profiling for tumor-site origin in patients with metastatic or poorly differentiated cancer: impact on diagnosis, treatment, and survival.

PURPOSE: The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000- gene-expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers. METHODS: Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians' working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test's usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy. RESULTS: Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years. CONCLUSION: In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary.