Assessing the filtration efficiency and regulatory status of N95s and nontraditional filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has severely disrupted supply chains for many types of Personal Protective Equipment (PPE), particularly surgical N95 filtering facepiece respirators (FFRs; "masks"). As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed use of industrial N95 respirators and importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of masks in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer or supplier. We then assembled a testing apparatus at a university laboratory and performed a modified test of filtration performance using KCl and ambient particulate matter on masks from hospital inventories; an accompanying website shows how to build and use the testing apparatus. RESULTS: Over 100 different makes and models of traditional and nontraditional filtering facepiece respirators (N95-type masks) were in the inventory of surveyed U.S. teaching hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many are not correctly labelled and do not perform to accepted standards and a subset are obviously dangerous; many of these masks are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers and inconsistent labeling of KN95 masks, it is difficult to distinguish between legitimate and counterfeit products. CONCLUSIONS: Many FFRs available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations to assist end users in acquiring legitimate products. Institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for regulatory agencies regarding labeling and public disclosure aimed at increasing pandemic resilience.

Off-label use of prescription analgesics among hospitalized children in the United States.

PURPOSE: Analgesics are the most frequently administered medications among hospitalized children. However, current analgesic prescribing patterns have not been well defined among hospitalized children. In addition, it is unknown what proportion of prescription analgesics is approved for use in children and what proportion is used "off-label." METHODS: Nationally representative data from 52 tertiary care children's hospitals in the Pediatric Health Information System were queried to determine prescribing rates of analgesic medications. We analyzed hospitalizations for children <18 years occurring between 1 April 2010 and 30 June 2018. Food and Drug Administration (FDA) drug labels were reviewed for pediatric information, and prescriptions were classified as on- or off-label based on age, route, and formulation. RESULTS: Among 4.9 million hospitalizations, 1.8 million (37.6%, 95% confidence interval [CI] = 37.6-37.7) were associated with use of a prescription analgesic. Overall, 36.7% (95% CI = 36.7-36.7) of hospitalizations included off-label analgesic therapy, with 26.4% (95% CI = 26.4-26.5) associated with two or more off-label analgesics. Off-label analgesic use was higher among hospitalizations in the intensive care unit (61.5%) or with an operating room procedure (92.8%). Rates of off-label prescribing increased with age, peaking at 50.5% for adolescents. Prescription analgesics administered most frequently were morphine, fentanyl, and ketorolac, with off-label use occurring in 24.5%, 23.1%, and 11.3% of hospitalizations, respectively. CONCLUSIONS: Over a third of pediatric hospitalizations were associated with the administration of prescription analgesics that have not been labeled for use in children. Our findings highlight the critical need to ensure that safe and effective analgesics are developed for children and that pediatric labeling is expanded for existing analgesics to inform treatment decisions.

Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE.

The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including of N95 masks (filtering facepiece respirators; FFRs). These masks are intended for single use but their sterilization and subsequent reuse has the potential to substantially mitigate shortages. Here we investigate PPE sterilization using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD), in a sealed environment chamber. The efficacy of sterilization by iHP was assessed using bacterial spores in biological indicator assemblies. After one or more iHP treatments, five models of N95 masks from three manufacturers were assessed for retention of function based on their ability to form an airtight seal (measured using a quantitative fit test) and filter aerosolized particles. Filtration testing was performed at a university lab and at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain filtration efficiency up to ten cycles, the maximum number tested to date. A typical iHP environment chamber with a volume of ~ 80 m3 can treat ~ 7000 masks and other items (e.g. other PPE, iPADs), making this an effective approach for a busy medical center.

Pediatric Drug Policies Supporting Safe And Effective Use Of Therapeutics In Children: A Systematic Analysis.

Several policies have been implemented in the US to promote the evidence-based use of therapeutics in pediatric populations. Under the Best Pharmaceuticals for Children Act of 2002 and the Pediatric Research Equity Act of 2003, the Food and Drug Administration (FDA) can request pediatric studies for new drug and biologic indications. The acts have been credited with generating pediatric information for hundreds of drugs. However, concerns have been raised that delays and noncompliance with study requests contribute to high rates of off-label and potentially unsafe or ineffective medication use in children. We used publicly available FDA documents to analyze all indications for new drugs and biologics approved by the FDA from 2002 through 2018. During this time the FDA issued 389 pediatric study requests (141 under the Best Pharmaceuticals for Children Act and 248 under the Pediatric Research Equity Act) for 274 new drugs and biologics, representing 320 indications. We found that as of December 31, 2018, fewer than a third of these study requests had been completed. Overall, 64 percent of new drug and biologic indications deemed relevant to pediatric patients lacked pediatric prescribing information at five years after FDA approval. Enforcement of pediatric drug study policies should be strengthened to reduce non-evidence-based medication use in pediatric patients.

Considerations for the Selection and Use of Disinfectants Against SARS-CoV-2 in a Health Care Setting.

Proper disinfection using adequate disinfecting agents will be necessary for infection control strategies against coronavirus disease 2019 (COVID-19). However, limited guidance exists on effective surface disinfectants or best practices for their use against severe acute respiratory coronavirus 2. We outlined a process of fully characterizing over 350 products on the Environmental Protection Agency List N, including pH, method of delivery, indication for equipment sterilization, and purchase availability. We then developed a streamlined set of guidelines to help rapidly evaluate and select suitable disinfectants from List N, including practicality, efficacy, safety, and cost/availability. This resource guides the evaluation of ideal disinfectants amidst practical considerations posed by the COVID-19 pandemic.

Assessing the quality of nontraditional N95 filtering face-piece respirators available during the COVID-19 pandemic.

BACKGROUND: During the current COVID-19 pandemic, supply chains for Personal Protective Equipment (PPE) have been severely disrupted and many products, particularly surgical N95 filtering facepiece respirators (FFRs; "masks") are in short supply. As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. METHODS: We conducted a survey of mask in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer. We then assembled a simple apparatus for performing a necessary (but not sufficient) test of filtration performance and tested masks from the inventory; an accompanying website shows how to build and use the testing apparatus. RESULTS: Our survey showed that, seven months after the start of the COVID-19 pandemic, over 100 different makes and models of N95-type masks are in the inventory of local hospitals as opposed to 2-5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many did not perform to accepted standards and are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers in the FDA EUA and confusing or inconsistent labeling of KN95 masks, it is difficult to distinguish legitimate and counterfeit products. CONCLUSIONS: Many of the FFR masks available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations for end users to assist in acquiring legitimate products. In particular, institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for U.S and Chinese regulatory agencies with regard to labeling and public disclosure aimed at increase pandemic resilience.

Analysis of SteraMist ionized hydrogen peroxide technology in the sterilization of N95 respirators and other PPE: a quality improvement study.

OBJECTIVE: The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including filtering facepiece respirators (FFRs) such as N95 masks. These masks are normally intended for single use, but their sterilization and subsequent reuse could substantially mitigate a world-wide shortage. DESIGN: Quality assurance. SETTING: A sealed environment chamber installed in the animal facility of an academic medical center. INTERVENTIONS: One to five sterilization cycles using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD). MAIN OUTCOME MEASURES: Personal protective equipment, including five N95 mask models from three manufacturers, were evaluated for efficacy of sterilization following iHP treatment (measured with bacterial spores in standard biological indicator assemblies). Additionally, N95 masks were assessed for their ability to efficiently filter particles down to 0.3um and for their ability to form an airtight seal using a quantitative fit test. Filtration efficiency was measured using ambient particulate matter at a university lab and an aerosolized NaCl challenge at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. RESULTS: The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain function up to five cycles, the maximum number tested to date. Some but not all PPE could also be sterilized using an iHP environmental chamber, but pre-treatment with a handheld iHP generator was required for semi-enclosed surfaces such as respirator hoses. CONCLUSIONS: A typical iHP environment chamber with a volume of ~80 m3 can treat ~7000 masks per day, as well as other items of PPE, making this an effective approach for a busy medical center.

Children's rare disease cohorts: an integrative research and clinical genomics initiative.

While genomic data is frequently collected under distinct research protocols and disparate clinical and research regimes, there is a benefit in streamlining sequencing strategies to create harmonized databases, particularly in the area of pediatric rare disease. Research hospitals seeking to implement unified genomics workflows for research and clinical practice face numerous challenges, as they need to address the unique requirements and goals of the distinct environments and many stakeholders, including clinicians, researchers and sequencing providers. Here, we present outcomes of the first phase of the Children's Rare Disease Cohorts initiative (CRDC) that was completed at Boston Children's Hospital (BCH). We have developed a broadly sharable database of 2441 exomes from 15 pediatric rare disease cohorts, with major contributions from early onset epilepsy and early onset inflammatory bowel disease. All sequencing data is integrated and combined with phenotypic and research data in a genomics learning system (GLS). Phenotypes were both manually annotated and pulled automatically from patient medical records. Deployment of a genomically-ordered relational database allowed us to provide a modular and robust platform for centralized storage and analysis of research and clinical data, currently totaling 8516 exomes and 112 genomes. The GLS integrates analytical systems, including machine learning algorithms for automated variant classification and prioritization, as well as phenotype extraction via natural language processing (NLP) of clinical notes. This GLS is extensible to additional analytic systems and growing research and clinical collections of genomic and other types of data.