Development and validation of technologies suitable for the decontamination and re-use of contaminated N95 filtering facepiece respirators in response to the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has brought significant challenges to society globally, particularly in the area of healthcare provision. A pressing need existed in protecting those tasked with delivering healthcare solutions during the COVID-19 crisis by providing solutions for preserving adequate supplies of effective personal protective equipment (PPE). AIM: To evaluate and validate available methods for the decontamination of N95 filtering facepiece respirators (FFRs) while maintaining functionality during re-use. METHODS: Multiple low-temperature steam and vaporized hydrogen peroxide (VHP) technologies were assessed for inactivation of Mycobacterium spp. and feline calicivirus (employed as representatives of the contamination challenge). FINDINGS: Virus (≥3log10) and Mycobacterium spp. (≥6log10) inactivation was achieved on various types of N95 FFRs using an array of heat (65-71oC), humidity (>50% relative humidity) and VHP without affecting the performance of the PPE. CONCLUSION: The methods have been validated and were authorized by the US Food and Drug Administration under a temporary emergency use authorization. Based on the findings, opportunities exist for development and deployment of decontamination methods made from simple, general purpose materials and equipment should a future need arise.

Opportunities for the application of real-time bacterial cell analysis using flow cytometry for the advancement of sterilization microbiology.

Medical devices provide critical care and diagnostic applications through patient contact. Sterility assurance level (SAL) may be defined as the probability of a single viable micro-organism occurring on an item after a sterilization process. Sterilization microbiology often relies upon using an overkill validation method where a 12-log reduction in recalcitrant bacterial endospore population occurs during the process that exploits conventional laboratory-based culture media for enumeration. This timely review explores key assumptions underpinning use of conventional culture-based methods in sterilization microbiology. Consideration is given to how such methods may limit the ability to fully appreciate the inactivation kinetics of a sterilization process such as vaporized hydrogen peroxide (VH2O2) sterilization, and consequently design efficient sterilization processes. Specific use of the real-time flow cytometry (FCM) is described by way of elucidating the practical relevance of these limitation factors with implications and opportunities for the sterilization industry discussed. Application of FCM to address these culture-based limitation factors will inform real-time kinetic inactivation modelling and unlock potential to embrace emerging opportunities for pharma, medical device and sterilization industries including potentially disruptive applications that may involve reduced usage of sterilant.

Terminal sterilization of medical devices using vaporized hydrogen peroxide: a review of current methods and emerging opportunities.

Medical devices are an important and growing aspect of healthcare provision and are increasing in complexity to meet established and emerging patient needs. Terminal sterilization plays a vital role in the provision of safe medical devices. While terminal sterilization technologies for medical devices include multiple radiation options, ethylene oxide remains the predominant nonthermal gaseous option, sterilizing c. 50% of all manufactured devices. Vaporized hydrogen peroxide (abbreviated VH2O2 by the International Organization for Standardization) is currently deployed for clinical sterilization applications, where its performance characteristics appear aligned to requirements, constituting a viable alternative low-temperature process for terminal processing of medical devices. However, VH2O2 has operational limitations that create technical challenges for industrial-scale adoption. This timely review provides a succinct overview of VH2O2 in gaseous sterilization and addresses its applicability for terminal sterilization of medical devices. It also describes underappreciated factors such as the occurrence of nonlinear microbial inactivation kinetic plots that may dictate a need to develop a new standard approach to validate VH2O2 for terminal sterilization of medical devices.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

European and Polynesian admixture in the Norfolk Island population.

The Norfolk Island population in the South Pacific is primarily the product of recent admixture between a small number of British male and Polynesian female founders. We identified and genotyped 128 Ancestry Informative Markers (AIMs) spread across the autosomes, X/Y chromosomes and mitochondrial DNA genome, to explore and quantify the current levels of genetic admixture in the Norfolk Islanders. On the basis of autosomal AIMs, the population shows mean European and Polynesian ancestry proportions of 88 and 12%, respectively. However, there is a substantial variation between individuals ranging from total European ancestry to near total Polynesian origin. There is a strong correlation between individual genetic estimates of Polynesian ancestry and those derived from the extensive pedigree and genealogical records of Islanders. Also in line with historical accounts, there is a substantial asymmetry in the maternal and paternal origins of the Islanders with almost all Y-chromosomes of European origin whereas at least 25% of mtDNAs appear to have a Polynesian origin. Accurate knowledge of ancestry will be important in future attempts to use the Island population in admixture mapping approaches to find the genes that underlie differences in the risk to some diseases between Europeans and Polynesians.

A 13-year longitudinal analysis of risk factors and clinic visitation patterns of patients with repeated gonorrhea.

A retrospective study of 2498 patients who made multiple visits to a sexually transmitted disease clinic over a 13-year period analyzed risk factors, default patterns, and repeated infections associated with gonococcal urethritis. An analysis of visitation patterns found that being young, black, and male and having a history of gonococcal urethritis before visiting the clinic was positively related to the total time a patient remained involved with the clinic. Default rates for all patients increased with successive clinic visits. A focused analysis was carried out on the records of 146 patients who returned to the clinic within 12 months with a second diagnosis of gonococcal urethritis. It was found that this group of "repeaters," who comprised 15% of the total population with gonococcal urethritis, accounted for approximately 29% of all diagnoses of this infection over the 13-year study period. Repeaters were found to be more frequently male, black, single, and to be less likely to return for a test-of-cure culture. Longitudinal analysis found that the median time repeaters remained involved with the clinic was approximately 130 days. The relatively brief clinic "half-life" and rapid rates of removal of repeaters are discussed in terms of the development of strain-specific immunity to Neisseria gonorrhoeae in a closed population of patients.