The codification of hazard and its impact on the hazard versus risk controversy

The long running controversy about the relative merits of hazard-based versus risk-based approaches has been investigated. There are three levels of hazard codification: level 1 divides chemicals into dichotomous bands of hazardous and non-hazardous; level 2 divides chemicals into bands of hazard based on severity and/or potency; and level 3 places each chemical on a continuum of hazard based on severity and/or potency. Any system which imposes compartments onto a continuum will give rise to issues at the boundaries, especially with only two compartments. Level 1 schemes are only justifiable if there is no variation in severity, or potency or if there is no threshold. This is the assumption implicit in GHS/EU classification for carcinogenicity, reproductive toxicity and mutagenicity. However, this assumption has been challenged. Codification level 2 hazard assessments offer a range of choices and reduce the built-in conflict inherent in the level 1 process. Level 3 assessments allow a full range of choices between the extremes and reduce the built-in conflict even more. The underlying reason for the controversy between hazard and risk is the use of level 1 hazard codification schemes in situations where there are ranges of severity and potency which require the use of level 2 or level 3 hazard codification. There is not a major difference between level 2 and level 3 codification, and they can both be used to select appropriate risk management options. Existing level 1 codification schemes should be reviewed and developed into level 2 schemes where appropriate.

1475 Management of Appendicitis During COVID19 - A Shift to Conservative Management

Introduction The COVID19 pandemic posed challenges in dealing with common surgical conditions, by causing a redirect of manpower and resources as well as having correlation of added morbidity if present in patients undergoing surgery Aim To find out the proportion of patients undergoing conservative management and their outcomes compared to operative management Method Retrospective data collection of patients admitted with appendicitis from 25/03/2020 to 15/07/2020. Results A total of 72 encounters had a discharge diagnosis of appendicitis.35 (48.6%) patients were treated with conservative management. while 37 (51.4%) patients had operative management. In the conservative group CT scan was done in 64%, which showed simple appendicitis in 78% and complicated in 17 %, whereas in the operative group CT scan was done in 59.4% , 86 % had simple appendicitis and 9% and complicated appendicitis. Median length of stay in both groups were 2 days. There were no readmissions in the operative group and 84.3% patients had no readmissions in the conservative group in the study in a follow up period up to 6 months. 2 patients initially treated conservative were eventually offered surgery on readmission. Conclusions 1. Conservative management of appendicitis has proved to be a valuable alternative to surgical management during this pandemic 2. Patients should be offered a choice of conservative management for simple appendicitis with prior discussion of benefits of avoiding surgery versus risk to recurrence (up to 39% reported in literature for uncomplicated appendicitis)

Testing for Interactions Between APOE and Klotho Genotypes on Cognitive, Dementia, and Brain Imaging Metrics in UK Biobank

Recent research suggests genetic variation in the Klotho locus may modify the association between APOE ɛ4 and cognitive impairment. We tested for associations and interactions between these genotypes versus risk of dementia, cognitive abilities, and brain structure in older UK Biobank participants. Klotho status was indexed with rs9536314 heterozygosity (versus not), in unrelated people with versus without APOE ɛ4 genotype, corrected for various confounders. APOE ɛ4 associated with increased risk of dementia, worse cognitive abilities, and brain structure. Klotho was associated with better reasoning. There were no interactions; potentially suggesting an age- and pathology-dependent Klotho effect.