Consent for critical care research after death from COVID-19: Arguments for a waiver

Pandemics challenge clinicians and scientists in many ways, especially when the virus is novel and disease expression becomes variable or unpredictable. Under such circumstances, research becomes critical to inform clinical care and protect future patients. Given that severely ill patients admitted to intensive care units are at high risk of mortality, establishing the cause of death at a histopathological level could prove invaluable in contributing to the understanding of COVID-19. Postmortem examination including autopsies would be optimal. However, in the context of high contagion and limited personal protective equipment, full autopsies are not being conducted in South Africa (SA). A compromise would require tissue biopsies and samples to be taken immediately after death to obtain diagnostic information, which could potentially guide care of future patients, or generate hypotheses for finding needed solutions. In the absence of an advance written directive (including a will or medical record) providing consent for postmortem research, proxy consent is the next best option. However, obtaining consent from distraught family members, under circumstances of legally mandated lockdown when strict infection control measures limit visitors in hospitals, is challenging. Their extreme vulnerability and emotional distress make full understanding of the rationale and consent process difficult either before or upon death of a family member. While it is morally distressing to convey a message of death telephonically, it is inhumane to request consent for urgent research in the same conversation. Careful balancing of the principles of autonomy, non-maleficence and justice becomes an ethical imperative. Under such circumstances, a waiver of consent, preferably followed by deferred proxy consent, granted by a research ethics committee in keeping with national ethics guidance and legislation, would fulfil the basic premise of care and research: first do no harm. This article examines the SA research ethics framework, guidance and legislation to justify support for a waiver of consent followed by deferred proxy consent, when possible, in urgent research after death to inform current and future care to contain the pandemic in the public interest

A severity-of-illness score in patients with tuberculosis requiring intensive care

Background. We previously retrospectively validated a 6-point severity-of-illness score aimed at identifying patients at risk of dying of tuberculosis (TB) in the intensive care unit (ICU). Parameters included septic shock, HIV infection with a CD4 count <200 cells/µL, renal dysfunction, a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F) <200 mmHg, a chest radiograph demonstrating diffuse parenchymal infiltrates, and no TB treatment on admission.Objectives. To prospectively validate the severity-of-illness scoring system in patients with TB requiring intensive care, and to refine and simplify the score in order to expand its clinical utility.Methods. We performed a prospective observational study with a planned post hoc retrospective analysis, enrolling all adult patients with confirmed TB admitted to the medical ICU of a tertiary hospital in Cape Town, South Africa, from 1 February 2015 to 31 July 2018. The admission data of all adult patients with TB requiring admission to the ICU were used to calculate the 6-point severity-of-illness score and a refined 4-point score (based on the planned post hoc analysis). Descriptive statistics and χ2 or Fisher’s exact tests (where indicated) were performed on dichotomous categorical variables, and t-tests on continuous data. Patients were categorised as hospital survivors or non-survivors.Results. Forty-one of 78 patients (52.6%) died. The 6-point scores of non-survivors were higher than those of survivors (mean (standard deviation (SD)) 3.5 (1.3) v. 2.7 (1.2); p=0.01). A score ≥3 v. <3 was associated with increased mortality (64.0% v. 32.1%; odds ratio (OR) 3.75; 95% confidence interval (CI) 1.25 - 10.01; p=0.01). Post hoc, a P/F ratio <200 mmHg and no TB treatment on admission failed to predict mortality, whereas any immunosuppression did. A revised 4-point score (septic shock, any immunosuppression, acute kidney injury and lack of lobar consolidation) demonstrated higher scores in non-survivors than survivors (mean (SD) 2.8 (1.1) v. 1.6 (1.1); p<0.001). A score ≥3 v. ≤2 was associated with increased mortality (78.4% v. 29.3%; OR 8.76; 95% CI 3.12 - 24.59; p<0.001).Conclusions. The 6-point severity-of-illness score identified patients at increased risk of death. We were able to derive and retrospectively validate a simplified 4-point score with superior predictive power

Reconstructing Sparticle Mass Spectra using Hadronic Decays

Most sparticle decay cascades envisaged at the Large Hadron Collider (LHC) involve hadronic decays of intermediate particles. We use state-of-the art techniques based on the \kt jet algorithm to reconstruct the resulting hadronic final states for simulated LHC events in a number of benchmark supersymmetric scenarios. In particular, we show that a general method of selecting preferentially boosted massive particles such as W, Z or Higgs bosons decaying to jets, using sub-jets found by the \kt algorithm, suppresses QCD backgrounds and thereby enhances the observability of signals that would otherwise be indistinct. Consequently, measurements of the supersymmetric mass spectrum at the per-cent level can be obtained from cascades including the hadronic decays of such massive intermediate bosons.Comment: 1+29 pages, 12 figure

Five-year follow-up of participants diagnosed with chronic airflow obstruction in a South African Burden of Obstructive Lung Disease (BOLD) survey

Background. A community-based prevalence survey performed in two suburbs in Cape Town, South Africa (SA), in 2005, using the international Burden of Obstructive Lung Disease (BOLD) method, confirmed a prevalence of chronic airflow obstruction (CAO) in 23.1% of adults aged >40 years. Objectives. To study the clinical course and prognosis over 5 years of patients with CAO identified in the 2005 survey. Methods. Patients with CAO in 2005 were invited to participate. Standard BOLD and modified questionnaires were completed. Spirometry was performed using spirometers of the same make as in 2005. Results. Of 196 eligible participants from BOLD 2005, 45 (23.0%) had died, 8 from respiratory causes, 10 from cardiovascular causes and 6 from other known causes, while in 21 cases the cause of death was not known. On multivariate analysis, only age and Global initiative for Obstructive Lung Disease (GOLD) stage 4 disease at baseline were significantly associated with death. Of the 151 survivors, 11 (5.6% of the original cohort) were unavailable and 33 (16.8%) declined or had medical exclusions. One hundred and seven survivors were enrolled in the follow-up study (54.6%, median age 63.1 years, 45.8% males). Post-bronchodilator spirometry performed in 106 participants failed to confirm CAO, defined as a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of <0.7, in 16 participants (15.1%), but CAO was present in 90. The median decline in FEV1 was 28.9 mL/year (interquartile range –54.8 - 0.0) and was similar between GOLD stages. The median total decline in FVC was 75 mL, and was significantly greater in GOLD stage 1 (–350 mL) than in stages 2 or 3 (–80 mL and +140 mL, respectively; p<0.01). Fifty-eight participants with CAO in 2005 (64.4%) remained in the same GOLD stage, while 21 (23.3%) deteriorated and 11 (12.2%) improved by ≥1 stage. Only one-third were receiving any treatment for chronic obstructive pulmonary disease (COPD). Conclusions. The prevalence, morbidity and mortality of CAO and COPD in SA are high and the level of appropriate treatment is very low, pointing to underdiagnosis and inadequate provision of and access to effective treatments and preventive strategies for this priority chronic non-communicable disease.info:eu-repo/semantics/publishedVersio

Generating project value through design for reliability : on the development and implementation of a potential value framework

The current trend to economically exploit deepwater hydrocarbon reserves is to reduce the capital expenditure; accomplished by deploying subsea equipment. The financial benefit afforded is offset by the risk of high operational costs associated with failure. Recognition of the life cycle cost implications of subsea reliability have led to the development of the reliability strategy. This strategy adopts a risk based approach to design for reliability where only analyses (and their subsequent recommended actions) perceived to add to whole project value are implemented. While life cycle costing has been developed to address through life cost, analyses are traditionally considered a source of cost accumulation rather than value creation. This thesis proposes a potential reliability value decision making framework to assist in the design for reliability planning process. The framework draws on the existing concepts of life cycle costing to explicitly consider the through life value of investing in reliability analyses. Fundamental to the framework are the potential reliability value index and an associated value breakdown structure intended as central decision support for decentralised decision making. Implementation of the framework is reliant on synergies within the project organization; including relationships between organizations and project functions. To enhance synergy between functions and dismantle some of the recognised barriers to implementing the reliability strategy an organizational structure, for projects, guided centrally by the reliability value framework is proposed. This structure requires the broadening of each project functions’ skill set to enable the value added implementation of the strategy’s activities. By widening the scope of application, the reliability analysis toolkit becomes the central guidance of the design process and awareness of the causes of unreliability and how they can be avoided increases. As this capability improves so the cost-efficiency with which reliability is managed in design (introduced as the reliability efficiency frontier) also increases.EThOS - Electronic Theses Online ServiceGBUnited Kingdo