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.http://www.samj.org.zaam2021Immunolog

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

Global burden of disease due to rifampicin-resistant tuberculosis in 2020: a mathematical modelling analysis

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission

Improving lung health in low-income and middle-income countries: from challenges to solutions

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage

Supplementary Material for: A Systematic Review of the Association between Pulmonary Tuberculosis and the Development of Chronic Airflow Obstruction in Adults

<b><i>Background:</i></b> Chronic obstructive pulmonary disease (COPD) is a major public health concern, accounting for 3 million deaths annually, 90% of which occur in low- and middle-income countries. Pulmonary tuberculosis (PTB) as a contributory factor in the aetiology of COPD is under debate, with most epidemiologic evidence suggesting a positive association. <b><i>Objectives:</i></b> To compile a systematic review of evidence for an association between PTB and the development of chronic airflow obstruction (CAO). <b><i>Methods:</i></b> We performed a systematic review of original English-language, peer-reviewed literature using the PubMed/MEDLINE database. CAO was defined by spirometry [FEV₁:FVC ratio <0.70 or <i>Results:</i> Nineteen studies (1 case series, 3 case-control studies, 4 cohort studies, 8 single-centre cross-sectional studies and 3 multi-centre cross-sectional studies) met the eligibility criteria. All but 2 reported a positive association between PTB and CAO. Three of 4 large population-based surveys (n = 4,291-8,066) confirmed a significant association between PTB and CAO (OR 1.37 - 2.94). A formal meta-analysis was not possible owing to marked heterogeneity between studies. <b><i>Conclusions: </i></b>This systematic review confirms evidence for a positive association between a past history of tuberculosis and the presence of CAO. The association is independent of cigarette smoking. Causality is likely but cannot be assumed

Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort

Contains fulltext : 189933.pdf (publisher's version ) (Open Access

Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study

Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022–2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030

Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort

Background. An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype.Objective. To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB.Methods. Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (&lt;–950 HU), gas trapping (&lt;–860 HU) and fibrosis (&gt;–200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features.Results. One hundred and seven of 196 eligible subjects (54.6%) were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on history and HRCT findings, subjects were categorised as no previous PTB (NPTB, n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39). Subjects with DPTB had a lower diffusing capacity (Δ=–17.7%; p=0.001) and inspiratory capacity (Δ=–21.5%; p=0.001) than NPTB subjects, and higher gas-trapping and fibrosis but not emphysema scores (Δ=+6.2% (p=0.021), +0.36% (p=0.017) and +3.5% (p=0.098), respectively).Conclusions. The mechanisms of CAL associated with previous PTB appear to differ from those in the more common smoking-related COPD and warrant further study