Peri-operative pulse oximetry in low-income countries: a cost–effectiveness analysis

Abstract Objective: To evaluate the cost–effectiveness of pulse oximetry – compared with no peri-operative monitoring – during surgery in low-income countries. Methods: We considered the use of tabletop and portable, hand-held pulse oximeters among patients of any age undergoing major surgery in low-income countries. From earlier studies we obtained baseline mortality and the effectiveness of pulse oximeters to reduce mortality. We considered the direct costs of purchasing and maintaining pulse oximeters as well as the cost of supplementary oxygen used to treat hypoxic episodes identified by oximetry. Health benefits were measured in disability-adjusted life-years (DALYs) averted and benefits and costs were both discounted at 3% per year. We used recommended cost–effectiveness thresholds – both absolute and relative to gross domestic product (GDP) per capita – to assess if pulse oximetry is a cost–effective health intervention. To test the robustness of our results we performed sensitivity analyses. Findings: In 2013 prices, tabletop and hand-held oximeters were found to have annual costs of 310 and 95 United States dollars (US$), respectively. Assuming the two types of oximeter have identical effectiveness, a single oximeter used for 22 procedures per week averted 0.83 DALYs per annum. The tabletop and hand-held oximeters cost US$ 374 and US$115 per DALY averted, respectively. For any country with a GDP per capita above US$ 677 the hand-held oximeter was found to be cost–effective if it prevented just 1.7% of anaesthetic-related deaths or 0.3% of peri-operative mortality. Conclusion: Pulse oximetry is a cost–effective intervention for low-income settings

Protocol for evaluation of the cost-effectiveness of ePrescribing systems and candidate prototype for other related health information technologies

Background: This protocol concerns the assessment of cost-effectiveness of hospital health information technology (HIT) in four hospitals. Two of these hospitals are acquiring ePrescribing systems incorporating extensive decision support, while the other two will implement systems incorporating more basic clinical algorithms. Implementation of an ePrescribing system will have diffuse effects over myriad clinical processes, so the protocol has to deal with a large amount of information collected at various ‘levels’ across the system. Methods/Design: The method we propose is use of Bayesian ideas as a philosophical guide. Assessment of cost-effectiveness requires a number of parameters in order to measure incremental cost utility or benefit – the effectiveness of the intervention in reducing frequency of preventable adverse events; utilities for these adverse events; costs of HIT systems; and cost consequences of adverse events averted. There is no single end-point that adequately and unproblematically captures the effectiveness of the intervention; we therefore plan to observe changes in error rates and adverse events in four error categories (death, permanent disability, moderate disability, minimal effect). For each category we will elicit and pool subjective probability densities from experts for reductions in adverse events, resulting from deployment of the intervention in a hospital with extensive decision support. The experts will have been briefed with quantitative and qualitative data from the study and external data sources prior to elicitation. Following this, there will be a process of deliberative dialogues so that experts can “re-calibrate” their subjective probability estimates. The consolidated densities assembled from the repeat elicitation exercise will then be used to populate a health economic model, along with salient utilities. The credible limits from these densities can define thresholds for sensitivity analyses. Discussion: The protocol we present here was designed for evaluation of ePrescribing systems. However, the methodology we propose could be used whenever research cannot provide a direct and unbiased measure of comparative effectiveness

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

An approach to prioritization of medical devices in low-income countries : an example based on the Republic of South Sudan

Background: Efficient and evidence-based medical device and equipment prioritization is of particular importance in low-income countries due to constraints in financing capacity, physical infrastructure and human resource capabilities. Methods: This paper outlines a medical device prioritization method developed in first instance for the Republic of South Sudan. The simple algorithm offered here is a starting point for procurement and selection of medical devices and can be regarded as a screening test for those that require more labour intensive health economic modelling. Conclusions: A heuristic method, such as the one presented here, is appropriate for reaching many medical device prioritization decisions in low-income settings. Further investment and purchasing decisions that cannot be reached so simply require more complex health economic modelling approaches

Peri-operative pulse oximetry in low-income countries : a cost–effectiveness analysis

he pulse oximeter is a non-invasive medical device that monitors oxygen saturation and pulsation. When used continuously during surgery, it can provide early warning of hypoxia, hypovolaemia and impending cardiac arrest. Since oximetry can warn of problems such as misplaced endotracheal tubes – which can readily be rectified – the World Federation of Societies of Anaesthesiologists recommends its routine use for every patient undergoing anaesthesia in the world.1,2 The World Health Organization (WHO) includes pulse oximetry as a component of its Surgical Safety Checklist, which is recommended for use in every operating theatre.1 However, it has recently been estimated that pulse oximetry is unavailable in 51–70% of operating theatres in low-income countries,3 partly because of the high purchase cost of a standard commercial tabletop pulse oximeter – approximately 1000 United States dollars (US$).4 The Lifebox oximetry project, which currently operates alongside the WHO Safe Surgery Saves Lives initiative, provides a hand-held pulse oximeter for low- and middle-income countries that costs US$ 250.4 However, even this smaller sum is a considerable investment for resource-constrained settings. Furthermore, because no evidence of the cost–effectiveness of pulse oximetry for peri-operative monitoring in low-income countries has yet been published, it is not clear how oximetry should be prioritized among the many cost–effective interventions available.5 In this paper, we conducted a cost–effectiveness analysis of pulse oximetry – compared with no peri-operative monitoring – for patients undergoing surgery in low-income countries. This study is based on a synthesis of data from previously published studies from a large number of different countries. While the group of low-income countries is heterogeneous, the analysis presented here is readily adaptable to specific national contexts

Phylogenetic background and habitat drive the genetic diversification of Escherichia coli

International audienceEscherichia coli is a commensal of birds and mammals, including humans. It can act as an opportunistic pathogen and is also found in water and sediments. Since most population studies have focused on clinical isolates, we studied the phylogeny, genetic diversification, and habitat-association of 1,294 isolates representative of the phylogenetic diversity of more than 5,000, mostly non-clinical, isolates originating from humans, poultry, wild animals and water sampled from the Australian continent. These strains represent the species diversity and show large variations in gene repertoires within sequence types. Recent gene transfer is driven by mobile elements and determined by habitat sharing and by phylogroup membership, suggesting that gene flow reinforces the association of certain genetic backgrounds with specific habitats. The phylogroups with smallest genomes had the highest rates of gene repertoire diversification and fewer but more diverse mobile genetic elements, suggesting that smaller genomes are associated with higher, not lower, turnover of genetic information. Many of these small genomes were in freshwater isolates suggesting that some lineages are specifically adapted to this environment. Altogether, these data contribute to explain why epidemiological clones tend to emerge from specific phylogenetic groups in the presence of pervasive horizontal gene transfer across the species

Temperature-sensitive alleles of RSW2 link the korrigan endo-1,4-beta-glucanase to cellulose synthesis and cytokinesis in arabidopsis.

An 8.5-kb cosmid containing the KORRIGAN gene complements the cellulose-deficient rsw2-1 mutant of Arabidopsis. Three temperature-sensitive alleles of rsw2 show single amino acid mutations in the putative endo-1,4-β-glucanase encoded by KOR. The F1 fro