Health Resource Utilisation and Disparities: an Ecological Study of Admission Patterns Across Ethnicity in England Between 2017 and 2020.

BACKGROUND AND AIM: The COVID-19 pandemic highlighted adverse outcomes in Asian, Black, and ethnic minority groups. More research is required to explore underlying ethnic health inequalities. In this study, we aim to examine pre-COVID ethnic inequalities more generally through healthcare utilisation to contextualise underlying inequalities that were present before the pandemic. DESIGN: This was an ecological study exploring all admissions to NHS hospitals in England from 2017 to 2020. METHODS: The primary outcomes were admission rates within ethnic groups. Secondary outcomes included age-specific and age-standardised admission rates. Sub-analysis of admission rates across an index of multiple deprivation (IMD) deciles was also performed to contextualise the impact of socioeconomic differences amongst ethnic categories. Results were presented as a relative ratio (RR) with 95% confidence intervals. RESULTS: Age-standardised admission rates were higher in Asian (RR 1.40 [1.38-1.41] in 2019) and Black (RR 1.37 [1.37-1.38]) and lower in Mixed groups (RR 0.91 [0.90-0.91]) relative to White. There was significant missingness or misassignment of ethnicity in NHS admissions: with 11.7% of admissions having an unknown/not-stated ethnicity assignment and 'other' ethnicity being significantly over-represented. Admission rates did not mirror the degree of deprivation across all ethnic categories. CONCLUSIONS: This study shows Black and Asian ethnic groups have higher admission rates compared to White across all age groups and when standardised for age. There is evidence of incomplete and misidentification of ethnicity assignment in NHS admission records, which may introduce bias to work on these datasets. Differences in admission rates across individual ethnic categories cannot solely be explained by socioeconomic status. Further work is needed to identify ethnicity-specific factors of these inequalities to allow targeted interventions at the local level.

Natural History and Trajectory of non-COVID-19 Acute Respiratory Distress Syndrome patients. An observational study for comparison to COVID-19 populations

Introduction: Previous studies on acute respiratory distress syndrome (ARDS) relate trajectories to initial degree of hypoxia1,2 Further work is required to deduce whether previous ARDS frameworks are applicable to COVID-19 ARDS patients. Objectives: How does hypoxia progression influence outcomes in non-COVID ARDS patients and does this differ from COVID-19 ARDS patients? Methods: Mechanically ventilated patients that met the Berlin ARDS Criteria1 were selected from the Medical Information Mart for Intensive Care (MIMIC) database.3 Daily blood gas and ventilatory settings were analysed, from the point of intubation to death or discharge, allowing longitudinal analysis with high granularity. Our primary outcome was how the trajectory of patients was dependent on their hypoxia progression. Secondary outcomes included how base characteristics and initial clinical parameters affect trajectory and outcomes. Comparative analysis was performed between the results of this study and a previous large COVID-19 ARDS study4 Results: 1,575 ICU admissions were included in the study. All results report this study first followed by the COVID-19 study.4 Overall survival rate was higher (70.2% vs 57.7%);less patients had initial moderate or severe hypoxia (54.5% vs 76.8%);less patients had worsening of hypoxia over the first 7 days (18.9% vs 31.8%);and more patients improved their hypoxia status (33.1% vs 23.5%). This study showed a smaller proportion of hypoxia nonresolvers compared to the COVID study (32.6% vs 57.9%). However, non-resolvers in the two studies had similar survival rates (58.6% vs 60.4%). Length of ICU stay (LOS) and duration of invasive mechanical ventilation (IMV) was significantly less in this study compared to the COVID-19 study regardless of hypoxia resolver status. Conclusions: Non-COVID ARDS patients have a more predictable natural history and trajectory compared to COVID-19 ARDs patients. Respiratory failure occurs less frequently and is quicker to resolve, resulting in a lower proportion of hypoxia non-resolvers. However hypoxia non-resolvers of both populations have similar survival outcomes. Despite this, COVID ARDS patient have much longer ICU length of stay and length of ventilation which has significant implications for provision of critical care resources. Further analysis of the impact of COVID-19 therapies on these outcomes is needed.

ESG: disentangling the governance pillar

In 2004, the World Bank’s International Financial Corporation (IFC) laid a cornerstone for the debate with the publication of the report “Who Cares Wins”, which provided principles where interpretations of the idea of ESG could stand. Since the release of IFC’s report, the construction of the idea of ESG has gained momentum – and there is no sign that the movement will cool down (Cappucci, 2018;Clementino & Perkins, 2020;Eccles, Ioannou, & Serafeim, 2014;Paolone, Cucari, Wu, & Tiscini, 2021;Schoenmaker & Schramade, 2019). [...]it is expected that these contractual interfaces will establish clear procedures for the voicing of concerns and the renegotiation of the terms of the relationship over time. [...]this choice is nothing more than the selection of a specific way in which this contractual interface will be managed – which, of course, will depend on how the preferences of relevant stakeholders are gathered and articulated into specific strategies. [...]our message is straightforward: the idea of governance within the ESG cannot be reduced to the notion of corporate governance. Effective ESG-based governance policies should provide an answer to two related challenges: the existence of decision-making costs, which affect the participation of stakeholders and may impair the definition of priorities that reflect the preferences of stakeholders at the corporate governance level;and the existence of contractual costs, which limit our ability to design efficient governance mechanisms in a competitive environment (Hansmann, 1996).

Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England.

The Covid-19 mortality rate varies between countries and over time but the extent to which this is explained by the underlying risk in those infected is unclear. Using data on all adults in England with a positive Covid-19 test between 1st October 2020 and 30th April 2021 linked to clinical records, we examined trends and risk factors for hospital admission and mortality. Of 2,311,282 people included in the study, 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days of a positive Covid-19 test. We found significant variation in the case hospitalisation and mortality risk over time, which remained after accounting for the underlying risk of those infected. Older age groups, males, those resident in areas of greater socioeconomic deprivation, and those with obesity had higher odds of admission and death. People with severe mental illness and learning disability had the highest odds of admission and death. Our findings highlight both the role of external factors in Covid-19 admission and mortality risk and the need for more proactive care in the most vulnerable groups.

Safety and Tolerability of Intra-Venous Ascorbic Acid in Allogeneic Hematopoietic Cell Transplant Recipients: A Matched Historical Control Study

Intravenous (IV) ascorbic acid (AA) improves organ function and reduces inflammation in sepsis, an inflammatory state similar to the post-hematopoietic cell transplant (HCT) milieu. This salutary effect is mediated by antioxidant activity as well transcriptional modulation by AA. HCT recipients are deficient in AA, therefore we evaluated the safety and efficacy of patients receiving parenteral AA after myeloablative conditioning for allogeneic HCT compared to similarly treated historical controls who did not receive AA. Methods: Patients with hematologic malignancies, AML (48% of patients), ALL (28%), and CML+MDS (25%) were enrolled in an IRB approved prospective phase 2 clinical trial (NCT03613727). IV AA 50 mg/kg/d divided in 3 doses was given on days 1-14 after HCT, followed by oral AA 500 mg bid from day 15 until 6 months post HCT (FDA-IND 138924). Conditioning regimens utilized included;fludarabine & melphalan (45%), cyclophosphamide with either busulfan (30%) or total body irradiation (25%). GVHD prophylaxis included calcineurin inhibitors and methotrexate or cellcept along with anti-thymocyte globulin (ATG). Primary endpoint was reduction in TRM at 1 year. Propensity score matching was used for matching study patients with similarly treated historical controls, matching for diagnosis, conditioning regimen, and CIBMTR disease risk category for comparison of clinical outcomes. Cox-proportional hazard models were used to estimate adjusted hazard ratios (AHR) between the time-to-event outcomes and study group, adjusted for patient age, donor type, stem cell source, diagnosis, conditioning regimen, and CIBMTR disease risk. Results of an interim analysis following a period of COVID 19 mandated suspension of study accrual are reported. Results: As of March 2020, 40 patients have received IV AA: these include HLA-matched related donor (MRD;n=11), and either 10/10 or 9/10 HLA- matched unrelated donor (MUD;n=22 & 7 respectively) recipients. Graft source was either peripheral blood (n=38) or bone marrow (n=2);88% patients had CIBMTR high risk disease. Median age was 55 years;males (19). All patients enrolled were deficient in AA at day 0, median AA level 0.3 mg/dL (range: 0.1-0.5);post AA infusion level was normal at 1.6 (1.2-5.7) on day 14. Median neutrophil and platelet recovery was by 12 days (range: 9-15 & 8-21 days respectively) with sustained donor engraftment. Median absolute CD3+ cell count at day 30 was 330 cells/microL. With a median follow up of 220 days in AA recipients, no statistically significant difference was observed in transplant related mortality between propensity matched historical controls and study patients (AHR 0.6, 95% CI: 0.2-1.5;p-value = 0.27);univariate survival analysis is depicted in Figure 1. Relapse was also similar (AHR 1.2, 95% CI: 0.3-4.5;p-value = 0.82), and despite a larger number of HLA mismatched unrelated donor recipients, acute GVHD (Grade II-IV) rates were similar in the two groups for both grade II-IV (AHR 0.8, 95% CI: 0.7-1.7;p-value = 0.65) and grade III-IV disease (AHR 0.6, 95% CI: 0.2-1.6;p-value = 0.32). Chronic GVHD rates were also similar (AHR 0.4, 95% CI: 0.1-2.7;p-value = 0.74). There are no attributable grade 3 - 4 toxicities from AA;CMV and EBV reactivation rates were not different in the two groups. Conclusions: In patients undergoing myeloablative allogeneic HCT the administration of IV ascorbic acid is safe and does not negatively impact myeloid engraftment or immune reconstitution. In this interim analysis, transplant related mortality, relapse and GVHD are not increased in IV AA recipients compared to historical controls. Thus, given its safety and tolerability, and possible salutary impact on survival and relapse in these high-risk patients, we posit the feasibility of a randomized phase 3 trial with IV AA in the post-transplant setting to determine its effect on relapse and TRM. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

A comparison of clinic versus home spirometry in the captain study

Rationale: Many respiratory consultations are currently taking place virtually due to the ongoing SARS-CoV-2 pandemic, while traditional lung function testing in clinic is difficult to perform. Therefore, there is increasing interest in whether home measurements of lung function could be used in place of clinic testing. However, little is known as to whether home spirometry accurately reflects clinic measurements, and whether it provides sufficient precision to inform treatment decisions. Therefore, we evaluated the agreement between home and clinic measurements of trough FEV1 using data from the CAPTAIN study. Methods: This Phase IIIA, double-blind, 24-52- week, parallel-group study randomized adults with uncontrolled asthma despite inhaled corticosteroid/long-acting β2-agonist therapy. Treatment: once-daily FF/VI (100/25, 200/25mcg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, 200/62.5/25mcg) (ELLIPTA inhaler). Trough FEV1 and other spirometry measurements were taken in clinic at approximately the same time in the morning using a MasterScope device. Patients also measured trough FEV1 each morning at home using a peak flow meter (AM3 device);three measurements were performed at each time point, with the highest measurement recorded. We used the Bland-Altman method to assess agreement between clinic trough FEV1 and the average of the home trough FEV1 measurements collected on the same day and 2 days prior to the clinic measurement, at baseline and at Week 24 (post hoc analyses). Only patients with a value for both clinic and home trough FEV1 were included (baseline: n=2434, Week 24: n=2261). Results: Agreement between clinic and home trough FEV1 measurements was poor (Figure). At baseline, the lower and upper limits of agreement were -812 mL and 943 mL, respectively, while at Week 24 these were -771 mL and 980 mL, respectively. In total, 6% of patients were outside the limits of agreement at baseline (n=151) and Week 24 (n=143) (Figure). Conclusions: This comparison of home and clinic spirometry in the CAPTAIN study suggests that home spirometry performed with the AM3 device cannot be used as an alternative to clinic spirometry, and that caution should be exercised when using home spirometry data in research or clinical care. The reason for the lack of agreement between home and clinic trough FEV1 measurements is not clear. Possible explanations include the different devices and methodologies, and lack of supervision and coaching for home measurements. However, it is possible that home spirometry may provide different and potentially complementary information to clinic measurements. Further investigation is warranted.

Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.

BACKGROUND: The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery. METHODS: Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001). CONCLUSIONS: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

The younger age profile of COVID-19 deaths in developing countries

This paper examines why a larger share of COVID-19 deaths occurs among young and middle-aged adults in developing countries than in high-income countries. Using novel data at the country, city, and patient levels, we investigate the drivers of this gap in terms of the key components of the standard Susceptible-Infected-Recovered framework. We obtain three main results. First, we show that the COVID-19 mortality age gap is not explained by younger susceptible populations in developing countries. Second, we provide indirect evidence that higher infection rates play a role, showing that variables linked to faster COVID-l9 spread-such as residential crowding and labor informality-are correlated with younger mortality age profiles across cities. Third, we show that lower recovery rates in developing countries account for nearly all of the higher death shares among young adults, and for almost half of the higher death shares among middle-aged adults. Our evidence suggests that lower recovery rates in developing countries are driven by a higher prevalence of preexisting conditions that have been linked to more severe COVID-19 complications, and by more limited access to hospitals and intensive care units in some countries.

Resource requirements for reintroducing elective surgery during the COVID-19 pandemic: modelling study.

BACKGROUND: The COVID-19 response required the cancellation of all but the most urgent surgical procedures. The number of cancelled surgical procedures owing to Covid-19, and the reintroduction of surgical acivirt, was modelled. METHODS: This was a modelling study using Hospital Episode Statistics data (2014-2019). Surgical procedures were grouped into four urgency classes. Expected numbers of surgical procedures performed between 1 March 2020 and 28 February 2021 were modelled. Procedure deficit was estimated using conservative assumptions and the gradual reintroduction of elective surgery from the 1 June 2020. Costs were calculated using NHS reference costs and are reported as millions or billions of euros. Estimates are reported with 95 per cent confidence intervals. RESULTS: A total of 4 547 534 (95 per cent c.i. 3 318 195 to 6 250 771) patients with a pooled mean age of 53.5 years were expected to undergo surgery between 1 March 2020 and 28 February 2021. By 31 May 2020, 749 247 (513 564 to 1 077 448) surgical procedures had been cancelled. Assuming that elective surgery is reintroduced gradually, 2 328 193 (1 483 834 - 3 450 043) patients will be awaiting surgery by 28 February 2021. The cost of delayed procedures is €5.3 (3.1 to 8.0) billion. Safe delivery of surgery during the pandemic will require substantial extra resources costing €526.8 (449.3 to 633.9) million. CONCLUSION: As a consequence of the Covid-19 pandemic, provision of elective surgery will be delayed and associated with increased healthcare costs.