Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Impact of rural-urban energy equality on environmental sustainability and the role of governance

Globally, rural areas suffer from less infrastructure relative to urban areas. Political and development economists have mainly attributed this disparity in infrastructure distribution to governance. The literature has sufficiently discussed the role that rural-urban infrastructure inequality plays in development outcomes such as poverty. However, not much is known about the effect of the rural-urban infrastructure gap on the environment. To contribute to knowledge and policy discussions, we investigate the impact of rural-urban energy access (in)equality on environmental degradation and the role governance plays using data from 47 sub-Saharan African countries from 2000–2020. Evidence from the heteroskedasticity-based instrumental variable regression consistent with Driscoll and Kraay's estimation revealed that bridging rural-urban energy access inequality is associated with reduction in environmental degradation. We also documented that the direct effect of the governance-related variables used is mixed. The moderation and marginal effect estimates showed that improving governance quality conditions equality in rural-urban energy access to reduce environmental degradation. From a policy perspective, these findings suggest that the implementation of rural electrification policies supported by a good governance system would play a crucial role in mitigating environmental degradation in developing countries

Unveiling the effect of transport infrastructure and technological innovation on economic growth, energy consumption and CO<inf>2</inf> emissions

This study investigates the impact of transport infrastructure and technological innovation on economic growth (GDP), energy consumption (EC) and carbon emissions (CO2e) in the European Union (EU) using the dynamic system-generalised method of moment and data from 1995 to 2019. The results indicate that EC unidirectionally increases GDP, while GDP and EC reduce and increase CO2e, respectively. The results also demonstrate that innovation directly increases GDP and EC; however, freight transport infrastructure increases GDP and CO2e while reducing EC. The nonlinear analysis reveals that innovation has a U-shaped relationship with GDP and an inverted U-shaped relationship with EC. Furthermore, our results demonstrate that freight and rail infrastructure have an inverted U-shaped relationship with CO2e and no nonlinear relationship with GDP. Again, the rail infrastructure has a U-shaped relationship with EC. The conditional effect analysis reveals that freight and rail infrastructure interact with innovation to raise GDP. The findings indicate that freight transport infrastructure interacts with innovation to reduce EC and CO2e. Finally, rail and freight infrastructure interact with trade and foreign direct investment to influence GDP, EC and CO2e. Subsequently, EU countries must emphasise and enhance technological innovation to achieve energy efficiency

Conditions associated with severe orofacial infections: The kath experience

Background: Severity of orofacial infections is dependent on a balance between host immunity and causative microbe related factors. Severe orofacial infections (SOI), if not controlled, could lead to serious complications.Aim: The aim of this study was to determine the conditions associated with severe orofacial infections seen at the Komfo Anokye Teaching Hospital (KATH).Materials and Methods: This was a 2-year retrospective study of all cases of orofacial infections admitted to the oral and maxillofacial surgery ward of KATH from January 2017 to December 2018. A specially designed form was used to collect relevant information from patients’ records. Data was entered into Excel and later transported to SPSS for analysis. Ethical approval was obtained.Results: A total of one hundred and twenty (120) patients were seen during the period comprising 75 males and 45 females, giving a male to female ratio of 1.6:1. Eighty-one (67.5%) of the patients had low haemoglobin levels at the time of admission and 11.7% were known hypertensives on medication while 10.3% were newly diagnosed cases of hypertension. 17.0% were known diabetes mellitus (DM) patients and were on oral hypoglycemic agents but only 56.8% of them took their medication regularly. An additional 23.7% were newly diagnosed with DM. Sixty-four (64) has liver impairment, 79 had renal impairment.Conclusion: Anemia was the major condition associated with the SOI. This meant that in the management of SOI, correction of anaemia should be prioritized. DM, uncontrolled hypertension, renal and liver diseases were also seen to be associated with SO

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.

BACKGROUND No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. METHOD This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC. CONCLUSION Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer