Mahmoud ElFiky

BackgroundImproving women's health is a critical component of the sustainable development goals. Although obstetric outcomes in Africa have received significant focus, non-obstetric surgical outcomes for women in Africa remain under-examined.
Methods
We did a secondary analysis of the African Surgical Outcomes Study (ASOS) and International Surgical Outcomes Study (ISOS), two 7-day prospective observational cohort studies of outcomes after adult inpatient surgery. This sub-study focuses specifically on the analysis of the female, elective, non-obstetric, non-gynaecological surgical data collected during these two large multicentre studies. The African data from both cohorts are compared with international (non-African) outcomes in a risk-adjusted logistic regression analysis using a generalised linear mixed-effects model. The primary outcome was severe postoperative complications including in-hospital mortality in Africa compared with non-African outcomes.
Results
A total of 1698 African participants and 18 449 international participants met the inclusion criteria. The African cohort were younger than the international cohort with a lower preoperative risk profile. Severe complications occurred in 48 (2.9%) of 1671, and 431 (2.3%) of 18 449 patients in the African and international cohorts, respectively, with in-hospital mortality after severe complications of 23/48 (47.9%) in Africa and 78/431 (18.1%) internationally. Women in Africa had an adjusted odds ratio of 2.06 (95% confidence interval, 1.17–3.62; P=0.012) of developing a severe postoperative complication after elective non-obstetric, non-gynaecological surgery, compared with the international cohort.
Conclusions
Women in Africa have double the risk adjusted odds of severe postoperative complications (including in-hospital mortality) after elective non-obstetric, non-gynaecological surgery compared with the international incidence.

BackgroundImproving women's health is a critical component of the sustainable development goals. Although obstetric outcomes in Africa have received significant focus, non-obstetric surgical outcomes for women in Africa remain under-examined.
Methods
We did a secondary analysis of the African Surgical Outcomes Study (ASOS) and International Surgical Outcomes Study (ISOS), two 7-day prospective observational cohort studies of outcomes after adult inpatient surgery. This sub-study focuses specifically on the analysis of the female, elective, non-obstetric, non-gynaecological surgical data collected during these two large multicentre studies. The African data from both cohorts are compared with international (non-African) outcomes in a risk-adjusted logistic regression analysis using a generalised linear mixed-effects model. The primary outcome was severe postoperative complications including in-hospital mortality in Africa compared with non-African outcomes.
Results
A total of 1698 African participants and 18 449 international participants met the inclusion criteria. The African cohort were younger than the international cohort with a lower preoperative risk profile. Severe complications occurred in 48 (2.9%) of 1671, and 431 (2.3%) of 18 449 patients in the African and international cohorts, respectively, with in-hospital mortality after severe complications of 23/48 (47.9%) in Africa and 78/431 (18.1%) internationally. Women in Africa had an adjusted odds ratio of 2.06 (95% confidence interval, 1.17–3.62; P=0.012) of developing a severe postoperative complication after elective non-obstetric, non-gynaecological surgery, compared with the international cohort.
Conclusions
Women in Africa have double the risk adjusted odds of severe postoperative complications (including in-hospital mortality) after elective non-obstetric, non-gynaecological surgery compared with the international incidence.

{Dear EditorDuring the COVID-19 pandemic, multiple theories were proposed based on the observation that countries with an ongoing national Bacillus Calmette-Guérin (BCG) immunization programme had lower SARS-CoV-2 case rates and COVID-19 mortality than countries that had stopped BCG vaccine administration. There was, however, no evidence supporting or disputing this theory1,2. Owing to the uncertainty on the role of BCG vaccine on the outcomes of patients with perioperative SARS-CoV-2 infection, this international study aimed to determine whether previous BCG vaccination was associated with reduced postoperative pulmonary complications (PPC) and 30-day mortality in patients undergoing surgery who developed SARS-CoV-2 infection.}

Summary Esophageal atresias/tracheoesophageal fistulas (EA/TEF) are rare congenital anomalies caused by aberrant development of the foregut. Previous studies indicate that rare or de novo genetic variants significantly contribute to EA/TEF risk, and most individuals with EA/TEF do not have pathogenic genetic variants in established risk genes. To identify the genetic contributions to EA/TEF, we performed whole genome sequencing of 185 trios (probands and parents) with EA/TEF, including 59 isolated and 126 complex cases with additional congenital anomalies and/or neurodevelopmental disorders. There was a significant burden of protein-altering de novo coding variants in complex cases (p = 3.3 × 10−4), especially in genes that are intolerant of loss-of-function variants in the population. We performed simulation analysis of pathway enrichment based on background mutation rate and identified a number of pathways related to endocytosis and intracellular trafficking that as a group have a significant burden of protein-altering de novo variants. We assessed 18 variants for disease causality using CRISPR-Cas9 mutagenesis in Xenopus and confirmed 13 with tracheoesophageal phenotypes. Our results implicate disruption of endosome-mediated epithelial remodeling as a potential mechanism of foregut developmental defects. Our results suggest significant genetic heterogeneity of EA/TEF and may have implications for the mechanisms of other rare congenital anomalies.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001).Conclusions The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.Data are available on reasonable request. Deidentified date will be shared on request.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001).Conclusions The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.Data are available on reasonable request. Deidentified date will be shared on request.

Summary SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.

Summary We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05?1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4?7 days or ≥ 8 days of 1.25 (1.04?1.48), p = 0.015 and 1.31 (1.11?1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

SummaryBackground
Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in-hospital mortality.
Methods
We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for those at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30-day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov, NCT03853824.
Findings
Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported.
Interpretation
This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa.
Funding
Bill & Melinda Gates Foundation and the World Federation of Societies of Anaesthesiologists.
Translations
For the Arabic, French and Portuguese translations of the abstract see Supplementary Materials section.

SummaryBackground
Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality.
Methods
We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis.
Findings
We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation
Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030.
Funding
Wellcome Trust.

The various malformations of the aerodigestive tract collectively known as esophageal atresia/tracheoesophageal fistula (EA/TEF) constitute a rare group of birth defects of largely unknown etiology. Previous studies have identified a small number of rare genetic variants causing syndromes associated with EA/TEF. We performed a pilot exome sequencing study of 45 unrelated simplex trios (probands and parents) with EA/TEF. Thirteen had isolated and 32 had nonisolated EA/TEF; none had a family history of EA/TEF. We identified de novo variants in protein-coding regions, including 19 missense variants predicted to be deleterious (D-mis) and 3 likely gene-disrupting (LGD) variants. Consistent with previous studies of structural birth defects, there is a trend of increased burden of de novo D-mis in cases (1.57-fold increase over the background mutation rate), and the burden is greater in constrained genes (2.55-fold, p = 0.003). There is a frameshift de novo variant in EFTUD2, a known EA/TEF risk gene involved in mRNA splicing. Strikingly, 15 out of 19 de novo D-mis variants are located in genes that are putative target genes of EFTUD2 or SOX2 (another known EA/TEF gene), much greater than expected by chance (3.34-fold, p value = 7.20e−5). We estimated that 33% of patients can be attributed to de novo deleterious variants in known and novel genes. We identified APC2, AMER3, PCDH1, GTF3C1, POLR2B, RAB3GAP2, and ITSN1 as plausible candidate genes in the etiology of EA/TEF. We conclude that further genomic analysis to identify de novo variants will likely identify previously undescribed genetic causes of EA/TEF.

SummaryCongenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

BackgroundThe African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery.
Methods
Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity.
Results
The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3–7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1–6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1–6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9–5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2–9.4).
Conclusions
ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork.
Clinical trial registration
ClinicalTrials gov NCT03853824.

{Dear EditorThe COVID-19 pandemic has had profound impacts on safe healthcare delivery, particularly within surgical specialties1. There has been clear evidence of pulmonary complications and death associated with surgery following perioperative COVID infection2,3. Mitigation of COVID-related risk for patients depends upon several primary tenets of safe surgery, including implementation of appropriate COVID-secure treatment pathways4, provision of adequate testing for patients to ensure COVID-negative status and protection of staff members through suitable personal protective equipment (PPE). Following the initial peaks of SARS-CoV-2 infection, healthcare service provision was afforded time for preparation and reorganization before subsequent waves of infection. An ability to use this window of opportunity was dependent not only on strategic decision making but also national financial resources and healthcare capabilities.}

{This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection.This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P \< 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P \< 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P \< 0.001).Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.This study compared death rates in patients who developed pulmonary complications of surgery before and during the pandemic in two large, international studies. Patients who underwent surgery during the pandemic tended to be younger and fitter. Overall, 4.3 per cent were diagnosed with SARS-CoV-2 infection after surgery in the pandemic cohort. Deaths within 30 days after surgery tripled during the first wave of the pandemic (from 0.7 to 2.0 per cent), whereas the rate of pulmonary complications remained the similar (7.1 to 6.3 per cent). Over half of these excess deaths (54.8 per cent) were estimated to be related to SARS-CoV-2 infection.}

Background Pneumonia is a common and severe complication of abdominal surgery, it is associated with increased length of hospital stay, healthcare costs, and mortality. Further, pulmonary complication rates have risen during the SARS-CoV-2 pandemic. This study explored the potential cost-effectiveness of administering preoperative chlorhexidine mouthwash versus no-mouthwash at reducing postoperative pneumonia among abdominal surgery patients. Methods A decision analytic model taking the South African healthcare provider perspective was constructed to compare costs and benefits of mouthwash versus no-mouthwash-surgery at 30 days after abdominal surgery. We assumed two scenarios: (i) the absence of COVID-19; (ii) the presence of COVID-19. Input parameters were collected from published literature including prospective cohort studies and expert opinion. Effectiveness was measured as proportion of pneumonia patients. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainties. The results of the probabilistic sensitivity analysis were presented using cost-effectiveness planes and cost-effectiveness acceptability curves. Results In the absence of COVID-19, mouthwash had lower average costs compared to no-mouthwash-surgery, $3,675 (R 63,770) versus $3,958 (R 68,683), and lower proportion of pneumonia patients, 0.029 versus 0.042 (dominance of mouthwash intervention). In the presence of COVID-19, the increase in pneumonia rate due to COVID-19, made mouthwash more dominant as it was more beneficial to reduce pneumonia patients through administering mouthwash. The cost-effectiveness acceptability curves shown that mouthwash surgery is likely to be cost-effective between $0 (R0) and $15,000 (R 260,220) willingness to pay thresholds. Conclusions Both the absence and presence of SARS-CoV-2, mouthwash is likely to be cost saving intervention for reducing pneumonia after abdominal surgery. However, the available evidence for the effectiveness of mouthwash was extrapolated from cardiac surgery; there is now an urgent need for a robust clinical trial on the intervention on non-cardiac surgery.

PURPOSEAs cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway.PATIENTS AND METHODSThis international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation).RESULTSOf 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76).CONCLUSIONWithin available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.

BACKGROUND: The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort.

METHODS: All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes.

RESULTS: Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%).

CONCLUSIONS: Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.

Introduction Childhood cancers are a leading cause of non-communicable disease deaths for children around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases is currently undertaking the first international cohort study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short-term to medium-term impacts on childhood cancer outcomes.Methods and analysis This is a multicentre, international cohort study that will use routinely collected hospital data in a deidentified and anonymised form. Patients will be recruited consecutively into the study, with a 12-month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anticancer treatment for the following cancers: acute lymphoblastic leukaemia, Burkitt lymphoma, Hodgkin lymphoma, Wilms tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas and neuroblastomas. Patients must be newly presented or must be undergoing active anticancer treatment from 12 March 2020 to 12 December 2020. The primary objective of the study was to determine all-cause mortality rates of 30 days, 90 days and 12 months. This study will examine the factors that influenced these outcomes. χ2 analysis will be used to compare mortality between low-income and middle-income countries and high-income countries. Multilevel, multivariable logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for publication in a peer-reviewed journal.