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Assessment of Mitochondrial Function and Oxygen Consumption Measured During Ex Vivo Normothermic Machine Perfusion of Injured Pig Kidneys Helps to Monitor Organ Viability.
Donor kidney assessment may improve organ utilisation. Normothermic Machine Perfusion (NMP) has the potential to facilitate this advance. The mechanism of action is not yet determined and we aimed to assess mitochondrial function during NMP. Anaesthetised pigs (n = 6) had one kidney clamped for 60 min. The healthy contralateral kidney was removed and underwent NMP for 8 h (healthy control (HC), n = 6). Following 60 min warm ischaemia the injured kidney underwent HMP for 24 h, followed by NMP for 8 h (n = 6). Mitochondria were extracted from fresh tissue for analysis. Injured kidneys were analysed as two separate groups (IMa, n = 3 and IMb, n = 3). Renal resistance was higher (0.39ï, ± 0.29 vs. 1.65ï, ± 0.85; p = 0.01) and flow was lower (55ï, ± 28 vs. 7ï, ± 4; p = 0.03) during HMP in IMb than IMa. NMP blood flow was higher in IMa versus IMb (2-way ANOVA; p < 0.001) After 60 min NMP, O2 consumption was significantly lower in IMb versus IMa (p ≤ 0.002). State-3 respiration was significantly different between the groups (37ï, ± 19 vs. 24ï, ± 14 vs. 10ï, ± 8; nmolO2/min/mg; p = 0.049). Lactate levels were significantly lower in IMa versus IMb (p = 0.028). Mitochondrial respiration levels during NMP may be suggestive of kidney viability. Oxygen consumption, renal blood flow and lactate can differentiate severity of kidney injury during NMP.
Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.
Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.
Bariatric surgery improves access to renal transplantation and is safe in renal failure as well as after transplantation: A systematic review and meta-analysis.
INTRODUCTION: Effective workup and listing of end-stage renal disease (ESRD) patients for renal transplantation, often with multiple co-morbidities, poses a challenge for transplant teams. Obesity is a common co-morbidity associated with adverse outcomes in ESRD and kidney transplant (KT) recipients. Bariatric and metabolic surgery (BMS) has long been established as a safe and effective treatment for morbid obesity. In this study, the authors aimed to evaluate the strength of evidence for both the efficacy and safety of bariatric surgery in patients with ESRD or kidney transplantation. METHODS: A literature search was performed using key terms including "transplantation", "kidney", "renal", "obesity", and "bariatric". Databases searched include MEDLINE, EMBASE and Web of Science from inception to date (April 2021). Methodological quality was assessed using the Newcastle-Ottawa tool. Selected articles were then categorised into patients awaiting waiting list acceptance, patients awaiting transplantation, patients undergoing simultaneous BMS + KT and patients undergoing BMS following a previous renal transplant. Summary effects are presented with a level of statistical significance and 95% Confidence Intervals. RESULTS: A total of 28 articles were selected following the literature search. Fourteen studies on patients awaiting listing (n = 1903), nine on patients on the KT waiting list (n = 196), a single study on simultaneous BMS and KT and ten studies on patients undergoing BMS following KT (n = 198). Mean change in BMI for patients awaiting listing was -11.3 kg/m2 (95%CI: -15.3 to -7.3, p
SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis Patients.
Patients on hemodialysis (HD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mount poor neutralizing antibody responses after two-dose vaccination. Although serological responses have been associated with reduced rates of reinfection, the relationship between cellular immunogenicity and protection has not been established. We report, for the first time, high incidence of reinfection in patients on HD who are vaccine naive (25%), which identifies that T cell responses do not predict protection against reinfection. Instead, patients on HD who went on to become reinfected had mounted highly variable and sometimes robust proliferative T cell responses to a broad array of SARS-CoV-2 peptide pools during the primary infection. The understanding that SARS-CoV-2–specific T cell responses are not predictive of protection against future infection will be a critical issue when measuring clinical efficacy of vaccination in these vulnerable cohorts, particularly when facing rapidly emerging variants of concern.
Abdominal multiorgan procurement from slaughterhouse pigs: a bespoke model in organ donation after circulatory death for ex vivo organ perfusion compliant with the 3 Rs (Reduction, Replacement & Refinement).
BACKGROUND: Advances in organ preservation, reconditioning and assessment have been driven by the increasing necessity to utilise organs from extended criteria donors, particularly donors after circulatory death. Research efforts in this area have aided translation of machine perfusion technology into clinical practice. Pigs are anatomically and physiologically similar to humans and are an excellent model. However, conducting large animal experimental research is challenging and typically limited by ethical and economic constraints. Here we describe a reproducible, cost-effective multi-organ abdominal procurement model of porcine organs from the slaughterhouse. METHODS: Domestic pigs are electrically stunned and exsanguinated following the standard abattoir process. Via a longitudinal midline incision, the thoracoabdominal viscera are removed en bloc by incising along the anterior vertebral plane. The abdominal organs are isolated, perfused and separated preserving their respective vasculature, allowing individual organ use for specific experiments. RESULTS: The warm ischaemic time is kept between 15-30 minutes. Using this highly protocolized procurement technique we have procured 12 livers, 162 kidneys and 12 pancreata for research, the majority of which have been utilized for ex situ perfusion experiments. CONCLUSIONS: We have described a reliable and reproducible procedure for abdominal multi-organ procurement from slaughterhouse pigs.
Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation.
Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.
Abstract 1369: Predicting clinical pharmacokinetics and toxicity of current and emerging oncology therapeutics by normothermic perfusion of isolated human-sized organs
Abstract Novel cancer therapeutics have less than a 12% probability of translating from bench to bedside. Unwarranted toxicity and inadequate therapeutic delivery due to uptake by clearance organs, not predicted by current preclinical methods, have contributed towards this high rate of attrition. In the present work, we propose normothermic machine perfusion of human or human-sized organs as a more predictive, closer-to-human model to investigate drug pharmacokinetics and toxicity. Over the past decade, developments in the field of organ preservation for transplantation have enabled prolonged (>12 hours) normothermic machine perfusion (NMP) of isolated porcine or human organs ex vivo, maintaining quasi-physiological haemodynamic, synthetic and metabolic function using a packed red cell perfusate with physiological oxygenation and nutrient levels at normal body temperature. This preserves physiological processes such as metabolism and drug elimination, and enables easy access to tissue, blood and excreted biological fluids, with NMP livers producing bile and NMP kidneys producing urine. We hypothesise that this will provide a physiologically relevant platform to investigate drug pharmacokinetics and toxicity. We selected a widely used small-molecule chemotherapeutic (Irinotecan hydrochloride 2mg/ml, Medac, UK) which has seen decades of clinical use and benefits from extensive clinical pharmacokinetic data. The small-molecule drug was infused into isolated porcine and human livers and kidneys, with quantification of concentration time profiles of the prodrug and its main metabolites in plasma, bile and urine over 16-24 hours of NMP. In addition to irinotecan (CPT11), three of its metabolites (APC, SN38G, SN38) were successfully detected and quantified, demonstrating peak plasma concentrations (Cmax ~ 10,000 ng/mL, 1000 ng/mL, 100 ng/g, 30 ng/g), plasma decay rates and percentages of injected dose in bile (%ID ~20%, 8%, 25%, 1%) and urine (%ID ~20%, 0.06%, 0.5%,0.1%) that are comparable to clinical data. Drug-tissue toxicity could also be adequately replicated in the NMP model. In conclusion, we have demonstrated that human-sized isolated, normothermically perfused livers and kidneys accurately represent the clinically observed pharmacokinetic and toxicity profiles of an established small-molecule therapeutic. Further model validation is ongoing for biologics and other nanomedicines which are susceptible to clearance by the mononuclear phagocytic system or are hepato- or nephrotoxic. If this proves successful, normothermic machine perfusion of isolated porcine and human organs could greatly aid the early screening of candidate therapeutics and significantly enhance the pace and success rate with which they are translated into patients. Citation Format: Tamsyn Clark, Luca Bau, Fungai Dengu, Daniel Voyce, Robert Carlisle, Peter Friend, Constantin Coussios. Predicting clinical pharmacokinetics and toxicity of current and emerging oncology therapeutics by normothermic perfusion of isolated human-sized organs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1369.
The etiology of pediatric hydrocephalus across Asia: a systematic review and meta-analysis.
OBJECTIVE: Despite the high prevalence and significant implications of pediatric hydrocephalus, the etiological distribution of pediatric hydrocephalus across the diverse Asian demographic is poorly understood. This study aimed to inform clinical guidelines and public health decisions by identifying the etiological distribution of pediatric hydrocephalus across Asia. METHODS: In this systematic review and meta-analysis, the authors searched EMBASE, MEDLINE, CENTRAL, Global Health, Global Index Medicus, and Scopus, with no language restriction, from inception to January 27, 2023. Observational or experimental studies with pediatric data on the causes of hydrocephalus in a country within Asia were included. Pooled proportions of postinfectious hydrocephalus, nonpostinfectious hydrocephalus, and hydrocephalus related to spinal dysraphism were calculated using a random-effects model. Subgroup analyses were performed on prespecified moderators. Methodological study quality was assessed using the modified Newcastle-Ottawa Score and Cochrane's risk-of-bias tool as per the registered protocol on PROSPERO. RESULTS: The search yielded 5110 results, for which 79 articles were included, with data on 11,529 children from 18 Asian countries. The pooled proportion of nonpostinfectious hydrocephalus was 29.0% (95% CI 22.9-35.5); postinfectious hydrocephalus was 10.7% (95% CI 7.7-14.1); and hydrocephalus secondary to dysraphism was 7.6% (95% CI 5.1-10.5). The pooled proportion of postinfectious hydrocephalus was greatest in lower-middle-income countries (19.2% [95% CI 12.8-26.3]). There was a negative association between the proportion of postinfectious hydrocephalus and Human Development Index (-1.45 [95% CI -2.21 to -0.69]; p < 0.001); urbanization of the country (-0.008 [95% CI -0.012 to -0.004]; p < 0.001); and increasing distance from the equator (-0.016 [95% CI -0.026 to -0.006]; p = 0.002). The pooled proportion of nonpostinfectious hydrocephalus was greatest in high-income countries (36.7% [95% CI 27.6-46.3]). Certain etiologies of pediatric hydrocephalus were more common in different cultural regions, with postinfectious hydrocephalus most common in South Asia (23.2% [95% CI 15.8-31.5]); nonpostinfectious in East Asia (38.3% [95% CI 26.6-50.7]); and dysraphism in West Asia (11.9% [95% CI 6.4-18.8]). CONCLUSIONS: Geographic and economic characteristics are associated with the etiological distribution of pediatric hydrocephalus in Asia, with implications for prevention and management strategies. The large proportion of hydrocephalus cases in which the etiology was unclear highlights the need for both improved diagnostics as well as clear and strict universal guidelines on the etiological classification of hydrocephalus.
The Risk of Adhesive Bowel Obstruction in Children With Appendicitis: A Systematic Review.
OBJECTIVE: Complicated appendicitis is associated with a higher risk of postoperative complications, including adhesive bowel obstruction. The aim of this meta-analysis is to investigate the difference in rates of postoperative bowel obstruction in paediatric patients with complicated versus simple appendicitis and whether this is influenced by the surgical approach. METHODS: A systematic literature search following PRISMA guidelines was conducted using MEDLINE, Embase and Cochrane Library for studies that analysed incidence of adhesive bowel obstruction in paediatric patients after appendicectomy. Studies from 1998 to 2022 were included in analysis. The study protocol was registered on PROSPERO (ID CRD42022309769). RESULTS: Pooled analysis of 6 studies with low risk of bias and adequate follow up periods, considering 58,962 cases of appendicectomy, revealed complex appendicitis was associated with a near two-fold increase in incidence of SBO (pooled odds ratio 2.02 (95% CI 1.35-2.69)). Interestingly, a similar pooled analysis of 10 studies, considering 62,433 cases of appendicectomy, revealed no significant difference between open and laparoscopic management of complex appendicitis (pooled odds ratio 0.93 (95% CI 0.24 to 1.62)). CONCLUSION: Complex appendicitis is associated with a two-fold increase in the rates of adhesive bowel obstruction. Whilst there are cosmetic advantages of a laparoscopic approach, surgical expertise should be favoured in decision making relating to surgical approach (laparoscopic versus open) as the evidence for a laparoscopic approach reducing risks of adhesive bowel obstruction is not convincing. LEVEL OF EVIDENCE: Level II.
A landscape analysis of the key global stakeholders working on interventions around preterm birth that improve neonatal mortality and morbidity.
Background Over a decade after the landmark ‘Born too Soon’ report, preterm birth remains a leading cause of under-five mortality. Addressing its global burden is key to meeting United Nations Sustainable Development Goal 3; to end preventable deaths of newborns and children by 2030. We conducted a landscape analysis to explore the types of organisations addressing preterm birth, highlight the scope of interventions and initiatives, and identify gaps and opportunities for shared learning. Methods We combined google searches with citation searching, and opinion of experts in child health, to identify the major global stakeholders working to improve outcomes of preterm birth, with evidence of activity since 2012. We conducted a thematic analysis and narrative synthesis of key stakeholder websites to categorise their functions and priorities, and the types of interventions they were implementing. Results A total of 38 key organisations and 28 interventions were derived from the searches. Organisations were thematically grouped into knowledge sharing (n = 15), knowledge production (n = 12), funders (n = 6), legislation and advocacy (n = 15), implementer (n = 14) and network organisations (n = 11). Interventions covered a wide scope of functions including education (n = 11), research (n = 10), resources (n = 7), legislation (n = 2), and health systems (n = 2) interventions. The majority of global stakeholders were funded from and headquartered within high-income settings. Discussion There is scope for significant learning across global stakeholders, in particular to support carers in low-resource settings. Further opportunities for impact include a need for community-based initiatives and whole systems approach that address the long-term needs of preterm babies and their families, particularly in low- and middle-income countries (LMIC) settings. Greater knowledge production and funding from LMICs is needed to create contextually relevant resources and address implementation challenges.
An evidence-based approach towards sustainable anaesthesia
Health and social care currently account for between 4-5% of UK annual emissions1. Recognising this, the NHS has set a net zero goal for direct emissions by 2040, alongside an 80% reduction goal before 20322. Net zero here refers to a balance between residual emissions and carbon offsets. To this end, trusts are exploring measures to reduce their direct emissions through changes in practice, renewable electricity generation, and energy efficiency improvements. The NHS will then offset any remaining emissions after 2040. Surgery and anaesthesia together account for 8% of the carbon footprint associated with acute trusts at present, with nearly half of this due to the use of anaesthetic vapours and gases, predominantly nitrous oxide and desflurane3. The NHS net zero panel expect 2% of its total emissions reduction will be achieved through changes to the delivery of anaesthesia4. This raises the question: what changes can be made to anaesthetic practise to achieve this goal?
Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies.
Subarachnoid haemorrhage (SAH) is a subtype of stroke that predominantly impacts younger individuals. It is associated with high mortality rates and can cause long-term disabilities. This review examines the contribution of the initial blood load and the dynamics of clot clearance to the pathophysiology of SAH and the risk of adverse outcomes. These outcomes include hydrocephalus and delayed cerebral ischaemia (DCI), with a particular focus on the impact of blood located in the cisternal spaces, as opposed to ventricular blood, in the development of DCI. The literature described underscores the prognostic value of haematoma characteristics, such as volume, density, and anatomical location. The limitations of traditional radiographic grading systems are discussed, compared with the more accurate volumetric quantification techniques for predicting patient prognosis. Further, the significance of red blood cells (RBCs) and their breakdown products in secondary brain injury after SAH is explored. The review presents novel interventions designed to accelerate clot clearance or mitigate the effects of toxic byproducts released from erythrolysis in the cerebrospinal fluid following SAH. In conclusion, this review offers deeper insights into the complex dynamics of SAH and discusses the potential pathways available for advancing its management.
Delivering medical leadership training through the Healthcare Leadership Academy: a four year analysis.
BACKGROUND: Formal leadership training is typically targeted at senior health professionals. The Healthcare Leadership Academy (HLA) was formed in 2016 to provide a leadership programme for students and early-career health professionals. This study analyses the effectiveness of the HLA scholarship programme as an intervention for improving interest in and preparing scholars for future leadership roles. METHODS: Survey data was used to assess the effectiveness of the HLA Scholarship program in cultivating leadership development. Questions required either multiple-choice, free text, ranking or Likert scale ('strongly agree', 'agree', 'neither agree nor disagree', 'disagree', 'strongly disagree) responses. Participants spanned six regions (London, Newcastle, Bristol, Belfast, Edinburgh, and Amsterdam) in four countries (England, Scotland, Northern Ireland, and the Netherlands). Descriptive statistical analyses were conducted, and insights were drawn from the open-ended survey questions using a leadership framework. RESULTS: Seventy participants who underwent the course between 2016 and 2020 completed the questionnaire. Nearly all (99%) found that the training provided on the programme had equipped them to be more effective leaders, with 86% of respondents stating that they were more likely to take on leadership roles. Nearly all (97.1%) found the course to be either of good or very good quality. Nineteen insights were identified from free text responses that fitted under one of the four themes of the leadership framework: "optimising", "resolving uncertainty", "enhancing adaptability", and "promulgating a vision". CONCLUSIONS: Healthcare leadership is a non-negotiable component of healthcare delivery in the 21st Century. As healthcare professionals, it is our duty to be effective leaders confident and competent in navigating the increasingly complex systems within which we operate for the benefit of ourselves, colleagues, and patients. By accounting for known shortcomings and developing ameliorative measures, the HLA Scholarship programme addresses unmet needs in a structured manner to support effective long-term healthcare leadership development.
Epilepsy care and outcome in low- and middle-income countries: A scoping review
Objectives: Epilepsy is a common neurological condition in low- and middle-income countries (LMICs). This study aims to systematically review, analyze, evaluate, and synthesize information on the current state of medical and surgical management and outcomes of epilepsy in LMICs. Materials and Methods: Systematic searches were conducted on MEDLINE, EMBASE, World Health Organization Global Index Medicus, African Journals Online, WOS, and Scopus, covering the period from the inception of the databases to August 18th, 2021, focusing on studies reporting management and outcomes of epilepsy in LMICs. Results: A total of 2298 unique studies were identified, of which, 48 were included (38035 cases). The mean age was 20.1 ± 19.26 years with a male predominance in 60.92% of cases. The type of seizure commonly reported in most of the studies was absence seizures (n = 8302, 21.82%); partial focal seizure (n = 3891, 10.23%); and generalized tonic-clonic seizures (n = 3545, 9.32%) which were the next most common types of seizures. Mesiotemporal epilepsy was less frequently reported (n = 87, 0.22%). Electroencephalogram was commonly used (n = 2516, 6.61%), followed by computed tomography scan (n = 1028, 2.70%), magnetic resonance imaging (n = 638, 1.67%), and video telemetry (n = 484, 1.27%) in the care of patients with seizures. Primary epilepsy was recorded in 582 patients (1.53%) whereas secondary epilepsy was present in 333 patients (0.87%). Carbamazepine was the most used anti-epileptic drug (n = 2121, 5.57%). Surgical treatment was required for 465 (1.22%) patients. Conclusion: In LMICs, epilepsy is underreported. There is still a lack of adequate tools for the diagnosis of primary or secondary epilepsy as well as adequate access to medical management of those reported.
Investigating Wilms' Tumours Worldwide: A Report of the OxPLORE Collaboration-A Cross-Sectional Observational Study.
BACKGROUND: Childhood cancer is neglected within global health. Oxford Pediatrics Linking Oncology Research with Electives describes early outcomes following collaboration between low- and high-income paediatric surgery and oncology centres. The aim of this paper is twofold: to describe the development of a medical student-led research collaboration; and to report on the experience of Wilms' tumour (WT). METHODS: This cross-sectional observational study is reported as per STROBE guidelines. Collaborating centres included three tertiary hospitals in Tanzania, Rwanda and the UK. Data were submitted by medical students following retrospective patient note review of 2 years using a standardised data collection tool. Primary outcome was survival (point of discharge/death). RESULTS: There were 104 patients with WT reported across all centres over the study period (Tanzania n = 71, Rwanda n = 26, UK n = 7). Survival was higher in the high-income institution [87% in Tanzania, 92% in Rwanda, 100% in the UK (X2 36.19, p
A Journey Undertaken by Families to Access General Surgical Care for their Children at Muhimbili National Hospital, Tanzania; Prospective Observational Cohort Study.
BACKGROUND: A majority of the 2 billion children lacking access to safe, timely and affordable surgical care reside in low-and middle-income countries. A barrier to tackling this issue is the paucity of information regarding children's journey to surgical care. We aimed to explore children's journeys and its implications on accessing general paediatric surgical care at Muhimbili National Hospital (MNH), a tertiary centre in Tanzania. METHODS: A prospective observational cohort study was undertaken at MNH, recruiting patients undergoing elective and emergency surgeries. Data on socio-demographic, clinical, symptoms onset and 30-days post-operative were collected. Descriptive statistics and Mann-Whitney, Kruskal-Wallis and Fisher's exact tests were used for data analysis. RESULT: We recruited 154 children with a median age of 36 months. The majority were referred from regional hospitals due to a lack of paediatric surgery expertise. The time taken to seeking care was significantly greater in those who self-referred (p = 0.0186). Of these participants, 68.4 and 31.1% were able to reach a referring health facility and MNH, respectively, within 2 h of deciding to seek care. Overall insurance coverage was 75.32%. The median out of pocket expenditure for receiving care was $69.00. The incidence of surgical site infection was 10.2%, and only 2 patients died. CONCLUSION: Although there have been significant efforts to improve access to safe, timely and affordable surgical care, there is still a need to strengthen children's surgical care system. Investing in regional hospitals may be an effective approach to improve access to children surgical care.
Impact of the COVID-19 pandemic on paediatric patients with cancer in low-income, middle-income and high-income countries: protocol for a multicentre, international, observational cohort study.
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.
Building back better children's surgical services toward universal health coverage: Perspectives from Bangladesh and Zimbabwe.
INTRODUCTION: This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Children's surgical services are crucial, yet underappreciated, for children's health and must be sufficiently addressed to make and sustain progress toward universal health coverage (UHC). Despite their considerable burden and socioeconomic cost, surgical diseases have been relatively neglected in favor of communicable diseases living up to their inauspicious moniker: 'the neglected stepchild of global health'. This article aims to raise awareness around children's surgical diseases and offers perspectives from two prototypical LMICs on strengthening surgical services in the context of health systems recovery following the COVID-19 experience to make and sustain progress toward UHC. APPROACH: We used a focused literature review supplemented by the perspectives of local experts and the 6-components framework for surgical systems planning to present two case studies of Bangladesh and Zimbabwe. The lived experiences of the authors are used to describe the impact of COVID-19 on respective surgical systems and offer perspectives on building back the health system and recovering essential health services for sustainability and resilience. FINDINGS: We found that limited high-level policy and planning instruments, an overburdened and under-resourced health and allied workforce, underdeveloped surgical infrastructure (from key utilities to essential medical products), lack of locally generated research, and the specter of prohibitively high out-of-pocket costs for children's surgery are common challenges in both countries that have been exacerbated by the COVID-19 pandemic. DISCUSSION: Continued chronic underinvestment and inattention to children's surgical diseases coupled with the devastating effect of the COVID-19 pandemic threaten progress toward key global health objectives. Urgent attention and investment in the context of health systems recovery is needed from policy to practice levels to improve infrastructure; attract, retain and train the surgical and allied health workforce; and improve service delivery access with equity considerations to meet the 2030 Lancet Commission goals, and make and sustain progress toward UHC and the SDGs.