Action against birth defects: if not now, when?

BACKGROUND: More children are surviving through interventions to address the infectious causes of under-5 mortality; subsequently, the proportion of deaths caused by birth defects is increasing. Prevention, diagnosis, treatment and care interventions for birth defects are available but are needed where the burden is highest, low-and-middle-income countries. OBJECTIVES: A selection of birth defect focused publications, conferences, and World Health Assembly resolutions from 2000 to 2017 show that global efforts were made to raise the profile of birth defects in global public health. However, recent donor support and national government interest has waned. Without concerted global action to improve primary prevention and care for children born with birth defects, the Sustainable Development Goal targets for child survival will not be met. RESULTS: Birth defects make up 8% and 10% of global under-5 and neonatal deaths respectively, making them significant contributors to preventable loss of life for children. Survivors face long-term morbidity and lifelong disability which compounds the health and economic woes of individuals, families, communities and society as a whole. Demographic changes in sub-Saharan Africa portend a growing number of births with 1.6 billion projected from 2021 to 2050. More births and better survival without effective prevention and treatment for birth defects translates into more mortality and disability from birth defects. CONCLUSIONS: We recommend interventions for prevention of birth defects. These are evidenced-based and affordable, but require low- and middle-income countries to strengthened their health systems. Action against birth defects now will prevent premature deaths and long-term disability, and lead to stronger, more resilient health systems.

The importance of global bioethics to paediatric health care.

The paradigm of values adopted by the global health community has a palpable, albeit often unseen, impact on patient health care. In this Viewpoint, we investigate an inherent tension in the core values of medical ethics and clinical practice that could explain why paediatric health care faces resource constraints despite compelling economic and societal imperatives to prioritise child health and wellbeing. The dominant narrative in the philosophy of medicine tends to disproportionately underscore values of independence and self-determination, which becomes problematic in the context of paediatric patients, who by their very nature epitomise vulnerability and dependence. A double-jeopardy situation arises when disadvantaged children see their inherent dependence leveraged against them. We illustrate this predicament through specific examples relating to rights and obligations and to autonomy. Alternative value perspectives-communitarianism and relational autonomy-might offer more robust protection for vulnerable children. A shift away from the dominant narrative towards a more explicit and inclusive discussion of values is necessary. Such a shift requires giving a legitimate platform to diverse perspectives, with the presumption that collective moral progress is possible; this endeavour is embodied by global bioethics. Successful implementation of global bioethics, in turn, hinges on close collaboration between practicing clinicians and bioethicists. Taking global bioethics seriously and actively pursuing collaboration could help the global health community achieve more equitable health care.

Revising Destiny - Surgical Care in Birth Defects.

Birth Defects are accountable for the substantial surgical burden of disease worldwide. It can bring upon death, chronic illness, disability [physical or mental or both], financial burden, social stigma, abandonment, feticide and Infanticide. Availing timely and safe surgery can minimize the potential fatalities and sufferings caused by birth defects. Yet surgery is not treated as essential for the management of birth defects, especially in lower middle-income countries. It causes potentially correctable conditions to exacerbate, which can lead to death or lifelong disabilities. Surgical care cannot only correct birth defects but also can avert potential Disability Adjusted Life Years (DALYs) and financial burden. Furthermore, surgical correction facilitates social inclusion. Such transformation can be equated to "Revising Destiny". A "whole of society" approach focused on surgical care is instrumental for addressing the health, financial, and social implications of birth defects. LEVEL OF EVIDENCE V: Expert Opinion.

A Prospective Observational Study of Preoperative Anaemia Management Aided by Bedside Haemoglobin Testers in a Low-Resource Setting.

AIM: Paediatric-preoperative anaemia management is challenging in settings where clinical judgment is used to diagnose anaemia owing to a lack of timely, affordable preoperative haemoglobin testing. We analysed anaemia management in such a setting after the introduction of point-of-care bedside haemoglobin testers. METHOD: 1033 children who underwent surgery at a hospital in Bangladesh were included in this study. 569 underwent major surgery, and 464 underwent minor surgery and belonged to predominantly ASA category 1 or 2. RESULTS: 940/1033 children underwent preoperative anaemia testing. Average haemoglobin was 11.7 g/dL. 103/1033 children were deemed clinically anaemic. However, 285 children were found to have anaemia based on bedside testing. Sensitivity of clinical judgement was 33.68% (95 % CI 28.22%-39.49%), and the specificity was 99.08% (95 % CI 98.02%-99.66%). 63/1033 had preoperative anaemia treatment, of whom 60 underwent transfusion. Subgroup analysis of children with haemoglobin <10 g/dL (n = 124) was done to compare conservative vs liberal transfusion strategy. 43/124 of this subset was transfused. Average length of stay for those transfused was 11.7 days, and those who weren't was 9.9 days (p = 0.087). 4 patients in the transfused subgroup required post-op ICU, and only 1 patient in the conservatively managed arm required ICU (p = 0.048). CONCLUSION: This study demonstrates the positive impact of bedside haemoglobin testers as they have resulted in a significantly higher proportion of children diagnosed with anaemia at a fraction of the cost and logistics involved in laboratory testing. Further research on haemoglobin thresholds is required to understand the safety and long-term impact of restrictive transfusion in the surgical context. LEVEL OF EVIDENCE: 2c (Grading as per the Oxford Centre for Evidence Based Medicine).

Anorectal malformations in low and middle-income countries- spectrum, burden and management.

The clinical presentation, diagnosis and management of anorectal malformation has been well described in the literature, however the experience with these conditions in low-and middle-income countries is often shaped in unique ways due to the social, cultural and economic factors at work in these regions. This leads to adaptation of modifications in management options for these babies that usually present as delayed cases with added poor prognostic factors like sepsis leading to need for emergency resuscitation and overall increased morbidity and mortality. This article explores the anomaly from a global surgery lens and outlines the spectrum of the anomaly, burden faced in the resource constrained environment and the management options adopted for successful management under the available circumstances.

Correction: Academic global surgical competencies: A modified Delphi consensus study.

[This corrects the article DOI: 10.1371/journal.pgph.0002102.].

Patients' characteristics and 30-day mortality for those undergoing elective surgeries during the COVID-19 pandemic in Bangladesh.

BACKGROUND: The COVID-19 pandemic has significantly impacted the surgical practice throughout the world, including elective surgical care. This study investigated the characteristics of patients undergoing elective surgery, the prevalence of COVID-19 infection, the surgical procedures performed, and 30-day mortality in general and pediatric surgical settings in selected tertiary-level hospitals in Bangladesh from November 2020 to August 2021. METHODS: This serial cross-sectional study included 264 patients scheduled for elective surgeries during the study period. All patients underwent COVID-19 real-time polymerase chain reaction (RT-PCR) testing within 24 hours before surgery. Data on age, sex, common comorbidities, surgical procedures, and 30-day mortality were collected and analyzed. Furthermore, comparisons were made between COVID-19 positive and negative patients. RESULTS: The prevalence of COVID-19 infection among patients was 10.6%. Older age, a history of major surgery within the last three months, hypertension, and diabetes mellitus were significantly associated with COVID-19 infection. All COVID-19-negative patients underwent surgery, while only 46.4% of COVID-19-positive patients underwent surgery. The most common surgical procedures were related to the digestive system, breast, and urinary system. Only one patient (0.4%) died within 30 days after surgery among the COVID-19-negative patients, whereas two patients (7.1%) died among the COVID-19-positive patients: one before surgery and one after surgery. CONCLUSIONS: This study provides valuable insights into the characteristics, burden of COVID-19 infection, and 30-day mortality of patients undergoing elective surgery in tertiary care centers in Bangladesh during the pandemic.

Academic global surgical competencies: A modified Delphi consensus study.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

Surgically Correctable Congenital Anomalies: Reducing Morbidity and Mortality in the First 8000 Days of Life.

BACKGROUND: Congenital anomalies are a leading cause of morbidity and mortality worldwide. We aimed to review the common surgically correctable congenital anomalies with recent updates on the global disease burden and identify the factors affecting morbidity and mortality. METHOD: A literature review was done to assess the burden of surgical congenital anomalies with emphasis on those that present within the first 8000 days of life. The various patterns of diseases were analyzed in both low- and middle-income countries (LMIC) and high-income countries (HIC). RESULTS: Surgical problems such as digestive congenital anomalies, congenital heart disease and neural tube defects are now seen more frequently. The burden of disease weighs more heavily on LMIC. Cleft lip and palate has gained attention and appropriate treatment within many countries, and its care has been strengthened by global surgical partnerships. Antenatal scans and timely diagnosis are important factors affecting morbidity and mortality. The frequency of pregnancy termination following prenatal diagnosis of a congenital anomaly is lower in many LMIC than in HIC. CONCLUSION: Congenital heart disease and neural tube defects are the most common congenital surgical diseases; however, easily treatable gastrointestinal anomalies are underdiagnosed due to the invisible nature of the condition. Current healthcare systems in most LMICs are still unprepared to tackle the burden of disease caused by congenital anomalies. Increased investment in surgical services is needed.

Recommendations for developing effective and safe paediatric and congenital heart disease services in low-income and middle-income countries: a public health framework.

The global burden of paediatric and congenital heart disease (PCHD) is substantial. We propose a novel public health framework with recommendations for developing effective and safe PCHD services in low-income and middle-income countries (LMICs). This framework was created by the Global Initiative for Children's Surgery Cardiac Surgery working group in collaboration with a group of international rexperts in providing paediatric and congenital cardiac care to patients with CHD and rheumatic heart disease (RHD) in LMICs. Effective and safe PCHD care is inaccessible to many, and there is no consensus on the best approaches to provide meaningful access in resource-limited settings, where it is often needed the most. Considering the high inequity in access to care for CHD and RHD, we aimed to create an actionable framework for health practitioners, policy makers and patients that supports treatment and prevention. It was formulated based on rigorous evaluation of available guidelines and standards of care and builds on a consensus process about the competencies needed at each step of the care continuum. We recommend a tier-based framework for PCHD care integrated within existing health systems. Each level of care is expected to meet minimum benchmarks and ensure high-quality and family centred care. We propose that cardiac surgery capabilities should only be developed at the more advanced levels on hospitals that have an established foundation of cardiology and cardiac surgery services, including screening, diagnostics, inpatient and outpatient care, postoperative care and cardiac catheterisation. This approach requires a quality control system and close collaboration between the different levels of care to facilitate the journey and care of every child with heart disease. This effort was designed to guide readers and leaders in taking action, strengthening capacity, evaluating impact, advancing policy and engaging in partnerships to guide facilities providing PCHD care in LMICs.

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.

Evidence-based surgical guidelines for treating children with Wilms tumor in low-resource settings.

BACKGROUND: Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes. OBJECTIVE: Provide resource-sensitive recommendations for the surgical management of WT. METHODS: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations. RECOMMENDATIONS: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis. CONCLUSION: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.

Financing Pediatric Surgery: A Provider's Perspective from the Global Initiative for Children's Surgery.

BACKGROUND: Half the world's population is at risk of catastrophic health expenditure (CHE, out-of-pocket spending of more than 10% of annual expenditure) should they require surgery. Protection against CHE is a key indicator of successful health care delivery and has been identified as a priority area by the Global Initiative for Children's Surgery (GICS). Data specific to pediatric surgical patients is limited. This study examines the financial risks for pediatric surgical patients and their families from a provider's perspective. METHODS: We surveyed GICS members about the existing financial protection mechanisms and estimated expenditures for their patients. Questions were structured based on the National Surgical, Obstetric and Anesthesia Planning Surgical Indicators and finalized based on multi-institutional consensus between high-income country and low-and middle-income country (LMIC) providers. Chi-squared test, Fisher's exact test and student's t-test were used as appropriate. RESULTS: Among 107 respondents, 72.4% were from low income or lower-middle income (LIC/LMIC) countries, and 55.1% were attending or consultant physicians. Families were most likely to decline surgery in LIC/LMIC due to inability to afford treatment (mean Likert = 3.77 ± 1.06). The odds of incurring CHE after children's surgery are up to 17 times greater in LIC/LMIC (P = 0.001, unadjusted OR 17.28, 95%CI 2.13-140.02). Over 50% of families of children undergoing major surgery in these settings face CHE. An estimated 5.1% of providers in LIC/LMIC and 56.2% (P < 0.001) of providers in UMIC/HIC reported that families are able to pay for their direct medical costs with the assistance available to them and were more likely to sell assets (74.4% vs. 33.3%, P = 0.005). CONCLUSION: Patients in LMICs are at greater risk for CHE and have less financial risk protection than their HIC counterparts. Given this disparity, intervention is needed to make safe surgery affordable for children worldwide.

An Observational Study of Paediatric Preoperative Transfusion Practice in a Resource-Limited Setting.

BACKGROUND: Paediatric anaemia is highly prevalent in low-middle-income countries and can negatively impact postoperative outcomes. Currently, there are no guidelines for the management of paediatric preoperative anaemia. To ensure optimal care in resource-limited settings: balancing the risks of anaemia and using resources such as blood transfusion, we first need to understand current practices. To address this, a joint UK-Bangladesh team conducted an observational study at a paediatric surgical centre in Bangladesh. METHODS: A total of 464 patients ≤16 years who underwent elective and emergency surgery were categorised into major (351/464), moderate (92/464) and minor (21/464) surgery groups according to anticipated blood loss. Preoperative anaemia testing and transfusion was assessed retrospectively through patient notes. RESULTS: Median age was 4 years and 73% were male. 32.5% (151/464) patients had preoperative blood testing for anaemia. 17.5% (81/464) children were transfused preoperatively. Of those children transfused, 40.7% (33/81) underwent transfusion solely based on visible signs of anaemia on clinical examination. Seventy-five percentage (36/48) of children who underwent transfusion after blood testing had haemoglobin ≥80 g/L. Major surgery category had the highest proportion of children who were transfused and tested for anaemia. CONCLUSION: A liberal transfusion approach is evident here. Discussion with local clinicians revealed that this was due to limitations in obtaining timely blood results and reduction in laboratory costs incurred by families when clinical suspicion of anaemia was high. Further research is needed to analyse the potential of using bedside haemoglobin testers in conjunction with patient blood management strategies to limit blood transfusions and its associated risks.

Delayed presentation of congenital rectal stenosis associated with Down's syndrome and hypothyroidism: Case report.

Rectal stenosis is a rare variety of rectal atresia. A membrane separates the rectum from the anal canal in the presence of a normal anus. We report a case of rectal stenosis associated with Down's syndrome and hypothyroidism in whom rectal stenosis was diagnosed at the age of 17 years.

Online action planning forums to develop a roadmap to mitigate the impact of COVID-19 on the delivery of global children's surgical care.

PURPOSE: We aimed to understand the challenges facing children's surgical care providers globally and realistic interventions to mitigate the catastrophic impact of COVID-19 on children's surgery. METHODS: Two online Action Planning Forums (APFs) were organized by the Global Initiative for Children's Surgery (GICS) with a geographically diverse panel representing four children's surgical, anesthesia, and nursing subspecialties. Qualitative analysis was performed to identify codes, themes, and subthemes. RESULTS: The most frequently reported challenges were delayed access to care for children; fear among the public and patients; unavailability of appropriate personal protective equipment (PPE); diversion of resources toward COVID-19 care; and interruption in student and trainee hands-on education. To address these challenges, panelists recommended human resource and funding support to minimize backlog; setting up international, multi-center studies for systematic data collection specifically for children; providing online educational opportunities for trainees and students in the form of large and small group discussions; developing best practice guidelines; and, most importantly, adapting solutions to local needs. CONCLUSION: Identification of key challenges and interventions to mitigate the impact of the COVID-19 pandemic on global children's surgery via an objective, targeted needs assessment serves as an essential first step. Key interventions in these areas are underway.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.