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Purpose: Peripartum cardiomyopathy (PPCM) affects women in late pregnancy and postpartum. Cardiovascular magnetic resonance (CMR) can contribute to PPCM diagnosis and management. We explored CMR findings in PPCM, including myocardial strain and late gadolinium enhancement (LGE) patterns. Materials and Methods: This retrospective single-centre study included patients with PPCM who underwent CMR from 2010 to 2018. Exclusions were other cardiomyopathy causes. CMR parameters, including ventricular function, LGE, and myocardial strain, were compared between the PPCM group and healthy controls. Transthoracic echocardiographic data were reviewed to assess functional improvement in PPCM patients. Results: Thirty-two women with PPCM (mean age 42 ± 6 years) and 26 controls (mean age 43 ± 14 years) were included. PPCM patients had significantly lower left ventricular (LV) ejection fractions (median 37.5% vs 60.5%, P < .001), higher LV end-diastolic volumes (median 108 ml/m² vs 76 ml/m², P < .001), and reduced global LV strain compared to controls. Eighteen PPCM patients (58%) had non-ischaemic pattern LGE, with no LGE in controls besides hingepoint LGE (23%). LGE was most prevalent in the basal and mid anteroseptum. LGE patterns included linear mid-wall, subepicardial, and right ventricular side of the septum. Twenty-four patients (92%) showed improvement in LVEF at follow-up echocardiogram (mean LVEF 28% ± 1.9% at diagnosis and 45% ± 3% at follow-up, P < .001). Conclusion: We identified a non-ischaemic pattern LGE that is nonspecific in isolation but could suggest PPCM in the correct clinical context along with abnormal CMR strain values. Future studies should evaluate the clinical application of these findings to facilitate earlier diagnosis and enhance management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  Medication non-compliance is a significant healthcare issue that is widespread. Extensive research has identified factors that contribute to medication non-compliance in different healthcare settings. As a result, there was a need to develop a conceptual framework to facilitate medication compliance among adults living with depression., Objectives:  The purpose of this study was to develop a conceptual framework for psychiatric nurses to facilitate medication compliance among adults living with depression., Method:  A qualitative, exploratory, descriptive and contextual research design was utilised to investigate the experiences of adults living with depression who are non-compliant with medication. The study consisted of three phases: an empirical phase, a classification of concepts and a development phase. Following the empirical phase, a conceptual framework was developed based on the classified concepts., Results:  Three sets of results were merged for the cross-validation analysis, combining findings from the systematic review, the researcher's previously conducted and published minor dissertation and the current study., Conclusion:  A conceptual framework was developed to assist psychiatric nurses in effectively promoting an internal locus of control among adults living with depression. The resulting conceptual framework provides valuable insights and serves as a valuable tool for future research endeavours aimed at enhancing medication compliance among adults living with depression.Contribution: This framework serves as a valuable guide for future studies that aim to explore medication compliance among adults living with depression, specifically by focussing on the concept of internal locus of control.

Purpose: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers., Methods: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers., Results: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%., Conclusion: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

Aim: To implement a childhood cancer-specific nutritional algorithm adapted for the South African context for interventions at time-set intervals to evaluate differences in the nutritional status of newly diagnosed children with cancer., Method: Children with newly diagnosed cancer were assessed for stunting, underweight, wasting, and moderate to severe malnutrition (MUAC < -2SD and < - 3 SD) between October 2018 and December 2020 in a longitudinal nutritional assessment study with monthly assessments. Two pediatric oncology units (POUs) served as the intervention group that implemented the nutritional algorithm-directed intervention and three other POUs formed the control group that implemented standard supportive nutritional care., Results: A total of 320 patients were enrolled with a median age of 6.1 years (range three months to 15.3 years) and a male-to-female ratio of 1.1:1. The malnourished patients in the intervention group showed significant improvement at six months after diagnosis for stunting (P = 0.028), underweight (P < 0.001), and wasting until month five (P = 0.014). The improvements in the control group were not significant. Moderate acute malnutrition (MAM) significantly improved over the first six months of cancer treatment in the intervention group (P < 0.001), while MAM improvement was only significant in the control group for the children under five years of age (P = 0.004). The difference in mean z-scores over time for the nutritional parameters between the intervention and control groups was insignificant., Conclusion: We established that the nutritional algorithm adapted for South Africa as an intervention tool for childhood cancer assisted in optimizing nutritional interventions and improved nutritional outcomes over the first six months of cancer treatment., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Non-compliance with psychiatric medication among patients diagnosed with depression ranges from 28% to 52% exacerbating illness and reducing treatment effectiveness. There is a paucity of research on medication non-compliance and its causes in South Africa and globally, and an urgent need to develop appropriate interventions., Aim: This study aimed to explore and describe the experiences of adults living with depression who are non-compliant with their psychiatric medication and formulate recommendations to facilitate their medication compliance., Setting: The study was conducted in a psychiatric ward at a public hospital in Gauteng, South Africa., Methods: The study employed a qualitative, exploratory, descriptive and contextual research design. Ten adults' lived experiences were explored using in-depth individual interviews, and Tech's coding method was used to analyse data., Results: Two themes emerged from the data: adults living with major depression offered several reasons for non-compliance, and adults living with major depression experienced non-compliance, which created a setback to their recovery., Conclusion: Non-compliance with medication is a common challenge among adults receiving mental health care and treatment. Ensuring compliance to medication is crucial for improving the prognosis of psychiatric conditions. Therefore, it is essential for healthcare practitioners in the field of psychiatry to have a comprehensive understanding of medication compliance and to effectively address any challenges that may arise in this area., Contribution: This paper contributes to the research field and adds knowledge to clinical nursing practice by exploring adults' experiences with non-compliance to psychiatric medications while living with depression in the South African context., Competing Interests: The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Colorectal cancer (CRC), found in the intestinal tract, is initiated and progresses through various mechanisms, including the dysregulation of signaling pathways. Several signaling pathways, such as EGFR and MAPK, involved in cell proliferation, migration, and apoptosis, are often dysregulated in CRC. Although cannabidiol (CBD) has previously induced apoptosis and cell cycle arrest in vitro in CRC cell lines, its effects on signaling pathways have not yet been determined. An in silico analysis was used here to assess partner proteins that can bind to CBD, and docking simulations were used to predict precisely where CBD would bind to these selected proteins. A survey of the current literature was used to hypothesize the effect of CBD binding on such proteins. The results predict that CBD could interact with EGFR, RAS/RAF isoforms, MEK1/2, and ERK1/2. The predicted CBD-induced inhibition might be due to CBD binding to the ATP binding site of the target proteins. This prevents the required phosphoryl transfer to activate substrate proteins and/or CBD binding to the DFG motif from taking place, thus reducing catalytic activity.

Purpose: Retinoblastoma, a curable childhood cancer, has been identified as a tracer cancer in the WHO Global Initiative for Childhood Cancer. To document the outcomes of children with retinoblastoma in South Africa, treated as per the first prospective standard national treatment guidelines for childhood cancer in South Africa., Patients and Methods: All children diagnosed with retinoblastoma between 2012 and 2016 in five South African pediatric oncology units were treated with a standard treatment on the basis of the International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries guidelines for high-income settings. Treatment included focal therapy with/without chemotherapy, or enucleation with/without chemotherapy, and orbital radiotherapy, depending on enucleated eye histology. The end point was survival at 24 months, using Kaplan-Meier curves with log-rank (Mantel-Cox) and chi-square (χ2) tests with respective P values reported., Results: A total of 178 children were included in the study; 68% presented with unilateral disease. The median age was 27 months (range 0-118 months) with a male:female ratio of 1:0.75. The overall survival was 79% at 24 months with significant association with stage at diagnosis ( P < .001) and older age over 2 years as opposed to younger than 2 years ( P < .001). Causes of death were disease progression/relapses in 90% (34 of 38) and unknown in 2% (1 of 38), whereas treatment abandonment was 1.7% (3 of 178)., Conclusion: Efficacy with national treatment guidelines was confirmed, and feasibility of implementing standard national childhood cancer treatment guidelines was documented, involving multidisciplinary teams in South Africa. Outcome was significantly associated with stage at diagnosis and age.

Introduction: Zambia is experiencing a critical shortage of radiologists responsible for interpreting X-ray images. Nine radiologists serve the entire population of over 18 million people. Consequently, referring physicians can receive reports late and often receive X-ray images without radiological reports attached, which may lead to delayed diagnoses and treatment of critically injured patients. This challenge could be alleviated if radiographers could assist with interpreting X-ray images. This study was undertaken to subject a cohort of Zambian radiographers to a training intervention, however, the COVID-19 pandemic necessitated using a novel approach to the intervention by delivering the training mainly through social media but also through face-to-face lectures., Methods: A cohort of 27 radiographers employed at eight public hospitals in the Copperbelt Province of Zambia undertook a training intervention using face-to-face training and image discussions on the social media WhatsApp® platform. The participants underwent a pre-and post-test in which they were asked to interpret 20 adult trauma CXR images. For the training intervention, the radiographers attended a face-to-face image interpretation lecture, after which they received training images with a radiologist report weekly for eight weeks via the WhatsApp® platform. Participants were encouraged to discuss and pose questions via the platform., Results: The cohort of radiographers (n = 27) showed an improvement in their interpretation skills for trauma CXR images. The interpretation median scores ranged from approximately 82% to 93% in the pre-test and 85% to 97% in the post-test. The Wilcoxon signed-rank tests revealed significant differences in the interpretation ability skills for 12 of the 20 CXR images after the 8-week training, demonstrating the successful implementation of the program. When comparing three categories of radiographers' years of experience (1-5; >5-10; and >10 years), the Kruskal Wallis test could not identify significant differences in the CXR image interpretation skills among the different categories of experience (P = 0.1616). When comparing the interpretation skills of radiographers working at the three different hospital levels (Level 3 with a full-time radiologist and more than ten radiographers; Level 1 and 2 without a full-time radiologist; Level 2 with six to ten radiographers; and Level 1 with five or less radiographers), the Kruskal Wallis test revealed that the level of the hospital where the radiographers were employed significantly influenced their skills to interpret the CXR images (P = 0.0323)., Conclusion: This type of novel training intervention is urgently required in the Copperbelt Province of Zambia. The results show that the training process was implemented successfully to improve radiographers' image interpretation skills of adult trauma CXR images., Implications for Practice: Promoting radiographers' involvement in image interpretation will likely improve imaging services in Zambia, considering the critical shortage of radiologists., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy., Patients and Methods: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum., Results: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996., Conclusions: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

The impact of scoliosis bracing combined with physiotherapeutic scoliosis-specific exercises (PSSE) on trunk muscle endurance in adolescents with idiopathic scoliosis is unknown. ScoliBrace ® , a rigid, three-dimensional, over-corrective thoraco-lumbar-sacral orthosis (TLSO), and ScoliBalance ® , a PSSE program, were used to treat adolescent idiopathic scoliosis (AIS) patients. A retrospective study of the trunk muscle endurance of 33 AIS patients who received ScoliBrace ® and ScoliBalance ® was conducted. The patients were treated with ScoliBrace ® and an individualized ScoliBalance ® program. Trunk extensor muscle endurance (TE) and abdominal muscle endurance (AE) tests were performed at initial assessment and then at averages of 6.6 and 24.4 weeks of treatment. The data were analyzed using the Wilcoxon signed-rank test, Stata version 15.1. The participants were aged 13.24 years (SD = 1.64) with a mean Cobb angle of 38.97° (SD = 9.49°). TE improved significantly ( p < 0.001) at both short- and medium-term intervals using ScoliBalance ® and ScoliBrace ® in the AIS patients. AE also showed significant improvement between baseline and short-term follow-up, with non-significant improvement at medium-term follow-up. Overall, trunk muscle endurance showed improvement in the AIS patients using ScoliBrace ® and ScoliBalance ® . Future research is required to determine the individual and combined effects of each treatment. However, it seems likely that trunk muscle endurance will not deteriorate in AIS patients with this combined treatment.

Background and Objectives: Improving hospitalised patients' psychological well-being (PWB) is relevant to their recovery and overall quality of life. Virtual Reality (VR) holds the potential to emerge as a novel tool for increasing the PWB of hospitalised patients. This study critically reviewed existing research concerning the use and impact of VR on the PWB of hospitalised patients with serious illnesses. The primary aim of this study was to evaluate the efficacy and practical applicability of VR in enhancing the PWB for hospitalised patients dealing with serious illnesses., Methodology: In the initial search, the authors identified 106 sources that provided valuable insights into the broader field of VR, PWB, and the influence of VR on the psychological functioning of hospitalised patients. However, only eight articles were selected for the critical review, following the SALSA method. The SALSA method comprises the following steps: (S) Search, (AL) Appraisal, (S) Synthesis and (A) Analysis. Data extracted from these eight articles were subjected to reflexive thematic analysis, through which patterns were identified to examine the use and impact of VR on the PWB of hospitalised patients with serious illnesses. The thematic analysis process involves data gathering and familiarisation, code identification, and formulating and refining various themes to produce a thematic analysis report., Results: The themes that emerged from the analysis were (i) positive psychological effects (with sub-themes including the effectiveness of VR in improving psychological symptoms, its role as an equivalent or adjunctive treatment, and symptom reduction), (ii) perceptions and the adoption of novel technology, (iii) characteristics that influence the effectiveness of VR, and (iv) statistical and practical applicability and diversity of VR., Conclusion and Recommendation: The use of VR to increase the PWB of hospitalised patients is a relatively recent innovation. Nevertheless, the themes identified in this study indicate that the use of VR within the context of hospitalised patients can benefit their psychological functioning, ultimately contributing to an improvement in their overall PWB. Further in-depth studies are needed to provide a comprehensive conclusion on the potential benefits of VR on the PWB of hospitalised patients dealing with serious illnesses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Globally, the high prevalence of mental disorders among university students is a growing public health problem, yet a small minority of students with mental health problems receive treatment. Digital mental health solutions could bridge treatment gaps and overcome many barriers students face accessing treatment. However, there is scant evidence, especially in South Africa (SA), relating to university students' use of and intention to use digital mental health solutions or their attitudes towards these technologies. We aim to explore university 2students attitudes towards and perceptions of digital mental health solutions, and the factors associated with their intention to use them., Methods: University students from four SA universities ( n  = 17 838) completed an online survey to assess experience with, attitudes and perceptions of, and intentions to use, digital mental health solutions. We conducted an exploratory factor analysis to identify factors underlying attitudes and perceptions, and then used multivariate ordinal regression analysis was used to investigate the factors' association with students' intention to use digital mental health solutions., Results: Intention to use digital mental health solutions was high, and attitudes towards and perceptions of digital mental health solutions were largely positive. Importantly, our analysis also shows that 12.6% of users were willing to utilise some form of digital mental health solutions but were unwilling to utilise traditional face-to-face therapies. The greatest proportion of variance was explained by the factor 'Attitudes towards digital technologies' utility to improve student counselling services, provided they are safe'., Conclusion: SA university students are already engaging with digital mental health solutions, and their intention to do so is high. Certain attitudes and perceptions, particularly concerning the utility, effectiveness, and safety, underlie willingness to engage with these solutions, providing potential targets for interventions to increase uptake., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Dual antiplatelet therapy (DAPT) is standard care for intracranial stenting to prevent thrombotic complications. Clopidogrel resistance has resulted in patients receiving newer P2Y12 inhibitors like Prasugrel, which may reduce thrombotic complications but could increase haemorrhagic complications. This study, utilising platelet reactivity testing, compared thrombotic and haemorrhagic complications associated with Clopidogrel or 20 mg Prasugrel loading in patients treated with flow diverters (FD) for intracranial aneurysms., Methods: We retrospectively analysed prospectively collected data from 225 consecutive FD procedures. All patients received aspirin. 147 cases received Clopidogrel and 82 received Prasugrel. All patients had VerifyNow testing before the procedure., Results: P2Y12 non-responders were significantly more likely to have thrombotic complications than responders and hyper-responders (7% vs. 2%, p = 0.01). Low-dose Prasugrel resulted in a significantly lower rate of non-responders when compared with Clopidogrel (7% vs. 25%, p < 0.01). We found no statistically significant difference in rates of haemorrhage between the Clopidogrel and Prasugrel groups (2.4% vs. 3.9%, p = 0.47). There were 12 complications (≤7 days) in the Clopidogrel group versus 6 in the Prasugrel group (9% vs. 7.8%, respectively, p = 0.91) and a non-significant reduction in thrombotic complications in the Prasugrel group (5.2% vs. 3.9%, p = 0.88). No significant difference was shown in long-term complications between the groups (p = 0.33)., Conclusion: These results support the use of platelet reactivity testing and the safety of low-dose Prasugrel for FD treatment of intracranial aneurysms., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To document the histological changes observed in renal units subjected to elevated intrarenal pressures (IRPs) and postulate the possible mechanisms of infectious complications after ureteroscopy., Materials and Methods: Ex vivo studies were performed on porcine renal models. Each ureter was cannulated with a 10-F dual-lumen ureteric catheter. A pressure-sensing wire was inserted through one lumen and with the sensor positioned in the renal pelvis for IRP measurement. Undiluted India ink stain was irrigated through the second lumen. Each renal unit was subjected to ink irrigation at target IRPs of 5 (control), 30, 60, 90, 120, 150, and 200 mmHg. Three renal units were subjected to each target IRP. After irrigation, each renal unit was processed by a uropathologist. Macroscopically, the amount of renal cortex stained by ink was calculated as a percentage of the total perimeter. Microscopically, presence of ink reflux into collecting ducts or distal convoluted tubules, and pressure-related features, was noted at each IRP., Results: Signs of pressure, as represented by collecting duct dilatation, was first observed at 60 mmHg. Ink staining was consistently observed in the distal convoluted tubules at IRPs ≥60 mmHg, and all renal units above this pressure showed renal cortex involvement. At ≥90 mmHg, ink staining was observed in venous structures. At 200 mmHg, ink staining was observed in supportive tissue, venous tributaries in the sinus fat, peritubular capillaries, and glomerular capillaries., Conclusion: Using an ex vivo porcine model, pyelovenous backflow occurred at IRPs of ≥90 mmHg. Pyelotubular backflow occurred when irrigation IRPs were ≥60 mmHg. These findings have implications for the development of complications after flexible intrarenal surgery., (© 2023 BJU International.)

Background: Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12 consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs., Objective: To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12 consecutive weeks., Methods: A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company's database. Retrospective data of medicine claims for phentermine, from 1  January 2015 to 31  December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently., Results: A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group 'severe PDDIs', tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group., Conclusion: There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.

Background: We aim to compare the safety and efficacy of WEB with coiling for acutely ruptured aneurysms.METHODS: All consecutive ruptured aneurysms with width suitable for WEB (2-10 mm) treated over 5 years (1/1/2015 to 31/12/2019) were included. We recorded WFNS, Fisher grade, patient demographics and aneurysm characteristics (size, location, D/W and aspect ratio, lobulation). Primary endpoints were mRS status at 3 months, aneurysm occlusion on latest available imaging follow-up, retreatment rate and procedural complications. We applied propensity score matching using aneurysm morphology (size, D/N ratio, ASPECT ratio and lobulation) to optimise matching for WEB versus coil comparison and minimise the effects of confounding., Result: A total of 493 patients were identified, 97 treated with the WEB device. 1:1 propensity score matching was used to establish a matched group of 97 patients treated with coiling. The WEB arm showed 3% procedural complication rate, with no haemorrhagic complications and use of adjunctive device in 4%. Satisfactory occlusion on follow-up (mean 14 months) was 79%, with 19% retreatment rate. The coil arm had 8% complication rate, with use of an adjunctive device in 52% of cases (balloon 44%, stent 8%). Satisfactory occlusion on follow-up (mean 22 months) was 90%, with 8% retreatment rate., Conclusion: Treatment of ruptured wide-necked bifurcation aneurysms with WEB has a lower complication rate than coiling with high rate of satisfactory occlusion. However, there was a higher retreatment rate when compared with patients treated with coiling. An adjunct device (balloon or stent), was used in over 50% of aneurysms in the coiling group.

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa's Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shabir Madhi reports financial support was provided by GlaxoSmithKline. Shabir Madhi reports financial support was provided by AstraZeneca. Shabir Madhi reports financial support was provided by BMGF. Shabir Madhi reports financial support was provided by South African Medical Research Council. Shabir Madhi reports financial support was provided by Pfizer. Shabir Madhi reports financial support was provided by Minervax. Shabir Madhi reports financial support was provided by Novavax. Shabir Madhi reports financial support was provided by Providence. Shabir Madhi reports financial support was provided by Greenstone. Shabir Madhi reports financial support was provided by ImmunityBio. Clare L. Cutland reports financial support was provided by BMGF. Clare L. Cutland reports financial support was provided by Pfizer. Clare L. Cutland reports financial support was provided by Biovac. Lee Fairlie reports financial support was provided by South African Medical Research Council. Lee Fairlie reports financial support was provided by Bill and Melinda Gates Foundation. Mookho Malahleha reports financial support was provided by Synergy Biomed Research Institute. Andrew J. Pollard reports financial support was provided by University of Oxford. Andrew J. Pollard reports financial support was provided by Shionogi. Andrew J. Pollard reports financial support was provided by AstraZeneca. Andrew J. Pollard reports financial support was provided by National Institute for Health and Care Research. Qasim Ebrahim Bhorat reports financial support was provided by Wits Health Consortium. Qasim Ebrahim Bhorat reports financial support was provided by Regeneron Pharmaceuticals. Qasim Ebrahim Bhorat reports financial support was provided by GlaxoSmithKline. Qasim Ebrahim Bhorat reports financial support was provided by Avillion. Qasim Ebrahim Bhorat reports financial support was provided by Sanofi. Qasim Ebrahim Bhorat reports financial support was provided by NovoNordisk. Qasim Ebrahim Bhorat reports financial support was provided by Bill & Melinda Gates Foundation. Qasim Ebrahim Bhorat reports financial support was provided by South African Medical Research Council. Qasim Ebrahim Bhorat reports financial support was provided by Novavax. Qasim Ebrahim Bhorat reports financial support was provided by AstraZeneca. Qasim Ebrahim Bhorat reports financial support was provided by Clover BioPharmaceticals. Tonya L. Villafana reports financial support was provided by AstraZeneca. Clare L. Cutland reports a relationship with BMGF that includes: employment and funding grants. Mookho Malahleha reports a relationship with RTI that includes: consulting or advisory. Andrew J. Pollard reports a relationship with UK Joint Committee on Vaccines and Immunization that includes: board membership. Andrew J. Pollard reports a relationship with World Health Organisation SAGE that includes: board membership. Sarah Gilbert reports a relationship with Vaccitech that includes: equity or stocks. Teresa Lambe reports a relationship with Vaccitech that includes: consulting or advisory. Mookho Malahleha reports a relationship with Synergy Biomed Research Institute that includes: board membership, employment, and equity or stocks. Sarah Gilbert has patent issued to Vaccitech. Teresa Lambe has patent issued to Vaccitech., (Copyright © 2023. Published by Elsevier Ltd.)

Halogenated platinum salts are known respiratory sensitizers in the workplace, and occupational exposure to platinum via the respiratory system and skin has been reported. The aim of this study was to compare the permeability and skin retention of potassium hexachloroplatinate to previously published data of potassium tetrachloroplatinate. Experiments were performed using female Caucasian skin and Franz diffusion cells with the application of 0.3 mg Pt/mL in the donor solution for 24-h. After 8-h of exposure, 1.87 ng/cm 2 of Pt was detected in the receptor solution with exposure to potassium hexachloroplatinate, whereas 0.47 ng/cm 2 was detected with exposure to potassium tetrachloroplatinate. After 24-h of exposure the Pt retention in the skin was 1861.60 ng/cm 2 and 1486.32 ng/cm 2 with exposure to potassium hexa- and tetrachloroplatinate respectively. The faster rate of Pt permeation from exposure to potassium hexachloroplatinate was confirmed by the flux and permeability coefficient values. The results indicate a higher permeability and skin retention of Pt when exposed to potassium hexachloroplatinate, confirming a higher risk associated with occupational exposure to this platinum compound relative to potassium tetrachloroplatinate., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof A Franken reports financial support was provided by Johnson Matthey. Prof A Franken reports financial support was provided by The International Platinum Group Metals Association. Barbara Sylvia Bosch reports financial support was provided by International PGM Association (IPA). Johnson Matthey (UK) provided the analysis of the samples., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

Many South African children live in poverty and food insecurity; therefore, malnutrition within the context of childhood cancer should be examined. Parents/caregivers completed the Poverty-Assessment Tool (divided into poverty risk groups) and the Household Hunger Scale questionnaire in five pediatric oncology units. Height, weight, and mid-upper arm circumference assessments classified malnutrition. Regression analysis evaluated the association of poverty and food insecurity with nutritional status, abandonment of treatment, and one-year overall survival (OS). Nearly a third (27.8%) of 320 patients had a high poverty risk, associated significantly with stunting ( p  = 0.009), food insecurity ( p  < 0.001) and residential province ( p  < 0.001) (multinomial regression). Stunting was independently and significantly associated with one-year OS on univariate analysis. The hunger scale was significant predictor of OS, as patients living with hunger at home had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; p  = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; p  = 0.046) compared to those with food security. Evaluating sociodemographic factors such as poverty and food insecurity at diagnosis is essential among South African children to identify at-risk children and implement adequate nutritional support during cancer treatment.

Background: Intensive care outreach nurses (ICONs) can reduce deterioration and death of patients in hospitals., Purpose: Evaluate outcomes associated with implementation of the ICON role across 4 UAE hospitals., Methods: Trend analyses and χ 2 tests were used to measure changes before ICON program, during ICON year 1, ICON year 2, when the service coverage extended 24/7, and until the end of 2019., Results: From year 1 to year 2, failures to escalate decreased from a rate of 14.8 to 5.6 episodes per 1000 admissions for all sites combined ( P < .001). The cardiac arrest rate went from 4.04 to 1.42 per 1000 admissions in year 2 and continued downward to 0.72 per 1000 ( P < .001). Transfer from ward or readmission to intensive care unit/high dependency unit varied by site, although there was a statistically significant trend for all hospitals combined., Conclusion: The ICON role contributed to fewer failure to escalate incidents and lower cardiac arrest rates., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with &gt;2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this 'In Practice' article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.

Objective: To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol., Methods: A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy-proven MEGCTs from birth up to and including 16 years of age., Results: Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (hazard ratio [HR] 0.284, p = .037) and higher socio-economic status (SES) (HR 0.071, p = .039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I: 96%; stage II: 94.3%; stage III: 75.5% (p = .017) and stage IV (60.1%; p < .001). There was a significant association between earlier stage at presentation and higher SES (p = .03). Patients with a serum alpha-fetoprotein (AFP) level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p = .002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p < .001)., Conclusions: The cohort demonstrated a 5-year OS of 80.3% with an event-free survival (EFS) of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000 ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide., (© 2021 Wiley Periodicals LLC.)

Background: Traumatic brain injury (TBI) is a common cause of paediatric morbidity and mortality, with higher TBI rates in low- and middle-income countries. Non-contrast brain CT is the gold standard for diagnosing intracranial injuries; however, it exposes patients to ionising radiation. The Paediatric Emergency Care Applied Research Network (PECARN) clinical decision rule (CDR) aids clinicians in their decision-making processes whilst deciding whether a patient at very low risk of a clinically important TBI (ciTBI) requires a CT scan., Objectives: To establish whether the introduction of the PECARN CDR would affect CT utilisation rates for paediatric patients presenting with minor blunt head injuries to an academic hospital in Gauteng, South Africa., Method: This was an audit of paediatric patients who presented with minor blunt head injuries and were referred for CT imaging at an academic hospital in Gauteng, compared with PECARN CDR recommendations, over a 1-year period., Results: A total of 100 patients were referred for CT imaging. Twenty patients were classified as very low risk, none of whom had any CT findings of a TBI or ciTBI ( p < 0.01). A total of 61 patients were classified as intermediate risk and 19 as high risk. In all, 23% of the intermediate and 47% of the high-risk patients had CT features of a TBI, whilst 8% and 37% had a ciTBI, respectively., Conclusion: Computed tomography brain imaging may be omitted in patients classified as very low risk without missing a clinically important TBI. Implementing the PECARN CDR in appropriate patients would reduce CT utilisation rates., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

Aims: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes., Materials and Methods: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five 'primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated., Results: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers., Conclusions: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB., Materials and Methods: We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected., Results: We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30-72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1-36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm).An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%).Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) - one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up., Conclusion: The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths., Competing Interests: The authors have declared that no competing interests exist.

Background: Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem., Methods: Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution., Results: SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS., Conclusions: COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Diagnostic and post-induction 123 I-meta-iodobenzylguanidine ( 123 I-mIBG) scans have prognostic significance in the treatment of neuroblastoma, but data from low- and middle-income countries are limited due to resource constraints. The aim of this study was to determine the association between neuroblastoma-associated tumour markers (lactate dehydrogenase [LDH], ferritin and MYCN amplification) and 123 I-mIBG scans (modified Curie scores and metastatic disease patterns) in predicting complete metastatic response rates (mCR) and overall survival., Materials and Methods: Two hundred and ninety patients diagnosed with high-risk neuroblastoma in South Africa between January 2000 and May 2018 and a subanalysis of 78 patients with diagnostic 123 I-mIBG scans were included. Data collection included LDH, ferritin and MYCN amplification at diagnosis. Two nuclear physicians independently determined the modified Curie scores and pattern of distribution for each diagnostic and post-induction 123 I-mIBG scans with high inter-rater agreement (r = 0.952) and reliability (K = 0.805). The cut-off values for the diagnostic and post-induction modified Curie scores of ≥7.0 (P = 0.026) and 3 (P = 0.009), respectively, were generated. The association between the tumour markers and the modified Curie score of the 123 I-mIBG scans was determined using post-induction mCR and 2-year overall survival., Results: Diagnostic LDH (P < 0.001), ferritin (P < 0.001) and the diagnostic modified Curie scores (P = 0.019) significantly predicted mCR. Only ferritin correlated with diagnostic modified Curie scores (P = 0.003) but had a low correlation coefficient of 0.353. On multivariable analysis, the only significant covariate for 2-year overall survival at diagnosis was LDH <750 U/l (P = 0.024). A post-induction chemotherapy modified Curie score ≤3.0 had a 2-year overall survival of 46.2% compared with 30.8% for a score >3.0 (P = 0.484)., Conclusion: LDH, ferritin and the diagnostic 123 I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the 123 I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol., Materials and Methods: Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival., Results: Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up., Conclusions: Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children's Cancer Study Group., Methods: The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process., Results: The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation., Conclusion: The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible.

This comprehensive review introduces occupational (industrial) hygienists and toxicologists to the seven basic additive manufacturing (AM) process categories. Forty-six articles were identified that reported real-world measurements for all AM processes, except sheet lamination. Particles released from powder bed fusion (PBF), material jetting (MJ), material extrusion (ME), and directed energy deposition (DED) processes exhibited nanoscale to submicron scale; real-time particle number (mobility sizers, condensation nuclei counters, miniDiSC, electrical diffusion batteries) and surface area monitors (diffusion chargers) were generally sufficient for these processes. Binder jetting (BJ) machines released particles up to 8.5 µm; optical particle sizers (number) and laser scattering photometers (mass) were sufficient for this process. PBF and DED processes (powdered metallic feedstocks) released particles that contained respiratory irritants (chromium, molybdenum), central nervous system toxicants (manganese), and carcinogens (nickel). All process categories, except those that use metallic feedstocks, released organic gases, including (but not limited to), respiratory irritants (toluene, xylenes), asthmagens (methyl methacrylate, styrene), and carcinogens (benzene, formaldehyde, acetaldehyde). Real-time photoionization detectors for total volatile organics provided useful information for processes that utilize polymer feedstock materials. More research is needed to understand 1) facility-, machine-, and feedstock-related factors that influence emissions and exposures, 2) dermal exposure and biological burden, and 3) task-based exposures. Harmonized emissions monitoring and exposure assessment approaches are needed to facilitate inter-comparison of study results. Improved understanding of AM process emissions and exposures is needed for hygienists to ensure appropriate health and safety conditions for workers and for toxicologists to design experimental protocols that accurately mimic real-world exposure conditions. ABBREVIATIONS ABS : acrylonitrile butadiene styrene; ACGIH® TLV® : American Conference of Governmental Industrial Hygienists Threshold Limit Value; ACH : air change per hour; AM : additive manufacturing; ASA : acrylonitrile styrene acrylate; AVP : acetone vapor polishing; BJ : binder jetting; CAM-LEM : computer-aided manufacturing of laminated engineering materials; CNF : carbon nanofiber; CNT : carbon nanotube; CP : co-polyester; CNC : condensation nuclei counter; CVP : chloroform vapor polishing; DED : directed energy deposition; DLP : digital light processing; EBM : electron beam melting; EELS : electron energy loss spectrometry; EDB : electrical diffusion batteries; EDX : energy dispersive x-ray analyzer; ER : emission rate; FDM™ : fused deposition modeling; FFF : fused filament fabrication; IAQ : indoor air quality; LSP : laser scattering photometer; LCD : liquid crystal display; LDSA : lung deposited particle surface area; LOD : limit of detection; LOM : laminated object manufacturing; LOQ : limit of quantitation; MCE : mixed cellulose ester filter; ME : material extrusion; MJ : material jetting; OEL : occupational exposure limit; OPS : optical particle sizer; PBF : powder bed fusion; PBZ : personal breathing zone; PC : polycarbonate; PEEK : poly ether ether ketone; PET : polyethylene terephthalate; PETG : Polyethylene terephthalate glycol; PID : photoionization detector; PLA : polylactic acid; PM 1 : particulate matter with aerodynamic diameter less than 1 µm; PM 2.5 : particulate matter with aerodynamic diameter less than 2.5 µm; PM 10 : particulate matter with aerodynamic diameter less than 10 µm; PSL : plastic sheet lamination; PVA : polyvinyl alcohol; REL : recommended exposure limit; SDL : selective deposition lamination; SDS : safety data sheet; SEM : scanning electron microscopy; SL : sheet lamination; SLA : stereolithography; SLM : selective laser melting; SMPS : scanning mobility particle sizer; SVOC : semi-volatile organic compound; TEM : transmission electron microscopy; TGA : thermal gravimetric analysis; TPU : thermo polyurethane; UAM : ultrasonic additive manufacturing; UC : ultrasonic consolidation; TVOC : total volatile organic compounds; TWA : time-weighted average; VOC : volatile organic compound; VP : vat photopolymerization.

Background: Oral administration of statins for the treatment of familial hypercholesterolemia results in poor therapeutic outcomes and patient compliance. An alternative administration route is proposed to circumvent the current limitations. This research is aimed at developing nano-emulsions and nano-emulgels as the ultimate potential delivery systems of statins for administration via the transdermal route., Methods: Oil-in-water (o/w) nano-formulations (nano-emulsions and nano-emulgels) containing 2% (w/w) of the selected statin and 8% apricot kernel oil as oil phase were formulated. The nano-formulations were characterized using transmission electron microscopy (TEM), pH, viscosity, droplet size and zeta-potential., Results: Nano-emulsions' and nano-emulgels' droplet size ranged between 114.23-169.83 nm and 149.83-267.53 nm, respectively. The addition of Carbopol® Ultrez 20 increased the nano-emulsions' viscosity (3.59-8.38 cP) resulting in the formation of nano-emulgels (viscosity: 1911.00-46,090.00 cP). The entrapment efficiency (90.77-99.55%) confirmed the incorporation of the statins. Membrane release studies indicated that statins were released at higher flux values in nano-emulsions compared to their respective nano-emulgels. Ex vivo (skin diffusion) studies indicated higher median values in the nano-emulgels compared to their nano-emulsion counterparts., Conclusions: The results indicate the benefits of nano-emulsions and nano-emulgels as potential alternative delivery systems for the transdermal delivery of statins.

Background: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa., Methods: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×10 10 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose., Results: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups., Conclusions: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132)., (Copyright © 2021 Massachusetts Medical Society.)

Background: Neuregulin 4 (Nrg4), a novel adipokine enriched in brown adipose tissue has been observed to negatively regulate de novo hepatic lipogenesis and limit nonalcoholic fatty liver disease (NAFLD) progression to nonalcoholic steatohepatitis (NASH) in rodents. However, the role of Nrg4 in human NAFLD remains unclear to date. We analysed Nrg4 plasma levels and its association with liver disease severity together with the transcriptional profile of the Nrg4 pathway in liver and visceral adipose tissue (VAT) of NAFLD patients., Methods: Plasma Nrg4 levels were measured in 65 NAFLD patients and 43 healthy controls (HC). Hepatic steatosis and fibrosis were diagnosed and quantified with chemical shift MRI and transient elastography respectively. Furthermore, blood lipid levels, HOMA-IR and systemic pro-inflammatory cytokines (TNF-α, IL-6 and IFN-γ) were analysed. Microarray analyses to assess differences in the Nrg4 and its receptor family ErbB pathway in liver and VAT from an independent patient group with biopsy proven NAFL (simple steatosis) (n = 4), NASH (n = 5) and normal liver (n = 6) were performed., Results: Plasma Nrg4 levels were not significantly different between NAFLD patients and HC (p = 0.622). Furthermore, plasma Nrg4 levels did not correlate with the hepatic fat fraction (r = -0.028, p = 0.829) and were not significantly different between NAFLD patients with or without hepatic fibrosis (p = 0.087). Finally, the expression profile of 82 genes related to the Nrg4-ErbB pathway in liver and VAT was not significantly different between NAFL, NASH or obese controls., Conclusion: Our study does not support a role for Nrg4 in the pathophysiology of human NAFLD., Competing Interests: The authors have declared that no competing interests exist.

Aim: To examine the use of continuous pulse oximetry monitoring (CPOM) of newborns as a non-invasive and non-intrusive standard of care for promoting early and safe skin-to-skin contact between mothers and newborns immediately after birth and to gather acceptability feedback from midwifery staff and mothers., Methods: All babies receiving skin-to-skin contact (SSC) had continuous pulse oximetry monitoring (CPOM) for the first-hour postbirth. Staff were trained with education sessions before implementation. Midwives and mothers were surveyed post-implementation and again after distribution of an education brochure regarding CPOM., Results: Seventy per cent of midwives and 66% of mothers responded to the survey. The majority of midwives received the practice positively and felt reassured by the use of CPOM in the immediate postpartum period. The survey identified gaps in maternal knowledge of the risk and benefits of SSC which improved significantly after the distribution of the educational brochure (P = .01)., Conclusion: Continuous pulse oximetry monitoring with a compact monitor in the first-hour postbirth is a simple, non-invasive and innovative approach to enhance safe skin-to-skin care by improving vigilance of newborns. Our study confirmed the acceptance of such approach by midwives and mothers in our population., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point., Methods: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests., Results: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis., Conclusion: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa., (© 2021 Wiley Periodicals LLC.)

Background: The magnitude of the incidence and impact of nausea on patients receiving intravenous chemotherapy seems to be underestimated by healthcare professionals. Development of effective anti-emetic treatment has contributed to the resolution of chemotherapy-induced nausea and vomiting (CINV). However, there is a concern that vomiting has been the initial focus of anti-emetic research and nausea was perceived as a secondary endpoint. Through focusing on the incidence of nausea independently of the incidence of vomiting, valuable information has been gained on this distressing side effect, including identifying patient risk factors contributing to the increased experience of nausea., Methods: The study followed a prospective, observational study design in a private oncology centre in Johannesburg, South-Africa. Ethical approval was obtained before commencement of the study, followed by the recruitment of one hundred patients over a seven-month period. Patient-reported outcome measures (PROMs) were used to measure nausea with an amended version of the Multinational Association of Supportive Care in Cancer antiemesis tool (MAT). Patients documented information in their diaries on the incidence, duration and severity of nausea, during the acute phase (0-24 hours), the delayed phase (25-120 hours), day 7 and day 10 after infusion of chemotherapy, with episodes of vomiting being recorded as a secondary endpoint. The demographic and clinical variables of the subjects, as well as patient risk factors known to cause CINV, were tabulated and summarised using descriptive statistics., Results: The population consisted of 68 females and 27 males with a mean age of 57 years (25-84 years). The emetogenicity of chemotherapy regimens administered were well represented with 26.3% low emetogenic chemotherapy, 25.3% moderately emetogenic chemotherapy and 48.4% highly emetogenic chemotherapy (HEC). Despite all patients receiving guideline consistent CINV prophylaxis, nausea was still experienced by 57.9% patients during cycle one, 50.6% patients during cycle two and 45.6% patients during cycle three. The incidence of patients experiencing nausea (in the absence of vomiting) was 35%, compared to 2% of patients experiencing vomiting (in the absence of nausea). Patient characteristics with a known risk to impact CINV were documented, and significant impact in this study was found in female gender, age <60 years, history of motion sickness and history of morning sickness., Conclusions: Guideline consistent CINV prophylaxes seem to have vomiting under control for most patients receiving intravenous chemotherapy. Nausea, however, still seems to be a persistent adverse event during treatment. Female gender, age <60 years, history of motion sickness and history of morning sickness increases the risk of experiencing nausea. A different approach is needed to manage nausea in the clinic setting, along with standardised tools to measure nausea specifically. More studies need to be done with nausea as the primary endpoint to address this ongoing medical need.

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16-18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637&#95;643del (p.Tyr213Lysfs*6)) in FANCG. The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group., Methods: Cross-sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA)., Results: Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 3 (IGFBP-3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23)., Conclusion: Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype-phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF-1 and IGFBP-3., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The Langenskiöld classification is the most commonly utilized classification system for the radiological features of Blount's disease. Although there is only a single study found on the interobserver variability and none found on the intraobserver variability, it is commonly used for prognostication and guiding management decisions. The aim of this study was to determine the reliability and reproducibility of the Langenskiöld classification. A retrospective review of radiographs was done of patients treated for infantile and juvenile Blount's disease at Chris Hani Baragwanath Academic Hospital from 2006 to 2016. There were 70 radiographs of acceptable quality, which were reviewed and staged on two occasions according to the Langenskiöld classification by three orthopaedic consultants and three orthopaedic surgery senior residents. Pearson correlation coefficients, percentage agreements, and κ statistics were used to evaluate both the reliability and reproducibility. Of the 70 images staged, only two (2.9%) were staged the same by all six observers, and 20 (28.6%) images differed by a single stage. The consultants had 17 (24.3%) images staged the same whereas the residents had 12 (17.1%) images staged the same. The overall κ for all six observers showed a fair agreement of 0.24. Again, the consultants had a higher κ-value compared to residents of 0.25 and 0.24, respectively. The reproducibility amongst all observers was fair with a κ-value of 0.38. The consultants had a higher mean score of 0.48 compared to 0.26 for the residents. There was only a fair overall reliability and reproducibility amongst the six observers. We recommend the Langenskiöld classification be used with caution when being used for prognostication and management planning as well as when interpreting any research relying on this classification. Level of evidence: Level III, diagnostic study.

There has been a substantial burden of healthcare worker infection during the current coronavirus (COVID-19) pandemic, likely due to a lack of adequate preparedness, suboptimal institutional infection control measures, atypical patient presentation, poor compliance with personal protective equipment (PPE) and exposure to high-risk aerosol generating procedures, such as endotracheal intubation. There is significant concern that developing countries will face heightened levels of staff exposure during the COVID-19 pandemic. To mitigate this exposure risk during procedures, such as endotracheal intubation, various "aerosol boxes" have been designed by frontline healthcare workers. However, in practice these boxes were found to hamper endotracheal intubation and other procedures due to the limited space and manoeuvrability they allow. To further reduce particle dispersion and to improve on the practicality and ergonomic design of the prototype "aerosol box", the Intubox was developed by staff at the Charlotte Maxeke Johannesburg Academic Hospital after instituting several changes to the prototype design., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Motara et al.)

A quality-by-design and characterization approach was followed to ensure development of self-emulsifying drug delivery systems (SEDDSs) destined for topical delivery of the highly lipophilic clofazimine. Solubility and water-titration experiments identified spontaneous emulsification capacity of different excipient combinations and clofazimine. After identifying self-emulsification regions, check-point formulations were selected within the self-emulsification region by considering characteristics required to achieve optimized topical drug delivery. Check-point formulations, able to withstand phase separation after 24 h at an ambient temperature, were subjected to characterization studies. Experiments involved droplet size evaluation; size distribution; zeta-potential; self-emulsification time and efficacy; viscosity and pH measurement; cloud point assessment; and thermodynamic stability studies. SEDDSs with favorable properties, i.e., topical drug delivery, were subjected to dermal diffusion studies. Successful in vitro topical clofazimine delivery was observed. Olive oil facilitated the highest topical delivery of clofazimine probably due to increased oleic acid levels that enhanced stratum corneum lipid disruption, followed by improved dermal clofazimine delivery. Finally, isothermal microcalometric experiments studied the compatibility of excipients. Potential interactions were depicted between argan oil and clofazimine as well as between Span ® 60 and argan-, macadamia- and olive oil, respectively. However, despite some mundane incompatibilities, successful development of topical SEDDSs achieved enhanced topical clofazimine delivery.

Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n  = 126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) ( p  = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) ( p  = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) ( p  = 0.037). On multivariate analysis LDH ( p  = 0.023), ferritin ( p  = 0.002) and INSS stage ( p  = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS ( p  = 0.18), but significant for EFS ( p  = 0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatment-related deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.

Purpose: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa., Methods: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both., Results: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries., Conclusion: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma.