Taking stock of population-level interventions targeting risk factors for hypertension and diabetes in Rwanda and South Africa: methodological reflections and lessons learnt from conducting a multi-component situational analysis.

BACKGROUND: Hypertension and diabetes are on the rise both in Rwanda and South Africa. The responsibility for NCD risk factors cut across different sectors, which makes it complex to effectively manage. Policy-relevant intervention research is thus critical for addressing the NCD challenge. We conducted a situational analysis in both countries to identify and describe current population-level interventions targeting risk factors for diabetes and hypertension. This paper presents this methodology and shares challenges encountered, and lessons learnt in applying the methodology. METHODS: We describe a multi-component methodology for conducting a situational analysis, which included a desk review, stakeholder mapping, survey, key informant interviews, and a consultative workshop. This methodology was applied in a standardized manner in two African countries. Following the analysis, the authors held iterative team consultations to reflect on challenges and lessons learnt during this process. RESULTS: Key challenges and lessons learnt relate to i) stakeholder recruitment, engagement and retainment; ii) utilization and triangulation of multiple sources of data; and iii) evolving circumstances, particularly related to the Covid-19 pandemic. It proved challenging to recruit stakeholders outside the health sector and in the private sector, as they often do not consider themselves as making or influencing policies and thus were reluctant to engage. The difficulties with responsiveness were often overcome through face-to-face visits, an opportunity to explain the relevance of their participation. With regards to health sector stakeholders and all other stakeholders, continued engagement over prolonged periods of time also turned out to be challenging. Covid-19 restrictions were preserved to be an impediment throughout the conduct of the situational analysis, specifically in South Africa. The use of multi-stage mixed methods was found to be appropriate for addressing the study objectives, as each step yielded unique data, concepts, and perspectives that complemented the other data. CONCLUSION: Conducting a situational analysis is crucial for understanding the current state of interventions and identifying opportunities for new interventions. The multi-component methodology used in two African countries was found to be feasible, appropriate, and informative. Others planning to conduct situational analysis may follow, adapt and improve upon our approach, reacting to the challenges encountered.

The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress.

As an essential part of the National Cancer Institute (NCI)-funded Pediatric Brain Tumor Consortium (PBTC), the Neuroimaging Center (NIC) is dedicated to infusing the study of pediatric brain tumors with imaging "best practice" by producing a correlative research plan that 1) resonates with novel therapeutic interventions being developed by the wider PBTC, 2) ensures that every PBTC protocol incorporates an imaging "end point" among its objectives, 3) promotes the widespread implementation of standardized technical protocols for neuroimaging, and 4) facilitates a quality assurance program that complies with the highest standards for image data transfer, diagnostic image quality, and data integrity. To accomplish these specific objectives, the NIC works with the various PBTC sites (10 in all, plus NCI/ National Institute of Neurological Diseases and Stroke representation) to ensure that the overarching mission of the consortium--to better understand tumor biology and develop new therapies for central nervous system tumors in children--is furthered by creating a uniform body of imaging techniques, technical protocols, and standards. Since the inception of the NIC in 2003, this broader mandate has been largely accomplished through a series of site visits and meetings aimed at assessing prevailing neuroimaging practices against NIC-recommended protocols, techniques, and strategies for achieving superior image quality and executing the secure transfer of data to the central PBTC. These ongoing evaluations periodically examine investigations into targeted drug therapies. In the future, the NIC will concentrate its efforts on improving image analysis for MR imaging and positron-emission tomography (PET) and on developing new ligands for PET; imaging markers for radiation therapy; and novel systemic, intrathecal, and intralesional therapeutic interventions.

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

BACKGROUND AND PURPOSE: Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. RESULTS: Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (Ktrans), rate constant from extracellular extravascular space back into blood plasma (Kep), and extracellular extravascular volume fraction (Ve) were all significantly correlated with tumor grade; high-grade tumors showed higher Ktrans, higher Kep, and lower Ve. Although all 3 parameters had high specificity (range, 82%-100%), Kep had the highest specificity for both grades. Optimal sensitivity was achieved for Ve, with a combined sensitivity of 76% (compared with 71% for Ktrans and Kep). CONCLUSIONS: Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors.

X-linked creatine transporter defect: a report on two unrelated boys with a severe clinical phenotype.

We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of the 3' end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.