How to (or Not to) Integrate Vertical Programmes for the Control of Major Neglected Tropical Diseases in Sub-Saharan Africa

Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.

OBJECTIVE: Hexarelin is a synthetic six-amino-acid compound capable of releasing GH in animals and in man. Its mechanism of action is not understood and little is known about the GH response after repeated administration. The aim of this study was to determine the GH response to the administration of two intravenous boluses of hexarelin, growth hormone releasing hormone (GHRH) or hexarelin with GHRH. DESIGN: Single boluses of hexarelin (1 microgram/kg), GHRH-(1-29)-NH2 (1 microgram/kg) or hexarelin with GHRH-(1-29)-NH2 were administered intravenously. Each study was performed on two further occasions, with a second bolus being administered 60 or 120 minutes after the first. A control study was performed giving saline intravenously. Studies were performed in a random order. SUBJECTS: Six healthy adult males (25.4-34.1 years) were studied. MEASUREMENTS: Serum GH was measured by radioimmunoassay. GH secretion rates were derived from the measured serum GH concentrations using the technique of deconvolution analysis. RESULTS: The peak GH secretion rate following the first intravenous bolus of hexarelin was greater than that following the first bolus of GHRH-(1-29)-NH2 (P < 0.001), and was greatest following the administration of hexarelin with GHRH-(1-29)-NH2 (P < 0.001). The coadministration of the two secretagogues resulted in peak GH secretion rates significantly greater than the arithmetic sum of those following their isolated administration (P = 0.001), demonstrating synergism. Compared to saline, the administration of a second bolus of hexarelin, GHRH-(1-29)-NH2 or both resulted in significant further GH secretion (P = 0.02, P = 0.002, P = 0.03, respectively). The administration of a second bolus of hexarelin or hexarelin with GHRH-(1-29)-NH2 120 minutes after the first bolus resulted in lower peak GH secretion rates (P = 0.03). The reductions in peak GH secretion rates following the 60-minute boluses were not statistically significant. The peak GH secretion rates following the first GHRH-(1-29)-NH2 boluses were similar to those following the 60 and 120-minute GHRH-(1-29)-NH2 boluses (P = NS). Irrespective of the interval between the boluses of hexarelin with GHRH-(1-29)-NH2, the peak GH secretion rates following the second boluses were not significantly different from the arithmetic sum of those following the administration of the second boluses of hexarelin or GHRH-(1-29)-NH2, indicating loss of synergism on repeated administration. CONCLUSION: This study shows that hexarelin is a potent GH secretagogue active after two successive doses; the magnitude of the GH response to the second dose was influenced by the dosing interval. Hexarelin and GHRH-(1-29)-NH2 are synergistic, a property which is lost after repeated administration. These findings may help our understanding of GHRPs and may have implications for the potential use of hexarelin and other GHRPs as therapeutic agents