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SUMMARYThe role of in¯ammatory effector cells in the pathogenesis of airway allergy has been the subject of much investigation. However, whether systemic factors are involved in the development of local responses in both upper and lower airways has not been fully clari®ed. The present study was performed to investigate aspects of the pathogenesis of isolated allergic rhinitis in a murine model sensitized to ovalbumin (OVA). Both upper-and lower-airway physiological responsiveness and in¯ammatory changes were assessed, as well as bone marrow progenitor responses, by culture and immunohistological methods. Signi®cant nasal symptoms and hyper-responsiveness appeared after intranasal OVA challenge (P<0 . 0001 and P<0 . 01, respectively), accompanied with signi®-cant nasal mucosal changes in CD4+ cells (P<0 . 001), interleukin (IL)-4 + cells (P<0 . 01), IL-5 + cells (P<0 . 01), basophilic cells (P<0 . 02) and eosinophils (P<0 . 001), in the complete absence of hyper-responsiveness or in¯ammatory changes in the lower airway. In the bone marrow, there were signi®cant increases in CD34 + cells, as well as in eosinophils and basophilic cells. In the presence in vitro of mouse recombinant IL-5, IL-3 or granulocyte±macrophage colony-stimulating factor (GM-CSF), the level of bone marrow eosinophil/basophil (Eo/Baso) colony-forming cells increased signi®cantly in the OVA-sensitized group. We conclude that, in this murine model of allergic rhinitis, haemopoietic progenitors are upregulated, which is consistent with the involvement of bone marrow in the pathogenesis of nasal mucosal in¯ammation. Both local and systemic events, initiated in response to allergen provocation, may be required for the pathogenesis of allergic rhinitis. Understanding these events and their regulation could provide new therapeutic targets for rhinitis and asthma.

IntroductionA major barrier to improving childhood cancer survival is the perception that paediatric oncology services are too costly for low-income and middle-income country (LMIC) health systems. We conducted a systematic review to synthesise existing evidence on the costs and cost-effectiveness of treating childhood cancers in LMICs.MethodsWe searched multiple databases from their inception to March 2019. All studies reporting costs or cost-effectiveness of treating any childhood cancer in an LMIC were included. We appraised included articles using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Where possible, we extracted or calculated the cost per disability-adjusted life year (DALY) averted using reported survival and country-specific life expectancy. Cost/DALY averted was compared with per capita gross domestic product (GDP) as per WHO-Choosing Interventions that are Cost-Effective guidelines to determine cost-effectiveness.ResultsOf 2802 studies identified, 30 met inclusion criteria. Studies represented 22 countries and nine different malignancies. The most commonly studied cancers were acute lymphoblastic leukaemia (n=10), Burkitt lymphoma (n=4) and Wilms tumour (n=3). The median CHEERS checklist score was 18 of 24. Many studies omitted key cost inputs. Notably, only 11 studies included healthcare worker salaries. Cost/DALY averted was extracted or calculated for 12 studies and ranged from US$22 to US$4475, although the lower-end costs were primarily from studies that omitted key cost components. In all 12, cost/DALY averted through treatment was substantially less than country per capita GDP, and therefore considered very cost-effective.ConclusionMany included studies did not account for key cost inputs, thus underestimating true treatment costs. Costs/DALY averted were nonetheless substantially lower than per capita GDP, suggesting that even if all relevant inputs are included, LMIC childhood cancer treatment is consistently very cost-effective. While additional rigorous economic evaluations are required, our results can inform the development of LMIC national childhood cancer strategies.

PurposeNo published study to date has examined total cost and cost-effectiveness of maintaining a pediatric oncology treatment center in an African setting, thus limiting childhood cancer advocacy and policy efforts.MethodsWithin the Korle Bu Teaching Hospital in Accra, Ghana, costing data were gathered for all inputs related to operating a pediatric cancer unit. Cost and volume data for relevant clinical services (eg, laboratory, pathology, medications) were obtained retrospectively or prospectively. Salaries were determined and multiplied by proportion of time dedicated toward pediatric patients with cancer. Costs associated with inpatient bed use, outpatient clinic use, administrative fees, and overhead were estimated. Costs were summed for a total annual operating cost. Cost-effectiveness was calculated based on annual patients with newly diagnosed disease, survival rates, and life expectancy.ResultsThe Korle Bu Teaching Hospital pediatric cancer unit treats on average 170 new diagnoses annually. Total operating cost was $1.7 million/y. Personnel salaries and operating room costs were the most expensive inputs, contributing 45% and 21% of total costs. Together, medications, imaging, radiation, and pathology services accounted for 7%. The cost per disability-adjusted life-year averted was $1,034, less than the Ghanaian per capita income, and thus considered very cost effective as per WHO-CHOICE methodology.ConclusionTo our knowledge, this study is the first to examine institution-level costs and cost-effectiveness of a childhood cancer program in an African setting, demonstrating that operating such a program in this setting is very cost effective. These results will inform national childhood cancer strategies in Africa and other low- and middle-income country settings.

Recent studies have demonstrated an important role for IL-5-dependent bone marrow eosinophil progenitors in allergic inflammation. However, studies using anti-IL-5 mAbs in human asthmatics have failed to suppress lower airway hyperresponsiveness despite suppression of eosinophilia; therefore, it is critical to examine the role of IL-5 and bone marrow responses in the pathogenesis of allergic airway disease. To do this, we studied the effects of IL-5 deficiency (IL-5−/−) on bone marrow function as well as clinical and local events, using an established experimental murine model of allergic rhinitis. Age-matched IL-5+/+ and IL-5−/− BALB/c mice were sensitized to OVA followed by 2 wk of daily OVA intranasal challenge. IL-5−/− OVA-sensitized mice had significantly higher nasal mucosal CD4+ cells and basophilic cell counts as well as nasal symptoms and histamine hyperresponsiveness than the nonsensitized group; however, there was no eosinophilia in either nasal mucosa or bone marrow; significantly lower numbers of eosinophil/basophil CFU and maturing CFU eosinophils in the presence of recombinant mouse IL-5 in vitro; and significantly lower expression of IL-5Rα on bone marrow CD34+CD45+ progenitor cells in IL-5−/− mice. These findings suggest that IL-5 is required for normal bone marrow eosinophilopoiesis, in response to specific Ag sensitization, during the development of experimental allergic rhinitis. However, the results also suggest that suppression of the IL-5-eosinophil pathway in this model of allergic rhinitis may not completely suppress clinical symptoms or nasal histamine hyperresponsiveness, because of the existence of other cytokine-progenitor pathways that may induce and maintain the presence of other inflammatory cell populations.

Background The treatment of childhood cancer often is assumed to be costly in African settings, thereby limiting advocacy and policy efforts. The authors determined the cost and cost‐effectiveness of maintaining childhood cancer centers across 4 hospitals throughout sub‐Saharan Africa. Methods Within hospitals representing 4 countries (Kenya, Nigeria, Tanzania, and Zimbabwe), cost was determined either retrospectively or prospectively for all inputs related to operating a pediatric cancer unit (eg, laboratory costs, medications, and salaries). Cost‐effectiveness was calculated based on the annual number of newly diagnosed patients, survival rates, and life expectancy. Results Cost per new diagnosis ranged from $2400 to $31,000, attributable to variances with regard to center size, case mix, drug prices, admission practices, and the treatment abandonment rate, which also affected survival. The most expensive cost input was found to be associated with medication in Kenya, and medical personnel in the other 3 centers. The cost per disability‐adjusted life‐year averted ranged from 0.3 to 3.6 times the per capita gross national income. Childhood cancer treatment therefore was considered to be very cost‐effective by World Health Organization standards in 2 countries and cost‐effective in 1 additional country. In all centers, abandonment of treatment was common; modeling exercises suggested that public funding of treatment, additional psychosocial personnel, and modifications of inpatient policies would increase survival rates while maintaining or even improving cost‐effectiveness. Conclusions Across various African countries, childhood cancer treatment units represent cost‐effective interventions. Cost‐effectiveness can be increased through the control of drug prices, appropriate policy environments, and decreasing the rate of treatment abandonment. These results will inform national childhood cancer strategies across Africa.

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Mounting evidence suggests that participation in clinical trials confers neither advantage nor disadvantage on those enrolled. Narrow focus on the question of a "trial effect," however, distracts from a broader mechanism by which patients may benefit from ongoing clinical research. We hypothesize that the existence of clinical trials infrastructure-the organizational culture, systems, and expertise that develop as a product of sustained participation in cooperative clinical trials research-may function as a quality improvement lever, improving the quality of care and outcomes of all patients within an institution or region independent of their individual participation in trials. We further contend that this "infrastructure effect" can yield particular benefits for patients in low- and middle-income countries (LMICs). The hypothesis of an infrastructure effect as a quality improvement intervention, if correct, justifies enhanced research capacity in LMIC as a pillar of health system development.