A continuous quality improvement strategy to strengthen screening practices and facilitate the routine use of intravenous iron for treating anaemia in pregnant and postpartum women in Nigeria: a study protocol.

BACKGROUND: Pregnancy-related anaemia is a public health challenge across Africa. Over 50% of pregnant women in Africa get diagnosed with this condition, and up to 75% of these are caused by iron deficiency. The condition is a significant contributor to the high maternal deaths across the continent and, in particular, Nigeria, which accounts for about 34% of global maternal deaths. Whereas oral iron is the mainstay treatment for pregnancy-related anaemia in Nigeria, this treatment is not very effective given the slow absorption of the medication, and its gastrointestinal adverse effects which lead to poor compliance by women. Intravenous iron is an alternative therapy which can rapidly replenish iron stores, but fears of anaphylactic reactions, as well as several misconceptions, have inhibited its routine use. Newer and safer intravenous iron formulations, such as ferric carboxymaltose, present an opportunity to overcome some concerns relating to adherence. Routine use of this formulation will, however, require addressing misconceptions and systemic barriers to adoption in the continuum of care of obstetric women from screening to treatment. This study aims to test the options to strengthen routine screening for anaemia during and immediately after pregnancy, as well as evaluate and improve conditions necessary to deliver ferric carboxymaltose to pregnant and postpartum women with moderate to severe anaemia. METHODS: This study will be conducted in a cluster of six health facilities in Lagos State, Nigeria. The study will employ continuous quality improvement through the Diagnose-Intervene-Verify-Adjust framework and Tanahashi's model for health system evaluation to identify and improve systemic bottlenecks to the adoption and implementation of the intervention. Participatory Action Research will be employed to engage health system actors, health services users, and other stakeholders to facilitate change. Evaluation will be guided by the consolidated framework for implementation research and the normalisation process theory. DISCUSSION: We expect the study to evolve transferable knowledge on barriers and facilitators to the routine use of intravenous iron that will inform scale-up across Nigeria, as well as the adoption of the intervention and strategies in other countries across Africa.

Health-Related Quality of Life Among Patients With Sickle Cell Disease in an Adult Hematology Clinic in a Tertiary Hospital in Lagos, Nigeria.

Background Sickle cell disease (SCD) is a genetic disease of public health concern. Improved quality healthcare has increased the life expectancy of these patients; however, they also face an increased frequency of vaso-occlusive crises and other SCD complications. These complications affect their quality of life, an area of care, which healthcare providers often overlook. We sought to determine the health-related quality of life among patients living with sickle cell disease in Lagos, Nigeria.  Materials and methods We conducted a cross-sectional study of 198 patients with sickle cell disease who attended the adult sickle cell clinic at a tertiary hospital in Lagos, Nigeria, during the period from October 1, 2018, to February 28, 2019. A self-administered questionnaire was used to obtain the clinical and socio-demographic characteristics of the patients and the 35-item Short-Form Health Survey (SF-36) questionnaire was used to determine their health-related quality of life (HRQoL). Determinants of HRQoL were established using bivariate and multivariate regression analysis.  Results The mean age of the 198 patients who participated in the study was 28.4±9.1 years, mean steady-state hemoglobin was 8.2 ± 1.3 g/dl, and 85 (42.9%) patients had a monthly income of 150 USD or less. In the previous year, 65 (32.1 %) and 33 (16.6%) patients, respectively, suffered one to two episodes (s) of acute bone pain crises and acute chest syndrome, and 43 (24.7%) had blood transfusion. Using the scoring system for SF-36 provided by RAND Health, role limitation due to physical health had the lowest median score of 50 (interquartile range {IQR}: 0-100). On bivariate analysis, bone pain crisis was associated with statistically significant low scores across all the 8 HRQoL domains of the SF36 questionnaire. Other variables, including having received blood transfusion, recent hospitalization, acute chest syndrome, lower level of income, and younger age, were also associated with significantly low scores. On regression analysis, bone pain crisis, level of income, and acute chest syndrome were found to be independent determinants of quality of life in the patients. Conclusion Sickle cell disease has a negative impact on the health-related quality of life of those affected. The presence of bone pain crisis is an important predictor of health-related quality of life in sickle cell disease patients. To improve patient outcomes, healthcare providers should take a holistic approach in evaluating and managing this disease, taking into cognizance how the complications and the financial burden of this disease impact the quality of life of affected patients.

SMAC Mimetic/IAP Inhibitor Birinapant Enhances Radiosensitivity of Glioblastoma Multiforme.

Birinapant is a novel SMAC peptidomimetic molecule in clinical development. It suppresses the inhibitor of apoptosis proteins (IAPs) and promotes cytochrome-C/Apaf-1/caspase-9 activation to induce effective apoptosis. Because IAP inhibition has been shown to enhance the sensitivity of cancer cells to radiation, we investigated the role of birinapant in radiosensitization of glioblastoma cells in vitro and in vivo. Two glioblastoma cell lines, U-251 and U-87, were used to analyze radiosensitization in vitro with 7-AAD cell death/apoptosis and clonogenic assays. Subcutaneous flank (U-251 and U-87) and intracranial orthotopic (U-251) xenografts in nude mice were used to evaluate radiosensitization in vivo. TNF-α levels in media and serum were measured using electrochemiluminescence. Radiosensitization in vitro was more prominent for U-251 cells than for U-87 cells. In vivo, in both tumor models, significant tumor growth delay was observed with combination treatment compared to radiation alone. There was a survival benefit with combination treatment in the orthotopic U-251 model. TNF-α levels in media correlated directly with radiation dose in vitro. These findings show that birinapant can enhance the radiosensitivity of glioblastoma cell lines in cell-based assays and tumor models via radiation-induced TNF-α. Further study into the use of birinapant with radiation therapy is warranted.

Pulmonary dysfunction among adolescents and adults with sickle cell disease in Nigeria: Implications for monitoring.

BACKGROUND: Pulmonary complications of sickle cell disease (SCD) contribute to excess morbidity and mortality. The burden of pulmonary dysfunction among Nigerians with SCD has not been well elucidated. OBJECTIVES: The objectives of this study are to describe the frequency and pattern of spirometry abnormalities in SCD and to explore the association between pulmonary dysfunction and selected parameters. METHODS: A cross-sectional study among adolescents and adults with SCD attending a University Teaching Hospital and healthy age- and gender-matched controls. Respiratory symptoms, oxygen saturation, spirometry, complete blood counts, and fetal hemoglobin (Hb) were measured. RESULTS: A total of 245 participants with SCD and 216 controls were included in the study. Frequency of respiratory symptoms was similar between the two groups. The median forced expiratory volume 1 (FEV1), forced vital capacity (FVC), and the FEV1/FVC were significantly lower in SCD as compared to controls (P = 0.000 in all instances). The frequency of abnormal pulmonary patterns was higher in SCD as compared to controls with abnormal spirometry pattern in 174 (71%) and 68 (31.5%) of participants with SCD and controls, respectively (P = 0.000). The suggestive of restrictive pattern was predominant (48% vs. 23%), but obstructive (11.8% vs. 7.4%) and mixed patterns (11% vs. 0.9%) were also found among SCD versus controls. Hb concentration was positively associated with FEV1 and FVC, whereas white cell count and age were negatively associated with FVC and FEV1, respectively. CONCLUSION: There is a high burden of pulmonary dysfunction in SCD among Nigerians which may be related to the severity of disease. There is a need for further research to explore the effectiveness of potential interventions so as to harness the benefits from monitoring and early detection.