Role and use of evidence in policymaking: an analysis of case studies from the health sector in Nigeria.

Background Health policymaking is a complex process and analysing the role of evidence is still an evolving area in many low- and middle-income countries. Where evidence is used, it is greatly affected by cognitive and institutional features of the policy process. This paper examines the role of different types of evidence in health policy development in Nigeria. Methods The role of evidence was compared between three case studies representing different health policies, namely the (1) integrated maternal neonatal and child health strategy (IMNCH); (2) oral health (OH) policy; and (3) human resource for health (HRH) policy. The data was collected using document reviews and 31 in-depth interviews with key policy actors. Framework Approach was used to analyse the data, aided by NVivo 10 software. Results Most respondents perceived evidence to be factual and concrete to support a decision. Evidence was used more if it was perceived to be context-specific, accessible and timely. Low-cost high-impact evidence, such as the Lancet series, was reported to have been used in drafting the IMNCH policy. In the OH and HRH policies, informal evidence such as experts’ experiences and opinions, were reported to have been useful in the policy drafting stage. Both formal and informal evidence were mentioned in the HRH and OH policies, while the development of the IMNCH was revealed to have been informed mainly by more formal evidence. Overall, respondents suggested that formal evidence, such as survey reports and research publications, were most useful in the agenda-setting stage to identify the need for the policy and thus initiating the policy development process. International and local evidence were used to establish the need for a policy and develop policy, and less to develop policy implementation options. Conclusion Recognition of the value of different evidence types, combined with structures for generating and using evidence, are likely to enhance evidence-informed health policy development in Nigeria and other similar contexts

Antimicrobial activities of lactic acid bacteria isolated from akamu and kunun-zaki (cereal based non-alcoholic beverages) in Nigeria

Three lactic acid bacteria (LAB) isolates designated AS1, AS2 and KN4 isolated from kunun-zaki (a sorghum based non-alcoholic beverage widely consumed in Northern Nigeria) and identified as Lactobacillus plantarum, Lactobacillus brevis and Lactobacillus delbruckii, respectively, produced significant inhibitory compounds in broth. The partially purified inhibitory compounds were screened by agar spot assay method for antagonistic activity against target Gram positive and negative bacteria as well as yeasts associated with food spoilage. The partially purified compounds exhibited strong activity against Staphylococcus aureus ATCC 12600, Bacillus cereus and Escherichia coli ATCC 11775. The inhibitory compound produced by AS1 and KN4 inhibited Bacillus subtilis. Only the inhibitory compound produced by AS1 affected Candida albicans and Candida krusei. Analysis of variance indicated that there was a significant difference (P<0.05) in the susceptibility of the different target organisms to partially purified inhibitory compounds. Gram positive bacteria were affected more than yeasts. Proteolytic enzymes, trypsin and pepsin, but not catalase and α-amylase, completely inactivated antagonistic activity of the compounds demonstrating their proteinacious nature. The inhibitory compounds were fairly heat stable and also stable over broad pH ranges. The use of these or related GRAS isolates in the production of this and related beverage may increase the safety, shelf life and marketing appeal of such beveragesKeywords: Bacteriocins, lactic acid bacteria (LAB), target organisms, antimicrobial activity.African Journal of Biotechnology, Vol 13(29) 2977-298

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study

Abstract Background Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. Methods We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. Results Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. Conclusions We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. Trial registration NCT05338931; Date: 2022–04-01