Linking communities and health facilities to improve child health in low-resource settings: a systematic review.

Community-facility linkage interventions are gaining popularity as a way to improve community health in low-income settings. Their aim is to create/strengthen a relationship between community members and local healthcare providers. Representatives from both groups can address health issues together, overcome trust problems, potentially leading to participants' empowerment to be responsible for their own health. This can be achieved via different approaches. We conducted a systematic literature review to explore how this type of intervention has been implemented in rural and low or lower-middle-income countries, its various features and how/if it has helped to improve child health in these settings. Publications from three electronic databases (Web of Science, PubMed and Embase) up to 03 February 2022 were screened, with 14 papers meeting the inclusion criteria (rural setting in low/lower-middle-income countries, presence of a community-facility linkage component, outcomes of interest related to under-5 children's health, peer-reviewed articles containing original data written in English). We used Rosato's integrated conceptual framework for community participation to assess the transformative and community-empowering capacities of the interventions, and realist principles to synthesize the outcomes. The results of this analysis highlight which conditions can lead to the success of this type of intervention: active inclusion of hard-to-reach groups, involvement of community members in implementation's decisions, activities tailored to the actual needs of interventions' contexts and usage of mixed methods for a comprehensive evaluation. These lessons informed the design of a community-facility linkage intervention and offer a framework to inform the development of monitoring and evaluation plans for future implementations.

Whose knowledge counts? Involving communities in intervention and trial design using community conversations.

BACKGROUND: Current debates in Global Health call for expanding methodologies to allow typically silenced voices to contribute to processes of knowledge production and intervention design. Within trial research, this has typically involved small-scale qualitative work, with limited opportunities for citizens to contribute to the structure and nature of the trial. This paper reports on efforts to move past typical formative trial work, through adaptation of community conversations (CCs) methodology, an action-oriented approach that engages large numbers of community members in dialogue. We applied the CC method to explore community perspectives about pneumonia and managing the health of children under-5 in Northern Nigeria to inform our pragmatic cluster randomised controlled trial evaluating a complex intervention to reduce under-5 mortality in Nigeria. METHODS: We conducted 12 rounds of community conversations with a total of 320 participants, in six administrative wards in Kiyawa Local Government Area, Jigawa state, our intervention site. Participants were male and female caregivers of children under five. Conversations were structured around participatory learning and action activities, using drawings and discussion to reduce barriers to entry. During activities participants were placed in subgroups: younger women (18-30 years of age), older women (31-49 years) and men (18 years above). Discussions were conducted over three 2-h sessions, facilitated by community researchers. Following an initial analysis to extract priority issues and perspectives on intervention structure, smaller focus group discussions were completed with participants in five new sites to ensure all 11 administrative wards in our study site contributed to the design. RESULTS: We identified enabling and limiting factors which could shape the future trial implementation, including complex power relationships within households and wider communities shaping women's health decision-making, and the gendered use of space. We also noted the positive engagement of participants during the CC process, with many participants valuing the opportunity to express themselves in ways they have not been able to in the past. CONCLUSIONS: CCs provide a structured approach to deep meaningful engagement of everyday citizens in intervention and trial designs, but require appropriate resources, and commitment to qualitative research in trials. TRIAL REGISTRATION: ISRCTN39213655. Registered on 11 December 2019.

Community perceptions matter: a mixed-methods study using local knowledge to define features of success for a community intervention to improve quality of care for children under-5 in Jigawa, Nigeria.

OBJECTIVES: In this study, we used the information generated by community members during an intervention design process to understand the features needed for a successful community participatory intervention to improve child health. DESIGN: We conducted a concurrent mixed-methods study (November 2019-March 2020) to inform the design and evaluation of a community-facility linkage participatory intervention. SETTING: Kiyawa Local Government Area (Jigawa State, Nigeria)-population of 230 000 (n=425 villages). PARTICIPANTS: Qualitative data included 12 community conversations with caregivers of children under-5 (men, older and younger women; n=9 per group), 3 focus group discussions (n=10) with ward development committee members and interviews with facility heads (n=3). Quantitative data comprised household surveys (n=3464) with compound heads (n=1803) and women (n=1661). RESULTS: We analysed qualitative data with thematic network analysis and the surveys with linear regression-results were triangulated in the interpretation phase. Participants identified the following areas of focus: community health education; facility infrastructure, equipment and staff improvements; raising funds to make these changes. Community involvement, cooperation and empowerment were recognised as a strategy to improve child health, and the presence of intermediate bodies (development committees) was deemed important to improve communication and solve problems between community and facility members. The survey showed functional community relations' dynamics, with high levels of internal cohesion (78%), efficacy in solving problems together (79%) and fairness of the local leaders (82%). CONCLUSIONS: Combining the results from this study and critical theories on successful participation identified community-informed features for a contextually tailored community-facility link intervention. The need to promote a more inclusive approach to future child health interventions was highlighted. In addition to health education campaigns, the relationship between community and healthcare providers needs strengthening, and development committees were identified as an essential feature for successfully linking communities and facilities for child health. TRIAL REGISTRATION NUMBER: ISRCTN39213655.

Pneumonia knowledge and care seeking behavior for children under-five years in Jigawa, Northwest Nigeria: a cross-sectional study.

Background: Between 2013 and 2022, Nigeria did not meet globally defined targets for pneumonia control, despite some scale-up of vaccinations, oxygen and antibiotics. A deliberate focus on community-based programs is needed to improve coverage of protective, preventive and treatment interventions. We therefore aimed to describe caregiver knowledge and care seeking behaviour for childhood pneumonia, in a high child mortality setting in Nigeria, to inform the development of effective community-based interventions for pneumonia control. Methods: We conducted a cross-sectional household survey in Kiyawa Local Government Area, Jigawa State, Nigeria between December 2019 and March 2020. We asked caregivers about their knowledge of pneumonia symptoms, prevention, risks, and treatment. A score of 1 was assigned for each correct response. We showed them videos of pneumonia specific symptoms and asked (1) if their child had any respiratory symptoms in the 2-weeks prior; (2) their subsequent care-seeking behaviour. Multivariate regressions explored socio-demographic and clinical factors associated with care seeking. Results: We surveyed 1,661 eligible women, with 2,828 children under-five. Only 4.9% of women could name both cough and difficulty/fast breathing as pneumonia symptoms, and the composite knowledge scores for pneumonia prevention, risks and treatment were low. Overall, 19.0% (536/2828) of children had a report of pneumonia specific symptoms in the prior two-weeks, and of these 32.3% (176/536) were taken for care. The odds of care seeking was higher among children: with fever (AOR:2:45 [95% CI: 1.38-4.34]); from wealthiest homes (AOR: 2:13 [95% CI: 1.03-4.38]) and whose mother first married at 20-26 years compared to 15-19 years (AOR: 5.15 [95% CI: 1.38-19.26]). Notably, the caregiver's knowledge of pneumonia was not associated with care seeking. Conclusion: While some socio-demographic factors were associated with care seeking for children with symptoms of Acute Respiratory Infection (ARI), caregiver's knowledge of the disease was not. Therefore, when designing public health interventions to address child mortality, information-giving alone is likely to be insufficient.

Pulse oximetry and oxygen services for the care of children with pneumonia attending frontline health facilities in Lagos, Nigeria (INSPIRING-Lagos): study protocol for a mixed-methods evaluation.

INTRODUCTION: The aim of this evaluation is to understand whether introducing stabilisation rooms equipped with pulse oximetry and oxygen systems to frontline health facilities in Ikorodu, Lagos State, alongside healthcare worker (HCW) training improves the quality of care for children with pneumonia aged 0-59 months. We will explore to what extent, how, for whom and in what contexts the intervention works. METHODS AND ANALYSIS: Quasi-experimental time-series impact evaluation with embedded mixed-methods process and economic evaluation. SETTING: seven government primary care facilities, seven private health facilities, two government secondary care facilities. TARGET POPULATION: children aged 0-59 months with clinically diagnosed pneumonia and/or suspected or confirmed COVID-19. INTERVENTION: 'stabilisation rooms' within participating primary care facilities in Ikorodu local government area, designed to allow for short-term oxygen delivery for children with hypoxaemia prior to transfer to hospital, alongside HCW training on integrated management of childhood illness, pulse oximetry and oxygen therapy, immunisation and nutrition. Secondary facilities will also receive training and equipment for oxygen and pulse oximetry to ensure minimum standard of care is available for referred children. PRIMARY OUTCOME: correct management of hypoxaemic pneumonia including administration of oxygen therapy, referral and presentation to hospital. SECONDARY OUTCOME: 14-day pneumonia case fatality rate. Evaluation period: August 2020 to September 2022. ETHICS AND DISSEMINATION: Ethical approval from University of Ibadan, Lagos State and University College London. Ongoing engagement with government and other key stakeholders during the project. Local dissemination events will be held with the State Ministry of Health at the end of the project (December 2022). We will publish the main impact results, process evaluation and economic evaluation results as open-access academic publications in international journals. TRIAL REGISTRATION NUMBER: ACTRN12621001071819; Registered on the Australian and New Zealand Clinical Trials Registry.

Integrated Sustainable childhood Pneumonia and Infectious disease Reduction in Nigeria (INSPIRING) through whole system strengthening in Jigawa, Nigeria: study protocol for a cluster randomised controlled trial.

BACKGROUND: Child mortality remains unacceptably high, with Northern Nigeria reporting some of the highest rates globally (e.g. 192/1000 live births in Jigawa State). Coverage of key protect and prevent interventions, such as vaccination and clean cooking fuel use, is low. Additionally, knowledge, care-seeking and health system factors are poor. Therefore, a whole systems approach is needed for sustainable reductions in child mortality. METHODS: This is a cluster randomised controlled trial, with integrated process and economic evaluations, conducted from January 2021 to September 2022. The trial will be conducted in Kiyawa Local Government Area, Jigawa State, Nigeria, with an estimated population of 230,000. Clusters are defined as primary government health facility catchment areas (n = 33). The 33 clusters will be randomly allocated (1:1) in a public ceremony, and 32 clusters included in the impact evaluation. The trial will evaluate a locally adapted 'whole systems strengthening' package of three evidence-based methods: community men's and women's groups, Partnership Defined Quality Scorecard and healthcare worker training, mentorship and provision of basic essential equipment and commodities. The primary outcome is mortality of children aged 7 days to 59 months. Mortality will be recorded prospectively using a cohort design, and secondary outcomes measured through baseline and endline cross-sectional surveys. Assuming the following, we will have a minimum detectable effect size of 30%: (a) baseline mortality of 100 per 1000 livebirths, (b) 4480 compounds with 3 eligible children per compound, (c) 80% power, (d) 5% significance, (e) intra-cluster correlation of 0.007 and (f) coefficient of variance of cluster size of 0.74. Analysis will be by intention-to-treat, comparing intervention and control clusters, adjusting for compound and trial clustering. DISCUSSION: This study will provide robust evidence of the effectiveness and cost-effectiveness of community-based participatory learning and action, with integrated health system strengthening and accountability mechanisms, to reduce child mortality. The ethnographic process evaluation will allow for a rich understanding of how the intervention works in this context. However, we encountered a key challenge in calculating the sample size, given the lack of timely and reliable mortality data and the uncertain impacts of the COVID-19 pandemic. TRIAL REGISTRATION: ISRCTN 39213655 . Registered on 11 December 2019.

Community and caregivers' perceptions of pneumonia and care-seeking experiences in Nigeria: A qualitative study.

BACKGROUND: Appropriate and timely care seeking can reduce pneumonia deaths, but are influenced by caregivers and community norms of health and illness. We explore caregiver and community perceptions, and care-seeking experience, of childhood pneumonia, to understand contexts that drive pediatric service uptake in Nigeria. METHODS: Community group discussions and qualitative interviews with caregivers in Lagos and Jigawa states were completed between 1 November 2018 and 31 May 2019. Participants were recruited from purposively sampled health facility catchment areas with assistance from facility staff. We used episodic interviews, asking caregivers (Jigawa = 20; Lagos = 15) to recount specific events linked to quests for therapy. Community group discussions (n = 3) used four vignettes from real pneumonia cases to frame a discussion around community priorities for healthcare and community-led activities to improve child survival. Data were analyzed using the framework method. RESULTS: We found poor knowledge of pneumonia-specific symptoms and risk factors among caregivers and community members, with many attributing pneumonia to cold air exposure. Interviews highlighted that care-seeking decision making involved both husbands and wives, but men often made final decisions. In Lagos, older female relatives also shaped quests for therapy. Cost was a major consideration. In both states, there were accounts of dissatisfaction with health workers' attitudes and a general acceptance of vaccination services. CONCLUSION: There is a need for community-based approaches to improve caregiver knowledge and care seeking for under-five children with pneumonia. Messaging should attend to knowledge of symptoms, risk factors, family dynamics, and community responsibilities in healthcare service delivery and utilization.

AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer.

Inhibition of vascular endothelial growth factor-A (VEGF) signaling is a promising therapeutic approach that aims to stabilize the progression of solid malignancies by abrogating tumor-induced angiogenesis. This may be accomplished by inhibiting the kinase activity of VEGF receptor-2 (KDR), which has a key role in mediating VEGF-induced responses. The novel indole-ether quinazoline AZD2171 is a highly potent (IC50 < 1 nmol/L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro. Concordant with this activity, in human umbilical vein endothelial cells, AZD2171 inhibited VEGF-stimulated proliferation and KDR phosphorylation with IC50 values of 0.4 and 0.5 nmol/L, respectively. In a fibroblast/endothelial cell coculture model of vessel sprouting, AZD2171 also reduced vessel area, length, and branching at subnanomolar concentrations. Once-daily oral administration of AZD2171 ablated experimental (VEGF-induced) angiogenesis in vivo and inhibited endochondral ossification in bone or corpora luteal development in ovary; physiologic processes that are highly dependent upon neovascularization. The growth of established human tumor xenografts (colon, lung, prostate, breast, and ovary) in athymic mice was inhibited dose-dependently by AZD2171, with chronic administration of 1.5 mg per kg per day producing statistically significant inhibition in all models. A histologic analysis of Calu-6 lung tumors treated with AZD2171 revealed a reduction in microvessel density within 52 hours that became progressively greater with the duration of treatment. These changes are indicative of vascular regression within tumors. Collectively, the data obtained with AZD2171 are consistent with potent inhibition of VEGF signaling, angiogenesis, neovascular survival, and tumor growth. AZD2171 is being developed clinically as a once-daily oral therapy for the treatment of cancer.

ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration.

ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine]is a potent, p.o. active, low molecular weight inhibitor of kinase insert domain-containing receptor [KDR/vascular endothelial growth factor receptor (VEGFR) 2] tyrosine kinase activity (IC(50) = 40 nM). This compound has some additional activity versus the tyrosine kinase activity of fms-like tyrosine kinase 4 (VEGFR3;IC(50) = 110 nM) and epidermal growth factor receptor (EGFR/HER1; IC(50) = 500 nM) and yet demonstrates selectivity against a range of other tyrosine and serine-threonine kinases. The activity of ZD6474 versus KDR tyrosine kinase translates into potent inhibition of vascular endothelial growth factor-A (VEGF)-stimulated endothelial cell (human umbilical vein endothelial cell) proliferation in vitro (IC(50) = 60 nM). Selective inhibition of VEGF signaling has been demonstrated in vivo in a growth factor-induced hypotension model in anesthetized rat: administration of ZD6474 (2.5 mg/kg, i.v.) reversed a hypotensive change induced by VEGF (by 63%) but did not significantly affect that induced by basic fibroblast growth factor. Once-daily oral administration of ZD6474 to growing rats for 14 days produced a dose-dependent increase in the femoro-tibial epiphyseal growth plate zone of hypertrophy, which is consistent with inhibition of VEGF signaling and angiogenesis in vivo. Administration of 50 mg/kg/day ZD6474 (once-daily, p.o.) to athymic mice with intradermally implanted A549 tumor cells also inhibited tumor-induced neovascularization significantly (63% inhibition after 5 days; P < 0.001). Oral administration of ZD6474 to athymic mice bearing established (0.15-0.47 cm(3)), histologically distinct (lung, prostate, breast, ovarian, colon, or vulval) human tumor xenografts or after implantation of aggressive syngeneic rodent tumors (lung, melanoma) in immunocompetent mice, produced a dose-dependent inhibition of tumor growth in all cases. Statistically significant antitumor activity was evident in each model with at least 25 mg/kg ZD6474 once daily (P < 0.05, one-tailed t test). Histological analysis of Calu-6 tumors treated with 50 mg/kg/day ZD6474 for 24 days showed a significant reduction (>70%) in CD31 (endothelial cell) staining in nonnecrotic regions. ZD6474 also restrained growth of much larger (0.9 cm(3) volume) Calu-6 lung tumor xenografts and induced profound regression in established PC-3 prostate tumors of 1.4 cm(3) volume. ZD6474 is currently in Phase I clinical development as a once-daily oral therapy in patients with advanced cancer.