Strengths and weaknesses of the humanitarian Cluster Approach in relation to sexual and reproductive health services in northern Uganda.

Implementation of the Cluster Approach has been a major recent development in the humanitarian system. The aim of this study was to explore the strengths and weaknesses of the humanitarian Cluster Approach in relation to services for sexual and reproductive health (SRH) [including gender-based violence (GBV)] in northern Uganda, which is recovering from over 20 years of armed conflict. Face-to-face and telephone, semistructured, qualitative interviews were conducted in 2009 with purposively selected key informants from governmental, non-governmental, United Nations and donor agencies working in northern Uganda. Respondents noted a number of contributions of the Cluster Approach, including improved co-ordination of SRH services and stronger advocacy. However, concerns were raised about the low prioritisation, limited leadership and capacity, and standard setting for SRH services. Concerns were also raised about limited planning and capacity for dissolution of the Clusters in the transition to recovery and development in northern Uganda. Despite a number of contributions made by the Cluster Approach, particularly for responding to GBV, there were many concerns about its limited influence on SRH services. There were also concerns that the transition to recovery and development in northern Uganda may not result in reproductive health services being sufficiently strengthened

Community engagement strategy for increased uptake of routine immunization and select perinatal services in north-west Ethiopia: A descriptive analysis.

BACKGROUND: Routine immunization coverage has stagnated over the past decade and fallen short of WHO targets in Ethiopia. Community engagement strategies that reach beyond traditional health systems may reduce dropout and increase coverage. This evaluation assesses changes in immunization, postpartum family planning, and antenatal care coverage after implementation of an enhanced community engagement and defaulter tracing strategy, entitled "Fifth Child" project, across two districts in Benishangul-Gumuz Regional State (BGRS), Ethiopia. METHODS AND FINDINGS: A formative evaluation was conducted to examine the contribution of the strategy on immunization, postpartum family planning and antenatal care utilization in Assosa and Bambasi districts of BGRS. The quantitative findings are presented here. Routine and project-specific data were analyzed to assess changes in uptake of childhood vaccinations, postpartum family planning and antenatal care. Between January 2013 and December 2016, pentavalent-3 coverage increased from 63% to 84% in Assosa, and from 78% to 93% in Bambasi. Similarly, measles vaccine coverage increased from 77% to 81% in Assosa, and from 59% to 86% in Bambasi. Approximately 54% of all eligible infants across both woredas defaulted on scheduled vaccinations at least once during the period. Among defaulting children, 84% were identified and subsequently caught up on the vaccinations missed. Secondary outcomes of postpartum family planning and antenatal care also increased in both woredas. CONCLUSION: The "Fifth Child" project likely contributed to enhanced immunization performance and increased utilization of immunization and select perinatal health services in two woredas of BGRS. Further research is required in order to determine the impact of this community engagement strategy

Tumor-Penetrating Delivery of siRNA against TNFα to Human Vestibular Schwannomas

Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened. Nanoparticles directed by the tumor-homing peptide iRGD were selectively taken up by primary VS cultures in vitro via interactions with αvβ3/β5 integrins and neuropilin-1 (NRP-1). Cellular uptake was inhibited by a neutralizing antibody against αv integrin in a dose-dependent manner. When applied to primary VS cultures, iRGD-targeted nanoparticles delivered siRNA directed against TNFα in a receptor-specific fashion to potently silence gene expression and protein secretion. Taken together, our results provide a proof of principle for tumor-targeted, nanoparticle-mediated delivery of siRNA to VS and establish a novel platform for the development and pre-clinical screening of molecular therapeutics against VS

Tackling the Mouse‐on‐Mouse Problem in Cochlear Immunofluorescence: A Simple Double‐Blocking Protocol for Immunofluorescent Labeling of Murine Cochlear Sections with Primary Mouse Antibodies

The mouse is the most widely used animal model in hearing research. Immunohistochemistry and immunofluorescent staining of murine cochlear sections have, thus, remained a backbone of inner ear research. Since many primary antibodies are raised in mouse, the problem of "mouse-on-mouse" background arises due to the interaction between the anti-mouse secondary antibody and the native mouse immunoglobulins. Here, we describe the pattern of mouse-on-mouse background fluorescence in sections of the postnatal mouse cochlea. Furthermore, we describe a simple double-blocking immunofluorescence protocol to label mouse cochlear cryosections. The protocol contains a conventional blocking step with serum, and an additional blocking step with a commercially available anti-mouse IgG blocking reagent. This blocking technique virtually eliminates the "mouse-on-mouse" background in murine cochlear sections, while adding only a little time to the staining protocol. We provide detailed instructions and practical tips for tissue harvesting, processing, and immunofluorescence-labeling. Further protocol modifications are described, to shorten the duration of the protocol, based on the primary antibody incubation temperature. Finally, we demonstrate examples of immunofluorescence staining performed using different incubation times and various incubation temperatures with a commercially available mouse monoclonal primary antibody

What mechanisms drive uptake of family planning when integrated with childhood immunisation in Ethiopia? A realist evaluation.

BACKGROUND: Maternal and child health are key priorities among the Sustainable Development Goals, which include a particular focus on reducing morbidity and mortality among women of reproductive age, newborns, and children under the age of five. Two components of maternal and child health are family planning (FP) and immunisation. Providing these services through an integrated delivery system could increase the uptake of vaccines and modern contraceptive methods (MCMs) particularly during the post-partum period. METHODS: A realist evaluation was conducted in two woredas in Ethiopia to determine the key mechanisms and their triggers that drive successful implementation and service uptake of an intervention of integrated delivery of immunisations and FP. The methodological approach included the development of an initial programme theory and the selection of relevant, published implementation related theoretical frameworks to aid organisation and cumulation of findings. Data from 23 semi-structured interviews were then analysed to determine key empirical mechanisms and drivers and to test the initial programme theory. These mechanisms were mapped against published theoretical frameworks and a revised programme theory comprised of context-mechanism-outcome configurations was developed. A critique of theoretical frameworks for abstracting empirical mechanisms was also conducted. RESULTS: Key contextual factors identified were: the use of trained Health Extension Workers (HEWs) to deliver FP services; a strong belief in values that challenged FP among religious leaders and community members; and a lack of support for FP from male partners based on religious values. Within these contexts, empirical mechanisms of acceptability, access, and adoption of innovations that drove decision making and intervention outcomes among health workers, religious leaders, and community members were identified to describe intervention implementation. CONCLUSIONS: Linking context and intervention components to the mechanisms they triggered helped explain the intervention outcomes, and more broadly how and for whom the intervention worked. Linking empirical mechanisms to constructs of implementation related theoretical frameworks provided a level of abstraction through which findings could be cumulated across time, space, and conditions by theorising middle-range mechanisms

The genetics of cholesteatoma. A systematic review using narrative synthesis

Objective: A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology. Data Sources: A systematic search of MEDLINE (EBSCO) and 2 databases of curated genetic research (OMIM and Phenopedia) was conducted. Study Selection: The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants. Data Extraction: The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis. Data Synthesis: A narrative synthesis was conducted and data were tabulated to record characteristics, including study design; genetic data; and author conclusions. Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case-reports, congenital and acquired cholesteatoma have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation. Conclusions: This is the first systematic review about the genetics of cholesteatoma; and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies

Context-acceptability theories: example of family planning interventions in five African countries.

BACKGROUND: Family planning (FP) can lengthen birth intervals and potentially reduce the risk of foetal death, low birthweight, prematurity, and being small for gestational age. Effective FP is most easily achieved through access to and acceptability of modern contraceptive methods (MCMs). This study aimed to identify mechanisms of acceptability and the contexts in which they are triggered and to generate theories to improve the selection and implementation of effective interventions by studying an intervention integrating FP with childhood immunisation services. METHODS: Qualitative interpretative synthesis of findings from realist evaluations of FP interventions in five African countries was guided by an analytical framework. Empirical mechanisms of acceptability were identified from semi-structured interviews and focus group discussions with key stakeholders (N = 253). The context in which these mechanisms were triggered was also defined. Empirical mechanisms of acceptability were matched to constructs of a theoretical framework of acceptability. Context-acceptability theories (CATs) were developed, which summarised constructs of acceptability triggered for specific actors in specified contexts. Examples of interventions that may be used to trigger acceptability for these actors were described. RESULTS: Seven CATs were developed for contexts with strong beliefs in religious values and with powerful religious leaders, a traditional desire for large families, stigmatisation of MCM use, male partners who are non-accepting of FP, and rumours or experiences of MCM side effects. Acceptability mechanisms included alignment with values and beliefs without requiring compromise, actors' certainty about their ability to avoid harm and make the intervention work, and understanding the intervention and how it works. Additionally, acceptability by one group of actors was found to alter the context, triggering acceptability mechanisms amongst others. CONCLUSIONS: This study demonstrated the value of embedding realist approaches within implementation research. CATs are transferable theories that answer the question: given the context, what construct of acceptability does an intervention need to trigger, or more simply, what intervention do we need to apply here to achieve our outcomes? CATs facilitate transfer of interventions across geographies within defined contexts

"As a woman who watches how my family is… I take the difficult decisions": a qualitative study on integrated family planning and childhood immunisation services in five African countries.

BACKGROUND: Family planning (FP) has the potential to improve maternal and child health outcomes and to reduce poverty in sub-Saharan Africa. However, substantial unmet need for modern contraceptive methods (MCMs) persists in this region. Current literature highlights multi-level barriers, including socio-cultural norms that discourage the use of MCMs. This paper explores women's choices and decision-making around MCM use and examines whether integrating FP services with childhood immunisations influenced women's perceptions of, and decision to use, an MCM. METHODS: 94 semi-structured interviews and 21 focus group discussions with women, health providers, and community members (N = 253) were conducted in health facilities and outreach clinics where an intervention was delivering integrated FP and childhood immunisation services in Benin, Ethiopia, Kenya, Malawi and Uganda. Data were coded using Nvivo software and an analytical framework was developed to support interpretative and thematic analyses on women's decision-making about MCM use. RESULTS: Most women shared the reproductive desire to space or limit births because of the perceived benefits of improved health and welfare for themselves and for their children, including the economic advantages. For some, choices about MCM use were restricted because of wider societal influences. Women's decision to use MCMs was driven by their reproductive desires, but for some that was stymied by fears of side effects, community stigma, and disapproving husbands, which led to clandestine MCM use. Health providers acknowledged that women understood the benefits of using MCMs, but highlighted that the wider socio-cultural norms of their community often contributed to a reluctance to use them. Integration of FP and childhood immunisation services provided repeat opportunities for health providers to counter misinformation and it improved access to MCMs, including for women who needed to use them covertly. CONCLUSIONS: Some women chose to use MCMs without the approval of their husbands, and/or despite cultural norms, because of the perceived health and economic benefits for themselves and for their families, and because they lived with the consequences of short birth intervals and large families. Integrated FP and childhood immunisation services expanded women's choices about MCM use and created opportunities for women to make decisions autonomously

Effectiveness of Mechanisms and Models of Coordination between Organizations, Agencies and Bodies Providing or Financing Health Services in Humanitarian Crises: A Systematic Review.

BACKGROUND: Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes. METHODS: We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach. RESULTS: Of 14,309 identified citations from databases and organizations' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality. CONCLUSION: This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field