Study protocol for a single-centre observational study of household wellbeing and poverty status following a diagnosis of advanced cancer in Blantyre, Malawi - ‘Safeguarding the Family’ study

Background: Many households in low-and-middle income countries face the additional burden of crippling out-of-pocket expenditure when faced with a diagnosis of life-limiting illness. Available evidence suggests that receipt of palliative care supports cost-savings for cancer-affected households. This study will explore the relationship between receipt of palliative care, total household out-of-pocket expenditure on health and wellbeing following a first-time diagnosis of advanced cancer at Queen Elizabeth Central Hospital in Blantyre, Malawi. Protocol: Patients and their primary family caregivers will be recruited at the time of cancer diagnosis. Data on healthcare utilisation, related costs, coping strategies and wellbeing will be gathered using new and existing questionnaires (the Patient-and-Carer Cancer Cost Survey, EQ-5D-3L and the Integrated Palliative Care Outcome Score). Surveys will be repeated at one, three and six months after diagnosis. In the event of the patient’s death, a brief five-item questionnaire on funeral costs will be administered to caregivers not less than two weeks following the date of death. Descriptive and Poisson regression analyses will assess the relationship between exposure to palliative care and total household expenditure from baseline to six months. A sample size of 138 households has been calculated in order to detect a medium effect (as determined by Cohen’s f2=0.15) of receipt of palliative care in a regression model for change in total household out-of-pocket expenditure as a proportion of annual household income. Ethics and dissemination: The study has received ethical approval. Results will be reported using STROBE guidelines and disseminated through scientific meetings, open access publications and a national stakeholder meeting. Conclusions: This study will provide data on expenditure for healthcare by households affected by cancer in Malawi. We also explore whether receipt of palliative care is associated with a reduction in out-of-pocket expenditure at household level

Enhanced patient research participation: a Photovoice study in Blantyre Malawi

ObjectivesPatient involvement in palliative care research is a desirable if challenging goal. Photovoice is an action research method in which affected communities gather photographs to document and discuss their communities’ strengths and concerns. Engagement with policymakers is a separately stated goal. Photovoice is increasingly used in health-related research but has not been widely described in the palliative care literature. We report on experiences and lessons learnt using Photovoice in Blantyre, Malawi to encourage its wider use in research and practice.MethodsThirteen co-researchers (six patients and seven household carers, mean age 47 years) receiving community-based palliative care, attended nine half-day group sessions over a 4-month period. Co-researchers produced, selected and analysed photographs. On completion of data collection, they conducted an advocacy event, including a photographic exhibition, to which media representatives and community leaders were invited.ResultsProcedures to ensure safety of co-researchers and to obtain consent of individuals identified in the photographs were developed during the planning phase. Co-researchers engaged with the Photovoice process with enthusiasm, although frailty and physical disability (poor sight) limited participation for some older adults. Inclusion of palliative care staff within the research team helped to facilitate open dialogue and clinical review where appropriate.ConclusionsIn this Photovoice study, patients and family members receiving palliative care engaged in an exploration of household well-being using photography, participatory analysis and an advocacy event. With appropriate planning, Photovoice can be adapted to a range of settings to enhance patient participation.</jats:sec

Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: Identification of apoptotic genes as targets for demethylation

<p>Abstract</p> <p>Background</p> <p>Methylation-mediated silencing of genes is one epigenetic mechanism implicated in cancer. Studies regarding the role of modulation of gene expression utilizing inhibitors of DNA methylation, such as decitabine, in osteosarcoma (OS) have been limited. A biological understanding of the overall effects of decitabine in OS is important because this particular agent is currently undergoing clinical trials. The objective of this study was to measure the response of the OS cell line, U2OS, to decitabine treatment both <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Microarray expression profiling was used to distinguish decitabine-dependent changes in gene expression in U2OS cells, and to identify responsive loci with demethylated CpG promoter regions. U2OS xenografts were established under the sub-renal capsule of immune-deficient mice to study the effect of decitabine <it>in vivo </it>on tumor growth and differentiation. Reduced nuclear methylation levels could be detected in xenografts derived from treated mice by immunohistochemistry utilizing a 5-methylcytidine antibody. Decitabine treatment reduced tumor xenograft size significantly (p < 0.05). Histological analysis of treated U2OS xenograft sections revealed a lower mitotic activity (p < 0.0001), increased bone matrix production (p < 0.0001), and a higher number of apoptotic cells (p = 0.0329). Microarray expression profiling of U2OS cultured cells showed that decitabine treatment caused a significant induction (p < 0.0025) in the expression of 88 genes. Thirteen had a ≥2-fold change, 11 of which had CpG-island-associated promoters. Interestingly, 6 of these 11 were pro-apoptotic genes and decitabine resulted in a significant induction of cell death in U2OS cells <it>in vitro </it>(p < 0.05). The 6 pro-apoptotic genes (<it>GADD45A</it>, <it>HSPA9B</it>, <it>PAWR</it>, <it>PDCD5</it>, <it>NFKBIA</it>, and <it>TNFAIP3</it>) were also induced to ≥2-fold <it>in vivo</it>. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG-island DNA demethylationas a result of U2OS decitabine treatment both <it>in vitro </it>and in xenografts</p> <p>Conclusion</p> <p>These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS.</p

Palliative care within universal health coverage: the Malawi Patient-and-Carer Cancer Cost Survey

Objective Evidence of the role of palliative care to reduce financial hardship and to support wellbeing in low- and middle-income countries (LMIC) is growing, though standardised tools to capture relevant economic data are limited. We describe the development of the Patient-and-Carer Cancer Cost Survey (PaCCCt survey) which can be used to gather data on health care use and out-of-pocket expenditure (OOPE) in households affected by cancer in LMIC. Methods To identify relevant content qualitative data were gathered using Photovoice to detail concepts of wellbeing and cost areas of importance in households receiving palliative care in Blantyre, Malawi. Existing approaches and tools used to capture OOPE were mapped through a review of the literature. The WHO TB patient cost survey was chosen for adaptation. Face and content validity of a zero-draft of the PaCCCt survey were developed through review by health care professionals and a national stakeholder group. The final survey was translated into local language (Chichewa) and piloted. Results The PaCCCt survey is a tablet-based, third-party administered survey recording health care service utilisation and related direct and indirect costs. Coping strategies (loans and dissaving etc.), funeral costs and wellbeing at household level are included. Completion time is less than 30 minutes. Conclusion The PaCCCt survey can be used as part of economic evaluations in populations in need of palliative care in LMIC. Such evidence can support calls for the inclusion of palliative care within Universal Health Coverage which requires end-user protection from financial hardship

Regulating services

No abstract available

Inpatient signs and symptoms and factors associated with death in children aged 5 years and younger admitted to two Ebola management centres in Sierra Leone, 2014: a retrospective cohort study

Background Médecins Sans Frontières (MSF) opened Ebola management centres (EMCs) in Sierra Leone in Kailahun in June, 2014, and Bo in September, 2014. Case fatality in the west African Ebola virus disease epidemic has been highest in children younger than 5 years. Clinical data on outcomes can provide important evidence to guide future management. However, such data on children are scarce and disaggregated clinical data across all ages in this epidemic have focussed on symptoms reported on arrival at treatment facilities, rather than symptoms and signs observed during admission. We aimed to describe the clinical characteristics of children aged 5 years and younger admitted to the MSF EMCs in Bo and Kailahun, and any associations between these characteristics and mortality. Methods In a retrospective cohort study, we included data from children aged 5 years and younger with laboratoryconfi rmed Ebola virus disease admitted to EMCs between June and December, 2014. We described epidemiological, demographic, and clinical characteristics and viral load (measured using Ebola virus cycle thresholds [Ct]), and assessed their association with death using Cox regression modelling. Findings We included 91 children in analysis; 52 died (57·1%). Case fatality was higher in children aged less than 2 years (76·5% [26/34]) than those aged 2–5 years (45·6% [26/57]; adjusted HR 3·5 [95% CI 1·5–8·5]) and in those with high (Ct<25) versus low (Ct≥25) viral load (81·8% [18/22] vs 45·9% [28/61], respectively; adjusted HR 9·2 [95% CI 3·8–22·5]). Symptoms observed during admission included: weakness 74·7% (68); fever 70·8% (63/89); distress 63·7% (58); loss of appetite 60·4% (55); diarrhoea 59·3% (54); and cough 52·7% (48). At admission, 25% (19/76) of children were afebrile. Signs signifi cantly associated with death were fever, vomiting, and diarrhoea. Hiccups, bleeding, and confusion were observed only in children who died. Interpretation This description of the clinical features of Ebola virus disease over the duration of illness in children aged 5 years and younger shows symptoms associated with death and a high prevalence of distress, with implications for clinical management. Collection and analysis of age-specifi c data on Ebola is very important to ensure that the specifi c vulnerabilities of children are addressed

The factors affecting household transmission dynamics and community compliance with Ebola control measures: a mixed-methods study in a rural village in Sierra Leone.

BACKGROUND: Little is understood of Ebola virus disease (EVD) transmission dynamics and community compliance with control measures over time. Understanding these interactions is essential if interventions are to be effective in future outbreaks. We conducted a mixed-methods study to explore these factors in a rural village that experienced sustained EVD transmission in Kailahun District, Sierra Leone. METHODS: We reconstructed transmission dynamics using a cross-sectional survey conducted in April 2015, and cross-referenced our results with surveillance, burial, and Ebola Management Centre (EMC) data. Factors associated with EVD transmission were assessed with Cox proportional hazards regression. Following the survey, qualitative semi-structured interviews explored views of community informants and households. RESULTS: All households (n = 240; 1161 individuals) participated in the survey. 29 of 31 EVD probable/confirmed cases died (93·5% case fatality rate); six deaths (20·6%) had been missed by other surveillance systems. Transmission over five generations lasted 16 weeks. Although most households had ≤5 members there was a significant increase in risk of Ebola in households with > 5 members. Risk of EVD was also associated with older age. Cases were spatially clustered; all occurred in 15 households. EVD transmission was better understood when the community experience started to concord with public health messages being given. Perceptions of contact tracing changed from invading privacy and selling people to ensuring community safety. Burials in plastic bags, without female attendants or prayer, were perceived as dishonourable. Further reasons for low compliance were low EMC survival rates, family perceptions of a moral duty to provide care to relatives, poor communication with the EMC, and loss of livelihoods due to quarantine. Compliance with response measures increased only after the second generation, coinciding with the implementation of restrictive by-laws, return of the first survivor, reduced contact with dead bodies, and admission of patients to the EMC. CONCLUSIONS: Transmission occurred primarily in a few large households, with prolonged transmission and a high death toll. Return of a survivor to the village and more effective implementation of control strategies coincided with increased compliance to control measures, with few subsequent cases. We propose key recommendations for management of EVD outbreaks based on this experience