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Introduction The Emergency Department (ED) of Mbarara Regional Referral Hospital serves a largely rural population of 4 million people in western Uganda. Here, ED patients with incurable illness often have prolonged stays. Palliative care (PC) is a low-cost intervention that focuses on alleviating pain and suffering for patients with incurable disease, while improving satisfaction with care and optimizing healthcare utilization. This is especially important in low resource settings. A prior needs assessment in our ED revealed that 50% of patients have PC needs. The ED is an optimal location to initiate PC, yet this rarely happens. There is a great need to identify factors affecting initiation of ED PC in our resource-limited setting. Methods A semi-structured questionnaire and chart review was conducted from March to August 2020. Patients admitted from the ED were assessed for PC needs. Those who met criteria were approached for inclusion and flagged for initiation of PC. The follow-up period was 7 days. Results Sixty two percent of those subjects flagged for initiation of PC received it. By day seven, 36.1 of the study population had died. ED initiation of PC varied significantly by diagnosis, with cancer patients more likely to receive PC (p = 0.0097). Conclusion Important barriers to PC initiation were identified in our Ugandan ED, related to diagnosis. These barriers could be overcome by improving awareness of PC amongst patients and providers alike and implementing a PC screening tool for all admissions. Future research is needed to identify other barriers, as well as strategies for improved hospital-wide uptake of PC in this resource-limited setting.

Patient-reported outcomes and economic aspects of Palliative Care (PC) provision in low-income countries (LIC) are under-studied. Demonstrating the economic value of PC is key to sustainability and guiding health care policy. Our preliminary data in Ethiopia demonstrated a widespread need for PC, poor access to it, and high out of pocket payments (OOP). We suspect that in this and other LIC, PC may function not only to reduce suffering but also as a poverty reduction strategy. We are conducting a randomized controlled trial of standard Oncology care versus standard Oncology care plus PC in newly diagnosed cancer patients in Addis Ababa. Ninety-seven adults presenting to Oncology Clinic will be randomized in a 1:1 ratio. Subjects receiving PC will meet with a PC provider at time of enrollment and at follow up visits in their homes. All subjects will be assessed via questionnaire at enrollment and follow-up Oncology visits at 8 ± 4 and 12 ± 4 weeks. A cost-consequence analysis will be performed, to include: patient-reported OOP and healthcare utilization, the latter to be assessed through chart adjudication. Outcomes will include change in African Palliative Care Association Palliative Outcome Score, changes in OOP and healthcare utilization. We hypothesize that the cost of home-based PC will be offset by improvements in patient-reported outcomes, decreased OOP and healthcare utilization, rendering PC cost-effective in this LIC. These findings may lead to widespread dissemination of an effective, sustainable and cost-saving public PC delivery strategy that would improve the quality of life and death for millions of people. Trial registration Clinicaltrials.gov NCT03712436 .

Palliative care aims to reduce physical suffering and the emotional, spiritual, and psychosocial distress of life-limiting illness. Palliative care is a human right, yet there are vast disparities in its provision: of the 40 million people globally in need of palliative care, less than 10% receive it, largely in high-income countries. There is a particular paucity of data on palliative care needs across the spectrum of incurable disease in Ethiopia.The aims of this research were to assess the overall burden of life-limiting illness, the costs associated with life-limiting illness, and barriers to accessing palliative care in Ethiopia.Mixed-methods case-series.One hundred adults (mean age: 43.7 ± 14 years, 64% female) were recruited at three outpatient clinics (oncology, HIV, noncommunicable disease) and hospice patient homes in Ethiopia.Four internationally validated questionnaires were used to assess physical symptoms, psychosocial distress, and disability. In-depth interviews gauged poverty level, costs of care, and end-of-life preferences. Qualitative data were analyzed by thematic content, quantitative data by standard descriptive, frequency and regression analyses.In oncology, 95.5% of the population endorsed moderate or severe pain, while 24% were not prescribed analgesia. Importantly, 80% of the noncommunicable disease population reported moderate or severe pain. The mean psychosocial distress score was 6.4/10. Severe disability was reported in 26% of the population, with mobility most affected. Statistically significant relationships were found between pain and costs, and pain and lack of well-being. Very high costs were reported by oncology patients. Oncology withstanding, the majority of subjects wished to die at home. Oncology patients cited pain control as the top reason they preferred a hospital death.There are extensive unmet palliative care needs in Ethiopia. Untreated pain and high costs of illness are the major contributors to psychosocial distress and financial crisis in this Ethiopian population.

IntroductionOf the 40 million people globally in need of palliative care (PC), just 14% receive it, predominantly in high-income countries. Within fragile health systems that lack PC, incurable illness is often marked by pain and suffering, as well as burdensome costs. In high-income settings, PC decreases healthcare utilisation, thus enhancing value. Similar cost-effectiveness models are lacking in low-income and middle-income countries and with them, the impetus and funding to expand PC delivery.MethodsWe conducted a systematic search of seven databases to gather evidence of the cost-effectiveness of PC in low-income and middle-income countries. We extracted and synthesised palliative outcomes and economic data from original research studies occurring in low-income and middle-income countries. This review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and includes a quality appraisal.ResultsOur search identified 10 eligible papers that included palliative and economic outcomes in low-income and middle-income countries. Four provided true cost-effectiveness analyses in comparing the costs of PC versus alternative care, with PC offering cost savings, favourable palliative outcomes and positive patient-reported and family-reported outcomes.ConclusionsDespite the small number of included studies, wide variety of study types and lack of high-quality studies, several patterns emerged: (1) low-cost PC delivery in low-income and middle-income countries is possible, (2) patient-reported outcomes are favourable and (3) PC is less costly than the alternative. This review highlights the extraordinary need for robust cost-effectiveness analysis of PC in low-income and middle-income countries in order to develop health economic models for the delivery of PC, direct resource allocation and guide healthcare policy for PC delivery in low-income and middle-income countries.

The Neisseria gonorrhoeae genome encodes a homologue of the Escherichia coli FNR protein (the fumarate and nitrate reductase regulator). Despite its similarity to E. coli FNR, the gonococcal FNR only partially complemented an E. coli fnr mutation. After error-prone PCR mutagenesis of the gonococcal fnr gene, we identified four mutant fnr derivatives carrying the same S18F substitution, and we showed that the mutant FNR could activate transcription from a range of class I and class II FNR-dependent promoters in E. coli . Prompted by the similarities between gonococcal and E. coli FNR, we made changes in gonococcal fnr that created substitutions that are equivalent to previously characterized substitutions in E. coli FNR. First, our experiments showed that cysteine, C116, in the gonococcal FNR, equivalent to C122 in E. coli FNR, is essential, presumably because, as in E. coli FNR, it binds to an iron-sulfur center. Second, the L22H and D148A substitutions in gonococcal FNR were made. These changes are equivalent to the L28H and D154A changes in E. coli FNR, which had been shown to increase FNR activity in the presence of oxygen. We show that the effects of these substitutions in gonococcal FNR are distinct from those of the S18F substitution. Similarly, substitutions in the putative activating regions of gonococcal FNR were made. We show that the activity of gonococcal FNR in E. coli can be increased by transplanting certain activating regions from E. coli FNR. The effects of these substitutions are additive to those due to S18F. From these data, we conclude that the effects of the S18F substitution in gonococcal FNR are distinct from the effects of the other substitutions. S18 is immediately adjacent to one of three N-terminal cysteine residues that coordinate the iron-sulfur center, and thus the S18F substitution is most likely to stabilize this center. Support for this came from complementary experiments in which we created the S24F substitution in E. coli FNR, which is equivalent to the S18F substitution in gonococcal FNR. Our results show that the S24F substitution changes the activity of E. coli FNR and that the changes are distinct from those due to previously characterized substitutions.

A cytochrome c peroxidase (CCP) produced by Neisseria gonorrhoeae has been shown to have novel characteristics by investigating its location, expression and role in Neisseria gonorrhoeae and by expression in Escherichia coli. Analysis of the N-terminus of CCP indicated that it is a lipoprotein with a signal peptide for cleavage by signal peptidase II. Expression of the gonococcal CCP in E. coli revealed that it is first synthesized as a pro-apo-cytochrome that is translocated across the cytoplasmic membrane. The signal peptide is cleaved and haem is attached in the periplasm. The gonococcal CCP was associated with the membrane of both E. coli and N. gonorrhoeae. The expression of a MalE–CCP fusion protein has allowed characterization of CCP in vitro. Evidence is presented that CCP protects gonococci from hydrogen peroxide, presumably in the periplasmic compartment of the cell. The expression of CCP is dependent on the transcription factor FNR, but is repressed by nitrite, indicating that it could be most important in the stationary-phase response. These data support the hypothesis that the gonococcal lipoprotein CCP is anchored to the membrane in the periplasm, where it might be responsible for the reduction of hydrogen peroxide. Other putative CCP lipoproteins have been identified, representing a new subclass of bacterial CCP proteins.