Telemedicine’s Potential to Support Good Dying in Nigeria: A Qualitative Study

Objectives

This qualitative study explores Nigerian health care professionals’ concepts of good dying/a good death and how telemedicine technologies and services would fit the current Nigerian palliative care practice.

Materials and Methods

Supported by the Centre for Palliative Care Nigeria (CPCN) and the University College Hospital (UCH) in Ibadan, Nigeria, the authors organized three focus groups with Nigerian health care professionals interested in palliative care, unstructured interviews with key role players for palliative care and representatives of telecom companies, and field visits to primary, secondary and tertiary healthcare clinics that provided palliative care. Data analysis consisted of open coding, constant comparison, diagramming of categorizations and relations, and extensive member checks.

Results

The focus group participants classified good dying into 2 domains: a feeling of completion of the individual life and dying within the community. Reported barriers to palliative care provision were socio-economic consequences of being seriously ill, taboos on dying and being ill, restricted access to adequate medical–technical care, equation of religion with medicine, and the faulty implementation of palliative care policy by government. The addition of telemedicine to Nigeria’s palliative care practice appears problematic, due to irregular bandwidth, poor network coverage, and unstable power supply obstructing interactivity and access to information. However, a tele-education ‘lite’ scenario seemed viable in Nigeria, wherein low-tech educational networks are central that build on non-synchronous online communication.

Discussion

Nigerian health care professionals’ concepts on good dying/a good death and barriers and opportunities for palliative care provision were, for the greater part, similar to prior findings from other studies in Africa. Information for and education of patient, family, and community are essential to further improve palliative care in Africa. Telemedicine can only help if low-tech solutions are applied that work around network coverage problems by focusing on non-synchronous online communication.     

Estimating incidence of infection from diverse data sources: Zika virus in Puerto Rico, 2016

Emerging epidemics are challenging to track. Only a subset of cases is recognized and reported, as seen with the Zika virus (ZIKV) epidemic where large proportions of infection were asymptomatic. However, multiple imperfect indicators of infection provide an opportunity to estimate the underlying incidence of infection. We developed a modeling approach that integrates a generic Time-series Susceptible-Infected-Recovered epidemic model with assumptions about reporting biases in a Bayesian framework and applied it to the 2016 Zika epidemic in Puerto Rico using three indicators: suspected arboviral cases, suspected Zika-associated Guillain-Barré Syndrome cases, and blood bank data. Using this combination of surveillance data, we estimated the peak of the epidemic occurred during the week of August 15, 2016 (the 33^rd week of year), and 120 to 140 (50% credible interval [CrI], 95% CrI: 97 to 170) weekly infections per 10,000 population occurred at the peak. By the end of 2016, we estimated that approximately 890,000 (95% CrI: 660,000 to 1,100,000) individuals were infected in 2016 (26%, 95% CrI: 19% to 33%, of the population infected). Utilizing multiple indicators offers the opportunity for real-time and retrospective situational awareness to support epidemic preparedness and response.     

A comprehensive phylogeny of Neurospora reveals a link between reproductive mode and molecular evolution in fungi

The filamentous ascomycete genus Neurospora encompasses taxa with a wide range of reproductive modes. Sexual reproduction in this genus can be divided into three major modes; heterothallism (self-incompatibility), homothallism (self-compatibility) and pseudohomothallism (partial self-compatibility). In addition to the sexual pathway, most of the heterothallic taxa propagate with morphologically distinct, vegetative dissemination propagules (macroconidia), while this feature is undetected in the majority of the homothallic taxa. In this study, we used sequence information of seven nuclear gene loci from 43 taxa (295 of the possible 301 locus-by-taxon combinations) to create a phylogeny of Neurospora. The results suggest that transitions in reproductive mode have occurred at multiple times within this group of fungi. Although a homothallic ancestor would imply fewer switches in reproductive mode, we argue that the ancestor of Neurospora was likely heterothallic and that homothallism has evolved independently at least six times in the evolutionary history of the genus. Furthermore, the two pseudohomothallic taxa of Neurospora (N. tetrasperma and N. tetraspora) represent two independent origins of pseudohomothallism. Likelihood ratio tests of substitution rates among branches in the phylogeny indicate that reproductive mode is an important factor driving genome evolution in Neurospora. First, an increased level of non-synonymous/synonymous substitutions in branches delineating homothallic taxa was found, suggesting a reduced efficiency of purifying selection in these taxa. Furthermore, elevated nucleotide substitution rates were found in heterothallic, conidia-producing, lineages as compared to the homothallic non-conidiating lineages. The latter finding is likely due to the presence of conidia, i.e., a higher rate of mitotic divisions inducing mutations, and/or that the homothallic taxa have evolved a lower mutation rate to avoid genomic degeneration.     

Production and characterization of a chimeric protein targeting synuclein epitopes for immunotherapy against synucleinopathies

The aggregation and spread of alpha-synuclein (αSyn) is associated with several pathogenic pathways that lead to neurodegeneration and, ultimately, to synucleinopathies development. Hence, the establishment of a safe and effective disease-modifying therapy that limits or prevents the spread of toxic αSyn aggregation could lead to positive clinical outcomes. A rational vaccine design can be focused on the selection of specific epitopes able to induce the immune response desired, for example, antibodies able to mediate the clearance of αSyn aggregates without the induction of inflammatory responses. To develop a rapid system for the evaluation of a vaccine candidate against synucleinopathies, rLTB-Syn (an antigen based on three B cell epitopes from αSyn and the B subunit of the heat-labile Escherichia coli enterotoxin [LTB] as adjuvant/carrier) was produced using recombinant E. coli (Rosetta DE3) as the expression host. The bacterial version of rLTB-Syn was produced as soluble protein at yields up to 1.72 mg/g biomass. A method for the purification of rLTB-Syn (~18 kDa) was developed based on ion exchange chromatography, reaching purity >93% with a final concentration of 82.6 μg/mL. Furthermore, the purified soluble rLTB-Syn retained GM1 binding activity, suggesting proper folding and pentameric structure. The results from this study establish a fast and effective method to obtain rLTB-Syn, making it useful in the design of novel vaccine formulations targeting synucleinopathies.     

Decreased development of necrotizing enterocolitis in IL-18-deficient mice

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease predominantly of prematurely born infants, characterized in its severest from by extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. Proinflammatory cytokines have been implicated in the development of NEC, and we have previously shown that IL-18 is significantly elevated in the well-established neonatal rat model of NEC. To determine whether IL-18 contributes to intestinal pathology in NEC, we subjected IL-18 knockout mice to the protocol used to develop experimental NEC in newborn rats. Newborn B6.129P2-Il18(tm1Aki)/J (NEC IL-18(-/-)) and wild-type (NEC WT) mice were hand fed every 3 h with cow's milk-based formula and exposed to asphyxia and cold stress twice daily. After 72 h, animals were killed and distal ileum and liver were removed. Disease development was determined via histological changes in the ileum as scored by a blinded evaluator. The number of TNF-alpha-, IL-12-, and IL-1beta-positive cells and macrophages were determined in both ileum and liver via immunohistology. IkappaB-alpha and IkappaB-beta were determined from protein extracts from both ileum and liver using Western blot analysis. The incidence and severity of NEC was significantly reduced in NEC IL-18(-/-) mice compared with NEC WT. Furthermore, mean ileal macrophages and hepatic IL-1beta were significantly reduced in IL-18(-/-) mice subjected to the NEC protocol. There were no statistically significant changes in Kupffer cells, hepatic TNF-alpha, ileal IL-1beta, or IL-12. IkappaB-alpha and IkappaB-beta were significantly increased in NEC IL-18(-/-) mice ileum and liver, respectively. These results confirm that IL-18 plays a crucial role in experimental NEC pathogenesis.     

Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice

Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3(-/-) mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-) mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation.     

CIGB-300, a novel proapoptotic peptide that impairs the CK2 phosphorylation and exhibits anticancer properties both in vitro and in vivo

Protein Kinase CK2 is a serine-threonine kinase frequently deregulated in many human tumors. Here, we hypothesized that a peptide binder to the CK2 phosphoacceptor site could exhibit anticancer properties in vitro, in tumor animal models, and in cancer patients. By screening a random cyclic peptide phage display library, we identified the CIGB-300 (formerly P15-Tat), a cyclic peptide which abrogates the CK2 phosphorylation by blocking recombinant substrates in vitro. Interestingly, synthetic CIGB-300 led to a dose-dependent antiproliferative effect in a variety of tumor cell lines and induced apoptosis as evidenced by rapid caspase activation. Importantly, CIGB-300 elicited significant antitumor effect both by local and systemic administration in murine syngenic tumors and human tumors xenografted in nude mice. Finally, we performed a First-in-Man trial with CIGB 300 in patients with cervical malignancies. The peptide was found to be safe and well tolerated in the dose range studied. Likewise, signs of clinical benefit were clearly identified after the CIGB-300 treatment as evidenced by significant decrease of the tumor lesion area and histological examination. Our results provide an early proof-of-principle of clinical benefit by using an anti-CK2 approach in cancer. Furthermore, this is the first clinical trial where an investigational drug has been used to target the CK2 phosphorylation domain.     

Risk factors for infection with chikungunya and Zika viruses in southern Puerto Rico: A community-based cross-sectional seroprevalence survey

Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1–50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018–2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16–41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1–10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71–3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42–0.61) and air conditioning (aOR 0.64; 95% CI 0.54–0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1–10y olds up to 19% among 41–50y olds (aOR 3.23; 95% CI 2.16–4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09–1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54–0.82) and air conditioning (aOR 0.69; 95% CI 0.57–0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection prevalence by age, and the presence of screens and air conditioners in the home decreased infection risk from both viruses by as much as 50%.     

The combined effects of treated sewage discharge and land use on rivers

Freshwater ecosystems are increasingly threatened by multiple anthropogenic stressors. Release of treated sewage effluent and pollution from agricultural or urban sources can independently reduce water quality with implications for ecological communities. However, our knowledge of the combined effects of these stressors is limited. We performed a field study to quantify the combined effect of treated sewage discharge and land use on nutrient concentrations, sewage fungus presence and communities of macroinvertebrates and benthic algae. Over three seasons in four rivers we found that a model which included an interaction between sewage pollution and time of the year (i.e. months) was the best predictor of nutrient concentrations and the abundance of algae and sewage fungus. Both macroinvertebrate and algae communities shifted downstream of sewage input. Specifically, more tolerant groups, such as cyanobacteria and oligochaetes, were more abundant. The EPT (Ephemeroptera, Plecoptera and Tricoptera) water quality score was best explained by an interaction between month and agriculture in the surrounding landscape. Overall, our results show that sewage discharge has a significant impact on water quality and benthic riverine communities, regardless of the surrounding land uses. Agricultural inputs, however, could be more important than treated sewage discharge in reducing the abundance of sensitive invertebrate taxa. We need both improvements to wastewater treatment processes and reductions in agricultural pollution to reduce threats to vulnerable freshwater communities.