A web-based telemedicine system for low-resource settings 13 years on: insights from referrers and specialists

Background: One way to tackle health inequalities in resource-poor settings is to establish links between doctors and health professionals there and specialists elsewhere using web-based telemedicine. One such system run by the Swinfen Charitable Trust has been in existence for 13 years which is an unusually long time for such systems. Objective: We wanted to gain some insights into whether and how this system might be improved. Methods: We carried out a survey by questionnaire of referrers and specialists over a six months period. Results: During the study period, a total of 111 cases were referred from 35 different practitioners, of whom 24% were not doctors. Survey replies were received concerning 67 cases, a response rate of 61 per cent. Eighty-seven per cent of the responding referrers found the telemedicine advice useful, and 78% were able to follow the advice provided. As a result of the advice received, the diagnosis was changed in 22% of all cases and confirmed in a further 18 per cent. Patient management was changed in 33 per cent. There was no substantial difference between doctors and non-doctors. During the study period, the 111 cases were responded to by 148 specialists, from whom 108 replies to the questionnaire were received, a response rate of 73 per cent. About half of the specialists (47%) felt that their advice had improved the management of the patients. There were 62 cases where it was possible to match up the opinions of the referrer and the consultants about the value of a specific teleconsultation. In 34 cases (55%) the referrers and specialists agreed about the value. However, in 28 cases (45%) they did not: specialists markedly underestimated the value of a consultation compared to referrers. Both referrers and specialist were extremely positive about the system which appears to be working well. Minor changes such as a clearer referral template and an improved web interface for specialists may improve it

Precise phylogenetic analysis of microbial isolates and genomes from metagenomes using PhyloPhlAn 3.0

Microbial genomes are available at an ever-increasing pace, as cultivation and sequencing become cheaper and obtaining metagenome-assembled genomes (MAGs) becomes more effective. Phylogenetic placement methods to contextualize hundreds of thousands of genomes must thus be efficiently scalable and sensitive from closely related strains to divergent phyla. We present PhyloPhlAn 3.0, an accurate, rapid, and easy-to-use method for large-scale microbial genome characterization and phylogenetic analysis at multiple levels of resolution. PhyloPhlAn 3.0 can assign genomes from isolate sequencing or MAGs to species-level genome bins built from >230,000 publically available sequences. For individual clades of interest, it reconstructs strain-level phylogenies from among the closest species using clade-specific maximally informative markers. At the other extreme of resolution, it scales to large phylogenies comprising >17,000 microbial species. Examples including Staphylococcus aureus isolates, gut metagenomes, and meta-analyses demonstrate the ability of PhyloPhlAn 3.0 to support genomic and metagenomic analyses

Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly

Background Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored. Results We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon. Conclusions We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.Peer reviewe

Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations

Funding This work was supported by NIH NHGRI grant R01HG005220, NIDDK grant R24DK110499, NIDDK grant U54DE023798, and CMIT grant 6935956 to C.H., and by the European Research Council (ERC-STG project MetaPG-716575), MIUR “Futuro in Ricerca” RBFR13EWWI_001, the European Union (H2020-SFS-2018-1 project MASTER-818368 and H2020-SC1-BHC project ONCOBIOME-825410), and the National Cancer Institute of the National Institutes of Health (1U01CA230551) to N.S. Further support was provided by the Programma Ricerca Budget prestazioni Eurac 2017 of the Province of Bolzano, Italy to F.M., and by the EU-H2020 (DiMeTrack-707345) to E.P. and N.S. D.B., S.H.D., P.L., A.W.W. and The Rowett Institute received core funding support from the Scottish Government Rural and Environmental Sciences and Analytical Services (SG-RESAS). Availability of data and materials All datasets used in this study are publicly available and matched with their respective PMID (Additional file 5). The high-quality E. rectale MAGs in fasta format and a metadata file are available at http://segatalab.cibio.unitn.it/data/Erectale_Karcher_et_al.html and in the following Zenodo repository: https://doi.org/10.5281/zenodo.3763191 [80]. The two new isolate genomes L2–21 and T3BWe13 have been uploaded to NCBI and can be found in RefSeq under the accession numbers GCF_008122485.1 [81] and GCF_008123415.1 [82], respectively.Peer reviewedPublisher PD

Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. Methods We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Results Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therap

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course

Experience with low-cost telemedicine in three different settings. Recommendations based on a proposed framework for network performance evaluation

BACKGROUND: Telemedicine has been used for many years to support doctors in the developing world. Several networks provide services in different settings and in different ways. However, to draw conclusions about which telemedicine networks are successful requires a method of evaluating them. No general consensus or validated framework exists for this purpose. OBJECTIVE: To define a basic method of performance measurement that can be used to improve and compare teleconsultation networks; to employ the proposed framework in an evaluation of three existing networks; to make recommendations about the future implementation and follow-up of such networks. METHODS: Analysis based on the experience of three telemedicine networks (in operation for 7-10 years) that provide services to doctors in low-resource settings and which employ the same basic design. FINDINGS: Although there are many possible indicators and metrics that might be relevant, five measures for each of the three user groups appear to be sufficient for the proposed framework. In addition, from the societal perspective, information about clinical- and cost-effectiveness is also required. The proposed performance measurement framework was applied to three mature telemedicine networks. Despite their differences in terms of activity, size and objectives, their performance in certain respects is very similar. For example, the time to first reply from an expert is about 24 hours for each network. Although all three networks had systems in place to collect data from the user perspective, none of them collected information about the coordinator's time required or about ease of system usage. They had only limited information about quality and cost. CONCLUSION: Measuring the performance of a telemedicine network is essential in understanding whether the network is working as intended and what effect it is having. Based on long-term field experience, the suggested framework is a practical tool that will permit organisations to assess the performance of their own networks and to improve them by comparison with others. All telemedicine systems should provide information about setup and running costs because cost-effectiveness is crucial for sustainability

350 Needs in Low Resource Settings

This presentation was given by Dr. Maria Zolfo at the Med-e-tel 2005 Conference in Luxembourg on April 7th, 2005.eHealth and Education: Telemedicine is a way to deliver health care in remote areas. Meeting the goal of accessing health information in developing countries and facing the necessity to scale up the use of antiretrovirals (ARVs) in low resource settings, the Institute of Tropical Medicine, Antwerp (ITMA) set up a computer aided training programme for health providers, working in disadvantaged areas. Expert advice from HIV/AIDS specialists about ARVs and management of Opportunistic Infections (OIs) has been offered to colleagues working in different resource limited settings.Institute of Tropical Medicine, Antwerp, Belgiu