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

The role of information communication technology (ICT) towards universal health coverage: the first steps of a telemedicine project in Ethiopia

Background: Eighty-five per cent of the Ethiopian population lives in remote areas, without access to modern health services. The limited health care budget, chronic shortage of health care workers and lack of incentives to retain those in remote areas further jeopardize the national health care delivery system. Recently, the application of information communication technology (ICT) to health care delivery and the use of telemedicine have raised hopes.Objective: This paper analyzes the challenges, failures and successes encountered in setting-up and implementing a telemedicine program in Ethiopia and provides possible recommendations for developing telemedicine strategies in countries with limited resources.Design: Ten sites in Ethiopia were selected to participate in this pilot between 2004 and 2006 and twenty physicians, two per site, were trained in the use of a store and forward telemedicine system, using a dial-up internet connection. Teledermatology, teleradiology and telepathology were the chosen disciplines for the electronic referrals, across the selected ten sites.Results: Telemedicine implementation does not depend only on technological factors, rather on e-government readiness, enabling policies, multisectoral involvement and capacity building processes. There is no perfect ‘one size fits all’ technology and the use of combined interoperable applications, according to the local context, is highly recommended.Conclusions: Telemedicine is still in a premature phase of development in Ethiopia and other sub-Saharan African countries, and it remains difficult to talk objectively about measurable impact of its use, even though it has demonstrated practical applicability beyond reasonable doubts

Pregnant Women's Access to PMTCT and ART Services in South Africa and Implications for Universal Antiretroviral Treatment

We describe pregnant womens' access to PMTCT and HAART services and associated birth outcomes in South Africa.Women recuperating in postnatal wards of a referral hospital participated in an evaluation during February-May 2010 during which their maternity records were examined to describe their access to VCT, CD4 Counts, dual ART or HAART during pregnancy.Of the 1609 women who participated in this evaluation, 39% (95%CI36.7-41.5%) tested HIV-positive during their pregnancy. Of the HIV-positive women 2.9% did not have a CD4 count done and an additional 31.3% did not receive their CD4 results. The majority (96.8%) of the HIV-positive women commenced dual ART at their first antenatal visit independent of their CD4 result. During February-May 2010, 48.0% of the women who had a CD4 result were eligible for HAART (CD4<200 cells/mm(3)) and 29.1% of these initiated HAART during pregnancy. Under the current South African PMTCT guidelines 71.1% (95%CI66.4-75.4%) of HIV positive pregnant women could be eligible for HAART (CD4<350 cells/mm(3)). There were significantly more preterm births among HIV-positive women (p = 0.01) and women who received HAART were no more at risk of preterm deliveries (AOR 0.73;95%CI0.39-1.36;p = 0.2) as compared to women who received dual ART. Nine (2.4%; 95%CI1.1-4.5%) HIV exposed infants were confirmed HIV infected at birth. The in-utero transmission rate was highest among women who required HAART but did not initiate treatment (8.5%) compared to 2.7% and 0.4% among women who received HAART and women who were not eligible for HAART and received PMTCT prophylaxis respectively.In this urban South African community the antenatal HIV prevalence remains high (39%) and timeous access to CD4 results during pregnancy is limited. Under the current South African guidelines, and assuming that access to CD4 results has improved, more than 70% of HIV-positive pregnant women in this community would be requiring HAART

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