Objective To examine the costs and cost effectiveness of telehealth in addition to standard support and treatment, compared with standard support and treatment.Design Economic evaluation nested in a pragmatic, cluster randomised controlled trial.Setting Community based telehealth intervention in three local authority areas in England.Participants 3230 people with a long term condition (heart failure, chronic obstructive pulmonary disease, or diabetes) were recruited into the Whole Systems Demonstrator telehealth trial between May 2008 and December 2009. Of participants taking part in the Whole Systems Demonstrator telehealth questionnaire study examining acceptability, effectiveness, and cost effectiveness, 845 were randomised to telehealth and 728 to usual care.Interventions Intervention participants received a package of telehealth equipment and monitoring services for 12 months, in addition to the standard health and social care services available in their area. Controls received usual health and social care.Main outcome measure Primary outcome for the cost effectiveness analysis was incremental cost per quality adjusted life year (QALY) gained. ResultsWe undertook net benefit analyses of costs and outcomes for 965 patients (534 receiving telehealth; 431 usual care). The adjusted mean difference in QALY gain between groups at 12 months was 0.012. Total health and social care costs (including direct costs of the intervention) for the three months before 12 month interview were £1390 (€1610; $2150) and £1596 for the usual care and telehealth groups, respectively. Cost effectiveness acceptability curves were generated to examine decision uncertainty in the analysis surrounding the value of RESEARCHthe cost effectiveness threshold. The incremental cost per QALY of telehealth when added to usual care was £92 000. With this amount, the probability of cost effectiveness was low (11% at willingness to pay threshold of £30 000; >50% only if the threshold exceeded about £90 000). In sensitivity analyses, telehealth costs remained slightly (non-significantly) higher than usual care costs, even after assuming that equipment prices fell by 80% or telehealth services operated at maximum capacity. However, the most optimistic scenario (combining reduced equipment prices with maximum operating capacity) eliminated this group difference (cost effectiveness ratio £12 000 per QALY). ConclusionsThe QALY gain by patients using telehealth in addition to usual care was similar to that by patients receiving usual care only, and total costs associated with the telehealth intervention were higher. Telehealth does not seem to be a cost effective addition to standard support and treatment.Trial registration ISRCTN43002091.

Strains of the same bacterial species often show considerable genomic variation. To examine the extent of such variation in Rhizobium etli, the complete genome sequence of R. etli CIAT652 and the partial genomic sequences of six additional R. etli strains having different geographical origins were determined. The sequences were compared with each other and with the previously reported genome sequence of R. etli CFN42. DNA sequences common to all strains constituted the greater part of these genomes and were localized in both the chromosome and large plasmids. About 700 to 1,000 kb of DNA that did not match sequences of the complete genomes of strains CIAT652 and CFN42 was unique to each R. etli strain. These sequences were distributed throughout the chromosome as individual genes or chromosomal islands and in plasmids, and they encoded accessory functions, such as transport of sugars and amino acids, or secondary metabolism; they also included mobile elements and hypothetical genes. Sequences corresponding to symbiotic plasmids showed high levels of nucleotide identity (about 98 to 99%), whereas chromosomal sequences and the sequences with matches to other plasmids showed lower levels of identity (on average, about 90 to 95%). We concluded that R. etli has a pangenomic structure with a core genome composed of both chromosomal and plasmid sequences, including a highly conserved symbiotic plasmid, despite the overall genomic divergence.

bIn this work, we isolated and characterized 14 bacteriophages that infect Rhizobium etli. They were obtained from rhizosphere soil of bean plants from agricultural lands in Mexico using an enrichment method. The host range of these phages was narrow but variable within a collection of 48 R. etli strains. We obtained the complete genome sequence of nine phages. Four phages were resistant to several restriction enzymes and in vivo cloning, probably due to nucleotide modifications. The genome size of the sequenced phages varied from 43 kb to 115 kb, with a median size of ϳ45 to 50 kb. A large proportion of open reading frames of these phage genomes (65 to 70%) consisted of hypothetical and orphan genes. The remainder encoded proteins needed for phage morphogenesis and DNA synthesis and processing, among other functions, and a minor percentage represented genes of bacterial origin. We classified these phages into four genomic types on the basis of their genomic similarity, gene content, and host range. Since there are no reports of similar sequences, we propose that these bacteriophages correspond to novel species. Bacteriophages have an enormous impact on the ecology and evolution of bacteria (1-3). It is well-known that bacteriophages are agents of gene mobilization across bacterial populations and that the majority of bacterial genomes harbor prophages as well as individual genes of phage origin (4-6). Conversely, temperate phages often carry bacterial genes as a result of prophage induction and recombination (7,8). Some reports indicate that phages exist for almost every known bacterial species (9). In the case of symbiotic nitrogen-fixing bacteria, such as Sinorhizobium meliloti (10, 11), Rhizobium leguminosarum (12-14), Mesorhizobium spp. (15), and Bradyrhizobium spp. (16), phages have been isolated and characterized, but no genome sequences have been reported. As a consequence, genomic comparisons have not been made. To date, only the complete genome sequence of phage 16-3 of S. meliloti has been determined (17).Lytic and temperate phages that infect rhizobial species have been isolated from soils and from lysogens induced after UV light treatment or mitomycin C exposure (11). The presence of phageresistant and -sensitive strains of Rhizobium suggests that phages play a substantial role in the selection or elimination of certain genotypes (11,(18)(19)(20). For instance, bacteriophages reduce the population density of susceptible strains of Rhizobium trifolii on the root surface, allowing resistant strains to form nodules (21,22). In field experiments, the persistence of genetically modified rhizobia has been explained in part by their resistance to phages (19).In the completely sequenced genomes of Rhizobium etli strains CFN42 and CIAT652 (23, 24), there are some open reading frames (ORFs) with relatively high degrees of identity to bacteriophage genes, such as DNA integrases, DNA transferases, lysozymes, and the small and large subunits of DNA terminase. In this work, we obtained a collection of 14 R. etli ...

This perspective examines the challenge posed by COVID-19 for social care services in England and describes responses to this challenge. People with social care needs experience increased risks of death and deteriorating physical and mental health with COVID-19. Social isolation introduced to reduce COVID-19 transmission may adversely affect well-being. While the need for social care rises, the ability of families and social care staff to provide support is reduced by illness and quarantine, implying reductions in staffing levels. Consequently, COVID-19 could seriously threaten care availability and quality. The government has sought volunteers to work in health and social care to help address the threat posed by staff shortages at a time of rising need, and the call has achieved an excellent response. The government has also removed some barriers to effective coordination between health and social care, while introducing measures to promote the financial viability of care providers. The pandemic presents unprecedented challenges that require well-co-coordinated responses across central and local government, health services, and non-government sectors.

Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF(165) gene transfer (pVEGF(165)) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with (99m)Tc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF(165) 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were done in a blinded fashion. Five weeks later, pVEGF(165)-treated pigs showed a significantly higher density of small (8-50 microm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.