Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients

Abstract Background: Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis. Results: HTLV-1 antibodies were first detected 16–39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16–23 and increased by 2–3 log by day 38–45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation. Conclusions: In recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early antiHTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis.

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1-88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94-1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Regional input-output analysis and agriculture

This article examines the use of the input-output approach in the understanding and analysis of the role of agriculture in regional economies. Though this work is more or less equally divided between regional analysis in industrialised and developing countries, the focus is on the former. The constraints and opportunities offered by the technique are considered, together with extensions such as Social Accounts and CGE modelling. Some of the potential of the technique is illustrated by recent work related to agriculture and rural development in the regional economy of Wales.Analyse input-output régionale et agriculture. L'intérêt du modèle input-output pour analyser les performances d'une agriculture régionale est désormais reconnu. En effet, cette technique permet de prendre en compte la spécialisation du secteur et son intégration croissante dans l'économie globale grâce au calcul des multiplicateurs économiques régionaux, d'une part, et de ceux qui relient l'économie d'une région donnée à l'économie nationale, de l'autre. Dans cet article, les auteurs examinent les apports et les limites du modèle input-output régional et de ses prolongements récents que sont la matrice de comptabilité sociale et le modèle d'équilibre général calculable. L'estimation des coefficients régionaux fait l'objet d'une analyse détaillée ; en effet, le coût — en temps et en ressources diverses — des enquêtes sur lesquels ils sont basés limite sérieusement l'obtention de coefficients permettant une évaluation fiable des effets multiplicateurs régionaux. Le reste de l'article est consacré à la construction d'un modèle input-output de l'économie du Pays de Galles, centré sur l'agriculture et les secteurs qui lui sont liés. Il est utilisé pour analyser la diversification des sources de revenu des ménages agricoles, selon deux modalités susceptibles d'améliorer le caractère durable de l'agriculture galloise d'un point de vue social et environnemental. Dans un premier exemple, on compare l'intérêt de la restauration de forêts anciennes non entretenues dépendant d'exploitations agricoles et de nouvelles plantations. C'est la reprise progressive de la gestion et de l'entretien des forêts caduques actuellement abandonnées qui procure l'amélioration la plus sensible du revenu rural au Pays de Galles, alors que l'accent mis aujourd'hui sur les nouvelles plantations est moins justifié du point de vue du revenu et des emplois qu'elle génère. Le deuxième thème concerne l'agriculture biologique. On compare la réduction de la demande d'intrants à l'accroissement de l'utilisation locale des produits qu'elle génère et on évalue l'effet probable de son développement graduel sur l'économie des régions rurales galloises. Des simulations prenant en compte des degrés croissants de conversion de systèmes conventionnels à l'agriculture biologique montrent que cette évolution conduirait à de faibles baisses du revenu et de l'emploi, même si elle concernait des zones assez étendues. De plus, les aménités fournies par l'agrobiologie en ce qui concerne la qualité de l'environnement et la baisse de la production justifient tout à fait de lui apporter un soutien. Ces exemples montrent l'intérêt des techniques input-output pour l'analyse de nombre de questions concernant la politique agricole et le développement rural, et en particulier lorsque des problèmes économiques, sociaux et d'environnement sont en cause.Midmore Peter, Medcalf Rebecca, Harrisson-Mayfield Lucy. Regional input-output analysis and agriculture. In: Cahiers d'Economie et sociologie rurales, N°42-43, 1er et 2e trimestres 1997. économie du développement. Education ; pauvreté ; commerce international. pp. 7-31

Acute kidney injury identification for pharmacoepidemiologic studies:Use of laboratory electronic acute kidney injury alerts versus electronic health records in Hospital Episode Statistics

PURPOSE: A laboratory-based acute kidney injury (AKI) electronic-alert (e-alert) system, with e-alerts sent to the UK Renal Registry (UKRR) and collated in a master patient index (MPI), has recently been implemented in England. The aim of this study was to determine the degree of correspondence between the UKRR-MPI and AKI International Classification Disease-10 (ICD-10) N17 coding in Hospital Episode Statistics (HES) and whether hospital N17 coding correlated with 30-day mortality and emergency re-admission after AKI. METHODS: AKI e-alerts in people aged ≥18 years, collated in the UKRR-MPI during 2017, were linked to HES data to identify a hospitalised AKI population. Multivariable logistic regression was used to analyse associations between absence/presence of N17 codes and clinicodemographic features. Correlation of the percentage coded with N17 and 30-day mortality and emergency re-admission after AKI were calculated at hospital level. RESULTS: In 2017, there were 301 540 adult episodes of hospitalised AKI in England. AKI severity was positively associated with coding in HES, with a high degree of inter-hospital variability-AKI stage 1 mean of 48.2% [SD 14.0], versus AKI stage 3 mean of 83.3% [SD 7.3]. N17 coding in HES depended on demographic features, especially age (18-29 years vs. ≥85 years OR 0.22, 95% CI 0.21-0.23), as well as sex and ethnicity. There was no evidence of association between the proportion of episodes coded for AKI with short-term AKI outcomes. CONCLUSION: Coding of AKI in HES is influenced by many factors that result in an underestimation of AKI. Using e-alerts to triangulate the true incidence of AKI could provide a better understanding of the factors that affect hospital coding, potentially leading to improved coding, patient care and pharmacoepidemiologic research

Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study

Abstract Background The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors — age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. Methods Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. Results The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. Conclusions The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities