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Heide A Stirnadel-Farrant,1 George Mu,2 Selin Cooper-Blenkinsopp,1 Rosemary O Schroyer,3 Kevin S Thorneloe,4 Ewen M Harrison,5 Susan MS Andrews6 1Department of WorldWide Epidemiology, GlaxoSmithKline, London, UK; 2Department of Data, Methods, and Analytics, GlaxoSmithKline, Collegeville, PA, USA; 3Department of Biostatistics, GlaxoSmithKline, Collegeville, PA, USA; 4Department of Translational Medicine, GlaxoSmithKline, Collegeville, PA, USA; 5Department of Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK; 6Department of Global Clinical Operations Development R&D, GlaxoSmithKline, Research Triangle Park, NC, USACorrespondence: Susan MS Andrews, Global Clinical Operations Development R&D GlaxoSmithKline Five Moore Drive, Research Triangle Park, NC, 27709-3398, USA, Tel +1-(919) 649-3944, Email susan.m.andrews@gsk.comPurpose: A variety of definitions for delayed graft function (DGF) have been proposed, but none has consistently been shown to be superior for predicting long-term graft outcomes for kidney donation after circulatory death (DCD) transplantation. In this study, real-world clinical outcome data following DCD transplantation were explored to determine the value of various DGF definitions for predicting graft survival.Patients and Methods: Data from 4 centers registered in the UK-based National Health Service Blood and Transplant registry (2010 to mid-2015) were used to assess 4 definitions of DGF in this retrospective chart review study.Results: Depending on the definition used, the frequency of DGF ranged from 119/362 (32.9%) when DGF was determined with available registry data and based on a requirement for dialysis within 7 days post-transplantation, to 224/315 (71.1%) when based on failure to achieve a 10% fall in serum creatinine (SCr) versus baseline per 24 hours averaged over the first 72 hours. Patients without clinical DGF as determined by a physician upon chart review, or when defined as < 30% reduction in baseline SCr within 7 days post-transplantation with or without dialysis, had significantly better graft survival probability 1 year (hazard ratio 2.08 and 4.48, respectively) and 5 years post-transplant, whereas serum creatinine level over the first 72 hours post-transplant was not predictive of graft survival at 1 year. Patients with clinical DGF upon physician chart review also had higher SCr, lower estimated glomerular filtration rate levels, and were dialyzed more (2.3 days) versus patients without (0.2 days).Conclusion: Delayed graft function, determined clinically or using a functional definition, is associated with poorer renal function and remains a useful predictor of graft survival at 1 year after DCD kidney transplantation.Keywords: delayed graft function, DGF, donation after circulatory death, DCD, serum creatinine, SCr

ObjectiveThis retrospective analysis evaluated the prognostic value of renal response status 2 years after biopsy-proven lupus nephritis (LN) for the prediction of long-term renal outcomes.MethodsEligible patients with SLE as per American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria and biopsy-proven class III, IV, V or mixed LN were identified from the Hopkins Lupus Cohort, and categorised into binary renal response categories (modified primary efficacy renal response (mPERR) or no mPERR at 2 years post biopsy). These categories were defined by a modified version of the Belimumab International Lupus Nephritis Study (BLISS-LN) protocol using urine protein:creatinine ratio (≤0.7 g/day) and estimated glomerular filtration rate (≥60 mL/min/1.73 m2or ≤20% below the baseline value) criteria. Long-term renal survival (defined as survival without end-stage renal disease (ESRD) or death) and chronic renal insufficiency-free survival were assessed in Kaplan–Meier plots with log-rank test and covariate-adjusted Cox proportional hazards models.ResultsOf the 173 eligible patients, 91.3% were female; the mean (SD) age at biopsy was 36.2 (11.8) years. At 2 years post biopsy, 114 (65.9%) patients achieved mPERR. These patients showed a lower risk of ESRD/death and chronic renal insufficiency in the follow-up period (HR (95% CI) 0.33 (0.13 to 0.87), p=0.0255; and HR (95% CI) 0.26 (0.14 to 0.47), pConclusionsThe 2-year post-biopsy renal response status, defined per 2019-updated BLISS-LN criteria, has prognostic value for long-term renal survival and lower risk of chronic renal insufficiency in patients with LN.

There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.\ud \ud

The aims of this study were to estimate the incidence rate of clinical mastitis (IRCM) and identify risk factors for clinical mastitis in suckler ewes to generate hypotheses for future study. A postal questionnaire was sent to 999 randomly selected English sheep farmers in 2010 to gather data on farmer reported IRCM and flock management practices for the calendar year 2009, of which 329 provided usable information. The mean IRCM per flock was 1.2/100 ewes/year (CI:1.10:1.35). The IRCM was 2.0, 0.9 and 1.3/100 ewes/year for flocks that lambed indoors, outdoors and a combination of both, respectively.\ud \ud Farmers ran a variety of managements before, during and after lambing that were not comparable within one model, therefore six mixed effects over-dispersed Poisson regression models were developed.\ud \ud Factors significantly associated with increased IRCM were increasing percentage of the flock with poor udder conformation, increasing mean number of lambs reared/ewe and when some or all ewes lambed in barns compared with outdoors (Model 1).\ud \ud For ewes housed in barns before lambing (Model 2), concrete, earth and other materials were associated with an increase in IRCM compared with hardcore floors (an aggregate of broken bricks and stones). For ewes in barns during lambing (Model 3), an increase in IRCM was associated with concrete compared with hardcore flooring and where bedding was stored covered outdoors or in a building compared with bedding stored outdoors uncovered. For ewes in barns after lambing (Model 4), increased IRCM was associated with earth compared with hardcore floors, and when fresh bedding was added once per week compared with at a frequency of ≤2 days or twice/week.\ud \ud The IRCM was lower for flocks where some or all ewes remained in the same fields before, during and after lambing compared with flocks that did not (Model 5). Where ewes and lambs were turned outdoors after lambing (Model 6), the IRCM increased as the age of the oldest lambs at turnout increased.\ud \ud We conclude that the reported IRCM is low but highly variable and that the complexity of management of sheep around lambing limits the insight into generating hypotheses at flock level for risks for clinical mastitis across the whole industry. Whilst indoor production was generally associated with an increased IRCM, for ewes with large litter size indoor lambing was protective, we hypothesise that this is possibly because of better nutrition or reduced exposure to poor weather and factors associated with hygiene.

We read with interest the study by Moccia et al 1 showing seasonality of searches for multiple sclerosis (MS) using Google, reflecting trends reported for disease relapses.2 The analysis of social media (eg, Twitter and Facebook) is an additional tool that is being used increasingly to answer research questions about disease spatiotemporal epidemiology.3 Patients are more and more using web technologies such as social media, blogs and forums to generate real-world evidence of potentially medically important issues. This content therefore serves as an important source of data about disease burden. Given the study by Moccia et al , we therefore sought to investigate whether or not there is seasonality to tweets regarding MS, as this may better reflect the ‘patient voice’. Tweets from 2010–2015 that contained the words ‘MS relapse’ …

A longitudinal study of 67 suckler ewes on a commercial sheep farm near Wolverhampton, England was carried out from March to July 2010. Data on ewe teat lesions and udder and teat conformation were collected together with data on lamb health and weight at lambing and at 14-day intervals until lambs were 8–10 weeks old. Each ewe was examined on 4–5 occasions. Teat lesions were categorised as traumatic or non-traumatic based on appearance. Risk factors for the development of each type of teat lesion were investigated using mixed effect binomial regression models. The incidence of traumatic teat lesions was greatest 3–4 weeks after lambing with 27.9% new cases by udder half. There was an increased risk of traumatic teat lesions in 2 year old ewes (OR 3.5, CI 1.2, 10.5) compared with 6 year old ewes and in ewes with abnormal compared with normal teat placement, a wide or narrow udder width compared with a normal udder width, a heavy total litter weight, body condition score (BCS) < 2.5, compared with BCS of 2.5 14-days previously, and in ewes with abnormal udder skin (waxy, dry or chapped) compared with normal udder skin. The incidence of non-traumatic teat lesions was greatest 7–10 weeks after lambing with 21.4% new cases. Non-traumatic lesions were more likely to occur in ewes with BCS = 3 compared with BCS of 2.5. The risk factors for traumatic and non-traumatic teat lesions differ. Traumatic lesions are associated with teat and udder morphology, ewe age and BCS, and lamb growth rate, whereas non-traumatic lesions are associated with ewe BCS.

A cohort study of 67 suckler ewes from 1 farm was carried out from January to May 2010 to investigate associations between udder conformation, udder half milk somatic cell count (SCC), and lamb weight. Ewes and lambs were observed at lambing. Ewe health and teat condition and lamb health and weight were recorded on 4 to 5 further occasions at 14-d intervals. At each observation, a milk sample was collected from each udder half for somatic cell counting. Two weeks after lambing, ewe udder conformation and teat placement were scored. Low lamb weight was associated with ewe SCC400,000 cells/mL (-0.73 kg), a new teat lesion 14 d previously (-0.91 kg), suboptimal teat position (-1.38 kg), rearing in a multiple litter (-1.45 kg), presence of diarrhea at the examination (-1.19 kg), and rearing by a 9-yr-old ewe compared with a 6-yr-old ewe (-2.36 kg). High lamb weight was associated with increasing lamb age (0.21 kg/d), increasing birth weight (1.65 kg/kg at birth), and increasing number of days the ewe was given supplementary feed before lambing (0.06 kg/d). High udder half SCC was associated with pendulous udders (9.6% increase in SCC/cm of drop) and greater total cross-sectional area of the teats (7.2% increase of SCC/cm(2)). Low SCC were associated with a heavier mean litter weight (6.7% decrease in SCC/kg). Linear, quadratic, and cubic terms for days in lactation were also significant. We conclude that poor udder and teat conformation are associated with high levels of intramammary infection, as indicated by increased SCC and that both physical attributes of the udder and SCC are linked to lamb growth, suggesting that selection of suckler ewes with better udder and teat conformation would reduce intramammary infection and increase lamb growth rate.