Patient Work Personas of Type 2 Diabetes—A Data-Driven Approach to Persona Development and Validation

Introduction: Many have argued that a “one-size-fits-all” approach to designing digital health is not optimal and that personalisation is essential to achieve targeted outcomes. Yet, most digital health practitioners struggle to identify which design aspect require personalisation. Personas are commonly used to communicate patient needs in consumer-oriented digital health design, however there is often a lack of reproducible clarity on development process and few attempts to assess their accuracy against the targeted population. In this study, we present a transparent approach to designing and validating personas, as well as identifying aspects of “patient work,” defined as the combined total of work tasks required to manage one's health and the contextual factors influencing such tasks, that are sensitive to an individual's context and may require personalisation. Methods: A data-driven approach was used to develop and validate personas for people with Type 2 diabetes mellitus (T2DM), focusing on patient work. Eight different personas of T2DM patient work were constructed based physical activity, dietary control and contextual influences of 26 elderly Australian participants (median age = 72 years) via wearable camera footage, interviews, and self-reported diaries. These personas were validated for accuracy and perceived usefulness for design, both by the original participants and a younger (median age bracket = 45–54 years) independent online cohort f 131 T2DM patients from the United Kingdom and the United States. Results: Both the original participants and the independent online cohort reported the personas to be accurate representations of their patient work routines. For the independent online cohort, 74% (97/131) indicated personas stratified to their levels of exercise and diet control were similar to their patient work routines. Findings from both cohorts highlight aspects that may require personalisation include daily routine, use of time, and social context. Conclusion: Personas made for a specific purpose can be very accurate if developed from real-life data. Our personas retained their accuracy even when tested against an independent cohort, demonstrating their generalisability. Our data-driven approach clarified the often non-transparent process of persona development and validation, suggesting it is possible to systematically identify whether persona components are accurate or. and which aspects require more personalisation and tailoring

Obesity affects graft function but not graft loss in kidney transplant recipients

Background: There is an ongoing debate regarding the suitability for transplantation of the high Body Mass Index (BMI) kidney transplant recipients (KTRs). Methods: Retrospective analysis of 370 consecutive KTRs stratified according to the World Health Organisation Body Mass Index categories. As a measure of allograft function eGFR was used. Results: Mean BMI was 26.2: 148 (40%) pre-obese, 47 (12.7%) class I obese, 11 (3%) class II obese, 9 (2.4%) class III obese. A linear trend from the normal BMI group moving through the progressively higher groups was observed for male sex and younger age. Overweight and obese KTRs had higher incidence of pre-transplant diabetes (P = 0.021), but there was no difference in new-onset hyperglycemia post-transplant (P = 0.35). Obesity was not a significant risk factor for lower eGFR at 1 year follow-up, but it became at 2 and 3 years follow up. No statistical difference in Delayed Graft Function and hospital length of stay was observed. 28 patients lost their grafts, and 25 patients died during follow-up. Kaplan-Meier analysis showed no difference in all-cause allograft loss between the different BMI groups (log rank P = 0.8) in a mean follow-up of 42 months (0-58). Conclusion: Obesity affects eGFR in the long-term. The allograft survival was lower but not significant

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4–12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection

Structure, dynamics, and molecular inhibition of the Staphylococcus aureus m1A22-tRNA methyltransferase TrmK

This work was supported by a Wellcome Trust Seed Award in Science [208980/Z/17/Z] to RGdS; a University of St Andrews/Scottish Funding Council St Andrews Restarting Research Fund to RGdS; and a Wellcome Trust Institutional Strategic Support Fund [204821/Z/16/Z] to the University of St Andrews. ES is the recipient of a Cunningham Trust PhD studentship (PhD-CT-18-41).The enzyme m1A22-tRNA methyltransferase (TrmK) catalyzes the transfer of a methyl group to the N1 of adenine 22 in bacterial tRNAs. TrmK is essential for Staphylococcus aureus survival during infection but has no homolog in mammals, making it a promising target for antibiotic development. Here, we characterize the structure and function of S. aureus TrmK (SaTrmK) using X-ray crystallography, binding assays, and molecular dynamics simulations. We report crystal structures for the SaTrmK apoenzyme as well as in complexes with methyl donor SAM and co-product product SAH. Isothermal titration calorimetry showed that SAM binds to the enzyme with favorable but modest enthalpic and entropic contributions, whereas SAH binding leads to an entropic penalty compensated for by a large favorable enthalpic contribution. Molecular dynamics simulations point to specific motions of the C-terminal domain being altered by SAM binding, which might have implications for tRNA recruitment. In addition, activity assays for SaTrmK-catalyzed methylation of A22 mutants of tRNALeu demonstrate that the adenine at position 22 is absolutely essential. In silico screening of compounds suggested the multifunctional organic toxin plumbagin as a potential inhibitor of TrmK, which was confirmed by activity measurements. Furthermore, LC-MS data indicated the protein was covalently modified by one equivalent of the inhibitor, and proteolytic digestion coupled with LC-MS identified Cys92 in the vicinity of the SAM-binding site as the sole residue modified. These results identify a cryptic binding pocket of SaTrmK, laying a foundation for future structure-based drug discovery.Publisher PDFPeer reviewe

Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.

Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy