Supplementary Material for: Patient Experience and Preferences for the Assessment of Olfaction: The Patient International Clinical Assessment of Smell Survey

Introduction: Olfactory dysfunction (OD) is common and carries significant personal and societal burden of disease. Accurate assessment of olfaction is required for good clinical care and affords patients insight into their condition. However, the accuracy of assessment varies with technique used, and there is presently little standardisation of clinical practice. We therefore aimed to determine experience of and preferences for olfactory assessment in healthcare-seeking adults. Methods: An anonymous patient co-produced survey was developed in collaboration with a UK-based OD charity. Distribution was via their social media patient forum. “Healthcare seeking” adults (i.e., who had undergone olfactory assessment by a healthcare professional [any care level/speciality] or may do so in the future) were included. Results: 576 people (88.5% female, mean 46 years) responded. Hyposmia, parosmia, and retronasal OD were most frequently reported. 55.2% had been assessed by a healthcare professional – GP most commonly, followed by ENT. Importantly, only 15.6% and 16.9% of respondents had undergone systematic assessment with smell tests or symptom questionnaires, respectively. Most respondents had not undergone imaging. Mean satisfaction was higher in those seen by ENT. Interestingly, respondents prioritise orthonasal odour identification over other forms of smell test. Unfortunately, many felt that healthcare professionals (across specialities) were dismissive towards OD and lacked appropriate knowledge of both its pathophysiology and effects. We propose simple steps that can be taken to improve olfactory assessment, including education and establishment of robust referral networks. Conclusion: We hope these results and supporting practical recommendations will inform future service planning, funding allocation and research, as well as better aligning patient and clinician priorities

Supplementary Material for: Uromodulin mRNA from Urinary Extracellular Vesicles Correlate to Kidney Function Decline in Type 2 Diabetes Mellitus

<b><i>Background:</i></b> Extracellular vesicles (EVs) enclose mRNA derived from their cell of origin and are considered a source of potential biomarkers. We examined urinary EV mRNA from individuals with diabetic kidney disease (DKD), chronic kidney disease, type 2 diabetes (T2DM), and obese and healthy controls to determine if such biomarkers had the potential to classify kidney disease and predict patients at higher risk of renal function decline. <b><i>Methods:</i></b> A total of 242 participants enrolled in this study. Urinary EV mRNA from all subjects were isolated by a filter-based platform, and the expression of 8 target genes were determined by quantitative polymerase chain reaction (qPCR). Changes in estimated glomerular filtration rate (eGFR) in 161 T2DM patients were evaluated for 2 consecutive years and compared with EV RNA profiles at baseline. <b><i>Results:</i></b> We observe that mild and severe DKD groups show a significant 3.2- and ­4.4-fold increase in UMOD compared to healthy controls and expression increases linearly from healthy, diabetic, and DKD subjects. UMOD expression is significantly correlated to albumin creatinine ratio (ACR), eGFR, and HbA1c. Using linear discriminant analyses with mRNA from severe DKD and T2DM as training data, a multi-gene signature classified DKD and ­non-DKD with a sensitivity of 93% and specificity of 73% with area under the receiver operating characteristic (ROC) curve (AUC) = 0.90. Although 6% of T2DM were determined to have a > 80% posterior probability of developing DKD based on this mRNA profile, eGFR changes observed within the 2-year follow-up did not reveal a decline in kidney function. <b><i>Conclusion:</i></b> Urinary EV UMOD mRNA levels are progressively elevated from T2DM to DKD groups and correlate with widely used eGFR and ACR diagnostic criteria. An EV mRNA signature could identify DKD with greater than 90% sensitivity and 70% specificity