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IMPORTANCE: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. OBJECTIVE: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. INTERVENTIONS: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. RESULTS: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of −2.0% (1-sided 97.5% CI, −∞ to 1.2%; P

This file provides supplementary information on the costing methods used in the study and on the techniques used to handle missing resource use data [ 17 , 18 , 29 , 30 ]. (DOCX 30 kb)

Purpose The Quality of Life Alzheimer’s Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available. Methods Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error. Results The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset. Conclusions The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Introduction: To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Research design and methods: We assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation. Results: Genital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; 5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07). Conclusions: Female sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.

Additional file 1. Landeiro HR QOL SLR appendices. Additional back-up information to support the main paper.