National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia:The ALL-STAR study protocol

Introduction More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers.Methods and analysis This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008–2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors.Ethics and dissemination The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018–519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure

Sensory nerve conduction studies in probable painful neuropathy: comparing surface and near-nerve nerve conduction techniques

INTRODUCTION: We compared sensory nerve conduction studies (NCS) using surface and near-nerve recording electrodes in 53 patients with clinical probable painful neuropathy. Our aim was to validate the use of both recording techniques in that limited patient group. METHODS: Patients had sensory NCS using two established recording methods and quantitative sensory tests (QST). We compared normalised amplitudes of sensory sural nerve action potentials (SNAP) and sensory thresholds and used receiver operated curve (ROC) analysis of absolute SNAP amplitudes to find discriminatory levels predicting abnormal sensory thresholds. RESULTS: Mean sural SNAP z-scores differed depending on recording techniques (surface −1.0: SD 1.9; near-nerve −2.5: SD 1.7) with a numeric mean difference of −1.49 (Bland-Altman test: CI −1.872 to −1.12) with surface technique giving the z-value closest to zero. We documented a significant bias between the methods. Fifteen patients (28.3%) and 30 (56.6%) patients had abnormal results, respectively (χ2 test: p<0.001). Sural SNAP amplitudes correlated significantly with vibration thresholds using the near-nerve (p<0.02) but not using the surface technique (p=0.11). ROC analysis gave an optimal discriminative value of SNAP amplitudes for each QST measure, which were similar to our lower limit of normal values from investigating normal controls using near-nerve but not surface recording. CONCLUSION: In patients with probable painful neuropathy, choosing sensory NCS technique introduces a bias in the diagnostic outcome. Differences in test performance suggest that using a normal sural NCS alone to delineate small fibre neuropathy from mixed neuropathy could result in poorly defined diagnostic groups