Study protocol for two stepped-wedge interventional trials evaluating the effects of holistic information technology-based patient-oriented management in older multimorbid patients with cancer: The GERONTE trials.

INTRODUCTION: Current hospital-based care pathways are generally single-disease centred. As a result, coexisting morbidities are often suboptimally evaluated and managed, a deficiency becoming increasingly apparent among older patients who exhibit heterogeneity in health status, functional abilities, frailty, and other geriatric impairments. To address this issue, our study aims to assess a newly developed patient-centred care pathway for older patients with multimorbidity and cancer. The new care pathway was based on currently available evidence and co-designed by end-users including health care professionals, patients, and informal caregivers. Within this care pathway, all healthcare professionals involved in the care of older patients with multimorbidity and cancer will form a Health Professional Consortium (HPC). The role of the HPC will be to centralise oncologic and non-oncologic treatment recommendations in accordance with the patient's priorities. Moreover, an Advanced Practice Nurse will act as case-manager by being the primary point of contact for the patient, thus improving coordination between specialists, and by organising and leading the consortium. Patient monitoring and the HPC collaboration will be facilitated by digital communication tools designed specifically for this purpose, with the added benefit of being customisable for each patient. MATERIALS AND METHODS: The GERONTE study is a prospective international, multicentric study consisting of two stepped-wedge trials performed at 16 clinical sites across three European countries. Each trial will include 720 patients aged 70 years and over with a new or progressive cancer (breast, lung, colorectal, prostate) and at least one moderate or severe multimorbidity. The patients in the intervention group will receive the new care pathway whereas patients in the control group will receive usual oncologic care. DISCUSSION: GERONTE will evaluate whether this kind of holistic, patient-oriented healthcare management can improve quality of life (primary outcome) and other valuable endpoints in older patients with multimorbidity and cancer. An ancillary study will assess in depth the socio-economic impact of the intervention and deliver concrete implementation guidelines for the GERONTE intervention care pathway. TRIAL REGISTRATION: FRONE: NCT05720910 TWOBE: NCT05423808.

Yeast models of human mitochondrial diseases: from molecular mechanisms to drug screening.

Mitochondrial diseases are rare diseases most often linked to energy in the form of ATP-depletion. The high number of nuclear- and mitochondrial-DNA-encoded proteins (>500), required for ATP production and other crucial mitochondrial functions such as NADH re-oxidation, explains the increasing number of reported disorders. In recent years, yeast has revealed to be a powerful model to identify responsible genes, to study primary effects of pathogenic mutations and to determine the molecular mechanisms leading to mitochondrial disorders. However, the clinical management of patients with mitochondrial disorders is still essentially supportive. Here we review some of the most fruitful yeast mitochondrial disorder models and propose to subject these models to highthroughput chemical library screening to prospect new therapeutic drugs against mitochondrial diseases.