Evaluating the effect of short-course rifapentine-based regimens with or without enhanced behaviour-targeted treatment support on adherence and completion of treatment for latent tuberculosis infection among adults in the UK (RID-TB: Treat): protocol for an open-label, multicentre, randomised controlled trial.

INTRODUCTION: The successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion. METHODS AND ANALYSIS: A pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The National Health Service Health Research Authority (20/LO/1097). All participants will be required to provide written informed consent. We will share the results in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2020-004444-29.

Type 2 Diabetes Mellitus (T2DM) and Carbohydrate Metabolism in Relation to T2DM from Endocrinology, Neurophysiology, Molecular Biology, and Biochemistry Perspectives.

Type 2 diabetes mellitus (T2DM) is a severe disease caused by metabolic disorders, particularly carbohydrate metabolism disorders. The disease is a fatal global trouble characterised by high prevalence rates, causing death, blindness, kidney failure, myocardial infarction, amputation of lower limps, and stroke. Biochemical metabolic pathways like glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis are critical pathways that regulate blood glucose levels with the glucokinase (GK) enzyme playing a central role in glucose homeostasis. Any factor that perturbs the aforementioned biochemical pathways is detrimental. Endocrinological, neurophysiological, and molecular biological pathways that are linked to carbohydrate metabolism should be studied, grasped, and manipulated in order to alleviate T2DM global chaos. The challenge, howbeit, is that, since the body is an integration of systems that complement one another, studying one "isolated" system is not very useful. This paper serves to discuss endocrinology, neurophysiology, and molecular biology pathways that are involved in carbohydrate metabolism in relation to T2DM.