Protocols of a diagnostic study and a randomized controlled non-inferiority trial comparing televisits vs standard in-person outpatient visits for narcolepsy diagnosis and care: TElemedicine for NARcolepsy (TENAR).

BACKGROUND: Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown. METHODS: TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm). DISCUSSION: TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise. TRIAL REGISTRATION: Number of the Tele-multidisciplinary care study NCT04316286. Registered 20 March 2020.

Multidisciplinary care of patients with narcolepsy during coronavirus disease 2019 pandemic in Italy via televisit: the TElemedicine for NARcolepsy feasibility study.

STUDY OBJECTIVES: Narcolepsy is a rare chronic central disorder of hypersomnolence with frequent endocrine-metabolic comorbidities. To address the complex care needs of patients during the COVID-19 emergency, we carried out a feasibility study of the TElemedicine for NARcolepsy (TENAR) protocol with the aim of assessing the feasibility of a multidisciplinary care approach via televisit for patients with narcolepsy. METHODS: A feasibility single open-arm study on the multidisciplinary care of children (>7 y.o.) and adults with narcolepsy who required a follow-up visit was realized during the COVID-19 pandemic emergency period in Italy. The study included a sleep, metabolic, and psychosocial assessment via televisit at baseline, at 6, and at 12 months from the study inclusion period (15th May-26th June 2020). RESULTS: In total 39 out of 44 eligible patients (89%) entered the study (30 adults, nine children); 37 patients (95%) ended the 12-month follow-up. At baseline, the median Epworth sleepiness scale score (ESS) was 10 (IQR 8-14), and the median body mass index (BMI) was 25.6 (IQR 22.1-30.9). During the follow-up period, the ESS score decreased from the 6th month onward (p = 0.003), and BMI decreased at the 1-year follow-up (p = 0.047), while there were no differences in depressive and anxiety symptoms, quality of life, compliance with treatment, adverse drug reactions, or accidents. CONCLUSIONS: High response and retention rates, stability of ESS, and lack of side effects indicate that telemedicine is a feasible and safe approach for adults and children with narcolepsy.

Impact of COVID-19 pandemic lockdown on narcolepsy type 1 management.

STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID-19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. METHODS: In the period between 10 April and 15 May 2020, we performed routine follow-up visits by telephone (as recommended during the COVID-19 emergency) to 50 patients >18 years old (40% males) under stable long-term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job ("lost occupation"). Current sleep-wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. RESULTS: At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep-related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. CONCLUSIONS: Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight.

Obesity and Androgens in Women.

Androgen excess is often associated with obesity states, at any age of life, because of changes in the pattern of secretion or metabolism of androgens and in their actions at the level of target tissues, particularly the adipose tissue. Androgen excess plays an important role in favouring the expansion of visceral fat, which characterize so-called visceral obesity. Moreover, there is evidence that the combination of androgen excess and obesity may favour the development of metabolic disorders, such as the metabolic syndrome and type 2 diabetes. In obese adolescent girls, androgen excess may also suggest the potential development of the polycystic ovary syndrome (PCOS). A new hypothesis, based on long-term lifestyle intervention programs or bariatric surgery, supports the concept that a "PCOS secondary to obesity" may exist, as confirmed by the complete resolution of all features defining PCOS after considerable weight loss. Obesity can also develop after long-term exposure to chronic stress, which is characterized by increased activity of the hypothalamic-pituitary-adrenal axis and the sympathetic system combined with higher than normal androgen production rates in women. This increasingly observed condition, often underestimated, should be considered more carefully, not only in mature women but also in girls during adolescence. The presence of a hyperandrogenic state can also be detected in menopausal women, as a consequence of the rearrangement of the sex hormone balance which, in turn, may play some role in determining the development of both visceral adiposity and even obesity and, consequently, metabolic disorders. Undoubtedly, the recognition of the potential negative effects of androgen excess in obese women may open new therapeutic perspectives aimed at achieving a sustained weight loss and its maintenance for as long as possible.

Taste and the Gastrointestinal tract: from physiology to potential therapeutic target for obesity.

Flavor is the combination of gustatory, olfactory and trigeminal sensations, representing the three main sensory pathways that allow detecting environmental chemical substances. Taste, in particular, is a complex chemosensory path that allows identification of substances present in ingested foods and beverages. In this manuscript, we propose a conceptual roadmap from aspects related to the evolution and the physiological role of taste, up to the current knowledge about its implication in the modulation of a healthy state, or obesity. More specifically, we focused on the role of stimulation of taste receptors in releasing gut hormones (also known as enterohormones), and their effects on the regulation of food intake, by inducing satiety, either by locally acting (in the gastrointestinal tract), or centrally (in the brain). Recent evidence demonstrated that some enterohormones are able to modulate gastrointestinal motility, thus affecting an orexigenic responses in the central nervous system. In keeping with this, we discuss the ability of the gustatory system to be a final checkpoint control for food intake regulation, and we speculate about taste perception manipulation in the management of obesity.