Melatonin use in children and adolescents: A scoping review of caregiver perspectives.

Despite melatonin's popularity as a pediatric sleep-aid, little has been investigated around caregivers' understanding and perception of melatonin use for their dependent. This scoping review analyzes the current literature on pediatric melatonin use, to understand how caregivers' perceptions around melatonin are shaped by their illness/medication-related beliefs, treatment experience and preferences. A literature search was conducted across Embase, Medline, PsycINFO, PubMed and Scopus, generating 184 results for screening against the inclusion criteria. Nineteen studies were retrieved, comprising of 1561 children and adolescents, aged 8.7 ± 2.3 years (range: 0-44 years), conducted primarily in the United States of America (n = 6), Canada (n = 3) and the Netherlands (n = 3). Studies were evaluated for their study design and caregiver-centered outcomes, encompassing: 1) illness/treatment-related beliefs, 2) treatment satisfaction/effectiveness, 3) treatment preference/acceptability, and 4) impact of child's sleep disturbance on caregivers' quality-of-life. Sleep disturbances necessitating melatonin use occurred alongside congenital/neurodevelopmental comorbidities in 18 studies (95%). Melatonin was commonly associated with "naturalness" and "safety". Concepts of treatment satisfaction versus effectiveness were minimally differentiated within included studies. Caregivers preferred concurrent use of melatonin and behavioral interventions for management of their dependents' sleep. Improved sleep in the dependent generally led to better quality-of-life for caregivers and their family.

Pharmacists' perspectives and attitudes towards the 2021 down-scheduling of melatonin in Australia using the Theoretical Domains Framework: a mixed-methods study.

BACKGROUND: In Australia, prescription melatonin became a 'Pharmacist Only Medicine' for people over 55 with insomnia from June 2021. However, little is known about pharmacists' views on melatonin down-scheduling and perceived impacts on practice. AIM: To explore Australian community pharmacists' views on and attitudes towards the down-scheduling of melatonin. METHOD: A convenience sample of community pharmacists and pharmacy interns were recruited. Participants completed a survey capturing demographic and professional practice details, and rated their knowledge, beliefs and attitudes towards melatonin. This was followed by an online semi-structured interview. Interviews were guided by a schedule of questions developed using the Theoretical Domains Framework and explored the perceived role of melatonin, preparation/response to down-scheduling, practice changes and patient interactions. Interviews continued until data saturation and were digitally recorded, transcribed verbatim and analysed using the Framework Approach. RESULTS: Twenty-four interviews were conducted with community pharmacists (n = 19) and intern pharmacists (n = 5), all practicing in metropolitan areas. Pharmacists/intern pharmacists welcomed the increased accessibility of melatonin for patients. However, pharmacists perceived a disconnect between the guidelines, supply protocols and pack sizes with practice, making it difficult to monitor patient use of melatonin. The miscommunication of eligibility also contributed to patient-pharmacist tension when supply was denied. Importantly, most participants indicated their interest in upskilling their knowledge in melatonin use in sleep, specifically formulation differences and dosage titration. CONCLUSION: While pharmacists welcomed the down-scheduling of melatonin, several challenges were noted, contributing to pharmacist-patient tensions in practice. Findings highlight the need to refine and unify melatonin supply protocols and amend pack sizes to reflect guideline recommendations as well as better educating the public about the risk-benefits of melatonin.

Travelers' perceptions of jetlag and travel fatigue: A scoping review.

Effective management strategies for jetlag have largely been studied and evaluated through the lens of circadian science and biological rhythms. Jetlag is mostly self-managed by the individual. The most effective strategies require individuals to make behavioral changes to carefully alter sleep-wake schedules and time light exposure. However, travelers' perceptions, including their experiences, beliefs about jetlag/travel fatigue, and management expectations remain unclear. Therefore, the aim of this scoping review was to systematically synthesize the literature to understand what is currently known about travelers' perceptions of jetlag and travel fatigue. A literature search was conducted through EMBASE, PsycINFO, PubMed and Scopus generating 1164 results (2 articles known to authors), which were screened against our inclusion criteria. Twenty-two studies including data from 3952 participants were evaluated for its study design and traveler-centered outcome measures across the domains of: 1) Traveler Health Beliefs and Knowledge about Jetlag and Travel Fatigue; 2) Experience of Jetlag and Travel Fatigue 3) Traveler Priorities; 4) Self-reported Management Strategies for Jetlag and Travel Fatigue; and 5) User Experiences of Management Strategies. Synthesis of results suggests a potential mismatch between researchers' focus on circadian misalignment and travelers' focus on air travel comfort. A better understanding of the beliefs, attitudes, knowledge, satisfaction, experiences, and expectations about jetlag and travel fatigue will better enable the development of interventions that align with traveler priorities.

Antisense oligonucleotides and nucleic acids generate hypersensitive platelets.

INTRODUCTION: Despite the great promise for therapies using antisense oligonucleotides (ASOs), their adverse effects, which include pro-inflammatory effects and thrombocytopenia, have limited their use. Previously, these effects have been linked to the phosphorothioate (PS) backbone necessary to prevent rapid ASO degradation in plasma. The main aim of this study was to assess the impact of the nucleic acid portion of an ASO-type drug on platelets and determine if it may contribute to thrombosis or thrombocytopenia. METHODS: Platelets were isolated from healthy donors and men with advanced prostate cancer. Effects of antisense oligonucleotides (ASO), oligonucleotides, gDNA, and microRNA on platelet activation and aggregation were evaluated. A mouse model of lung thrombosis was used to confirm the effects of PS-modified oligonucleotides in vivo. RESULTS: Platelet exposure to gDNA, miRNA, and oligonucleotides longer than 16-mer at a concentration above 8 mM resulted in the formation of hypersensitive platelets, characterized by an increased sensitivity to low-dose thrombin (0.1 nM) and increase in p-Selectin expression (6-8 fold greater than control; p < 0.001). The observed nucleic acid (NA) effects on platelets were toll-like receptor (TLR) -7 subfamily dependent. Injection of a p-Selectin inhibitor significantly (p = 0.02) reduced the formation of oligonucleotide-associated pulmonary microthrombosis in vivo. CONCLUSION: Our results suggest that platelet exposure to nucleic acids independent of the presence of a PS modification leads to a generation of hypersensitive platelets and requires TLR-7 subfamily receptors. ASO studies conducted in cancer patients may benefit from testing the ASO effects on platelets ex vivo before initiation of patient treatment.