Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: The introduction of home therapy for hemophilia has empowered patients and their families to manage the disease more independently. However, the self-management of hemophilia is demanding and complex. The uses of innovative interventions delivered by telehealth routes, such as social media, web-based and mobile applications, may help to monitor bleeding events and promote the appropriate use of clotting factors among patients with hemophilia. Objective: This review aims to systematically summarize the literature evaluating the effectiveness of telehealth interventions for improving health outcomes in patients with hemophilia, and provides direction for future research. Methods: A search was conducted on Ovid MEDLINE, EMBASE and PubMed for studies that (1) focused on patients with hemophilia A or B; (2) tested the use of remote telehealth interventions via Internet, wireless, satellite, telephone and mobile phone media; (3) and reported on at least one of the following outcomes: quality of life; monitoring of bleeding episodes, joint damage or other measures of functional status; medication adherence; patient knowledge or any other outcomes related to empowering patients to be active decision makers in the emotional, social or medical management of their illness. Reviews, commentaries or case reports comprising 10 or fewer cases, were excluded. Results: Sixteen articles fulfilled the inclusion criteria. The majority of the interventions (n=13) were designed with the primary objective of empowering patients and caregivers to manage their condition and treatment more independently. The components of the interventions were rather homogenous and typically involved electronic (1) logging and reminders for prophylactic infusions; (2) reporting of spontaneous and traumatic bleeding events; (3) monitoring of infusion product usage and home inventory and (4) real-time communication with healthcare professionals and hemophilia clinics. Telemedicine-supported education and information interventions seemed to be particularly effective among adolescent and young adult patients. Although the patients reported improvements in their health-related quality of life and perception of illness, telemonitoring devices did not appear to have a significant effect on quantifiable health outcomes, such as joint health. Longitudinal studies seemed to suggest that the response and compliance rates decreased over time. Conclusions: Preliminary evidence from this review suggests that telehealth-delivered interventions could feasibly improve patients’ adherence to medication use and promote independence in disease management. Given the complexity and resources involved in developing a mature and established system, support from a dedicated network of hemophilia specialists and data managers will be required to maintain the technology, improve compliance and validate the electronic data locally.

We review grounding issues that influence the scientific usefulness of any biomedical multiscale model (MSM). Groundings are the collection of units, dimensions, and/or objects to which a variable or model constituent refers. To date, models that primarily use continuous mathematics rely heavily on absolute grounding, whereas those that primarily use discrete software paradigms (e.g., object-oriented, agent-based, actor) typically employ relational grounding. We review grounding issues and identify strategies to address them. We maintain that grounding issues should be addressed at the start of any MSM project and should be reevaluated throughout the model development process. We make the following points. Grounding decisions influence model flexibility, adaptability, and thus reusability. Grounding choices should be influenced by measures, uncertainty, system information, and the nature of available validation data. Absolute grounding complicates the process of combining models to form larger models unless all are grounded absolutely. Relational grounding facilitates referent knowledge embodiment within computational mechanisms but requires separate model-to-referent mappings. Absolute grounding can simplify integration by forcing common units and, hence, a common integration target, but context change may require model reengineering. Relational grounding enables synthesis of large, composite (multi-module) models that can be robust to context changes. Because biological components have varying degrees of autonomy, corresponding components in MSMs need to do the same. Relational grounding facilitates achieving such autonomy. Biomimetic analogues designed to facilitate translational research and development must have long lifecycles. Exploring mechanisms of normal-to-disease transition requires model components that are grounded relationally. Multi-paradigm modeling requires both hyperspatial and relational grounding.

Introduction: Both daily and on‐demand regimens have been proven effective for pre‐exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM.Methods: A randomized, controlled, open‐label, crossover trial was conducted in a teaching hospital in Hong Kong. Participants were sexually active HIV‐negative MSM aged 18 years or above with normal renal function and without chronic hepatitis B infection. Oral tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2‐week lead‐in with daily TDF/FTC for treatment‐naïve MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily‐first or on‐demand‐first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed‐over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP‐covered CLAI by intention‐to‐treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHK_CCRB00606, and is closed to accrual.Results: Between 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily‐first arm (n = 59) and on‐demand‐first arm (n = 60) with an 87% overall completion rate (n = 103). With 96% and 54% of days on PrEP during daily and on‐demand periods, respectively, the proportion of days with PrEP‐covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time‐limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on‐demand periods, respectively. At the end of the study, a similar proportion favoured daily or on‐demand regimen.Conclusions: High prevention‐effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on‐demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs.