RESUMO
Background: As a principal cause of mortality and disability worldwide, stroke imposes considerable burdens on society and effects on the lives of patients, families, and communities. Owing to their growing global popularity, health-related applications (apps) offer a promising approach to stroke management but show a knowledge gap regarding mobile apps for stroke survivors. Methods: This review was conducted across the Android and iOS app stores in September-December 2022 to identify and describe all apps targeting stroke survivors. Apps were included if they were designed for stroke management and contained at least one of the following components: medication taking, risk management, blood pressure management, and stroke rehabilitation. Apps were excluded if they were unrelated to health, not in Chinese or English, or the targeted users were healthcare professionals. The included apps were downloaded, and their functionalities were investigated. Results: The initial search yielded 402 apps, with 115 eligible after title and description screening. Some apps were later excluded due to duplicates, registration problems, or installation failures. In total, 83 apps were included for full review and evaluated by three independent reviewers. Educational information was the most common function (36.1%), followed by rehabilitation guidance (34.9%), communication with healthcare providers (HCPs), and others (28.9%). The majority of these apps (50.6%) had only one functionality. A minority had contributions from an HCP or patients. Conclusion: With the widespread accessibility and availability of smartphone apps across the mHealth landscape, an increasing number of apps targeting stroke survivors are being released. One of the most important findings is that the majority of the apps were not specifically geared toward older adults. Many of the currently available apps lack healthcare professionals' and patients' involvement in their development, and most offer limited functionality, thus requiring further attention to the development of customized apps.
RESUMO
Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural tube defects (NTDs) in newborns associated with exposure to dolutegravir at the time of conception. Folate deficiency is a common cause of NTDs. Dolutegravir and other HIV integrase inhibitor drugs were evaluated in vitro for inhibition of folate transport pathways: proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and folate receptor α (FRα)-mediated endocytosis. Inhibition of folate transport was extrapolated to the clinic by using established approaches for transporters in intestine, distribution tissues, and basolateral and apical membranes of renal proximal tubules (2017 FDA Guidance). The positive controls, methotrexate and pemetrexed, demonstrated clinically relevant inhibition of PCFT, RFC, and FRα in folate absorption, distribution, and renal sparing. Valproic acid was used as a negative control that elicits folate-independent NTDs; valproic acid did not inhibit PCFT, RFC, or FRα At clinical doses and exposures, the observed in vitro inhibition of FRα by dolutegravir and cabotegravir was not flagged as clinically relevant; PCFT and RFC inhibition was not observed in vitro. Bictegravir inhibited both PCFT and FRα, but the observed inhibition did not reach the criteria for clinical relevance. Elvitegravir and raltegravir inhibited PCFT, but only raltegravir inhibition of intestinal PCFT was flagged as potentially clinically relevant at the highest 1.2-g dose (not the 400-mg dose). These studies showed that dolutegravir is not a clinical inhibitor of folate transport pathways, and it is not predicted to elicit clinical decreases in maternal and fetal folate levels. Clinically relevant HIV integrase inhibitor drug class effect on folate transport pathways was not observed. SIGNIFICANCE STATEMENT: Preliminary analysis of ongoing birth surveillance study identified evidence of potential increased risk for neural tube defects (NTDs) in newborns associated with exposure to the HIV integrase inhibitor dolutegravir at the time of conception; folate deficiency is a common cause of NTDs. Dolutegravir and other HIV integrase inhibitor drugs were evaluated in vitro for inhibition of the major folate transport pathways: proton-coupled folate transporter, reduced folate carrier, and folate receptor α-mediated endocytosis. The present studies showed that dolutegravir is not a clinical inhibitor of folate transport pathways, and it is not predicted to elicit clinical decreases in maternal and fetal folate levels. Furthermore, clinically relevant HIV integrase inhibitor drug class effect on folate transport pathways was not observed.
