Multicomponent Support Program for Secondary Prevention of Stroke Using Digital Health Technology: Co-Design Study With People Living With Stroke or Transient Ischemic Attack.

BACKGROUND: Few individuals (<2%) who experience a stroke or transient ischemic attack (TIA) participate in secondary prevention lifestyle programs. Novel approaches that leverage digital health technology may provide a viable alternative to traditional interventions that support secondary prevention in people living with stroke or TIA. To be successful, these strategies should focus on user needs and preferences and be acceptable to clinicians and people living with stroke or TIA. OBJECTIVE: This study aims to co-design, with people with lived experience of stroke or TIA (referred to as consumers) and clinicians, a multicomponent digital technology support program for secondary prevention of stroke. METHODS: A consumer user needs survey (108 items) was distributed through the Australian Stroke Clinical Registry and the Stroke Association of Victoria. An invitation to a user needs survey (135 items) for clinicians was circulated via web-based professional forums and national organizations (eg, the Stroke Telehealth Community of Practice Microsoft Teams Channel) and the authors' research networks using Twitter (subsequently rebranded X, X Corp) and LinkedIn (LinkedIn Corp). Following the surveys, 2 rounds of user experience workshops (design and usability testing workshops) were completed with representatives from each end user group (consumers and clinicians). Feedback gathered after each round informed the final design of the digital health program. RESULTS: Overall, 112 consumers (male individuals: n=63, 56.3%) and 54 clinicians (female individuals: n=43, 80%) responded to the survey; all items were completed by 75.8% (n=85) of consumers and 78% (n=42) of clinicians. Most clinicians (46/49, 94%) indicated the importance of monitoring health and lifestyle measures more frequently than current practice, particularly physical activity, weight, and sleep. Most consumers (87/96, 90%) and clinicians (41/49, 84%) agreed that providing alerts about potential deterioration in an individual's condition were important functions for a digital program. Intention to use a digital program for stroke prevention and discussing the data collected during face-to-face consultations was high (consumers: 79/99, 80%; clinicians 36/42, 86%). In addition, 7 consumers (male individuals: n=5, 71%) and 9 clinicians (female individuals: n=6, 67%) took part in the user experience workshops. Participants endorsed using a digital health program to help consumers manage stroke or TIA and discussed preferred functions and health measures in a digital solution for secondary prevention of stroke. They also noted the need for a mobile app that is easy to use. Clinician feedback highlighted the need for a customizable clinician portal that captures individual consumer goals. CONCLUSIONS: Following an iterative co-design process, supported by evidence from user needs surveys and user experience workshops, a consumer-facing app that integrates wearable activity trackers and a clinician web portal were designed and developed to support secondary prevention of stroke. Feasibility testing is currently in progress to assess acceptability and use.

Vascular Calcification Heterogeneity from Bench to Bedside: Implications for Manifestations, Pathogenesis, and Treatment Considerations.

Vascular calcification (VC) is the ectopic deposition of calcium-containing apatite within vascular walls, exhibiting a high prevalence in older adults, and those with diabetes or chronic kidney disease. VC is a subclinical cardiovascular risk trait that increases mortality and functional deterioration. However, effective treatments for VC remain largely unavailable despite multiple attempts. Part of this therapeutic nihilism results from the failure to appreciate the diversity of VC as a pathological complex, with unforeseeable variations in morphology, risk associates, and anatomical and molecular pathogenesis, affecting clinical management strategies. VC should not be considered a homogeneous pathology because accumulating evidence refutes its conceptual and content uniformity. Here, we summarize the pathophysiological sources of VC heterogeneity from the intersecting pathways and networks of cellular, subcellular, and molecular crosstalk. Part of these pathological connections are synergistic or mutually antagonistic. We then introduce clinical implications related to the VC heterogeneity concept. Even within the same individual, a specific artery may exhibit the strongest tendency for calcification compared with other arteries. The prognostic value of VC may only be detectable with a detailed characterization of calcification morphology and features. VC heterogeneity is also evident, as VC risk factors vary between different arterial segments and layers. Therefore, diagnostic and screening strategies for VC may be improved based on VC heterogeneity, including the use of radiomics. Finally, pursuing a homogeneous treatment strategy is discouraged and we suggest a more rational approach by diversifying the treatment spectrum. This may greatly benefit subsequent efforts to identify effective VC therapeutics.

Pulmonary embolism response teams. A description of the first 36-month Australian experience.

BACKGROUND: High/intermediate-risk pulmonary embolism (PE) confers increased risk of cardiovascular morbidity and mortality. International guidelines recommend the formation of a PE response team (PERT) for PE management because of the complexity of risk stratification and emerging treatment options. However, there are currently no available Australian data regarding outcomes of PE managed through a PERT. AIMS: To analyse the clinical and outcome data of patients from an Australian centre with high/intermediate-risk PE requiring PERT-guided management. METHODS: We performed a retrospective observational study of 75 consecutive patients with high/intermediate-risk PE who had PERT involvement, between August 2018 and July 2021. We recorded clinical and interventional data at the time of PERT and assessed patient outcomes up to 30 days from PERT initiation. We used unpaired t tests to compare right to left ventricular (RV/LV) ratios by computed tomography criteria or transthoracic echocardiogram (TTE) at baseline and after interventions. RESULTS: Data were available for 74 patients. Initial computed tomography pulmonary angiography RV/LV ratio was increased at 1.65 ± 0.5 and decreased to 1.30 ± 0.29 following PERT-guided interventions (P < 0.001). TTE RV/LV ratio also decreased following PERT-guided management (1.09 ± 0.19 vs 0.93 ± 0.17; P < 0.001). 20% of patients had any bleeding complication, but two-thirds were mild, not requiring intervention. All-cause mortality was 6.8%, and all occurred within the first 7 days of admission. CONCLUSION: The PERT model is feasible in a large Australian centre in managing complex and time-critical PE. Our data demonstrate outcomes comparable with existing published international PERT data. However, successful implementation at other Australian institutions may require adequate centre-specific resource availability and the presence of multispeciality input.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Epigallocatechin-3-gallate Synergistically Enhanced Arecoline-Induced Cytotoxicity by Redirecting Cycle Arrest to Apoptosis.

Carcinogens, such as arecoline, play a crucial role in cancer progression and continuous gene mutations by generating reactive oxygen species (ROS). Antioxidants can reduce ROS levels and potentially prevent cancer progression but may paradoxically enhance the survival of cancer cells. This study investigated whether epigallocatechin-3-gallate (EGCG), an antioxidant from green tea, could resolve this paradox. Prostate cancer cells (PC-3 cell line) were cultured and treated with arecoline combined with NAC (N-acetylcysteine) or EGCG; the combined effects on intracellular ROS levels and cell viability were examined using the MTT and DCFDA assays, respectively. In addition, apoptosis, cell cycle, and protein expression were investigated using flow cytometry and western blot analysis. Our results showed that EGCG, similar to NAC (N-acetylcysteine), reduced the intracellular ROS levels, which were elevated by arecoline. Moreover, EGCG not only caused cell cycle arrest but also facilitated cell apoptosis in arecoline-treated cells in a synergistic manner. These were evidenced by elevated levels of cyclin B1 and p27, and increased fragmentation of procaspase-3, PARP, and DNA. Our findings highlight the potential use of EGCG for cancer prevention and therapy.

Protocol to study immunodynamics in the tumor microenvironment using a tyramide signal amplification-based immunofluorescent multiplex panel.

Immunodynamics in the tumor microenvironment can be precisely examined by using multiple antigen identification approaches. Here, we present a protocol for capturing expression levels of multiple target proteins in the same specimen at single-cell resolution using a tyramide signal amplification-based immunofluorescent multiplexing system. We describe steps for tumor tissue microarray preparation, multiplex immunohistochemistry staining, image acquisition, and quantification. This protocol can quantify immune cells in tissues from patients or experimental disease models at a protein level. For complete details on the use and execution of this protocol, please refer to Chung et al. (2023),1 Tang et al. (2022),2 and Tang et al. (2022).3.