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  • Exploring the relationship between school-supervised asthma therapy and social determinants of health in pediatric asthma care

    Al-Halbouni, Layana; Ryan, Grace W; Radu, Sonia; Spano, Michelle; Sabnani, Reshma; Phipatanakul, Wanda; Gerald, Lynn B; Garg, Arvin; Pbert, Lori; Trivedi, Michelle (2024-05-16)
    Background: Social determinants of health (SDoH), including access to care, economic stability, neighborhood factors, and social context, strongly influence pediatric asthma outcomes. School-supervised asthma therapy (SST) is an evidence-based strategy that improves asthma outcomes, particularly for historically marginalized children, by providing support for daily medication adherence in school. However, little is known about the relationship between these programs and the adverse SDoH commonly affecting underrepresented minority and marginalized children with asthma. Methods: We examined qualitative data from interviews (n = 52) conducted between 2017 and 2020 with diverse multi-level partners involved in Asthma Link, a SST intervention. Participants included end-users (children and their parents), deliverers (school nurses and pediatric providers), and systems-level partners (e.g., insurers, legislators, and state officials). We used inductive coding to determine themes and subthemes and deductive coding using the Healthy People 2030 SDoH framework. Results: Three themes emerged: (1) SST mitigates adverse SDoH (improves access to preventive healthcare and asthma health literacy), (2) SST benefits children experiencing specific adverse SDoH (provides a consistent medication routine to children with unstable family/housing situations) and (3) specific adverse SDoH impede SST implementation (economic instability, culture and language barriers). Conclusion: This study suggests an important relationship between SDoH and SST that warrants further evaluation in our future work on this community-based asthma intervention. Moreover, our findings underscore the importance of measuring SDoH in the implementation and evaluation of pediatric asthma interventions, particularly given the strong influence of these social factors on child health outcomes.
  • Factors Impacting the Implementation of Mobile Integrated Health Programs for the Acute Care of Older Adults

    O'Connor, Laurel; Behar, Stephanie; Refuerzo, Jade; Mele, Xhenifer; Sundling, Elsa; Johnson, Sharon A; Faro, Jamie M; Lindenauer, Peter K; Mattocks, Kristin M (2024-03-28)
    Objective: Emergency services utilization is increasing in older adult populations. Many such encounters may be preventable with better access to acute care in the community. Mobile integrated health (MIH) programs leverage mobile resources to deliver care and services to patients in the out-of-hospital environment and have the potential to improve clinical outcomes and decrease health care costs; however, they have not been widely implemented. We assessed barriers, potential facilitators, and other factors critical to the implementation of MIH programs with key vested partners. Methods: Professional and community-member partners were purposefully recruited to participate in recorded structured interviews. The study team used the Practical Robust Implementation and Sustainability Model (PRISM) framework to develop an interview guide and codebook. Coders employed a combination of deductive and inductive coding strategies to identify common themes across partner groups. Results: The study team interviewed 22 participants (mean age 56, 68% female). A cohort of professional subject matter experts included physicians, paramedics, public health personnel, and hospital administrators. A cohort of lay community partners included patients and caregivers. Coders identified three prominent themes that impact MIH implementation. First, MIH is disruptive to existing clinical workflows. Second, using MIH to improve patients' experience during acute care encounters is key to intervention adoption. Finally, legislative action is needed to augment central financial and regulatory policies to ensure the adoption of MIH programs. Conclusions: Common themes impacting the implementation of MIH programs were identified across vested partner groups. Multilevel strategies are needed to address patient adoption, clinical partners' workflow, and legislative policies to ensure the success of MIH programs.
  • Short and medium-term outcomes in individuals hospitalized with acute myocardial infarction and multiple chronic conditions: The Worcester heart attack study

    Zammitti, Christopher; Tisminetzky, Mayra; Mehawej, Jordy; Abu, Hawa O; Miozzo, Ruben; Gore, Joel M; Lessard, Darleen; Bamgbade, Benita A; Yarzebski, Jorge; Gurwitz, Jerry H; et al. (2024-03-27)
    Background: Multiple chronic conditions (MCCs) are common in patients hospitalized with acute myocardial infarction (AMI). We examined the association of 12 MCCs with the risk of a 30-day hospital readmission and/or dying within one year among those discharged from the hospital after an AMI. We also examined the five most prevalent pairs of chronic conditions in this population and their association with the principal study endpoints. Methods: The study population consisted of 3,294 adults hospitalized with a confirmed AMI at the three major medical centers in central Massachusetts on an approximate biennial basis between 2005 and 2015. Patients were categorized as ≤1, 2-3, and ≥4 chronic conditions. Results: The median age of the study population was 67.9 years, 41.6% were women, and 15% had ≤1, 32% had 2-3, and 53% had ≥4 chronic conditions. Patients with ≥4 conditions tended to be older, had a longer hospital stay, and received fewer cardiac interventional procedures. There was an increased risk for being rehospitalized during the subsequent 30 days according to the presence of MCCs, with the highest risk for those with ≥4 conditions. There was an increased, but attenuated, risk for dying during the next year according to the presence of MCCs. Individuals with diabetes/hypertension and those with heart failure/chronic kidney disease were at particularly high risk for developing the principal study outcomes. Conclusion: Development of guidelines that include complex patients, particularly those with MCCs and those at high risk for adverse short/medium term outcomes, remain needed to inform best treatment practices.
  • Persistent False Positive Covid-19 Rapid Antigen Tests

    Herbert, Carly; McManus, David D; Soni, Apurv (2024-02-22)
    Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. The percentage of rapid antigen tests with false positive results is reported to be less than 1%. However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders.
  • Hydroxyapatite deposition disease, an overlooked differential diagnosis in the emergency department: a case series and review of literature

    Patel, Jay; Tai, Ryan; Sereni, Christopher; Joshi, Ganesh (2024-02-15)
    Hydroxyapatite crystal deposition disease (HADD) poses diagnostic challenges in the emergency department (ED) as it may clinically present similarly to infection and other musculoskeletal conditions. Misdiagnosis often leads to unnecessary treatments and resource over-utilization. This review article provides an overview of HADD in seven patients who presented to the ED secondary to an acute presentation of this disease process. HADD is a prevalent pathology, which commonly involves the shoulder, followed by the hip, elbow, wrist, and knee. Predisposing risk factors, such as diabetes and certain genetic factors, have also been identified. Clinical history and imaging, particularly radiographs, play a vital role in diagnosing HADD, with characteristic calcification patterns observed in different stages of the disease. Conservative nonsurgical therapy is the mainstay of treatment, providing effective symptom relief in over 90% of cases. By recognizing HADD as a crucial differential diagnosis for patients with acute or chronic pain, healthcare resource utilization can be optimized, leading to improved patient care in the ED.
  • Participant Perspectives on the Implementation of a School-Linked Text-Message Intervention to Improve Pediatric Asthma Medication Adherence

    Radu, Sonia; Zarinafsar, Sheerin; Ryan, Grace W; Chainani, Sanjay; Becker, Sarah; Arenas, Juliana; Spano, Michelle A; Shillan, Holly N; Hoque, Shushmita; Sadasivam, Rajani S; et al. (2024-02-07)
    Background: Poor adherence to inhaled corticosteroids (ICS) is a significant challenge in pediatric asthma, contributing to health inequities. Text-message reminders for ICS therapy are an evidence-based approach that improves pediatric asthma medication adherence, yet has not been widely adopted into practice, partly due to lack of (1) participant input on design and implementation and (2) use of sustainable community linkages. Remote Asthma Link™ (RAL) seeks to fill this gap as a school-linked text-message intervention wherein parents of children with poorly controlled asthma received daily, 2-way text-message reminders for preventive inhaler use. Responses were shared with school nurses who conducted remote check-ins with families. Enrolled children, largely from underserved backgrounds, experienced improvements in medication adherence and asthma health outcomes. While initial results were promising, we have yet to elicit participant input to refine the protocol for more widespread implementation. Objective: Examine participant perspectives on barriers and facilitators of RAL implementation. Methods: Semistructured interviews were conducted May-June 2022 with intervention participants: 10 parents, 7 school nurses, and 4 pediatric providers (n = 21) until thematic saturation was reached. Interview transcripts were coded using thematic analysis. Results: Several facilitators for RAL implementation were identified, including ease of use and accessibility, personal connection to the school nurse, and receipt of a visual notification for habit formation. Barriers included challenges with school nurses reaching parents, poor understanding of program expectations, and lack of reimbursement structure. Participant-proposed solutions to barriers included utilizing alternate communication methods (eg, social media), educational sessions, and meeting with payors to consider reimbursement models. Conclusion: RAL is a school-linked text-message intervention demonstrating promise in improving outcomes and equity in asthma care. Key implementation facilitators, barriers, and proposed solutions will inform protocol adaptations to promote successful implementation of this and other text-message interventions into clinical practice.
  • Opioid Overdose Recognition: A Survey of Perceived Preparedness and Desire for Curricular Integration Among Current US Medical Students

    Walsh, Lindsay; Chapman, Brittany P; Carey, Jennifer; Loycano, Kayla; Carreiro, Stephanie (2024-01-10)
    Objectives: Opioid overdose deaths remain a major health issue in the United States (US). As future physicians, medical students must receive comprehensive training to recognize and manage opioid overdoses. This study aimed to highlight training gaps at the medical student level and understand students' attitudes toward patients with opioid use disorder (OUD). Methods: We assessed baseline knowledge of and attitudes toward the management of opioid overdoses and naloxone administration among medical students in the US. Two validated survey tools (Opioid Overdose Knowledge Scale and Opioid Overdose Attitude Scale) were administered to medical students training at accredited institutions along with supplemental questions measuring knowledge and attitudes towards opioid overdose management, naloxone administration, and prior training. Results: The final sample had N = 73 participants from US medical schools with a mean age of 25.3 (range of 22-37): 72.6% of respondents were female. Although most respondents reported personal/professional experience with OUD before medical school, they expressed interest in additional training. Knowledge surrounding opioid overdoses increased insignificantly over the 4 years of medical school. However, there was a significant increase in both perceived competence in overdose recognition/management and in concerns about intervening from the first to fourth year of medical school. Female respondents had significantly lower perceived competence and readiness to intervene sub-scores than male counterparts; however, there was no significant difference in overall attitude and knowledge scores when stratified by sex. Incorporating opioid overdose prevention training (OOPT) into early medical education was favorable among respondents, who expressed an overwhelming interest in learning and supporting patients with OUD. Conclusions: Given the ongoing opioid crisis, medical students are ideally placed to identify and manage opioid overdoses. Medical students are ready to receive this training, thus strengthening the argument for OOPT integration into early medical student curricula.
  • Evaluation of ChatGPT and Google Bard Using Prompt Engineering in Cancer Screening Algorithms

    Nguyen, Daniel; Swanson, Daniel; Newbury, Alex; Kim, Young H (2023-12-15)
    Large language models (LLMs) such as ChatGPT and Bard have emerged as powerful tools in medicine, showcasing strong results in tasks such as radiology report translations and research paper drafting. While their implementation in clinical practice holds promise, their response accuracy remains variable. This study aimed to evaluate the accuracy of ChatGPT and Bard in clinical decision-making based on the American College of Radiology Appropriateness Criteria for various cancers. Both LLMs were evaluated in terms of their responses to open-ended (OE) and select-all-that-apply (SATA) prompts. Furthermore, the study incorporated prompt engineering (PE) techniques to enhance the accuracy of LLM outputs. The results revealed similar performances between ChatGPT and Bard on OE prompts, with ChatGPT exhibiting marginally higher accuracy in SATA scenarios. The introduction of PE also marginally improved LLM outputs in OE prompts but did not enhance SATA responses. The results highlight the potential of LLMs in aiding clinical decision-making processes, especially when guided by optimally engineered prompts. Future studies in diverse clinical situations are imperative to better understand the impact of LLMs in radiology.
  • Mixed methods evaluation of Asthma Link implementation: A community-clinical linkage intervention of school supervised asthma therapy

    Ryan, Grace W; Nanavati, Janvi; Mendoza Martinez, Daniel; Pereira, Kali; Almeida, John; Spano, Michelle; Gerald, Lynn; Lemon, Stephenie C; Pbert, Lori; Trivedi, Michelle (2023-12-12)
    Background: Asthma Link is a community-clinical linkage intervention wherein children with poorly controlled asthma receive school-supervised asthma therapy. This intervention supports collaboration between medical providers who identify and enroll children, families who consent and bring medications to their child’s school, and school nurses who supervise daily preventive medication administration. This intervention has shown promise in reducing asthma exacerbations, however implementation outcomes (adoption and acceptability), have not previously been assessed. Methods: Using mixed-methods, we assessed adoption (defined as uptake of multiple process steps leading to children receiving supervised preventive asthma medication at school) and acceptability of Asthma Link. We generated descriptive statistics from surveys with practice staff(n=8), parents of enrolled children(n=29), and school nurses(n=14), as well as data tracking logs. We also interviewed medical providers and staff(n=8) and used rapid qualitative analysis. Finally, we triangulated qualitative and quantitative findings. Findings: Regarding adoption, first, 100% of trained providers offered the program. Providers identified 66 eligible children and enrolled 47%(n=31). The preventive asthma medication was brought into school an average of 2.6 (SD=2.9) weeks after enrollment and medication was available to students for 95% of the time they were in school over twelve months of enrollment. One medical provider reflected on adoption: “It’s not for lack of trying...but the family is not willing to.” Acceptability was high in surveys and interviews: 77% of providers, 78% of parents, and 79% of school nurses strongly agreed that the program was acceptable. One provider reported “It was an excellent, excellent program.” Implications for D&I Research: We found excellent adoption of Asthma Link once children were enrolled and high acceptability of the intervention. Qualitative interviews provided important context to quantitative implementation data and will inform future adaptations to promote intervention uptake. For example, we will develop implementation strategies to better support parents, who are identified by providers as “not willing” to participate, which could increase adoption. The use of mixed-methods to assess implementation outcomes at the level of intervention deliverers (medical providers, practice staff, school nurses) and end-users (parents) provided nuanced, actionable information on implementation. This approach should be considered in future implementation evaluations.
  • Vestibular damage affects the precision and accuracy of navigation in a virtual visual environment

    Chari, Divya A; Ahmad, Maimuna; King, Susan; Boutabla, Anissa; Fattahi, Cameron; Panic, Alexander S; Karmali, Faisal; Lewis, Richard F (2023-12-08)
    Vestibular information is available to the brain during navigation, as are the other self-generated (idiothetic) and external (allothetic) sensorimotor cues that contribute to central estimates of position and motion. Rodent studies provide strong evidence that vestibular information contributes to navigation but human studies have been less conclusive. Furthermore, sex-based differences have been described in human navigation studies performed with the head stationary, a situation where dynamic vestibular (and other idiothetic) information is absent, but sex differences in the utilization of vestibular information have not been described. Here, we studied men and women with severe bilateral vestibular damage as they navigated through a visually barren virtual reality environment and compared their performance to normal men and women. Two navigation protocols were employed, which either activated dynamic idiothetic cues ('dynamic task', navigate by turning, walking in place) or eliminated them ('static task', navigate with key presses, head stationary). For both protocols, we employed a standard 'triangle completion task' in which subjects moved to two visual targets in series and then were required to return to their perceived starting position without localizing visual information. The angular and linear 'accuracy' (derived from response error) and 'precision' (derived from response variability) were calculated. Comparing performance 'within tasks', navigation on the dynamic paradigm was worse in male vestibular-deficient patients than in normal men but vestibular-deficient and normal women were equivalent; on the static paradigm, vestibular-deficient men (but not women) performed better than normal subjects. Comparing performance 'between tasks', normal men performed better on the dynamic than the static paradigm while vestibular-deficient men and both normal and vestibular-deficient women were equivalent on both tasks. Statistical analysis demonstrated that for the angular precision metric, sex had a significant effect on the interaction between vestibular status and the test paradigm. These results provide evidence that humans use vestibular information when they navigate in a virtual visual environment and that men and women may utilize vestibular (and visual) information differently. On our navigation paradigm, men used vestibular information to improve navigation performance, and in the presence of severe vestibular damage, they utilized visual information more effectively. In contrast, we did not find evidence that women used vestibular information while navigating on our virtual task, nor did we find evidence that they improved their utilization of visual information in the presence of severe vestibular damage.
  • Exploring Zentangle as a virtual mindfulness-based art intervention for people with serious mental illness

    Stojcevski, Marko; Cheung, Amy; Agwu, Victor; Fan, Xiaoduo (2023-11-30)
    Introduction: Zentangle is an emerging art intervention that incorporates mindfulness into creative drawing. This pilot study explored Zentangle as a novel adjunct treatment for people with serious mental illness (SMI). Methods: Six participants with SMI completed an 8-week Zentangle program. Psychiatric outcomes were evaluated using the Brief Psychiatric Rating Scale (BPRS), Mindful Attention Awareness Scale (MAAS), Perceived Stress Scale (PSS), and Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q-SF). A focus group was conducted to better understand the experiences of the participants. Results: A significant reduction in psychiatric symptoms was observed as measured by the total score on the BPRS between baseline and 5-week post-intervention (40.7 ± 9.1 vs. 33.7 ± 8.9, mean ± SD, p = 0.02). Participants also showed a significant increase in mindful attention using the average score on the MAAS between 1- and 5-week post-intervention (3.5 ± 0.4 vs. 4.2 ± 0.7, mean ± SD, p = 0.04). Four themes were generated from the focus group: (1) approaching mindfulness through Zentangle; (2) power of uncomplicated art creation; (3) understanding the value of self-appreciation; and (4) fostering a positive environment. Discussion: Our preliminary data suggest that the use of Zentangle for participants with SMI may have a positive impact on overall psychiatric symptoms and mindfulness. Moreover, the Zentangle Method encourages positive emotions like gratitude and self-accomplishment to counteract negative feelings of self-criticism and failure in participants.
  • Cathepsin W, T-cell receptor-associated transmembrane adapter 1, lymphotactin and killer cell lectin like receptor K1 are sensitive and specific RNA biomarkers of canine epitheliotropic lymphoma

    Olayinka, Jadesola Temitope; Nagarkar, Akanksha; Ma, Diana Junyue; Wong, Neil B; Romasco, Andrew; Piedra-Mora, Cesar; Wrijil, Linda; David, Clement N; Gardner, Heather L; Robinson, Nicholas A; et al. (2023-11-03)
    Cutaneous T-cell lymphoma (CTCL) is an uncommon type of lymphoma involving malignant skin-resident or skin-homing T cells. Canine epitheliotropic lymphoma (EL) is the most common form of CTCL in dogs, and it also spontaneously arises from T lymphocytes in the mucosa and skin. Clinically, it can be difficult to distinguish early-stage CTCLs apart from other forms of benign interface dermatitis (ID) in both dogs and people. Our objective was to identify novel biomarkers that can distinguish EL from other forms of ID, and perform comparative transcriptomics of human CTCL and canine EL. Here, we present a retrospective gene expression study that employed archival tissue from biorepositories. We analyzed a discovery cohort of 6 canines and a validation cohort of 8 canines with EL which occurred spontaneously in client-owned companion dogs. We performed comparative targeted transcriptomics studies using NanoString to assess 160 genes from lesional skin biopsies from the discovery cohort and 800 genes from the validation cohort to identify any significant differences that may reflect oncogenesis and immunopathogenesis. We further sought to determine if gene expression in EL and CTCL are conserved across humans and canines by comparing our data to previously published human datasets. Similar chemokine profiles were observed in dog EL and human CTCL, and analyses were performed to validate potential biomarkers and drivers of disease. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CD244, CXCL10, and CCL5 in EL in dogs compared to healthy controls. Importantly, CTSW, TRAT1 and KLRK1 distinguished EL from all other forms of interface dermatitis we studied, providing much-needed biomarkers for the veterinary field. XCL1/XCL2 were also highly specific of EL in our validation cohort. Future studies exploring the oncogenesis of spontaneous lymphomas in companion animals will expand our understanding of these disorders. Biomarkers may be useful for predicting disease prognosis and treatment responses. We plan to use our data to inform future development of targeted therapies, as well as for repurposing drugs for both veterinary and human medicine.
  • Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study

    Fleming, Victoria; Prasad, Abhinav; Ge, Connie; Crawford, Sybil; Meraj, Shazeb; Hough, Catherine L; Lo, Bernard; Carson, Shannon S; Steingrub, Jay; White, Douglas B; et al. (2023-10-21)
    Background: Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown. Methods: We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians' and surrogates' characteristics and prognostic estimates for the patient's hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician's and surrogate's estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making. Results: The median shared decision-making score was 7 (IQR 5-8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were "discussing uncertainty"(89%) and "assessing family understanding"(86%); least frequent elements were "assessing the need for input from others"(36%) and "eliciting the context of the decision"(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029). Conclusion: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.
  • Phosphaturic mesenchymal tumor: two cases highlighting differences in clinical and radiologic presentation

    Gu, Joey; Ge, Connie; Joshi, Ganesh; Most, Mathew; Tai, Ryan (2023-10-04)
    Phosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make-patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided.
  • Surface modification of neurovascular stents: from bench to patient

    Zoppo, Christopher T; Mocco, J; Manning, Nathan W; Bogdanov, Alexei A. Jr.; Gounis, Matthew J (2023-10-04)
    Flow-diverting stents (FDs) for the treatment of cerebrovascular aneurysms are revolutionary. However, these devices require systemic dual antiplatelet therapy (DAPT) to reduce thromboembolic complications. Given the risk of ischemic complications as well as morbidity and contraindications associated with DAPT, demonstrating safety and efficacy for FDs either without DAPT or reducing the duration of DAPT is a priority. The former may be achieved by surface modifications that decrease device thrombogenicity, and the latter by using coatings that expedite endothelial growth. Biomimetics, commonly achieved by grafting hydrophilic and non-interacting polymers to surfaces, can mask the device surface with nature-derived coatings from circulating factors that normally activate coagulation and inflammation. One strategy is to mimic the surfaces of innocuous circulatory system components. Phosphorylcholine and glycan coatings are naturally inspired and present on the surface of all eukaryotic cell membranes. Another strategy involves linking synthetic biocompatible polymer brushes to the surface of a device that disrupts normal interaction with circulating proteins and cells. Finally, drug immobilization can also impart antithrombotic effects that counteract normal foreign body reactions in the circulatory system without systemic effects. Heparin coatings have been explored since the 1960s and used on a variety of blood contacting surfaces. This concept is now being explored for neurovascular devices. Coatings that improve endothelialization are not as clinically mature as anti-thrombogenic coatings. Coronary stents have used an anti-CD34 antibody coating to capture circulating endothelial progenitor cells on the surface, potentially accelerating endothelial integration. Similarly, coatings with CD31 analogs are being explored for neurovascular implants.
  • Adolescent cancer prevention in rural, pediatric primary care settings in the United States: A scoping review

    Ryan, Grace W; Whitmire, Paula; Batten, Annabelle; Goulding, Melissa; Baltich Nelson, Becky; Lemon, Stephenie C; Pbert, Lori (2023-09-29)
    Adolescence is a critical period for establishing habits and engaging in health behaviors to prevent future cancers. Rural areas tend to have higher rates of cancer-related morbidity and mortality as well as higher rates of cancer-risk factors among adolescents. Rural primary care clinicians are well-positioned to address these risk factors. Our goal was to identify existing literature on adolescent cancer prevention in rural primary care and to classify key barriers and facilitators to implementing interventions in such settings. We searched the following databases: Ovid MEDLINE®; Ovid APA PsycInfo; Cochrane Library; CINAHL; and Scopus. Studies were included if they reported on provider and/or clinic-level interventions in rural primary care clinics addressing one of these four behaviors (obesity, tobacco, sun exposure, HPV vaccination) among adolescent populations. We identified 3,403 unique studies and 24 met inclusion criteria for this review. 16 addressed obesity, 6 addressed HPV vaccination, 1 addressed skin cancer, and 1 addressed multiple behaviors including obesity and tobacco use. 10 studies were either non-randomized experimental designs (n = 8) or randomized controlled trials (n = 2). The remaining were observational or descriptive research. We found a dearth of studies addressing implementation of adolescent cancer prevention interventions in rural primary care settings. Priorities to address this should include further research and increased funding to support EBI adaptation and implementation in rural clinics to reduce urban-rural cancer inequities.
  • Association of neighborhood-level sociodemographic factors with Direct-to-Consumer (DTC) distribution of COVID-19 rapid antigen tests in 5 US communities

    Herbert, Carly; Shi, Qiming; Baek, Jonggyu; Wang, Biqi; Kheterpal, Vik; Nowak, Christopher; Suvarna, Thejas; Singh, Aditi; Hartin, Paul; Durnam, Basyl; et al. (2023-09-22)
    Background: Many interventions for widescale distribution of rapid antigen tests for COVID-19 have utilized online, direct-to-consumer (DTC) ordering systems; however, little is known about the sociodemographic characteristics of home-test users. We aimed to characterize the patterns of online orders for rapid antigen tests and determine geospatial and temporal associations with neighborhood characteristics and community incidence of COVID-19, respectively. Methods: This observational study analyzed online, DTC orders for rapid antigen test kits from beneficiaries of the Say Yes! Covid Test program from March to November 2021 in five communities: Louisville, Kentucky; Indianapolis, Indiana; Fulton County, Georgia; O'ahu, Hawaii; and Ann Arbor/Ypsilanti, Michigan. Using spatial autoregressive models, we assessed the geospatial associations of test kit distribution with Census block-level education, income, age, population density, and racial distribution and Census tract-level Social Vulnerability Index. Lag association analyses were used to measure the association between online rapid antigen kit orders and community-level COVID-19 incidence. Results: In total, 164,402 DTC test kits were ordered during the intervention. Distribution of tests at all sites were significantly geospatially clustered at the block-group level (Moran's I: p < 0.001); however, education, income, age, population density, race, and social vulnerability index were inconsistently associated with test orders across sites. In Michigan, Georgia, and Kentucky, there were strong associations between same-day COVID-19 incidence and test kit orders (Michigan: r = 0.89, Georgia: r = 0.85, Kentucky: r = 0.75). The incidence of COVID-19 during the current day and the previous 6-days increased current DTC orders by 9.0 (95% CI = 1.7, 16.3), 3.0 (95% CI = 1.3, 4.6), and 6.8 (95% CI = 3.4, 10.2) in Michigan, Georgia, and Kentucky, respectively. There was no same-day or 6-day lagged correlation between test kit orders and COVID-19 incidence in Indiana. Conclusions: Our findings suggest that online ordering is not associated with geospatial clustering based on sociodemographic characteristics. Observed temporal preferences for DTC ordering can guide public health messaging around DTC testing programs.
  • Application of Causal Inference Methods to Pooled Longitudinal Non- Randomized Studies: A Methodological Systematic Review [preprint]

    Hufstedler, Heather; Mauer, Nicole; Yeboah, Edmund; Carr, Sinclair; Rahman, Sabahat; Danzer, Alexander M; Debray, Thomas P A; Jong, Valentijn M T; Campbell, Harlan; Gustafson, Paul; et al. (2023-08-30)
    Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.
  • Heterozygous FOXJ1 Mutations Cause Incomplete Ependymal Cell Differentiation and Communicating Hydrocephalus

    Hou, Connie C; Li, Danielle; Berry, Bethany C; Zheng, Shaokuan; Carroll, Rona S; Johnson, Mark D; Yang, Hong Wei (2023-08-24)
    Heterozygous mutations affecting FOXJ1, a transcription factor governing multiciliated cell development, have been associated with obstructive hydrocephalus in humans. However, factors that disrupt multiciliated ependymal cell function often cause communicating hydrocephalus, raising questions about whether FOXJ1 mutations cause hydrocephalus primarily by blocking cerebrospinal fluid (CSF) flow or by different mechanisms. Here, we show that heterozygous FOXJ1 mutations are also associated with communicating hydrocephalus in humans and cause communicating hydrocephalus in mice. Disruption of one Foxj1 allele in mice leads to incomplete ependymal cell differentiation and communicating hydrocephalus. Mature ependymal cell number and motile cilia number are decreased, and 12% of motile cilia display abnormal axonemes. We observed decreased microtubule attachment to basal bodies, random localization and orientation of basal body patches, loss of planar cell polarity, and a disruption of unidirectional CSF flow. Thus, heterozygous FOXJ1 mutations impair ventricular multiciliated cell differentiation, thereby causing communicating hydrocephalus. CSF flow obstruction may develop secondarily in some patients harboring FOXJ1 mutations. Heterozygous FOXJ1 mutations impair motile cilia structure and basal body alignment, thereby disrupting CSF flow dynamics and causing communicating hydrocephalus.
  • A novel intrasaccular aneurysm device with high complete occlusion rate: initial results in a rabbit model

    Zoppo, Christopher T; Kolstad, Josephine W; King, Robert M; Wolfe, Thomas; Kraitem, Afif; Vardar, Zeynep; Badruddin, Aamir; Pereira, Edgard; Guerrero, Boris Pabón; Rosqueta, Arturo S; et al. (2023-08-01)
    Background: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. Methods: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. Results: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. Conclusion: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks.

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