Publications by Year: 2026

INTRODUCTION: The "Learning Health System" (LHS) relies on meaningful patient and public engagement to foster innovation in healthcare. However, effective methods for involving these stakeholders in LHS research are unclear. This scoping review examines the use of Human-Centered Design (HCD) to engage patients and the public in LHS research.

METHODS: Following Joanna Briggs Institute methodology and PRISMA-ScR guidelines, we searched MEDLINE, Cochrane Library, Embase, and Web of Science for LHS research studies using HCD to engage patients and the public. Data were categorized by: (1) Study Characteristics, (2) Participant Characteristics and Group Dynamics, (3) HCD Approach, Stages, and Methods, (4) Participant Satisfaction and Engagement, and (5) Focused Demographic Participation.

RESULTS: Among the included studies, participants in the HCD process included children and adults with conditions such as cancer, dementia, and stroke, often joined by their families and healthcare clinicians. Research spanned innovations in patient engagement, digital health, quality improvement, care delivery, environmental design, and clinical support tools. Participatory workshops were the most used HCD method. Group activities fostered creativity and diverse perspectives; individual activities offered deeper insights. A common challenge was limited engagement in later design stages, particularly prototyping. Studies involving harder-to-reach populations implemented extreme user design, creative design tools like photovoice and the 1-2-4-All technique, and community-based participatory research principles, all integrated into the HCD process.

CONCLUSIONS: Our review found HCD to be an effective method for engaging patients and the public in LHS research. It has been applied to engage individuals across a wide range of health conditions, age groups, and socioeconomic backgrounds, driving targeted innovations and system-level improvement. Its adaptability allows real-time adjustments in research pace and design, enabling iteration, strategy refinement, and inclusion of new populations as insights emerge. Blending discussion-based methods (e.g., interviews, workshops) with experiential approaches (e.g., role-playing, prototyping) boosts participant engagement and satisfaction. Future research should identify optimal group sizes, the most appropriate methods for each design stage, and the impact of integrating HCD with other research approaches.

Cardiovascular diseases, and most notably coronary artery disease (CAD), carry a large burden of mortality and morbidity, highlighting the need for better risk prediction and prevention. Several risk scoring tools for CAD have been developed to improve early detection, reduce the risk of acute cardiac events, and ensure adequate monitoring and follow-up of high-risk individuals. One that seized attention, especially with the groundbreaking advancements in disease's genetic buildup, was the polygenic risk score (PRS) for CAD. It was developed for potentially improving risk prediction at an early age, with individualized patient care. Our review aims to review the latest advances in this field of polygenic risk prediction, highlighting background information about PRS, current evidence supporting the utility of PRS for CAD, challenges associated with its implementation, and its complementary role with the coronary artery calcium score (CAC). Our review demonstrates that PRS could be a strong predictive indicator of CAD, especially when combined with other clinical factors. However, concerns remain regarding its applicability to genetically diverse populations, the ethical and psychological challenges, and practical feasibility. Lastly, PRS can augment and predict CAC in terms of risk discrimination and reclassification. In conclusion, PRS is a valuable tool that is upscaling with wider adoption. This requires a proper handling of its associated challenges to better shape the future of individualized care.

BACKGROUND: Radicular pain may originate from various etiologies, among which epidural fibrosis is a significant contributor. Epidural scarring can induce pain through multiple pathophysiological mechanisms, notably by entrapping spinal nerve roots and disrupting the integrity of the myelin sheath.

OBJECTIVE: To present a safe and practical technique for performing neuroplasty via the S1 foramen, utilizing a Tuohy or introducer needle guided by a reference spinal needle under fluoroscopic imaging. This caudal-to-cephalic approach ensures precise catheter advancement and builds upon previously described methods by Silva et al.

DESIGN: Technical note.

METHODS: For the described approach, we considered the anatomical dimensions of the sacral canal, with particular attention to the measurements at the level of the S1 foramen. This measurement is crucial, as it determines the available space for positioning the introducer needle and safely advancing the neuroplasty catheter in a caudal-to-cephalic direction.

CONCLUSION: This technique enables safer and more effective S1 foraminal neuroplasty by incorporating depth information through the use of reference spinal needles under fluoroscopic guidance. It facilitates tunnel-view access, which was previously unattainable, and improves procedural outcomes, particularly benefiting clinicians with less experience in fluoroscopically guided interventions.

PURPOSE: To evaluate the incidence and clinical characteristics of ocular graft-versus-host disease (oGVHD) associated with tapering of systemic immunosuppression after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODS: This retrospective study included adult allo-HSCT recipients diagnosed with oGVHD during or after immunosuppression tapering at a single tertiary center (1998-2023). Data collected included transplant indications and donor characteristics, GVHD prophylaxis regimens, immunosuppression status at engraftment and at oGVHD onset, and systemic and ocular GVHD manifestations. Cumulative incidence of oGVHD was estimated using Kaplan-Meier survival analyses.

RESULTS: Fifty-six patients (mean age, 56 ± 12 years; 59% male) developed oGVHD at a median of 9 months posttransplant (interquartile range, 6.8-13). The predominant prophylaxis regimen at engraftment was tacrolimus with methotrexate (62.5%). At the time of oGVHD diagnosis, 25.0% of patients were fully tapered off systemic immunosuppression, whereas 28.5% remained on tacrolimus monotherapy. Kaplan-Meier analysis showed a rapid rise in oGVHD incidence within the first year, with 75% of cases diagnosed by month 14. Systemic GVHD preceded ocular involvement in 62% of patients, whereas 18% developed isolated oGVHD. Most patients required escalation of ocular surface therapy-including lubrication, punctal occlusion, and topical antiinflammatory or immunomodulatory agents-although no patient required reinstatement or escalation of systemic immunosuppression solely for ocular disease.

CONCLUSIONS: oGVHD frequently emerges during the late phase of systemic immunosuppression tapering, with many cases occurring after complete discontinuation or reduction to monotherapy. Given the high incidence within the first posttransplant year and the occurrence of isolated ocular disease, these findings support routine ophthalmic evaluation for all allo-HSCT recipients as systemic immunosuppression is withdrawn. Early detection and timely escalation of topical therapy are essential to prevent ocular surface damage while permitting safe continuation of systemic tapering.

BackgroundThe Lieber Institute for Brain Development (LIBD) has one of the largest postmortem human brain banks for the study of neuropsychiatric disorders in the world. The postmortem evaluation involves neuropathological assessment for age-related protein accumulations, specifically phosphorylated tau (p-tau) and amyloid-β (Aβ).ObjectivePresent the LIBD semiquantitative assessment methodology for p-tau and Aβ by comparing proteinopathy by age and by apolipoprotein E (APOE) genotype.MethodsPostmortem brain tissue samples were from 1509 people aged 50 or greater (median age at death = 63 years; range = 50-102). Seven brain regions (four neocortical areas, hippocampal formation, midbrain, and cerebellum) were examined by routine histopathology, p-tau immunohistochemistry (AT8; hippocampus and four neocortical samples), and Aβ immunohistochemistry (BAM01; four neocortical samples). APOE genotyping was performed in a subgroup. Semiquantitative assessments include modified CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and modified Braak approaches.ResultsThere were 63.8% rated as B1 (modified Braak I or II), 30.4% rated as B2 (modified Braak III or IV), and 5.8% rated as B3 (modified Braak V or VI). For those in their early 70 s, half had modified Braak stage III-IV ratings. For decedents in their 80 s, approximately 1 in 4 had modified Braak stage V-VI ratings. Aβ was present in 48.8% (C0 = 51.2%, C1 = 17.2%, C2 = 24.5%, and C3 = 7.1%). Age and APOE genotype were significant predictors of Aβ plaques.ConclusionsThe LIBD protocol assessing p-tau and Aβ burden identified significant associations with age and APOE genotype. More research is needed to understand the spectrum of age-related proteinopathy versus neurodegenerative disease neuropathology.

BACKGROUND: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications.

METHODS: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included.

RESULTS: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce.

CONCLUSIONS: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes.

BACKGROUND/OBJECTIVES: Drug-resistant epilepsy (DRE) is a significant health problem leading to cognitive impairment and reduced quality of life. This study aimed to investigate the incidence and etiology of DRE in children in Estonia.

METHODS: A retrospective, population-based study of childhood DRE was conducted in Estonia from 1 January 2013, to 31 December 2017. All cases were identified through the only two pediatric neurology departments in the country, both located at tertiary care hospitals (Tartu University Hospital and Tallinn Children's Hospital), ensuring complete nationwide coverage. Epidemiological, magnetic resonance imaging (MRI), and genetic data (chromosomal microarray, single-gene tests, gene panels, and exome/genome sequencing) were collected.

RESULTS: The incidence rate of childhood epilepsy was 84.1 per 100,000. DRE developed in 10% of children with new-onset epilepsy, corresponding to an incidence rate of 8.5 per 100,000. Etiologically relevant MRI abnormalities were identified in 43% of patients with DRE, most commonly congenital brain malformations (19%). Pathogenic single-gene sequence variants were detected in 25 of 110 patients (23%), copy number variants in four patients (4%), and chromosomal aberrations in one patient (1%). Novel candidate disease genes of uncertain pathogenicity were identified in four patients (4%). The most frequent etiology of DRE was structural (29%), followed by genetic (19%), with combined etiologies (13%) also contributing significantly.

CONCLUSIONS: Our study is the first epidemiological study of DRE in children in Estonia and the Baltic region. The relatively low incidence observed may reflect the comprehensive national ascertainment and centralized management of pediatric epilepsy in tertiary care centers.

BACKGROUND: The COVID-19 pandemic led to disruptions in cardiovascular care in mid-2020, but less is known about how patterns of care and clinical outcomes changed for older adults with cardiovascular (CV) risk factors and/or established cardiovascular disease (CVD) in the later stages of the pandemic.

OBJECTIVES: This study sought to identify changes in utilization of health care services and all-cause mortality among Medicare beneficiaries with CV risk factors or CVD in the "late pandemic" (January 2021 to December 2022) overall and across subgroups based on rurality and social vulnerability index.

METHODS: The study included all Medicare fee-for-service and Medicare Advantage beneficiaries with CV risk factors (hypertension, diabetes mellitus, hyperlipidemia) or CVD (coronary heart disease, heart failure, atrial fibrillation, stroke) from January 2018 to December 2022. A Poisson-lognormal regression model was fitted to compare the adjusted incidence rate ratio (aIRR) of acute care visits, outpatient visits, and all-cause mortality during the late pandemic (January 2021 to July 2022) compared with the prepandemic period (January 2018 to December 2019).

RESULTS: There were 51,355,577 beneficiaries in the prepandemic period and 55,214,638 in the late pandemic period with CV risk factors or CVD. Hospital visit rates were lower in the late pandemic period compared with the prepandemic period (aIRR: 0.918; 95% CI: 0.915-0.922), and declines were evident among rural and urban beneficiaries, as well as across all levels of social vulnerability and in both fee-for-service and Medicare Advantage. In contrast, use of outpatient visits was higher during the late pandemic period (aIRR: 1.141; 95% CI: 1.134-1.149); these increases were on average higher among urban communities and Medicare Advantage beneficiaries. Mortality was higher during the late pandemic period (aIRR: 1.248; 95% CI: 1.240-1.257), and surges in mortality among this population tracked with national COVID-19 mortality. Beneficiaries in the most socially vulnerable communities (aIRR: 1.116; 95% CI: 1.106-1.124) and those covered by Medicare Advantage (aIRR: 1.342; 95% CI: 1.329-1.356]) experienced the greatest increase.

CONCLUSIONS: In the later stages of the COVID-19 pandemic, among Medicare beneficiaries with CV risk factors or established CVD, hospitalizations were lower than before the pandemic, outpatient care was used more frequently, and mortality was significantly elevated across risk groups and geographies, with the greatest increases seen in vulnerable communities and those covered by Medicare Advantage.

BACKGROUND: Axillary and inferior periscapular pain often presents with scapulothoracic abnormal motion and observable winging and can be debilitating for patients. Our hypothesis is that endoscopic long thoracic nerve (LTN) decompression in the thoracic segment is effective at improving axillary and inferior periscapular border pain.

METHODS: A retrospective chart review was performed of all patients diagnosed with persistent axillary and inferior periscapular border pain receiving endoscopic LTN decompression at a single institution, performed by 2 surgeons between 2020 and 2024. Patient demographics and patient pre- and postoperative patient-reported outcome measures were collected.

RESULTS: Thirty-one patients receiving endoscopic LTN decompression were identified and included for analysis. The average follow-up was 25.1 ± 10.9 months, with an average patient age of 45.2 ± 18.1 years. Fifteen (n = 15/31; 48.4%) had prior ipsilateral upper-extremity surgery. Nineteen (n = 19/31; 61.2%) patients received a concomitant pectoralis minor release, 11 (n = 11/31; 35.5%) arthroscopic brachial plexus neurolysis, 10 (n = 10/31; 32.2%) arthroscopic scapulothoracic decompression, and 2 biceps tenodesis (n = 2/31; 6.5%) at the time of their arthroscopic LTN decompression. Visual analog scores (VAS) (7.7 ± 2.1 vs. 2.7 ± 2.7; P < .001) and subjective shoulder value (38.0 ± 24.2% vs. 85.6 ± 8.2%; P = .02) significantly improved after surgery. Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form 7a (P = .35), PROMIS global physical (P = .58), PROMIS mental health (P = .65), and quick disabilities of the arm, shoulder, and hand (P = .11) did not significantly change after surgery. Measured forward elevation (127 ± 41° vs. 157 ± 10°; P = .003), abduction (117 ± 29° vs. 136 ± 14°; P = .01), and external rotation (54 ± 19° vs. 58 ± 4°; P = .009) significantly improved after surgery, while internal rotation (L1 ± 3 levels vs. T11 ± 2 levels; P = .11) remained unchanged. There were 4 (n = 4/31; 12.9%) complications characterized as persistent pain after surgery. There was one revision endoscopic LTN release (n = 1/31; 3.2%). There was no predictive patient (age, sex, body mass index, American Society of Anesthesiologists score, smoking status, diabetes, prior ipsilateral surgery) or surgical (operating room time) factors predisposing to surgical complications using logistic regression.

CONCLUSION: Thoracic-based, endoscopic decompression of the LTN improves pain, patient-reported outcome measures, and range of motion with minimal complications. Further study is required to determine long-term pain relief and outcomes.

The connectivity and interdependence of our world and its inhabitants' health have come under increasing focus. Elucidation of the common and interdependent mechanisms of health and disease requires approaches that facilitate understanding of complex systems behavior and probing of both individual and collective system parameters. To this end, multiscale physical and computational modeling offers a particularly powerful tool to predict behavior over vast time and length scales. Other novel technologies, e.g., rapid isolation nanotechnology developed to analyze nanoscale small extracellular vesicles in ocular tears, enable tracking of "fingerprints" from diseases as diverse as ocular to neurodegenerative (e.g., dementia) and cancer. In the future, it will be possible to track the health and disease of ecosystems and their inhabitants, using geospatial and epidemiological approaches, as well as novel biotechnologies, to prevent and mitigate disease processes and enhance well-being. These concepts are applied by way of an exemplary approach to understand and address the impact of toxic, recalcitrant manmade chemicals (i.e., PFAS) on the health of ecosystems and their diverse inhabitants. Such convergent efforts will be necessary and a priority for solving the complex problems threatening the health of our planet and its inhabitants.