David A. Williams

Identifying the neural correlates of chronic pain and their relationship to clinically relevant measures of disease has proven challenging due to high variability in individual patterns of functional brain connectivity and the rarity of ecologically valid scanning paradigms. Here, we address these limitations using data from the Multidisciplinary Approach to the Study of Pelvic Pain Symptom Patterns Study, which recruited a large sample of urologic chronic pain patients (n = 382) imaged repeatedly (range = 2-4) over 36 months. Intrinsic brain connectivity was recorded before and after a naturalistic challenge designed to elicit symptomatic pain and discomfort. Linear mixed-effects models revealed 2 neuroanatomically distinct patterns: pain at the time of scan was linked to connectivity within sensory-discriminative regions, while past-week recalled pain was associated with distributed patterns across regions implicated in memory, salience, and affective processing. These findings emphasize the dynamic roles of brain regions for different aspects of chronic pain.

Background: Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods: Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results: Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions: BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

Background Chronic spinal pain with widespread symptoms often responds poorly to peripherally focused treatments. Cognitive-behavioral therapy (CBT) can help but typically yields modest effects. This trial evaluated whether adding resilience-enhancing activities to medical assistant-coached CBT (PRISM-CBT) improves outcomes. Methods Adults with spinal pain and fibromyalgia symptoms were randomized to PRISM-CBT (n=119), standard CBT (n=120), or usual care (UC; n=60). The primary outcome was the Fibromyalgia Impact Questionnaire-Revised (FIQR) global impact score at 8 weeks (0–100; higher=worse). Secondary outcomes were pain interference and pain severity measured with the Brief Pain Inventory (BPI) (0–10; higher=worse). Results The primary outcome showed no difference between PRISM-CBT and usual care at 8 weeks, with an adjusted between-group difference of 0.20 points (95% CI –4.81 to 5.20, p=0.939). Yet, by 12 months, PRISM-CBT demonstrated a 7.4-point greater improvement compared with usual care (95% CI 0.15 to 14.64, p=0.045) and a 4.8-point greater improvement versus CBT at 8 weeks (95% CI 0.00 to 9.57, p=0.050). PRISM-CBT produced the most consistent benefit in BPI pain interference. Compared with usual care, interference was lower by 0.88 points at both 8 weeks (95% CI 0.25 to 1.50, p=0.006) and 6 months (95% CI 0.23 to 1.54, p=0.009) and by 1.42 points at 12 months (95% CI 0.53 to 2.32, p=0.002). Compared with standard CBT, interference was lower at 8 weeks (0.98 points, 95% CI 0.38 to 1.57, p=0.001), 6 months (0.63 points, 95% CI 0.01 to 1.25, p=0.045), and 12 months (1.92 points, 95% CI 1.09 to 2.76, pConclusions This scalable, medical assistant-coached digital program shows promising benefits, including greater reductions in pain interference and a long-term improvement in global symptom burden, despite no difference at the primary endpoint.

INTRODUCTION: Some patients with chronic pancreatitis (CP) experience nociplastic pain due to central nervous system dysregulation, yet its recognition is limited by the lack of bedside tools. Self-reported body maps are used to assess pain widespreadedness and to differentiate pain mechanisms in chronic pain patients, but their utility in CP is unclear. This study aimed to determine whether pain widespreadedness, measured through a body map, is associated with features of nociplastic pain in CP. METHODS: We conducted a cross-sectional analysis of adults with definite CP enrolled in a single-center longitudinal cohort. Pain widespreadedness was assessed using the Michigan Body Map and categorized by the number of painful regions (0–7) and by the presence of localized vs widespread (≥3 regions) pain. Clinical features of nociplastic pain were measured using validated psychometric and pain surveys. Group comparisons were performed with multivariable regression models adjusted for demographics, comorbidities, and CP characteristics. RESULTS: Among 110 participants (mean age 54 years, 52% male), 93% reported abdominal pain. Of those with abdominal pain, 64% had widespread pain. Increasing the number of painful regions and widespread pain (vs localized) were independently associated with higher pain severity, pain interference, and neuropathic pain scores, as well as more fatigue, impaired physical functioning, greater chronic overlapping pain conditions, and poorer physical and mental health. DISCUSSION: Two-thirds of patients with CP had widespread pain assessed using a body map. This subgroup had more severe symptoms and features of nociplastic pain. This simple tool may facilitate targeted, mechanism-based pain management in CP.

Background: Chronic ocular surface pain (COSP), occurring either in isolation or as part of numerous ocular conditions, such as dry eye syndrome, is a leading cause of eye care visits in the United States. Conventional treatments directed at the ocular surface—the perceived pain source—are often inadequate for pain relief. We hypothesize that some individuals with COSP are experiencing symptoms driven by central nervous system (CNS) dysfunction, similar to chronic overlapping pain conditions, rather than solely pathological problems in the eye. Some individuals with chronic overlapping pain conditions (eg, fibromyalgia) show evidence of nociplastic pain mechanisms, where the pain results from amplified or dysregulated CNS signaling and sensory processing. Although data exist suggesting the presence of nociplastic pain features in COSP, there is a need for comprehensive studies. Objective: Our aim is to rigorously define the role of nociplastic pain in COSP with a large, representative cohort of 200 participants with COSP using established clinical, neurobiological, and treatment response features. We propose that as sign and symptom discordance increases, features indicative of nociplastic pain will also increase. Methods: In aim 1, we will clinically phenotype participants with COSP, using validated patient-reported outcome measures and standard ocular exams. In aim 2, we will compare the neurobiological features of nociplastic pain across the discordance spectrum among a subset of aim 1 participants using multimodal evoked sensory testing (pressure, thermal, and visual testing) at sites both local to and remote from the eye. Participants will also complete structural and functional brain magnetic resonance imaging to assess regions important for pain perception and modulation. In aim 3, we will examine and validate predictors of COSP pain responses before and after application of a topical anesthetic to the ocular surface, which should block peripherally induced discomfort to allow for clarification of pain origination. Results: We received funding for this project in August 2024. Recruitment and enrollment began in January 2025 after protocol development and piloting were completed. This study is ongoing with 59 participants enrolled and 51 participants completing the study visits as of January 2026. Conclusions: Findings from the study have the potential to fundamentally change the way ocular pain syndromes are conceptualized, diagnosed, and treated. This work will not only help identify new CNS-directed pain treatments for a subset of patients with COSP but also help us better understand why many peripherally directed therapies are destined to be ineffective in a subset of individuals experiencing COSP. International Registered Report Identifier (IRRID): DERR1-10.2196/84240

PCORnet ^® , a national resource funded by the Patient-Centered Outcomes Research Institute, is designed to enhance the nation’s capacity to conduct efficient, patient-centered health research. The robust and adaptable PCORnet infrastructure can be leveraged to support a variety of study designs. Within this framework, PCORnet ^® Studies, a distinguished subset of research studies that meets specific criteria and approval, serve as exemplary models of patient-centered research, standing out for their rigorous adherence to criteria that elevate the quality and impact of research. Over the past 10 years, over 300 studies have been completed using the PCORnet infrastructure, including 58 studies that have earned the distinction of being a meritorious PCORnet ^® Study, of which 19 have been completed. We explore several of these efforts, highlighting the study archetypes supported by the PCORnet infrastructure, as well as the clinical therapeutic areas of these studies, funding sources, and breadth of PCORnet institutional users. We also provide lessons learned from our accumulated experience that translates the PCORnet infrastructure into a continuously learning framework and highlight unique capabilities of the PCORnet infrastructure supporting innovation in future trials.

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: Chronic ocular surface pain (COSP), occurring either in isolation or as part of numerous ocular conditions, such as dry eye syndrome, is a leading cause of eye care visits in the United States. Conventional treatments directed at the ocular surface—the perceived pain source—are often inadequate for pain relief. We hypothesize that some individuals with COSP are experiencing symptoms driven by central nervous system (CNS) dysfunction, similar to chronic overlapping pain conditions, rather than solely pathological problems in the eye. Some individuals with chronic overlapping pain conditions (eg, fibromyalgia) show evidence of nociplastic pain mechanisms, where the pain results from amplified or dysregulated CNS signaling and sensory processing. Although data exist suggesting the presence of nociplastic pain features in COSP, there is a need for comprehensive studies. Objective: Our aim is to rigorously define the role of nociplastic pain in COSP with a large, representative cohort of 200 participants with COSP using established clinical, neurobiological, and treatment response features. We propose that as sign and symptom discordance increases, features indicative of nociplastic pain will also increase. Methods: In aim 1, we will clinically phenotype participants with COSP, using validated patient-reported outcome measures and standard ocular exams. In aim 2, we will compare the neurobiological features of nociplastic pain across the discordance spectrum among a subset of aim 1 participants using multimodal evoked sensory testing (pressure, thermal, and visual testing) at sites both local to and remote from the eye. Participants will also complete structural and functional brain magnetic resonance imaging to assess regions important for pain perception and modulation. In aim 3, we will examine and validate predictors of COSP pain responses before and after application of a topical anesthetic to the ocular surface, which should block peripherally induced discomfort to allow for clarification of pain origination. Results: We received funding for this project in August 2024. Recruitment and enrollment began in January 2025 after protocol development and piloting were completed. This study is ongoing with 59 participants enrolled and 51 participants completing the study visits as of January 2026. Conclusions: Findings from the study have the potential to fundamentally change the way ocular pain syndromes are conceptualized, diagnosed, and treated. This work will not only help identify new CNS-directed pain treatments for a subset of patients with COSP but also help us better understand why many peripherally directed therapies are destined to be ineffective in a subset of individuals experiencing COSP.

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5–12) and youths (ages 12–20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes are examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity is confirmed via PCR, serology, or antigen tests, while negativity requires negative test results and no related diagnoses. Risk differences reveal higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children face increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibit elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.