The Journal of Pain

BackgroundPersistent Spinal Pain Syndrome (PSPS) type II represents a challenging clinical entity with limited therapeutic options. Various spinal cord stimulation (SCS) modalities have emerged as potential treatments, but their comparative effectiveness remains unclear. ObjectiveOur goal in this paper is to systematically evaluate and compare the efficacy of different SCS modalities in patients with PSPS type II through meta-analysis of available randomized controlled trials. Evidence ReviewWe conducted a systematic review following PRISMA guidelines, searching major databases for randomized controlled trials evaluating SCS modalities in PSPS type II patients until the end of May 2025(search updated on October 3rd). Primary outcomes included pain intensity (VAS) and functional disability (ODI) at 6 and 12 months. Subgroup analyses compared tonic versus burst stimulation and high-frequency versus low-frequency SCS. FindingsNine randomized controlled trials were included, encompassing 565 patients across different SCS modalities. For the primary outcome of clinically meaningful pain relief ([&ge;]50% reduction), pooled analysis demonstrated that 45% (95% CI: 18-75%, I{superscript 2} = 92.2%) of patients achieved this threshold for back pain and 55% (95% CI: 45-65%, I{superscript 2} = 0%) for leg pain. Subgroup analysis revealed significant differences in back pain responder rates by stimulation modality: High-frequency SCS demonstrated responder rates of 92% (95% CI: 79-98%) versus 28% (95% CI: 13-49%) for conventional frequencies (p < 0.001). For leg pain, no significant difference was observed between tonic (51%, 95% CI: 37-65%) and burst stimulation (60%, 95% CI: 45-74%, p = 0.36) and mean VAS scores demonstrated significantly lower pain with high-frequency SCS (13.30, 95% CI: 8.82-17.78) compared to conventional frequency (28.42, 95% CI: 24.02-32.88, p<0.0001). For back pain, mean VAS scores decreased from a baseline of 73.03 to 41.67 (95% CI: 36.12-47.22, I{superscript 2}=22.8%) at 6 months and remained stable at 35.66 (95% CI: 25.39-45.93, I{superscript 2}=75.0%) at 12 months. Leg pain showed more pronounced improvement, with VAS scores declining from a baseline of 61.81 to 23.75 (95% CI: 17.69-29.81, I{superscript 2}=78.8%) at 6 months and 29.16 (95% CI: 24.81-33.52, I{superscript 2}=0%) at 12 months). Meta-regression identified longer pain duration and older age as positive predictors of response, while higher baseline leg pain predicted lower responder rates. Serious adverse events occurred in 10%, with a 16% revision surgery rate. Only two studies demonstrated a low risk of bias across all domains. ConclusionsCurrent evidence demonstrates that various SCS modalities provide clinically meaningful pain relief in PSPS type II patients, with approximately half achieving [&ge;]50% pain reduction. High-frequency SCS shows significantly superior responder rates for back pain compared to conventional tonic stimulation, while burst stimulation yields significantly superior reductions in continuous pain intensity metrics. However, the limited number of studies, substantial heterogeneity, and lack of head-to-head comparisons prevent definitive recommendations regarding optimal stimulation parameters. Future large-scale randomized trials with standardized protocols and responder-based outcomes are needed to establish evidence-based treatment algorithms for PSPS type II patients.

New-onset chronic pain is a common and debilitating symptom of Long COVID (LC) that remains not fully understood in terms of pathophysiology and therapeutic targets. A growing body of evidence in chronic pain syndromes similar to LC demonstrates an association between EEG alpha oscillatory activity and the experience of pain, with clinical studies showing maladaptive changes in oscillatory activity, particularly a slowing of alpha activity. This study aims to investigate the association between EEG alpha oscillatory activity and pain perception in new-onset LC-chronic pain. We recruited 31 individuals (20 females) with a clinical diagnosis of LC reporting new-onset chronic pain and 31 healthy pain-free age-and sex-matched controls. Participants completed questionnaires regarding symptoms and psychological functioning prior to recording eyes-open resting-state EEG. Peak alpha frequency (PAF) and spectral power within the alpha band (8-13 Hz) were extracted from EEG signals. Lower PAF over the posterior scalp region was significantly associated with higher LC-chronic pain severity when controlling for age and depression. This observation was consistent across PAF estimation methods. PAF was significantly increased, particularly in the posterior region, in the moderate pain LC subgroup compared to both severe pain subgroup and controls, while alpha power did not differ between the three groups and was not associated with pain severity. Our findings highlight associations between PAF and pain symptoms in a new post-infection chronic pain syndrome. PAF can thus be explored as a potential biomarker and therapeutic target for EEG-based neuromodulation interventions in LC-chronic pain. These results may have implications for other similar chronic pain syndromes. SummaryLower resting-state EEG peak alpha frequency in posterior scalp region is associated with higher severity of new-onset Long COVID chronic pain.

IntroductionChronic pain in fibromyalgia may be driven by abnormal ongoing activity in a subclass of C-fibre nociceptors known as Type1B or CMi nociceptors. As is common in C-nociceptor microneurography studies, the modest patient numbers in these prior studies generate large confidence intervals around the point estimate of the prevalence of this abnormal activity. This complicates the interpretation of the relative importance of this ongoing nociceptor activity as a pain generating mechanism in fibromyalgia. The study aims to improve precision via an adaptive Bayesian protocol that maximises the yield and quality of data collection whilst minimising patient burden. MethodsThe study employs an optimised microneurography protocol with an adaptive study design. The microneurography protocol incorporates early identification of CMi nociceptors via an abbreviated activity dependent slowing protocol to increase yields enabling efficient collection of the primary outcome data. The adaptive study design will use Bayesian principles to iteratively assess the predictive probability of futility, and terminate early if there is high confidence that the hypothesis is false. Furthermore, the study will employ questionnaires to explore links with pain in the area under study to the electrophysiology data. Finally, quantitative sensory testing will be used to investigate whether the irritable nociceptor phenotype is associated with abnormalities in CMi nociceptor physiology. Ethics & DisseminationThis study has received HRA REC approval in the UK. Participants will provide written informed consent, and may withdraw at any time without consequence. At the end of the study, the results will be disseminated through peer-reviewed publication, and the data made available via a data repository. Strengths & limitations of this studyBayesian predictive probability of futility to minimise patient burden in microneurography Microneurography for objective interrogation of the peripheral nervous system Optimised microneurography protocol to efficiently answer primary hypotheses Subjective elements of early termination criteria of the study assessed and co-developed with Patient and Public Inclusion and Engagement Group

BackgroundUnderstanding the associations among biopsychosocial factors is essential for improving research and treatment of chronic low back pain (CLBP). Here we characterized interrelations among biopsychosocial domains using network analysis and identified the most influential features in CLBP. MethodsData came from Quebec Low Back Pain Study, comprising 4,489 CLBP participants. We modeled relationships among baseline biopsychosocial features as networks, where nodes represent features and edges encode statistical or causal dependencies among them. Undirected network was inferred using distance correlation. Directed network was constructed using the Linear Non-Gaussian Acyclic Model, which estimates plausible causal directions. Influence maximization was performed using the Independent Cascade (IC) model to identify the most influential features in each network. ResultsIn the undirected network, physical function and pain interference were the most central nodes, followed by depression. In the directed network, fear of movement, catastrophizing, and widespread pain emerged as key downstream hubs receiving multiple causal inputs, whereas pain interference, physical function, and depression acted as major upstream drivers exerting broad causal influence. IC diffusion simulations further identified pain interference and physical function as the most influential features in the undirected and directed networks, respectively. ConclusionsPain interference, physical function, and depression consistently emerged as key components of the CLBP biopsychosocial network. These features exert causal effects on fear of movement, catastrophizing, and widespread pain, with diffusion analyses confirming their roles as system-wide drivers. Interventions targeting functionality and pain interference, rather than pain intensity alone, may yield broader benefits across psychological and functional domains.

In this randomized, double-blind, controlled trial of 8 weeks of repetitive transcranial magnetic stimulation (rTMS) for chronic pain, we compared the classic primary motor cortex (M1) rTMS with a novel target-selection strategy based on pre-therapy cortical connectivity. Guided by principles of homeostatic plasticity, we tested whether stimulating the cortical site with the lowest pre-therapy global connectivity would be more effective than two active comparators: stimulating the site with the highest pre-therapy global connectivity or stimulating M1 independent of connectivity. Before starting rTMS treatment, TMS-evoked EEG potentials were recorded from four cortical targets: M1, the dorsolateral prefrontal cortex, the anterior cingulate cortex, and the posterosuperior insular cortex. For each target, global connectivity was quantified using a distance-weighted, phase-based index (debiased weighted phase lag index, wPLI) derived from pre- and post-TMS-evoked EEG activity, capturing both the magnitude and spatial extent of TMS-induced oscillatory phase locking across cortical regions. Target allocation in the Low- and High-Connectivity groups was based on this global connectivity measure. Ninety patients with chronic pain were randomized to Low-Connectivity, High-Connectivity, or Classic-M1 groups. Treatment consisted of 12 rTMS sessions delivered over 8 weeks to the assigned target. The primary outcome was the proportion of patients achieving [&ge;] 30% reduction in pain intensity. Secondary outcomes included continuous change in pain intensity, pain interference, sleep, fatigue, mood, quality of life, and patient global impression of change. No between-group differences were observed for primary or secondary outcomes (p > 0.05). In prespecified exploratory analyses, we examined whether pre-therapy local connectivity (within-target wPLI) predicted treatment response. In the Classic-M1 group, lower pre-therapy local M1 connectivity was associated with a greater reduction in pain intensity (r = 0.50, p = 0.005). This association was not observed in the Low- or High-Connectivity groups. A regression model including group-by-connectivity interaction indicated that the relationship between local connectivity and pain reduction differed between the Classic-M1 and High-Connectivity groups (p = 0.038). The results of this clinical trial showed that connectivity-based target allocation using global connectivity did not improve clinical outcomes. However, lower local M1 connectivity was associated with greater pain reduction following Classic-M1 stimulation, suggesting that local M1 connectivity may serve as a potential biomarker of response.

BackgroundReverse total shoulder arthroplasty (rTSA) is an increasingly common surgical procedure often performed to treat pain related to glenohumeral osteoarthritis or to rotator cuff arthropathy. Although surgical outcomes are generally excellent, recent evidence has found that postoperative pain ([&ge;] 3/10) two years following surgery is reported by an estimated 18% of patients. Recently, the NIH Acute-to-Chronic Pain Signatures program recommended longitudinal studies using select biomarkers to describe and predict individual patient responses to surgery. These data are not yet available for rTSA procedures. MethodsThis was a longitudinal cohort study performed at a single academic medical center. Twenty participants undergoing rTSA surgery were included, recruited from a tertiary hospital system in the southern United States. The first objective of this study was to describe changes in general pain intensity (Numerical Pain Rating Scale), widespread body pain, anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), neuropathic pain symptoms (painDETECT), and quantitative sensory testing from baseline to 6 weeks following rTSA. The second objective was to identify the baseline demographic and pain-related factors associated with 6-week postsurgical improvements in pain intensity. ResultsFrom before to after surgery, our cohort demonstrated significant improvement in shoulder pain intensity, widespread body pain, PainDETECT score, and temporal summation magnitude measured at the surgical deltoid. Degree of 6-week pain intensity improvement was associated with baseline pain intensity (F=18.79, p=0.0004) and temporal summation magnitude of the tibialis anterior (F=5.06, p=0.0380). ConclusionsPain intensity, location, nature, and mechanism can serve as biomarkers of the short-term postsurgical changes that can be expected following rTSA. Baseline pain intensity and temporal summation magnitude of the tibialis anterior were associated with the degree of pain improvement, suggesting their use for preoperative risk assessment. Future research should evaluate whether these 6-week biomarker changes are associated with the development of chronic postoperative pain at longer durations after surgery. Level of EvidenceLevel I, Prognostic Study

IntroductionPatients undergoing anterior cruciate ligament (ACL) reconstruction experience substantial postoperative pain, which delays recovery and leads to both immediate and long-term opioid use. In other knee procedures, infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) has demonstrated analgesic and opioid reducing effects. However, the effect in patients undergoing ACL reconstruction has not been investigated. We aimed to investigate the real-world effect of IPACK in patients undergoing ACL reconstruction on immediate postoperative opioid consumption. ParticipantsIn this single-centre difference-in-differences cohort study, all patients who underwent ACL reconstruction surgery at Bispebjerg Hospital, Denmark, from 1 February 2024 to 30 June 2025 are included. The study further includes a similar reference cohort, comprising all patients who underwent trochleaplasty, Elmslie-Trillat, or medial patellofemoral ligament reconstruction during the same period, and at the same hospital. InterventionThe primary exposure is the implementation of IPACK as part of perioperative management for ACL reconstruction on 1 January 2025. The IPACK was performed under ultrasound guidance, immediately before surgery, administering 20 mL of ropivacaine 0.5% between the popliteal artery and the posterior knee capsule. OutcomesThe primary outcome is the cumulative opioid consumption from surgical incision to 2 hours postoperatively. Secondary outcomes include the cumulative opioid consumption from incision to 24 hours postoperatively, the worst reported pain score at 0-24h postoperatively, occurrence of postoperative nausea or vomiting (PONV) 0-24h postoperatively, length of PACU stay, length of hospital stay, and nerve injuries. As an exploratory outcome, carbon dioxide emissions will be investigated. Statistical analysisThe main analysis will be a standard two-way fixed effects DiD regression assessing the changes occurring at the time of implementation of IPACK in the ACL cohort, with adjustment for the underlying time trend. Continuous outcomes are reported as mean difference (95% confidence interval [CI]), and binary outcomes as absolute and relative risks (95% CI).

Resting-state electroencephalography (EEG) has been proposed as a scalable source of biomarkers for chronic pain, but its clinical potential remains uncertain. To systematically evaluate this potential, we benchmarked nine modeling strategies, spanning conventional machine learning with handcrafted features to state-of-the-art deep learning. Across 72 configurations of signal representations and model architectures, we trained models to predict self-reported pain intensity, using chronological age decoding as a positive control. Pain prediction performance was limited (R=0.15), with the best results achieved by conventional connectivity-based models. In contrast, age was robustly decoded from the same dataset (R=0.53), confirming technical efficacy. These findings indicate that resting-state EEG contains limited information about inter-individual differences in chronic pain intensity, making it unlikely to yield clinically actionable biomarkers in cross-sectional settings. Instead, its potential may lie in intra-individual modeling of pain dynamics, which could advance individualized mechanistic insights and more personalized treatment of chronic pain.

BackgroundPeople with hip or knee joint arthroplasties are commonly advised to avoid high-impact physical activities, despite increasing demand to return to sport and vigorous exercise. Current implant testing standards do not reflect real-world loading during high-impact tasks, and few studies have quantified implant loads in high-functioning individuals who have returned to such activities. MethodsHigh-functioning adults with a total hip arthroplasty (THA, n = 11), total knee arthroplasty (TKA, n = 4), or unicompartmental knee arthroplasty (UKA, n = 3) performed a range of low-to high-impact activities, including walking, running, hopping, countermovement jumps, landings, and change-of-direction tasks. Three-dimensional trunk and lower-limb kinematics and ground reaction forces were collected. Musculoskeletal modelling was used to quantify three-dimensional hip and knee joint contact forces. Linear mixed-effects models were used to rank implant loads across activities and to compare peak resultant joint loads with healthy controls from a prior study. ResultsFor people with THR, relative to walking, a 45{degrees} change of direction generated the highest predicted hip contact force (8.38 BW, 95% CI 7.70-9.06), followed by running and unilateral hopping (all >1.5x walking, p < 0.05). Unilateral hopping and running produced the highest predicted knee contact force in TKA and UKA participants (8.0-9.1 BW), and both significantly greater than walking (p < 0.05). Compared with healthy controls, THA participants exhibited a lower predicted HCF during walking (-1.58 BW, 95% CI -2.46 to -0.69), but no group differences were observed for running, hopping, or jumping. ConclusionHigh-impact activities vary widely in model-estimated hip and knee contact forces. Several tasks were not substantially higher than walking. These data provide a biomechanical basis for evidence-informed activity prescription, regulatory implant testing, and future computational simulation of implant performance under realistic loading conditions.

BackgroundThoracic spine mobilization (TSM) has been proposed to influence autonomic nervous system (ANS) activity, yet evidence remains inconsistent and feasibility of standardised protocols is unclear. This study aimed to evaluate whether a randomized TSM protocol can be implemented successfully in healthy participants and to provide preliminary estimates of its effects on heart rate variability (HRV) and heart rate (HR). MethodsA randomized feasibility trial was conducted with healthy young adults receiving six manual therapy sessions consisting of rotational mobilizations above Th5 over 14 days. Feasibility outcomes included adherence, absence of unexpected adverse events (UAE), and practicality of autonomic data acquisition. Physiological outcomes comprised HRV parameters, high-frequency (HF), low-frequency/high-frequency ratio (LF/HF) and HR, analyzed using autoregressive (AR) and fast Fourier transform (FFT) methods. ResultsProcedural safety and methodological integrity were confirmed (no UAE; complete datasets), but feasibility was only partially achieved due to adherence shortfalls, higher attrition, and device-related delays. Physiologically, large effect sizes were observed in the intervention group: at evening assessment, HF_AR showed ES = 0.80 (p = .008); at morning assessment, HF_FFT ES = 0.72 (p = .016), HF_AR ES = 0.78 (p = .010), and LF/HF_AR ES = 0.70 (p = .021). HR remained unchanged. These findings suggest repeated TSM may modulate HRV, primarily through HF-related changes associated with vagal activity, while LF/HF interpretation remains controversial. ConclusionA randomized TSM protocol is safe and methodologically viable with logistical refinements. Preliminary evidence indicates potential vagal modulation, warranting larger trials with respiratory control, ECG-based HRV, multimodal ANS measures, and clinical populations to confirm efficacy and translational relevance.

Background and AimFibromyalgia is an idiopathic chronic widespread pain syndrome affecting 2-4% of the general population globally. Besides widespread fibromyalgia pain, morning stiffness, associated neurologic as well as sleep problems are also reported. Disease is more prevalent in females of middle-age group with low socioeconomic status, thus deteriorating overall productivity and psychosocial health. There is no permanent cure of the disease. This study aimed to explore, validate and assess the effect of four weeks of supervised yogic intervention on pain status, quality of life, sleep, cortical excitability, flexibility and range of motion in fibromyalgia patients, as compared to standard therapy. MethodCase-control study, interventional study and assessor-blined randomized controlled trial, conducted in 120 fibromyalgia patients (60 yoga group: 60 waitlisted controls) and 60 age-matched healthy controls. Pain was assessed subjectively, using questionnaires and objectively, using quantitative sensory testing and ELISA. Sleep and quality of life were assessed using common and disease specific decsiptors. Flexibility and range of motion was assessed using sit and reach box, lateral goniometry and modified Schobers test. Transcranial magnetic stimulation on M1 was used to assess corticomotor excitability of participants. Study parameters were assessed at baseline and after four weeks of the intervention. ResultsA significantly poor sleep, flexibility and quality of life was reported in the fibromyalgia patients due to excruciating pain (VAS = 6.92{+/-}0.12); corticomotor function was also abnormal in the patients, which were restored after four weeks of yogic intervention. On subjective and objective assessment of pain, we found significant relief and improvement in pain status in the yoga group as compared to the waitlisted controls. Fibromyalgia impact, sleep, quality of life and flexibility were also found solely better in fibromyalgia patients undergoing yogic interventions. Cortical parameters, specifically RMT, MEPs and MEP recruitment curves showed a significant improvement in yoga group as compared to waitlisted controls. ConclusionFour weeks of regular and supervised yogic intervention may ameliorate pain, improve flexibility and range of motion and changes cortical plasticity in the Indian cohort of fibromyalgia patients, as compared to standard therapy. Yoga-based interventions can also improve overall quality of life and sleep impairmentsby reducing catastrophization and fibromyalgia impact.

Chronic pain has been identified as a risk factor for cognitive decline in later life. However, most studies measure pain at a single time point and none have investigated whether variations in pain severity are associated with changes in cognitive function over time. This project aimed to assess the relationship between individual-level change in pain severity and decline in cognitive function over time. We used data from the English Longitudinal Study of Ageing (ELSA), a cohort of nationally representative middle aged and older adults. Pain severity was measured at each wave using a 4-point scale (none, mild, moderate and severe) and cognitive function was assessed using 3 objective tests. We applied latent growth curve modelling, a method for longitudinal analysis, to 19,376 ELSA participants data collected over 11 waves, spanning more than 20 years, to examine the relationship between initial level and change of both pain and cognitive function. Adjusting for age and sex, worsening chronic pain severity was associated with accelerated decline in a general measure of cognitive function ({beta} = -0.053, p = 0.039). However, when additionally adjusting for ethnicity, socioeconomic status and comorbid chronic conditions, this association was attenuated to non-significance ({beta} = -0.025, p = 0.365). Greater initial pain severity was associated with steeper decline in cognitive function even in the fully adjusted model ({beta} = -0.104, p < 0.001). Our study suggests that baseline level of pain severity but not worsening pain severity is associated with steeper decline in cognitive function over time. SUMMARYAge- and sex-adjusted analyses find that higher baseline and worsening pain severity predict faster cognitive decline; only baseline pain remains significant after full adjustment.

BackgroundCannabinoid hyperemesis syndrome (CHS) is characterized by episodes of severe nausea, vomiting, and abdominal pain among those with heavy cannabis use. We estimated differences between those reporting CHS symptoms and other daily and less frequent cannabis users on drug use, psychiatric problems, other health problems, antisocial behavior, and personality. MethodsThe National Firearms, Alcohol, Cannabis, and Suicide survey was administered to 7034 US adults in 2025. Survey items assessed substance use, common psychiatric symptoms, personality traits, and symptoms of CHS. ResultsThose with CHS symptoms reported the highest rates and greatest variety of drug use compared to others who used cannabis. Those with CHS symptoms reported higher rates of other drug use than those who used cannabis daily without CHS symptoms across a variety of drug classes, including opioids, hallucinogens, and sedatives, higher rates of drug overdoses, and greater use of all drug classes than those with less-than-daily cannabis use. Those with CHS symptoms also reported more depression, anxiety, sleep problems, chronic pain, antisocial behavior, intimate partner violence, and disinhibited personality traits than those who used daily (mean d = 0.58) and less frequently (mean d = 0.69) and those with no cannabis use in the past 12 months (mean d = 0.99). ConclusionsThose with CHS symptoms exhibit a variety of psychological and behavioral problems including higher rates of other drug use, psychiatric symptoms, antisocial behavior, and dysfunctional personality traits. Results highlight the importance of understanding and addressing the broader psychosocial challenges faced by people experiencing CHS symptoms. Highlights O_LICHS symptoms are linked to greater polysubstance use and overdose risk C_LIO_LICHS symptoms are associated with depression, anxiety, sleep, and pain problems C_LIO_LICHS tied to antisocial behavior and intimate partner violence C_LIO_LICHS shows disinhibited personality traits and low well-being C_LIO_LINational survey identifies high-risk psychosocial CHS profile C_LI

Purpose: Human anatomy remains foundational to clinical practice, yet reduced instructional hours raise concerns about graduate competence and preparedness for patient care. Although trainees often report confidence, supervisors may perceive deficiencies, creating a gap between self-assessment and external evaluation. This study examined stakeholder perspectives on anatomical competence within physical therapy education to identify areas of discordance in perceived capability. Methods: A cross-sectional web-based survey collected responses from 165 stakeholders associated with an entry-level Doctor of Physical Therapy program featuring a 16-week dissection curriculum. Participants rated four domains of anatomical competence using a 5-point ordinal scale. Group differences were analyzed with the Kruskal-Wallis test appropriate for ordinal data. This methodology ensured robust assessment of stakeholder perceptions and comparative analysis. Results: Median ratings of preparedness and capability were 4 of 5 (quite prepared). Significant discordance emerged in three domains: recent graduates rated their foundational knowledge and ability to explain complex concepts to lay audiences higher than faculty or clinical instructors, whereas faculty expressed lower confidence in graduates' ability to explain patient symptoms using anatomical principles. No significant differences were observed in the ability to describe structures by location, suggesting shared perceptions of basic anatomical understanding despite variation in applied reasoning. Conclusions: Stakeholders generally viewed graduates as well prepared, yet disagreement persisted regarding clinical application of anatomical knowledge. Faculty skepticism about symptom explanation indicates that mastery of anatomy alone does not guarantee clinical reasoning. Curricular strategies emphasizing vertical integration and explicit connections between anatomical science and patient-centered reasoning may help bridge perception gaps and enhance professional competence.

2- AbstractO_ST_ABSOBJECTIVEC_ST_ABSTo compare, in a Brazilian population, the clinical efficacy and quality-of-life (QoL) impact of one-stage bilateral thoracic sympathectomy (BTS) versus unilateral sympathectomy on the dominant side (UniS), with additional analysis of patients who later underwent contralateral surgery (two-stage bilateral, 2stS). METHODSProspective, randomized, controlled, multicenter trial (11 centers) including 163 adults with primary palmar hyperhidrosis. Participants were randomized 1:1 to BTS or UniS. From 6 months onward, UniS patients could elect contralateral sympathectomy (2stS). Sweating severity was assessed using the Hyperhidrosis Disease Severity Scale (HDSS) across 18 anatomical sites at each visit. Compensatory sweating (CS) was defined as new sweating in previously unaffected areas (preoperative HDSS = 1) and graded by the magnitude of HDSS increase. QoL was measured with two complementary validated instruments: HidroQOL and the Horn questionnaire. RESULTSBaseline characteristics were similar between groups, with most participants presenting severe preoperative disease. Improvement in the operated (dominant) hand was comparable after BTS and UniS, whereas control of the non-operated hand favored BTS. In the UniS group, spontaneous contralateral improvement occurred in approximately one-seventh of untreated hands. The proportion of patients without CS was similar in both groups ([~]25%), but severe CS was more frequent after BTS (40.4% vs 21.0%, p = 0.0344). QoL improved in both groups, with larger and more sustained reductions in Horn and HidroQOL scores after BTS (p < 0.001). In the 2stS subgroup, contralateral surgery produced a consistent HDSS decrease and marked QoL improvement, with predominantly mild additional CS. CONCLUSIONSBTS provides more complete symptom control and greater QoL improvement, but at the cost of more severe CS. UniS offers excellent control on the treated side, may reduce severe CS, and supports a staged strategy in which some patients avoid a second procedure (requested by 22.5% in this study); when needed, contralateral completion tends to restore additional clinical and QoL gains.

BackgroundRecreational cannabis legalization has expanded rapidly across US states. The regulatory approaches states adopt vary widely, with varying implications for public health. This study aimed to characterize heterogeneity in recreational cannabis laws (RCLs) across US states and to identify state-level characteristics associated with these regulatory models. MethodsWe conducted Latent Class Analysis (LCA) of state-year RCL provisions from 2013 to 2024 (n=612) to identify distinct RCL approaches. Descriptive analyses and exploratory multinomial regression analyses were used to examine correlations between state characteristics and RCL approaches from 2020 to 2024, when sufficient cross-state variation in RCL adoption was available. Eleven recreational cannabis policy provisions spanning governance, potency limits, consumption restrictions, access controls, taxation, marketing regulations, and driving prohibitions are primarily from the Alcohol Policy Information System. State-level characteristics included cannabis use prevalence, market conditions, medical cannabis history, political factors, demographic, and socioeconomic covariates obtained from multiple secondary data sources. ResultsWe identified four latent classes of state-year RCL provisions representing different regulatory approaches: No RCL, Pre-commercial, Full Access, and Dispensary Access. The No RCL corresponded to state-years without RCL. The Pre-commercial class represented state-years in early-stage legalization with a minimal regulated approach in terms of commercial infrastructure. The Full Access class was characterized by permitting on-site retail consumption and home delivery and restricting (but not prohibiting) public use. In contrast, the Dispensary Access class limited retail sales to off-site consumption only, prohibited public use, and imposed stricter market controls. Higher past-month cannabis use prevalence was associated with a greater likelihood of membership in the Full Access class (RRR = 1.78; 95% CI: 1.21-2.62), relative to No RCL. A longer duration since medical cannabis legalization was associated with a higher likelihood of membership in the Dispensary access class (RRR = 1.47; 95% CI: 1.02-2.12). Higher beer excise taxes were associated with a lower likelihood of membership in any RCL class relative to No RCL. ConclusionsFrom 2013 to 2024, US recreational cannabis regulations clustered into four distinct regulatory approaches, with two distinct commercial models: one permitting on-site retail consumption and home delivery, the other restricting sales to off-premises only and prohibiting public use. Higher cannabis use prevalence and longer medical cannabis history were associated with more access-oriented and more restrictive commercial approaches, respectively.

BackgroundIndividuals with severe mobility impairments (SMI) often experience significant psychological distress and chronic pain. Virtual walking (VW) presents an innovative rehabilitation approach to improve mood and alleviate pain. This study aimed to develop a home-based VW system with integrated mood and symptom tracking and to report on its feasibility and usability in a user study with individuals with SMI. MethodsA multidisciplinary, iterative frame-work guided the systems development. Following initial contextual research and design iterations, a user study was conducted with 11 participants with SMI. A repeated measures pre-post design was employed. Feasibility and usability were primarily assessed through post-study qualitative interviews, analyzed via content analysis. Changes in mood and symptoms were measured immediately before and after each session. Momentary mood was captured using an in-virtual reality (in-VR) two-dimensional (2D) affect grid, while embedded single-item state ratings were used to track anxiety, depressed mood, and pain. Daily mood changes and symptom trajectories were analyzed using logistic regression and generalized estimating equations (GEE), respectively. ResultsContextual research guided the system design towards enhancing accessibility, ergonomics, and therapeutic engagement. The final VW system featured three core modules: locomotion, multi-sensory feedback, and mood/symptom tracking. Qualitative analysis of the user study revealed high acceptance for the VW system, alongside challenges related to content variety and hardware ergonomics. Each intervention session was significantly associated with an immediate positive mood shift (odds ratio (OR) = 1.83), as measured by the affect grid. Furthermore, GEE models revealed a significant reduction in self-reported depression and anxiety symptoms over the intervention period (all P < 0.01). ConclusionsThis study confirms the feasibility and acceptability of the novel VW system for home-based use by individuals with SMI. The preliminary evidence suggests the system has high potential as a tool for improving mood and alleviating psychological distress. Future large-scale randomized controlled trials are warranted to establish its clinical efficacy. Trial registration numberNCT07073144-07/17/2025.

ObjectiveAs cannabis use has increased in the United States, so has cannabinoid hyperemesis syndrome (CHS), a disorder characterized by severe nausea, vomiting, and abdominal pain among heavy cannabis users. We previously showed that CHS symptoms are associated with several behavioral and psychological characteristics linked to psychosocial impairment. We examined links between CHS symptoms and suicidal thoughts, behaviors, and proximal suicide risk factors. MethodsWe used data from the National Firearms, Alcohol, Cannabis, and Suicide survey, a nationally representative survey of 7,034 US adults. Items assessed symptoms of CHS and suicidal thoughts and behaviors. Comparisons focused on: those with daily cannabis use and CHS symptoms (n = 191), those with daily cannabis use without CHS symptoms (n = 882), those with past year cannabis use but not daily use (n = 1288), and those without past year cannabis use (n = 4673). ResultsThose with CHS symptoms reported the highest prevalence of suicidal thoughts and behaviors with most lifetime rates being significantly higher than those with daily cannabis use without CHS symptoms. Those with CHS symptoms also reported higher mean-levels of thoughts and feelings associated with suicide (i.e., perceived burdensomeness, thwarted belongingness, defeat, entrapment) than all the other groups. ConclusionsThose with CHS symptoms reported especially high rates of suicidal thoughts, behaviors, and attempts even when compared to others with daily cannabis use. People with CHS symptoms appear to be at high risk of suicide, possibly related to distress from their gastrointestinal symptoms and psychiatric, substance use, and medical comorbidities.

BackgroundSedentary behavior is highly prevalent following traumatic brain injury (TBI) and compounds existing risks for cardiovascular, neurodegenerative, and affective disorders. The cognitive and behavioral sequelae of TBI, including impaired decision-making, blunted reward processing, and cognitive fatigue, create particular barriers to adopting and maintaining an active lifestyle. Despite this, effective behavior change interventions targeting physical activity in community-dwelling TBI survivors remain scarce. Here, we evaluated the feasibility, compliance, and preliminary efficacy of a 12-week remotely delivered walking intervention combining planning, behavioral reminders, and monetary micro-incentives. MethodsFifty-six adults aged 40-80 years with a mild-to-moderate TBI diagnosed between 3 months and 15 years prior were randomized to either a planning, reminders, and micro-incentives intervention (n=23) or a health advice control condition (n=25). Participants wore a Fitbit Inspire 3 continuously throughout the study. Intervention participants completed weekly phone calls to plan five 30-minute walks for the following week, received daily text message or email reminders on planned walk days, and earned small monetary incentives upon walk completion. Control participants received weekly health education calls. Feasibility was assessed through recruitment, retention, and adverse event rates. Compliance was assessed via phone call completion rates and Fitbit wear time. Efficacy outcomes included weekly walk counts, walking duration, and step counts, modeled using Poisson generalized linear mixed models and linear mixed-effects models over 12 weeks. ResultsForty-eight participants completed the study (retention rate: 84.2%), with high phone call compliance in both groups (intervention: 98.4%; control: 98.1%). Intervention participants completed significantly more walks than controls from week 1 onward (aIRR = 5.33, 95% CI: 2.27-12.5, p < 0.001), with the group difference growing over time (interaction aIRR = 1.09 per week, 95% CI: 1.01-1.17, p = 0.029). Estimated marginal means indicated that intervention participants completed 5.5 times more walks than controls at week 1, increasing to 15.5 times more by week 12. The intervention group also walked significantly longer at week 1 (b = 62.14 min, 95% CI: 1.05-123.23, p = .046), with the advantage growing over time; by week 12, intervention participants walked 5.3 times longer than controls. Similarly, the intervention group accumulated significantly more steps during walks at week 1 (b = 4,779 steps, 95% CI: 45.50-9,513.00, p = .048), accumulating 3.1 times more steps than controls by week 12. ConclusionsA remotely delivered, multicomponent walking intervention targeting planning, behavioral reminders, and micro-incentives was feasible, well-tolerated, and produced meaningful increases in walking activity in community-dwelling adults with TBI. With high retention and compliance, and consistent effects on walk counts, duration, and steps across the intervention period, these findings provide compelling support for a larger, fully powered trial.

Executive dysfunction affects nearly 50% of individuals with traumatic brain injuries (TBI), yet interventions targeting the underlying neural mechanisms remain limited. This study examined whether aerobic exercise modulates functional connectivity to improve executive function in individuals with mild TBI and identified the neural pathways mediating these improvements. In this secondary analysis of a 12-week pilot randomized controlled trial, participants with mild TBI (n=24) were randomized to aerobic exercise (n=12) or active balance control (n=12). Resting-state fMRI with multivariate pattern analysis revealed that aerobic exercise selectively altered functional connectivity patterns of the anterior cingulate cortex (ACC) compared to balance control. Post-hoc seed-to-voxel analyses identified widespread ACC connectivity differences between groups post-intervention while controlling for baseline, across 19 cortical regions spanning default mode, frontoparietal control, and salience networks. Critically, greater anticorrelation between the ACC and insula following aerobic exercise was associated with improved Trail Making Test B-A performance in the aerobic group ({beta}=46.92, p=0.04) but not the balance group, indicating that participants who developed stronger ACC-insula functional segregation showed greater reductions in executive function completion times. These findings establish the ACC-insula circuit as a critical neural substrate mediating exercise-induced executive function recovery after TBI and identify this pathway as a promising therapeutic target for exercise-based rehabilitation interventions.