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Objective: To assess the efficacy, tolerability, and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol (E2), compared with placebo, for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women.Methods: Women with moderate to severe vasomotor symptoms (seven or more per day or 56 per week average) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 (n = 113) or 100 microg per day E2 (n = 112), or a placebo vaginal ring (n = 108). Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale. Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology. Participant satisfaction with the vaginal ring was evaluated via questionnaire.Results: Vasomotor symptoms significantly improved in both treatment groups, compared with placebo (P <.05). There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo. For women with vaginal atrophy at baseline (n = 60), the maturation index improved significantly in both treatment groups compared with placebo. Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups (P <.05) compared with placebo. The vaginal rings were well tolerated. Most adverse events were mild or moderate and consistent with estrogen therapy.Conclusion: A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms, compared with placebo. The E2 vaginal ring was well tolerated. [ABSTRACT FROM AUTHOR]

Context: The COVID-19 pandemic exposed governmental public health's outdated information technology and insufficient data science and informatics workforce capacity. The Centers for Disease Control and Prevention's Public Health Informatics Fellowship Program (PHIFP) is well positioned to strengthen public health data science and informatics workforce capacity., Program: Established in 1996, PHIFP is a 2-year, full-time, on-the-job training program. PHIFP includes a didactic curriculum, applied learning through informatics projects completed at the assigned host site, short-term technical assistance projects, and a final capstone project., Evaluation: Fellows have learned from and bolstered host site informatics capacity through the development or enhancement of information systems, evaluations, data integration, data visualization, and analysis. Among recent graduates, 54% are employed at Centers for Disease Control and Prevention and 16% are employed at other public health organizations, including local health departments., Discussion: Fellowships such as PHIFP, which recruit and train promising scientists in public health informatics, are important components of efforts to strengthen public health workforce capacity., Competing Interests: The authors declare that they have no conflicts of interests to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Cross-sectional radioanatomic study., Objective: To introduce a classification system using MRI to describe psoas morphology and examine the position of nearby neurovascular structures., Summary of Background Data: Oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) offer sagittal malignment correction and reduced morbidity. LLIF has a higher incidence of nerve injuries, while OLIF has a higher incidence of vascular injuries., Methods: Measurements were completed on the left psoas at the inferior L4 endplate. Class A was designated if the ventral border of the psoas muscle was >2 mm anterior; B if it was ≤ 2 mm anterior or posterior to the vertebral body, and C if >2 mm posterior to the vertebral body ventral border. Modified oblique corridor, measured as the distance between two lines, one at the medial border of the psoas muscle and the other at the lateral border of the nearest vascular structure, and a preferred LLIF trajectory was projected onto an axial image of the left psoas. If the trajectory violated the posterior third of the psoas, it was considered a dangerous approach due to potential iatrogenic nerve injury., Results: 100 patient MRIs (Class A: 44; Class B: 27; Class C: 29) were analyzed. Average modified oblique corridor was 7.49 mm. Modified oblique corridor varied amongst the three types of psoas morphologies (A: 8.99 mm vs. B: 8.10 mm vs. C: 4.66 mm, P=0.040). LLIF trajectory intersected the 'danger zone' in 34.1%, 3.7%, and 0.0% of patients, (P<0.001) respectively., Conclusion: Class A psoas had the largest modified oblique corridor but highest proportion of those with a dangerous LLIF trajectory. Class C psoas had the narrowest modified oblique corridor, but no dangerous LLIF trajectories were identified., Competing Interests: Conflict of Interest declaration: The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Persistent or chronic pain is the primary reason people seek medical care, yet current therapies are either limited in efficacy or cause intolerable side effects. Diverse mechanisms contribute to the basic phenomena of nociceptor hyperexcitability that initiates and maintains pain. Two prominent players in the modulation of nociceptor hyperexcitability are the transient receptor potential vanilloid type 1 (TRPV1) ligand-gated ion channel and the voltage-gated potassium channel, Kv7.2/3, that reciprocally regulate neuronal excitability. Across many drug development programs targeting either TRPV1 or Kv7.2/3, significant evidence has been accumulated to support these as highly relevant targets; however, side effects that are poorly separated from efficacy have limited the successful clinical translation of numerous Kv7.2/3 and TRPV1 drug development programs. We report here the pharmacological profile of 3 structurally related small molecule analogues that demonstrate a novel mechanism of action (MOA) of dual modulation of Kv7.2/3 and TRPV1. Specifically, these compounds simultaneously activate Kv7.2/3 and enable unexpected specific and potent inhibition of TRPV1. This in vitro potency translated to significant analgesia in vivo in several animal models of acute and chronic pain. Importantly, this specific MOA is not associated with any previously described Kv7.2/3 or TRPV1 class-specific side effects. We suggest that the therapeutic potential of this MOA is derived from the selective and specific targeting of a subpopulation of nociceptors found in rodents and humans. This efficacy and safety profile supports the advancement of dual TRPV1-Kv7.2/3 modulating compounds into preclinical and clinical development for the treatment of chronic pain., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2024 International Association for the Study of Pain.)

Context: Public health programs promote numerous tickborne disease (TBD) prevention measures. However, measures are not frequently or consistently performed., Objective: Describe barriers to consistent use of 4 commonly promoted TBD prevention measures., Design: We conducted an online survey (n = 1883) evaluating behaviors regarding TBD prevention measures including conducting tick checks, applying insect repellents, showering/bathing, and applying chemical or natural pesticides to residential yards. Respondents could select reasons for never, rarely, or sometimes performing these measures. Descriptive analysis and logistic regression modeling evaluated associations between the 3 most cited barriers for each measure and select demographic variables., Setting: The survey was administered to residents in high Lyme disease incidence counties of Connecticut and Maryland, 2016-2017., Results: For tick checks (n = 800), the most cited barriers were forgetting (63%), not spending time in tick habitat (28%), and too much trouble (11%). For applying insect repellents (n = 1303), the most cited barriers were forgetting (38%), personal safety concerns (24%), and too much trouble (19%). For showering/bathing 2 hours after outdoor activity in tick habitat (n = 1080), the most cited barriers were being unaware of the prevention measure (51%), too much trouble (18%), and forgetting (18%). For applying chemical pesticides to yards (n = 1320), the most cited barriers were having environmental (45%), pet safety (31%), and personal safety concerns (28%). Lastly, for applying natural pesticides to yards (n = 1357), the most cited barriers were being unaware of natural pesticides (31%), having cost concerns (23%), and not being concerned about ticks on property (16%)., Conclusions: Forgetting, too much trouble, unawareness, and safety concerns were primary barriers to using several TBD prevention measures. Education regarding effectiveness, safety, and timing may increase uptake of certain measures. These challenges can be difficult to address, highlighting the need for passive TBD prevention measures, such as a Lyme disease vaccine., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: As the incidence and survival rates of patients with cancer continues to grow, an increasing number of people are living with comorbidities, which often manifests as cancer-induced bone pain (CIBP). The majority of patients with CIBP report poor pain control from currently available analgesics. A conotoxin, Contulakin-G (CGX), has been demonstrated to be an antinociceptive agent in postsurgical and neuropathic pain states via a neurotensin receptor 2 (NTSR2)-mediated pathway. However, the efficacy and side effect profile of CGX have never been assessed in CIBP. Here, we evaluated CGX's antinociceptive potential in a rodent model of CIBP. We hypothesized that CGX engages the NTSR2 pathway, providing pain relief with minimal tolerance and motor side effects. Our results demonstrated that CGX intrathecal injection in mice with CIBP attenuated both spontaneous pain behaviors and evoked mechanical hypersensitivity, regardless of their sex. Furthermore, the antinociceptive effect of CGX was dependent upon expression of NTSR2 and the R-type voltage-gated calcium channel (Cav2.3); gene editing of these targets abolished CGX antinociception without affecting morphine antinociception. Examination of the side effect profile of CGX demonstrated that, unlike morphine, chronic intrathecal infusion maintained antinociception with reduced tolerance in rats with CIBP. Moreover, at antinociceptive doses, CGX had no impact on motor behavior in rodents with CIBP. Finally, RNAScope and immunoblotting analysis revealed expression of NTSR2 in both dorsal and ventral horns, while Cav2.3 was minimally expressed in the ventral horn, possibly explaining the sensory selectivity of CGX. Together, these findings support advancing CGX as a potential therapeutic for cancer pain., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Nav1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Nav1.9, SCN11a, that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Nav1.9 has been learned through the study of rodent sensory neurons, and there is only 76% identity between human and rodent homologs of SCN11a, there is reason to suggest that there may be differences in the biophysical properties of the channels in human and rodent sensory neurons, and consequently, the contribution of these channels to the control of sensory neuron excitability, if not pain. Thus, the purpose of this study was to characterize Nav1.9 currents in human sensory neurons and compare the properties of these currents with those in rat sensory neurons recorded under identical conditions. Whole-cell patch clamp techniques were used to record Nav1.9 currents in isolated sensory neurons in vitro. Our results indicate that several of the core biophysical properties of the currents, including persistence and a low threshold for activation, are conserved across species. However, we noted a number of potentially important differences between the currents in human and rat sensory neurons including a lower threshold for activation, higher threshold for inactivation, slower deactivation, and faster recovery from slow inactivation. Human Nav1.9 was inhibited by inflammatory mediators, whereas rat Nav1.9 was potentiated. Our results may have implications for the role of Nav1.9 in sensory, if not nociceptive signaling., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Chronic postsurgical pain (CPSP) is a highly prevalent condition. To improve CPSP management, we aimed to develop and internally validate generalizable point-of-care risk tools for preoperative and postoperative prediction of CPSP 3 months after surgery. A multicentre, prospective, cohort study in adult patients undergoing elective surgery was conducted between May 2021 and May 2023. Prediction models were developed for the primary outcome according to the International Association for the Study of Pain criteria and a secondary threshold-based CPSP outcome. Models were developed with multivariable logistic regression and backward stepwise selection. Internal validation was conducted using bootstrap resampling, and optimism was corrected by shrinkage of predictor weights. Model performance was assessed by discrimination and calibration. Clinical utility was assessed by decision curve analysis. The final cohort included 960 patients, 16.3% experienced CPSP according to the primary outcome and 33.6% according to the secondary outcome. The primary CPSP model included age and presence of other preoperative pain. Predictors in the threshold-based models associated with an increased risk of CPSP included younger age, female sex, preoperative pain in the surgical area, other preoperative pain, orthopedic surgery, minimally invasive surgery, expected surgery duration, and acute postsurgical pain intensity. Optimism-corrected area-under-the-receiver-operating curves for preoperative and postoperative threshold-based models were 0.748 and 0.747, respectively. These models demonstrated good calibration and clinical utility. The primary CPSP model demonstrated fair predictive performance including 2 significant predictors. Derivation of a generalizable risk tool with point-of-care predictors was possible for the threshold-based CPSP models but requires independent validation., (Copyright © 2024 International Association for the Study of Pain.)

Background: The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms., Methods: This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups., Results: There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae., Conclusions: These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other., Competing Interests: Conflicts of Interest: Dean B. Andropoulos, MD has been Medical Officer of SmartTots; he was not involved in funding decisions for the TREX Trial from the SmartTots organization., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Abstract: Chronic posttraumatic pain (CPTP) is common after traumatic stress exposure (TSE) and disproportionately burdens women. We previously showed across 3 independent longitudinal cohort studies that, in women, increased peritraumatic 17β-estradiol (E2) levels were associated with substantially lower CPTP over 1 year. Here, we assessed this relationship in a fourth longitudinal cohort and also assessed the relationship between E2 and CPTP at additional time points post-TSE. Furthermore, we used a well-validated animal model of TSE to determine whether exogenous E2 administration protects against mechanical hypersensitivity. Using nested samples and data from the Advancing Understanding of RecOvery afteR traumA study (n = 543 samples, 389 participants), an emergency department-based prospective study of TSE survivors, we assessed the relationship between circulating E2 levels and CPTP in women and men using multivariate repeated-measures mixed modeling. Male and ovariectomized female Sprague Dawley rats were exposed to TSE and administered E2 either immediately after or 3 days post-TSE. Consistent with previous results, we observed an inverse relationship between peritraumatic E2 and longitudinal CPTP in women only (β = -0.137, P = 0.033). In animals, E2 protected against mechanical hypersensitivity in female ovariectomized rats only if administered immediately post-TSE. In conclusion, peritraumatic E2 levels, but not those at post-TSE time points, predict CPTP in women TSE survivors. Administration of E2 immediately post TSE protects against mechanical hypersensitivity in female rats. Together with previous findings, these data indicate that increased peritraumatic E2 levels in women have protective effects against CPTP development and suggest that immediate post-TSE E2 administration in women could be a promising therapeutic strategy for reducing risk of CPTP., (Copyright © 2024 International Association for the Study of Pain.)

Objective: To understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people living with HIV (PLWH) ≥40 years on antiretroviral therapy (ART) in low- and middle-income countries (LMIC)., Design: We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020-2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA)., Methods: Ten-year CVD risk was calculated using 2019 World Health Organization non-laboratory and laboratory models. Transient elastography (TE) was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by Controlled Attenuation Parameter (CAP) ≥248 dB/m and liver stiffness measurement (LSM) ≥7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4 T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region., Results: There were 1,750 participants from nine LMIC. Median CVD risk was 3% for both non-laboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10% vs. <5%) were OR = 1.83 (95% confidence interval:(CI) = 1.21-2.76; P = 0.004) and OR = 1.62 (95% CI = 0.85-3.07; P = 0.14), respectively. Associations of CVD risk with steatosis were stronger in males and among participants at study sites outside Africa., Conclusions: Higher CVD risk was associated with steatosis but not with significant fibrosis in PLWH in our LMIC cohort., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Over the past 2 decades, the microbiome has received increasing attention for the role that it plays in health and disease. Historically, the gut microbiome was of particular interest to pain scientists studying nociplastic visceral pain conditions given the anatomical juxtaposition of these microorganisms and the neuroimmune networks that drive pain in such diseases. More recently, microbiomes both inside and across the surface of the body have been recognized for driving sensory symptoms in a broader set of diseases. Microbiomes have never been a more popular topic in pain research, but to date, there has not been a systematic review of the preclinical microbiome pain literature. In this article, we identified all animal studies in which both the microbiome was manipulated and pain behaviors were measured. Our analysis included 303 unique experiments across 97 articles. Microbiome manipulation methods and behavioral outcomes were recorded for each experiment so that field-wide trends could be quantified and reported. This review specifically details the animal species, injury models, behavior measures, and microbiome manipulations used in preclinical pain research. From this analysis, we were also able to conclude how manipulations of the microbiome alter pain thresholds in naïve animals and persistent pain intensity and duration in cutaneous and visceral pain models. This review summarizes by identifying existing gaps in the literature and providing recommendations for how to best plan, implement, and interpret data collected in preclinical microbiome pain experiments., (Copyright © 2024 International Association for the Study of Pain.)

Background: Gender dysphoria (GD) refers to psychological distress associated with the incongruence between one's sex and one's gender. In response to GD, birth-registered females may choose to undergo mastectomy. In this systematic review, we summarize and assess the certainty of the evidence on the effects of mastectomy., Methods: We searched MEDLINE, Embase, PsycINFO, Social Sciences Abstracts, LGBTQ+ Source, and Sociological Abstracts through June 20, 2023. We included studies comparing mastectomy to no mastectomy in birth-registered females under 26 years of age with GD. Outcomes of interest included psychological and psychiatric outcomes, and physical complications. Pairs of reviewers independently screened articles, abstracted data, and assessed risk of bias of the included studies. We performed meta-analysis and assessed the certainty of the evidence using the GRADE approach., Results: We included 39 studies. Observational studies (n=2) comparing mastectomy to chest binding provided very low certainty evidence for the outcome of GD. One observational study comparing mastectomy to no mastectomy provided very low certainty evidence for the outcomes global functioning and suicide attempts, and low certainty evidence for the outcome non-suicidal self-injury (aOR 0.47 [95% CI 0.22 to 0.97]). Before-after (n=2) studies provided very low certainty evidence for all outcomes. Evidence from case series (n=34) studies ranged from high to very low certainty., Conclusion: Case series studies demonstrated high certainty evidence for the outcomes of death, necrosis, and excessive scarring; however, these are limited in methodological quality. In comparative and before-after studies the evidence ranged from low to very low certainty., Competing Interests: Disclosure Statement: Management of conflicts of interest: We conducted this SR is part of a research agreement between the Society for Evidence-based Gender Medicine (SEGM), the sponsor, and McMaster University. None of the researchers conducting this SR and meta-analysis received direct financial compensation from the sponsor to conduct this work. The SR and meta-analysis research question was designed through a collaboration between SEGM representatives, independent researchers, and the methods team based at McMaster University. Independent researchers who do not have any financial or intellectual conflicts of interest or disclosures, and the methodology team based at McMaster University (the group of authors) conducted the rest of the SR and meta-analysis processes (i.e., search, data extraction, data analyses, manuscript writing, approval of final draft of manuscript). The methods team was solely responsible for the synthesis and interpretation of results, and for drawing conclusions. To minimize bias, a methodologist who was not involved in the data collection, synthesis, and interpretation (GG) ensured that results interpretation was consistent with the findings. This manuscript was drafted by the methods team and approved by all authors, and the sponsor did not have any say in its content. Conflicts of interest: Dr. Romina Brignardello and Anna Miroshnychenko provided methodological expertise for the SEGM initiative to summarize and appraise the quality of publications related to gender medicine for the SEGM online platform and received financial compensation from SEGM. Dr. Romina Brignardello-Petersen presented preliminary results at the conference titled International Perspectives of Evidence Based Treatment for Gender Dysphoric Youth (New York, 2023). Dr. Yetiani M Roldan, Sara Ibrahim, Dr. Steven Montante and Rachel Couban have no conflicts of interest to report., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Abstract: Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. Univariate analyses were performed to evaluate the association between racial/ethnic group or sex and the specified outcome measures-subjective pain rating, opioid name, order, and dosage recommendations-suggested by 2 LLMs (GPT-4 and Gemini). Four hundred eighty real-world patient cases were provided to each LLM, and responses included pharmacologic and nonpharmacologic interventions. Tramadol was the most recommended weak opioid in 55.4% of cases, while oxycodone was the most frequently recommended strong opioid in 33.2% of cases. Relative to GPT-4, Gemini was more likely to rate a patient's pain as "severe" (OR: 0.57 95% CI: [0.54, 0.60]; P < 0.001), recommend strong opioids (OR: 2.05 95% CI: [1.59, 2.66]; P < 0.001), and recommend opioids later (OR: 1.41 95% CI: [1.22, 1.62]; P < 0.001). Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups., (Copyright © 2024 International Association for the Study of Pain.)

Objectives: This study aimed to compare 30-day post-operative mortality, and revision for aseptic femoral component loosening and all-causes following hip hemiarthroplasty performed with or without pressurisation of the bone cement in neck of femur fracture patients., Methods: Design: Retrospective cohort study., Setting: Level I trauma center., Patient Selection Criteria: Patients ≥60 years with OTA/AO 31B who underwent a cemented hip hemiarthroplasty from 10th December 2007 (database inception) to 15th November 2023 (search date) were reviewed.Outcome Measures and Comparisons: Comparisons were made between patients who underwent hip hemiarthroplasty with versus without pressurisation of the bone cement for outcomes 30-day post-operative mortality, revision for aseptic femoral component loosening, and revision for all-causes., Results: 406 procedures among 402 patients, and 722 procedures among 713 patients were performed with and without pressurisation of the bone cement respectively. Mean ages were 83.1 and 84.3 years (p=0.018), with 72.2% and 68.6% (p=0.205) females in the pressurised and non-pressurised cement patient groups respectively. There were no differences in 30-day post-operative mortality (7.2% versus 8.2%; HR 0.89, 95%CI 0.46-1.73, p=0.727). There were no differences in all-cause revision (HR 1.04, 95%CI 0.27-4.04, p=0.953). No revisions were performed for aseptic loosening. Survival at 10 years post-operatively was 15.3% (95%CI 11.46-19.64) and 12.6% (95%CI 7.67-18.82) among patients who underwent hemiarthroplasty with and without bone cement pressurisation respectively., Conclusions: There were no differences in 30-day post-operative mortality among patients who underwent hemiarthroplasty with, compared to, without bone cement pressurisation. Bone cement pressurisation did not confer any advantages for revision outcomes which may be attributed in part to patients' high mortality rate and low survival beyond 10 years post-operatively., Level of Evidence: Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Potential Conflicts of Interest and Funding Sources: The authors report no conflicts of interest. This study was not funded., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Phantom limb pain (PLP) represents a significant challenge after amputation. This study investigated the use of phantom motor execution (PME) and phantom motor imagery (PMI) facilitated by extended reality (XR) for the treatment of PLP. Both treatments used XR, but PME involved overt execution of phantom movements, relying on the decoding of motor intent using machine learning to enable real-time control in XR. In contrast, PMI involved mental rehearsal of phantom movements guided by XR. The study hypothesized that PME would be superior to PMI. A multicenter, double-blind, randomized controlled trial was conducted in 9 outpatient clinics across 7 countries. Eighty-one participants with PLP were randomly assigned to PME or PMI training. The primary outcome was the change in PLP, measured by the Pain Rating Index, from baseline to treatment cessation. Secondary outcomes included various aspects related to PLP, such as the rate of clinically meaningful reduction in pain (CMRP; >50% pain decrease). No evidence was found for superiority of overt execution (PME) over imagery (PMI) using XR. PLP decreased by 64.5% and 68.2% in PME and PMI groups, respectively. Thirty-seven PME participants (71%) and 19 PMI participants (68%) experienced CMRP. Positive changes were recorded in all other outcomes, without group differences. Pain reduction for PME was larger than previously reported. Despite our initial hypothesis not being confirmed, PME and PMI, aided by XR, are likely to offer meaningful PLP relief to most patients. These findings merit consideration of these therapies as viable treatment options and alternatives to pharmacological treatments., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Current pediatric pressure injury (PI) prevention measures are based on risk factors related to PI development in adults. Children offer a unique concern for PI development because their bodies are still developing, and their skin responds differently to external pressure., Objective: To explore risk factors for the development of full-thickness PIs in children aged 21 weeks' gestation to 21 years., Methods: This retrospective, observational, correlational study included 799 hospitalized children who developed a PI. The pediatric and adult PI risk factors used in the study were identified from the International Pressure Ulcer Prevention and Treatment Guideline. A stepwise multivariate logistic regression model was used., Results: Multivariate analyses revealed that risk factors for predicting a full-thickness PI varied by age. For children aged 38 weeks to 12 months, risk factors included tissue perfusion and oxygenation: generalized edema, conditions of the OR, and nutrition deficits. For children aged 1 to 7 years, fragile skin status was a risk factor. For youth aged 8 to 21 years, the two risk factors were tissue perfusion and oxygenation: decreased oxygenation and extracorporeal membrane oxygenation. Across the total sample, extracorporeal membrane oxygenation, tissue perfusion and oxygenation: decreased oxygenation and malnutrition were risk factors for predicting a full-thickness PI., Conclusions: Full-thickness PI risk factors differ among the ages of pediatric patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Research has consistently suggested that media consumption plays a vital role in children's socialization, including the socialization of painful experiences. Past research examining young children's popular media revealed worrisome trends in media depictions of pain; it consisted of narrow depictions of pain, gender stereotypes, and an overwhelming lack of empathy from observers, which could contribute to pain-related stigma. Research has not yet examined how pain is portrayed in adolescent media, despite adolescence being the developmental period when chronic pain often emerges. The current study extracted a cross-section of popular adolescent media selected based on popularity, including 10 movies and the first seasons of 6 TV shows. Pain instances were coded using 2 established observational coding schemes assessing sufferer pain characteristics and observer responses. Across 616 instances of pain, there was a preponderance of violence and injuries, whereas everyday, chronic-type, and medical/procedural pains were seldom represented. Individuals from marginalized (ie, gender diverse, girls) and minoritized groups (individuals with racialized identities) were underrepresented in pain instances. Furthermore, regardless of observed gender or "race," observers displayed a lack of empathy for sufferers and rarely engaged in prosocial behaviors. Popular media may serve as an agent of socialization in adolescence; thus, pain depictions may be a powerful force in propagating pain-related stigma and inequities. An opportunity exists to harness popular media to adaptively and accurately portray pain to adolescents., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. Here, we quantify the accuracy of summaries (eg, mean and median) of pain outcomes obtained from EMA and the effect of thresholding these summaries to obtain binary clinical end points of chronic pain status (yes/no). Data applications and simulations indicate that binarizing empirical estimators (eg, sample mean, random intercept linear mixed model) can perform well. However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. Currently, treatment options for OIH are extremely lacking. In this study, we show that the ketogenic diet recovers the abnormal pain behavior caused by chronic morphine treatment in male mice, and we further show that the therapeutic effect of the ketogenic diet is mediated through gut microbiome. Our 16S rRNA sequencing demonstrates that chronic morphine treatment causes changes in mouse gut microbiota, specifically a decrease in short-chain fatty acids-producing bacteria, and the sequencing data also show that the ketogenic diet rescues those bacteria in the mouse gut. More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous etiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimizing side effects and reducing iatrogenic exacerbation of supine hypertension. A personalized management plan including rationalizing medications, patient education, identification, and avoidance of triggers, as well as nonpharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multidisciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there is a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: The authors declare no conflict of interests.

Abstract: Pathogenic variations in the NTRK1 can cause congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive inherited neuropathy. The precise diagnosis of CIPA relies on the identification of pathogenic genotypes. Therefore, it is essential to expand the NTRK1 variation spectrum and improve molecular diagnosis methods. In this study, 74 probands with typical manifestations of CIPA but unknown genotypes were recruited. A comprehensive molecular genetic analysis was performed to identify variations in the NTRK1 , using techniques including Sanger and next-generation sequencing, bioinformatic analysis, quantitative polymerase chain reaction (qPCR), gap-PCR, short tandem repeat (STR) genotyping, and reverse-transcription PCR. In addition, functional assays were conducted to determine the pathogenicity of variants of uncertain significance (VUS) and further characterized changes in glycosylation and phosphorylation of 14 overexpressed mutant vectors with variants at different domains in the TrkA protein, which is encoded by NTRK1 . A total of 48 variations in the NTRK1 were identified, including 22 novel ones. When combined with data from another 53 CIPA patients examined in our previous work, this study establishes the largest genotypic and phenotypic spectra of CIPA worldwide, including 127 CIPA families. Moreover, functional studies indicated that the pathogenicity of VUS mainly affected insufficient glycosylation in the extracellular domain and abnormal phosphorylation in the intracellular domain. This study not only provides important evidence for precise diagnosis of CIPA but also further enriches our understanding of the pathogenesis of this disease., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Lumbar medial branch radiofrequency neurotomy (RFN), a common treatment for chronic low back pain due to facet joint osteoarthritis (FJOA), may amplify paraspinal muscle atrophy due to denervation. This study aimed to investigate the asymmetry of paraspinal muscle morphology change in patients undergoing unilateral lumbar medial branch RFN. Data from patients who underwent RFN between March 2016 and October 2021 were retrospectively analyzed. Lumbar foramina stenosis (LFS), FJOA, and fatty infiltration (FI) functional cross-sectional area (fCSA) of the paraspinal muscles were assessed on preinterventional and minimum 2-year postinterventional MRI. Wilcoxon signed-rank tests compared measurements between sides. A total of 51 levels of 24 patients were included in the analysis, with 102 sides compared. Baseline MRI measurements did not differ significantly between the RFN side and the contralateral side. The RFN side had a higher increase in multifidus FI (+4.2% [0.3-7.8] vs +2.0% [-2.2 to 6.2], P = 0.005) and a higher decrease in multifidus fCSA (-60.9 mm 2 [-116.0 to 10.8] vs -19.6 mm 2 [-80.3 to 44.8], P = 0.003) compared with the contralateral side. The change in erector spinae FI and fCSA did not differ between sides. The RFN side had a higher increase in multifidus muscle atrophy compared with the contralateral side. The absence of significant preinterventional degenerative asymmetry and the specificity of the effect to the multifidus muscle suggest a link to RFN. These findings highlight the importance of considering the long-term effects of lumbar medial branch RFN on paraspinal muscle health., (Copyright © 2024 International Association for the Study of Pain.)

Purpose: The purpose of this study is to optimize a dMS-based urinary proteomic technique and evaluate the relationship between urinary proteome content and adaptive changes in bone microarchitecture during BCT., Methods: Urinary proteomes were analyzed with an optimized dMS technique in two groups of 13 recruits ( N = 26) at the beginning (Pre) and end (Post) of BCT. Matched by age (21 ± 4 yr), sex (16 W), and baseline tibial trabecular bone volume fractions (Tb.BV/TV), these groups were distinguished by the most substantial (High) and minimal (Low) improvements in Tb.BV/TV. Differential protein expression was analyzed with mixed permutation ANOVA and false discovery proportion-based adjustment for multiple comparisons., Results: Tibial Tb.BV/TV increased from pre- to post-BCT in High (3.30 ± 1.64%, P < 0.0001) but not Low (-0.35 ± 1.25%, P = 0.4707). The optimized dMS technique identified 10,431 peptides from 1368 protein groups that represented 165 integrative biological processes. Seventy-four urinary proteins changed from pre- to post-BCT ( P = 0.0019), and neutrophil-mediated immunity was the most prominent ontology. Two proteins (immunoglobulin heavy constant gamma 4 and C-type lectin domain family 4 member G) differed from pre- to post-BCT in High and Low ( P = 0.0006)., Conclusions: The dMS technique can identify more than 1000 urinary proteins. At least 74 proteins are responsive to BCT, and other principally immune system-related proteins show differential expression patterns that coincide with adaptive bone formation., (Copyright © 2024 by the American College of Sports Medicine.)

Abstract: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Findings suggest that cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) for chronic pain produce improvements through changes in putative mechanisms. Evidence supporting this notion is largely based on findings showing significant associations between treatment mechanism variables and outcomes. An alternative view is that treatments may work by reducing or decoupling the impact of changes in mechanism variables on changes in outcomes. We examined the degree to which relationships between previous changes in potential treatment mechanisms and subsequent changes in outcomes changed as treatment progressed and vice versa. Cognitive therapy, MBSR, BT, and treatment as usual (TAU) were compared in people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of putative treatment mechanisms and outcomes. Lagged analyses revealed mechanism × session number interactions and outcome × session number interactions, such that associations between mechanism and outcome variables were strong and significant in the first third of treatment, but weakened over time and became nonsignificant by the last third of treatment. These effects were similar across treatment conditions but did not emerge among people undergoing TAU. Results suggest that during the course of CT, MBSR, and BT, the links between changes in treatment mechanism variables became decoupled from subsequent changes in outcomes and vice versa. Thus, starting by midtreatment and continuing into late treatment, participants may have learned through participation in the treatments that episodes of maladaptive pain-related thoughts and/or spikes in pain need not have detrimental consequences on their subsequent experience., (Copyright © 2024 International Association for the Study of Pain.)

Objective: To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects., Design: Longitudinal observational clinical cohort of patients in HIV care in the US.Methods: Data from the CFAR Network for Integrated Clinical Systems (2016-2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined., Results: Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se  = 0.020; β = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma's impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators., Conclusions: Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250-nautical-mile circles implemented on March 15, 2021 (KAS250)., Methods: Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19., Results: In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant., Conclusions: The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant., Competing Interests: S.E.G. and D.N.V. were supported by a grant from the Mendez National Institute of Transplantation Foundation. A.B.M., D.L.S., and S.E.G. were supported by grant R01DK132395 from the National Institutes of Health. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mechanical power (MP) is a summary variable quantifying the risk of ventilator-induced lung injury (VILI). The original MP equation was developed using square flow ventilation. However, most children are ventilated using decelerating flow. It is unclear whether MP differs according to mode of flow delivery. We compared MP in children with acute respiratory distress syndrome (ARDS) who received both square and decelerating flow ventilation., Methods: This was a secondary analysis of a prospectively enrolled cohort of pediatric ARDS. Patients were ventilated on decelerating flow, and then placed in square flow and allowed to stabilize. Ventilator metrics from both modes were collected within 24 hours of ARDS onset. Paired t-tests were used to compare differences in MP between the modes., Results: We enrolled 185 subjects with a median oxygenation index of 9.5 (IQR 7, 13) and median age 8.3 years (IQR 1.8, 14). MP was lower in square flow (mean 0.46 J・min-1·Kg-1, SD 0.25, 95% CI 0.42-0.50) than in decelerating flow modes (mean 0.49 J・min-1·Kg-1, SD 0.28, 95% CI 0.45-0.53) with a mean difference of 0.03 J・min-1·Kg-1 (SD 0.08, 95% CI 0.014-0.038) (p<0.001). This result remained statistically significant when stratified by age < 2 years in square flow compared to decelerating flow and also when stratified by age >/= 2 years in square flow compared to decelerating flow. The elastic contribution in square flow was 70% and the resistive contribution was 30%., Conclusions: MP was marginally lower in square flow than in decelerating flow, although the clinical significance of this is unclear. Upward of 30% of MP may go towards overcoming resistance, regardless of age. This is nearly three-fold greater resistance compared to what has been reported in adults., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interests., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Objectives: To identify and critically analyze studies using artificial intelligence (AI) in occupational health., Methods: A systematic search of PubMed, IEEE Xplore, and Web of Science was conducted to identify relevant articles published in English between January 2014-January 2024. Quality was assessed with the validated APPRAISE-AI tool., Results: The 27 included articles were categorized as follows: health risk assessment (n = 17), return to work and disability duration (n = 5), injury severity (n = 3), and injury management (n = 2). 47 AI algorithms were utilized, with artificial neural networks, support vector machines, and random forest being most common. Model accuracy ranged from 0.60-0.99 and AUC from 0.7-1.0. Most studies (n = 15) were of moderate quality., Conclusions: While AI has potential clinical utility in occupational health, explainable models that are rigorously validated in real-world settings are warranted., Competing Interests: Conflict of Interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Objective: To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables., Background: CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making., Methods: Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator., Results: Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF., Conclusions: Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms., Competing Interests: Disclosures: No conflict of interests to declare, financial or otherwise., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The chronic impact of acetylcholinesterase (AChE) inhibitors and other toxicants on Gulf War (GW) veterans' health symptoms is unclear., Methods: Building on reports of adverse neuropsychological outcomes in GW pesticide applicators exposed to pesticides and pyridostigmine bromide (PB), we now report on health symptoms in this group., Results: In adjusted analyses, applicators with high exposures/impact to pesticides reported significantly more symptoms (18/34 symptoms) than applicators with lower exposures/impact and were more likely to meet modified Kansas and CDC Gulf War Illness criteria. The high PB exposure/impact group was three times more likely to report irregular heart rates. With regard to specific pesticide types, fly baits, pest-strips and delousers were the most associated with increased health symptom reporting., Conclusions: These results suggest that GW veterans with high AChE inhibitor and organochlorine exposures are most at risk for chronic health symptoms., Competing Interests: Conflict of Interest for ALL Authors - NONE DECLARED, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Abstract: Using cross-sectional data from the United States, England, China, and India, we examined the relationship between education and frequent pain, alongside the modification role of gender in this relationship. We further examined patterns of 3 pain dimensions among participants who reported frequent pain, including pain severity, interference with daily activities, and medication use (these pain dimension questions were not administered in all countries). Our analytical sample included 92,204 participants aged 50 years and above. We found a high prevalence of frequent pain across the 4 countries ranging from 28% to 41%. Probit models showed that higher education was associated with lower risk of pain (United States: -0.26, 95% CI: -0.33, -0.19; England: -0.32, 95% CI: -0.39, -0.25; China: -0.33, 95% CI -0.41, -0.26; India: -0.18, 95% CI -0.21, -0.15). Notably, in China and India, the negative association between higher education and frequent pain was less pronounced among women compared with men, which was not observed in the United States or England. Further analysis showed that individuals with higher education experiencing frequent pain reported less severity, fewer daily activity interferences, and less medication use compared with those with lower education. In the United States, these associations were stronger among women. Our findings highlight the prevalent pain among middle-aged and older adults in these 4 countries and emphasize the potentially protective role of higher education on frequent pain, with nuanced gender differences across different settings. This underscores the need for tailored strategies considering educational and gender differences to improve pain management and awareness., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog (Shh) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception., (Copyright © 2024 International Association for the Study of Pain.)