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Scott G Pritzlaff,1 Johnathan H Goree,2 Jonathan M Hagedorn,3 David W Lee,4 Kenneth B Chapman,5 Sandy Christiansen,6 Andrew Dudas,7 Alexander Escobar,8 Christopher J Gilligan,9 Maged Guirguis,10 Amitabh Gulati,11 Jessica Jameson,12 Christopher J Mallard,13 Melissa Murphy,14 Kiran V Patel,15 Raj G Patel,16 Samir J Sheth,17 Stephanie Vanterpool,18 Vinita Singh,19 Gregory Smith,2 Natalie H Strand,20 Chau M Vu,21 Tolga Suvar,22 Krishnan Chakravarthy,23 Leonardo Kapural,24 Michael S Leong,25 Timothy R Lubenow,22 Alaa Abd-Elsayed,26 Jason E Pope,21 Dawood Sayed,27 Timothy R Deer28 1Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 2Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 3Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Mayo Clinic, Rochester, MN, USA; 4Fullerton Orthopedic Surgery Medical Group, Fullerton, CA, USA; 5The Spine & Pain Institute of New York, New York, NY, USA; 6Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA; 7Mays & Schnapp Neurospine and Pain, Memphis, TN, USA; 8Department of Anesthesiology, University of Toledo, Toledo, OH, USA; 9Division of Pain Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, MA, USA; 10Division of Pain Management, Ochsner Health, New Orleans, LA, USA; 11Department of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Axis Spine Center, Coeur D’Alene, ID, USA; 13Department of Anesthesiology, University of Kentucky, Lexington, KY, USA; 14North Texas Orthopedics and Spine Center, Grapevine, TX, USA; 15Department of Anesthesiology and Pain Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY, USA; 16Capitol Pain Institute, Austin, TX, USA; 17Interventional Pain Management, Sutter Health, Roseville, CA, USA; 18Department of Anesthesiology, University of Tennessee, Knoxville, TN, USA; 19Department of Anesthesiology, Emory University, Atlanta, GA, USA; 20Interventional Pain Management, Mayo Clinic, Scottsdale, AZ, USA; 21Evolve Restorative Center, Santa Rosa, CA, USA; 22Department of Anesthesiology and Pain Medicine, Rush University Medical Center, Chicago, IL, USA; 23Coastal Pain and Spinal Diagnostics Medical Group, San Diego, CA, USA; 24Carolinas Pain Institute, Winston-Salem, NC, USA; 25Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA; 26Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 27Department of Anesthesiology, Pain and Perioperative Medicine, University of Kansas, Kansas City, KS, USA; 28The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Scott G Pritzlaff, University of California, Davis, 4860 Y Street, Suite 3020, Sacramento, CA, 95817, USA, Tel +1 916 734-6824, Fax +1 916 734-6827, Email spritzlaff@ucdavis.eduAbstract: The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.Keywords: neuromodulation, pain education, spinal cord stimulation, dorsal root ganglion stimulation, peripheral nerve stimulation, fellowship training

Kenneth B Chapman,1– 3 Dawood Sayed,4 Tim Lamer,5 Corey Hunter,6 Jacqueline Weisbein,7 Kiran V Patel,1– 3 David Dickerson,8,9 Jonathan M Hagedorn,10 David W Lee,11 Kasra Amirdelfan,12 Timothy Deer,13 Krishnan Chakravarthy14,15 1The Spine & Pain Institute of New York, New York, NY, USA; 2Department of Anesthesiology, Zucker School of Medicine at Hofstra Northwell, Manhasset, NY, USA; 3Department of Anesthesiology, NYU Langone Medical Center, New York, NY, USA; 4Department of Anesthesiology, The University of Kansas Medical Center (KUMC), Kansas City, KS, USA; 5Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA; 6Ainsworth Institute of Pain Management, New York, NY, USA; 7Napa Valley Orthopedic Medical Group, Napa, CA, USA; 8Department of Anesthesiology, Critical Care and Pain Medicine, NorthShore University Health System, Evanston, IL, USA; 9Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, USA; 10iSpine Pain Physicians, Maple Grove, MN, USA; 11Fullerton Orthopedic Surgery Medical Group, Fullerton, CA, USA; 12IPM Medical Group, Inc., Walnut Creek, CA, USA; 13The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 14Department of Anesthesiology and Pain Medicine, University of California San Diego Health Sciences, San Diego, CA, USA; 15VA San Diego Healthcare System, San Diego, CA, USACorrespondence: Kenneth B Chapman, NYU Langone Medical Center, Zucker School of Medicine at Hofstra/Northwell, Pain Medicine at Staten Island University Hospital, 1360 Hylan Boulevard, Staten Island, NY, 10305, USA, Email chapmanken@spinepainny.comAbstract: With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion stimulation (DRG-S) has significantly improved the treatment of complex regional pain syndrome (CRPS), and it has broad applicability across a wide range of other conditions. Through funding and organizational leadership by the American Society for Pain and Neuroscience (ASPN), this best practices consensus document has been developed for the selection, implantation, and use of DRG stimulation for the treatment of chronic pain syndromes. This document is composed of a comprehensive narrative literature review that has been performed regarding the role of the DRG in chronic pain and the clinical evidence for DRG-S as a treatment for multiple pain etiologies. Best practice recommendations encompass safety management, implantation techniques, and mitigation of the potential complications reported in the literature. Looking to the future of neuromodulation, DRG-S holds promise as a robust intervention for otherwise intractable pain.Keywords: dorsal root ganglion, neurostimulation, chronic pain, best practice, guidelines

Dawood Sayed,1 Ramana K Naidu,2,3 Kiran V Patel,4 Natalie H Strand,5 Pankaj Mehta,6 Christopher M Lam,1 Vinicius Tieppo Francio,7 Samir Sheth,8 Anthony Giuffrida,9 Brian Durkin,10 Nasir Khatri,11 Shashank Vodapally,12 Christopher O James,13 Benjamin D Westerhaus,9 Adam Rupp,7 Newaj M Abdullah,14 Kasra Amirdelfan,15 Erika A Petersen,16 Douglas P Beall,17 Timothy R Deer18 1Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Anesthesiology, California Orthopedics & Spine, Marin, CA, USA; 3Pain Management, MarinHealth Medical Center, Marin, CA, USA; 4Interventional Pain Management/ Anesthesiology, The Spine & Pain Institute of New York, New York City, NY, USA; 5Interventional Pain Management, Mayo Clinic, Scottsdale, AZ, USA; 6Clinical Research, Pain Specialists of Austin, Austin, TX, USA; 7Department of Rehabilitation Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 8Interventional Pain Management, Sutter Health, Roseville, CA, USA; 9Cantor Spine Center, Paley Orthopedic and Spine Institute, Fort Lauderdale, FL, USA; 10Pain Institute of Long Island, Port Jefferson, NY, USA; 11Interventional Pain Medicine, Novant Health, Charlotte, NC, USA; 12Physical Medicine and Rehabilitation, Michigan State University, East Lansing, MI, USA; 13Department of Physical Medicine and Rehabilitation, University of Kentucky, Lexington, KY, USA; 14Pain Medicine and Anesthesiology, University of Utah, Salt Lake City, UT, USA; 15Clinical Research, IPM Medical Group, Inc, Walnut Creek, CA, USA; 16Department of Neurosurgery, University of Arkansas for Medical Science, Little Rock, AR, USA; 17Comprehensive Specialty Care, Edmond, OK, USA; 18The Spine and Nerve Center of the Virginias, Charleston, WV, USACorrespondence: Dawood Sayed, The University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA, Tel +1 913-588-5521, Email dsayed1@yahoo.comAbstract: Chronic low back pain is a worldwide leading cause of pain and disability. Degenerative disc disease has been the presumptive etiology in the majority of cases of chronic low back pain (CLBP). More recent study and treatments have discovered that the vertebral endplates play a large role in CLBP in a term defined as vertebrogenic back pain. As the vertebral endplates are highly innervated via the basivertebral nerve (BVN), this has resulted in a reliable target in treating patients suffering from vertebrogenic low back pain (VLBP). The application of BVN ablation for patients suffering from VLBP is still in its early stages of adoption and integration into spine care pathways. BVN ablation is grounded in a solid foundation of both pre-clinical and clinical evidence. With the emergence of this therapeutic option, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidelines for the proper identification and selection of patients for BVN ablation in patients with VLBP. ASPN formed a multidisciplinary work group tasked to examine the available literature and form best practice guidelines on this subject. Based on the United States Preventative Task Force (USPSTF) criteria for grading evidence, gives BVN ablation Level A grade evidence with high certainty that the net benefit is substantial in appropriately selected individuals.Keywords: back pain, vertebrogenic pain, lumbar degenerative disc, radiofrequency ablation, basivertebral nerve, guidelines

Jonathan Greenberg,1,2 Ryan A Mace,1,2 Paula J Popok,1 Ronald J Kulich,2,3 Kushang V Patel,4 John W Burns,5 Tamara J Somers,6 Francis J Keefe,7 Michael E Schatman,8,9 Ana-Maria Vrancenanu1,2 1Integrated Brain Health Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Center for Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; 4Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA, USA; 5Division of Behavioral Sciences, Rush Medical College, Chicago, IL, USA; 6Psychiatry & Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA; 7Department of Medicine, Duke University School of Medicine, Durham, NC, US; 8Department of Diagnostic Sciences, Tufts University School of Dental Medicine, Boston, MA, USA; 9Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USACorrespondence: Ana-Maria Vrancenanu Email avranceanu@mgh.harvard.eduBackground: Improving all aspects of physical function is an important goal of chronic pain management. Few studies follow recent guidelines to comprehensively assess physical function via patient-reported, performance-based, and objective/ambulatory measures.Purpose: To test 1) the interrelation between the 3 types of physical function measurement and 2) the association between psychosocial factors and each type of physical function measurement.Methods: Patients with chronic pain (N=79) completed measures of: 1) physical function (patient-reported disability; performance-based 6-minute walk-test; objective accelerometer step count); 2) pain and non-adaptive coping (pain during rest and activity, pain-catastrophizing, kinesiophobia); 3) adaptive coping (mindfulness, general coping, pain-resilience); and 4) social-emotional dysfunction (anxiety, depression, social isolation and emotional support). First, we tested the interrelation among the 3 aspects of physical function. Second, we used structural equation modeling to test associations between psychosocial factors (pain and non-adaptive coping, adaptive coping, and social-emotional dysfunction) and each measurement of physical function.Results: Performance-based and objective physical function were significantly interrelated (r=0.48, p< 0.001) but did not correlate with patient-reported disability. Pain and non-adaptive coping (β=0.68, p< 0.001), adaptive coping (β=− 0.65, p< 0.001) and social-emotional dysfunction (β=0.65, p< 0.001) were associated with patient-reported disability but not to performance-based or objective physical function (ps> 0.1).Conclusion: Results suggest that patient-reported physical function may provide limited information about patients’ physical capacity or ambulatory activity. While pain and non-adaptive reactions to it, adaptive coping, and social-emotional dysfunction may potentially improve patient-reported physical function, additional targets may be needed to improve functional capacity and ambulatory activity.Trial Registration: ClinicalTrials.gov NCT03412916.Keywords: physical function, chronic pain, six-minute walk test, accelerometer, psychosocial factors

This article aims to compare the effects of morbid and comorbid medical conditions on disability in elderly Mexican and Mexican American adults. Data from the 2001 Mexican Health and Aging Study (N = 4,872) and 1993 to 1994 Hispanic Established Population for Epidemiologic Studies of the Elderly (N = 3,050) were analyzed. Prevalence of medical conditions and disability in activities of daily living were calculated and logistic models were used to test associations. Prevalence of disability in older Mexicans was 16.3% while it was slightly lower in Mexican Americans (13.1%). Prevalence of arthritis, cancer, diabetes, heart attack, and stroke were substantially higher in Mexican Americans than in older adults living in Mexico. Diabetes, stroke, and heart attack were comorbid conditions that raised the likelihood of disability in both populations among subjects with other medical conditions. Despite differences in prevalence, the associations of morbidity and comorbidity with disability had similar magnitudes in both populations. [ABSTRACT FROM AUTHOR]

PURPOSE: To determine whether neighborhood characteristics are associated with self-rated health in older Mexican Americans. METHODS: Epidemiologic data on 3050 older Mexican Americans residing in the southwestern United States during 1993 and 1994 were merged with 1990 US Census data. All subjects were matched to one of 210 census tracts (neighborhoods). Multilevel ordinal logit models were used to examine relationships between self-rated health and individual- and neighborhood-level variables. RESULTS: After adjusting for individual characteristics, older Mexican Americans were more likely to rate their health poorer if they lived in neighborhoods that were economically disadvantaged, less populated by other Hispanics, or located within 50 miles of the US-Mexico border. In addition, residence in a border community moderated the relationship between self-rated health and neighborhood economic disadvantage. The effect of neighborhood economic disadvantage on poorer self-rated health was two to three times stronger for subjects living near the border region than subjects living further away from the border. CONCLUSIONS: This study demonstrates the importance of considering several dimensions of neighborhood context, especially for Mexican Americans. Residence in a border community and neighborhood economic disadvantage were important predictors of poorer self-rated health status. In addition, older Mexican Americans experience a health benefit from living in neighborhoods populated with other Hispanics. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention., Objectives: To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool., Methods: This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis., Results: The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a "leave-one-out" analysis (all P < 0.001)., Conclusion: The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions., Competing Interests: R.S.T. reports consultancy fees from Medtronic, Nevro and Saluda Medical outside the submitted work. C.M.M. is employed by NAMSA, a company that provides consulting and testing services to medical device manufacturers. N.A.M. reports receiving grants from Neuros, Mesoblast, and Vivex Biologics, as well as consulting as a medical monitor for Saluda Medical, Nevro, Vivex Biologics, Mainstay, Sollis Therapeutics, and Vertos outside the submitted work. J.W.K. is an advisory board member for Boston Scientific, Medtronic, Abbott, and Saluda Medical. J.E.P. reports research and consulting fees from Saluda Medical during the conduct of the study; consultancy for Abbott, Medtronic, Saluda Medical, Flowonix, SpineThera, Vertos, Vertiflex, SPR Therapeutics, Tersera, Aurora, Spark, Ethos, Biotronik, Mainstay, WISE, Boston Scientific, and Thermaquil outside the submitted work; has received grant and research support from: Abbott, Flowonix, Aurora, Painteq, Ethos, Muse, Boston Scientific, SPR Therapeutics, Mainstay, Vertos, AIS, and Thermaquil outside the submitted work; and is a shareholder of Vertos, SPR Therapeutics, Painteq, Aurora, Spark, Celeri Health, Neural Integrative Solutions, Pacific Research Institute, Thermaquil, and Anesthetic Gas Reclamation. C.W.H. has received consultancy fees from Saluda Medical and Genecentrix outside the submitted work. S.J.C. reports receiving grants from Saluda Medical, Vertos, Mainstay, and Vivex outside the submitted work. L.K. reports receiving grants from Nevro, Neuros, Avanos, Medtronic, Neuralace, and Xalud Therapeutics and financial support from Nevro, Avanos, and Saluda Medical outside the submitted work. C.A.G. reports personal fees and other from SPR, and personal fees from Nevro, Nalu, Biotronik, Boston Scientific and Saluda Medical outside the submitted work. E.A.P. has received research support from Mainstay, Medtronic, Neuros Medical, Nevro Corp, ReNeuron, SPR, and Saluda Medical outside the submitted work, as well as personal fees from Abbott Neuromodulation, Biotronik, Medtronic Neuromodulation, Nalu, Neuros Medical, Nevro, Presidio Medical, Saluda Medical, and Vertos outside the submitted work. She holds stock options from SynerFuse and neuro42. K.V.P. is a consultant and speaker for Abbott. S.E. reports consultancy fees from Medtronic, and Mainstay Medical outside the submitted work. He has received department research funding from the National Institute of Health Research, Saluda Medical and Medtronic. R.M.L. is an uncompensated consultant for Biotronik, Abbott, Nalu, Saluda Medical, and Mainstay Medical and has stock options from Nalu and Saluda Medical. C.G. reports payment to his institution (for part of his salary) and stock options received from Mainstay, personal fees from Mainstay, Saluda Medical, Persica, and Iliad outside the submitted work, research funded by Sollis, expert witness testimony fees, and serves as Editor-in-Chief of Pain Practice. S.D. has received consulting payments from Averitas Pharma and Biotronik outside the submitted work. A.A. reports consultancy for Medtronic, Avanos, and StimWave outside the submitted work. P.B. reports consulting fees from Abbott and PainTEQ outside the submitted work. E.H., A.L., N.S. and R.V.D. are employees of Saluda Medical. R.V.D. has previously received consultancy fees from Mainstay Medical, Medtronic, and Saluda Medical. D.J.C. has consulted for AbbVie, Heron Therapeutics, Aptinyx, Neumentum, Regeneron Pharmaceuticals, Swing Therapeutics, Virios Therapeutics, Allergan Sales, Eli Lilly and Company, H. Lundback A/S, Pfizer, Samumed, Tonix Pharmaceuticals. T.J.N. has received consultancy fees from Saluda Medical outside the submitted work. The remaining authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Chronic pain affects a substantial portion of the population, posing a significant health challenge. Current treatments often come with limitations and side effects, necessitating novel therapeutic approaches. Our study focuses on disrupting the Cav3.2-USP5 interaction as a strategy for chronic pain management. Through structure-activity relationship studies of a tetrahydroquinoline (THQ) scaffold, we identified a family of lead molecules that demonstrated potent inhibition of the Cav3.2-USP5 interaction. In vitro pharmacokinetic assessments and in vivo studies support the efficacy and drug-like properties of the lead compounds in mouse models of acute and chronic pain. Dependence on the Cav3.2 channels was validated in Cav3.2 null mice, consistent with the proposed mode of action of these small molecules. These findings provide a novel chronic pain treatment strategy, highlighting the potential of these small molecules for further development.

Aims: Abnormalities in specific echocardiographic parameters and cardiac biomarkers have been reported among individuals with diabetes. However, a comprehensive characterization of diabetic cardiomyopathy (DbCM), a subclinical stage of myocardial abnormalities that precede the development of clinical heart failure (HF), is lacking. In this study, we developed and validated a machine learning-based clustering approach to identify the high-risk DbCM phenotype based on echocardiographic and cardiac biomarker parameters., Methods and Results: Among individuals with diabetes from the Atherosclerosis Risk in Communities (ARIC) cohort who were free of cardiovascular disease and other potential aetiologies of cardiomyopathy (training, n = 1199), unsupervised hierarchical clustering was performed using echocardiographic parameters and cardiac biomarkers of neurohormonal stress and chronic myocardial injury (total 25 variables). The high-risk DbCM phenotype was identified based on the incidence of HF on follow-up. A deep neural network (DeepNN) classifier was developed to predict DbCM in the ARIC training cohort and validated in an external community-based cohort (Cardiovascular Health Study [CHS]; n = 802) and an electronic health record (EHR) cohort (n = 5071). Clustering identified three phenogroups in the derivation cohort. Phenogroup-3 (n = 324, 27% of the cohort) had significantly higher 5-year HF incidence than other phenogroups (12.1% vs. 4.6% [phenogroup 2] vs. 3.1% [phenogroup 1]) and was identified as the high-risk DbCM phenotype. The key echocardiographic predictors of high-risk DbCM phenotype were higher NT-proBNP levels, increased left ventricular mass and left atrial size, and worse diastolic function. In the CHS and University of Texas (UT) Southwestern EHR validation cohorts, the DeepNN classifier identified 16% and 29% of participants with DbCM, respectively. Participants with (vs. without) high-risk DbCM phenotype in the external validation cohorts had a significantly higher incidence of HF (hazard ratio [95% confidence interval] 1.61 [1.18-2.19] in CHS and 1.34 [1.08-1.65] in the UT Southwestern EHR cohort)., Conclusion: Machine learning-based techniques may identify 16% to 29% of individuals with diabetes as having a high-risk DbCM phenotype who may benefit from more aggressive implementation of HF preventive strategies., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Abstract: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) prevent heart failure (HF) in patients with type 2 diabetes mellitus (T2DM) but prescription rates are low. The effect of an electronic health record (EHR) alert notifying providers of patients' estimated risk of developing HF on SGTL2i prescriptions is unknown., Methods: This was a pragmatic, randomized clinical trial that compared an EHR alert and usual care among patients with T2DM and no history of HF or SGLT2i use at a single center. The EHR alert notified providers of their patient's HF risk and recommended HF prevention strategies. Randomization was performed at the provider level across general and subspecialty internal medicine as well as family medicine outpatient clinics. The primary outcome was proportion of SGLT2i prescriptions within 30 days. Proportion of natriuretic peptide (NP) tests within 90 days was also assessed., Results: A total of 1524 patients (median age 75 years, 45% women, 23% Black) were enrolled between September 28, 2021, and April 29, 2022 from 189 outpatient clinics. SGLT2i were prescribed to 1.2% (9/780) of patients in the EHR alert group and 0% (0/744) of those in the usual care group ( P value = 0.009). Natriuretic peptide testing was performed within 90 days among 10.8% (84/780) of patients in the EHR alert group and 7.3% (54/744) of patients in the usual care group ( P value = 0.02)., Conclusions: In a single-center trial with low overall SGLT2i use, an EHR alert incorporating HF risk information significantly increased SGLT2i prescriptions and NP testing although the absolute rates were low., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MWS has received personal fees from Merck and serves on the advisory board at descendants DNA. KVP has received consultant fees from NovoNordisk. NK has received consultant fees from HeartSciences and Tricog Health. AP received grant funding outside this study from National Institute of Health, Gilead Sciences, Ultromics, Roche Diagnostics, and Applied Therapeutics; has received honoraria outside of this study as an advisor/consultant for Tricog Health Inc, Lilly, USA, Rivus, Roche Diagnostics, Axon Therapies, Semler Scientific, Medtronic, Edwards Lifesciences, Science37, Novo Nordisk, Bayer, Merck, Sarfez Pharamcuticals, Emmi Solutions, Palomarin Inc (Stocks compensation) and has received nonfinancial support from Pfizer and Merck. All other authors declare no competing interests.

Objective: The objective was to examine the associations of number and type of chronic conditions with use of rehabilitation services among older adults with bothersome back pain., Methods: We conducted a cohort study using the National Health and Aging Trends Study, a longitudinal survey of Medicare beneficiaries ≥65 years. We included community-dwelling older adults with bothersome back pain in 2015. We assessed 12 self-reported chronic conditions, including arthritis, depression, and anxiety. We used 2016 data to ascertain self-reported use of any rehabilitation services in the prior year. We used weighted, logistic regression to examine the association of conditions with rehabilitation use., Results: The sample size was 2443. A majority were age ≥ 75 years (59%); female (62%); and White, non-Hispanic (71%). The median number of chronic conditions was 3 (interquartile range, 2-4). Arthritis was the most common chronic condition (73%); 14% had anxiety and 16% had depression. For every additional chronic condition, adjusted odds of any rehabilitation use increased 21% (Odds Ratio = 1.21, 95% CI: 1.11-1.31). Those with ≥4 chronic conditions had 2.13 times higher odds (95% CI: 1.36-3.34) of any rehabilitation use in the next year versus those with 0-1 condition. Participants with arthritis had 1.96 times higher odds (95% CI: 1.41-2.72) of any rehabilitation use versus those without arthritis. Anxiety and depression were not significantly associated with rehabilitation use., Conclusions: Among older adults with back pain, a greater number of chronic conditions and arthritis were associated with higher use of rehabilitation services. Those with anxiety or depression had no difference in their use of rehabilitation care versus those without these conditions., Impact Statement: This pattern suggests appropriate use of rehabilitation for patients with back pain and multiple chronic conditions based on greater need, but there may be potential underuse for those with back pain and psychological conditions., (© 2024 American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is growing evidence that a relationship exists between mental and emotional wellbeing and the gut microbiota. Little is known regarding how the microbiota reacts to repeated acute stress events in dogs, and whether it is a predictor of stress response. In this study, we explored the impact on the gut microbiota and digestive health with two common events many pet dogs find stressful. Twenty healthy adult dogs, living within a colony, were exposed to either car travel or separation three times across eight-week intervals. Faecal samples were collected 24 h before, within 24 h, and 24-48 h after. Faecal quality and pH, and microbiota diversity and composition were analysed in context with wider published work on physiological stress measures. No significant changes were observed in faecal quality or pH with either stress event at any timepoint, indicating all pets remained in good digestive health. Microbiota analysis demonstrated no significant impact on alpha or beta diversity with either stressor. Microbial signatures previously linked to stress were not identified in these dogs and no changes were observed in the functional gut composition. Irrespective of whether the pet was considered "stressed" (i.e., exhibited an increase in serum cortisol), there was no effect on the microbiota and no taxa were predictive of stress response. Collectively, this work demonstrates, for this population, certain acute stress events have no meaningful impact on the canine gut microbiota, and it has no impact on the associated stress response., (© 2024. Mars, Incorporated and its Affiliates.)

Many proteins undergo a post-translational lipid attachment, which increases their hydrophobicity, thus strengthening their membrane association properties or aiding in protein interactions. Geranylgeranyltransferase-I (GGTase-I) is an enzyme involved in a 3-step post-translational modification (PTM) pathway that attaches a 20-carbon lipid group called geranylgeranyl at the carboxy-terminal cysteine of proteins ending in a canonical CaaL motif (C-cysteine, a-aliphatic, L-often leucine, but can be phenylalanine, isoleucine, methionine, or valine). Genetic approaches involving 2 distinct reporters were employed in this study to assess Saccharomyces cerevisiae GGTase-I specificity, for which limited data exist, toward all 8,000 CXXX combinations. Orthogonal biochemical analyses and structure-based alignments were also performed to better understand the features required for optimal target interaction. These approaches indicate that yeast GGTase-I best modifies the Cxa[L/F/I/M/V] sequence that resembles but is not an exact match for the canonical CaaL motif. We also observed that minor modification of noncanonical sequences is possible. A consistent feature associated with well-modified sequences was the presence of a nonpolar a2 residue and a hydrophobic terminal residue, which are features recognized by mammalian GGTase-I. These results thus support that mammalian and yeast GGTase-I exhibit considerable shared specificity., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The leading intent of the present questionnaire is to assess the ratio of the concerned population as well as the treatment approach of craniofacial deformities among Gujarat citizenry. The theme of Google Form was used for 100 partakers to record responses via sending the questionnaire in English and Gujarati languages through WhatsApp and Emails. From the 100 respondents which are from laymen of Gujarat, 62.25% of inhabitants are acquainted with craniofacial syndromes, 15% of residents have craniofacial deformities as their family history, 51.66% of denizens have some idea for the treatment approach of craniofacial malformations. A good number of Gujarat laymen have some clear concept for craniofacial syndromes., Competing Interests: There are no conflicts of int erest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Aims and Objectives: The purpose of this survey was to assess postgraduate students' knowledge of orthodontic direct printed aligners and their opinions of the treatment modalities that can be used with them., Materials and Methods: 198 postgraduate learners were given a questionnaire consisting of 25 questions via Google Forms as part of this web-based survey. Results: Compared to their male counterparts, women were more knowledgeable about direct printed aligners., Conclusion: The survey concluded that most postgraduate students have knowledge about direct printed aligners. Females are more aware about direct printed aligners than males. Orthodontists were the predominant source of knowledge regarding direct printed aligners., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: Orthodontic correction of dentofacial abnormalities is a crucial component of oral health because it enhances overall oral health-related quality of life, optimal function, periodontal health, and aesthetics. This study sought to determine whether otolaryngologists recommend patients to orthodontists, whether they are adequately knowledgeable about the fundamentals of orthodontics, and whether they check for orthodontic problems in their patients., Materials and Method: We conducted a survey study of otolaryngologists in Gujarat, India. Questionnaires were completed by 47 out of 60 otolaryngologists (response rate 78%)., Results: In the assessment of the mouth breathers, a very low frequency of "always" examining the extra-oral features (18%) was found. Reasons otolaryngologists referred patients to orthodontists varied from mouth breathing 48% (23/47) to face or teeth asymmetry 87% (41/47). In the multivariable analyses for the effect of gender, work sector, or years of experience in the decision for orthodontic referral, we could not identify any significant predictors. A low frequency of awareness of orthodontists' role in obstructive sleep apnoea, 48% (23/47) was found., Conclusion: In conclusion, the survey of otolaryngologists in Gujarat, India, revealed areas for improvement in awareness and practices related to orthodontic issues, particularly in cases of mouth breathing. The study highlighted a low frequency of examination of extraoral features and variability in referral patterns, emphasizing potential gaps in knowledge. Additionally, a low awareness of orthodontists' role in treating obstructive sleep apnea was identified. Targeted educational interventions are recommended to enhance interdisciplinary communication and collaboration between otolaryngologists and orthodontists, ultimately fostering a more comprehensive approach to patient care for individuals with dentofacial deformities in Gujarat and potentially influencing practices on a broader scale., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: Because orthodontists work long hours and maintain a relationship with each patient for many years prior to the end of treatment, they may encounter unusually stressful situations., Materials and Methods: A self-administered, anonymous survey was disseminated to orthodontic residents and practitioners in India. The survey includes 29 probable stressors., Result: Over 61% of respondents opined that these factors are the most stressful in orthodontic practice., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease., Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes., Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models., Results: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60])., Conclusions: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute (R01 HL071739 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-C-95169). The PREVEND cohort study was supported by The Dutch Kidney Foundation which supported the infrastructure of the PREVEND program from 1997 to 2003 (Grant E.033). The University Medical Center Groningen supported the infrastructure from 2003 to 2006. Dr Pandey is supported by the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics; has served on the advisory board for Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Segar has received speaker fees from Merck and is on the advisory board of descendantsDNA. Dr Shapiro has received grants from Amgen, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, and New Amsterdam; has served on scientific advisory boards for Amgen, Agepha, Ionis, Novartis, Precision BioScience, New Amsterdam, and Merck; and has served as a consultant to Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, and Novo Nordisk. Dr Connelly is an employee of Labcorp. Dr Rohatgi has received a research grant from CSL Behring; has served as a collaborator to Quest; has served as a consultant to HDL Diagnostics, JP Morgan, Johnson and Johnson, and Raydel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown., Methods: This is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m 2 or ≥27 kg/m 2 and metabolic syndrome. Participants were randomly assigned to a once-daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40-week follow-up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least-square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored., Results: Among the 128 participants with follow-up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow-up of 36 weeks was -2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: -0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was -0.24% (95% CI, -0.41 to -0.06, P-value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo., Conclusions: In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose of Review: This narrative review seeks to elucidate clinical and social factors influencing cardiovascular health, explore the challenges and potential solutions for enhancing cardiovascular health, and identify areas where further research is needed to better understand cardiovascular issues in native and American Pakistani populations., Recent Findings: The prevalence of cardiometabolic disease is high not only in Pakistan but also among its global diaspora. This situation is further complicated by the inadequacy of current cardiovascular risk assessment tools, which often fall short of accurately gauging the risk among Pakistani individuals, underscoring the urgent need for more tailored and effective assessment methodologies. Moreover, social determinants play a crucial role in shaping cardiovascular health. The burden of cardiovascular disease and upstream risk factors is high among American Pakistani individuals. Future research is needed to better understand the heightened risk of cardiovascular disease among Pakistani individuals., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

N-Heterocyclic ylides are important synthetic precursors to rapidly build molecular complexity. Pyrazolium ylides have largely been unexplored, and we demonstrate their diverse utility in this report. We show that these readily accessible building blocks can be used to construct different heterocyclic skeletons by varying the coupling partner. Indolizines can be formed via an N-deletion type mechanism when reacting pyrazolium salts with electron deficient alkynes. 1,2-Dihydropyrimidines can be formed via a rearrangement mechanism when reacting pyrazolium ylides with isocyanates. These reactions enable access to valuable heteroarenes without the need for transition metal catalysis, high temperatures, or strong bases., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Clinical practice guidelines encourage primary care providers (PCPs) to recommend nonpharmacologic treatment as first-line therapy for low back pain (LBP). However, the determinants of nonpharmacologic treatment use for LBP in primary care remain unclear, particularly in low-income settings., Objective: To pilot a framework-informed interview guide and codebook to explore determinants of nonpharmacologic treatment use in primary care., Methods: In this qualitative interview study, we enrolled PCPs and community health workers (CHWs) from four primary care clinics at a safety net hospital. A semistructured interview guide informed by the Consolidated Framework for Implementation Research (CFIR) guided inquiry on barriers/facilitators to nonpharmacologic treatments for LBP (eg, acupuncture, chiropractic care, physical therapy). We included questions on whether current CHW roles may address barriers to nonpharmacologic treatment use. Interviews were audio-recorded, transcribed verbatim, and independently coded by four investigators. An a priori codebook composed of CFIR determinants and known CHW roles guided deductive content analysis to identify major themes., Results: Eight individuals (six PCPs, two CHWs; age range: 32-51 years, five female) participated in hour-long interviews. Half had worked at the hospital for ≥15 years and all reported seeing patients with LBP (range: 2-20 patients per week). All participants identified the following CFIR factors as barriers/facilitators: nonpharmacologic treatment characteristics (perceived cost, relative advantage compared to other treatments); outer setting (patient needs/resources, limited connections with community-based nonpharmacologic treatment) and PCP characteristics (attitudes/beliefs about nonpharmacologic treatments). Although participants indicated several CHW roles could be adapted to address barriers (eg, care coordination, resource linking, case management), other roles seemed less feasible (eg, targeted health education) in our health care system., Conclusions: Preliminary insight on key determinants of nonpharmacologic treatments for LBP should be further examined in large multisite studies. Future studies may also determine whether a CHW-led strategy can improve nonpharmacologic treatment access and clinical outcomes in primary care., (© 2024 American Academy of Physical Medicine and Rehabilitation.)

Background: Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies., Methods: PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228)., Findings: Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight)., Interpretation: Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease., Funding: Wellcome and PredictImmune Ltd., Competing Interests: Declaration of interests NMN reports personal fees from Galapagos, Janssen, Lilly, SBK Healthcare, and Takeda outside the submitted work; and grants from Dr Falk, Pfizer, Pharmacosmos, and Tillotts Pharma outside the submitted work. JCL reports consultancy fees from AbbVie, AgPlus Diagnostics, PredictImmune, and C4X Discover outside the submitted work; and grants from GSK outside the submitted work. KVP reports personal fees from AbbVie, DrFalk, Galapagos, Janssen, PredictImmune, Pfizer, and Takeda outside the submitted work; grants from AbbVie, Celltrion, Dr Falk, Ferring, Janssen, Takeda, and Tillotts Pharma outside the submitted work; and fees from advisory board membership of AbbVie, Galapagos, Janssen, and Pfizer outside the submitted work. TA reports personal fees from Amgen, Celltrion, Janssen, Lilly, Pfizer, and Tillotts Pharma; and grants from Biogen, Celltrion, Galapagos, Nova Pharmaceuticals, Pfizer, Roche, and Takeda outside the submitted work. JWB reports personal fees from Janssen outside the submitted work. RC reports personal fees from AbbVie, Galapagos, and Lilly outside the submitted work, grants from Celltrion, Ferring, and Tillotts Pharma outside the submitted work; and fees from advisory board membership of AbbVie and Bristol Myers Squibb outside the submitted work. SD reports personal fees from AbbVie, Ferring, Janssen, and Takeda outside the submitted work; grants from AbbVie, Dr Falk, and Janssen, outside the submitted work; and fees from advisory board membership of AbbVie outside the submitted work. DD reports personal fees from Takeda outside the submitted work; and grants from AbbVie and Janssen outside the submitted work. PMI reports personal fees from AbbVie, Arena, Boehringer-Ingelheim, BMS, Celgene, Celltrion, Dr Falk, Galapagos, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Prometheus, Sandoz, Samsung Bioepis, Sapphire Medical, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott outside the submitted work; and grants from AbbVie and Takeda outside the submitted work. AJK reports personal fees from AbbVie, Galapagos, and Takeda outside the submitted work; grants from AbbVie, Janssen, and Tillotts Pharma outside the submitted work; and fees from advisory board membership of AbbVie and Janssen outside the submitted work. CM reports grants from Janssen outside the submitted work. CSP reports personal fees from Dr Falk outside the submitted work. TR reports personal fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Novartis, Numab, Janssen, Pfizer, Roche, Takeda, UCB, and XAP therapeutics outside the submitted work; grants from AbbVie outside the submitted work; and fees from data monitoring board membership of UCB outside the submitted work. SS reports personal fees from AbbVie, Celltrion, Dr Falk, Ipsen, Janssen, and Takeda outside the submitted work. HRTW reports fees from advisory board membership of Pfizer outside the submitted work. SV reports personal fees from AbbVie, Abivax, AbolerISPharma, AgomAb, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Surrozen, Takeda, Theravance, Tillotts Pharma, VectivBio, Ventyx, and Zealand Pharma outside the submitted work; and grants from AbbVie, Galapagos, J&J, Pfizer, and Takeda outside the submitted work. VJ reports personal fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, Avoro Capital, BMS, Celltrion, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GSK, Genentech, Gilead, Innomar, JAMP, Janssen, Lilly, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx, and Vividion outside the submitted work; and fees from advisory board membership of AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, BMS, Celltrion, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GSK, Genentech, Gilead, Innomar, JAMP, Janssen, Lilly, Merck, Metacran, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, SCOPE, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, Topivert, Ventyx, and Vividion outside the submitted work. GRDH reports personal fees from AbbVie, Alimentiv, AstraZeneca, Immunic, J&J, Lilly, Pfizer, Takeda, Tillotts, and Ventyx outside the submitted work; grants from AbbVie, BMS, Lilly, Pfizer, and Takeda outside the submitted work; and fees from advisory board membership of AstraZeneca, Galapagos, and Seres Health outside the submitted work. EFM reports being a co-founder and receiving consultancy fees from PredictImmune; and holds PredictImmune stock or stock options. PAL reports being a co-founder and receiving consultancy fees from PredictImmune; and holds PredictImmune stock or stock options. JOL reports personal fees from AbbVie, Atlantic Healthcare, Bristol Meyer Squibb, Celgene, Celltrion, Engytix, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Janssen, MSD, Norgine, Pfizer, Shire, and Takeda outside the submitted work; and grants from AbbVie, Ferring, Gilead, Takeda, and Shire outside the submitted work. NAK reports personal fees from Amgen, Bristol Myers Squibb, Celltrion, Falk, Galapagos, Janssen, Pfizer, Pharmacosmos, Takeda, and Tillotts Pharma outside the submitted work; and reports data monitoring board membership for the BEACON study outside the submitted work. KGCS reports being a co-founder and receiving consultancy fees from Predictimmune; consultancy fees from GSK outside the submitted work; and holds PredictImmune stock or stock options. MP reports personal fees from Janssen and Takeda outside the submitted work; and grants from AstraZeneca, Galapagos, Gilead, and Pfizer outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Abstract: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background and Aims: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD]., Methods: We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling., Results: Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20-0.60], p = 0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p = 0.0050), and tofacitinib (0.28 [0.14-0.57], p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p = 0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p = 0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p = 0.017), and tofacitinib (0.23 [0.10-0.56], p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 [r = 0.27; p = 0.0004] and H1N1 [r = 0.33; p < 0.0001]., Conclusions: Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)